malignant mixed Mullerian tumor (MMMT)

a reading list compiled by Giordano Beretta

Bifulco, G., V. D. Mandato, et al. "A case of mesonephric adenocarcinoma of the vagina with a 1-year follow-up." International Journal of Gynecological Cancer 0(0): ???-???

Bifulco G, Mandato VD, Mignogna C, Giampaolino P, Di Spiezio Sardo A, De Cecio R, De Rosa G, Piccoli R, Radice L, Nappi C. A case of mesonephric adenocarcinoma of the vagina with a 1-year follow-up. Int J Gynecol Cancer 2007. Mesonephric adenocarcinoma deriving from remnants of vaginal mesonephric ducts is one of the rarest tumors of the female genital tract with only three cases reported till date in international literature. Differential diagnosis from other aggressive tumors is complex and controversies exist in the literature regarding the biological behavior, prognosis, and optimal management strategies of these tumors. A 58-year-old woman presented with a large mass extending from the right adnexal region to the perineum and labia majora. CA125 was increased. A radical excision of the lesion with pelvic and para-aortic lymphadenectomy was performed. A well-capsulated mesonephric adenocarcinoma in a background of vaginal mesonephric remnants was diagnosed. Tumor cells showed immunoreactivity for pancytokeratin, cytokeratin (CK), CD 10, epithelial membrane antigen, vimentin, and calretinin; indeed they were negative for carcinoembryonic antigen, CK 20, estrogen receptor, and progesterone receptor. No evidence of lymph node involvement or metastatic disease was observed. The patient did not receive any adjuvant therapy and is alive and clinically free of disease at 1-year follow-up. In spite of the aggressive biological behavior attributed in literature to mesonephric carcinomas, which is probably due to the complex differential diagnosis with other mullerian tumors, the favorable course of our patient further supports the hypothesis that malignant mesonephric carcinomas may not behave aggressively and that radical surgery alone may be curative.

Hoskins, P. J. and N. Le "Preoperative tumor markers at diagnosis in women with malignant mixed müllerian tumors/carcinosarcoma of the uterus." International Journal of Gynecological Cancer 0(0): ???-???

Hoskins PJ, Le N. Preoperative tumor markers at diagnosis in women with malignant mixed mullerian tumors/carcinosarcoma of the uterus. Int J Gynecol Cancer 2008. CA125 is a well-recognized marker for endometrial cancer. Uterine malignant mixed mullerian tumors (MMMTs) are increasingly being recognized as an aggressive adenocarcinoma, not a sarcoma. There are no data in the literature regarding CA125 in this malignancy. One hundred twelve women with surgically staged MMMT, diagnosed between July 1990 and September 2005, had a retrospective chart review performed. Preoperative CA125 levels were available in 29 (26%) women. Seventeen (49%) women had levels above the upper limit of normal of 35 kmu/L. Mean levels increased with increasing surgical stage: stage I 53.4 kmu/L; stage II 122.5 kmu/L; stage III 147.1 kmu/L; and stage IV 428.4 kmu/L. Elevated levels of CA19-9, CEA, and CA15-3 were found in 8%, 12%, and 25%, respectively.

Tjalma, W. A. A. and W. Vaneerdeweg (2007). "Primary retroperitoneal mucinous cystadenocarcinomas are a distinct entity." International Journal of Gynecological Cancer 0(0): ???-???

Tjalma WAA, Vaneerdeweg W. Primary retroperitoneal mucinous cystadenocarcinomas are distinct entity. Int J Gynecol Cancer 2007. Primary retroperitoneal mucinous cystadenocarcinomas are rare tumors with a controversial pathogenesis. Present report describes a 74-year-old woman with a retroperitoneal cystic pelvic mass. Her past medical history included appendectomy, bilateral salpingo-oophorectomy, and a hysterectomy. An explorative laparotomy was performed and the mass was completely excised. Definitive pathology revealed a primary retroperitoneal mucinous cystadenocarcinoma of the ovarian type. Further management consisted of four cycles carboplatin. She had a recurrence after 8 months and died 31 months after the initial diagnosis. Primary retroperitoneal mucinous cystadenocarcinomas are distinct entity, with the same poor prognosis as their ovarian counterpart.

Temkin, S. M., M. Hellmann, et al. (2007). "Early-stage carcinosarcoma of the uterus: the significance of lymph node count." International Journal of Gynecological Cancer 17(1): 215-219.

Temkin SM, Hellmann M, Lee Y-C, Abulafia O. Early-stage carcinosarcoma of the uterus: the significance of lymph node count. Int J Gynecol Cancer 2007;17:215-219. Carcinosarcoma is a rare tumor of the uterus with a poor prognosis, even when identified and treated at an early stage. The purpose of this study was to identify and analyze prognostic pathologic features and treatment outcomes in patient with stages I and II carcinosarcoma of the uterus. Patients with carcinosarcoma of the uterus who received primary surgical treatment between 1984 and 2004 were identified through an institutional tumor registry. Inclusion criteria were clinical stage I/II disease following hysterectomy and selective pelvic and para-aortic lymph node sampling. Regression analysis was used to determine risk factors for recurrence and survival. Disease-free and overall survival were then determined using Kaplan-Meier analysis. Forty-seven patients with stages I and II carcinosarcoma of the uterus were identified. Age, heterologous or homologous histology, and type of adjuvant treatment were not associated with recurrence or survival. Depth of myometrial invasion was found to correlate to disease-free survival but not overall survival. The number of lymph nodes collected correlated to risk of recurrence and survival. Disease-free and overall survival were greater in patients with higher lymph node count. We conclude that the number of lymph nodes collected was the only risk factor that was found to be correlated to recurrence and survival in patients with early-stage carcinosarcoma. These results support mounting evidence that lymphadenectomy is crucial in patients with carcinomas of the uterus in order to discover occult metastatic disease and potentially provide patients with a therapeutic benefit.

Sovak, M. A., J. Dupont, et al. (2007). "Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study." International Journal of Gynecological Cancer 17(1): 197-203.

Sovak MA, Dupont J, Hensley ML, Ishill N, Gerst S, Abu-Rustum N, Anderson S, Barakat R, Konner J, Poyner E, Sabbatini P, Spriggs DR, Aghajanian C. Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. Int J Gynecol Cancer 2007;17:197-203. The aim of this study was to assess the efficacy and tolerability of paclitaxel and carboplatin (TC) in the treatment of patients with advanced or recurrent endometrial cancer. Patients eligible for this retrospective analysis had endometrial cancer with either advanced or recurrent measurable disease (untreated primary stage III/IV or stage III/IV patients with persistent, measurable disease [>=2 cm] after surgery), Eastern Cooperative Oncology Group (ECOG) performance status >=3, and received at least one cycle of TC. Response rates were determined using Response Evaluation Criteria in Solid Tumors criteria. Institutional Review Board approval was obtained prior to the initiation of this study. Eighty-five eligible patients, with a median age of 62 years (range 36-80) were identified. Fifty-seven (67%) of patients were treated at the time of recurrence. Prior radiation therapy had been used in the treatment of 36 (42%) patients, while 13 (15%) patients had received prior chemotherapy. Median follow-up time was 11.7 months (range 1.1-96.7 months), and the median number of cycles of therapy received was six (range 1-18). The overall response rate (ORR) was 43%, with a complete response rate of 5% and a partial response rate of 38%. Chemotherapy-naive patients had an ORR of 47%. Only seven (8%) patients had to discontinue therapy due to toxicity. Median progression-free survival was 5.3 months (95% CI, 4.6-7.4), with a median overall survival of 13.2 months (95% CI, 11.7-18.2). We conclude that TC is an active and tolerable regimen in the treatment of patients with advanced or recurrent endometrial cancer.

Silasi, D. A., J. L. Illuzzi, et al. (2007). "Carcinosarcoma of the ovary." International Journal of Gynecological Cancer 0(0): 0-0.

Silasi D-A, Illuzzi JL, Kelly MG, Rutherford TJ, Mor G, Azodi M, Schwartz PE. Carcinosarcoma of the ovary. Int J Gynecol Cancer 2007. The objective of this study was to evaluate the treatment and outcome in patients with ovarian carcinosarcoma. The Tumor Board Registry was reviewed for patients with ovarian carcinosarcoma treated at our institution from June 1993 to December 2004. The medical records were retrospectively analyzed with emphasis on cytoreduction, cytotoxic regimens, progression-free interval, and survival. Twenty-two patients were identified. All but two presented with advanced stage disease. The median survival for the entire cohort was 38 months. Median survival was 46 months for 18 optimally debulked (<1 cm) patients and 27 months for four suboptimally debulked (>1 cm) patients. Six patients were treated with optimal cytoreduction and adjuvant cisplatin (40 mg/m2 x 1 day) and ifosfamide (1200 mg/m2/day x 4 days) every 28 days. Median progression-free interval in the cisplatin and ifosfamide group was 13 months, and median survival was 51 months. The combination of carboplatin (AUC 5) and taxol (175 mg/m2) every 21 days was administered to four patients as first-line chemotherapy following optimal cytoreduction. In the carboplatin and taxol group, median progression-free interval was 6 months and median survival was 38 months. The difference in survival between the cisplatin and ifosfamide group and the carboplatin and taxol group was not statistically significant (P = 0.48). In conclusion, patients with ovarian carcinosarcoma usually present with advanced stage disease. Treatment consists of optimal cytoreduction and chemotherapy. The most effective cytotoxic regimen remains to be determined. First-line cisplatin and ifosfamide or carboplatin and taxol can achieve survival rates observed in epithelial ovarian cancer.

Schulten, H. J., J. Wolf-Salgo, et al. (2007). "Characterization of a newly established uterine carcinosarcoma cell line featuring the sarcomatous phenotype of the tumor in vitro." International Journal of Gynecological Cancer 0(0): ???-???

Schulten H-J, Wolf-Salgo J, Grundker C, Gunawan B, Fuzesi L. Characterization of a newly established uterine carcinosarcoma cell line featuring the sarcomatous phenotype of the tumor in vitro. Int J Gynecol Cancer 2007. We describe the newly established cell line CS-99 derived from a uterine carcinosarcoma retaining features of the sarcomatous phenotype in vitro. CS-99 cells exhibit a mesenchymal morphology with predominantly spindle-shaped cells at nonconfluence turning to pleomorphic appearance at confluence. The mesenchymal phenotype was evidenced immunohistochemically by strong vimentin and moderate SM-actin, which was similar to the sarcomatous component of the primary tumor. P53 was overexpressed in a subset of CS-99 cells. Epithelial membrane antigen was moderately expressed whereas other markers including pan CK, CK 5/6, CK 34, epidermal growth factor receptor, desmin, carcinoembryonic antigen, S100, KIT, ERBB2, and the hormone receptors, estrogen receptor and progesterone receptor revealed either weak or no specific staining in CS-99 cells. High self-renewal capacity corresponded to the population doubling time of 23 h in high passage. CS-99 cells were able to develop three-dimensional tumor spheroids in vitro. Cytogenetic analysis and multicolor fluorescence in situ hybridization of CS-99 demonstrated an almost stable karyotype including numerical changes +8, +18, and +20 and translocations, amongst others der(1)t(1;2), der(1)t(1;7), der(2)t(2;19), der(5)t(5;8), and der(5)t(5;14). Taken together, the cell line CS-99 exhibits strong growths dynamics and a complex but stable karyotype in higher passages, and can be further a useful in vitro model system for studying tumor biology of carcinosarcomas.

Pather, S., K. Atkinson, et al. (2007). "Virilization in pregnancy due to a borderline mucinous ovarian tumor." Journal of Obstetrics and Gynaecology Research 33(3): 384-387.

Abstract Virilization in pregnancy due to borderline mucinous ovarian tumors is very rare. A case of a 28-year-old patient who was noted at 28 weeks' gestation to have marked virilization with raised serum androgens, ascites and a large complex right adnexal mass is presented. Delivery was carried out by cesarean section and at surgery a large tumor was noted in the right ovary. Histology revealed a borderline mucinous ovarian tumor with stromal luteinization, but there was no evidence of stromal invasion. Serum androgens returned to normal levels following surgery and the maternal virilization had resolved at the 6-week postnatal visit. Stromal changes in borderline mucinous ovarian tumors may result in virilization due to androgen production; surgical removal is associated with an excellent clinical outcome.

Ozguroglu, M., A. Bilici, et al. (2007). "Determining predominating histologic component in malignant mixed müllerian tumors: is it worth it?" International Journal of Gynecological Cancer 0(0): ???-???

Ozguroglu M, Bilici A, Ilvan S, Turna H, Atalay B, Mandel N, Sahinler I. Determining predominating histologic component in malignant mixed mullerian tumors: is it worth it? Int J Gynecol Cancer 2007. Malignant mixed mullerian tumors (MMMT) are highly aggressive tumors, usually diagnosed in advanced stage. Cases of MMMT derive from either ovary or uterus. In our study, we investigated the role of carcinomatous and sarcomatous component on response to chemotherapy and disease outcome. We retrospectively analyzed 25 patients with MMMT who were treated in our outpatient clinic from 1998 to 2003. All the paraffin specimens were reevaluated according to the histopathologic features (primary site and percentages of carcinomatous and sarcomatous component) and the effect of predominant histologic type on response to treatment. Primary tumor sites were ovary and endometrium in 36% and 64% of patients, respectively. Ten of 25 patients (40%) were treated with a combination chemotherapy regimen of cisplatin-ifosfamide (PI) and 7 patients (28%) were treated with paclitaxel-carboplatin (PC) protocol. Despite chemotherapy, 17.6% of patients had progressive disease. The remaining 13 patients (54.2%) responded to chemotherapy. Response rates of patients treated with PC (100%) were remarkably higher than the response rates of patients treated with PI (66.6%). Moreover, patients with predominating carcinomatous component had a higher response rate (87.5%) than patients with predominating sarcomatous component (66.6%). MMMT are highly chemoresponsive tumors, irrespective of primary site. One of the best predictors to response is the histologic pattern. Predominating histopathologic feature (carcinoma or sarcoma) should be taken into consideration in predicting the response and planning the chemotherapy regimen.

Yemelyanova, A. V., J. A. Cosin, et al. (2007). "Pathology of stage I versus stage III ovarian carcinoma with implications for pathogenesis and screening." International Journal of Gynecological Cancer 0(0): ???-???

Yemelyanova AV, Cosin JA, Bidus MA, Boice CR, Seidman JD. Pathology of stage I versus stage III ovarian carcinoma with implications for pathogenesis and screening. Int J Gynecol Cancer 2007. The progression of ovarian carcinoma from stage I when it is confined to the ovaries and curable to disseminated abdominal disease, which is usually fatal, is poorly understood. An accurate understanding of this process is fundamental to designing, testing, and implementing an effective screening program for ovarian cancer. Pathologic features of the primary ovarian tumors in 41 FIGO stage I ovarian carcinomas were compared with those in 40 stage III carcinomas. The primary ovarian tumors in stage I cases, when compared with stage III, respectively, were significantly larger (15.4 versus 9.8 cm), were less frequently bilateral (12% versus 75%), more frequently contained a noninvasive component (88% versus 30%), had a higher proportion of a noninvasive component (42% versus 8%), and were more often nonserous (83% versus 20%) (P < 0.001 for all five comparisons). There are significant pathologic differences between the primary ovarian tumors in stage I and III ovarian carcinomas that are very difficult to explain by a simple temporal progression. These findings along with the growing body of literature suggest that early- and advanced-stage ovarian cancers are in many instances biologically different entities. This knowledge may have significant implications for our understanding of the biology of early- and advanced-stage ovarian cancer and therefore on the development of screening strategies for ovarian cancer.

Ihnen, M., S. Mahner, et al. (2007). "Current treatment options in uterine endometrial stromal sarcoma: report of a case and review of the literature." International Journal of Gynecological Cancer 17(5): 957-963.

Ihnen M, Mahner S, Janicke F, Schwarz J. Current treatment options in uterine endometrial stromal sarcoma: report of a case and review of the literature. Int J Gynecol Cancer 2007;17:957-963. Uterine sarcomas are a rare form of uterine cancer. They occur in women from 40 to 60 years and are generally characterized by poor prognosis, a high rate of local recurrence, and distant metastases. Endometrial stromal sarcoma (ESS) accounts for 0.2% of all gynecological malignancies. Forms of possible treatment include surgery, radiotherapy, chemotherapy, and endocrine treatment. Randomized trials analyzing these treatment options are limited due to the rarity of this disease; therefore, a standard therapy could not be established thus far. To present an overview of the current treatment options of ESS, a search of Medline, Embase, and the Cochrane Library was performed and the results concluded. We report the case of a 32-year-old woman who presented with FIGO stage II ESS. Initial treatment with tamoxifen and local perfusion with cisplatin resulted in disease progression and were discontinued. A novel, therapeutic approach using two cycles of combination chemotherapy with doxorubicin and ifosfamide followed by surgery was applied. Five years after surgery, the patient is still in complete remission. Thus, we conclude that although there is no data from randomized trials available, chemotherapy in advanced or metastatic ESS can provide an opportunity for surgical treatment and can lead to long-term remission.

Athavale, R., N. Thomakos, et al. (2007). "The effect of epithelial and stromal tumor components on FIGO stages III and IV ovarian carcinosarcomas treated with primary surgery and chemotherapy." International Journal of Gynecological Cancer 17(5): 1025-1030.

Athavale R, Thomakos N, Godfrey K, Kew F, Cross P, de Barros Lopes A, Hatem MH, Naik R. The effect of epithelial and stromal tumor components on FIGO stages III and IV ovarian carcinosarcomas treated with primary surgery and chemotherapy. Int J Gynecol Cancer 2007;17:1025-1030. The aim of this study is to assess the effect of epithelial and stromal tumor components on survival outcomes in FIGO stage III or IV ovarian carcinosarcomas (OCS) treated with primary surgery and adjuvant chemotherapy at the Northern Gynaecological Oncology Centre (NGOC), Gateshead. Women were identified from the histopathology/NGOC databases. Age, FIGO stage, details of histology, treatment, and overall survival were recorded. Of 34 cases (1994-2006, all FIGO stages), 17 were treated with primary surgery followed by adjuvant chemotherapy for FIGO stage III or IV. The median age was 66 years (52-85 years). Cytoreduction was optimal (n = 9) or complete (n = 1) in 10/17 (59%) cases. Epithelial predominant (EP) or stromal predominant (SP) tumor (defined as >50% of either component in the primary tumor) was noted in 12 and 5 cases, respectively. Epithelial types included serous (n = 9), endometrioid (n = 5), and mixed types (n = 3). Twelve women have died of disease. The median overall survival was 11.0 months (3-74 months). On univariate analysis, survival was not affected by optimal/suboptimal debulking, platinum/doxorubicin-containing chemotherapy, or homologous/heterologous stromal components. Stromal components (>25%) adversely affected survival (P = 0.02), and there was a trend to worse survival with serous compared with nonserous epithelial components (P = 0.07). Cox regression (multivariate analysis) showed that SP tumors (P = 0.04), suboptimal debulking (P = 0.01), age (P = 0.01), and tumors with serous epithelial component (P = 0.05) were adverse independent prognostic factors. Type of chemotherapy and homologous/heterologous components (P = 0.24) did not affect overall survival. In conclusion, our study suggests that SP-OCS have a worse survival outcome than EP tumors. Tumors with serous epithelial components adversely affected the survival compared with nonserous components. Larger studies are required to confirm these effects and to identify the optimum chemotherapy regimen for OCS.

Arits, A. H. M. M., J. E. G. M. Stoot, et al. (2007). "Preoperative serum CA125 levels do not predict suboptimal cytoreductive surgery in epithelial ovarian cancer." International Journal of Gynecological Cancer 0(0): ???-???

Arits AHMM, Stoot JEGM, Botterweck AAM, Roumen FJME, Voogd AC. Preoperative serum CA125 levels do not predict suboptimal cytoreductive surgery in epithelial ovarian cancer. Int J Gynecol Cancer 2007. The objective is to assess the ability of preoperative serum CA125 levels to identify patients at high risk of suboptimal cytoreductive surgery for epithelial ovarian cancer (EOC). One hundred and thirty-two women diagnosed with EOC between 1998 and 2004, who had serum CA125 levels measured preoperatively and received primary cytoreductive surgery, were retrospectively evaluated. The value of CA125 and patient and disease characteristics to predict suboptimal cytoreduction were determined, and a prognostic scoring system, based on statistically significant variables, was created. Optimal cytoreduction was achieved in 42.7% of the women with FIGO stage III/IV EOC. The optimal cutoff point of preoperative CA125 to predict surgical outcome in this group was 330 U/mL (sensitivity 80.0%; specificity 41.5%). The area under the receiver-operating characteristic curve (AUC) for preoperative CA125 predicting suboptimal surgery in FIGO stage III/IV was 0.576 (P = 0.617). Preoperative radiologic amount of ascites and weight loss (ie, >=10% in the last 6 months before diagnosis) were independent prognostic factors for suboptimal cytoreduction, showing an AUC of 0.76 (P < 0.001) in women with FIGO stage III/IV. A prognostic scoring system showed that the chance of suboptimal surgery was 84.6% in FIGO stage III/IV when both these factors are present preoperatively. The role of CA125 levels predicting suboptimal cytoreduction seems questionable. Instead, women with considerable weight loss and a gross amount of ascites have a higher risk of suboptimal cytoreduction. These patients may be candidates for neoadjuvant chemotherapy.

Banerjee, S. S. and B. Eyden (2007). "Divergent differentiation in malignant melanomas: a review." Histopathology 0(0): ???-???

Banerjee S S & Eyden B (2007) Histopathology Divergent differentiation in malignant melanomas: a review The aim of this review was to document and discuss diagnostic problems associated with divergent differentiation (metaplastic change) in malignant melanomas, defined as the development in these tumours of morphologically, immunohistochemically and/or ultrastructurally recognizable non-melanocytic cell or tissue components. Types of divergent differentiation reported in malignant melanoma include: fibroblastic/myofibroblastic, Schwannian and perineurial, smooth muscle, rhabdomyosarcomatous, osteocartilaginous, ganglionic and ganglioneuroblastic, neuroendocrine and probable epithelial. Divergent differentiation is certainly a rare phenomenon and, when it occurs, can be missed by unwary pathologists and lead to diagnostic uncertainty. A carefully chosen immunohistochemical panel and the input of electron microscopy can help to clarify the nature of the cellular differentiation of these tumours and lead to a correct final diagnosis. The clinical significance of such aberrations is uncertain, nor are the underlying mechanisms as yet well defined.

Lee, S. J., Y. L. Choi, et al. (2007). "Increased expression of calpain 6 in uterine sarcomas and carcinosarcomas: an immunohistochemical analysis." Int J Gynecol Cancer 17(1): 248-53.

Calpain 6 (Capn6) is one of the calcium-dependent intracellular nonlysosomal proteases. Recently, Capn6 was found to be overexpressed in leiomyosarcomas (LMSs) compared with normal myometrium. This investigation was performed to determine the expression of Capn6 in uterine sarcomas and carcinosarcomas and to determine whether there is a relationship between the clinical findings and the expression of Capn6. Seventeen cases, treated from 1994 to 2004, were evaluated. These included five LMS, seven endometrial stromal sarcomas, and five uterine carcinosarcomas (malignant mullerian mixed tumor [MMMT]). Formalin-fixed, paraffin-embedded tissue sections were immunostained with anti-Capn6 domain-II (anti-DII) and anti-Capn6 domain-T (anti-DT) antibodies. A semiquantitative assessment was performed. All 17 tumors expressed the Capn6 protein; this finding was in contrast to the absence of expression of the Capn6 protein in all of the normal control tissues. The distribution of staining was diffuse. The cytoplasm and nucleus were stained evenly. The mean age of the patients whose samples were stained strongly by anti-DII was higher (P= 0.031). There were no significant associations between tumor stage and staining intensity by anti-DII (P= 1.000) or anti-DT (P= 0.576). However, there was a marginally significant association between tumor subtype and staining intensity (P= 0.054 and P= 0.053, respectively). The expression of Capn6 had no association with disease-free survival (P= 0.367 and P= 0.166, respectively). All of the uterine sarcomas and MMMTs expressed Capn6 protein. This study showed that there were marginally significant associations between tumor subtypes and staining intensity, but no association was found with tumor stage and survival.

Lax, S. F. (2007). "Molecular genetic changes in epithelial, stromal and mixed neoplasms of the endometrium." Pathology 39(1): 46-54.

Endometrial carcinoma, endometrial stromal tumours and mixed malignant mesodermal tumours (MMMT) develop along distinctive molecular genetic pathways. Two distinctive types of endometrial carcinoma are distinguished, type I and type II, which develop along distinctive pathways and show different clinical behaviour and histological features. Type I carcinomas show endometrioid histology, are oestrogen-related and develop from atypical endometrial hyperplasia. The molecular tumorigenesis is comparable to colorectal carcinoma with a step-like progression and an accumulation of genetic alterations. Alterations of PTEN, K-Ras mutations and microsatellite instability are frequent and early events in type I carcinoma, whereas p53 mutations occur during progression to grade 3 carcinoma. Serous and clear cell carcinomas are considered type II carcinomas which are mostly unrelated to oestrogen. p53 mutations occur in almost all serous carcinomas and seem to occur early, leading to massive chromosomal instability and rapid tumour progression. Gene expression profiling has supported this dualistic model of endometrial carcinoma. There is evidence of molecular differences between serous and clear cell carcinomas as well as between endometrioid carcinomas with and without microsatellite instability. A dualistic model of tumorigenesis may be also suggested for endometrial stromal tumours. Endometrial stromal sarcomas (ESS; type I endometrial sarcoma) are oestrogen-related and seem to develop from endometrial stromal nodules (ESN). They are histologically and genetically distinct from undifferentiated endometrial sarcoma (UES) which seem to be mostly unrelated to oestrogen (type II endometrial sarcoma). ESS and ESN share the fusion gene JAZF1/JJAZ1 caused by a t(7;17)(p15;q21) translocation, whereas UES lacks a distinctive molecular alteration so far. In MMMT, which is considered a metaplastic carcinoma, p53 alteration occurs early, before clonal expansion and acquisition of genetic diversity during progression.

Lavie, O., O. Barnett-Griness, et al. (2007). "The risk of developing uterine sarcoma after tamoxifen use." International Journal of Gynecological Cancer 0(0): ???-???

Lavie O, Barnett-Griness O, Narod SA, Rennert G. The risk of developing uterine sarcoma after tamoxifen use. Int J Gynecol Cancer 2007. The treatment of breast cancer with tamoxifen results in an increased risk of uterine cancer. The objective of this study was to evaluate the association between tamoxifen use and the risk of developing uterine sarcomas and endometrial carcinomas in a historical cohort of women diagnosed with breast cancer in 1987-1988. The medical records of all women diagnosed in Israel with breast cancer in the years 1987-1988 were sought. Clinical data, including use of hormone therapy, were extracted from oncology records. In 2004, patient identifiers were linked to the Israel Cancer Registry database to identify all uterine cancers that occurred within 15 years of the diagnosis of breast cancer. The records for 1507 breast cancer cases (84%) were retrieved. Among these cases, 32 uterine malignancies were identified; 11 occurred prior to the diagnosis of breast cancer and 21 occurred during the follow-up period. Eight hundred seventy-five women in the cohort had used tamoxifen (59%). There were 17 uterine cancers observed among the 875 exposed to tamoxifen (1.9%), compared to 4 uterine cancers among the 621 women (0.6%) who did not use tamoxifen (odds ratio = 3.1; 95% CI: 1.0-9.1; P = 0.04). There were four uterine sarcomas among the tamoxifen users, but none among nonusers (P = 0.15). Five of the 875 tamoxifen users (0.6%) died of uterine cancer, compared to no deaths among nonusers (P = 0.08). We conclude that in this national breast cancer cohort, tamoxifen use was associated with elevated risks of uterine cancer incidence and mortality. Uterine sarcomas appear to be overrepresented among women who use tamoxifen.

Kwon, J. S., J. Lenehan, et al. (2007). "Prolonged survival among women with BRCA germline mutations and advanced endometrial cancer: a case series." International Journal of Gynecological Cancer 0(0): ???-???

Kwon JS, Lenehan J, Carey M, Ainsworth P. Prolonged survival among women with BRCA germline mutations and advanced endometrial cancer: a case series. Int J Gynecol Cancer 2007. It is unclear if BRCA mutation carriers diagnosed with advanced endometrial cancer have a better prognosis compared to sporadic cases. From a population database of BRCA1 and 2 mutation carriers in Southwestern Ontario, Canada, we identified three women with advanced-stage endometrial cancer. They were 57, 59, and 64 years of age, and of English/Scottish, Ashkenazi Jewish, and English heritage, respectively. They had different mutations in BRCA1 (Q1240X:C3837T; 68_69delAG; 1961delA). One had a sarcomatoid carcinoma and two had uterine papillary serous carcinoma. All had stage IVB disease, with surgery followed by adjuvant chemotherapy and/or radiotherapy. Follow-up has ranged from 3.3 to 14.6 years. They are still alive and well with no evidence of recurrent disease. This observation raises the question as to whether BRCA mutations may be associated with a better prognosis in patients with advanced endometrial cancer.

Kuroda, N., Y. Inui, et al. (2007). "Hyaline globule-like structures in undifferentiated sarcoma cells of malignant mullerian mixed tumor of the fallopian tube." Med Mol Morphol 40(1): 46-9.

Malignant müllerian mixed tumors (MMMTs) of the fallopian tube are very rare neoplasms, and we present such a case with unusual findings here. A 57-year-old Japanese woman, after she received a medical checkup, underwent salpingo-oophorectomy on the suspicion of ovarian cancer. At the time of operation, the main tumor was present predominantly in the fallopian tube. Microscopically, the tumor consisted of carcinoma and sarcoma components. The carcinoma showed moderately to poorly differentiated adenocarcinoma. The sarcoma consisted of predominantly undifferentiated sarcoma and focally rhabdomyosarcomatous cells with abundant eosinophilic cytoplasm. Immunohistochemically, the differentiation toward rhabdomyosarcoma was confirmed. Interestingly, the cytoplasm of undifferentiated sarcoma cells contained hyaline globule-like structures. These structures showed a positive reaction for PAS, and these structures were not digested by the diastase pretreatment. Ultrastructurally, hyaline globule-like structures corresponded to lysosomes. Finally, pathologists should keep in mind that undifferentiated sarcoma cells in MMMT of the fallopian tube may contain hyaline globule-like structures in the cytoplasm.

Konishi, Y., H. Sato, et al. (2007). "A case of primary uterine angiosarcoma: magnetic resonance imaging and computed tomography findings." International Journal of Gynecological Cancer 17(1): 280-284.

Konishi Y, Sato H, Fujimoto T, Tanaka H, Takahashi O, Tanaka T. A case of primary uterine angiosarcoma: magnetic resonance imaging and computed tomography findings. Int J Gynecol Cancer 2007;17:280-284. Primary uterine angiosarcoma is exceedingly rare and has a poor prognosis. Moreover, the radiologic findings of this disease have not been previously documented. We present a case of a 62-year-old woman with primary uterine angiosarcoma who underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. Histologically, interlacing vascular spaces were lined by endothelial cells showing nuclear pleomorphism and mitotic activity. Immunohistochemical staining was positive for the endothelial cell markers CD31, CD34, and Factor VIII, supporting the diagnosis of primary uterine angiosarcoma. Magnetic resonance imaging (MRI) revealed a heterogeneous mass with high and low signal intensity (T2 weighted) in the uterus and an intense contrast-enhanced anterior area within the mass (gadolinium enhanced, T1 weighted). The lesion was also enhanced on computed tomography (CT). Radiologically, the most helpful sign in the characterization of uterine angiosarcoma is marked heterogeneity on T2-weighted MRI with focal areas of high signal intensity, known as the "cauliflower-like appearance." In addition, findings of a strongly enhanced lesion on gadolinium-enhanced T1-weighted MRI and contrast-enhanced CT also support the diagnosis of angiosarcoma.

Ghaemmaghami, F., T. Ashraf-Ganjooie, et al. (2007). "Borderline ovarian tumors." Asia-Pacific Journal of Clinical Oncology 3(1): 12-18.

Abstract Borderline ovarian tumors account for approximately 15% of all epithelial ovarian tumors. In the early 1970s, borderline tumors were categorized as either serous or mucinous with overall survival rates of 75-90%. Since then, it has been recognized that the two categories are heterogonous. There are now many different groups following the recognition of serous tumors with microinvasion, non-invasive and invasive peritoneal implants and a micropapillary pattern, and of mucinous tumors with microinvasion, intraepithelial carcinoma and pseudomyxoma peritoneal implants, in addition to further delineation of endometrial, clear cell and transitional cell tumors with atypical proliferation. This review outlines the most recent information regarding the epidemiology, pathology and clinical management of borderline tumors. Surgical management to excise all visible tumors remains the cornerstone of therapy. Because borderline ovarian tumors often occur in reproductive-age women, fertility is an important issue. Conservative surgery is a safe in carefully selected patients. Effective non-surgical therapies are yet to be identified.

Ferreira, C. R., J. P. Carvalho, et al. (2007). "Mucinous ovarian tumors associated with pseudomyxoma peritonei of adenomucinosis type: immunohistochemical evidence that they are secondary tumors." International Journal of Gynecological Cancer 0(0): ???-???

Ferreira CR, Carvalho JP, Soares FA, Siqueira SAC, Carvalho FM. Mucinous ovarian tumors associated with pseudomyxoma peritonei of adenomucinosis type: immunohistochemical evidence that they are secondary tumors. Int J Gynecol Cancer 2007. Pseudomyxoma peritonei (PMP) is a clinical condition initially thought to be related to ovarian mucinous tumors; however, immunohistochemistry and molecular biology techniques have convincingly made the link to appendiceal mucinous neoplasms, resulting in changes in histologic and clinical approaches. The objective of this study was to compare the immunohistochemical profile of ovarian tumors associated with PMP and intestinal mucinous ovarian neoplasms without PMP. The study was retrospective and included 28 intestinal ovarian mucinous tumors selected from the files of the Division of Surgical Pathology of the University of Sao Paulo Medical School, from 1996 to 2005. Seven cases were associated with PMP of disseminated peritoneal adenomucinosis-type and all presented borderline histology. Immunohistochemical staining for mucin genes products (MUC1, MUC2, MUC5AC, and MUC6), CK7, CK20, CA19.9, and CA125 were performed in tissue microarrays. Of note, we detected differences in the expression of MUC2 and CK20 between cases with and without PMP. Comparisons of borderline histology with that of benign/malignant tumors also revealed differences in MUC2 and CK20. Our results confirm that there is a distinct profile of intestinal ovarian tumors associated with pseudomyxoma, particularly with respect to the expression of the gel-forming mucin MUC2. The profile of borderline tumors, even in cases without PMP, was distinct from that of other primary mucinous tumors of the intestinal type, suggesting that borderline histology may represent a secondary tumor or a less aggressive variant of PMP. An appendiceal origin seems the most probable for this group of neoplasias.

Cohn, D. E., K. E. Resnick, et al. (2007). "Non-Hodgkin's lymphoma mimicking gynecological malignancies of the vagina and cervix: a report of four cases." International Journal of Gynecological Cancer 17(1): 274-279.

Cohn DE, Resnick KE, Eaton LA, deHart J, Zanagnolo V. Non-Hodgkin's lymphoma mimicking gynecological malignancies of the vagina and cervix: a report of four cases. Int J Gynecol Cancer 2007;17:274-279. Although in the past two decades there has been a sharp rise in the incidence of extranodal primary lymphomas in the United States, non-Hodgkin's lymphoma (NHL) of the female genital tract is still rare. We present four cases of extranodal NHL presenting with signs and symptoms consistent with cancer of the vagina or cervix and lacking the "B" symptoms often associated with systemic lymphoma such as fever, weight loss, night sweat, and fatigue. It is important for gynecologists to be aware of this neoplastic disease and to include cervical or vaginal lymphoma in the differential diagnosis of patients presenting with examinations suggestive of cervical or vaginal cancer. A correct diagnosis leads to the appropriate therapy, and radical gynecological surgery can be avoided for primary cervical and vaginal lymphoma.

Chiang, Y. C., C. A. Chen, et al. (2007). "Synchronous primary cancers of the endometrium and ovary." International Journal of Gynecological Cancer 0(0): ???-???

Chiang Y-C, Chen C-A, Huang C-Y, Hsieh C-Y, Cheng W-F. Synchronous primary cancers of the endometrium and ovary. Int J Gynecol Cancer 2007. Simultaneous detection of malignancy in the endometrium and ovary represents an uncommon event. The objective of the study was to clarify the possible factors that influenced on the survival. From 1977 to 2005, totally 27 patients fulfilled the criteria and were included in the study. The medical records and the pathologic reports were reviewed. The histologic determination was followed by the World Health Organization Committee classification, and cancer stage was based on the staging system of the FIGO. The Kaplan-Meier survival analyses were generated and compared by the log-rank test. The incidence of synchronous primary endometrial and ovarian cancers was 3.3% in patients with endometrial cancer and 2.7% in patients with ovarian cancer. The mean survival in the group of similar histology (n = 15) was 63 months, and 48 months in the group of dissimilar histology (n = 12) (P = 0.63). The mean survival in the group of early stage (n = 21) was 68 months and 15 months in the group of advanced stage (n = 6) with statistic significance (P = 0.0003). However, the impact of adjuvant therapy on survival did not reach statistic significance (P = 0.15 for chemotherapy; P = 0.69 for radiotherapy). We conclude that the majority of the patients belonged to concordant endometrioid histology in endometrium and ovary, and it tends to be early stage and low grade with favorable prognosis. The stage had more significant influence on the survival than the histology. Adjuvant therapy should be given especially in patients with advanced stage although the optimal management remained to be determined.

Chekerov, R., C. Denkert, et al. (2007). "Online tumor conference in the clinical management of gynecological cancer: experience from a pilot study in Germany." International Journal of Gynecological Cancer 0(0): 0-0.

Chekerov R, Denkert C, Boehmer D, Suesse A, Widing A, Ruhmland B, Giese A, Mustea A, Lichtenegger W, Sehouli J. Online tumor conference in the clinical management of gynecological cancer: experience from a pilot study in Germany. Int J Gynecol Cancer 2007. The concept of the online tumor conference was established in 2004 as a pilot project. We developed specific web-based software to organize and conduct online tumor board meetings of gynecologists, surgeons, radiologists, oncologists, and pathologists from different hospitals and gynecological practitioners, discussing individual patient s cases, defining therapy options, and exchanging clinical experience. Following a didactic approach, patient data are presented to the participants, with a special focus toward patient s preference and late toxicity from prior therapy. Then different national (eg, Arbeitsgemeinschaft Gynaekologische Onkologie, Deutsche Gesellschag fur Gynaekologic und Geburtshilfe) and international guidelines (eg, American Society of Clinical Oncology, National Cancer Institute), current study results based on literature review and open clinical trials are discussed. An individual diagnosis and therapy recommendation for each patient is reached by consensus. All protocols, guidelines, and publication data are upgraded and dispersed via Internet for all participants. In the period from December 2004 to August 2006, 39 tumor board conferences were performed with a total of 667 participants. One hundred forty-four patients cases were presented, and 121 peer-reviewed second-opinions were sought. In an anonymous survey, 84% of the participants reported to be satisfied with the information content and 72% with the technical support. Overall 98% of the individual therapy recommendations were accepted and implemented. The tumor board conference presents an optimal possibility for extensive scientific discussions and exchange (92%) and improves advanced educational training (81%). In conclusion, the online tumor conference is feasible and represents a time-saving possibility for gynecological oncologist to receive a treatment recommendation based on the best available clinical and scientific evidence.

Buyukkurt, S., M. A. Vardar, et al. (2007). "Non-puerperal inversion of the uterus caused by leiomyosarcoma: A case report and clinical management." Journal of Obstetrics and Gynaecology Research 33(3): 402-406.

Abstract Uterine inversion is a rare complication of the postpartum period, but it is an even rarer complication of the non-puerperal period. A 49-year-old nulliparous woman was admitted to the hospital with the following complaints: abnormal vaginal bleeding, pain, anuria and a mass protruding from the vulva. The mass was removed by twisting and a laparotomy was required for massive bleeding due to the inversion. The diagnosis of complete inversion was made during the laparotomy. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed and the pathological examination revealed a leiomyosarcoma. Uterine inversion in the non-puerperal period is an extremely rare event and it should be kept in mind that the cause of the inversion may be a malignant disease, like leiomyosarcoma.

Athavale, R., N. Thomakos, et al. (2007). "The effect of epithelial and stromal tumor components on FIGO stages III and IV ovarian carcinosarcomas treated with primary surgery and chemotherapy." International Journal of Gynecological Cancer 0(0): 0-0.

Athavale R, Thomakos N, Godfrey K, Kew F, Cross P, de Barros Lopes A, Hatem MH, Naik R. The effect of epithelial and stromal tumor components on FIGO stages III and IV ovarian carcinosarcomas treated with primary surgery and chemotherapy. Int J Gynecol Cancer 2007. The aim of this study is to assess the effect of epithelial and stromal tumor components on survival outcomes in FIGO stage III or IV ovarian carcinosarcomas (OCS) treated with primary surgery and adjuvant chemotherapy at the Northern Gynaecological Oncology Centre (NGOC), Gateshead. Women were identified from the histopathology/NGOC databases. Age, FIGO stage, details of histology, treatment, and overall survival were recorded. Of 34 cases (1994-2006, all FIGO stages), 17 were treated with primary surgery followed by adjuvant chemotherapy for FIGO stage III or IV. The median age was 66 years (52-85 years). Cytoreduction was optimal (n = 9) or complete (n = 1) in 10/17 (59%) cases. Epithelial predominant (EP) or stromal predominant (SP) tumor (defined as >50% of either component in the primary tumor) was noted in 12 and 5 cases, respectively. Epithelial types included serous (n = 9), endometrioid (n = 5), and mixed types (n = 3). Twelve women have died of disease. The median overall survival was 11.0 months (3-74 months). On univariate analysis, survival was not affected by optimal/suboptimal debulking, platinum/doxorubicin-containing chemotherapy, or homologous/heterologous stromal components. Stromal components (>25%) adversely affected survival (P = 0.02), and there was a trend to worse survival with serous compared with nonserous epithelial components (P = 0.07). Cox regression (multivariate analysis) showed that SP tumors (P = 0.04), suboptimal debulking (P = 0.01), age (P = 0.01), and tumors with serous epithelial component (P = 0.05) were adverse independent prognostic factors. Type of chemotherapy and homologous/heterologous components (P = 0.24) did not affect overall survival. In conclusion, our study suggests that SP-OCS have a worse survival outcome than EP tumors. Tumors with serous epithelial components adversely affected the survival compared with nonserous components. Larger studies are required to confirm these effects and to identify the optimum chemotherapy regimen for OCS.

Alberts, D. S., P. Y. Liu, et al. (2007). "Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211)." International Journal of Gynecological Cancer 17(4): 784-788.

Alberts DS, Liu PY, Wilczynski SP, Jang A, Moon J, Ward JH, Beck JT, Clouser M, Markman M. Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211). Int J Gynecol Cancer 2007;17:784-788. Platinum-resistant ovarian cancer continues to be a difficult therapeutic problem. Clearly, molecularly targeted agents should be evaluated in this patient population. Patients were eligible for this phase II study with stage III or IV ovarian cancer, whose tumor expressed Kit (CD117) or platelet-derived growth factor receptor (PDGFR) and with relapse of measurable disease within 6 months of completing frontline, platinum- and taxane-based chemotherapy. Patients were treated daily with 400 mg of imatinib mesylate orally. It was assumed that the agent would be of no further interest if the population response rate was less than 10%. A two-stage design was used for patient accrual. A total of 34 patients were registered to the study. Of these, 15 were found to be ineligible or not evaluable (8 because their tumor samples were negative for both DC117 and PDGFR). Of 19 evaluable patients, 2 (11%) tested positively for c-Kit and 17 (89%) tested positively for PDGFR. There were no objective responders. Thirteen patients (68%) had increasing disease or symptomatic deterioration, and six (32%) went off protocol during the first month due to adverse events. Median progression-free survival was 2 months (95% CI 1-3 months) and median overall survival was 10 months (95% CI 6-18 months). Eleven percent of patients experienced grade 4 hematologic/metabolic toxicity and 37% experienced grade 3 nonhematologic toxicity. We conclude that imatinib mesylate as a single agent does not appear to have useful clinical activity in c-Kit and/or PDGFR positive, recurrent ovarian cancer in heavily pretreated patients with ovarian cancer.

(2007). "POSTER SESSION ABSTRACTS." Asia-Pacific Journal of Clinical Oncology 3(s1): A25-A36

Huang, Y. T., K. G. Huang, et al. (2006). "Irradiation-induced uterine malignant mixed mullerian tumor." Taiwan J Obstet Gynecol 45(4): 353-5.

OBJECTIVE: To report a case of a patient with cervical squamous cell carcinoma stage IIIB who was diagnosed with malignant mixed müllerian tumor (MMMT) 5 years after radiotherapy. CASE REPORT: A 57-year-old female patient with cervical squamous cell carcinoma FIGO stage IIIB received pelvic irradiation for her disease. After radiotherapy, she was followed-up every 6 months. At 60 months, Papanicolaou smear revealed abnormal cancer cells and secondary MMMT was diagnosed. The patient underwent surgical treatment followed by chemotherapy. However, the cancer recurred 8 months after surgery and the patient died 1 month later. CONCLUSION: Patients with cervical cancer administered irradiation many years previously remain at high risk of secondary malignancies. In these cases, long-term follow-up with extreme caution is mandatory. For patients with any types of symptoms, aggressive and immediate investigation is suggested in order to detect possible occult malignancies.

Hudelist, G., K. Unterrieder, et al. (2006). "Malignant mixed Mullerian tumor with heterologous component arising in the fallopian tube--a case report." Eur J Gynaecol Oncol 27(5): 509-12.

Primary malignant mixed Müllerian tumors (MMMTs) of the fallopian tube are rarities in gynecologic oncology with only 26 cases of MMMTs with a heterologous component reported thus far. We report a case of FIGO Stage II primary MMMT of the fallopian tube with a heterologous tumor portion in an 80-year-old woman presenting with abdominal discomfort at the time of primary diagnosis. After performance of total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy follow-up examination three months postoperatively did not show signs of disease recurrence. The patient finally presented six months after the initial diagnosis with extensive intraabdominal metastasis and died several days thereafter. The present report supports the aggressive nature of these neoplasms. The efficacy of chemotherapy and radiation remains to be defined in future studies.

van Wijk, F. H., F. J. Huikeshoven, et al. (2006). "Stage III and IV endometrial cancer: a 20-year review of patients." International Journal of Gynecological Cancer 16(4): 1648-1655.

van Wijk FH, Huikeshoven FJ, Abdulkadir L, Ewing PC, Burger CW. Stage III and IV endometrial cancer: a 20-year review of patients. Int J Gynecol Cancer 2006;16:1648-1655. In advanced endometrial cancer, the importance of peritoneal cytology and optimal surgical cytoreduction remain subjects of discussion. We evaluated our clinical experience of 67 patients with FIGO stage III and IV endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period with an emphasis on stage IIIA disease based on positive cytology only and optimal cytoreduction. Lymphadenectomy was not routinely performed and peritoneal cytology was examined in 74% of the patients. Stage IIIA disease was found in 33 patients, 10 of whom had positive cytology only. Analysis showed that incidence of recurrence and survival rates of patients with stage IIIA disease based on positive cytology only were comparable with stage IIIA disease based on other factors. In 50 patients, it was possible to remove all macroscopic tumor, whereas in 17 patients, an optimal cytoreduction was not achievable. The 2- and 5-year survival rates after optimal cytoreduction were 82.2% and 65.6%; where this could not be achieved, these figures were 50.8% and 40.6%. In advanced endometrial cancer patients, positive peritoneal cytology seems an important prognostic factor in stage IIIA disease if lymph node status is unknown. Survival is improved if optimal surgical cytoreduction is achievable.

Vaidya, A. P., N. S. Horowitz, et al. (2006). "Uterine malignant mixed mullerian tumors should not be included in studies of endometrial carcinoma." Gynecol Oncol.

OBJECTIVE: Uterine mixed malignant mullerian tumors (MMMT) have traditionally been excluded from clinical trials of endometrial cancer because of a belief that they are more correctly included in the sarcoma category. Recently, investigators have suggested that uterine MMMTs are actually dedifferentiated epithelial tumors and should be treated as such. The current study was undertaken to compare outcomes, stage for stage, of uterine MMMT with poor prognosis endometrial adenocarcinomas. METHODS: Cases of MMMT from 1996 to 2004 were identified from the Tumor Registry after IRB consent was obtained. Retrospective chart review was performed. Cases were matched by age, stage, performance status, and surgical procedure to controls consisting of grade 3 endometrioid, papillary serous, and clear cell endometrial carcinomas from the same time period. Overall survival was compared using the Log-Rank test. RESULTS: 68 patients with MMMT were identified. 23 were excluded due to incomplete records. Patients with MMMT ranged in age from 51 to 95 years (mean 75.3 years). Approximately half of the patients (53%) had stage III or IV disease. Of the controls, 31 (69%) had grade 3 endometrioid, 11 (24%) papillary serous, and 3 (7%) clear cell carcinoma. Median overall survival for all patients with MMMT was significantly shorter than for controls, 18 months (range 0.5-72) versus 36 months (range 0.5-123) (P = 0.02). Patients with early stage disease (stage I or II) had shorter median survival than controls, 26 months (range 3-7) vs. 95 months (range 4-123) (P = 0.003). There was no difference in median survival when comparing advanced disease (stage III or IV) to matched controls, 15 months (range 0.5-70) vs. 19 months (range 0.5-100) (P = NS). CONCLUSIONS: Patients with uterine MMMT have a poorer prognosis than those patients with high grade epithelial tumors, especially for those with early stage disease. Given the discrepancy in survival, these patients should not be included in studies of endometrial carcinoma. Further investigations are necessary to identify factors to improve survival of these patients.

Tangjitgamol, S., S. Manusirivithaya, et al. (2006). "Lymph node size in uterine cancer: a revisit." International Journal of Gynecological Cancer 16(5): 1880-1884.

Tangjitgamol S, Manusirivithaya S, Jesadapatarakul S, Leelahakorn S, Thawaramara T. Lymph node size in uterine cancer: a revisit. Int J Gynecol Cancer 2006;16:1880-1884. To study whether lymph node size is a good predictor of lymph node metastasis in uterine cancer, we reviewed the pathologic sections of pelvic and para-aortic lymph node removed from uterine cancer patients who underwent surgical staging in our institution from January 1994 to December 2004. The long axis of each individual node was measured. Out of 4280 total nodes obtained (178 cases), 86 nodes (28 cases) were positive for metastatic cancer (2.0% of total nodes or 15.7% of cases). Among the positive nodes, 11 nodes (12.8%) had nodal long axis <5 mm, 34 nodes (39.5%) had long axis of 5-9 mm, and 32 (37.2%) and 9 nodes (10.5%) had long axes of 10-19 mm and >20 mm, respectively. More than half (52.3%) of these positive nodal long axes were less than 10 mm. At lymph node size of 10 mm that was the common point of reference for pathologic enlargement, the sensitivity, specificity, negative and positive predictive value of lymph node to predict metastatic cancer were 47.7%, 76.7%, 98.6%, and 4.0%, respectively. From these findings, we tended to conclude that lymph node size is not a good predictor of lymph node metastasis in uterine cancer.

Robinson-Bennett, B., R. Z. Belch, et al. (2006). "Loss of p16 in recurrent malignant mixed mullerian tumors of the uterus." Int J Gynecol Cancer 16(3): 1354-7.

Uterine malignant mixed mullerian tumors (MMMTs) are rare and highly aggressive malignancies with poor clinical prognoses. We examined for differences in the oncoprotein profiles of primary versus recurrent MMMTs. Five cases of recurrent uterine MMMT were examined by paraffin immunohistochemistry for the expression of p53, p16, P-cadherin, and Cerb-B2. P16, p53, and P-cadherin were each expressed in 100%, 80%, and 60% of the primary cases, respectively. Three cases expressed all three oncoproteins. All five cases were negative for Cerb-B2. No difference in antigen expression was seen in the epithelial versus sarcomatous components. Primary and recurrent tumors were concordant for p53, P-cadherin, and Cerb-B2. However, three cases of recurrent tumors were negative for p16 expression. P53, p16, and P-cadherin are common tumor suppressor genes expressed in uterine MMMT. Interestingly, p16 protein expression was lost in some cases of MMMTs when they recurred. This suggests that the oncoprotein and possibly genetic profile of p16 changes over time. We did not observe any difference in antigen expression between areas of epithelial or sarcomatous differentiation, which would support a single pluripotential malignant clone in the histogenesis of these tumors.

Nur, S., L. Chuang, et al. (2006). "Immunohistochemical characterization of cancer antigen in uterine cancers." Int J Gynecol Cancer 16(5): 1903-10.

The pattern of cancer antigen (CA-125) expression by immunohistochemistry (IHC) was investigated in malignant and nonneoplastic endometrium in endometrial carcinoma. Ninety cases of primary uterine carcinomas (65 endometrioid [EM] carcinoma, 15 serous papillary [SP] carcinoma, 6 carcinosarcomas [malignant mixed müllerian tumors], and 4 clear cell carcinoma [CC]) and adjacent atrophic and/or hyperplastic endometrium were analyzed by IHC for CA-125 expression. The percentage and intensity of luminal, apical, basal, and diffuse cytoplasmic immunostaining of epithelial cells were categorized on a scale of 0-4. The immunoreaction score (IRS score) was calculated and correlated with the grade and stage of carcinoma according to the histologic type. CA-125 expression (3-4/4) was localized in apical borders of grade 1 and grade 2 EM carcinoma and was weak or negative (0-1/4) in grade 3 EM. Mucinous differentiation in EM was associated with intense luminal and apical staining. Squamous areas and stroma showed no staining at all. SP carcinoma and endometrial intraepithelial carcinoma showed much higher mean IRS score than EM. In malignant mixed müllerian tumors (MMMT), the epithelial component stained as above according to the type of epithelial cell differentiation of the neoplastic cells. Benign proliferative glands showed moderate apical luminal, basal, and cytoplasmic staining. Intense diffuse staining was observed in atypical complex hyperplasia. Different patterns of CA-125 immunostaining were observed in normal, hyperplastic, and neoplastic endometrium. IRS score correlated with the grade but not with the stage of EM carcinoma. The intense different staining pattern of endometrium with atypical complex hyperplasia suggests that CA-125 may be a useful diagnostic aid.

Mok, J. E., Y. M. Kim, et al. (2006). "Malignant mixed mullerian tumors of the ovary: experience with cytoreductive surgery and platinum-based combination chemotherapy." Int J Gynecol Cancer 16(1): 101-5.

This study reviews the clinical outcome and prognosis of patients with malignant mixed mullerian tumors (MMMTs) of the ovary treated with optimal cytoreductive surgery, leaving no residual disease, and platinum-based chemotherapy. Ten patients diagnosed with MMMT of the ovary after complete surgical staging from February 1993 to February 2004 at Asan Medical Center in Korea were studied retrospectively. All ten patients were treated with optimal cytoreductive surgery, leaving no gross residual disease. Seven patients received ifosfamide/cisplatin chemotherapy, and the remaining three patients received other platinum-based combination chemotherapy. Demographic data, pathologic findings, treatments, and survival time were reviewed. Of the ten patients, two were scored at FIGO stage IIC, seven were at stage IIIC, and one was at stage IV. The median survival time of all ten patients was 46 months. The overall survival rate was 60.0% at 1 year, 40.0% at 2 years, and 20.0% at 5 years. Platinum-based combination chemotherapy after optimal cytoreductive surgery may be effective in the treatment of ovarian MMMT.

Mitsuhashi, T., T. Itoh, et al. (2006). "Squamous cell carcinoma of the skin: dual differentiations to rare basosquamous and spindle cell variants." Journal of Cutaneous Pathology 33(3): 246-252.

Abstract: Basosquamous carcinoma (BSC) is defined as a tumor containing the areas of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a transition zone linking the two. Spindle cell squamous carcinoma (SCSC) may have a variable component of conventional SCC and spindle cells. We present a case of an 89-year-old woman with an eruption on the scalp for several decades. Grossly, the lesion measured 8.5 x 6.0 x 1.8 cm and consisted of a gray-white and focally black tumor. Microscopically, a non-ulcerated upper part of the tumor consisted of large polygonal squamoid cells with occasional keratinization (SCC), trabecular growth of basaloid cells with peripheral palisading (BCC), and an area in which both the components were intermingled. The rest of the tumor was a myxoid area with elongated fusiform spindle cells, which appeared to arise from conventional SCC. Immunohistochemically, the tumor cells in the SCSC (both conventional and spindle cell) area co-expressed CAM5.2, and vimentin. Ber-EP4 was positive in the BCC area with the transition zone of SCC and BCC showing diminished staining. Epithelial membrane antigen was focally positive in the conventional SCC area. To our knowledge, this is the first case report of SCC of the skin that has dual differentiations to BSC and SCSC. Mitsuhashi T, Itoh T, Shimizu Y, Ban S, Ogawa F, Hirose T, Shimizu M. Squamous cell carcinoma of the skin: dual differentiations to rare basosquamous and spindle cell variants

Maheshwari, A., S. Gupta, et al. (2006). "Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix." World J Surg Oncol 4: 36.

ABSTRACT: BACKGROUND: Malignant mixed mullerian tumors (MMMT) are rare biphasic malignant neoplasm. The commonest site of their occurrence in female genital tract is body of the uterus. MMMT of the cervix is extremely rare. CASE PRESENTATION: We report the clinical, pathological and immunohistochemical profile and diagnostic difficulties in a case of giant MMMT of the cervix in a postmenopausal woman who presented with a large cervical mass. On microscopic examination, initially tumor appeared to be endometrial stromal sarcoma, however, immunohistochemical examination revealed the biphasic nature of the tumor. The malignant epithelial component was basaloid squamous carcinoma with homologous sarcomatous component. The patient was treated with surgery. However, she experienced vaginal vault recurrence four months after the initial treatment, which was successfully treated with pelvic radiotherapy. CONCLUSION: Accurate diagnosis of cervical MMMT is important for appropriate treatment of the patient.

Lee, C. B., H.-J. Choi, et al. (2006). "Cystadenoma of the seminal vesicle." International Journal of Urology 13(8): 1138-1140.

Abstract Primary tumors of the seminal vesicle are quite rare with most reported cases being carcinomas. However, benign tumors of the seminal vesicle are extremely rare. We report a case of a cystadenomas of the seminal vesicles in a 46-year-old asymptomatic man, which was detected incidentally by computed tomography.

Kuroda, N., T. Shiotsu, et al. (2006). "Female urethral adenocarcinoma with a heterogeneous phenotype. Case report." APMIS 114(4): 314-318.

Kuroda N, Shiotsu T, Ohara M, Hirouchi T, Mizuno K, Miyazaki E. Female urethral adenocarcinoma with a heterogeneous phenotype. APMIS 2006;114:314-8. We here report a very rare case of female urethral adenocarcinoma. A 77-year-old woman presented with urinary retention. Cystoscopy showed a urethral tumor and the biopsy material showed adenocarcinoma. Macroscopically, the tumor measuring 3.0x3.0x2.4 cm was predominantly observed around the periurethral area on the proximal side. Histologically, patterns of columnar/mucinous adenocarcinoma, clear cell adenocarcinoma and papillary/micropapillary carcinoma were observed, but there was no evidence of a cribriform pattern. Immunohistochemically, neoplastic cells of at least one of three components were positive for CK7 and CK20 or CA125. We suggest that female urethral adenocarcinoma with a histologically and immunohistochemically heterogeneous phenotype may originate from cells within urethral or paraurethral tissue, such as urethritis glandularis or intestinal metaplastic epithelium and Mullerian tissue.

Goto, M., Y. Nomura, et al. (2006). "Malignant mixed mullerian tumor in a rabbit (Oryctolagus cuniculus): case report with immunohistochemistry." Vet Pathol 43(4): 560-4.

A rabbit (Oryctolagus cuniculus) with a homologous malignant mixed mullerian tumor (MMMT) of the uterus with decidualization in the sarcomatous components is described. On histologic examination, the neoplasm was characterized by a carcinomatous and a sarcomatous component with invasion of the myometrium. The epithelial component was a well-differentiated carcinoma, and the nonepithelial component contained large amounts of intracytoplasmic glycogen. The changes in stromal cells were morphologically similar to changes usually found in decidual cells in the pregnant uterus or in deciduosarcomas in rabbits. Results of immunohistochemical analysis indicated that the epithelial components stained positive with cytokeratin (CK7, AE1/3) and the decidual-stromal cells stained positive for vimentin, but did not stain with alpha-SMA, actin, and desmin. This case fulfills all the criteria of an MMMT in having a carcinomatous and a sarcomatous component, but differs from cases of MMMT in women in that the sarcomatous component had decidualized. To the authors' knowledge, this is the first report of a malignant mixed mullerian tumor in rabbits.

Zhang, C., H. Cui, et al. (2005). "[Clinical management and prognostic analysis of primary peritoneal neoplasms]." Zhonghua Fu Chan Ke Za Zhi 40(7): 464-8.

OBJECTIVE: To investigate the clinical management strategies and prognostic factors of primary peritoneal neoplasms. METHODS: We retrospectively reviewed the clinical and pathological records of 24 cases with primary peritoneal neoplasms treated in the People's Hospital, Peking University during May 1995 and April 2004. RESULTS: Among 24 cases, 15 patients were diagnosed as serous papillary adenocarcinoma (9 highly and intermediately differentiated, and 6 lowly differentiated), 6 as mixed epithelial carcinoma and 3 as mixed malignant Mullerian tumor (MMMT). All patients underwent cytoreductive surgery, 21 cases having, suboptimal debulking one. Then they received a platinum-based chemotherapy. Thirteen cases received paclitaxel + cisplatin (TP) and 9 received cisplatin + doxorubicin + cyclophosphamide (PAC) combination chemotherapy. The primary response reached 80% (complete response 55% and partial response 25%). The median survival of all patients was 42 months (95% CI = 22-62 months). Survival for patients with primary peritoneal serous papillary carcinoma (PPSPC), mixed epithelial carcinoma and MMMT was 44, 19 and 13 months respectively, with a significant difference between PPSPC and MMMT (P < 0.05). Patients receiving TP combination also exhibited longer survival than those receiving PAC regimen (mean survival 75 vs 28 months, P < 0.05). CONCLUSIONS: Patients with primary peritoneal neoplasms should be treated with appropriate cytoreductive surgery. A primary surgical protocol is bilateral salpingo-oophorectomy and omentectomy. Overestimating an optimal debulking surgery may have no benefit on the survival. TP combination therapy may bring longer survival than PAC regimen. Histopathologic types and chemotherapy regimens are the essential factors of the prognosis.

Wang, X., S. Tangjitgamol, et al. (2005). "Response of recurrent uterine high-grade malignant mixed mullerian tumor to letrozole." Int J Gynecol Cancer 15(6): 1243-8.

Uterine malignant mixed mullerian tumor (MMMT) is a rare malignancy occurring most often in postmenopausal women. Despite the use of multimodality treatments including surgery, chemotherapy, and radiotherapy, prognosis is still poor in most cases. We report the case of a 69-year-old woman with recurrent metastatic high-grade MMMT that responded to letrozole, an aromatase inhibitor. At the initial diagnosis of high-grade uterine MMMT in February 2001, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative pelvic radiotherapy. Two years later, an asymptomatic retroperitoneal mass was discovered on surveillance abdominal computed tomography scanning. The 3.5- x 3.0-cm mass was considered inoperable owing to its location near the aorta at the level of the renal vessels. The patient declined radiation or chemotherapy. Treatment with letrozole was begun at 2.5 mg daily. Serial computed tomography scans demonstrated marked tumor shrinkage; after 11 months of letrozole therapy, the tumor had shrunk to less than 25% of its original volume. Further study of letrozole for high-grade uterine MMMT is warranted.

Sotiropoulou, M., D. Haidopoulos, et al. (2005). "Primary malignant mixed mullerian tumor of the vagina immunohistochemically confirmed." Arch Gynecol Obstet 271(3): 264-6.

CASE REPORT: We report the case of a 74-year old woman who presented with an ulcerated mass of the vagina. Histology of the tumor showed malignant mixed mullerian tumor (MMMT) with squamous and spindle cell stromal components, associated with high-grade vaginal intraepithelial neoplasia (VaIN 3). Immunohistochemical study of the neoplasm revealed that the malignant stromal tumor was a high-grade leiomyosarcoma. Despite the multimodal therapeutic approach, the patient died within 11 months. CONCLUSION: The vagina is a rare site of presentation of primary MMMTs and the present case is the second one immunohistochemically confirmed.

Sharma, N. K., J. I. Sorosky, et al. (2005). "Malignant mixed mullerian tumor (MMMT) of the cervix." Gynecol Oncol 97(2): 442-5.

OBJECTIVES: To characterize the clinical characteristics, therapeutic options, and potential outcomes in patients diagnosed with malignant mixed mullerian tumor (MMMT) of the uterine cervix. METHODS: Five women ranging in age from 25 to 66 (mean 49.6 years) were diagnosed with MMMT of the cervix and treated at the University of Iowa Hospitals and Clinics between 1986 and 2001. Data were retrospectively analyzed from available charts and pathological reports with particular attention to patient demographics, presenting symptoms, treatment, and follow-up. RESULTS: Abnormal vaginal bleeding was a common presenting symptom in all but one patient, in whom an abnormal screening Pap smear was the primary reason for referral. FIGO disease staging at initial diagnosis included two patients with stage IB1 (ages 29 and 66 years), two patients with stage IB2 (ages 25 and 64 years), and one patient with stage IVB (age 64 years) MMMT of the cervix. Organ-confined, early stage lesions (stages IB1 and IB2) responded well to regimens of either surgery alone or surgery plus radiation therapy, with no evidence of recurrent disease at last follow-up 28, 35, 42, and 65 months later, respectively. The lone patient with advanced stage IVB disease, however, was unresponsive to both external beam radiation therapy and ifosfamide chemotherapy, and succumbed to disease within 5 months. CONCLUSIONS: Cervical MMMT is an uncommon disease, but long-term survival is possible in organ-confined early stage disease with primary therapy.

Shaco-Levy, R., N. Sion-Vardy, et al. (2005). "Primary peritoneal malignant mixed mullerian tumor associated with colonic adenocarcinoma." Eur J Gynaecol Oncol 26(5): 509-10.

BACKGROUND: Primary extragenital malignant mixed Mullerian tumors (MMMTs) are very rare neoplasms, with only 28 documented cases in the literature. Two cases coexisted with a colonic adenocarcinoma. CASE: We report on a primary peritoneal MMMT diagnosed shortly after resection of a colonic adenocarcinoma in an 85-year-old woman who presented with a large omental mass. Microscopic examination revealed a biphasic tumor with malignant carcinomatous and sarcomatous components, confirmed immunohistochemically, consistent with MMMT. Despite optimal debulking and uneventful postoperative recovery, the patient died of her disease shortly after surgery due to recurrent disseminated disease. CONCLUSIONS: This is the third case in the literature of primary extragenital MMMT occurring in association with colonic adenocarcinoma. This coexistence may be incidental, but it may also imply a possible linkage between these two tumors.

Ramondetta, L. M. (2005). "Novel strategies for the management of uterine malignant mixed mullerian tumors." International Journal of Gynecological Cancer 15(2): 405-405.

Uterine malignant mixed mullerian tumors (MMMTs), also referred to as carcinosarcomas, have historically been viewed and treated like uterine sarcomas. The present understanding of this tumor type is shifting toward that of uterine epithelial tumors. The fact that the epithelial component of uterine MMMTs is often the most influential in terms of survival is responsible for this shift. The best treatment for uterine MMMTs has yet to be determined. Yet given the poor response rates and high recurrent rates associated with current therapies, it is critical to increase the number of treatment options. First and foremost, future trials must evaluate sarcomas with different histologies individually. The histological, clinical, and molecular differences among sarcoma subtypes must be recognized. Second, the best treatment may be combined regional systemic therapy after optimal surgical debulking of the tumor. We know that adjuvant pelvic radiotherapy decreases the risk of pelvic recurrence. As more effective systemic and molecular therapy is developed to control microscopic distant disease, the role of radiation therapy to control locoregional disease in the pelvis and abdomen may become more important. Future research should consider programs that integrate surgery, radiation, chemotherapy, and molecularly directed therapy to maximize the probability of cure.

N'Kanza, A. L., S. Jobanputra, et al. (2005). "Central nervous system involvement from malignant mixed Mullerian tumor (MMMT) of the uterus." Arch Gynecol Obstet 273(1): 63-8.

The central nervous system is traditionally considered as an uncommon site for metastatic disease from the female genital tract, and cerebral metastasis as the primary manifestation of an occult gynecological malignancy is even more rare. Here, we report the case of a 61-year-old female who presented with neurological symptoms of confusion, headache, cerebellar ataxia and right-sided weakness. Magnetic resonance imaging of the brain revealed two solid lesions in the frontal lobe and the left cerebellar hemisphere. Endometrial biopsy of a uterine mass detected during search for the primary lesion showed malignant mixed Mullerian tumor (MMMT). The patient refused surgery. Cranial radiotherapy for progressive cerebral disease led to resolution of her neurological symptoms. Two months after the diagnosis of MMMT the patient died from local complications of advanced pelvic disease. At autopsy, only the epithelial component of the tumor had metastasized to the brain. Attention should be paid to possibility of unusual distant metastases associated to MMMT in order to avoid delay in diagnosis and treatment of these patients.

Mikami, M., Y. Kuwabara, et al. (2005). "Malignant mixed müllerian tumor of primary mesenteric origin." International Journal of Gynecological Cancer 15(6): 1249-1253.

Abstract. Mikami M, Kuwabara Y, Tanaka K, Komiyama S, Ishikawa M, Hirose T. Malignant mixed mullerian tumor of primary mesenteric origin. Int J Gynecol Cancer 2005;15:1249-1253. Malignant mixed mullerian tumor (MMMT) is a rare tumor. A literature search revealed very few reports on MMMT, especially those arising in the peritoneum. We recently encountered an MMMT of primary mesenteric origin associated with left fallopian tube cancer. There have been no previous reports about its occurrence in the mesentery. When cases of peritoneal MMMT were reviewed, the disease was found to be associated with synchronous or metachronous gynecologic tumors of mullerian duct origin (ie, ovarian tumors, primary serous carcinoma of the peritoneum, fallopian tube cancer, endometrial cancer, and adenocarcinoma of the cervix) in 12 out of 32 patients (37.5%). Peritoneal MMMT are frequently associated with gynecologic tumors.

Kuroda, N., T. Moriki, et al. (2005). "Malignant müllerian mixed tumor (carcinosarcoma) of the fallopian tube: an immunohistochemical study of neoplastic cells. Case report." APMIS 113(9): 643-646.

Kuroda N, Moriki T, Oguri H, Maeda N, Toi M, Miyazaki E, Hiroi M, Fukaya T, Enzan H. Malignant mullerian mixed tumor (carcinosarcoma) of the fallopian tube: an immunohistochemical study of neoplastic cells. Case report. APMIS 2005;113:643-6. The patient was a 65-year-old woman who complained of lower abdominal pain. Salpingo-oophorectomy and hysterectomy were performed due to suspicion of ovarian cancer. At surgery a polypoid mass was observed in the fimbria of the left fallopian tube. Histologically, proliferation of undifferentiated neoplastic cells with marked cytological atypia predominated in the tumor. Proliferation of rhabdomyoblastic cells or spindle cells, as well as adenocarcinoma arising from the mucosa of the fallopian tube, was observed. A diagnosis of malignant mullerian mixed tumor (MMMT) was made. CD10 was expressed in adenocarcinoma, undifferentiated, spindle and rhabdomyoblastic cells. Furthermore, rhabdomyoblastic cells were positive for desmin and myoglobin. Undifferentiated and spindle neoplastic cells were focally positive for ASMA and negative for h-caldesmon. Finally, our preliminary report suggests that MMMT of the fallopian tube may contain immature smooth muscle cells or cells with the myofibroblast-like immunohistochemical phenotype in the undifferentiated component.

Hara, N., M. Kawaguchi, et al. (2005). "Mixed epithelial and stromal tumor of the kidney in a 12-year-old girl." Pathology International 55(10): 670-676.

Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare kidney neoplasm that almost exclusively occurs in perimenopausal women, and long-term estrogen replacement is relevant to its pathogenesis. Herein is described an atypical case of MESTK uncovered in a 12-year-old premenarcheal girl without a history of prior estrogen use. On surgical specimen it was found that the well-circumscribed tumor measuring 14 cm arose from the lower pole of the right kidney, showing solid and fibrous-cystic areas. Microscopically, it was composed both of epithelial structures similar to renal tubules and stroma comprising non-specific spindle cells. Some intratumoral tubules showed affinities to distal-nephron-specific lectins, and those immunoreactive for proximal-tubule-specific CD15 were also present. In addition, primitive ductal structures were reactive both for CD15 and lectins, but immature epithelial elements typical of nephroblastoma were absent. Spindle cells were positive for actin, desmin and vimentin, and expressed progesterone and estrogen receptors. The tumor was comparable with MESTK, although some epithelia were associated with the immunophenotype of proximal tubules. The patient was free of disease postoperatively for 40 months. In the present case, remnants of the primitive periductal mesenchyme might be promoted to neoplastic cells by a sex-steroid surge during puberty.

Gagner, J. P. and K. Mittal (2005). "Malignant mixed Mullerian tumor of the fimbriated end of the fallopian tube: origin as an intraepithelial carcinoma." Gynecol Oncol 97(1): 219-22.

BACKGROUND: A paucity of examples of malignant mixed Mullerian tumors (MMMT) of the fimbriated end of the fallopian tube has been reported. CASE: We report a first case of FIGO Stage IV primary MMMT, heterologous type, in the right fimbria of a 77-year-old woman associated with symptomatic pleural spread who succumbed with recurrent disease 12 months after resection and postoperative paclitaxel and carboplatin chemotherapy. CONCLUSIONS: The identification of intraepithelial carcinoma in this tumor lends support to a role of the epithelial component in fimbrial MMMT histogenesis as seen for MMMT at other anatomic sites. Comparison of the clinical management of these tumors shows prolonged survival of patients whose treatment included postoperative pelvic external radiotherapy.

Fine, S. W., M. P. Lisanti, et al. (2005). "Caveolin-3 is a sensitive and specific marker for rhabdomyosarcoma." Appl Immunohistochem Mol Morphol 13(3): 231-6.

Caveolin-3 (Cav-3) is a principal structural protein of caveolae membrane domains. Animal studies have revealed that Cav-3 is expressed in skeletal and cardiac myocytes but absent in other types of cells. Recent studies have shown that abnormalities in the Cav-3 gene are associated with some forms of muscular dystrophy, while skeletal muscle abnormalities have been observed in Cav-3 transgenic and knockout mice. In this study the authors evaluated the distribution of Cav-3 in normal human tissues and compared the expression of Cav-3 with that of myogenin and myoD1 in rhabdomyosarcoma (RMS), malignant mixed mullerian tumor (MMMT), and an array of neoplasms that mimic RMS to assess the utility of Cav-3 as a diagnostic marker for tumors with skeletal muscle differentiation. In nonneoplastic human tissues, crisp membrane staining for Cav-3 was present in cardiac and skeletal myocytes and occasionally in arterial smooth muscle cells and prostatic stromal cells, while other cell types were negative for Cav-3. Eighty-eight percent (21/24) of RMS studied were positive for Cav-3. Positive staining was generally observed in the more maturely differentiated tumor cells but not the primitive tumor cells. Eight of nine cases of MMMT stained strongly with Cav-3 in their rhabdomyosarcomatous component but not in other components. Fifty-four other neoplasms (13 leiomyosarcomas, 8 neuroblastomas, 5 lymphomas, 6 Wilms tumors without skeletal muscle differentiation, 5 Ewing sarcomas, 4 malignant fibrous histiocytomas, 4 angiosarcomas, 6 malignant melanomas, and 3 synovial sarcomas) were negative for Cav-3 expression. Nearly all (96% [23/24]) cases of RMS were positive for myogenin, while 88% (21/24) were positive for myoD1. Primitive tumor cells showed significantly increased expression of myoD1 and myogenin; conversely, more differentiated tumor cells were negative or weakly stained. The rhabdomyosarcomatous component of MMMT stained focally with myogenin and myoD1, in contrast to the strong Cav-3 labeling in these cells. These results demonstrate that Cav-3 is specifically expressed in human cardiac and skeletal myocytes. Furthermore, its high specificity and relatively high sensitivity (88%) for tumors with skeletal muscle differentiation suggest that Cav-3 is a valuable marker for these tumors and may be used to assess the degree of differentiation of RMS and to identify residual tumor cells in post-chemotherapy specimens.

Evert, M., E. Wardelmann, et al. (2005). "Abdominopelvic perivascular epithelioid cell sarcoma (malignant PEComa) mimicking gastrointestinal stromal tumour of the rectum." Histopathology 46(1): 115-117.

Eftekhar, Z., P. Rahimi-Moghaddam, et al. (2005). "Non-puerperal uterine inversion caused by uterine sarcoma." The Australian and New Zealand Journal of Obstetrics and Gynaecology 45(1): 82-83.

Caudell, J. J., M. T. Deavers, et al. (2005). "Imatinib mesylate (gleevec)--targeted kinases are expressed in uterine sarcomas." Appl Immunohistochem Mol Morphol 13(2): 167-70.

The purpose of this study was to determine whether 3 tyrosine kinases known to be inhibited by imatinib mesylate are expressed in a variety of uterine sarcomas. The authors assessed c-kit, abl, and platelet-derived growth factor receptor-beta (PDGFR-beta) expression in 8 endometrial stromal sarcomas (ESSs), 5 leiomyosarcomas (LMSs), 4 high-grade endometrial sarcomas (HGESs), and 21 malignant mixed mullerian tumors (MMMTs). Tissue sections were stained with commercially available antibodies for c-kit, abl, and PDGFR-beta. Staining intensity was described as 0 (no staining), +1 (weak), +2 (moderate), and +3 (strong). Positive staining was defined as moderate to strong if found in more than 10% of tumor cells. Expression of c-kit ranged from 0% in LMSs to 25% in HGESs. Protein expression of abl was more significant, ranging from 25% in LMSs and ESSs to 43% in MMMTs. Only 1 LMS sample stained focally for abl (+1). Abl expression was observed in only the carcinomatous elements of the MMMTs, with diffuse staining in the cytoplasm and nucleus. In most, the staining intensity was +2. All tumors stained positive for PDGFR-beta. MMMT samples showed PDGFR-beta expression in both the carcinomatous and sarcomatous portions. In all samples, staining for PDGFR-beta was concentrated at the cell membrane and diffusely in the cytoplasm. These results indicate that many uterine sarcomas express 1 or more of the kinases targeted by imatinib mesylate and that further investigation of imatinib as a therapy for uterine sarcomas is warranted.

Auranen, A., S. Hietanen, et al. (2005). "Hormonal treatments and epithelial ovarian cancer risk." International Journal of Gynecological Cancer 15(5): 692-700.

Abstract. Auranen A, Hietanen S, Salmi T, Grenman S. Hormonal treatments and epithelial ovarian cancer risk. Int J Gynecol Cancer 2005;15:692-700. Exogenous sex hormones are widely used by women either for pregnancy prevention, as part of infertility treatment, or for treatment of menopausal symptoms. The role of these hormones in the development of ovarian cancer has been vastly explored. The protective effect of combined oral contraceptive pill is confirmed in multiple studies, but it is not clear whether this protection also covers women with a genetic predisposition to ovarian cancer. There is no conclusive evidence of infertility treatments increasing ovarian cancer risk, but infertility as such is a risk factor. Currently available data suggest that long-term users of hormone replacement therapy may have a slightly increased risk for ovarian cancer compared to women who have never used estrogen. The risk might particularly involve the endometrioid type of ovarian cancer. Most data on ovarian cancer and estrogen comes from epidemiological studies, since the normally high concentrations of estrogens in ovarian tissue and follicular fluid make direct biologic studies on the effects of exogenous estrogens on the ovarian cell difficult. This review discusses the risk of ovarian cancer associated with the use of sex steroid hormones, with special emphasis on the possible risk associated with estrogens.

Taranger-Charpin, C., S. Carpentier, et al. (2004). "[Immunohistochemical expression of PTEN antigen: a new tool for diagnosis of early endometrial neoplasia]." Bull Acad Natl Med 188(3): 415-27; discussion 427-9.

We examined immunohistochemical PTEN protein expression in endometrial samples obtained from perimenopausal women with uterine bleeding in order to diagnose early endometrial neoplasia. Paraffin sections of endometrial samples (biopsies, endometrium resection, hysterectomy) were reviewed and tested for immunocytochemical PTEN expression by epithelial cells. Immunohistochemical studies were performed with the Ventana Benchmark device and the immunoperoxidase technique with monoclonal anti-PTEN (6H2.1/Cascade Biosciences). We studied 45 samples of proliferative endometria, 42 samples of atypical hyperplasia (neoplasia), and 55 samples of endometrial carcinomas (30 endometrioid, 5 serous papillary, 10 clear cell, 5 adenosquamous, and 5 MMMT). A strong positive PTEN immunoreaction was observed in all 45 normal proliferative endometria, 2/30 endometrioid carcinomas, and 23/25 non endometrioid carcinomas. In contrast, PTEN immunoexpression was negative or weak in 40/42 atypical hyperplasia and 28/30 endometrioid carcinomas. Negative or weak PTEN expression correlated with endometrial neoplasia (atypical proliferation) (p < 0.001). Thus (i) PTEN immunoexpression in endometrial paraffin sections is a new diagnostic tool, distinguishing PTEN-positive cyclic abnormal monoclonal proliferative endometrium (anovulatory, non atypical, simple and complex hyperplasia) from PTEN-negative (or decreased) endometrial neoplasia, and especially early endometrial neoplasia (atypical simple and complex hyperplasia, in situ carcinoma, superficial carcinoma with focal invasion). (ii) Given the lack of reproducibility of histological identification of atypical (precancerous invasive) and non atypical (precancerous non invasive) endometrial hyperplasia, the new criteria (PTEN-negative crowded glands, gland/stroma ratio > 55%, nuclear pleomorphism, in areas > 1 mm) recently proposed to diagnose early endometrial neoplasia appear to be clinically relevant.

Park, H. M., M. H. Park, et al. (2004). "Mullerian adenosarcoma with sarcomatous overgrowth of the cervix presenting as cervical polyp: a case report and review of the literature." International Journal of Gynecological Cancer 14(5): 1024-1029.

An aggressive variant of adenosarcoma, mullerian adenosarcoma with sarcomatous overgrowth (MASO) in the cervix is extremely rare. This variant contains obvious, high-grade sarcoma in addition to a low-grade form. In this report, we describe a case of MASO of the uterine cervix and review the clinical and pathological features of these tumors. The patient was a 37-year-old woman with a cervical polypoid mass, which was morphologically considered as a benign endocervical polyp. Microscopically, polypoid cervical mass showed diffuse and dense malignant spindle cell proliferation around the benign endocervical glands and also an area of markedly anaplastic and pleomorphic spindle cell proliferation, so called, sarcomatous overgrowth. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection were performed. The patient has been followed-up and neither chemotherapy nor other adjuvant therapies have been administered. At present, she has been clinically free of disease for 9 months since she received surgery. It is extremely rare that MASO of the uterine cervix is presented in premenopausal woman. Gynecologists and pathologists should be aware of the difficulties associated with a delay in the diagnosis of MASO when the tumor is present as a benign looking cervical polyp.

Muller, H. and V. Nakchbandi (2004). "Cytoreductive surgery plus intraperitoneal hyperthermic perfusion is an effective treatment for metastasized malignant mixed mesodermal tumours (MMMT)--report of six cases." Eur J Surg Oncol 30(5): 573-7.

BACKGROUND: Malignant mixed mesodermal tumours (MMMT) of the female genital tract are rare and heterogeneous malignancies that impart grim prognosis. These tumours are characterized by an admixture of malignant epithelial and stromal elements comprising carcinomatous and sarcomatous neoplastic cells. Thus far, almost 350 cases of MMMT have been recorded in the international medical literature. Due to its rarity, there is no agreement on the best treatment strategy in women with metastasized MMMT. METHODS: Six women (mean age 59 years) with metastasized MMMT defined to the peritoneal cavity have been treated by cytoreductive surgery plus hyperthermic peritoneal perfusion plus postoperative adjuvant chemotherapy. All patients have been pre-treated by surgery for primary tumour and one by systemic chemotherapy. As cytostatics for hyperthermic peritoneal perfusion, we have used Mitomycin in a dosage of 18 mg/m2 plus Melphalan in a dosage of 25 mg/m2. As adjuvant treatment CDDP 40 mg/m2/dl, Mitomycin 7 mg/md2/dl and Ifosfamid 100 mg/kg 24 h/dl was applicated via intraaortic catheter three times with a treatment free interval of 3 weeks. RESULTS: A complete cytoreduction without remnant tumour formations in the peritoneal cavity could be carried out in all six patients. The postoperative course was uneventful in all cases except for one where a spontaneous small bowel perforation and prolonged gall secretion had to be treated by re-operation. One patient died 4 months later by pneumonia without evidence of disease. Four patients are without evidence of disease after 2, 4, 14 and 19 months, whereas one patient developed liver metastases after 9 months still treated by systemic chemotherapy. CONCLUSION: Complete cytoreduction plus hyperthermic peritoneal perfusion plus adjuvant chemotherapy seems to be an effective treatment for recurrent or metastasized MMMT. Further studies have to define the value of this new treatment strategy for this rare tumour entity.

Lim, B. J., J. W. Kim, et al. (2004). "Malignant mixed müllerian tumor of fallopian tube with multiple distinct heterologous components." International Journal of Gynecological Cancer 14(4): 690-693.

Lim BJ, Kim JW, Yang WI, Cho NH. Malignant mixed mullerian tumor of fallopian tube with multiple distinct heterologous components. We experienced a case of primary malignant mixed mullerian tumors (MMMTs) of the fallopian tube of FIGO stage I. In addition to endometrioid adenocarcinomas, multiple apparent heterologous elements encompassing myxoid chondrosarcoma, osteosarcoma, myxoid liposarcoma, and well-differentiated angiosarcoma were recognized separately in each nodule. Those findings that divergent sarcomatoid differentiations are apparently present masquerading malignant mesenchymoma have not been described in MMMTs of the female genital tract.

Koshiyama, M., M. Ueta, et al. (2004). "Müllerian adenosarcoma arising from the uterine cervix." Acta Obstetricia et Gynecologica Scandinavica 83(3): 315-316.

Ivy, J. J. and J. B. Unger (2004). "Malignant mixed mullerian sarcomas of the uterus--the LSUHSC Shreveport experience." J La State Med Soc 156(6): 324-6.

OBJECTIVE: To evaluate our experience with malignant mixed mullerian sarcomas of the uterus (MMMT) and the clinical factors affecting survival. STUDY DESIGN: The records of 18 women with MMMT who received treatment at our hospital between 1989-2002 were reviewed. We analyzed factors influencing survival such as stage, presence of heterologous components, and post-operative radiation. Survival analysis was performed using Kaplan-Meier survival curve. RESULTS: All women underwent surgical tumor debulking. Eleven women were Stage I, three were Stage II, two were Stage III, and two were Stage IV. Five women had tumors with heterologous elements. As expected, survival was most influenced by stage of disease, with the best overall survival in women with Stage I tumors, P < 0.001. Cumulative 5-year survival was 60% for Stage I disease, for Stage II, 34%, and 0% for Stage III and Stage IV. CONCLUSIONS: The initial stage of women presenting with MMMTs is the most important predictive factor for survival.

Hubalek, M., A. Ramoni, et al. (2004). "Malignant mixed mesodermal tumor after tamoxifen therapy for breast cancer." Gynecol Oncol 95(1): 264-6.

BACKGROUND: The risk of tamoxifen related endometrial neoplasm has been confirmed by multiple studies. Especially rare endometrial tumors seem to develop more frequently under tamoxifen therapy. A recent analysis showed a substantially higher risk for malignant mixed mesodermal tumor (MMMT; designated in the WHO classification of female genital tract neoplasms as carcinosarcoma) in association with tamoxifen intake. CASE: We are reporting a case of a 40-year-old multiparous premenopausal woman who received tamoxifen 20 mg daily for 2 years after the surgical treatment of breast cancer and subsequent adjuvant chemotherapy. Two years after initiation of tamoxifen treatment, the patient developed an MMMT of the uterus. More than 64 months after radical hysterectomy, salpingo-oophorectomy, and pelvic lymphadenectomy, she remains recurrence-free for MMMT. Unfortunately, she developed a local recurrence of her breast cancer in 2003. After surgical treatment, she is currently being treated with anastrozole. CONCLUSION: We are reporting a rare case of a premenopausal patient who developed a MMMT within short time of tamoxifen exposure for stage I breast cancer.

Hsieh, C. L., T. C. Chang, et al. (2004). "Excellent progression-free survival with liposomal doxorubicin for a patient with recurrent ovarian malignant mixed mullerian tumor: case report and literature review." Gynecol Oncol 94(3): 854-7.

INTRODUCTION: Ovarian malignant mixed mullerian tumor (MMMT) is a rare, highly aggressive, fatal disease. Patients have a median survival of 18 months and a 5-year survival rate of only 8%. Optimal cytoreduction surgery plus platinum-based combination chemotherapy are associated with better outcomes. CASE REPORT: A 65-year-old patient of stage IIIc ovarian MMMT having obtained a 41-month remission after four courses of aggressive surgical debulking procedures, platinum-containing chemotherapy, and intraoperative radiotherapy suffered from multi-focal recurrences and obtained another 22-month progression-free survival after treatment with monthly liposomal doxorubicin (Lipo-Dox) for 14 courses and Lipo-Dox/carboplatin for subsequent 6 courses without obvious toxicity. DISCUSSION: Liposomal doxorubicin might be useful as salvage chemotherapy for heavily pretreated, recurrent ovarian MMMT. A prospective trial is needed for more proof.

Hanprasertpong, J., V. Wootipoom, et al. (2004). "Non-puerperal uterine inversion and uterine sarcoma (malignant mixed müllerian tumor): Report of an unusual case." Journal of Obstetrics and Gynaecology Research 30(2): 105-108.

Abstract A 45-year-old woman with a history of cervical cancer (stage IIa), who had received complete radiation treatment 16 years previously, presented with a huge mass protruding from her vaginal introitus. She had had the condition for about 1 week. Diagnosis was difficult, and she elected to have a diagnostic laparoscopic procedure plus tumor removal. The pathologic investigation revealed a malignant mixed mullerian tumor of the endometrium. Post-operative course was uneventful. She underwent postoperative pelvic radiation. No recurrence was found during the 13 months follow up period. This rare case of chronic non-puerperal uterine inversion due to malignant mixed mullerian tumor (MMMT) is herein reported.

Ciris, M., Y. Erhan, et al. (2004). "Inhibin and expression in ovarian stromal tumors and their histological equivalences." Acta Obstetricia et Gynecologica Scandinavica 83(5): 491-496.

Inhibin is a heterodimeric protein hormone that appears to be a sensitive immunohistochemical marker of sex cord-stromal tumors. Although sex cord-stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. The purposes of this study were to examine inhibin alpha and beta immunoreactivity in a wide range of gonadal stromal neoplasms and to assess its value in the differential diagnosis of problematic tumors. A total of 108 paraffin-embedded ovarian and extraovarian tumors were examined immunohistochemically by using anti-alpha inhibin and anti-beta inhibin. Inhibin alpha immunostaining was identified in 46 (81%) of 57 gonadal stromal tumors, one (14%) of seven endometrial stromal tumors, and one (50%) of two primary ovarian carcinoid tumors. Inhibin beta immunostaining was detected in 55 (96%) of 57 gonadal stromal tumors, two (29%) of seven endometrial stromal tumors, one (50%) of two dysgerminomas, and in all of two (100%) primary ovarian carcinoid tumors. Inhibin alpha expression was not detected in any ovarian surface epithelial tumor cells. Some surface epithelial tumors showed stromal inhibin alpha (15% of cases) and inhibin beta (48% of cases) positivity. Weak immunoreactivity for inhibin beta was found in most (83% of cases) ovarian surface epithelial tumors. Two ovarian Burkitt lymphomas were negative for inhibin alpha and beta. Inhibin alpha is a sensitive immunohistochemical marker of gonadal stromal tumors and is of value in the differential diagnosis of ovarian neoplasia. Inhibin beta is a nonspecific marker for ovarian neoplasms, showing expression on tumor and stromal cells of different epithelial or stromal tumors.

Callister, M., L. M. Ramondetta, et al. (2004). "Malignant mixed Mullerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome." Int J Radiat Oncol Biol Phys 58(3): 786-96.

PURPOSE: To determine the survival outcomes, prognostic factors, and patterns of failure in patients with malignant mixed Mullerian tumor (MMMT) of the uterus. METHODS AND MATERIALS: Between 1954 and 1998, 300 patients with clinical Stage I-III MMMT of the uterus were treated with curative intent at The University of Texas M. D. Anderson Cancer Center. Their hospital records were reviewed to obtain patient and tumor characteristics; details of surgery, radiotherapy (RT), and chemotherapy; and long-term outcome. Surviving patients were followed for a median of 109 months (range 15-138). Survival rates were calculated using the Kaplan-Meier method, with differences assessed by log-rank tests. RESULTS: Of the 300 patients, 113 (38%) were treated with surgery alone, 160 (53%) with surgery plus adjuvant EBRT or ICRT, and 27 (9%) with RT alone. Forty-eight patients received adjuvant chemotherapy. At 5 years, the overall rates of survival and cause-specific survival were 31% and 33%, respectively. Women who were postmenopausal or had a history of prior pelvic RT, pain at presentation, clinical Stage II-III disease, uterine enlargement (>/=12 weeks), or an abnormal Papanicolaou smear finding had a significantly poorer prognosis than the other patients in the series. Of the 273 patients who underwent surgery, those who had positive abdominal washings, uterine length >10 cm, or extrauterine spread of disease to the cervix, adnexa, or peritoneum had a significantly worse prognosis than the other patients. Factors found on multivariate analysis to have an independent adverse influence on cause-specific survival included postmenopausal status (p = 0.0007, relative risk [RR] 3.3), uterine length >10 cm (p = 0.0001, RR 2.2), cervical involvement (p = 0.002, RR 1.8), and peritoneal involvement (p = 0.0001, RR 4.3). At 5 years, the rates of pelvic and distant disease recurrence for the entire group of 300 patients were 38% and 57%, respectively. The most common site of distant recurrence was the peritoneal cavity. Patients treated with pelvic RT had a lower rate of pelvic recurrence than patients treated with surgery alone (28% vs. 48%, p = 0.0002), but the overall survival rates (36% vs. 27%, p = 0.10) and distant metastasis rates (57% vs. 54%, p = 0.96) were not significantly different. However, patients treated with pelvic RT had a longer mean time to any distant relapse (17.3 vs. 7.0 months, p = 0.001) than patients treated with surgery alone. The use of adjuvant chemotherapy did not correlate with the survival rate or rate of distant metastasis. CONCLUSION: Adjuvant pelvic RT decreased the risk of pelvic recurrence and may delay the appearance of distant metastases after hysterectomy for MMMT. However, the survival rates remain poor because of a high rate of distant recurrence. As more effective systemic chemotherapy is developed to control microscopic distant disease, the role of RT in controlling locoregional disease in the pelvis and abdomen may become more important. Future research should consider programs that integrate surgery, RT, and chemotherapy to maximize the probability of cure.

Brown, E., M. Stewart, et al. (2004). "Carcinosarcoma of the ovary: 19 years of prospective data from a single center." Cancer 100(10): 2148-53.

BACKGROUND: A review of clinicopathologic features and outcome in women with carcinosarcoma of the ovary (also known as malignant mixed mesodermal tumor [MMMT]) compared with a group of women with serous adenocarcinoma (SAC) of the ovary was conducted. METHODS: Between 1984 and 2002, 1568 patients with epithelial ovarian carcinoma and 70 patients with ovarian carcinosarcoma underwent treatment at the Edinburgh Cancer Centre. Analysis was performed on 65 patients with MMMT, and 746 patients with SAC were selected as a group for comparison. Baseline variables were recorded prospectively and response to chemotherapy and progression-free and cause-specific survival between the groups were compared. RESULTS: Patients with carcinosarcoma had a mean age of 66.6 years, which is significantly older than those with SAC (62.0 years) (P < 0.001). The objective response rate to platinum-based chemotherapy was found to be significantly lower in patients with carcinosarcoma (25% vs. 60%; P = 0.02). Cause-specific survival in the carcinosarcoma group was poor and significantly shorter than that observed in the SAC group (median survival of 8.2 months vs. 20.7 months; P < 0.0001). Progression-free survival in patients with carcinosarcoma also was found to be significantly shorter compared with patients with SAC (median progression-free survival of 6.4 months vs. 12.1 months; P < 0.001). Achieving optimal debulking at the time of initial surgery was found to be a highly significant factor in patients with carcinosarcoma with regard to determining outcome (median survival of 14.8 months for patients with optimally debulked International Federation of Gynecology and Obstetrics Stage III disease vs. 3.1 months for patients with suboptimally/nondebulked Stage III disease; P < 0.001). CONCLUSIONS: Ovarian carcinosarcoma is a distinct entity with a poor prognosis. Patients with carcinosarcoma differ from those with SAC with regard to having an older mean age of onset, an inferior response to platinum-based chemotherapy, and worse progression-free and cause-specific survival. The extent of benefit from chemotherapy is unclear.

Bague, S., I. M. Rodriguez, et al. (2004). "Malignant mesonephric tumors of the female genital tract: a clinicopathologic study of 9 cases." Am J Surg Pathol 28(5): 601-7.

Nine malignant mesonephric tumors were obtained from the consultation files of one of the authors (J.P.) over a 13-year period (1988-2001). There were 4 adenocarcinomas (ACs) and 5 malignant mixed mesonephric tumors (MMMTs). The ACs were found in the cervix (3) and vagina (1). The MMMTs involved the uterus (1), cervix (3), and vagina (1). Most patients presented with abnormal vaginal bleeding. The 4 patients with mesonephric AC ranged in age from 24 to 54 years (mean, 41 years). The tumors measured 2 to 6 cm (mean, 3.7 cm). Two ACs were stage I and two were stage II. Two of the three patients with follow-up information were alive without clinical evidence of disease at 3 and 11.5 years, and the other was alive with recurrent tumor 8.5 years postoperatively. The 5 patients with MMMTs ranged in age from 37 to 62 years (mean, 49 years). The mean size of four tumors was 5.2 cm (range, 3.5-8 cm). The uterine MMMT infiltrated the entire myometrial wall extending to the endometrial cavity where it resembled an endometrial polyp. Although the most common histologic pattern in the current series was the glandular (ductal) pattern, retiform, tubular, and solid growth patterns were also encountered. Among the MMMT subgroup, the sarcomatous component was homologous in 3 cases (endometrial stromal or spindle cell) and heterologous in the other 2 cases (skeletal muscle and cartilage). Of the 4 patients with follow-up information available, 1 (stage II) died of disease 7 months after surgery, another (stage IV) was alive with bone metastases at 3.3 years, and the other 2 patients (stages IB and IC) had no clinical evidence of disease at 1 and 3.7 years, respectively. Evidence of mesonephric hyperplasia was found in 5 (42%) cases. The MMMT that arose in the corpus presented as an endometrial polyp. In this case, histologic differential diagnosis includes serous carcinoma, endometrial stromal sarcoma, and uterine tumor resembling ovarian sex cord-stromal tumor. Immunostainings are not helpful. Mesonephric ACs often present in early stage and have better prognosis than their mullerian counterparts. Surgery alone appears to be the treatment of choice. In contrast, MMMTs may present in advanced stage and are aggressive tumors, similar to malignant mixed mullerian tumors.

Yan, W. E. I., K. H. Burns, et al. (2003). "Genetic engineering to study testicular tumorigenesis." APMIS 111(1): 174-183.

In humans, Sertoli cell tumors account for approximately 4% of all testicular tumors, and 20% of these are malignant. The mechanisms underlying Sertoli cell tumorigenesis remain largely unknown. Using gene knockout technology, we previously generated mutant mice lacking the alpha subunit of inhibin dimers. The inhibin alpha-null male mice develop testicular Sertoli cell tumors with 100% penetrance. These tumors develop as early as 4 weeks of age and cause a cachexia-like wasting syndrome. Castrated inhibin alpha knockout mice develop sex steroidogenic adrenal cortical tumors. These studies have identified inhibins as secreted tumor suppressors with specificity for the gonads and adrenal glands. It had been suggested that endocrine factors play roles in Sertoli cell tumorigenesis by altering cell cycle machinery of the Sertoli cells. To test the potential of these factors to function as modifiers of Sertoli cell tumorigenesis, we have employed a genetic intercross strategy, breeding inhibin alpha mutant mice with mutant mice deficient in endocrine signaling factors including gonadotropin releasing hormone (hypogonadal, hpg mice), follicle stimulating hormone, anti-Mullerian hormone (MH), activin receptor type II, or androgen receptor (testicular feminization, tfm mice), or mice overexpressing follistatin. We are also investigating the effects of loss of critical cell cycle regulators, such as cyclin dependent kinase inhibitor p27, on Sertoli cell tumorigenesis in inhibin alpha knockout males. These studies clearly demonstrate the roles of these factors as modifiers of the Sertoli cell tumorigenesis. Activin signaling through activin receptor type II is responsible for the cachexia-like syndrome observed in the inhibin alpha knockout mice with tumors. The gonadotropin hormones are essential for testicular tumor development, but elevated FSH levels are not sufficient to cause Sertoli cell tumors. Absence of FSH, lack of androgen receptor, or overexpression of follistatin slows the tumor growth and minimizes the cachexia symptoms, thus prolonging the life span of these double mutant mice. In contrast, absence of AMH or p27 causes earlier onset and more aggressive development of testicular tumor, with an earlier death of double mutant mice. We are currently investigating roles of estrogen signaling pathways, and other cell cycle regulators, in tumor development in the inhibin alpha knockout mice by generating mice with double or triple mutations. Genetic engineering in mouse models provides a powerful tool to study the mechanisms of testicular tumorigenesis and define the important genetic modifiers in vivo.

Teleman, S., D. Scripcaru, et al. (2003). "[Malignant mixed mesodermal tumor: histo- and cytopathologic correlations]." Rev Med Chir Soc Med Nat Iasi 107(3): 650-3.

To correlate the cytopathological and the histopathological findings in uterine mixed mesodermal malignant tumor (MMMT) we have examined the cervical smear, endometrial curettage and hysterectomy specimen of a patient diagnosed with uterine tumor. The smear was stained by Papanicolaou staining and the tissue processed by routine technique and stained H&E. The original cytological diagnosis was adenosquamous carcinoma. The histopathological diagnosis was MMMT of heterologous type. A review of the smear revealed features which may orientate the diagnosis: multinucleate cells, isolated cells with cyanophilic cytoplasm, hyperchromatic nuclei and prominent nucleoli, elongated cyanophilic cells of sarcomatous origin. We conclude that the cytopathological diagnosis of the MMMT in cervical smears is very difficult. This may be sustained by the evidence of more cell types and cellular features orientating to a sarcomatous origin. The most important differential diagnosis is adenosquamous carcinoma.

Takeuchi, K., Y. Tsuzuki, et al. (2003). "Malignant mixed Mullerian tumor of the ovary growing into an inguinal hernia sac: report of a case." Surg Today 33(10): 797-800.

Malignant tumors presenting as an inguinal hernia are rare. We present the case of a malignant mixed Mullerian tumor (MMMT) of the ovary growing into an inguinal hernia sac. In this case, magnetic resonance imaging was useful in making a diagnosis of an ovarian neoplasm growing into the inguinal canal, and to the best of our knowledge, this is only the tenth case of a malignant ovarian tumor and the first case reported in the English-language literature of MMMT of an ovary which grew into an inguinal hernia sac.

Szybinski, Z., B. Huszno, et al. (2003). "Incidence of thyroid cancer in the selected areas of iodine deficiency in Poland." J Endocrinol Invest 26(2 Suppl): 63-70.

The aim of the study was to evaluate the incidence rate (IR), trend and histotype of the differentiated thyroid cancer in the selected areas with varying iodine deficiency. The study was carried out in three areas: Krakow, (Carpathian endemic goiter area with 1.99 million mixed rural and urban population), Gliwice (Upper Silesia--moderate iodine deficiency area mostly industrial with 4.89 million inhabitants) and Olsztyn (slight iodine deficiency area, mainly rural with 0.77 million inhabitants). Between 1990 and 2001, in the study area 2691 newly diagnosed cases of malignant neoplasms of the thyroid gland were registered. In over 80% of patients it was differentiated thyroid cancer: mainly in women over 40 years, with F/M ratio 5.8. The highest percentage of papillary cancer 72.9% was observed in Olsztyn and lowest--50.0%--in Krakow and Nowy Sacz districts. In this period of time incidence rate of differentiated thyroid cancer in women increased in Krakow, Gliwice, and Olsztyn from 1.51 to 9.34 in 1998 1.27 to 5.74 in 1999 and from 2.52 to 11.35 in 2001 respectively. In the youngest (0-20 years) age group no significant increase of IR was observed. Between 1998 and 2001 the dynamics of increase of the thyroid cancer incidence markedly diminished. In conclusion it was hypothesised that an increase in IR of differentiated thyroid cancer in the study area was caused mainly by the suspension of iodine prophylaxis in 1980 and was diminished by the introduction of an obligatory model of iodine prophylaxis in 1996/1997. It was modified in terms of histotype and dynamics of increase by exposure to ionizing radiation. A very specific group at risk on the population level were women aged 20-40 years in the reproductive age exposed to iodine deficiency after suspension of iodine prophylaxis in 1980 and to radiation after the Chernobyl accident in 1986.

Seidman, J. D. and S. Chauhan (2003). "Evaluation of the relationship between adenosarcoma and carcinosarcoma and a hypothesis of the histogenesis of uterine sarcomas." Int J Gynecol Pathol 22(1): 75-82.

The terminology of uterine sarcomas is confusing and has been inconsistently applied. The relationships among the various types of uterine sarcomas are unknown. To elucidate the relationship between carcinosarcoma (malignant mullerian mixed tumor) and adenosarcoma, a series of 26 consecutive endometrial carcinosarcomas was evaluated for the presence of an adenosarcoma-like component. Four of 26 carcinosarcomas (15%) had an adenosarcoma-like component. The clinical and pathologic features of these tumors were otherwise similar to ordinary endometrial carcinosarcomas. A histogenetic schema for uterine sarcomas is proposed, interrelating endometrial stromal sarcomas, adenosarcomas with and without sarcomatous overgrowth, and poorly differentiated sarcoma not otherwise specified. Although most carcinosarcomas are accepted as being metaplastic or sarcomatoid carcinomas, it is suggested that the carcinomatous component of 8% to 16% of carcinosarcomas arise within, or in the endometrium adjacent to, an adenosarcoma. This latter group is then integrated into the histogenetic schema. Observations based on our data and the limited data in the literature that support this hypothesis include: 13% of endometrial carcinosarcomas have gross and microscopic features of collision tumors, 13% have an adenosarcoma-like component, 16% have a low-grade stroma, and approximately 8% are biclonal indicative of a collision tumor. The most parsimonious interpretation of these data indicates that approximately 8% to16% of endometrial carcinosarcomas arise because of malignant transformation of the epithelial component within, or in the endometrium adjacent to an adenosarcoma.

Rushing, R. S., S. Shajahan, et al. (2003). "Uterine sarcomas express KIT protein but lack mutation(s) in exon 11 or 17 of c-KIT." Gynecol Oncol 91(1): 9-14.

OBJECTIVE: Several tumors express the protein product of the protooncogene c-KIT. Some of these respond to imatinib mesylate, a tyrosine kinase inhibitor. The tumors that respond frequently have mutation(s) in exon 11 of c-KIT that encodes for the regulatory juxtamembrane helix. Some tumors that express KIT protein have mutation(s) in exon 17 of c-KIT; however, these do not respond to imatinib mesylate. This investigation was performed to determine the expression of KIT protein and mutational status of exons 11 and 17 of c-KIT in uterine sarcomas. METHODS: Twenty-five uterine sarcomas treated from 1990 to 2002 were evaluated. These included 14 malignant mullerian mixed tumors (MMMT), 7 leiomyosarcomas (LMS), 2 endometrial stromal sarcomas (ESS), and 2 high-grade heterologous sarcomas (HGHS). Formalin-fixed, paraffin-embedded tissue sections were immunostained with anti-KIT antibody (Santa Cruz Biotechnology, Santa Cruz, CA) with a semiquantitative assessment. Normal myometrium when present in the section was used as an internal negative control. Areas of tumor were microdissected followed by DNA extraction, polymerase chain reaction (PCR) amplification of exons 11 and 17, single-strand conformational polymorphism (SSCP), and DNA sequencing to detect the presence of mutation(s). RESULTS: All 25 tumors expressed KIT protein at varying levels as assessed by immunohistochemistry. The staining was diffuse and of moderate to strong intensity in 22 tumors. In three tumors (one of each type except MMMT) the staining intensity was weak. In MMMT the epithelial and sarcomatous foci stained similarly. No mutation(s) in exons 11 or 17 of c-KIT were identified in 24/25 tumors. One LMS had deletion of both exons 11 and 17. CONCLUSIONS: Although uterine sarcomas express KIT protein, they lack KIT-activating mutation(s) in exon 11 or 17 of c-KIT. Therefore, these tumors are unlikely to respond to imatinib mesylate.

Ramondetta, L. M., T. W. Burke, et al. (2003). "A phase II trial of cisplatin, ifosfamide, and mesna in patients with advanced or recurrent uterine malignant mixed mullerian tumors with evaluation of potential molecular targets." Gynecol Oncol 90(3): 529-36.

OBJECTIVE: The aim of this study was to determine the efficacy of cisplatin, ifosfamide, and mesna in uterine malignant mixed mullerian tumor (MMMT) and to evaluate the expression of clinically relevant molecular markers. METHODS: Women with advanced or recurrent MMMT were treated every 28 days with cisplatin (75 mg/m(2)), ifosfamide (1.2 gm/m(2)), and mesna (240 mg/m(2)). Treatment continued until disease progression or for six courses in the case of nonmeasurable disease. Immunohistochemical analysis for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, C-kit, Abl, and PDGFR-beta expression were performed. RESULTS: Sixteen patients received 1-10 cycles; 2 died of disease progression after 1 cycle; 3 stopped after 1 cycle because of toxicity. Of 6 with measurable disease, 2 had a partial response, 1 had stable disease (SD), and 3 had progression (RR 33%). Partial response durations were 6 and 9 months; SD duration was 6 months. Of 5 patients without measurable disease, 4 received 6 cycles; 1 received 4 cycles. Four died of recurrent disease and 1 was without disease 6.5 years after treatment. Thirty-six percent experienced at least one neutropenic G3 or G4 event. All experienced G1 gastrointestinal toxicity. Four required dose reductions. At 7.5 months, only 1 with measurable disease was still living. Immunohistochemical analyses revealed that 24% expressed ER or PR, 19% expressed HER-2/neu, and none expressed C-kit. However, 45% expressed Abl and 100% expressed PDGFR-beta. CONCLUSION: Although the combination of cisplatin, ifosfamide, and mesna in patients with MMMT had moderate activity, the high toxicity and short response duration in this uncommon, aggressive malignancy suggest that this regiment continues to be a disappointing treatment choice for uterine MMMT. HER-2/Neu, Abl, or PDGFR-beta expression may be of value in order to investigate novel multimodality treatment strategies.

Park, S.-H., J. Y. Ro, et al. (2003). "Perivascular epithelioid cell tumor of the uterus: Immunohistochemical, ultrastructural and molecular study." Pathology International 53(11): 800-805.

A case of perivascular epithelioid cell tumor of the uterus is reported, occurring in a 32-year-old woman. The tumor (8.0 cm in dimension) showed exophytic growth from the outer half of the myometrium. Histopathologically, the tumor was composed of thick blood vessels and perivascular epithelioid cells. The neoplastic cells were strongly immunoreactive for HMB45 antigen, CD117 (c-kit), vimentin and the progesterone receptor, but completely negative for S-100 protein, smooth muscle actin, desmin, CD34, the estrogen receptor and p16. The Ki-67 labeling index was low (1.25%). Ultrastructurally, the neoplastic cells had numerous premelanosomes with some glycogen deposits. Single-stranded DNA conformational polymorphism of p53 and methylation-specific polymerase chain reaction of p16 revealed negative results. Definite melanosomes on electron microscopic analysis and coexpression of HMB45 antigen and stem cell factor receptor (CD117) may provide the clue to understanding perivascular epithelioid cell tumor because angiomyolipoma also coexpresses HMB45 antigen and CD117.

Oosterhuis, J. W. and L. H. J. Looijenga (2003). "Current views on the pathogenesis of testicular germ cell tumours and perspectives for future research: Highlights of the 5th Copenhagen Workshop on Carcinoma in situ and Cancer of the Testis." APMIS 111(1): 280-289.

This review article highlights the most important contributions presented at the 5th Copenhagen Workshop on Carcinoma in situ and Cancer of the Testis, which was held in Denmark, August 29-31, 2002. The major themes that emerged at the meeting are critically discussed and perspectives for future research in this field are presented.

Ng, J. S., A. C. Han, et al. (2003). "Oncoprotein profiles of primary peritoneal malignant mixed mullerian tumors." Int J Gynecol Cancer 13(6): 870-4.

Primary peritoneal malignant mixed mullerian tumors (MMMTs) are extremely rare and highly aggressive malignancies associated with poor clinical prognoses. We present a clinicopathologic review of three cases of this rare tumor by examining expression of selected oncoproteins by immunohistochemistry. Three consecutive cases of primary peritoneal MMMT were examined by paraffin immunohistochemistry for expression of p53, p16, BCL2, CerbB2, and classical cadherins E-cadherin, P-cadherin, and N-cadherin. All three cases expressed p16, but showed less consistent expression of other markers, with one case expressing p53 and one expressing BCL2. All cases were negative for membrane expression of Cerb-B2. The three classical cadherins were expressed in two cases with one case showing only weak N- and P-cadherin expression. No difference in antigen expression was seen in the epithelial compared to sarcomatous components. We conclude that p16 may be a common tumor suppressor gene expressed in peritoneal MMMT. P53 overexpression may be of lesser frequency in peritoneal MMMT compared to MMMT from the ovary and the uterus. We did not observe any difference in antigen expression between areas of epithelial or sarcomatous differentiation, which would support a single pluripotential malignant clone in the histogenesis of these tumors.

Neuber, K., U. Reinhold, et al. (2003). "Second-line chemotherapy of metastatic malignant melanoma with intravenous treosulfan: a phase II multicentre trial." Melanoma Res 13(1): 81-5.

The purpose of this multicentre phase II trial was to evaluate time to progression, survival time, rate of objective tumour response and toxicity of second-line intravenous treosulfan chemotherapy in stage IV melanoma patients. Thirty-one patients with measurable stage IV malignant melanoma and prior chemotherapy with a dacarbazine-containing regimen were included. Of this group, 26 patients were evaluable. All patients received treosulfan (8 g/m intravenously on day 1; cycle repeated every 28 days up to six courses). Patients were evaluated for tumour response, survival time and toxicity. No objective responses (complete or partial) were observed. Five patients (19%) showed no change and 21 had progressive disease after treosulfan treatment. Four patients experienced a minor or mixed response. The median time to progression was 1.8 months (95% confidence interval [CI] 1.6-2.1 months) and the median overall survival was 6.5 months (95% CI 3.1-10 months). The 1 year survival rate was 33.9% (95% CI 15.4-52.3%). Leukocytopenia and thrombocytopenia (Common Toxicity Criteria grades 3 and 4) occurred in 15% and 18% of cases, respectively. The non-haematological toxicity of this outpatient regimen was mild. In conclusion, intravenous treosulfan treatment does not induce objective response rates when used as a second-line treatment of metastatic malignant melanoma.

McCluggage, W. G., S. Delaloge, et al. (2003). "Letter to the Editor and reply." International Journal of Gynecological Cancer 13(5): 697-698.

Jaeckle, K. A., K. R. Hess, et al. (2003). "Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study." J Clin Oncol 21(12): 2305-11.

PURPOSE: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. PATIENTS AND METHODS: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. RESULTS: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%). CONCLUSION: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).

Inthasorn, P., P. Beale, et al. (2003). "Malignant mixed mullerian tumour of the ovary: prognostic factor and response of adjuvant platinum-based chemotherapy." Aust N Z J Obstet Gynaecol 43(1): 61-4.

OBJECTIVES: The purpose of the present study was to analyse retrospectively the data of a series of patients presenting to our unit with malignant mixed mullerian tumour (MMMT) of the ovary to identify the prognostic factors and relate them to survival. The role of platinum-based chemotherapy in the adjuvant treatment of this tumour was also evaluated. METHODS: All patients diagnosed with MMMT of the ovary from 1987 to 2000 were identified from the gynaecological tumour registry of King George V Hospital, Australia. The effect of clinical and histopathological variables on survival was analysed. The response of platinum-based adjuvant chemotherapy after surgery was also evaluated. RESULTS: Twenty patients with MMMT of the ovary were identified. Of the six patients with measurable disease, two (33%) had complete response after adjuvant platinum-based chemotherapy. The median survival of all patients was 8 months, while that of the patients receiving adjuvant platinum-based chemotherapy was 23 months. Women who were older (> 65 years) had a significantly worse survival rate than those who were younger (P = 0.02). The patients with optimal debulking had a better median survival than those with suboptimal debulking, but this difference was not statistically significant (P = 0.21). Sarcomatous component (homologous vs heterologous) was not found to be a significant prognostic factor for predicting survival. CONCLUSIONS: Malignant mixed mullerian tumour of the ovary is a rare and aggressive gynaecological tumour. The current study indicates that patient age was a significant prognostic factor for survival and surgical cytoreduction combined with platinum-based chemotherapy is the most effective management regimen identified to date to treat MMMT of the ovary.

Gunawan, B., D. Baumhoer, et al. (2003). "Polysomy 8 in three cases of homologous malignant mixed Mullerian tumors of the uterus." Anticancer Res 23(2B): 1379-83.

Unique genetical gain of 8q and/or polysomy 8 identified after short-term culture are presented in three cases of malignant mixed Mullerian tumors (MMMT) of the uterus. All tumors revealed abnormal karyotypes and modal chromosome numbers in the hyperdiploid range. Two out of three cases exclusively demonstrated numerical aberrations, most prominently polysomy 8. One tumor revealed tetrasomy 8 as the sole aberration. The third tumor showed a more complex karyotype, including two unbalanced translocations, leading to partial gain of 8q. These cytogenetic findings, together with 14 previously reported cases of MMMT and 5 cell lines, suggest a distinct subgroup of endometrial MMMT characterized by gain of chromosome 8 or 8q.

Demirag, F., S. Topcu, et al. (2003). "Malignant pleomorphic adenoma (malignant mixed tumor) of the trachea: a case report and review of the literature." Eur Arch Otorhinolaryngol 260(2): 96-9.

A case of malignant mixed tumor of the trachea in a 56-year-old man is described. His tumor was removed by segmental tracheal resection, and end-to-end anastomosis was performed. Histologically, the tumor was characterized by a biphasic composition showing admixtures of epithelial elements in varying proportions; these were cytologically atypical with prominent mitotic figures. However, stromal elements were osteoid and mixoid with a benign appearance. The patient had no evidence of disease in the head and neck region and had no history of previous surgery for a salivary gland tumor. These findings were interpreted as indicative of malignant pleomorphic adenoma of the trachea.

Cryns, P., N. J. Roofthooft, et al. (2003). "Malignant mixed mullerian tumor of the ovary and false negative punctures." Eur J Gynaecol Oncol 24(1): 70-2.

Malignant mixed mullerian tumour (MMMT) of the ovary is a rare and aggressive tumour with a poor prognosis. We present a case of a 57-year-old woman with a large pelvic mass, omental cake, ascites and pleural effusions, clinically highly suspect of an ovarian neoplasm. Paracentesis and ultrasound-guided biopsy of the ovary were negative for malignant disease. Therefore a CT-guided true cut biopsy was performed. The latter gave a histopathologic diagnosis of an endometrioid adenocarcinoma of the ovary. However after cytoreductive surgery anatomopathologic examination revealed a malignant mixed mullerian tumour of the ovary with heterologous differentiation. Apparently only one of the two components was found in the puncture. Adjuvant chemotherapy, active against the sarcomatous and the carcinomatous component, was given. At present the patient is well and disease free 35 months after the initial diagnosis. Cytological examination of ascites may be negative in the presence of malignant disease. If a tumour consists of two components, puncture can miss one, which may lead to undertreatment. Punctures should be discouraged as a diagnostic tool in patients in whom an ovarian malignancy is suspected.

Casey, M. B., J. L. Caudill, et al. (2003). "Cervicovaginal (Papanicolaou) smear findings in patients with malignant mixed Mullerian tumors." Diagn Cytopathol 28(5): 245-9.

Malignant mixed Mullerian tumor is a rare neoplasm that occurs most frequently in elderly patients. It is characterized by a mixture of malignant epithelial and sarcomatous components. Little has been published about Papanicolaou smear findings pertaining to malignant mixed Mullerian tumors. We present our experience, with an emphasis on cytologic detail. Nine patients (median age, 65 yr) met our study criteria. All available smears and surgical specimens were reviewed. Four smears were positive for malignancy, with a sensitivity of 44% (3 adenocarcinoma, and 1 squamous-cell carcinoma, small-cell type). The results of our study showed that Papanicolaou smear findings pertaining to malignant mixed Mullerian tumors are seen in patients with advanced-stage disease with involvement of the lower uterine segment or cervix. The usual finding is large numbers of high-grade epithelial malignant cells in a necrotic background. The mesenchymal component rarely sheds cells visible on Papanicolaou smear. Diagn. Cytopathol. 2003;28:245-249. Copyright 2003 Wiley-Liss, Inc.

Burns, B. A., J. P. Geisler, et al. (2003). "Malignant mixed mullerian tumor of the ovary and bilateral breast cancer: an argument for BRCA3, or a coincidental cluster of unconnected cancers?" Gynecol Oncol 91(2): 426-8.

OBJECTIVES: Malignant mixed mullerian tumors (MMMTs) of the ovary are a rare, aggressive subtype of ovarian cancer without a clear relationship to familial breast-ovarian cancer syndromes. CASE: We present the case of a woman with bilateral breast cancers who subsequently developed a stage IIIc MMMT of the ovary. The patient had a first-degree female relative with breast and ovarian cancer (not MMMT), as well as second- and third-degree female relatives each with bilateral breast cancers. BRCA1 and BRCA2 sequencing of germline DNA revealed no evidence of a heritable mutation. CONCLUSIONS: Ovarian MMMTs may be a hallmark of breast/ovarian cancer secondary to genetic risk independent of classic BRCA1/2 pathways.

Arstad, E., P. Hoff, et al. (2003). "Studies on the synthesis and biological properties of non-carrier-added [(125)i and (131)i]-labeled arylalkylidenebisphosphonates: potent bone-seekers for diagnosis and therapy of malignant osseous lesions." J Med Chem 46(14): 3021-32.

Arylalkylidenebisphosphonates labeled with nca [(125)I or (131)I] have been synthesized and their biological function investigated. The label was attached to the aromatic group in high yield and under mild conditions by means of iododesilylation. The bone affinities of the radioactive compounds were investigated in normal Balb/C mice. The compound 1-hydroxy(m-iodo[(125,131)I]-phenylethylidene)-1,1-bisphosphonate was found to possess superior bone affinity compared to others, and its in vivo deiodination was insignificant. The uptake in femur 24h after injection was 850 +/- 265% and 986 +/- 118% of injected dose per gram tissue times gram body weight in mice and rats, respectively. The therapeutic potential of the compound was investigated in two tumor models in athymic (nude) rats, one model for mixed lytic/sclerotic metastatic bone-lesions originating from breast cancer and the other model simulating osseous osteosarcoma. The effects in these models compare favorably to those observed for established treatment modalities. The experiments demonstrate that radioiodinated bisphosphonates may have a potential for diagnosis and therapy of malignant osseous lesions.

Abd-Elaziz, M., J.-i. Akahira, et al. (2003). "Nuclear receptor DAX-1 in human common epithelial ovarian carcinoma: An independent prognostic factor of clinical outcome." Cancer Science 94(11): 980-985.

DAX-1 is a member of the nuclear receptor superfamily and is thought to be involved in the regulation of steroidogenesis. Its expression has been detected primarily in endocrine neoplasms such as adrenocortical as well as pituitary tumors in human, but its biological roles have not been examined well in sex steroid-dependent neoplasms. The aim of this study is to detect the expression of DAX-1 in common epithelial ovarian carcinomas in order to evaluate its possible biological significance. DAX-1 immunoreactivity was examined using immunohistochemistry. The correlation between the status of DAX-1 immunoreactivity and clinicopathological parameters and disease-free survival of the patients in a series of 60 cases of common epithelial ovarian carcinoma was examined. The status of DAX-1 immunoreactivity was evaluated using H score. DAX-1 immunoreactivity was widely detected in the nuclei of common epithelial ovarian carcinoma cells. There was a significant positive correlation between DAX-1 immunoreactivity and clinical staging (P=0.0241), tumor grade (P=0.0115), the residual size of the tumor (P=0.0014) and Ki-67 labeling index (P=<0.0001). In univariate survival analysis, a significant association was detected between DAX-1 immunoreactivity and shortened patient survival (P=0.0157). Other significant prognostic parameters were clinical stage, residual size of tumor and Ki-67. In multivariate analysis, DAX-1 immunoreactivity, clinical stage, residual size of tumor and Ki-67 all turned out to be independent prognostic factors for shortened survival. In conclusion, DAX-1 immunoreactivity is considered to be a new independent marker of poor prognosis or adverse clinical outcome in patients with epithelial ovarian carcinoma, possibly through altering in situ steroids production.

Cura, M. A., M. Blanco, et al. (2002). "Axillary metastasis from a malignant mullerian mixed tumor." Breast J 8(5): 305-6.

Chatzistamou, I., A. V. Schally, et al. (2002). "Expression of growth hormone-releasing hormone in human primary endometrial carcinomas." Eur J Endocrinol 147(3): 381-6.

BACKGROUND: Hypothalamic GH-releasing hormone (GHRH) regulates GH release from the pituitary, but an ectopic production of GHRH has been detected in various non-hypothalamic tissues, especially cancers. OBJECTIVE: To investigate whether endometrial tumors produce GHRH. METHODS: Twenty-four endometrioid, three serous papillary (SP), three mixed type endometrioid/serous papillary adenocarcinomas and one malignant mixed Mullerian tumor (MMMT) were assessed for GHRH immunoreactivity by the polyclonal anti-rabbit antibody SV95 and for the expression of GHRH mRNA by in situ hybridization using an oligonucleotide probe. RESULTS: Increased GHRH immunoreactivity was detected in 15 out of 24 (63%) of the endometrioid tumors, including two out of three (66%) of the mixed type endometrioid/serous adenocarcinomas but not in the three SP or the MMMT tumor. Cytoplasmic staining was detected in all positive cases, while in three of them strong nuclear localization of GHRH was also revealed. In situ hybridization indicated the presence of GHRH mRNA in six cases, all characterized as positive for GHRH immunoreactivity. CONCLUSION: GHRH is expressed in a subset of endometrial tumors, of the endometrioid type in particular. A paracrine/autocrine role for GHRH in the development of the disease should be considered.

Ho, S. P. and T. H. Ho (2002). "Malignant mixed Mullerian tumours of the uterus--a ten-year experience." Singapore Med J 43(9): 452-6.

OBJECTIVES: To review the clinico-pathological features of malignant mixed Mullerian tumours of the uterine corpus, their prognosis and treatment outcome. METHODS: A retrospective study of malignant mixed Mullerian tumours of the uterus seen at KK Women's & Children's Hospital from January 1989 to December 1998. RESULTS AND CONCLUSION: Twenty-six patients with mean age of 56.5 years were analysed. Twenty (76.9%) were menopausal. None had previous pelvic irradiation. Vaginal bleeding and uterine enlargement were the commonest presenting symptom and sign. Diagnostic dilatation and curettage obtained the diagnosis in 15 patients. Majority of patients had surgery with adjuvant chemotherapy, while adjuvant radiotherapy was offered only recently. Positive peritoneal washings were significantly associated with advanced disease.There were seven patients with stage I, four with stage II, nine with stage III and four with stage IV disease. There were 17 homologous and nine heterologous tumours. Presence of heterologous stromal components did not influence the stage of the disease. Increasing depth of myometrial invasion was associated with poorer survival. Prognosis of patients with stage III and IV disease were poor, with none surviving to two years. All the patients with stage I disease were still alive at the end of the study period. In conclusion, malignant mixed Mullerian tumours of the uterine corpus are aggressive tumours associated with poor prognosis.

Manolitsas, T. P., S. Abdessalam, et al. (2002). "Chylous ascites following treatment for gynecologic malignancies." Gynecol Oncol 86(3): 370-4.

BACKGROUND: Chylous ascites is a rare complication following abdominal radiation or para-aortic lymph node dissection in the management of gynecologic malignancies. Treatment options include dietary restriction with addition of medium-chain triglycerides, serial paracenteses, total parenteral nutrition, and somatostatin. Current opinion advocates that surgical exploration and peritoneo-venous shunts be reserved for refractory cases. CASES: Two patients developed chylous ascites, one after completion of surgical staging and chemoradiation for stage IIB squamous carcinoma of the cervix and one following para-aortic lymph node dissection for recurrent malignant mixed mullerian tumor of the endometrium. In both cases resolution of the chylous ascites followed placement of a peritoneo-venous shunt. CONCLUSIONS: Chylous ascites should be considered in the differential diagnosis of ascites in patients with gynecologic malignancy treated with radiation or para-aortic lymph node dissection.

Mikami, Y., S. Hata, et al. (2002). "Expression of CD10 in malignant mullerian mixed tumors and adenosarcomas: an immunohistochemical study." Mod Pathol 15(9): 923-30.

CD10 has been demonstrated to be positive in endometrial stromal sarcoma (ESS) and thus is useful in establishing the diagnosis, but its expression in malignant mullerian mixed tumor (MMMT) and mullerian adenosarcoma remains to be clarified. In this study, 12 cases of MMMT (9 uterine, 2 tubal, and 1 metastatic), 6 cases of mullerian adenosarcoma (three corporeal, two cervical, and one tubal), and 7 cases of primary uterine sarcomas had their tissues examined immunohistochemically for expression of CD10, desmin, myoglobin, alpha-smooth muscle actin (SMA), and cytokeratin. Of the primary uterine sarcomas, two were primary rhabdomyosarcomas (one cervical and one corporeal), two were ESSs, two were high-grade leiomyosarcomas, and one was a high-grade endometrial sarcoma. Sarcomatous components in all cases of MMMT and mullerian adenosarcoma, as well as all uterine sarcomas, were positive for CD10, showing moderate to marked staining intensity with varying distribution except in one MMMT, which showed weak and very focal staining. In four MMMTs, three adenosarcomas, and one rhabdomyosarcoma, myoglobin- and/or desmin-positive rhabdomyoblastic cells were positive for CD10. The immunoreactivity for CD10 showed the same distribution for alpha-SMA and myoglobin in three and two MMMTs, respectively. In five cases of MMMT, carcinomatous components were focally positive for CD10, and in two cases small populations of round or short spindle cells in sarcomatous components were positive for CD10, alpha-SMA, and cytokeratin (CAM5.2). These results indicate that CD10 expression is not restricted to ESS but can be positive in MMMT and mullerian adenosarcoma as well as in a variety of uterine tumors including high-grade leiomyosarcoma and rhabdomyosarcoma. CD10 expression might be one of the characteristics of mullerian system-derived neoplastic mesenchymal cells.

Cohen, L., P. A. Parker, et al. (2002). "Quality of life in patients with malignant melanoma participating in a phase I trial of an autologous tumour-derived vaccine." Melanoma Res 12(5): 505-11.

Quality of life (QOL) plays an increasingly important role in the decision-making process and the ultimate acceptability of particular treatments for patients. We prospectively examined QOL in patients with advanced melanoma treated with surgery followed by heat-shock protein peptide complex 96 (HSPPC-96) vaccine, an active, patient-specific immunotherapy. QOL (the RAND 36-Item Health Survey; SF-36) and cancer-related intrusive thoughts (Impact of Event Scale; IES) were measured at the start of treatment, 3 weeks later on the final day of treatment, and at follow-up 1 month later in 30 patients with stage III or IV malignant melanoma. Mixed model analyses revealed no significant change over time in the SF-36 Physical or Mental Component Summary scores, or the IES scores. In comparisons with other populations, at the 1 month follow-up assessment, melanoma patients reported similar QOL to patients with metastatic renal cell carcinoma who received the same treatment, significantly worse QOL on the physical dimensions and similar QOL on the psychosocial and emotional dimensions compared with the general population, similar QOL to patients with type II diabetes, and significantly better QOL on all three dimensions than patients with congestive heart failure. There was also a significant negative association between IES scores at baseline and mental health scores at each time point ( < 0.002 for all). QOL remained stable during treatment with the HSPPC-96 vaccine. In addition, patients who reported high levels of cancer-related intrusive thoughts at the start of treatment reported worse mental health at the end of the treatment.

McCluggage, W. G. (2002). "Uterine carcinosarcomas (malignant mixed Mullerian tumors) are metaplastic carcinomas." Int J Gynecol Cancer 12(6): 687-90.

Uterine carcinosarcomas (malignant mixed mullerian tumors) are metaplastic carcinomas. Uterine carcinosarcomas (malignant mixed Mullerian tumors) have been traditionally regarded as a subtype of uterine sarcoma. Adjuvant oncological treatments have often been similar to those directed against high-grade uterine sarcomas such as leiomyosarcoma and undifferentiated uterine sarcoma. However, there is now convincing evidence that most uterine carcinosarcomas are monoclonal neoplasms and are in reality metaplastic carcinomas. Although aggressive, the behavior of uterine carcinosarcoma is more akin to that of high-grade endometrioid type endometrial adenocarcinoma and aggressive morphological subtypes of uterine carcinoma. The sarcomatous component is derived from the carcinomatous element which is the driving force. Although the designation carcinosarcoma is likely to remain, adjuvant treatments should probably be similar to those directed against aggressive high grade endometrial carcinomas. Prospective studies should be performed to ascertain whether such adjuvant therapies are more effective than traditional sarcoma based therapies in the treatment of these aggressive neoplasms.

Bouchardy, C., H. M. Verkooijen, et al. (2002). "Increased risk of malignant mullerian tumor of the uterus among women with breast cancer treated by tamoxifen." J Clin Oncol 20(21): 4403.

Pillay, K., D. Govender, et al. (2002). "ALK protein expression in rhabdomyosarcomas." Histopathology 41(5): 461-7.

AIMS: The ALK p80 chimeric protein is thought to be up-regulated as a result of the t(2;5) as classically seen in anaplastic large cell lymphoma. However, rhabdomyosarcomas (in particular, the alveolar subtype) have also been noted to show expression of this protein. This study set out to examine ALK expression in a large number of rhabdomyosarcomas. METHODS AND RESULTS: Eighty-three cases of rhabdomyosarcomas and 16 cases of malignant mixed mullerian tumours with a rhabdomyosarcomatous component were retrieved from the archives of the Department of Anatomical Pathology for the period 1983-2001. The sections were stained with polyclonal ALK antibody. There were 52 male and 30 female patients. In one case, the gender of the patient was not indicated. The ages ranged from 1 week to 77 years. The most common site was the head and neck region, followed by the pelvis and extremities. Thirty-one cases were of the alveolar subtype while 40 cases were embryonal. There were four mixed embryonal/alveolar, six pleomorphic and two unclassifiable rhabdomyosarcomas. Fourteen of the 31 (45%) alveolar rhabdomyosarcomas stained positively for the ALK protein, while only six of the 40 embryonal (15%) cases showed positivity. One case each of the mixed embryonal/alveolar, pleomorphic and unclassified cases was also immunopositive. The rhabdomyosarcomatous component in the malignant mixed mullerian tumours was positive in four of the 16 cases. CONCLUSION: We conclude that a proportion of alveolar rhabdomyosarcomas (in particular) exhibit ALK protein expression. However, ALK expression is not restricted to this subtype. An extension of this study is to determine if this over-expression is as a result of the t(2;5) translocation.

Saffer, H., A. Wahed, et al. (2002). "Clusterin expression in malignant lymphomas: a survey of 266 cases." Mod Pathol 15(11): 1221-6.

Clusterin expression has been reported to be characteristic of systemic anaplastic large cell lymphoma and usually negative in cutaneous anaplastic large cell lymphoma as well as other lymphoma types. We surveyed clusterin expression using immunohistochemical methods in 266 cases of non-Hodgkin's lymphoma and Hodgkin's disease to further assess the diagnostic utility of this marker. Clusterin immunostaining was observed in 40 of 49 (82%) systemic anaplastic large cell lymphomas and 12 of 29 (41%) cutaneous anaplastic large cell lymphomas. Clusterin also was expressed in 5 of 43 (12%) diffuse large B-cell lymphomas (4 of 5 CD30+), 1 of 14 (7%) peripheral T-cell lymphomas, 1 of 32 (3%) cases of nodular sclerosis Hodgkin's disease, and 1 case of mycosis fungoides in large cell transformation. Clusterin was negative in all other neoplasms assessed including follicular lymphoma of all grades (n = 24), mantle cell lymphoma (n = 13), marginal zone B-cell lymphoma (n = 12), precursor T-cell or B-cell lymphoblastic leukemia/lymphoma (n = 10), mixed cellularity Hodgkin's disease (n = 8), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7), Burkitt lymphoma (n = 7), mycosis fungoides (n = 4), nodular lymphocyte predominant Hodgkin's disease (n = 3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (n = 2), and plasmacytoma (n = 2). We conclude that clusterin is a marker of anaplastic large cell lymphoma and that addition of clusterin to antibody panels designed to distinguish systemic anaplastic large cell lymphoma from classical Hodgkin's disease is useful. However, clusterin is also positive in a substantial subset of cutaneous anaplastic large cell lymphomas, a smaller subset of diffuse large B-cell lymphomas, and rarely in cases of peripheral T-cell lymphoma and nodular sclerosis Hodgkin's disease.

Wang, X., U. S. Khoo, et al. (2002). "Cervical and peritoneal fluid cytology of uterine sarcomas." Acta Cytol 46(3): 465-9.

OBJECTIVE: To study the cytologic features of uterine sarcoma. STUDY DESIGN: The pathology records of 102 patients with uterine sarcoma were reviewed. Four patients, including one case of leiomyosarcoma (LMS), one high grade stromal sarcoma (HGSS) and two malignant mixed mullerian tumor (MMMT), had abnormal cervical and/or peritoneal cytologic findings. Three abnormal cervical smears and two abnormal peritoneal fluids from these patients, including immunohistochemically stained sections of cell block, were reviewed. RESULTS: The diagnostic cells appeared in clusters or in isolation. They had enlarged and hyperchromatic nuclei. Occasional mitotic figures were seen. The cells were considered suspicious for malignancy in cervical smears of HGSS and in the peritoneal fluid of LMS. Adenocarcinoma cells were identified in both the cervical smear and peritoneal fluid of one patient with MMMT. Atypical cells were found in another patient with MMMT. CONCLUSION: Positive cervical or peritoneal cytology is uncommonly detected in association with uterine sarcomas. Even when abnormal cells are found, it may be difficult to give a definitive diagnosis of uterine sarcoma based directly on the cytomorphologic characteristics of cervical or peritoneal smears. However, such a possibility should be kept in mind by the cytopathologist to avoid missing the diagnosis.

Clement, P. B. and R. H. Young (2002). "Endometrioid carcinoma of the uterine corpus: a review of its pathology with emphasis on recent advances and problematic aspects." Adv Anat Pathol 9(3): 145-84.

This review considers the pathologic features of endometrioid carcinoma of the uterine corpus, which accounts for approximately 80% of endometrial adenocarcinomas, with an emphasis on its histologic features, recent advances, and problematic aspects. In addition to typical endometrioid carcinoma, the variants of endometrioid carcinoma covered include secretory carcinoma, villoglandular endometrioid carcinoma, endometrioid carcinoma with small nonvillous papillae, endometrioid carcinomas with microglandular and sertoliform patterns, and endometrioid carcinomas with metaplastic changes. These changes include a variety of different appearances of squamous epithelia (ranging from mature and keratinizing to immature with only subtle evidence of a squamous nature), clear cells, surface changes resembling syncytial metaplasia or microglandular hyperplasia, ciliated cells, oxyphilic cells, and spindled epithelial cells (sarcomatoid carcinoma). The last is one of several variants that may cause a biphasic appearance, all of which should be distinguished from the malignant mullerian mixed tumor. Rare findings in endometrioid carcinomas include hyalinization, psammoma bodies, and foci of stromal metaplasia such as osteoid. Unusual growth patterns of endometrioid carcinomas include involvement of adenomyosis, the "diffusely" infiltrating pattern of myoinvasion, and a previously unemphasized pattern of myoinvasion with "pinched off" glands that may be cystic or have a pseudovascular appearance, often with a myxoid stromal reaction. Other aspects of endometrioid carcinoma discussed are its immunoprofile, grading, cervical involvement (including a hitherto undescribed "burrowing" pattern of extension within the cervix that can result in underdiagnosis of stage IIB disease), carcinoma arising in the lower uterine segment, carcinoma arising in polyps and adenomyomas, carcinoma in young women, tamoxifen-related carcinoma, associated ovarian endometrioid carcinoma, and peritoneal keratin granulomas. Finally, the differential diagnosis of endometrioid carcinoma is briefly considered with a section on benign mimics, including curettage-related changes, menstrual changes, adenomyosis-related problems, metaplastic changes, atypical polypoid adenomyoma, radiation atypia, and papillary proliferations, and a section on metastatic colonic carcinoma.

Ribeiro-Silva, A., A. Novello-Vilar, et al. (2002). "Malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation." Int J Gynecol Cancer 12(2): 223-7.

Malignant mixed Mullerian tumors (MMMTs) are rare neoplasms. We report the clinical, pathologic, and immunohistochemical features of an MMMT primary of uterine cervix. This lesion was composed of a poorly differentiated epithelial component (cytokeratin positive) and a spindle cell component (vimentin positive) with heterologous (myoblastic) differentiation (focal 1A4 positive). There were also cells with neuroendocrine features that expressed S-100 and chromogranin A. Along with a brief review of this amazing neoplasm, some histogenetic concepts relevant to this case are discussed. To our knowledge this is the first report of a malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation.

Granter, S. R., K. N. Weilbaecher, et al. (2002). "Role for microphthalmia transcription factor in the diagnosis of metastatic malignant melanoma." Appl Immunohistochem Mol Morphol 10(1): 47-51.

Microphthalmia transcription factor (Mitf), a protein critical for the embryonic development and postnatal viability of melanocytes, is a master lineage regulator and modulates extracellular signals. Recently, an anti-Mitf antibody, D5, was shown to be both a sensitive and a specific marker of epithelioid melanoma. Those data suggested that Mitf expression was specific for melanocytic differentiation because it was not detected in six different carcinoma types. To broaden the spectrum of melanomatous and nonmelanomatous tumors tested with this antibody, the authors investigated the sensitivity and specificity of the D5 anti-Mitf antibody in 36 metastatic melanomas and 102 nonmelanomatous tumors. Twenty-nine of 36 (81%) melanomas examined were reactive for D5. Of these, 29 of 32 (91%) epithelioid melanomas were reactive, whereas all 4 melanomas with spindle cell morphology were nonreactive. Six of 102 (5.8%) nonmelanomatous tumors (1 breast carcinoma, 1 malignant mixed mullerian tumor, 2 renal cell carcinomas, and 2 leiomyosarcomas) were reactive for D5. All melanomas were reactive for S-100 protein (a criteria for inclusion in the study), whereas 8 of 102 (7.8%) of nonmelanomatous tumors were reactive. Twenty-five of 36 melanomas (69%) were reactive for HMB-45, whereas no nonmelanomatous tumors were reactive. Twenty-one of 28 (75%) melanomas were reactive for Melan-A. Reactivity for Melan-A was detected in 5 of 102 (4.9%) nonmelanomatous tumors. As with D5, HMB-45 and Melan-A failed to detect all spindle-cell melanomas. Results of this study confirm that D5 is a sensitive marker for epithelioid melanomas; however, the authors found D5 neither quite as sensitive nor quite as specific as in previous studies. Nevertheless, the authors believe that positive staining for D5 when taken in clinical, histologic, and immunohistochemical context may be diagnostically useful. In particular, D5 is helpful in the evaluation of epithelioid neoplasms, but not spindle-cell tumors.

Cho, H. Y., M. K. Kim, et al. (2002). "Endometrial stromal sarcoma of the sigmoid colon arising in endometriosis: a case report with a review of literatures." J Korean Med Sci 17(3): 412-4.

Most of malignant tumors arising in ovarian and extraovarian endometriosis are carcinomas. Mixed mullerian tumor and endometrial stromal sarcoma arising in intestinal endometriosis are rarely described, but its clinicopathologic features have not been well characterized. Here we report a case of endometrial stromal sarcoma of the sigmoid colon arising in endometriosis with a review of six additional cases of endometrial stromal sarcoma arising in intestinal endometriosis found in English literatures. The patients ranged in age from 36 to 64 yr. Presenting symptoms were pain, bloody diarrhea, and tenesmus. Some patients had a previous history of endometriosis. Most of the tumors arose in the rectosigmoid colon. The histologic features were the same as their uterine counterpart. No death of disease had been reported. This rare tumor should not be confused with gastrointestinal stromal tumor clinically and histologically.

Duska, L. R., A. Garrett, et al. (2002). "Paclitaxel and platinum chemotherapy for malignant mixed mullerian tumors of the ovary." Gynecol Oncol 85(3): 459-63.

OBJECTIVE: Malignant mixed mullerian tumor (MMMT) of the ovary is a rare tumor with a dismal prognosis. The most effective therapy is unknown. The current study was undertaken to characterize a group of patients treated as if they had aggressive epithelial ovarian tumors, with cytoreductive surgery and combination paclitaxel/platinum chemotherapy. METHODS: Retrospective analysis of data obtained from tumor registry and hospital records of cases of malignant mixed mullerian tumor between January 1, 1992 and January 1, 2000 treated at the Massachusetts General Hospital, Brigham and Women's Hospital, and University of Vermont was performed. Only patients treated with combination paclitaxel and platinum therapy were included in the analysis. Data were collected regarding cytoreduction, response to chemotherapy, disease-free interval, and survival. RESULTS: Fifty-five patients were identified with MMMT. Twenty-eight patients with a clearly ovarian primary had received treatment with combination paclitaxel and platinum. Paclitaxel and carboplatin was given as second-line therapy in 2 patients who had chemoresponsive but incurable disease; the remaining patients were treated with paclitaxel and platinum therapy as first-line therapy. These 28 patients had a median (range) age of 66 (46-84 years) and stage was I in 2 patients, II in 3, III in 18, and IV in 5. Treatment was generally well tolerated. Sixteen patients of 26 treated with paclitaxel and platinum as first-line therapy achieved a complete clinical response (55%) and 6 patients achieved partial response for a total response rate of 72%. Optimal cytoreduction was associated with increased time to recurrence (P = 0.001) but not with survival. Overall median survival for the 28 patients is 27.1 months. CONCLUSION: Although treatment fails many patients, a minority of patients with MMMT in this highly selected population do unexpectedly well. An aggressive approach with surgery and combination paclitaxel-platinum chemotherapy appears to offer very effective therapy.

Inthasorn, P., J. Carter, et al. (2002). "Analysis of clinicopathologic factors in malignant mixed Mullerian tumors of the uterine corpus." Int J Gynecol Cancer 12(4): 348-53.

The aim of this study was to retrospectively analyze the clinical and pathologic data of a series of patients presenting to our unit with uterine malignant mixed Mullerian tumors (MMMT) to attempt to identify prognostic factors and relate them to survival. Thirty-seven patients diagnosed with MMMT of the uterus from 1988 through 2000 were identified from the gynecological tumor registry. Data was abstracted and analyzed. The effect of a variety of clinical, histopathologic, and surgical variables on recurrence and survival were analyzed by univariate and multivariate analyses. Patients tended to be postmenopausal, overweight, hypertensive, and presented with abnormal bleeding. Preoperatively 28 (76%) were thought to have clinical stage I-II disease. Nine (32%) were upstaged based on surgical data. Five (56%) of these patients were found to have gross extrauterine disease and four (44%) were found subsequently to have microscopic extrauterine disease. Twenty (54%) patients underwent lymph node dissection and positive nodes were found in seven (35%) patients. Nine patients underwent omentectomy and disease was found in three (33%). Peritoneal washings were positive in three of 16 patients (19%). At the completion of primary surgery, 27 (75%) patients had no residual disease. Twelve (44%) of these patients had recurrence of disease. Median disease-free interval prior to first recurrence was 15 months. Median overall survival was 30 months. Log-rank analysis performed on multiple variables, including stage, age, residual disease, and depth of myometrial invasion showed a statistically significant association with overall survival probability. Only stage remained a significant independent variable predictive of overall survival (P = 0.034). We found that stage was an independent prognostic factor for overall survival in patients with uterine MMMT. Age, depth of myometrial invasion, and residual tumor were significant prognostic factors on univariate analysis. These factors may be a guide in order to select a group of high risk patients that may benefit from adjuvant therapy.

Gallardo, A., X. Matias-Guiu, et al. (2002). "Malignant mullerian mixed tumor arising from ovarian serous carcinoma: a clinicopathologic and molecular study of two cases." Int J Gynecol Pathol 21(3): 268-72.

The clinical, histologic, and molecular pathologic features of two cases of malignant mullerian mixed tumor (MMMT) arising from ovarian papillary serous carcinoma are presented. Identical p53 mutations were detected in the primary ovarian carcinoma and the subsequent MMMT in each case.

Levine, P. H. and K. Mittal (2002). "Rhabdoid epithelioid leiomyosarcoma of the uterine corpus: a case report and literature review." Int J Surg Pathol 10(3): 231-6.

A case of epithelioid leiomyosarcoma of the uterus with rhabdoid phenotype and early rhabdomyoblastic differentiation is described. A 72-year-old woman with a 5-week history of increased abdominal girth was found to have a large pelvic mass. The uterus revealed a large intramyometrial and left adnexal necrotic tumor that had spread to the small bowel mesentery and to the anterior abdominal peritoneum. The tumor was an epithelioid leiomyosarcoma with rhabdoid phenotype and focal early rhabdomyoblastic differentiation, as confirmed by immunohistochemical and ultrastructural techniques. Also called composite extrarenal rhabdoid tumor (CERT), this lesion should be differentiated from malignant mixed mullerian tumor, rhabdomyosarcoma, endometrial stromal sarcoma, and pure rhabdoid tumors of the uterus. The recognition of a rhabdoid phenotype is of clinical importance since these tumors are prone to be aggressive.

Iyengar, T. D. and T. J. Herzog (2002). "Management of symptomatic ascites in recurrent ovarian cancer patients using an intra-abdominal semi-permanent catheter." Am J Hosp Palliat Care 19(1): 35-8.

Ascites is commonly present in women with advanced-stage ovarian cancer. No standardized protocol exists for the treatment of the patient with recurrent ovarian cancer and rapidly reaccumulating malignant ascites. Palliation of symptoms is most commonly achieved through repeated paracentesis, a procedure that potentially results in injury to intra-abdominal organs, infection, and patient discomfort. Our goal was to improve patient comfort by alleviating symptoms and reducing the need for paracentesis. The Pleurx' catheter offers a number of potential advantages over traditional treatment modalities. Clearly, larger study numbers are required to quantify the morbidity associated with the Pleurx catheter.

McCluggage, W. G., T. F. Lioe, et al. (2002). "Rhabdomyosarcoma of the uterus: report of two cases, including one of the spindle cell variant." Int J Gynecol Cancer 12(1): 128-32.

Most uterine sarcomas fall into the category of leiomyosarcoma, endometrial stromal sarcoma, or undifferentiated sarcoma. Pure rhabdomyosarcomas are extremely rare, although a rhabdomyosarcomatous element may be present as a component of an adenosarcoma or carcinosarcoma (malignant mixed mullerian tumor). This report describes two uterine rhabdomyosarcomas in 28- and 67-year-old women. These were of spindle cell and pleomorphic types, respectively. At presentation the pleomorphic rhabdomyosaroma was stage IV, exhibiting massive pelvic and abdominal dissemination that mimicked an ovarian neoplasm. The spindle cell rhabdomyosarcoma was stage I, being confined to the uterus. Grossly, both uterine tumors had a polypoid appearance. Immunohistochemically, tumor cells were positive with the skeletal muscle markers sarcomeric actin, myoglobin, and myoD1. The patient with stage IV disease died within a short time of diagnosis and the other patient is alive and well at 2 years' follow-up. This report adds to the published literature on uterine rhabdomyosarcomas. This is the first reported uterine case of the spindle cell variant of embryonal rhabdomyosarcoma. Based on these cases and the published literature, rhabdomyosarcoma, especially the pleomorphic variant, appears to be a very aggressive neoplasm with an extremely poor prognosis. Immunohistochemical demonstration of skeletal muscle differentiation is necessary for a definitive diagnosis.

Woodward, P. J., R. Sohaey, et al. (2002). "From the archives of the AFIP: tumors and tumorlike lesions of the testis: radiologic-pathologic correlation." Radiographics 22(1): 189-216.

Testicular carcinoma represents only 1% of all neoplasms in men, but it is the most common malignancy in the 15-34-year-old age group. Germ cell tumors constitute 95% of all testicular tumors. Germ cell tumors are a varied group of neoplasms whose imaging features reflect their underlying histologic characteristics. Seminomas are generally well-defined homogeneous lesions, whereas the nonseminomatous tumors (embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, and mixed germ cell tumor) have a much more varied appearance. Germ cell tumors follow a predictable pattern of spread via the lymphatic drainage to the retroperitoneal nodes. Choriocarcinoma, which has a proclivity for early hematogenous spread, is a notable exception. Testicular tumors may also arise from the sex cords (Sertoli cells) and stroma (Leydig cells). Although 90% of these tumors are benign, there are no reliable imaging criteria to differentiate them from malignant masses. Some benign testicular masses can be recognized, obviating an unwarranted orchiectomy. A dilated rete testis is a normal variant and appears as a series of small tubules near the mediastinum testis. Other benign lesions that can be suspected on the basis of imaging findings and history include intratesticular cysts, epidermoid cysts, congenital adrenal hyperplasia, and sarcoidosis.

Nicotina, P. A., A. Zanghi, et al. (2002). "Uterine malignant mixed Mullerian tumor (Metaplasic carcinoma) in the cat: clinicopathologic features and proliferation indices." Vet Pathol 39(1): 158-60.

A homologous malignant mixed Mullerian tumor of the uterus occurring in an 8-year-old Persian cat was described with regard to its clinical and pathologic features. A polypoid multinodular mass of the right uterine horn was shown by an ultrasound examination. Grossly, the right uterine horn was enlarged because of a vegetative and infiltrating tumor, grayish-white in color, that penetrated the uterine wall to the level of the perimetrium. Many metastatic nodules were found in abdominal and thoracic cavities. Histologically, the neoplasm had both carcinomatous and sarcomatous components and was diagnosed as an uterine malignant mixed Mullerian tumor. This is the fourth case reported in cats. The histologic features and proliferation rate of this tumor were similar to the corresponding human neoplasms, which occur mainly in postmenopausal women. The possible hormone dependence of the tumor is briefly discussed.

Ramos, P., A. Ruiz, et al. (2002). "Mullerian adenosarcoma of the cervix with heterologous elements: report of a case and review of the literature." Gynecol Oncol 84(1): 161-6.

BACKGROUND: Mullerian adenosarcoma (MA) is a rare neoplasm composed of benign epithelial and malignant stromal components. Its location in the cervix and the presence of heterologous elements are extremely infrequent (to our knowledge, only 14 more cases have been reported in the English literature). We describe another case of MA of the uterine cervix with heterologous elements and review the clinical and pathological features of these tumors. CASE REPORT: A nulliparous 25-year-old woman was admitted to the hospital because of metrorrhagia and recurrent masses, dependent on the cervix, initially considered endocervical polyps. Microscopically, the last curettage performed revealed a tumor composed of two elements, epithelial and mesenchymal. The epithelial elements were benign endocervical type glands, and the mesenchymal were sarcomatous, containing minor foci of cartilage. A diagnosis of endocervical heterologous adenosarcoma was reached, and a total hysterectomy and bilateral salpingo-oophorectomy were performed. The patient is alive 2 years after the surgical procedure. Neither chemotherapy nor other adjuvant therapies have been administered, and she is clinically free of disease at the moment. CONCLUSION: Because MA with heterologous elements seems to appear at the earliest stages of the reproductive lifespan in women, commonly with a history of recurrent polyps, and because its malignant potential is uncertain, gynecologists and pathologists should be aware and think about the possibility of this tumor. Long-term follow-up is essential and so is the accumulation of individual cases to provide further experience with these unusual neoplasms.

Wei, L., J. Wang, et al. (2002). "Primary omental malignant mixed mullerian tumor in a 67-year-old woman." Chin Med J (Engl) 115(1): 138-40.

Shappell, H. W., M. A. Riopel, et al. (2002). "Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas." Am J Surg Pathol 26(12): 1529-41.

Ovarian endocervical-type (mullerian) mucinous tumors and tumors composed of a mixture of endocervical-type mucinous, serous, endometrioid, squamous, and indifferent cells with abundant eosinophilic cytoplasm reported to date have been primarily limited to borderline and microinvasive types, with only one report of a disease-related death. The clinicopathologic features of 54 endocervical-type and mixed cell-type mucinous tumors, defined as tumors with papillary architecture resembling serous tumors but containing endocervical-type mucinous epithelium, were evaluated. Thirty-four tumors (64%) were classified as atypical proliferative (borderline) tumors based on the absence of stromal invasion and the absence of micropapillary architecture measuring >5 mm. Five tumors (9%) qualified as intraepithelial carcinoma based on the presence of marked cytologic atypia or a complex cribriform growth pattern involving the epithelium covering the surface of papillae or lining cystic spaces. Eight tumors (15%) with stromal invasion < or =5 mm were classified as microinvasive carcinoma. Seven tumors (13%) with either stromal invasion (five tumors) or micropapillary architecture measuring >5 mm (two tumors) were classified as carcinoma. Sixteen tumors (30%) were bilateral, and endosalpingiosis was identified in 41% of cases. Serous-type differentiation was present in all cases. Of the 29 patients with atypical proliferative tumors, intraepithelial carcinomas, and microinvasive carcinomas for whom follow-up was available, there were no disease-related deaths. In contrast, of the seven patients whose tumors had either stromal invasion or micropapillary architecture >5 mm, two stage III patients died of disease (one with frank invasion and one with a micropapillary tumor that lacked stromal invasion). One other stage III patient with a noninvasive micropapillary carcinoma was alive with disease at 84 months. The remaining four patients (three stage I and one stage III) were alive with no evidence of disease. In summary, most endocervical-type atypical proliferative tumors are stage I and benign. The presence of either intraepithelial carcinoma or microinvasion has no adverse effect on behavior. Rare endocervical-type mucinous tumors demonstrate histologically malignant features and aggressive behavior that warrant designation as carcinoma. As with serous tumors, micropapillary architecture without frank invasion in endocervical-type mucinous tumors is associated with disease recurrence and death when presenting as advanced-stage disease. All the tumors in this study were composed of a heterogeneous population of cells, consisting mainly of serous (ciliated) and endocervical-type mucinous cells. In addition, they all contained endometrioid-type cells, hobnail cells, and indifferent cells with abundant eosinophilic cytoplasm to a varying degree. Accordingly, it appears that tumors that feature endocervical-type mucinous cells are rarely if ever pure but almost invariably of mixed cell type. Despite containing mucinous epithelium, the papillary architecture, serous-type differentiation, association with endosalpingiosis, frequent bilaterality, size, and clinical behavior of endocervical-type mucinous tumors closely resemble serous tumors. We therefore recommend the term "seromucinous" for these tumors, which acknowledges both their serous and mucinous features.

Robins, H. I., S. M. Chang, et al. (2002). "A phase II trial of thymidine and carboplatin for recurrent malignant glioma: a North American Brain Tumor Consortium Study." Neuro-oncol 4(2): 109-14.

This phase II study in recurrent high-grade glioma evaluated the response rate, toxicities, and time to treatment failure of high-dose carboplatin modulated by a 24-h infusion of thymidine (75 g/m(2)). The trial was based on preclinical data and a prior phase I study ( J. Clin. Oncol. 17, 2922-2931, 1999); a phase II recurrent high-grade glioma study was initiated in July of 1998. Thymidine was given over 24 h; carboplatin was given over 20 min at hour 20 of the thymidine infusion. The starting dose of carboplatin had a value of 7 for the area under the curve (AUC), with allowance for dose escalation of 1 AUC unit per cycle if grade 2 toxicity was observed. Treatment cycles were repeated every 4 weeks. Accrual as of September 1999 was 45 patients [4 were unevaluable]: 76% with glioblastoma multiforme (GBM), 20% with anaplastic oligodendroglioma, 2% with mixed type, and 2% with anaplastic astrocytoma. Most patients had prior chemotherapy (78%). As observed in the earlier phase I study (in which carboplatin pharmacokinetics were unaltered by thymidine or antiseizure medications), thymidine was myeloprotective, resulting in a minimal need for dose reduction for patients having a >2 grade toxicity (in only 4% of the courses of treatment). Of 101 total courses, the number of courses (at the AUCs) was 3 (5), 4 (6), 58 (7), 20 (8), 11 (9), and 5 (10). Grade 3 nonhematologic toxicities included headache (4%), altered consciousness (3%), fatigue (1%), and nausea (3%). Responses included 2 partial (1 oligodendroglioma, 1 GBM; 5%); 3 minor (1 anaplastic astrocytoma, 2 GBM; 7.3%); 6 stable disease (14.6%); and 30 progressive disease (73.2%). For GBM patients, median survival was 23 weeks (with a 95% confidence interval of 20 to 50 weeks), and progression-free survival was 8 weeks (with a 95% confidence interval of 7-16 weeks). These results in GBM were comparable to other phase II GBM trials and thus do not represent a therapeutic advance in the treatment of GBM. Taken collectively, however, results are consistent with continued investigation of thymidine in combination with chemotherapeutic agents for high-grade glioma and other malignant diseases. The significant myeloprotection afforded by thymidine may have particular relevance to polychemotherapeutic regimens.

Akahira, J.-i., T. Suzuki, et al. (2002). "Differential Expression of Progesterone Receptor Isoforms A and B in the Normal Ovary, and in Benign, Borderline, and Malignant Ovarian Tumors." Cancer Science 93(7): 807-815.

Human epithelial ovarian neoplasm is well-known to be sex steroid-related, but the possible biological significance of progesterone actions in these tumors remains controversial. In this study, we examined the differential expression patterns of the two progesterone receptor (PR) isoforms, PRA and PRB, using immunohistochemistry and real-tune quantitative RT-PCR in normal and neoplastic ovarian tissues, and in cell lines derived from a normal ovarian surface epithelium and an ovarian epithelial carcinoma in order to further elucidate the possible involvement of progesterone in the development of ovarian neoplasms. The median H scores for PR isoforms in normal (n=8), benign (n=10), borderline (n=8) and malignant (n=24) ovarian tissues were as follows; PRA: 194.0, 171.0, 49.5, 0 (P<0.05), and PRB: 175.0, 180.5, 251.5, 168.5, respectively. In ovarian cancer cell lines (OVCAR-3 and Caov-3), the PRB/PRAB mRNA ratio was increased by 17beta-estradiol, both tune-and dose-dependently. However, this ratio was unaltered following the addition of 17beta-estradiol in a normal ovarian epithelial cell line (NOV-31). Immunoblotting analysis demonstrated that PRB protein expression was markedly up-regulated in OVCAR-3, whereas the PRA and PRB isoforms both appeared to be increased in NOV-31. These results suggest that down-regulation of PRA is associated with the development of ovarian epithelial carcinoma.

Yamamura, T., M. Ueda, et al. (2002). "Immunosuppressive and anticancer effect of a mammalian ribonuclease that targets high-affinity interleukin-2-receptors." Eur J Surg 168(1): 49-54.

OBJECTIVE: To target high-affinity interleukin (IL)-2 receptors involved in lymphocyte proliferation processes such as allograft rejection, autoimmune disorders, and certain haematological malignancies, using a minimally immunogenic mammalian-derived enzyme, bovine RNaseA, which becomes cytotoxic on entering cytoplasm. DESIGN: Laboratory study. SETTING: Teaching hospital, Japan. MATERIAL: Human lymphocytes isolated from healthy histoincompatible donors in mixed lymphocyte cultures or stimulated with phytohemagglutinin (PHA) to promote IL-2Ralpha expression. MJ, an HTLV-1-infected malignant T-cell line that overexpresses IL-2Ralpha, and the IL-2Ralpha-negative cell lines MOLT-4F and MT-1, were used as controls. INTERVENTIONS: Bovine RNaseA was chemically conjugated to 7G7B6, a monoclonal antibody to the alpha-chain of human IL-2 receptors, and several concentrations of the conjugates were added to the lymphocyte cultures. MAIN OUTCOME MEASURES: Inhibition of cell proliferation as a percentage of 3H-thymidine incorporation in 24 hours. RESULTS: 7G7B6-RNaseA dose-dependently inhibited cell proliferation in PHA-stimulated human lymphocytes at a 50% inhibitory concentration (IC50) of 2 x 10(-7) M. whereas RNase alone and RNase plus antibody had no inhibitory effect. 7G7B6-RNaseA also dose-dependently inhibited the human mixed lymphocyte reaction at an IC50 of 2 x 10(-6) M, whereas RNase alone did not. The conjugate also inhibited cell proliferation in MJ cells, a cell line that is infected with HTLV-I and overexpresses the high-affinity IL-2 receptor, at an IC50 of 5 x 10(-7) M. However the conjugate had no inhibitory effect on the IL-2 receptor non-expressing human T-cell lymphoblastic leukaemia cell lines MOLT-4F or MT-1. CONCLUSION: 7G7B6-RNaseA can inhibit cell proliferation in antigen- or mitogen-stimulated lymphocytes that overexpress high-affinity IL-2 receptors, and it may be safer than conventional chemotherapy or immunotoxins in the treatment of transplant rejection, certain lymphocytic malignancies, and other IL-2R-associated diseases, because it contains a mammalian cytotoxic enzyme.

Chao, K. C., P. H. Wang, et al. (2001). "Establishment and characterization of a cell line, MT-213-VGH, isolated from a mixed mullerian tumor of the uterus." Acta Cytol 45(5): 683-90.

OBJECTIVE: To establish a cell line from a woman with malignant mixed mullerian tumor of the uterus and to examine the biologic properties of this cell line (MT-213-VGH). STUDY DESIGN: Cells were cloned by the limiting dilution method. Histologic staining of mixed mullerian (mesodermal) tumor (MMMT) cells was performed with May-Grunwald-Giemsa and hematoxylin and eosin stain. After more than 20 passages, cells were used to estimate the population-doubling time and colony-forming efficiency of MMMT cells. The cell line exhibited considerable variation in the degree of sensitivity to diverse chemotherapy drugs in vitro. RESULTS: MMMT cells containing antigens for vimentin and myoglobin were detected, but those for CA-125, carcinoembryonic antigen, cytoskeleton, desmin, epithelial membrane antigen and fibronectin were not found. In addition, MT-213-VGH cells contained a mucinous substance; its chromosome model number is 45. This cell line showed differential sensitivities to chemotherapeutic agents, such as bleomycin, cisplatin, 5-fluorouracil and vinblastine. CONCLUSION: The establishment and availability of the number cell line MT-213-VGH for a malignant mixed mullerian tumor of the uterus should assist in research on new methods of managing this type of gynecologic cancer.

Friebe, M., A. Mahmood, et al. (2001). "[99mTc]oxotechnetium(V) complexes amine-amide-dithiol chelates with dialkylaminoalkyl substituents as potential diagnostic probes for malignant melanoma." J Med Chem 44(19): 3132-40.

[99mTc]oxotechnetium(V) complexes of amine-amide-dithiol (AADT) chelates containing tertiary amine substituents were synthesized and shown to have affinity for melanoma. For complexation the AADT-CH2[CH2]nNR2 (n = 1, 2; R = Et, n-Bu) ligand was mixed with a [99mTc]oxotechnetium(V)-glucoheptonate precursor to make the AADT-[99mTc]oxotechnetium(V) complexes in nearly quantitative yield. Structurally analogous nonradioactive oxorhenium(V) complexes were also synthesized and characterized. In vitro sigma-receptor affinity measurements indicate these complexes to possess sigma-affinity in the low micromolar range with K(i) values in the 7.8-26.1 and 0.18-2.3 microM range for the sigma1- and sigma2-receptors, respectively. In vitro cell uptake of the 99mTc complexes in intact B16 murine melanoma cells at 37 degrees C after a 60-min incubation ranged from 12% for complex 2 (n = 1, R = n-Bu) to 68% for complex 4 (n = 2, R = n-Bu). In vivo evaluation of complexes 1-Tc-4-Tc in the C57Bl/B16 mouse melanoma model demonstrated significant tumor localization. Complex 1-Tc (n = 1, R = Et) displayed an in vivo tumor uptake of 7.6% ID/g at 1 h after administration with initial melanoma/blood (M/B), melanoma/spleen (M/S), and melanoma/lung (M/L) ratios >4; these ratios increased to 10.8, 10.1, and 7.3, respectively, at 6 h. While complex 3-Tc (n = 3, R = Et) had an initial tumor uptake of 3.7% ID/g 1 h after administration with M/B, M/S, and M/L ratios >2, a greater tumor retention and slightly faster clearance from nontumor-containing organs resulted in M/B, M/S, and M/L ratios of 19.1, 19.1, and 12.7, respectively, at 6 h. The high tumor uptake and significant tumor/nontumor ratios indicate that such small technetium-99m-based molecular probes can be developed as in vivo diagnostic agents for melanoma and its metastases.

Jazaeri, A. A., K. J. Nunes, et al. (2001). "Well-differentiated endometrial adenocarcinomas and poorly differentiated mixed mullerian tumors have altered ER and PR isoform expression." Oncogene 20(47): 6965-9.

Both the estrogen receptor (ER) and the progesterone receptor (PR) have two subtypes: ER-alpha and beta, and PR-A and -B, respectively. These subtypes differ in function and expression, and recent reports have correlated changes in the normal proportions of these isoforms with neoplastic states. We investigated ER and PR isoform expression in normal pre- and post-menopausal endometrium, well-differentiated endometrial adenocarcinoma, and poorly differentiated malignant mixed mullerian tumors (MMMTs). Semi-quantitative RT-PCR and immunoblotting were used to measure receptor mRNA and protein expression. Estrogen receptor-alpha/beta mRNA ratios were significantly higher in postmenopausal (27.3) compared to premenopausal endometrium (4.9) mainly as a result of lower ER-beta expression in the former. Compared to age-matched postmenopausal controls, the ER-alpha/beta ratio was reduced in both grade I adenocarcinoma and MMMT specimens (3.3 and 6.8, respectively), due to a selective loss of ER-alpha. The relative abundance of PR-A and PR-B mRNA remained unchanged between all tissue subtypes. Total PR protein, however, was significantly reduced in MMMTs compared to all other groups. Thus, sex steroid receptor expression is significantly and differentially altered in well-differentiated and poorly-differentiated endometrial cancers. Both cancers exhibit decreased ER-alpha expression and the MMMTs also demonstrate a significant loss of PR protein.

Storey, M. R., A. S. Garden, et al. (2001). "Postoperative radiotherapy for malignant tumors of the submandibular gland." Int J Radiat Oncol Biol Phys 51(4): 952-8.

PURPOSE: This retrospective study assessed the outcome and patterns of failure for patients with malignant submandibular tumors treated with surgery and postoperative radiation. METHODS AND MATERIALS: Between 1965 and 1995, 83 patients aged 11-83 years old received postoperative radiotherapy after resection of submandibular gland carcinomas. The most common radiation technique was an appositional field to the submandibular gland bed using electrons either alone or mixed with photons. Primary tumor bed doses ranged from 50 to 69 Gy (median, 60 Gy). Regional lymph nodes (ipsilateral Levels I-IV) were irradiated in 66 patients to a median dose of 50 Gy. Follow-up time ranged from 5 to 321 months (median, 82 months). RESULTS: Actuarial locoregional control rates were 90%, 88%, and 88% at 2, 5, and 10 years, respectively. The corresponding disease-free survival rates were 76%, 60%, and 53%, because 27 of 74 patients (36%) who attained locoregional control developed distant metastases. Adenocarcinoma, high-grade histology, and treatment during the earlier years of the study were associated with worse locoregional control and disease-free survival. The median survival times for patients with and without locoregional control were 183 months and 19 months, respectively. Actuarial 2-, 5-, and 10-year survival rates were 84%, 71%, and 55%, respectively. Late complications occurred in 8 patients (osteoradionecrosis, 5 patients). CONCLUSIONS: High-risk cancers of the submandibular gland have a historic control rate of approximately 50% when treated with surgery alone. In the current series, locoregional control rates for high-risk patients with submandibular gland cancers treated with surgery and postoperative radiotherapy were excellent, with an actuarial locoregional control rate of 88% at 10 years.

Modak, S., K. Kramer, et al. (2001). "Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors." Cancer Res 61(10): 4048-54.

Tumor-restricted surface antigens may be targets for diagnosis and immune-based therapies. Monoclonal antibody 8H9 is a murine IgG1 hybridoma derived from the fusion of mouse myeloma SP2/0 cells and splenic lymphocytes from BALB/c mice immunized with human neuroblastoma. By immunohistochemistry, 8H9 was highly reactive with human brain tumors, childhood sarcomas, and neuroblastomas, and less so with adenocarcinomas. Among primary brain tumors, 15 of 17 glioblastomas, 3 of 4 mixed gliomas, 4 of 11 oligodendrogliomas, 6 of 8 astrocytomas, 2 of 2 meningiomas, 3 of 3 schwannomas, 2 of 2 medulloblastomas, 1 of 1 neurofibroma, 1 of 2 neuronoglial tumors, 2 of 3 ependymomas, and 1 of 1 pineoblastoma tested positive. Among sarcomas, 21 of 21 Ewing's/primitive neuroectodermal tumor, 28 of 29 rhabdomyosarcomas, 28 of 29 osteosarcomas, 35 of 37 desmoplastic small round cell tumors, 2 of 3 synovial sarcomas, 4 of 4 leiomyosarcomas, 1 of 1 malignant fibrous histiocytoma, and 2 of 2 undifferentiated sarcomas tested positive with 8H9. Eighty-seven of 90 neuroblastomas, 12 of 16 melanomas, 3 of 4 hepatoblastomas, 7 of 8 Wilms' tumors, 3 of 3 rhabdoid tumors, and 12 of 27 adenocarcinomas also tested positive. In contrast, 8H9 was nonreactive with normal human tissues including bone marrow, colon, stomach, heart, lung, muscle, thyroid, testes, pancreas, and human brain (frontal lobe, cerebellum, pons, and spinal cord). Reactivity with normal cynomolgus monkey tissue was restricted similarly. Indirect immunofluorescence localized the antigen recognized by 8H9 to the cell membrane. The antigen is proteinase sensitive and is not easily modulated off the cell surface. 8H9 immunoprecipitated a M(r) 58,000 band after N-glycanase treatment, most likely a protein with a heterogeneous degree of glycosylation. This novel antibody-antigen system may have potential for tumor targeting.

Cokelaere, K., P. Michielsen, et al. (2001). "Primary mesenteric malignant mixed mesodermal (mullerian) tumor with neuroendocrine differentiation." Mod Pathol 14(5): 515-20.

Extragenital malignant mixed mesodermal (mullerian) tumors (MMMT) are rare neoplasms, with but 24 well documented cases in the literature. Neuroendocrine differentiation in mixed mullerian neoplasms has been mentioned only anecdotally. We report on the clinical, pathological, and immunohistochemical features of a hitherto-undescribed extragenital MMMT with prominent neuroendocrine differentiation arising from the jejunal mesentery. This lesion was composed of a poorly differentiated epithelial component and a spindle cell component with heterologous (rhabdomyoblastic) differentiation. The bulk of the tumor consisted of small cell neuroendocrine carcinoma, which exhibited strong immunoreactivity for NSE, LEU-7, chromogranin A and synaptophysin. Electronmicroscopy confirmed the presence of neurosecretory dense-core granules. The primary mesenteric origin of the tumor was established at autopsy. Along with a brief review of previously reported extragenital MMMT some histogenetic concepts relevant to this case are discussed.

Crescenzi, E. and G. Palumbo (2001). "Bcl-2 exerts a pRb-mediated cell cycle inhibitory function in HEC1B endometrial carcinoma cells." Gynecol Oncol 81(2): 184-92.

OBJECTIVE: In various human tumors the expression of Bcl-2 appears to vary significantly during the transformation process. Indeed, in several glandular systems, Bcl-2 levels appear to be sustained in premalignant lesions and rather low after the malignant change. Since we recently reported that transformed human endometrial cells display constitutively low levels of Bcl-2, we set out to investigate the biological meaning of this down-regulation. To this end we analyzed the effects of Bcl-2 forced overexpression in a moderately differentiated endometrial cell line of human origin. METHODS: Bcl-2 overexpression was obtained by transfecting HEC1B human endometrial adenocarcinoma cells with a suitable bcl-2 vector. The effects of Bcl-2 overepression were evaluated in several transfectants (cell clones and mixed populations) by FACS, growth rates, cloning efficiencies, and modification of the phosphorylation status of the pRb protein. Accompanying changes in the expression of the CDK inhibitor p21(WAF1/CIP1) were evaluated as well. RESULTS: Bcl-2 overexpression resulted in a reduced cell proliferation rate, decreased cloning efficiency, appreciable cell morphology changes, G2/M cell cycle arrest, remarkable accumulation of the dephosphorylated form of retinoblastoma protein, and a significant rise in p21(WAF1/CIP1). CONCLUSIONS: From these observation it may be deduced that the observed loss and down-regulation of the antiapoptotic protein in endometrial glandular human tumors is not random but possibly related to the cellular transformation process. It may be also inferred that the coincidence of a progressive fading of both Bcl-2 and cyclin inhibitor p21(WAF1/CIP1) expressions, together with accumulation of the hyperphosphorylated form of the retinoblastoma protein, may be seen as a potential indicator of ongoing malignant changes.

Shen, D. H., U. S. Khoo, et al. (2001). "Primary peritoneal malignant mixed Mullerian tumors. A clinicopathologic, immunohistochemical, and genetic study." Cancer 91(5): 1052-60.

BACKGROUND: Primary peritoneal malignant mixed Mullerian tumors (MMMTs) are rarely reported in the literature. METHODS: The clinical, pathologic, and immunohistochemical features of five cases of MMMT of female peritoneum were analyzed. The tumors were also investigated for expression of hormone receptors, specific BRCA-1 mutations, and clonality. RESULTS: The patients' ages ranged from 33 to 67 years. They presented with abdominal pain or mass. One case of peritoneal MMMT was associated with a synchronous endometrial carcinoma whereas another case was detected 2 years after the diagnosis of a primary adenocarcinoma of the fallopian tube. One patient died 1 month after diagnosis whereas 2 patients died with disease within 1 year. Both carcinomatous and sarcomatous elements are present in all the tumors. Squamous differentiation was noted in two cases. Heterologous elements, including chondroid, rhabodomyoblastic, and osteoid differentiation were detected in all tumors. Immunohistochemical studies confirm the biphasic differentiation with variable demonstration of neural and smooth muscle differentiation. All five MMMTs were negative for estrogen and progestogen receptors although the related endometrial and tubal carcinomas were positive. Heteroduplex analysis used to screen for specific BRCA-1 mutations were negative in all five MMMTs. Clonality study of the two MMMTs found in association with endometrial carcinoma and tubal carcinoma was inconclusive. CONCLUSIONS: Our study confirmed that primary peritoneal MMMTs were aggressive tumors with poor prognosis. The presence of synchronous or metachronous genital carcinomas suggests multifocal tumorigenesis from tissue of same embryologic origin. The lack of hormone receptor in these tumors indicates deviation from hormonal control. Specific BRCA-1 mutations found in ovarian carcinoma in Chinese patients could not be detected in our series.

Grayson, W., L. F. Taylor, et al. (2001). "Carcinosarcoma of the uterine cervix: a report of eight cases with immunohistochemical analysis and evaluation of human papillomavirus status." Am J Surg Pathol 25(3): 338-47.

Carcinosarcomas (malignant Mullerian mixed tumors [MMMTs]) of the uterine cervix are rare neoplasms. This report describes the morphology, immunohistochemical profiles, and human papillomavirus (HPV) status of eight cervical MMMTs. Patients' ages ranged from 32 to 93 years (mean, 61 years). Seven cases showed in situ squamous cell carcinoma (SCC). The invasive epithelial component (EC) was composed of combined adenoid basal carcinoma, basaloid SCC, and adenoid cystic carcinoma (ACC) in two cases. Keratinizing SCC, large cell nonkeratinizing SCC, undifferentiated carcinoma, and basaloid SCC predominated in the remaining tumors, one of which had admixed ACC. The sarcomatous component (SC) was homologous and spindled with admixed myxoid areas in three lesions. The ECs and SCs in six MMMTs showed dual immunostaining with epithelial membrane antigen and the pan-keratin marker, MNF116. The SC was vimentin-positive in seven cases. Five tumors had a vimentin-positive EC. The SC was positive for muscle specific actin and/or smooth muscle actin in seven lesions, of which four were desmin-positive. Polymerase chain reaction (PCR) using GP5+/GP6+ L1 consensus primers detected HPV DNA in all eight cases. Nonisotopic in situ hybridization with digoxigenin-labeled probes to HPV types 6, 11, 16, 18, 31 and 33 demonstrated integrated HPV 16 in three cases, not only in the EC, but also in nuclei of the SC. This is the first study to implicate HPV in the evolution of cervical MMMTs. The above observations lend support to a metaplastic theory of histogenesis.

Hummel, P., J. F. Cangiarella, et al. (2001). "Transthoracic fine-needle aspiration biopsy of pulmonary spindle cell and mesenchymal lesions: a study of 61 cases." Cancer 93(3): 187-98.

BACKGROUND: Spindle cell and mesenchymal lesions of the lung encompass a wide variety of benign and malignant conditions. However, to the authors' knowledge, because of their rarity, few reports concerning their cytologic findings are available in the literature. The current review emphasizes the cytomorphologic features, differential diagnosis, and potential pitfalls associated with these lesions. METHODS: Seven hundred seventy-nine percutaneous lung fine-needle aspiration (FNA) specimens were retrieved from the authors' cytopathology files over a period of 5 years. Sixty-one cases (7.8%) in which a spindle cell component was the dominant or key feature were identified. The authors reviewed the cytologic smears, immunocytochemical studies, and corresponding surgical material and clinical information. RESULTS: Of these 61 aspirates, 33 (54%) were reactive processes (31 granulomas, 1 organizing pneumonia, and 1 inflammatory pseudotumor). Five cases (0.8%) were benign neoplasms (2 hamartomas, 2 solitary fibrous tumors, and 1 schwannoma). Twenty-three cases (38%) were malignant neoplasms (8 cases were primary tumors [including 5 carcinomas with spindle cell or sarcomatoid features, 1 spindle cell carcinoid tumor, 1 leiomyosarcoma, and 1 synovial sarcoma] and 15 cases were secondary tumors [including 9 melanomas, 2 leiomyosarcomas, 1 malignant fibrous histiocytoma, 1 meningioma, 1 sarcomatoid renal cell carcinoma, and 1 uterine malignant mixed mullerian tumor]). A specific diagnosis was rendered in 52 cases (85%). No false-positive cases were encountered but there was one false-negative case. One patient who was diagnosed with granulomatous inflammation on FNA was found to have nonsmall cell lung carcinoma on subsequent transbronchial biopsy. No malignant cells were identified in the smears on review. The FNA from the organizing pneumonia was interpreted as a solitary fibrous tumor whereas the inflammatory pseudotumor was diagnosed as granulomatous inflammation. The FNA from one pulmonary hamartoma initially was considered to be nondiagnostic. One solitary fibrous tumor and the schwannoma were diagnosed as smooth muscle tumor and spindle cell tumor, not otherwise specified, respectively. Among the malignant tumors, the primary synovial sarcoma and one of the metastatic malignant melanomas initially were interpreted as primitive neuroectodermal tumor/Ewing sarcoma and poorly differentiated carcinoma, respectively. CONCLUSIONS: Spindle cell lesions of the lung rarely are encountered on transthoracic lung FNA and are comprised of a wide variety of benign and malignant entities. By correlating clinical and radiologic data, cytologic findings, and ancillary studies, a high diagnostic accuracy rate can be achieved with FNA.

Bellil, K., S. Haouet, et al. (2001). "[Endometrial adenofibroma]." Gynecol Obstet Fertil 29(6): 447-50.

We report a case of papillary adenofibroma of the uterine corpus in a 31 year-old woman who was initially examined for vaginal bleeding. Pelvic examination showed a large polypoid mass protruding through the cervix canal. A pelvic ultrasound revealed a polypoid cystic mass apparently arising from the uterus. A polypectomy was performed. The tumor was composed histologically by begin epithelial and mesenchymal components. Uterine adenofibroma is a extremely rare tumor which considered to be a mixed tumor of Mullerian origin. This lesion appears to be clinically and histologically benign but must be differentiated from other malignant lesions of the uterus, particularly from the adenosarcoma.

Meyer, J. S., D. J. Gersell, et al. (2001). "Cell proliferation in ovarian carcinoma: superior accuracy of S-phase fraction (SPF) by DNA labeling index versus flow cytometric SPF, lack of independent prognostic power for SPF and DNA ploidy, and limited effect of SPF on tumor growth rate." Gynecol Oncol 81(3): 466-76.

OBJECTIVES: The goal of this work was to test the hypotheses that S-phase fraction (SPF) by DNA labeling index (SPF-LI) would predict the course of the disease for ovarian/peritoneal carcinomas and that SPF-LI would correlate better with pathologic classification and outcome than SPF by DNA flow cytometry (SPF-F). METHODS: Tritiated thymidine (1985-1988) and bromodeoxyuridine (1988-1999) DNA labeling (SPF-LI) was evaluated in vitro on 178 tumors. Cellular DNA and SPF-F were measured flow cytometrically. During this time, 90% of ovarian/peritoneal tumors accessioned in surgical pathology were studied. RESULTS: Tumors of low malignant potential (LMP, "borderline") had low SPF-LI (median = 1.2%). High-grade invasive carcinomas of various types and carcinosarcomas all had high SPF-LI (medians = 11.2-23.4%). Serous low-grade invasive carcinomas (median = 1.05) resembled LMP tumors. SPF-LI of ovarian carcinomas other than LMP tumors increased slightly as FIGO stage increased (P = 0.07). Survival of patients with high-grade ovarian carcinomas was not predicted by SPF-LI or SPF-F, nor was DNA ploidy predictive. SPF-LI produced tighter distributions for various tumor types than did SPF-F. Neither SPF nor DNA ploidy contributed to prediction of outcome when tumor type and stage were included in multivariate models. We calculated the mean cell loss rate of high-grade carcinomas to be 94%. CONCLUSIONS: LMP ovarian/peritoneal tumors have low proliferation rates in contrast to high-grade carcinomas. Proliferation correlated with tumor type and stage, but neither it nor DNA ploidy predicted survival independently. Proliferation rate is growth limiting only when low. At higher levels cell loss limits growth. SPF-LI measures proliferation more accurately than SPF-F; SPF-F is not sufficiently reliable for clinical use.

Jordan, L. B., M. Abdul-Kader, et al. (2001). "Uterine serous papillary carcinoma: histopathologic changes within the female genital tract." Int J Gynecol Cancer 11(4): 283-9.

The histopathologic features of 25 patients with uterine serous papillary carcinoma (USPC) were presented, with particular emphasis on the changes seen in the remaining mullerian epithelium. The mean age at presentation was 68.9 years; 52% of patients were stage III at the time of presentation and 40% died of their disease within 24 months of diagnosis. Histologic assessment revealed: 1) pure serous carcinoma in 56% of patients and mixed differentiation of serous and endometrioid in the remainder; 2) malignant epithelium reminiscent of that of USPC and akin to carcinoma in situ, frequently seen in the remaining endometrium, cervix, and, less commonly, the fallopian tube; 3) residual endometrium that, when identified (11/25 cases), was atrophic in all cases; 4) various types of cervical involvement in 17 cases (68%); 5) tumor within the fallopian tube in three cases (12%); and 6) carcinoma with in situ-like features in five cases (20%). In conclusion, it appears that USPC is frequently associated with malignant epithelial changes (as with carcinoma in situ) in the remaining mullerian epithelium. This finding suggests either a field change or, more likely, a transepithelial tumor spread. The latter theory is preferable, because this type of spread is frequently seen on serosal surfaces in cases of serous ovarian carcinoma. Uterine serous papillary carcinoma is, therefore, biologically more akin to its ovarian counterpart.

Bhandare, D., C. Madiwale, et al. (2001). "Mullerian adenosarcoma of the uterine cervix." Indian J Pathol Microbiol 44(3): 371-2.

Sarcomas in the uterine cervix are rare, the incidence being 0.5% to 1% of all cervical malignancies. This is a report of cervical mullerian adenosarcoma, which was encountered in a hysterectomy performed for prolapse. The tumor was composed of benign glandular elements and malignant stromal component, thus justifying its nomenclature. We wish to emphasize the distinctive morphological features of this rare cervical tumor.

Kindler, H. L., F. Millard, et al. (2001). "Gemcitabine for malignant mesothelioma: A phase II trial by the Cancer and Leukemia Group B." Lung Cancer 31(2-3): 311-7.

PURPOSE: The CALGB conducted a phase II multicenter trial to evaluate the activity of gemcitabine in malignant mesothelioma (CALGB protocol 9530). PATIENTS AND METHODS: Seventeen patients were accrued between February 1996 and May 1996 and received gemcitabine 1500 mg/m(2) by intravenous infusion over 30 min weekly for 3 weeks, followed by a 1 week break. Eligibility included a performance status of 0-2 by CALGB criteria, and no prior chemotherapy. Nine patients had epithelial cell type and eight had mixed or sarcomatoid cell types. There were 11 cases with measurable disease and six with evaluable disease. RESULTS: There were no complete or partial responders. Eight patients had stable disease, seven developed progressive disease, and two were not evaluable for tumor response. Two patients had minor responses. Median survival from study entry was 4.7 months (95% CI 3.1-12.9 months); one year survival was 24% (95% CI 10-55%). One patient remains alive at 37 months. There were two early deaths, one from disease progression and one from pneumonia. Toxicity was mild and included anemia, lymphopenia and infection; no patient experienced grades three or four thrombocytopenia. CONCLUSION: No antitumor activity was observed for single-agent gemcitabine in patients with malignant mesothelioma in this multicenter phase II study.

Airoldi, M., F. Pedani, et al. (2001). "Phase II randomized trial comparing vinorelbine versus vinorelbine plus cisplatin in patients with recurrent salivary gland malignancies." Cancer 91(3): 541-7.

BACKGROUND: Some previous studies have shown that vinorelbine (VNB) is active in recurrent salivary gland tumors. METHODS: Between April 1993 and April 1997, 36 patients in a Phase II randomized trial received either cisplatin, 80 mg/m(2), on Day 1 plus VNB, 25 mg/m(2), on Days 1 and 8 (every 3 weeks) (for a minimum of 3 cycles (Arm A [16 patients]), or VNB, 30 mg/m(2)/week, (for a minimum of 9 wks) (Arm B [20 patients]). There were 23 males and 13 females with a median age of 59 years (range, 20-74 years) and a median Eastern Cooperative Oncology Group performance status of 1 (range, 0-2). Four patients had been treated with prior surgery (S) or radiotherapy (RT), 27 patients had been treated with S plus RT, and 5 patients had been treated with S plus RT plus mitoxantrone. Eighteen patients had major salivary gland tumors, and 18 patients had minor salivary gland tumors; 9 patients had adenocarcinoma, 22 patients had adenoid cystic carcinoma, 1 patient had a malignant mixed carcinoma, 3 patients had undifferentiated carcinoma, and 1 patient had a mucoepidermoid carcinoma. The site of recurrence was local in 16 patients, local plus metastatic in 5 patients, and metastatic only in 15 patients. These characteristics were well balanced between the 2 arms. RESULTS: In Arms A and B a complete response (CR) was noted in 3 patients (19%) and no patients, respectively; a partial response (PR) was noted in 4 patients (25%) and 4 patients (20%), respectively; no change was noted in 6 patients (37.5%) and 9 patients (45%), respectively; and progressive disease was noted in 3 patients (19%) and 7 patients (35%), respectively. The median duration of the CR was 15+ months (range, 6-27+ months) and for PR the median duration was 7.5 months (range, 3-11+ months) and 6 months (range, 3-9 months) in Arms A and B, respectively. Number of patients surviving > 12 months was 6 versus 1 in Arms A and B, respectively (P < 0.05). Grade 2-3 nausea and emesis was statistically higher (P < 0.001) in Arm A; there was no significant difference with regard to other side-effects between the two treatment arms. CONCLUSIONS: VNB is a drug with moderate activity in salivary gland malignancies. The combination of cisplatin plus VNB was found to be more active than VNB alone, with a good number of CRs and long-term survivors reported in the current study.

Liao, Q., J. Wang, et al. (2001). "[Clinical and pathological analysis on 106 cases with uterine sarcoma]." Zhonghua Fu Chan Ke Za Zhi 36(2): 104-7.

OBJECTIVE: To analyze the clinical features and factors affecting the prognosis of uterine sarcoma with different histological types. METHODS: One hundred and six cases with uterine sarcoma treated were analyzed retrospectively, among which there were 67 cases with leiomyosarcoma (63.2%), 23 with malignant endometrial interstitial sarcomas (21.7%), 16 with malignant Mullerian mixed tumor (15.1%). According to Union Internationale Contre le Cancer (UICC) staging, 70 cases were on stage I, 12 cases were on stage II, 19 cases belonged to stage III, and 5 cases belonged to stage IV. RESULTS: (1) The patients with leiomyosarcoma and endometrial interstitial sarcoma were relatively younger, the patients of them aged under 50 amounted to 70.1% (47/67) and 60.9% (14/23) respectively, and those aged under 40 amounted to 29.9% (20/67) and 39.1% (9/23) respectively. The patients usually manifested with abnormal vaginal bleeding (67.0%), palpable mass of lower abdomen (32.1%), vaginal discharge (27.4%), pain on lower abdomen (28.4%), symptoms of oppression (25.5%), and discomfort feeling (28.3%). (2) The rate of preoperative diagnosis was 65.9%, especially that of leiomyosarcoma was lowest (42.9%). (3) In treatment, 16.0% of patients was treated by hysterectomy; bilateral salpingo-oophorectomy and pelvic lymphadenectomy; 75.5% of them by hysterectomy and bilateral salpingo-oophorectomy; after operation, 74.5% of them were treated by chemotherapy, 11.3% by radiotherapy, 6.6% by additional progesterone. (4) The survival period of the patients was related to pathologic types and clinical stages and ages of the patients. The prognosis of the patients with leiomyosarcoma younger earlier stage was better. CONCLUSIONS: The clinical symptom of uterine sarcoma is nonspecific (mostly abnormal vaginal bleeding) and the prognosis is poor. The patients with leiomyosarcoma are younger and have better prognosis, but the rate of preoperative diagnosis is low. The prognosis of uterine sarcoma is related to pathologic types, clinical stage and ages of the patients.

Oster-Schmidt, C., A. Rutten, et al. (2001). "[Occult dermal primary melanoma in congenital nevus-cell nevus]." Hautarzt 52(2): 143-6.

Malignant melanomas normally arise at the dermoepidermal junction. Development of these tumours in deeper layers of the dermis without having contact with the junction is rare. A small congenital melanocytic nevus localized in the region of the waist band was excised because of mechanical irritation; it had not shown any changes over years. A thorough examination of the whole body did not give any clue to a malignant melanoma. Histologically a compound nevus with the typical architecture of a congenital melanocytic nevus was found. In the deeper dermis there was an isolated nodule of extremely atypical melanocytes with minimal pigmentation of melanin. S100 antigen could be demonstrated throughout the whole tumour whereas HMB45 was only found at the dermoepidermal junction. There was no marking of the tumour cells with a pancytokeratin antibody. A histological relationship between the new tumour and a mixed tumour of the left testicle, which had been excised 3 years ago, could be excluded. We did not find any metastases neither by image-aided methods nor by sentinel lymph node biopsy.

Reddy, K. R., S. Kligerman, et al. (2001). "Benign and solid tumors of the liver: relationship to sex, age, size of tumors, and outcome." Am Surg 67(2): 173-8.

From 1983 through 1997, our center diagnosed 130 cases of benign neoplasms: 27 with focal nodular hyperplasia (FNH), 25 with hepatic adenoma, 71 with cavernous hemangioma, and seven with mixed tumors of different diagnoses. Most often these lesions were seen in females [female-to-male ratio (f/m): 5.5/1]. Hepatic adenomas and mixed tumors were seen exclusively in females and FNH predominantly in females (f/m: 26/1). Hemangiomas, however, were not uncommon in men (f/m: 52/19) relative to the other tumors (P < 0.001). Furthermore patients with hemangioma were older (mean age: 49 years) whereas patients with hepatic adenoma, FNH, and mixed tumors were often younger (mean age: 33, 35, and 44 years respectively; P < 0.004). Oral contraceptive steroid use was related by 21 of 25 patients (84%) with hepatic adenoma, 22 of 26 (85%) females with FNH, five of seven (71%) females with mixed tumors, and 10 of 52 (19%) patients with hemangioma. Ninety-five of the 130 patients (73%) had one or more symptoms. There was no statistically significant correlation between symptoms and the size of the lesion, the final diagnosis, and whether there were solitary or multiple masses. Three of 25 (12%) with hepatic adenoma presented with rupture, and one of 27 (4%) with FNH had such a consequence. None of the hemangiomas presented with rupture or progressed to such a state. One patient with hepatic adenoma (4%) had a focus of malignancy. Surgical removal of benign tumors was performed in 82 of 130 patients (63%), and there was one operative mortality (1.2%) in a patient who had a caudate lobe FNH. The types of surgical procedures included segmentectomy (62%), lobectomy (34%), and trisegmentectomy (4%). In two of 84 patients who had undergone laparotomy resection was not technically possible. Resection is recommended in all cases of hepatic adenoma because of fear of rupture or associated focus of malignancy. FNH was not observed to undergo a malignant transformation and will rarely rupture. Surgery is only recommended for symptomatic hemangioma, and size of the lesion is not a criterion for excision.

Di Filippo, A., F. Marini, et al. (2001). "[Sevoflurane in stop-flow interventions. Hemodynamics study]." Minerva Anestesiol 67(12): 849-53.

BACKGROUND: The so called stop-flow operation is based on locoregional perfusion with an antiblastic hypoxic solution of the region invaded by malignant tissue. Cardiocirculatory complications are common, mainly consisting of reduction of cardiac index, increase of arterial pulmonary pressure, systemic vascular resistance and heart rate. Sevoflurane has been used for its stable hemodynamic profile to reduce cardiocirculatory troubles. METHODS: Six patients were submitted to stop-flow operation. General anaesthesia was performed with Sevoflurane 1 MAC in Air/O2. The following parameters were recorded: nitroglycerin infusion m order to maintain the position of the balloon of the catheters, arterial oxygen saturation, end-tidal carbon dioxide, mean arterial pressure, central venous pressure, arterial pulmonary pressure, heart rate and mixed oxygen venous saturation; recordings were performed before stop-flow (T1), during stop-flow (T2) and 10' after reperfusion (T3). RESULTS: Before stop-flow (T1) all the parameters were normal. At T2 heart rate, cardiac index and pulmonary capillary wedge pressure increased whilst mean arterial pressure, systemic vascular resistance and pulmonary vascular resistance decreased. Ten minutes after the end of perfusion (T3) absence of variations in systemic vascular resistance, in pulmonary vascular resistance, in pulmonary capillary wedge pressure, in cardiac index and in mixed oxygen venous saturation were noticed. Heart rate and central venous pressure showed a tendency to decrease. CONCLUSIONS: The hemodynamic profile during stop-flow appears to be stable with general anaesthesia with Sevoflurane.

Gastrell, F. H., H. D. Brasch, et al. (2001). "Malignant mixed Mullerian tumour of the cervix treated with concurrent chemoradiation." Aust N Z J Obstet Gynaecol 41(3): 352-4.

Malignant mixed Mullerian tumours of the cervix are very uncommon. Of the 26 cases reported in the literature only 8 consist of homologous sarcoma with squamous cell carcinoma. Historically, treatment has been with radiation or surgery or a combination of both. We describe a locally advanced case treated with concurrent chemoradiation.

Muc, R. S., W. Grayson, et al. (2001). "Adult extrarenal Wilms tumor occurring in the uterus." Arch Pathol Lab Med 125(8): 1081-3.

Five previous cases of extrarenal Wilms tumor (EWT) occurring in the uterus have been reported. The oldest patient was 22 years. We report a case of uterine EWT occurring in a 42-year-old woman. Histologically, there was typical triphasic differentiation, including epithelial, blastemal, and mesenchymal elements. The important differential diagnosis in this age group, the malignant mixed mullerian tumor, is excluded by the absence of glomeruloid structures and primitive tubules. The exact histogenesis of EWT is unknown but most likely relates to the presence of nephrogenic rests occurring in the female genital tract.

Manolitsas, T. P., G. V. Wain, et al. (2001). "Multimodality therapy for patients with clinical Stage I and II malignant mixed Mullerian tumors of the uterus." Cancer 91(8): 1437-43.

BACKGROUND: The role of adjuvant therapy in the management of patients with malignant mixed Mullerian tumors (MMMT) of the uterus has not been defined. The outcome of planned multimodality therapy for patients with apparent early stage disease was assessed. METHODS: A pilot study was performed on 38 patients with clinical Stage I or II MMMTs of the uterus who were offered treatment according to a standard protocol. The protocol consisted of removal of the uterus, fallopian tubes, and ovaries and surgical staging followed by tailored radiation therapy and chemotherapy, consisting of cisplatin and epirubicin. RESULTS: The overall survival was 74% (28 of 38 patients), with a mean duration of follow-up for survivors of 55 months (range, 17-121 months). The mean time to death from disease was 26 months (range, 7-87 months). The survival rate for those patients who completed treatment according to the multimodality protocol was 95% (20 of 21 patients), with a disease free survival rate of 90% (19 of 21 patients). The overall survival of patients who did not receive the recommended treatment protocol for various reasons was 47% (8 of 17 patients). An analysis of survival curves demonstrated that there was a significant survival advantage for those patients who completed the treatment according to the multimodality protocol (P = 0.01). CONCLUSIONS: In this pilot study, patients with clinical Stage I or II MMMTs who underwent surgical staging and aggressive adjuvant radiation and chemotherapy had an excellent survival rate. The results justify a randomized prospective study of this approach.

Shintaku, M. and T. Matsumoto (2001). "Primary mullerian carcinosarcoma of the retroperitoneum: report of a case." Int J Gynecol Pathol 20(2): 191-5.

A mullerian carcinosarcoma or malignant mesodermal mixed tumor (MMMT) originated from the retroperitoneum of a 51-year-old woman; only two previous similar cases have been reported. The 1,040 gm tumor was found in the left retroperitoneal space; the center of the tumor was extensively liquified. The uterus, fallopian tubes, and ovaries were unremarkable. The histopathological features of the tumor were typical of MMMT, homologous type. The adenocarcinomatous component of the tumor was immunohistochemically positive for cytokeratin 7 and negative for cytokeratin 20. MMMTs arising in extragenital sites are rare, and most of them arise from the peritoneum. The histogenesis of extragenital MMMTs remains speculative, but the origin from the "secondary mullerian system" is most likely.

Azevedo, P., C. F. Verschraegen, et al. (2001). "Malignant mixed mesodermal tumor of the ovary treated with a cisplatin-irinotecan combination: case report." Eur J Gynaecol Oncol 22(5): 319-21.

Cho, S. B., C. M. Park, et al. (2001). "Malignant mixed mullerian tumor of the ovary: imaging findings." Eur Radiol 11(7): 1147-50.

OBJECTIVE: We describe the imaging findings of malignant mixed mullerian tumor (MMMT) of the ovary, which have not previously been reported. MATERIALS AND METHODS: We experienced 13 cases of ovarian MMMT in eight patients. All patients underwent surgical resection and the MMMTs were confirmed pathologically. US (n = 8), CT (n = 8), and MRI (n = 1) examinations were performed before operation. Imaging features were analyzed retrospectively for bilaterality, tumor solidity (cystic or solid), size, and contrast enhancement of the tumor on CT and MRI. Presence of ascites and other evidence of peritoneal seeding, adjacent organ invasion, distant metastasis, and surgical staging were also evaluated. RESULTS: There were bilateral ovarian MMMTs in five patients and unilateral MMMTs in three patients. Two of the MMMTs were multiseptated cystic, and 11 were mixed (solid and cystic). The diameter of the largest dimension was less than 5 cm in one case, 5-10 cm in two cases, and larger than 10 cm in 10 cases. Dense homogeneous contrast enhancement of the solid component was seen in 11 mixed masses. Ascites were found in all patients. Other evidence of peritoneal seeding and direct invasion into adjacent organ such as the uterus or sigmoid colon was seen in five patients each. Pleural metastasis was present in one patient. Surgical stages were FIGO classification IIIb and IV in one patient each, and IIIc in six patients. CONCLUSION: Ovarian MMMTs usually present as aggressive, bilateral, large, solid and cystic tumors, combined with ascites, frequent peritoneal seeding, and adjacent organ invasion.

Melilli, G. A., L. Nappi, et al. (2001). "Malignant mixed mullerian tumor of the ovary: report of four cases." Eur J Gynaecol Oncol 22(1): 67-9.

INTRODUCTION: Malignant mixed mullerian tumor (MMMT) of the ovary is an extremely rare gynaecologic neoplasm that represents 1% of the malignances of this organ. Stage I disease is rare because it is asymptomatic in early stage. We describe four cases. CASE REPORTS: In the Department of Obstetrics and Gynecology of the University of Bari four cases of MMMT of the ovary were diagnosed. Three patients were in stage IIIC and one of them was a homologous MMMT; the fourth patient was affected by a heterologous stage IV MMMT. All women were treated with surgery and chemotherapy. Two patients are alive 14 and 12 months after diagnosis. The other two died after 37 months and one month, respectively. CONCLUSIONS: The malignant mixed mullerian tumor (MMMT) of the ovary is a particularly aggressive tumor, especially in advanced stages. The survival rate is very low in spite of surgery, chemotherapy and radiotherapy. The optimal treatment for this neoplasm is unknown because of its rarity. Our experience, when considering survival, seems to confirm the use of cisplatin and ifosfamide and to give new horizons to taxol.

Topuz, E., Y. Eralp, et al. (2001). "The role of chemotherapy in malignant mixed mullerian tumors of the female genital tract." Eur J Gynaecol Oncol 22(6): 469-72.

Thirteen patients with malignant mixed mullerian tumor of the female genital tract, treated and followed in our clinic from 1989 to 1999 were retrospectively evaluated. Seven patients (53.8%) with advanced disease or postoperative residual tumor were treated with adjuvant chemotherapy. The median age at diagnosis was 64 years (range: 26-79). All patients underwent primary surgical cytoreduction. Tumors were localized to the endometrium in five (62.5%), to the ovaries in two (25%) and to the fallopian tube in one (12.5%) patient. One patient with endometrial carcinosarcoma had a simultaneous second primary ovarian epithelial carcinoma. Two patients (25%) had a heterologous sarcomatous component. Myometrial involvement included less than half the thickness in one patient, while there was no myometrial invasion encountered in two patients. Five patients (38.5%) had more than 50% of the myometrium invaded. Two patients received additional radiotherapy. Six patients received cisplatinum-based chemotherapy (4 had doxorubicin including combinations), while one patient was treated with a doxorubicin+ifosphamide combination. Five patients (71.4%) had a complete response (CR) to chemotherapy. Response duration in patients with a CR was +13, +67, +10, +14 and +2 months, respectively. After a median follow-up period of 20 months (3-115 months), six patients have died, five are being followed-up with no evidence of disease, one is alive with metastatic disease and one patient is under treatment. Malignant mixed mullerian tumor of the female genital tract is highly responsive to multimodality treatment strategies. Further prospective studies are required to identify distinct prognostic groups that may benefit from various treatment modalities.

Kalogeraki, A., J. Panayiotides, et al. (2000). "Cytological diagnosis of malignant mixed mullerian tumor of the uterus in ascitic fluid." Anticancer Res 20(5C): 4005-8.

The malignant mixed Mullerian tumour (MMMT) is a rare and aggressive neoplasm of the uterus, seen in postmenopausal women. In this case, an uncommon neoplasm was diagnosed cytologically in the ascitic fluid of a woman 58 years old and was confirmed histologically after hysterectomy and bilateral adnexectomy.

(2000). "NTP Toxicology and Carcinogenesis Studies of Gallium Arsenide (CAS No. 1303-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies)." Natl Toxicol Program Tech Rep Ser 492: 1-306.

Gallium arsenide is used primarily to make light- emitting diodes, lasers, laser windows, and photodetectors and in the photoelectronic transmission of data through optical fibers. Gallium arsenide was nominated for study because of its widespread use in the microelectronics industry, the potential for worker exposure, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to gallium arsenide particles (greater than 98% pure; mass median aerodynamic diameter = 0.8 to 1.0 µm) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed to gallium arsenide for 14 weeks. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. All rats survived to the end of the study. The final mean body weights of all exposed groups of males and females were similar to those of the chamber controls. Compared to chamber controls, the liver and lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased; the thymus weights of all exposed groups of males were decreased. Gallium arsenide particles were visible in the alveolar spaces and, to a lesser extent, within alveolar macrophages of exposed rats. Moderate proteinosis (surfactant mixed with small amounts of fibrin) and minimal histiocytic cellular infiltrate were observed in the alveoli of exposed males and females. Epithelial hyperplasia and squamous metaplasia of the larynx were observed primarily in males exposed to 150 mg/m(3). 16-DAY STUDY IN MICE: Groups of five male and four or five female mice were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 µm at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. The final mean body weights were similar among exposed and chamber control groups. Compared to chamber controls, the lung weights of males and females exposed to 10 mg/m(3) or greater were increased. Gallium ar senide particles were visible in alveolar spaces and macrophages in some mice exposed to 150 mg/m(3). Moderate proteinosis, mild epithelial hyperplasia, and histiocytic infiltration of the lung were observed in males and females exposed to 10 mg/m(3) or greater. In the larynx, mild squamous metaplasia was seen in mice exposed to 10 mg/m(3) or greater, and mild chronic inflammation occurred in mice exposed to 75 or 150 mg/m(3). 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. All rats survived until the end of the study. The final mean body weight and body weight gain of males exposed to 75 mg/m(3) were significantly less than those of the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in exposed groups of rats. There were also increases in platelet and neutrophil counts, a transient decrease in leukocyte counts, and increases in the serum activities of alanine aminotransferase and sorbitol dehydrogenase. These changes were of greater magnitude in male rats. The lung weights of all exposed groups of rats were increased, while testis, cauda epididymis, and epididymis weights of males exposed to 37 or 75 mg/m(3) were generally less than those of chamber controls. Total spermatid heads and spermatid counts were significantly decreased in males exposed to 75 mg/m(3), while epididymal spermatozoa motility was significantly reduced in males ees exposed to 10 mg/m(3) or greater. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of exposed rats. Minimal to marked proteinosis and minimal histiocytic cellular infiltration of the alveoli were observed in all exposed groups; minimal squamous metaplasia in the larynx and lymphoid cell hyperplasia of the mediastinal lymph node were observed in some males and females exposed to 37 or 75 mg/m(3). Exposure-related increases in the incidences of plasma cell hyperplasia of the mandibular lymph node, testicular atrophy, epididymal hypospermia, bone marrow hyperplasia (males), and hemosiderosis in the liver were observed in the 37 and 75 mg/m(3) groups. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. One female mouse exposed to 75 mg/m(3) died before the end of the study. Final mean body weights and body weight gains of males in the 75 mg/m(3) group were signifi cantly less than the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide affected the circulating erythroid mass and induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in male and female mice. There were also increases in platelet and neutrophil counts. Compared to the chamber controls, the lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased. Testis, cauda epididymis, and epididymis weights, total spermatid heads, spermatid counts, and concentration and motility of epididymal spermatozoa were generally decreased. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of mice exposed to 1 mg/m(3) or greater. Mild to marked proteinosis, histiocytic infiltration, and epithelial hyperplasia were observed in the alveoli of males and females exposed to 1 mg/m(3) or greater. Minimal to mild suppurative inflammation and granuloma in the lung and squamous metaplasia in the larynx were present in males and females exposed to 10 mg/m(3) or greater. Min imal hyperplasia was observed in the tracheobronchial lymph node of males exposed to 10 mg/m(3) or greater and females exposed to 37 or 75 mg/m(3). Exposure- related increases in the incidences of testicular atrophy, epididymal hypospermia, hematopoietic cell proliferation of the spleen, and hemosiderosis of the liver and spleen were observed in groups of male and female mice exposed to 10 mg/m(3) or greater. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.01, 0.1, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights: Survival of exposed male and female rats was similar to the chamber controls. Mean body weights of males exposed to 1.0 mg/m(3) were generally less than those of the chamber controls throughout the study; females exposed to 1.0 mg/m(3) had slightly lower mean body weights during the second year. Pathology Findings: Compared to the chamber controls, the incidences of alveolar/bronchiolar neoplasms were significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control ranges. Exposure-related nonneoplastic lesions in the lungs of male and female rats included atypical hyperplasia, alveolar epithelial hyperplasia, chronic active inflammation, proteinosis, and alveolar epithelial metaplasia. In the larynx of males exposed to 1.0 mg/m(3), the incidences of hyperplasia, chronic active inflammation, squamous metaplasia, and hyperplasia of the epiglottis were significantly increased. The incidences of benign pheochromocytoma of the adrenal medulla occurred with a positive trend in female rats, and the incidence was significantly increased in the 1.0 mg/m(3) group and exceeded the historical control range. The incidence of mononuclear cell leukemia was significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control range. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 0.5, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 (males) or 106 (females) weeks. Survival and Body Weights: Survival of male and female mice was similar to the chamber controls. Mean body weights of exposed groups of males were similar to those of the chamber controls throughout the study; mean body weights of exposed groups of females were greater than those of the chamber controls from week 13 until the end of the study. Pathology Findings: Exposure-related nonneoplastic lesions in the lung of all groups of exposed mice included suppurative focal inflammation, chronic focal inflammation, histiocyte cellular infiltration, alveolar epithelial hyperplasia, and proteinosis. Increased incidences of minimal lymphoid hyperplasia of the tracheobronchial lymph node occurred in mice exposed to 1.0 mg/m(3) and in 0.5 mg/m(3)mg/m(3) males. GENETIC TOXICOLOGY: Gallium arsenide was not mutagenic in several strains of Salmonella typhimurium, with or without S9 metabolic activation enzymes, and no increase in the frequency of micronucleated erythrocytes was observed in peripheral blood of male or female mice exposed to gallium arsenide by inhalation for 14 weeks. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of gallium arsenide in male F344/N rats exposed to 0.01, 0.1, or 1.0 mg/m(3). There was clear evidence of carcinogenic activity in female F344/N rats based on increased incidences of benign and malignant neoplasms in the lung. Increased incidences of benign neoplasms of the adrenal medulla and increased incidences of mononuclear cell leukemia were also considered to be exposure related. There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to 0.1, 0.5, or 1.0 mg/m(3). Exposure to gallium arsenide caused a spectrum of nonneoplastic lesions in the lung of rats and mice, the larynx of male rats and hyperplasia of the tracheobronchial lymph node in mice. Synonym: Gallium monoarsenide.

Attanoos, R. L., S. D. Dojcinov, et al. (2000). "Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms." Histopathology 37(3): 224-31.

AIMS: To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms. METHODS AND RESULTS: Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Mullerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified. CONCLUSIONS: Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.

Oliva, E., P. B. Clement, et al. (2000). "Endometrial stromal tumors: an update on a group of tumors with a protean phenotype." Adv Anat Pathol 7(5): 257-81.

Endometrial stromal tumors are reviewed with emphasis on their wide morphologic spectrum and problems in differential diagnosis, highlighting issues that have received particular attention in the recent literature. These neoplasms are divided into two major categories--endometrial stromal nodules and endometrial stromal sarcomas--a distinction made on the basis of the lack of significant infiltration at the periphery of the former. The division of endometrial stromal sarcomas into low-grade and high-grade categories has fallen out of favor and the designation endometrial stromal sarcoma is now considered best restricted to neoplasms that were formally referred to as "low-grade" stromal sarcoma. Endometrial sarcomas without recognizable evidence of a definite endometrial stromal phenotype, designated poorly differentiated "endometrial sarcomas," are almost invariably high grade and often resemble the mesenchymal component of a malignant mullerian mixed tumor. Two features of endometrial stromal tumors that may cause confusion are smooth muscle differentiation and epithelial patterns. Cases in the former category often have a characteristic "starburst" pattern of collagen formation. The most common epithelial patterns resemble those seen in ovarian sex-cord stromal tumors. Much less common is endometrioid gland differentiation. Some endometrial stromal tumors have a prominent fibrous or myxoid appearance and the myxoid tumors should be distinguished from myxoid leiomyosarcoma. Other unusual features of endometrial stromal tumors are also discussed. Lesions in the differential diagnosis of uterine endometrial stromal neoplasms include highly cellular leiomyoma, cellular intravenous leiomyomatosis, adenomyosis with sparse glands, metastatic carcinoma, and lymphoma. Endometrial stromal sarcomas at extrauterine sites may be primary or metastatic from a uterine tumor, the latter sometimes being occult and difficult to definitively establish, particularly if there is a history of a remote hysterectomy for "leiomyomas." Endometrial stromal sarcomas of the ovary, whether primary or metastatic, may be difficult to distinguish from ovarian sex-cord stromal tumors. Extragenital endometrial stromal sarcomas may be confused with diverse lesions such as gastrointestinal stromal tumors, hemangiopericytoma, lymphangiomyomatosis, or mesenchymal cystic hamartoma of the lung. Immunohistochemistry may play a role in evaluating these tumors and in some instances establishing the diagnosis although conventional light microscopic analysis suffices in the majority of cases. The unusual tumor, the "uterine tumor resembling an ovarian sex-cord tumor," is also considered in this review as it is almost certainly of endometrial stromal derivation in many cases. These neoplasms may have a striking resemblance to granulosa cell tumors or Sertoli cell tumors, including those with a retiform pattern, and have recently been shown to be frequently inhibin positive.

Sheyn, I., J. L. Mira, et al. (2000). "Concomitant well-differentiated adenocarcinoma and leiomyosarcoma of the uterus." Arch Pathol Lab Med 124(10): 1539-41.

We describe a case of a concomitant well-differentiated endometrial endometrioid adenocarcinoma and leiomyosarcoma of the uterus in a 66-year-old woman who presented with a 6-month history of vaginal bleeding. The patient underwent total hysterectomy for endometrial carcinoma diagnosed by endometrial biopsy. Gross examination of the specimen revealed an endometrial mass bulging into the endometrial cavity and an underlying well-circumscribed nodule separated from the endometrial mass by a myometrial band. Frozen section performed at the time of the total hysterectomy rendered a diagnosis of malignant mixed-mullerian tumor. Histologic examination of the permanent sections revealed well-differentiated endometrial endometrioid adenocarcinoma clearly separated from a high-grade leiomyosarcoma. Differential diagnosis included malignant mixed-mullerian tumor. However, no admixture of carcinomatous and sarcomatous elements was present. There were no heterologous elements. To the best of our knowledge, no similar case has been described in the English literature.

Sit, A. S., F. V. Price, et al. (2000). "Chemotherapy for malignant mixed Mullerian tumors of the ovary." Gynecol Oncol 79(2): 196-200.

OBJECTIVE: The aim of this study was to review the chemotherapy experience at Magee-Womens Hospital for malignant mixed mullerian tumor (MMMT) of the ovary. Patients were treated with either paclitaxel/carboplatin (PC) outpatient chemotherapy or platinum/ifosfamide (PI) inpatient chemotherapy as first- or second-line therapy. METHODS: Thirteen patients diagnosed with MMMT of the ovary after complete surgical staging from 1990 to 1999 were studied retrospectively. Six patients received PC combination chemotherapy, of which 3 patients received PC as first-line treatment. The other 3 patients received PC as second-line therapy. Eight patients were treated with PI. Demographic data, pathology, cytoreductive surgery, treatment, and survival rates were reviewed. Complete clinical response (CR) was defined as the disappearance of all measurable disease or normalization of elevated CA 125 level after chemotherapy. Kaplan-Meier analysis was used for survival analysis. RESULTS: The median survival time of patients receiving PC was 19 months. One patient, after receiving PC as first-line treatment, demonstrated a CR and is free of disease beyond 33 months. The median survival time of patients managed with PI was 23 months. Three patients with suboptimal disease demonstrated CR after receiving PI. CONCLUSIONS: Optimal chemotherapy regimen for MMMT of ovary remains to be determined. Platinum-based chemotherapy in combination with ifosfamide or paclitaxel may be active against this rare malignancy.

Fotiou, S., G. Hatjieleftheriou, et al. (2000). "Long-term tamoxifen treatment: a possible aetiological factor in the development of uterine carcinosarcoma: two case-reports and review of the literature." Anticancer Res 20(3B): 2015-20.

Two cases of uterine carcinosarcoma developing after long-term tamoxifen (TAM) treatment are presented. The patients, 67 and 72 years old, were treated with TAM for 6 and 7 years, continuously. They both developed an heterologous malignant mixed Mullerian tumor (mmMt). At laparotomy, an advanced stage of disease was found with peritoneal spread. In spite of the surgical and the postoperative treatment, they both died of disease, 3 and 10 months later. There are only 10, well documented, similar cases reported. Another 7 were identified in series of uterine malignancies developing after TAM treatment. Considerable evidence suggests that mmMt represents an epithelial cancer with sarcomatous dedifferentiation. Prolonged (> 5 years) TAM treatment may represent a causative factor in the development of this highly lethal disease (80% of the reported patients had a dismal prognosis). Large uterine polyps with special histological features, may represent an intermediate step in the tumor formation. Close follow-up of the patients is warranted.

Pautier, P., C. Genestie, et al. (2000). "Analysis of clinicopathologic prognostic factors for 157 uterine sarcomas and evaluation of a grading score validated for soft tissue sarcoma." Cancer 88(6): 1425-31.

BACKGROUND: Uterine sarcomas (US) are rare and carry a poor prognosis characterized by high rates of local recurrence and metastasis. The aim of this study was to test, for what the authors believe was the first time with US, the prognostic impact of the histologic grade validated by the French Federation of Anticancer Centers (FNCLCC) for soft tissue sarcomas (STS). The grade is the sum of the scores allocated for three major histologic criteria: tumor differentiation, mitotic count, and tumor necrosis. Other histologic and clinical factors were tested as well. METHODS: The study included 157 patients in whom 78 leiomyosarcomas (LMS), 52 malignant mixed mullerian tumors (MMMT), and 27 endometrial stroma sarcomas (ESS) were documented. RESULTS: The median follow-up was 54 months (range, 6-230 months). The median OS and EFS were 33 and 13 months, respectively. The FNCLCC grade validated in soft tissue sarcomas was not a prognostic factor for survival or relapse for any of the US histologic subtypes. For LMS, stage and mitotic count were the only factors that had an influence on survival and relapse. For MMMT, stage and age were the only prognostic factors, and none of the histologic criteria impacted on the outcome. For ESS, the grade defined by Norris and Taylor was an important prognostic factor, particularly for survival. CONCLUSIONS: The FNCLCC grading score could not be used as a prognostic indicator for uterine sarcomas. The diagnosis of US is in itself an unfavorable prognostic factor, except when the diagnosis is low grade ESS.

Psarras, K., M. Ueda, et al. (2000). "Targeting activated lymphocytes with an entirely human immunotoxin analogue: human pancreatic RNase1-human IL-2 fusion." Cytokine 12(6): 786-90.

A hybrid human protein was produced in E. coli by fusing the genes encoding human pancreatic RNase1 (hpRNase1) and human IL-2 (hIL-2). The recombinant hpRNase1-hIL-2 inhibited protein synthesis in HTLV-1-infected, malignant T cells, which hyperproduce high affinity IL-2 receptors, with an IC(50)of 2x10(-8) M, whereas no inhibition was detectable in control cells with lower affinity receptors. HpRNase1 alone had an IC(50)of almost 10(-3) M. A molar excess of hIL-2 blocked the protein synthesis inhibition dose-dependently. In a human mixed lymphocyte culture, hpRNase1-hIL-2 inhibited the proliferation of responder cells with potency comparable to that of cyclosporine, while non-effective doses of FK506 importantly improved its potency. Despite its short half-life in animals, hpRNase1-hIL-2 rapidly enters cells in a few minutes and arrests the protein translation in less than 10 h. Thus, hpRNase1-hIL-2 may be useful to selectively eliminate activated lymphocytes hyperproducing high affinity IL-2 receptors, as in allograft rejection, graft-versus-host disease, autoimmune disorders, adult T cell leukaemia and other lymphoproliferative or retroviral malignancies including HIV infection, without inducing general immunosuppression. As an entirely human "immunotoxin analogue" it may alleviate the dose limiting toxicity and immunogenicity of conventional immunotoxins.

Judson, P. L., A. M. Temple, et al. (2000). "Vaginal adenosarcoma arising from endometriosis." Gynecol Oncol 76(1): 123-5.

OBJECTIVE: Malignant transformation of endometriosis has been well documented. Endometrioid adenocarcinoma is the most common malignancy to occur in this setting, although other carcinomas and rarely stromal tumors can be seen. We present the first case in the literature of adenosarcoma, a rare mixed mullerian or mesodermal tumor, arising in extrauterine vaginal endometriosis. CASE: A 42-year-old woman underwent multiple medical therapies and surgeries for aggressive endometriosis. A pelvic exenteration was abandoned secondary to severe fibrosis, and low-dose radiotherapy was used to control bleeding from vaginal endometriosis. The pathologic diagnosis of recurrent endometriosis was confirmed multiple times over her 4-year course. Excision of a recurrent vaginal mass revealed adenosarcoma with heterologous elements. CONCLUSION: It is important to biopsy or excise recurrent endometriosis, as malignant transformation can occur, giving rise to epithelial, stromal, or mixed epithelial-mesenchymal tumors.

Khuu, H. M., C. P. Crisco, et al. (2000). "Carcinosarcoma of the uterus associated with a nongestational choriocarcinoma." South Med J 93(2): 226-8.

Choriocarcinoma has been reported in association with endometrial carcinoma and as a metaplastic change in multiple carcinomas, including liver, urinary bladder, lung, and the gastrointestinal tract. We report choriocarcinoma in conjunction with a carcinosarcoma (also called malignant mullerian mixed tumor) in a 71-year-old woman whose hysterectomy specimen revealed two polypoid lesions of the endometrium, one arising from the anterior endometrium and one arising from the posterior endometrium. Histologic examination revealed three histologic patterns. The anterior endometrial lesion showed a FIGO grade 2 endometrioid endometrial adenocarcinoma. The posterior endometrial lesion showed a carcinosarcoma composed of a high-grade adenocarcinoma and scant homologous stromal sarcoma. In addition, a choriocarcinoma was identified intermixed with the adenocarcinoma. The syncytiocytotrophoblasts and cytotrophoblasts stained strongly with 0 human chorionic gonadotropin (beta-hCG) and human placental lactogen (hPL). The patient's beta-hCG levels on postoperative days 14, 27, and 42 were 283, 32, and 7 mIU/mL, respectively. This unusual case suggests the importance of identifying the choriocarcinomatous component, since the serum beta-hCG can serve as a marker of tumor recurrence postoperatively.

Costa, M. J. and D. Guinee, Jr. (2000). "CD34 immunohistochemistry in female genital tract carcinosarcoma (malignant mixed mullerian tumors) supports a dominant role of the carcinomatous component." Appl Immunohistochem Mol Morphol 8(4): 293-9.

Female genital carcinosarcomas (FGTCSs) are aggressive biphasic malignant neoplasms with histologic features of both carcinomas and sarcomas. However, their behavior is dominated by the carcinomatous component. CD34 is useful in distinguishing carcinomas with sarcomatoid features from epithelioid sarcomas, as it is never expressed in carcinomas although often expressed in epithelioid sarcomas. This investigation hypothesizes that CD34 expression in FGTCSs will contribute useful histogenetic and clinical information. Paraffin sections from a surgical series of 43 FGTCSs were stained using anti-CD34 with an automated immunohistochemical stainer, antigen retrieval, and appropriate external/internal controls. Reactions were graded as follows: negative (N) or S1-3, strong reactivity in <10% = S1, 10-50% = S2, or >50% = S3 of cells, respectively. The series included 31 endometrial, 6 ovarian, 5 cervical, and 1 fallopian tubal FGTCSs, 70% exhibiting heterologous elements (22 rhabdomyosarcomas, 11 chondrosarcomas, 1 osteosarcoma, and 1 liposarcoma). The carcinomatous component included 19 endometrioid, 12 serous, 6 adenosquamous, 4 clear cell, and 2 poorly differentiated carcinomas: modified International Federation of Gynecologic Oncology grade I, 9%; II, 21%; and III, 70%. CD34 reactivity was 100% N in the carcinomatous components. CD 34 stained 21 % of sarcomatous components as follows: 2S1, 6S2, and 1S3 (three homologous and six heterologous). Of the heterologous components, only rhabdomyosarcoma stained with the following patterns: 1S1, 2S2, 1S3. Two of six heterologous FGTCSs exhibited staining of only the homologous sarcomatous component with the following pattern: 2S2, as the heterologous sarcomatous component (pure rhabdomyosarcoma in both cases) showed no staining. The staining pattern was unrelated to primary site of the FGTCSs. The pattern of CD34 expression (N in the carcinomatous component like carcinomas) supports the generally accepted opinion of dominance of FGTCS by the carcinomatous component. The staining of the sarcomatous component was rare (21%) and focal (only one of nine was S3). CD34 staining may help distinguish FGTCSs from epithelioid sarcomas, which strongly express CD34.

Huh, Y. O. and S. Ibrahim (2000). "Immunophenotypes in adult acute lymphocytic leukemia. Role of flow cytometry in diagnosis and monitoring of disease." Hematol Oncol Clin North Am 14(6): 1251-65.

Flow cytometry has revolutionized the study of hematopoietic cells. Immunophenotyping by multiparameter flow cytometry supplements conventional morphologic diagnosis by providing information on cell lineage and differentiation in ALL and helps monitor disease by improving sensitivity in detecting minimal residual disease. The use of multiple MoAbs and multicolor study by flow cytometry has revealed heterogeneity among ALL and mixed-lineage acute leukemia, which are assigned to the same diagnostic categories by morphology. As technology has improved, clinical and research applications of flow cytometry have expanded to include evaluation of nuclear markers, oncogene proteins, apoptosis, cytokine receptors, and drug resistance. Expanded identification of MoAbs against leukemia-specific markers and the use of QFCM be a significant in managing patients with ALL in the future. In addition, flow cytometry and flow cytometric sorting will be combined more and more with other technologies, such as molecular probing or fluorescence in situ hybridization (FISH). The sorting of rare malignant cells based on immunophenotype and subsequent confirmation by PCR or FISH has already been proven feasible. Ultimately, it is hoped that further definition of subgroups of ALL by immunophenotyping using prognostically significant markers and the use of hybrid technologies of flow cytometry and molecular analysis or cytogenetics will improve treatment strategies for patients with ALL.

Koseki, K., T. Takizawa, et al. (2000). "Distinction of differentiated type early gastric carcinoma with gastric type mucin expression." Cancer 89(4): 724-32.

BACKGROUND: Intestinal and diffuse gastric carcinomas differ in morphology and growth behavior. Differentiated type gastric carcinoma (DGC), which corresponds roughly with the intestinal type of Lauren, can demonstrate phenotypic properties associated with mucin expression and brush border. However, their clinical significance is controversial. A classification based on mucin phenotype and brush border was performed to determine the clinicopathologic diversity of DGCs in their early stage. METHODS: A total of 120 specimens from 116 DGC patients with definite submucosal invasion were evaluated both macroscopically and histologically. All sections were examined immunohistochemically with human gastric mucin, Muc-2, and CD10 and with mucin histochemically with paradoxical concanavalin A staining and high iron Diamine-Alcian Blue. They were classified into gastric type (G-type), intestinal type (I-type), mixed gastric and intestinal type (M-type), or null type (N-type) phenotypes. The immunoreactivity of E-cadherin and beta-catenin also was investigated to determine the correlation between mucin phenotype and clinicopathologic factors. RESULTS: The G-type phenotype was found to be in contrast to I-type: G-type was an independent factor associated with lymph node metastasis. Significant correlations were observed between the G-type phenotype and the complex type carcinoma found that was histologically: lymphatic invasion, lymph node metastasis, and the abnormal expression of E-cadherin. A significant difference in the proportion of mucin phenotypes between papillary type and tubular type carcinoma was observed. G-type was found to be the predominant phenotype in papillary carcinoma in contrast to tubular carcinoma. CONCLUSIONS: The G-type mucin phenotype and papillary adenocarcinoma should be distinguished from other types of DGCs because of their increased malignant potential in the incipient phase of invasion and metastasis. The significance of G-type and papillary adenocarcinoma should be reflected in the treatment of patients with early stage DGCs, including endoscopic mucosal resection.

Katso, R. M., S. Manek, et al. (2000). "Overexpression of H-Ryk in epithelial ovarian cancer: prognostic significance of receptor expression." Clin Cancer Res 6(8): 3271-81.

H-Ryk is an atypical receptor tyrosine kinase that is expressed in a differentiation-specific manner in epithelial tissues. We have previously shown by in situ hybridization and immunohistochemistry that H-Ryk is overexpressed in malignant ovarian tumors. In addition, we have demonstrated that overexpression of H-Ryk is transforming in vitro and in vivo. To evaluate whether expression of H-Ryk is a prognostic factor in epithelial ovarian cancer, we carried out a retrospective study of 88 primary malignant ovarian tumors (28 serous tumors, 11 mucinous tumors, 29 endometrioid tumors, 13 clear cell tumors, 3 malignant mixed Mullerian tumors, 1 mixed epithelial tumor, 1 primary peritoneal tumor, 1 undifferentiated tumor, and 1 transitional carcinoma) diagnosed between 1990 and 1993 using immunohistochemistry. On univariate analysis, overall survival decreased significantly with age (P = 0.01); in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II (P = 0.008), FIGO stage III (P < 0.001), and FIGO stage IV (P < 0.001) disease; and in patients with residual disease (residual disease < or = 2 cm, P = 0.007; residual disease > 2 cm, P < 0.001) after surgery. In addition, overexpression of the H-Ryk receptor in malignant epithelium (P = 0.04) and blood vessel (P = 0.01) was associated with a significantly decreased overall survival. H-Ryk blood vessel overexpression (P = 0.03), residual disease > 2 cm (P = 0.006), and residual disease < or = 2 cm (P = 0.01) conferred a significantly shorter progression-free survival. No correlation was found between H-Ryk overexpression and age, histological subtype, degree of differentiation, FIGO stage, or residual disease. Overall, after adjustment for all of the prognostic factors by multivariate analysis (Cox proportional hazards model), residual disease was the most powerful prognostic indicator for overall survival (P < 0.001) and progression-free survival (P = 0.01) in this patient subset. This implies that H-Ryk acts cooperatively with other biological factors in the pathogenesis of ovarian cancer.

Dallenbach-Hellweg, G., D. Schmidt, et al. (2000). "The endometrium in breast cancer patients on tamoxifen." Arch Gynecol Obstet 263(4): 170-7.

We restudied histologically and immunohistochemically 17 endometrial carcinomas, 2 malignant mixed tumors and 180 endometria with benign changes during or after tamoxifen therapy. The carcinomas were subtyped according to the 1994 WHO-classification. Endometrial biopsies were taken only if the endometrial thickness was > 8 mm sonographically, when a polyp was seen, or for postmenopausal bleeding. About half of the endometrial specimens showed simple or cystic atrophy, 55-76% had cystic-atrophic polyps or regressive hyperplasia. Depending upon the dose of tamoxifen, 7-19% (30 mg) to 27-36% (20 mg) showed moderate glandular proliferation. 20-33% had foci of mucinous, clear cell or serous-papillary metaplasia. 68-70% revealed diffuse extensive fibrosis of the endometrial stroma. None of 11 patients biopsied before starting tamoxifen therapy had advanced endometrial glandular proliferation in the second endometrial biopsy after tamoxifen treatment. None of the 19 endometrial neoplasms after tamoxifen therapy was of the endometrioid type: 11 were mucinous adenocarcinomas, 4 clear cell carcinomas, 2 serous-papillary carcinomas, one carcinosarcoma and one malignant Mullerian mixed tumor. The reasons for discrepancies between suspicious sonograms and endometrial atrophy are discussed.

Rebischung, C., P. Pautier, et al. (2000). "Alpha-fetoprotein production by a malignant mixed Mullerian tumor of the ovary." Gynecol Oncol 77(1): 203-5.

Elevated levels of alpha-fetoprotein (AFP), a fetal serum protein, usually signal the development of hepatoma or germ cell tumors, including endodermal sinus tumors. We report the case of a 52-year-old woman with an alpha-fetoprotein-producing malignant mixed Mullerian tumor (MMMT) of the ovary. Serum AFP was 5348 ng/ml at diagnosis. Immunohistochemistry confirmed that the carcinomatous component of this biphasic tumor was the seat of AFP production. After three cycles of combination chemotherapy, the patient achieved a complete remission. Serum AFP was strongly correlated with response to treatment. This is the first report of AFP production by a MMMT of the ovary without a yolk sac component.

Sinkre, P., J. Albores-Saavedra, et al. (2000). "Endometrial endometrioid carcinomas associated with Ewing sarcoma/peripheral primitive neuroectodermal tumor." Int J Gynecol Pathol 19(2): 127-32.

Three uterine tumors, each consisting of endometrioid carcinoma and Ewing's sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) are described. The diagnosis of ES/pPNET in each case was first established in the hysterectomy specimen because each ES/pPNET was misinterpreted on the endometrial biopsy specimens as a high-grade homologous sarcoma. The ES/pPNET element in each case consisted of solid masses of small- to medium-sized round cells without Homer-Wright pseudorosettes, glial or ganglion cells, true rosettes with central lumens, or medulloepithelial tubules. Each ES/pPNET exhibited focal positive immunostaining for neuron-specific enolase, diffuse staining for vimentin, and strong cell membrane immunoreactivity for O13 (CD99), the last finding providing the first clue to the diagnosis of ES/pPNET in each case. The diagnosis in each case was confirmed by detection of EWS/FLI-1 fusion transcript through reverse transcription polymerase chain reaction. We also examined O13 immunoreactivity retrospectively in 40 cases of malignant mixed mullerian tumors (MMMT) with homologous or heterologous elements. O13 immunoreactivity was not observed in the malignant epithelium or in the homologous or heterologous sarcomas. The immunoreactivity of O13 in round cell endometrial sarcomas provides a clue to the diagnosis of ES/pPNET.

Wei, C. F., S. H. Hwang, et al. (2000). "Malignant mixed mullerian tumors of the ovary." Zhonghua Yi Xue Za Zhi (Taipei) 63(4): 344-8.

Malignant mixed Mullerian tumor (MMMT) of the ovary is very rare, and to the best of our knowledge, only a few cases have been reported in the literature from Taiwan. We report two recent cases of ovarian MMMT at our hospital. Case 1 was a 59-year-old female with stage IIIC MMMT of the ovary, with a tumor having carcinomatous and sarcomatous elements. The carcinomatous component was composed of a high-grade epithelial malignancy including serous, endometrioid, clear cell and undifferentiated carcinoma elements. The sarcomatous component was composed of a homologous malignant mesenchymal element with conspicuous hyaline globules. The patient died of the disease six months after debulking surgery. Case 2 was a 42-year-old female with ovarian stage IIC MMMT. The carcinomatous component was composed of grade II-III clear cell carcinoma and the sarcomatous component was composed of high-grade non-specific spindle cell sarcoma, which was positive for vimentin, but negative for cytokeratin, desmin and S-100 protein on immunostaining. The patient died of the disease four months after debulking surgery. These two patients both underwent hysterectomy, bilateral salpingo-oophorectomy and omentectomy and both received platinum-based chemotherapy after debulking surgery.

Meyberg, R., C. Villena-Heinsen, et al. (2000). "Heterologous mullerian mixed tumor after whole body irradiation because of Hodgkin's disease in stage IV." Eur J Gynaecol Oncol 21(2): 160-3.

PURPOSE: With an incidence of 1.5% of all malignant diseases of the uterus as specified in the literature, the mullerian mixed tumor is a rarity amongst the malignancies of the female genital tract. METHODS: A retrospective analysis of an individual case report with the occurrence of heterologous mullerian mixed tumor years after irradiation because of Hodgkin's disease. RESULTS: This case reports describes the occurrence of a mullerian mixed tumor 12 years after the treatment of Hodgkin's disease by whole body irradiation. To our knowledge, the incidence of a mullerian mixed tumor after the treatment of Hodgkin's disease has rarely been described up to now in the literature. CONCLUSION: This case report appears to indicate the possible carcinogenic potency of radiotherapy when administered many years before. A causal connection between the administration of whole body irradiation and the development of a mullerian mixed tumor cannot be established.

Piura, B., A. Rabinovich, et al. (2000). "Mullerian adenosarcoma of the uterus: case report and review of literature." Eur J Gynaecol Oncol 21(4): 387-90.

Mullerian adenosarcoma--a variant of mullerian mixed mesodermal tumor of the uterus--is typically composed of benign but sometimes mildly atypical glandular epithelial elements admixed with malignant sarcomatous stroma. This rare tumor, which accounts for only about 8% of all uterine sarcomas, usually originates in the endometrium and grows as a polypoid mass within the endometrial cavity. The most prevailing presenting symptom is abnormal vaginal bleeding and the most common finding is a polypoid mass protruding through a dilated cervical canal. The case of a woman, who at age 62 presented with symptoms and signs of acute pelvic inflammatory disease and on vaginal examination an infected mullerian adenosarcoma protruding through a dilated cervical canal was discovered, is reported. Treatment consisted of extensive antibiotic treatment and surgery comprised of total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by postoperative adjuvant pelvic radiotherapy. One year later, the patient is alive with no evidence of disease.

Aprosina, Z. G., V. V. Serov, et al. (1999). "[Extrahepatic manifestations of chronic viral liver diseases]." Arkh Patol 61(5): 51-5.

The study of large groups of patients with chronic liver diseases of viral etiology (including those induced by HBV and HCV) has revealed extrahepatic manifestations which by their mechanisms formed 2 groups. The first group represents disorders related to delayed hypersensitivity in combination with immunocomplex reactions (lesions of the joints, skeletal muscles, lungs, myocardium, etc). The second group includes disorders of primarily immunocomplex genesis (vasculitis): skin vasculitis, Raynaud's syndrome, nodular periiarteritis, mixed cryoglobulinemia, etc.). Special group represents diseases of blood: immune cytopenias, monoclonal immunoglobulinopathy, malignant lymphoproliferative diseases. These findings and literature data on extrahepatic replication of HBV and HCV validate the diagnosis of "chronic generalized HBV or HCV infection" with listing of all manifestations of these infections.

Yung, W. K., M. D. Prados, et al. (1999). "Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group." J Clin Oncol 17(9): 2762-71.

PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.

Kauppila, S., F. Stenback, et al. (1999). "Characterization of type I collagen synthesis and maturation in uterine carcinosarcomas." Cancer 86(7): 1299-306.

BACKGROUND: Epithelial malignancies often induce an enhanced expression of interstitial collagens in the fibroblasts within the tumor tissue and the surrounding non-neoplastic stroma. In uterine carcinosarcomas (malignant mixed mullerian tumors [MMMTs]) both the stroma and the epithelium are malignant. METHODS: In this investigation, both in situ hybridization and immunohistochemical staining were applied with two different antibodies that were capable of distinguishing between newly synthesized and mature, trivalently cross-linked Type I collagen to define Type I procollagen mRNA expression and the synthesis and maturation of the corresponding protein in MMMTs. RESULTS: In the better differentiated parts of these tumors, in which anticytokeratins stained only clearly carcinomatous cells, Type I procollagen mRNA expression was limited to stromal fibroblasts; mature Type I collagen bundles were abundant and regular. In poorly differentiated areas, in which anticytokeratins stained only a few individual cells, Type I procollagen mRNA was expressed peculiarly by three morphologically different cell types. In addition to benign mesenchymal cells, Type I procollagen mRNA was present in atypical epithelial and mesenchymal cells. In these tumors, the collagen bundles close to the malignant cells were comprised of newly synthesized Type I collagen, with only little evidence of the presence of mature, fully cross-linked collagen. CONCLUSIONS: These results strongly suggest that the undifferentiated cells of MMMTs are capable of producing their own stroma with irregularly arranged collagen bundles.

Gaertner, E. M., J. H. Farley, et al. (1999). "Collision of uterine rhabdoid tumor and endometrioid adenocarcinoma: a case report and review of the literature." Int J Gynecol Pathol 18(4): 396-401.

Extrarenal malignant rhabdoid tumors have been reported in a variety of anatomic sites but infrequently in the female genital tract. In the uterus, they have been described as a pure tumor, in association with endometrial stromal sarcomas, and as a component of a malignant mullerian mixed tumor. This study reports an unusual uterine neoplasm in a 49-year-old woman, in which a malignant rhabdoid tumor occurred as a collision tumor with a well-differentiated endometrioid adenocarcinoma. The tumor was a 14-cm polypoid mass that filled the endometrial cavity. The two neoplastic components were distinct on microscopic and immunohistochemical examination. Ultrastructural examination confirmed the rhabdoid phenotype of the sarcomatous component. The patient died of disease 4 months after diagnosis with progression of the malignant rhabdoid tumor. The highly aggressive behavior of the rhabdoid (i.e., nonepithelial) component in this collision tumor lends support for a distinction of this neoplasm from a malignant mullerian mixed tumor, with which it may be confused.

Kindler, H. L., C. P. Belani, et al. (1999). "Edatrexate (10-ethyl-deaza-aminopterin) (NSC #626715) with or without leucovorin rescue for malignant mesothelioma. Sequential phase II trials by the cancer and leukemia group B." Cancer 86(10): 1985-91.

BACKGROUND: The Cancer and Leukemia Group B (CALGB) conducted sequential Phase II multicenter trials to evaluate the activity of edatrexate alone (E) or with leucovorin rescue (EL) in patients with malignant pleural mesothelioma (CALGB Protocol 9131). METHODS: Twenty patients were accrued to the E portion of the study and received edatrexate, 80 mg/m(2), intravenously over 20-30 minutes weekly. After a protocol amendment precipitated by excessive toxic events with E, 40 patients were enrolled in the EL arm and received the same dose of edatrexate with leucovorin, 15 mg orally, every 6 hours for 4 doses beginning 24 hours after edatrexate. Eligibility criteria included a CALGB performance status of 0-2 and no prior chemotherapy. A central pathology review was performed. Of the 58 patients included in this analysis (20 receiving E and 38 receiving EL), 36 had epithelial cell type and 22 had mixed or sarcomatous cell types. There were 31 patients with measurable disease and 27 with evaluable disease. RESULTS: The overall response rate was 25% for E (95% confidence interval [95% CI], 9-49%) and 16% for EL (95% CI, 6-31%). There was a 5% complete response [CR] rate, a 10% partial response [PR] rate, and a 10% regression [R] rate for E and a 0% CR rate, a 3% PR rate, and a 13% R rate for EL. The median survival duration from study entry was 9.6 months and 6.6 months, respectively, for E and EL; 1-year survival was 50% and 32%, respectively, for E and EL. There were four early deaths with the E regimen (including two from neutropenic sepsis) and one early death with the EL regimen (from progressive disease). Principal toxicities included mu cositis, myelosuppression, and rash, which were less frequent with leucovorin rescue. CONCLUSIONS: Moderate antitumor activity has been observed with both regimens. Leucovorin rescue ameliorated the mucosal, hematologic, and dermatologic toxicities of edatrexate, but also may have reduced its efficacy.

Sreekantaiah, C., E. Kwark, et al. (1999). "Cytogenetic and molecular characterization of a malignant mixed mullerian tumor of the uterus with a t(8;22)(q24.1;q12)." Cancer Genet Cytogenet 115(1): 73-6.

We report the cytogenetic and molecular findings in a malignant mixed Mullerian tumor of the uterus in a 65-year-old woman. Karyotypic analysis revealed a t(8;22)(q24.1;q12) as the sole abnormality in all 20 cells analyzed. Southern blot analysis of two positional candidate genes, MYC at 8q24, and EWS at 22q12, showed no genomic rearrangement. The finding of the t(8;22) as the only abnormality may be of etiologic significance.

Bertolo, F., S. De Vita, et al. (1999). "Lack of Fas and Fas-L mutations in patients with lymphoproliferative disorders associated with Sjogren's syndrome and type II mixed cryoglobulinemia." Clin Exp Rheumatol 17(3): 339-42.

OBJECTIVE: Murine models (MRL/gld/gld mice) and recent evidence in humans suggest a possible role of Fas and Fas ligand (Fas-L) germline mutations in the pathogenesis of autoimmune-related lymphoproliferation, including adult cases. In this study, the presence of Fas and Fas-L germline mutations was investigated in a consecutive series of adult patients with lymphoproliferative disorders occurring in the context of Sjogren's syndrome (SS) and type II mixed cryoglobulinemia (MC). METHODS: 11 patients (8 primary SS and 3 type II MC; F/M: 10/1; mean age 64 yrs.) were investigated. All patients were suffering from atypical lymphoproliferative disorders or MALT lymphoproliferative lesions (mean duration 3.5 yrs.). Four patients later developed a malignant lymphoma. DNA from peripheral blood mononuclear cells from 11 patients and 10 controls was tested for germline mutations in the Fas gene (exons 4, 8 and 9) and Fas-L gene (exon 4) by the polymerase chain reaction-single strand conformation polymorphism (SSCP) method. RESULTS: All DNA samples from both patients and controls showed amplification of Fas and Fas-L specific fragments. Identical SSCP migration patterns were observed in all the cases, indicating the lack of mutations in the whole series. CONCLUSION: Although it cannot be excluded that Fas and Fas-L mutations might be present in exons different from those analyzed, our data do not support the hypothesis that germline mutations in these genes are responsible for a major subset of lymphoproliferative syndromes in adult patients with SS and type II MC. Additional studies would be worthwhile in SLE-related lymphoproliferation, which is, however, a subset of limited clinical relevance when considering all cases with autoimmune-related lymphoproliferation.

Kim, T. J., H. S. Kim, et al. (1999). "Clinical evaluation of follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears." Gynecol Oncol 73(2): 292-8.

OBJECTIVES: The aim of this study was to evaluate the efficacy of the follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears. METHODS: From May 1991 to December 1996, we have performed 407, 451 cervicovaginal Pap smears, of which 326 patients were identified as AGUS. Of the 326 patients, 268 patients were followed by repeat Pap smears, colposcopy, cone biopsy, or endometrial curettage. RESULTS: The incidence of AGUS on Pap smears is approximately 0.08%. The mean age of the patients was 43 years (range 22-79 years). The most common complaint was abnormal vaginal bleeding. The gross findings of the cervix were normal to mild erosion. The following past histories of patients could affect the AGUS results on Pap smear: 30 had cone biopsy, 21 had Pap smears on pregnancy and within 8 weeks after delivery or evacuation, 3 were on hormonal replacement therapy, 2 had intrauterine devices for contraception, and 5 were undergoing follow-up after treatment of cervical cancer. The benign lesions detected during follow-up periods were 6 microglandular hyperplasia of the cervix, 5 atypical squamous metaplasia of the cervix, 2 cervical endometriosis, 2 tubal metaplasia, 10 cervical myoma, 11 cervical polyps, 9 endometrial polyps, 3 uterine myoma, 1 pelvic endometriosis, 1 ovarian endometriosis, and 4 uterine adenomyosis. The premalignant or malignant lesions of the cervix were 4 low-grade squamous intraepithelial lesions, 24 high-grade squamous intraepithelial lesions, 8 glandular atypia/dysplasia, 5 adenocarcinoma in situ, 3 microinvasive adenocarcinoma, and 4 invasive adenocarcinoma. The neoplastic lesions of the uterus were 6 endometrial hyperplasia, 11 endometrial adenocarcinoma, 1 malignant mixed Mullerian tumor, and 1 metastatic endometrial adenocarcinoma. Sixty-seven (25%) of 268 patients followed up were identified as having clinically significant lesions of the cervix or uterus. The detection rates of abnormal lesions were 3.1% with repeated Pap smears (3/98), 28.4% with colposcopic-directed biopsy (31/109), 63.6% with cone biopsy (35/55), and 29.7% with endometrial curettage (19/64). CONCLUSION: AGUS on Pap smears showed various benign and malignant lesions of the cervix or uterus. The clinicians must communicate with the pathologists regarding the patient's clinical information as well as the origin of the atypical glandular cells in Pap smears. We recommend that patients with AGUS on Pap smear should undergo immediate intensive diagnostic studies, including colposcopic-directed biopsy with endocervical curettage or cone biopsy, to detect cervical lesions and endometrial curettage to detect endometrial lesions.

Lin, D., N. Lu, et al. (1999). "[Clinico-pathologic characteristics of malignant thymoma]." Zhonghua Zhong Liu Za Zhi 21(2): 136-8.

OBJECTIVE: To assess the histopathology, clinical staging and treatment of malignant thymoma in relation to prognosis. METHODS: Sixty four cases with malignant epithelial thymic tumors treated in the period of 1958-1995 were retrospectively studied. Archived specimens were categorized according to Levine and Rosai into type I malignant thymoma(MT) and type II thymic carcinoma (TC). MT was histologically classified according to Muller-Hermelink(M-H). Clinical staging was ascertained according to Masaoka's criteria. RESULTS: There were 41 cases of MT and 23 cases of TC. No medullary or mixed thymoma was observed in this series of MT. The 5-year survival rate of patients with MT of predominantly cortical, cortical, and well-differentiated thymic carcinoma (MDTC) subtypes was 75.3%, 44.7% and 43.3%, respectively. That of patients with TC of squamous-cell carcinoma and lympho-epithelioid subtypes was 27.5% and 60.0%, respectively. The 10-year survival rate of these 5 subtypes was 25.3%, 10.0%, 0, 0, 20.0%, respectively(P < 0.05). The 5-year and 10-year survival rates decreased with increase in staging. In 22 patients in stage III and IV who received thoracotomy with biopsy only, their survival rate was significantly lower than that in patients with their tumor resected. CONCLUSION: Histomorphology of the tumor, heterogeneity in cell types, clinical staging and the extent of tumor resection are factors affecting survival.

Okihiro, M. S. and D. E. Hinton (1999). "Progression of hepatic neoplasia in medaka (Oryzias latipes) exposed to diethylnitrosamine." Carcinogenesis 20(6): 933-40.

Progression of hepatic neoplasia was assessed in medaka (Oryzias latipes) following aqueous exposure to diethylnitrosamine (DEN). Larvae (2 weeks old) were exposed to 350 or 500 p.p.m. DEN for 48 h, while adults (3-6 months old) were exposed to 50 p.p.m. DEN for 5 weeks. Fish were maintained as long as possible to determine malignant potential of resultant neoplasms. A total of 423 medaka with 106 hepatic neoplasms were examined. There were marked differences in tumor prevalence between exposure groups including: (i) higher prevalence of hepatocellular carcinomas in medaka exposed as adults (100% of hepatocellular tumors in adult-exposed medaka were malignant, while only 51.5% of larval hepatocellular tumors were malignant); (ii) higher prevalence of biliary tumors in medaka exposed as larvae (46.4% of all tumors in larval-exposed medaka were biliary versus 8.1% in adult-exposed fish); (iii) higher prevalence of mixed hepato-biliary carcinomas in adult-exposed medaka (24.3%) compared with those exposed as larvae (3%). In addition, a unique hepatocellular lesion termed 'nodular proliferation' was only observed in adult-exposed medaka. The lesion was characterized by small size (50-300 microm), complete loss of normal tubular architecture and variable megalocytosis. Nodular proliferation was distinct from preneoplastic foci of cellular alteration and may represent microcarcinomas. There was a step-wise increase in mean diameter with age (days post-exposure) from nodular proliferation (174 microm, 17 days) to hepatocellular carcinoma (1856 microm, 62 days) and mixed carcinomas (3209 microm, 93 days) in adult-exposed medaka. Metastasis was observed with 19 neoplasms and tumors with the highest metastatic potential were hepatocellular and mixed carcinomas. The most common form of metastasis was trans-coelomic, followed by direct invasion and distant metastasis, presumably via the vascular route. Differences in tumor prevalence between exposure groups were believed to be the result of length of DEN exposure rather than age of fish at the time of exposure. In larval medaka with brief (48 h) DEN exposure, neoplasms are thought to be the result of dedifferentiation of hepatic cells, with slow progression of foci of cellular alteration to benign and then malignant tumors. In contrast, with adult medaka and prolonged (5 week) DEN exposure, neoplasms are believed to result from initiation of committed stem cells and formation of microcarcinomas ('nodular proliferation'), before progressing to larger hepatocellular and then mixed carcinomas.

Remstein, E. D., C. A. Arndt, et al. (1999). "Plexiform fibrohistiocytic tumor: clinicopathologic analysis of 22 cases." Am J Surg Pathol 23(6): 662-70.

Twenty-two cases of plexiform fibrohistiocytic tumor were reviewed to perform a clinicopathologic correlation with the behavior of the neoplastic entity. The tumor arises more frequently in children, adolescents, and young adults (mean age of presentation, 14.6 years), with strong female predilection (F:M, 6:1). It involves preferentially the upper extremity (64%), especially the fingers, hand, or wrist (45%). Most patients present with a small (average size, 2.5 cm; range, 0.5-8 cm) painless mass that slowly enlarges for months to years. All tumors involve subcutaneous adipose tissue, with extension into the dermis (19%), skeletal muscle (14%), or both (14%). Grossly, the tumors characteristically are poorly circumscribed and of firm consistency. Histologically, they are characterized by a plexiform proliferation of mononuclear histiocyte-like cells, multinucleated osteoclast-like cells, and spindle fibroblast-like cells in variable proportions and have three distinct growth patterns: fibrohistiocytic (36% of tumors), fibroblastic (32%), and mixed (32%), depending on the predominant cell type. Cellular atypia and pleomorphism are usually absent or minimal. Most tumors (78%) display mitotic activity, frequently <3 mitoses/10 high-power fields, and only 14% of the lesions display atypical mitoses. Vascular invasion was seen in only one tumor. Immunohistochemically, all tumors evaluated reacted with antibodies to CD68 that stained mainly the multinucleated giant cells and, to a lesser extent, mononuclear histiocyte-like cells and, occasionally, fibroblast-like cells. Less frequently, staining with antiactin antibodies was observed, restricted mainly to spindle cells. All nine tumors examined had a diploid DNA content. According to latest follow-up data (average period, 3.6 years) from 16 patients, 13 (82%) were alive with no evidence of disease (average, 3.6 years), 1 (6%) was alive with metastatic disease (follow-up, 2.3 years), 1 (6%) was alive with a stable pulmonary nodule of unknown nature (follow-up, 1.75 years), and 1 (6%) had died of disease 3 years after local recurrence and regional lymph node and pulmonary metastases developed. Two patients (12.5%) had local recurrence, 1 (6%) had regional lymph node metastasis, and 3 (19%) had pulmonary metastases. No proven association between clinicopathologic features and outcome was identified. In conclusion, plexiform fibrohistiocytic tumor is a rare mesenchymal neoplasm of young persons characterized by low-grade malignant behavior and is prone to recur locally and occasionally to metastasize regionally and systemically.

Imai, H., H. Kitamura, et al. (1999). "Mullerian carcinofibroma of the uterus. A case report." Acta Cytol 43(4): 667-74.

BACKGROUND: Mullerian carcinofibroma is composed of malignant epithelial tumor (cancer) and benign mesenchymal tumors. It is the least frequent among mixed mullerian tumors. There are eight reported cases of carcinofibroma or cases showing similar histology, with only two of these cases recurrent. CASE: A case of mullerian carcinofibroma arose in the uterine body. The patient was an 83-year-old, postmenopausal female whose endometrial cytology revealed cell clusters of adenocarcinoma and scattered nonepithelial cells with enlarged nuclei without nuclear atypism or mitosis. Histology of the resected uterus showed a mixture of well to poorly differentiated adenocarcinoma, and fibromatous and leiomyomatous nonepithelial tumors without a transition between them. There was no sign of recurrence nine months after hysterectomy. CONCLUSION: Mullerian carcinofibroma seems to have a better prognosis than malignant mixed mullerian tumor. When both cancer cells and an abundance of nonepithelial cells are seen on gynecologic cytology, it may be important to consider mixed mullerian tumor and to differentiate mullerian carcinofibroma from malignant mixed Mullerian tumor by careful observation of the nuclear size, nucleoli, nuclear atypism and mitosis of the nonepithelial cells.

Hellstrom, A. C., G. Tegerstedt, et al. (1999). "Malignant mixed mullerian tumors of the ovary: histopathologic and clinical review of 36 cases." Int J Gynecol Cancer 9(4): 312-316.

Among 2,895 malignant ovarian tumor cases referred to Radiumhemmet, Stockholm from 1975 through 1995, 36 were certified to be malignant mixed mullerian tumors. The overall prognosis was poor with only 18% five-year actuarial survival (median survival 16.6 months). Five patients are still surviving after 75, 68, 117, 121, and 168 months, respectively. Fifteen women treated with melphelan, doxorubicin (adriamycin) and cisplatin (MAP) had a five-year actuarial survival of 33.3% and a median survival of 19.8 months. In a multivariate analysis taking into account stage, age, radiation, type of chemotherapy, histopathologic type and completeness of surgery, the most important predictors for survival were stage (stages I-II vs stages III-IV, P < 0.05), histopathologic type (homologous vs heterologous, P < 0.05), and type of chemotherapy (MAP or CAP vs other types, P < 0.05). We concluded that homologous tumor and chemotherapy containing cisplatin, doxorubicin, and melphalan, as well as early stage of the tumor, provided the optimal survival rate.

Lam, K. Y., U. S. Khoo, et al. (1999). "Collision of endometrioid carcinoma and stromal sarcoma of the uterus: a report of two cases." Int J Gynecol Pathol 18(1): 77-81.

Two uterine collision tumors are reported, one in an 85-year-old woman and the other in a 47-year-old woman. Each tumor was composed of a smaller grade 1 endometrioid adenocarcinoma that was distinct from a larger component of high-grade stromal sarcoma. The separate components in these tumors could be detected on gross, microscopic, and immunohistochemical studies. The clinicopathologic features and indolent behavior of these tumors suggest that they should be distinguished from malignant mullerian mixed tumors.

Goldstein, S. M., N. A. Syed, et al. (1999). "Cancer-associated retinopathy." Arch Ophthalmol 117(12): 1641-5.

Patients with systemic cancer may have a variety of ocular complaints. Most commonly these are metastases or adverse effects of therapy. Paraneoplastic syndromes, like cancer-associated retinopathy, rarely cause ophthalmic symptoms. We describe a patient with a malignant mixed mullerian tumor and cancer-associated retinopathy who had circulating serum antibodies to recoverin and cells positive for recoverin in the tumor. We discuss the typical clinical symptoms as well as the pathophysiology of this uncommon disorder.

Rossi, A. (1999). "[Carcinosarcoma (malignant mixed Mullerian tumor) arising in an endometrial polyp. Report of a case]." Pathologica 91(4): 282-5.

Malignant degeneration of an endometrial polyp occurs rarely, i.e. approx. 0.36%. In literature the rare cases of carcinosarcomatous degeneration of an endometrial polyp described are mostly associated with a good prognosis. The following is a description of an other case of carcinosarcoma arisen and confined to an endometrial polyp, but characterised by a particularly aggressive clinical course.

Schmidt, C. J., L. Domenico, et al. (1999). "Aberrant antigen expression detected by multiparameter three color flow cytometry in intermediate and high grade B-cell lymphomas." Leuk Lymphoma 34(5-6): 539-44.

The aberrant expression of antigens (Ag) in lymphoproliferative disorders may cause a diagnostic problem when single parameter immunohistochemical assays are performed on frozen or paraffin sections because coexpression by relevant cells is not determined. This aberrant expression also raises the question as to whether mixed lineage (biphenotypic) lymphoid proliferations exist. Marrow (6) and extramedullary (20) tissues from 26 patients with diffuse, intermediate and high grade, B-cell lymphomas (IWF E=1, F=1, G=19, H=1 and J=4) were analyzed with 19 markers using 3-color flow cytometry. The percentages (%) of patients with double Ag coexpression in at least 20% of the CD19+ or CD20+ lymphoma cells were: stem cell (SC) Ag: CD10 = 58 and CD34 = 15; T-cell Ag: CD2 = 38, CD5 = 19 and CD7 = 19; myeloid (My) Ag: CD13 = 19 and CD33 = 8. The corresponding % with unusual triple Ag coexpression in at least 10% of the CD19+ B-cells were SC+T+ Ag: CD10CD2 = 50, CD10CD5 = 27, CD10CD7 = 38, CD34CD2 = 31, CD34CD5 = 19 and CD34CD7 = 27; T+T+ Ag: CD2CD5 = 35, CD2CD7 = 42 and CD5CD7 = 31; T+My+ Ag: CD2CD13 = 35 and CD2CD33 = 12; and My+My+ Ag: CD13CD33 = 12. Ten of 12 lymphomas tested showed clonal immunoglobulin (Ig) heavy chain gene rearrangements in the absence of clonal T-cell receptor (TCR) gene rearrangements. None (0%) of the My Ag positive cases showed immunoreactivity for myeloperoxidase. We conclude that the anomalous T and My Ag expression seen in the above B-cell lymphomas is not indicative of mixed lineage proliferation but represents the aberrant expression of these antigens by the malignant cells.

Baschinsky, D. Y., T. H. Niemann, et al. (1999). "Malignant mixed Mullerian tumor with rhabdoid features: a report of two cases and a review of the literature." Gynecol Oncol 73(1): 145-50.

Rhabdoid tumors were originally described as a type of pediatric renal neoplasm that contains cells resembling rhabdomyoblasts but lacking muscle differentiation. Extrarenal rhabdoid tumors have since been reported in multiple anatomic sites in the pediatric and adult population. These tumors are characterized by an aggressive clinical course, resistance to treatment, and a rapidly fatal outcome. Eight cases of uterine neoplasms with rhabdoid differentiation have been previously reported. In the three cases where clinical follow-up was available, the patients died of disease within 3 to 17 months after the diagnosis was established. We report two cases of uterine malignant mixed Mullerian tumor (carcinosarcoma) with rhabdoid differentiation. The findings and clinical outcome confirm the aggressive nature of uterine tumors with rhabdoid differentiation. One of the patients died of disease 3 months after initial operative treatment while the other patient's tumor recurred in 1 month and she died within 10 weeks. The poor prognosis of these neoplasms makes their histopathologic recognition important.

Gohda, T., H. Nakano, et al. (1999). "[A case of leukemic lymphoma complicated by M-proteinemia: effectiveness of long-term daily administration of oral low-dose etoposide in continuing remission]." Gan To Kagaku Ryoho 26(5): 703-7.

A 51-year-old man was admitted with systemic lymph node adenopathy. Hematological examination on admission revealed leukocytosis, and 35% of leukocytes were classified as pathologically abnormal. Moreover, increases in serum IgM (kappa type) and plasma viscosity were recognized. Following biopsy of the lymph node, a diagnosis of non-Hodgkin's lymphoma (diffuse, mixed type) was made. After the implementation of combination chemotherapy, the results of hematological and physical examinations improved. As the nadir receded, serum IgM increased once more, and nine courses of chemotherapy were necessary. In order to promote steady progress toward discharge, etoposide therapy was instituted. Subsequent low-dose etoposide therapy at 50 mg/day rarely resulted in an increase in serum IgM, subjective or objective adverse effects, except for mild lekopenia. After discharge the patient was placed on intermittent etoposide therapy and remained in a state of remission for approximately 11 months. Fortunately, his rehabilitation was successful, and he returned temporarily to his former position. The 2nd remission has continued for approximately seven months. Consequently, long-term low-dose etoposide therapy is speculated to be a significantly useful therapeutic technique for intractable malignant lymphoma.

Bridgewater, J. A. and G. J. Rustin (1999). "Management of non-epithelial ovarian tumours." Oncology 57(2): 89-98.

Ovarian tumours of non-epithelial origin are less common than those of epithelial origin but must be distinguished from these as their natural history and management differ. As these tumours are rare, histological review by an expert in the field is essential. There have been no randomised trials to outline the management of these tumours and therefore this paper represents a review of descriptive data. Non-epithelial ovarian tumours, which represent approximately 50% of all ovarian tumours and approximately 25% of malignant ovarian tumours, are outlined. Lymphomas and metastatic tumours should be treated the same as when found in other sites and will not be discussed further.

Eltabbakh, G. H. and R. Yadav (1999). "Good response of malignant mixed mullerian tumor of the ovary to paclitaxel and cisplatin chemotherapy." Eur J Gynaecol Oncol 20(5-6): 355-6.

Survival of patients with advanced stage malignant mixed mullerian tumor of the ovary is poor and the best treatment remains unknown. A 62-year-old woman diagnosed with stage IIIC heterologous malignant mixed mullerian tumor of the ovary underwent optimal cytoreductive surgery followed by paclitaxel (135 mg/m2 over 24 hours) and cisplatin (75 mg/m2) every 4 weeks for 6 courses. The patient tolerated chemotherapy well, had complete clinical response and remained without disease for 21 months following diagnosis. Paclitaxel and cisplatin may be effective in malignant mixed mullerian tumors of the ovary.

Gorson, K. C. (1999). "Clinical features, evaluation, and treatment of patients with polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS)." J Clin Apheresis 14(3): 149-53.

A number of common disorders of the peripheral nervous system are closely linked to a monoclonal gammopathy. In a minority of patients, the neuropathy represents the sentinel feature of a malignant plasma cell dyscrasia, such as multiple myeloma or its osteosclerotic variant, Waldenstrom's disease, amyloidosis, cryoglobulinemia or lymphoma; the vast majority have so-called "monoclonal gammopathy of undetermined significance" (MGUS). Sensory symptoms predominate with paresthesias, numbness, imbalance, and gait ataxia. Electrodiagnostic studies show mixed demyelinating and axonal features and often may be indistinguishable from findings in chronic inflammatory demyelinating polyneuropathy. Some have a pure axonal polyneuropathy, and in these patients the relationship to the paraprotein is less certain. With limited success, correlations have been made between the immunoglobulin type (IgM, IgG, or IgA) and the clinical and electromyographic characteristics of the neuropathy. The treatment of MGUS neuropathies poses a considerable challenge. Patients with IgG/IgA-MGUS have improved with corticosteroids or intravenous immune globulin. Only the benefit of plasma exchange has been substantiated in a controlled trial. The IgM neuropathies tend to be more refractory but often improve with similar regimens, particularly if cytotoxic agents are added in doses sufficient to reduce the amount of the M-protein. In addition to plasma exchange, chlorambucil, and cyclophosphamide, interferon-alpha is a novel therapy that holds promise for patients with IgM neuropathies associated with anti-myelin associated antibodies.

Guarino, M., P. Micheli, et al. (1999). "Pathological relevance of epithelial and mesenchymal phenotype plasticity." Pathol Res Pract 195(6): 379-89.

Epithelium and mesenchyme, two tissue types virtually found in every organ, are endowed with fundamentally different functional properties. Active motility, a capability that is limited to the mesenchymal repertoire, is the principal characteristic that distinguishes them. During embryonic development, conversions from epithelium to mesenchyme and from mesenchyme to epithelium normally occur, allowing morphogenetic processes and tissue remodelling to take place. However, there is now increasing evidence that the modulation between the epithelial and the mesenchymal phenotypes is not limited to embryonic life. Indeed, the pathogenesis of some adult diseases seems to implicate an inappropriate activation of this change. On the other hand, failure of normally occurring embryonic epithelial-mesenchymal interconversions could result in the development of some pathologies. It is now possible to study some molecular events underlying these phenotype transitions, since several biological agents implicated in the epithelial-mesenchymal interconversion, such as growth factors, extracellular matrix components and their receptors, transcription factors and oncogenes have been identified. The malignant potential of some oncogenes seems to express itself through the disruption of the mechanisms involved in the maintenance of the epithelial phenotype while, on the other hand, some observations suggest the existence of regulatory genes able to counteract the action of oncogenes by restoring epithelial characteristics. Therefore, the manipulation of the tissue phenotype could represent a novel strategy for the prevention and treatment of diseases in the future.

Soong, R., S. Knowles, et al. (1999). "p53 protein overexpression and gene mutation in mixed Mullerian tumors of the uterus." Cancer Detect Prev 23(1): 8-12.

Alteration of the p53 tumor suppressor gene is associated with poor prognosis in many human cancer types. We examined the incidence and prognostic significance of p53 gene alterations in a series of uterine malignant mixed Mullerian tumors (MMT). Nuclear overexpression of p53 protein detected by immunohistochemistry (IHC) with the DO-7 antibody was observed in 12 of 24 (50%) tumors. Mutation of the p53 gene detected by single-strand conformation polymorphism (SSCP) of exons 5 to 8 was found in 11 of 24 (46%) tumors. The incidence of p53 alteration in uterine MMT was significantly higher than in several common epithelial tumor cell types previously investigated in our laboratory using identical techniques. However, unlike these tumors alteration of the p53 gene does not appear to be of prognostic importance in uterine MMT.

Banerjee, S. S., J. D. Coyne, et al. (1998). "Diagnostic lessons of mucosal melanoma with osteocartilaginous differentiation." Histopathology 33(3): 255-60.

AIMS: To document the clinical, morphological and immunohistochemical features of two cases of primary mucosal melanoma with osteocartilaginous differentiation. MATERIALS AND METHODS: Two cases of mucosal melanoma with cartilage and bone formation are reported, one arising in the vagina of a 79-year-old woman and one in the oral cavity of a 67-year-old man. The vaginal melanoma exhibited only cartilaginous differentiation. The oral cavity mucosal melanoma exhibited both bone and cartilage formation and was remarkable for its multifocality, long history not associated with metastases and its lengthy manifestation of dual morphologies: some of the tumours were typical in situ/invasive melanotic melanomas whilst the others were composed of amelanotic spindle and epithelioid cells with osteocartilaginous tissue. One of the lesions exhibited in situ and invasive melanoma with transition to an osteogenic tumour in places. The patient also developed nonosteogenic malignant melanomas in the nasal cavity and nasopharynx. CONCLUSIONS: Malignant melanomas showing foci of osteocartilaginous differentiation are extremely rare with only 18 cases reported. Primary mucosal malignant melanomas of vagina and oral cavity showing osteocartilaginous differentiation have not previously been documented. Primary vaginal melanoma with cartilaginous differentiation must be distinguished from primary malignant mixed Mullerian tumour whilst malignant change in a pleomorphic adenoma, sarcomatoid carcinoma, osteogenic sarcoma and mesenchymal chondrosarcoma are included in the differential diagnosis of primary oral mucosal melanomas with osteocartilaginous differentiation. In this context, immunohistochemistry using antibodies to cytokeratin, S100 protein and MIC2 is of value.

Di Vagno, G., G. Cormio, et al. (1998). "Prolonged survival of stage IV malignant mixed Mullerian tumor of the ovary after carboplatin, mesna, ifosfamide, and cis-platin chemotherapy: case report." J Chemother 10(5): 418-21.

Malignant mixed mullerian tumors (MMMT) of the ovary are rare, aggressive and rapidly progressive tumors. According to the available literature, the presence of metastatic disease rarely permits long term survival. We report on a 64-year old patient with stage IV ovarian MMMT who achieved a surgically-documented complete response (CR) after 6 cycles of carboplatin, mesna, ifosfamide, cis-platin. Pelvic recurrence was diagnosed 14 months later; the patient received 6 cycles of the same regimen used as first-line chemotherapy which resulted in a second complete response lasting for 4 months. The patient died 37 months after initial diagnosis due to intestinal occlusion. In the current case Ca 125 was significantly increased at clinical presentation of disease but not at the time of recurrence.

Dammacco, F., P. Gatti, et al. (1998). "Hepatitis C virus infection, mixed cryoglobulinemia, and non-Hodgkin's lymphoma: an emerging picture." Leuk Lymphoma 31(5-6): 463-76.

Hepatitis C virus (HCV) is a single-stranded RNA agent which expresses its genetic informations in the form of a single, large polyprotein encoded by an open reading frame (ORF) that extends through most of its genomic RNA. Proteolytic cleavage of the ORF product is essential for the virogenesis and the production of viral progeny. HCV is responsible for chronic liver disease, cirrhosis and possibly hepatocellular carcinoma. Viral persistence is considered the greatest problem in the management of HCV infection. It may result from several mechanisms, two of which are established. In the first, the high rate of genetic variations during viral replication results in the production of mutants capable of escaping the immune attack. In the second, the virus infects cells of the immune system itself, which represent a privileged site that cannot be reached by virus-specific T cell response. Involvement of lymphoid cells in the early stages of HCV infection may provide insight into the pathobiologic patterns of extrahepatic dissemination (lymph nodes, major salivary glands, kidneys, blood vessels). Dissemination of HCV-infected lymphoid cells throughout the organism is likely to maintain a mobile and extensive reservoir of the virus. In this respect, extrahepatic sites may act as a source of continuous reinfection of hepatocytes. Studies of intrahepatic B lymphocytes indicate that they are infected with HCV, clonally expanded and activated to secrete IgM molecules with rheumatoid factor activity. This strongly suggests that HCV directly stimulates B cell expansion, which may result in an indolent stage of lymphoproliferation (i.e., mixed cryoglobulinemia) or in frank B cell non-Hodgkin's lymphoma (NHL). The frequency of NHL, however, is much lower than that of HCV infection, suggesting that HCV alone is not able to induce tumors and that cellular events, in addition to the presence of virus and virus-encoded products, are necessary in order to obtain a malignant B cell phenotype. The demonstration of HCV productive infection in bone marrow-recruited and circulating pluripotent hematopoietic CD34+ stem cells indicates that HCV replication occurs in the early differentiation stages of hematopoietic progenitors. These are stable cell populations and are likely to represent the initial site of infection and a continuous source of virus production.

Ermilova, V. D., A. V. Smirnov, et al. (1998). "[Malignant mesodermal (Mullerian) mixed tumor of the ovary: histologic, immunohistochemical and cytologic study]." Arkh Patol 60(3): 48-52.

A rare case of aggressive ovarian tumor in a 38-year-old female is described. Cytological diagnosis of the intraoperative smears was difficult because of the presence of the epithelial and non-epithelial components. The latter consisted of two types: spindle cells and roundish undifferentiated cells with multinuclear forms. Histologically, it was a malignant mesodermal (Mullerian) mixed tumor. Round mesenchymal cells expressed desmin and vimentin while spindle cells expressed myoglobin. Non-epithelial component was verified as leiomyosarcoma and rhabdomyosarcoma. Cells of the epithelial component expressed cytokeratins and epithelial membrane antigen.

Guarino, M., F. Giordano, et al. (1998). "Malignant mixed mullerian tumor of the uterus. Features favoring its origin from a common cell clone and an epithelial-to-mesenchymal transformation mechanism of histogenesis." Tumori 84(3): 391-7.

AIMS AND BACKGROUND: Various histogenetic mechanisms have been postulated to explain the biphasic carcinomatous-sarcomatous appearance of malignant mixed mullerian tumors (MMMTs), but the nature of these uncommon neoplasms is still unclear. Some evidence would suggest that MMMT displays similarities with sarcomatoid carcinoma, a tumor arising in extragenital sites that also features a mixed appearance. To gain further insight into the histogenesis of this tumor, we have studied by immunohistochemistry a case of uterine MMMT showing an extensive rhabdomyosarcomatous component. METHODS: A panel of antibodies including reactivity for p53, cytokeratin, vimentin, desmin, muscle actin, epithelial membrane antigen (EMA), myoglobin, type IV collagen, laminin, and tenascin was applied to paraffin tumor sections by means of the avidin-biotin complex technique. RESULTS: p53 immunoreactivity was observed in approximately the same number of cells in carcinomatous and sarcomatous tissue. The former stained for vimentin, cytokeratin and EMA, while the latter, in addition to expressing vimentin, desmin, muscle actin and myoglobin, also exhibited immunoreactivity for epithelial markers such as cytokeratin and EMA. At the borders between carcinoma and sarcoma the basement membrane pattern, as seen by staining for type IV collagen and laminin, showed interruptions in correspondence with areas of transition between the two tissues. Antibody to tenascin strongly labeled the sarcomatous tissue immediately around carcinomatous elements. CONCLUSIONS: A similar immunoreactivity for p53 in both carcinomatous and sarcomatous components, expression of epithelial markers in the sarcomatous cells, and disruption of the basement membrane profile in areas of transition between carcinomatous and sarcomatous tissue, would all suggest, as has been postulated for extragenital sarcomatoid carcinomas, an origin from a common epithelial clone and an epithelial-to-mesenchymal transformation-based mechanism of development for this MMMT. In addition, these findings provide further analogies between these categories of tumors, supporting a unifying nosological concept for MMMTs and sarcomatoid carcinomas of non-genital tract origin.

Sood, A. K., J. I. Sorosky, et al. (1998). "Primary ovarian sarcoma: analysis of prognostic variables and the role of surgical cytoreduction." Cancer 82(9): 1731-7.

BACKGROUND: Data regarding the value of cytoreduction and cell histology in ovarian sarcomas are limited. The goal of this study was to assess the value of surgical cytoreduction, preoperative CA 125 levels, stage, histology, and platinum-based chemotherapy in the primary treatment of ovarian sarcomas. METHODS: A retrospective analysis of 47 women with primary ovarian sarcomas was performed. RESULTS: Forty-one patients (87%) presented with advanced stage disease (International Federation of Gynecology and Obstetrics Stage III or IV). Optimal surgical cytoreduction (< 1 cm residual tumor burden) was achieved in 25 patients (53%). Forty patients (85%) had a malignant mixed mullerian tumor whereas 7 patients had a pure sarcoma. Eighteen women with mixed mullerian tumors had homologous tumors and 22 had heterologous elements. Patients treated with platinum-based chemotherapy were significantly more likely to have a response (P = 0.008) compared with those treated with other regimens. Treatment with platinum-based chemotherapy also showed a survival advantage (P = 0.03). Preoperative CA 125 levels were elevated (> 35 U/mL) in 93% of patients with ovarian sarcomas. A preoperative CA 125 level < 75 U/mL was significantly associated with better survival (P = 0.01). In univariate analysis, other significant predictors of improved survival were early stage (P = 0.04), homologous tumors (P < 0.05), and optimal surgical cytoreduction (P < 0.001). In multivariate analysis of various prognostic variables, optimal surgical cytoreduction (P < 0.001) was the most significant factor, followed by histologic subtype (P < 0.02). CONCLUSIONS: Ovarian sarcomas are rare malignancies with a poor prognosis. All women with suspected ovarian carcinoma or sarcoma should have a preoperative CA 125 level taken. Surgical cytoreduction to a residual tumor burden of < or = 1 cm improves outcome and should be the goal of surgery. Although the optimal consolidation chemotherapy regimen remains unknown, platinum should be included as part of the regimen.

Ayala, A. G. and J. Y. Ro (1998). "Testicular tumors: clinically relevant histological findings." Semin Urol Oncol 16(2): 72-81.

Testicular germ cell neoplasms affect young men in the prime of life. Although the overwhelming majority are malignant, they are curable. In addition to the stage of the disease and the presence of serum markers, there are important pathological changes that have clinical significance. These include (1) the cell type, (2) the amount of the component, and (3) the presence or absence of vascular invasion. Pure embryonal carcinoma or embryonal carcinoma in excess of 80% in a mixed tumor and vascular/lymphatic invasion are high-risk factors as they are predictors of relapse. These factors should be recognized by the pathologist and should be taken into account by the oncologist when selecting the management of a patient with a germ cell tumor of the testis.

Wong, E. T., E. F. Jackson, et al. (1998). "Correlation between dynamic MRI and outcome in patients with malignant gliomas." Neurology 50(3): 777-81.

We assessed the correlation between dynamic MRI results and clinical outcomes in patients with malignant gliomas. Rapid serial MRIs were obtained after bolus injection of gadolinium that resulted in an initial fast uptake followed by a slow uptake of contrast. The maximum rate of uptake and delayed rate of uptake were correlated with survival and prognostic covariates such as age and histology. In 121 subjects, higher maximum uptake rates, 3.6 signal intensity units per second or greater, were associated with shorter survival (p = 0.0066). The correlation of delayed rate of uptake with survival was less significant. After adjusting for age, histology, and Karnofsky performance score, the maximum rate of uptake remained more significantly correlated with survival than the delayed rate of uptake. Thirty-one patients had surgery within 1 month of dynamic MRI, and those with glioblastoma multiforme or anaplastic gliomas had higher maximum rates of uptake than those with pure necrosis or mixed tumor and necrosis (p = 0.022). No correlation between delayed rate of uptake and histology was seen in this group of patients. Our results suggest that the maximum rate of uptake in dynamic MRI can be a prognostic measure for patients with malignant gliomas. Further prospective study is needed to assess the utility of this technique for evaluating brain tumors.

Macak, J. (1998). "[Molecular biology aspects of Hodgkin's disease]." Vnitr Lek 44(6): 370-2.

Immunohistological methods did not elucidate the etiology and pathogenesis of Hodgkin's disease. In "classical" cases the immunophenotype is based on evidence of three markers: CD30+, CD15+, CD20-. Despite the use of more recent methodical approaches a considerable percentage of Hodgkin and RS cells with CD15 antibody is negative. The Epstein-Barr virus (EBV) plays an important part in the development of malignant disease and at the same time a number of nuclear antigens can be detected: EBNA-1, EBNA-2, EBNA-3a,-3b,-3c,LP. Also latent membrane proteins LMP-1, -2a, -2b and two small ribonucleic acids described as EBER-1, EBER-2. Bcl-2 protein was detected in the majority of malignant lymphomas which reduces its value in differential diagnostic reflections. In Hodgkin and RS cells its positivity is not due to translocation or other disorders of the cell genoma. In these cells the expression of mRNA for bcl-2 is much more constant. Most probably there is no cooperation of bcl-2 and p53. Co-expression of the two genes was found only in a small percentage of patients with m.Hodgkin. The varied morphological picture in particular in the mixed type of m. Hodgkin is most probably associated with the formation and release of cytokines, factors which stimulate cell colonies (IL-3, GM-CSF, G-CSF, M-CSF). Non-tumourous cells chemotactically attracted to sites of tumour cells release further cytokines e.g. TGF-beta, IL-1, Il-2, which participate in the overall morphological appearance of the lesion.

Zelmanowicz, A., A. Hildesheim, et al. (1998). "Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors." Gynecol Oncol 69(3): 253-7.

OBJECTIVE: To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas. METHODS: A multicenter case-control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type. All participants were asked to respond to a questionnaire which ascertained information on exposure to factors postulated to be linked to the development of uterine tumors. RESULTS: Women with endometrial carcinomas and MMMTs were similar with respect to age and educational attainment. Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous estrogen use, and nulliparity were related to risk of both tumor types. Marked obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development. Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5). Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral contraceptive use protected against the development of both carcinomas (OR = 0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34; 95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not carcinoma development (OR = 0.81; 95% CI = 0.56,1.2). CONCLUSION: Results from this study suggest that MMMTs and carcinomas have a similar risk factor profile. This observation is compatible with the hypothesis that the pathogenesis of these two histological types of uterine tumors is similar.

Clement, P. B., J. T. Zubovits, et al. (1998). "Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus." Int J Gynecol Pathol 17(3): 211-22.

Malignant mullerian mixed tumors (MMMTs) of the uterine cervix are rare; less than 30 cases have been reported in the literature and only 14 have been described in detail. As a result, the clinical and pathologic features of these tumors are not well characterized. The clinicopathologic features of nine cervical MMMTs (all cases referred because of problems in differential diagnosis) are reported here and the literature on the previously described cases is reviewed. The patients ranged in age from 23 to 87 (mean 65) years. The initial manifestations were mainly vaginal bleeding or spotting or, less commonly, an abnormal Pap smear. All of the patients had a cervical mass on examination. Of the eight patients for whom staging information was available, seven were stage Ib and one was stage II. Treatment in six patients was hysterectomy with lymphadenectomy in five; postoperative radiation therapy, chemotherapy, or both were given to two of these patients. The remaining three patients were treated by local excision (with lymphadenectomy in one) followed by radiation therapy, chemotherapy, or both in two. Follow-up, available for seven patients, revealed recurrent pelvic tumor in two patients at 1.6 and 3.0 years, respectively; the former patient died from tumor at 3.5 years whereas the latter was alive with tumor at 4.5 years. Another patient was well for II years but died 13 years postoperatively from colonic adenocarcinoma. Four other patients were alive with no evidence of tumor at postoperative intervals of less than 2 years. Gross examination revealed polypoid or pedunculated masses 1.1 to 10.0 cm in maximal dimension that invaded the cervical wall in 50% of the hysterectomy specimens. On microscopic examination, three tumors contained a predominant or exclusive epithelial component of basaloid carcinoma, two contained squamous cell carcinoma, and four contained adenocarcinoma (endometrioid in three and nonspecific in one). In seven tumors, the sarcomatous component was homologous, usually resembling fibrosarcoma or endometrial stromal sarcoma; in four of these tumors, myxoid change was prominent. Two tumors contained heterologous sarcomatous elements. In three patients, a pure carcinoma abutted the MMMT: an adenoid basal carcinoma in two (with a minor component of in situ and invasive squamous cell carcinoma in each) and an endometrioid endocervical adenocarcinoma in one. These findings, combined with analysis of the previously reported cases, indicate that cervical MMMTs, compared to their counterparts in the corpus, are more commonly confined to the uterus at presentation, may have a better prognosis, and frequently have a nonglandular epithelial component.

Ebert, A. D., A. Perez-Canto, et al. (1998). "Stage I primary malignant mixed mullerian tumor of the fallopian tube. Report of a case with five-year survival after minimal surgery without adjuvant treatment." J Reprod Med 43(7): 598-600.

BACKGROUND: Sarcomas of the fallopian tube are rarities in gynecologic oncology, consisting of < 1% of all genital sarcomas. CASE: A 70-year-old woman with a stage I malignant mixed mullerian tumor (MMMT) (International Federation of Gynecology and Obstetrics classification of fallopian tube carcinomas) did not undergo radical surgery or adjuvant treatment because of the patient's refusal of them. The patient underwent only abdominal hysterectomy with bilateral salpingo-oophorectomy. She was discharged feeling well and without abnormal clinical findings. Sixty months after primary surgery there were no signs of recurrence. CONCLUSION: This case suggests the possibility of a good prognosis in early-stage MMMT, especially if there is no deep infiltration of the fallopian tube muscle layer or lymphatic permeation and if the peritoneal cytology is negative. The important feature of this report is the five year disease-free survival after nonradical surgery for prognostically favorable MMMT.

Lunel, F. and L. Musset (1998). "Hepatitis C virus infection and cryoglobulinaemia." Forum (Genova) 8(1): 95-103.

Mixed cryoglobulins (CG) are serum proteins that precipitate at low temperature and are commonly classified into two types according to the presence (type II) or not (type III) of monoclonal immunoglobulins. Mixed CG are observed in a wide variety of diseases. Some mixed cryoglobulinaemia occurs without evidence of an underlying disease and is considered as essential mixed cryoglobulinaemia (EMC). Many studies have underlined the possible involvement of liver diseases in the pathogenesis of cryoglobulinaemia and particularly viral hepatitis. Recently, it has been shown that 50 to 80% of patients with EMC are in fact infected with HCV. It has also been shown that CG may be found in about 50% of patients infected with HCV. HCV-RNA genomic sequences are specifically concentrated in CG as well as IgG reactive with HCV-related proteins, and monoclonal IgM with rheumatoid factor (RF) activity. The monoclonal IgM RF detected in HCV infected patients is highly restricted to the same cross-idiotype OWAO. In addition to hepatocytes, HCV-RNA has been found in both peripheral blood and BM mononuclear cells. These cells could represent a reservoir of virus and may play a major role in viral persistence; they also could act as effectors of tissue injury in various organs. HCV shows high genomic variability. It is not clear whether these genetic variations have a significant clinical impact (i.e. severity of the disease) but there is evidence that they may influence both the efficacy of the host immune response and the interferon treatment response. The role of viral factors has been studied but a clear relationship between the presence of cryoglobulinaemia, the viral load or the HCV genotype have not been demonstrated. The frequency of clinical symptoms related to mixed cryoglobulinaemia reported in the literature is extremely variable according to the series. The striking association between HCV infection and mixed type II CG (usually considered as a benign lymphoproliferative disorder) and the occurrence of HCV infection in patients with NHL suggest that HCV could be involved in the pathogenesis of some malignant lymphoproliferative disease. The progression to malignancy probably involves the accumulation of multiple mutations facilitated by chronic antigenic stimulation. The efficacy of anti-viral treatment on both CG levels and related symptoms argue strongly that HCV is involved in the production of CG.

Blom, R., C. Guerrieri, et al. (1998). "Malignant mixed Mullerian tumors of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 44 cases." Gynecol Oncol 68(1): 18-24.

AIM: The authors retrospectively analyzed the prognostic significance of p53, mdm-2, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathologic factors in patients with malignant mixed Mullerian tumors (MMMT) of the uterus. METHODS: Between 1970 and 1995, 44 uterine tumors were diagnosed as MMMT (21 stage I, 2 stage II, 10 stage III, and 11 stage IV). Thirty-two were homologous type and 12 were heterologous type. DNA flow cytometry and immunohistochemical analysis for p53 and mdm-2 overexpression were performed on paraffin-embedded archival tissue. RESULTS: 68% of the tumors were nondiploid and 61% had an SPF greater than 10%. Sixty-one percent overexpressed p53 and 25% were mdm-2-positive. Furthermore, 91% of the tumors had a mitotic count greater than 10/10 hpf and 95% had high-grade cytologic atypia. Twenty-seven (61%) patients died of tumor and 6 (14%) died of intercurrent disease. Eleven (25%) patients are alive with no evidence of disease. The median follow-up for patients still alive was 59 months (range, 28-178 months). The overall 5-year survival rate was 38%. In a univariate analysis that included stage, histologic type, DNA ploidy, SPF, p53, mdm-2, mitotic index, and age, and with survival as the end point, only stage reached statistically prognostic significance. CONCLUSION: The majority of the tumors had obvious signs of aggressiveness such as high grade, high mitotic count, nondiploid pattern, high SPF, and overexpression of p53. This study found that stage is the most important prognostic factor for survival in MMMTs of the uterus.

Kounelis, S., M. W. Jones, et al. (1998). "Carcinosarcomas (malignant mixed mullerian tumors) of the female genital tract: comparative molecular analysis of epithelial and mesenchymal components." Hum Pathol 29(1): 82-7.

Female genital tract carcinosarcomas (FGTCS) are biphasic neoplasms composed of an admixture of malignant epithelial and mesenchymal elements. Histogenesis of FGTCS centers on two theories: (1) simultaneous formation of independent tumors (biclonal theory), (2) multidirectional differentiation of a single neoplasm (monoclonal theory). In an attempt to resolve this histogenetic controversy, we determined the presence, specific genotype, and timing of p53 mutational change in each component of FGTCS using a topographic genotyping (TG) approach. We selected 43 FGTCS from the files of Magee-Womens Hospital, Pittsburgh, and initially immunostained them for p53 protein. Strong p53 immunopositivity was detected in 35 (82%) of 43 tumors. Subsequently, topographic genotyping (TG) was performed on a subset of nine immunopositive tumors with sufficiently distinct malignant components to enable effective sampling. All nine tumors showed point mutations in p53 exons 5 through 8. In each case, the identical point mutational genotype was present in both components. Furthermore, in all nine cases mutations were present with loss of the wild-type allele. P53 gene mutation is a frequent event in progression of FGTCS. Of importance, both p53 mutation and allelic loss occur before the differentiation into separate epithelial and mesenchymal malignant components. These molecular findings strongly support monoclonal, multidirectional histogenesis of FGTCS.

Mathoulin-Portier, M. P., F. Penault-Llorca, et al. (1998). "Malignant mullerian mixed tumor of the uterine cervix with adenoid cystic component." Int J Gynecol Pathol 17(1): 91-2.

Malignant mullerian mixed tumors of the uterine cervix are rare; <30 cases have been reported. We describe a new case in which the carcinomatous component was predominantly adenoid cystic carcinoma. Only one similar case has been reported.

Iwasa, Y., H. Haga, et al. (1998). "Prognostic factors in uterine carcinosarcoma: a clinicopathologic study of 25 patients." Cancer 82(3): 512-9.

BACKGROUND: Carcinosarcoma (malignant mixed mullerian tumor) of the female genital tract is a highly malignant neoplasm. The tumor stage and histologic grade of the carcinomatous component are among the important prognostic indicators cited in the literature for this tumor. METHODS: Twenty-five patients with uterine carcinosarcoma at 4 hospitals in the Kyoto and Nara areas of Japan were studied retrospectively. The clinicopathologic and immunohistochemical data including p53, bcl-2, Ki-67, and proliferating cell nuclear antigen (PCNA) staining were analyzed using univariate and multivariate analysis with the Cox proportional hazards model to investigate potential prognostic indicators for this neoplasm. RESULTS: The 5-year survival rate was 36.4% for all stages, 62.3% for Stage I, and 0% for Stages II-IV. From the univariate analysis, stage (P = 0.0001), endometrioid adenocarcinoma as a carcinomatous component (P = 0.0006), age (P = 0.0355), and a heterologous sarcomatous component (P = 0.0421) were found to be prognostically significant for patient survival. Stage was the only independent significant factor in the multivariate analysis (t = 2.212). None of the other factors (history of pregnancy and gestation, gross appearance of the tumors, grade of the carcinomatous component, mitotic count of the sarcomatous component, Ki-67 and PCNA reactivity, or p53 or bcl-2 positive staining) was found to be a significant prognostic indicator. CONCLUSIONS: Stage appears to be the only definite independent prognostic indicator of survival in patients with uterine carcinosarcoma. It is uncertain whether age, endometrioid adenocarcinoma as a carcinomatous component, or absence of a heterologous component in the sarcomatous area are prognostic factors. Immunohistochemical expression of p53, bcl-2, Ki-67, or PCNA is not a prognostic indicator. The immunohistochemical results of the current study may support the hypothesis of a common stem cell origin of this tumor.

Muthuphei, M. N. and H. J. Maluleke (1998). "Malignant mixed mullerian tumours of the body of the uterus: a clinicopathological study of 20 cases." Cent Afr J Med 44(2): 45-7.

OBJECTIVE: To review the clinical and histopathological data on malignant mixed mullerian tumours. DESIGN: A retrospective study of 20 cases of malignant mixed mullerian tumours seen over a period of five and half years. SETTING: Departments of Obstetrics and Gynaecology and Anatomical Pathology at Garankuwa Acdemic Hospital. SUBJECTS: Clinical and histopathological records of patients with malignant mixed mullerian tumours of the body of the uterus. METHODS: Clinical record and histopathological slides were reviewed. Age, clinical presentation and histological appearances of the cases were noted. RESULTS: The patient age ranged from 16 to 78 years with a median of 63 years (Q1 = 58.5, Q3 = 71.5). Of the 20 cases 14 died within 12 months of diagnosis. Clinical staging and histological staging had no effect on tumour behaviour and outcome of disease. CONCLUSION: Malignant mixed mullerian tumours are predominantly seen in post menopausal women. These tumours have a very poor prognosis irrespective of clinical stage, histological grade or the type of the stroma.

Roman, J., C. Martin, et al. (1998). "Importance of mixed chimerism to predict relapse in persistently BCR/ABL positive long survivors after allogeneic bone marrow transplantation for chronic myeloid leukemia." Leuk Lymphoma 28(5-6): 541-50.

Determination of hematological chimerism could be helpful in understanding the biology of leukemic relapse after allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML), because the detection of malignant residual cells carrying the bcr/abl message by qualitative RT-PCR is of limited value in predicting disease progression for individual patients. We have studied the chimerism pattern and the bcr/abl status by Southern-blot in 15 CML patients (M/F:6/9) transplanted with unmanipulated BM from HLA identical sibling donors, persistently bcr/abl positive by RT-PCR. The median age of the series was 31 years (18-49) and disease status at BMT was: chronic phase: 11, accelerated phase: 3 and blast crisis: 1 patient. Of the 15 patients, 9 are alive and in complete remission (CR), 4 have died in CR and 2 are alive but suffered relapse at + 19 and +26 months post-BMT. The median follow-up is 81 months (13,7-168). Rearrangement of the BCR gene was performed by Southern-blot using P32-labeled transprobe-1. PCR analysis of chimerism was assessed using primers for the following VNTR loci: D1S80, D1S111, 33.1, APO-B, YNZ-22, lambdag3 and DXS52. Seventy-nine samples were analyzed (median per patient 5 (range 2-9)). Thirteen patients showed complete chimerism and lacked BCR rearrangement over time by Southern-blot. The 2 patients who relapsed showed mixed chimera status from +9 and +5 months respectively until the end of the study. Persistent BCR rearrangement was observed in these 2 patients from +12 and +11 months respectively. Our data suggest that mixed chimerism may predict hematologic or cytogenetic relapse by several months in those patients who are persistently PCR-positive post-BMT.

Thai, T. H., F. Du, et al. (1998). "Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers." Hum Mol Genet 7(2): 195-202.

Germline alterations of BRCA1 result in susceptibility to breast and ovarian cancer. The protein encoded by BRCA1 interacts in vivo with the BRCA1-associated RING domain (BARD1) protein. Accordingly, BARD1 is likely to be a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. We have now determined the genomic structure of BARD1 and performed a mutational analysis of 58 ovarian tumors, 50 breast tumors and 60 uterine tumors. Seven polymorphisms were detected within the 2.34 kb coding sequence of BARD1 . Somatically acquired missense mutations were observed in one breast carcinoma and one endometrial tumor; in at least one of these cases, tumor formation was accompanied by loss of the wild-type BARD1 allele, following the paradigm for known tumor suppressor genes. In addition, a germline alteration of BARD1 was identified in a clear cell ovarian tumor (Gln564His); again, loss of the wild-type BARD1 allele was observed in the malignant cells of this patient. The Gln564His patient was also diagnosed with two other primary cancers: a synchronous lobular breast carcinoma and a stage IA clear cell endometrioid cancer confined to an endometrial polyp 6 years earlier. These findings suggest an occasional role for BARD1 mutations in the development of sporadic and hereditary tumors.

Khouri, I. F., M. Keating, et al. (1998). "Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies." J Clin Oncol 16(8): 2817-24.

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma. PATIENTS AND METHODS: Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present. RESULTS: Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04). CONCLUSION: These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.

Neesham, D., P. Kerdemelidis, et al. (1998). "Primary malignant mixed Mullerian tumor of the vagina." Gynecol Oncol 70(2): 303-7.

A 74-year-old woman presented with postmenopausal bleeding. Examination showed a 5.5-cm ulcerated, partly necrotic vaginal polyp arising anteriorly near the hymenal ring. Histology showed a malignant mixed Mullerian tumor (MMMT) with squamous and glandular epithelial and undifferentiated spindle cell stromal components, cytological atypia, and frequent mitoses. The tumor was closely associated with overlying vaginal intraepithelial neoplasia, grade III, from which it appeared to be arising. The patient was treated by surgical excision, followed by radiotherapy. Six months later, she developed a left supraclavicular lymph node metastasis. MMMT is a rare primary vaginal neoplasm, but, including this case, there have been at least 7 cases reported in the English language literature.

Lim, S. C., D. C. Kim, et al. (1998). "Malignant mixed Mullerian tumor (homologous type) of the adnexa with neuroendocrine differentiation: a case report." J Korean Med Sci 13(2): 207-10.

Malignant mixed mullerian tumors (MMMT) are unusual neoplasms occurring mostly in the uterus. In the ovary, they are very rare and represent fewer than 1% of all ovarian malignancies; in the salpinx, they are even rarer than those of the ovary. We report a carcinosarcoma of the left adnexa having features of neuroendocrine differentiation in a 69-year-old female. The tumor contained both adenocarcinoma and squamous cell carcinoma having dear cell change admixed with an undifferentiated malignant mesenchymal component. The sarcoma components consisted of spindle cells, small-round cells and bizarre giant cells mimicking rhabdomyoblast. Almost all of the carcinomatous glandular components and some foci of the squamous cell and undifferentiated carcinomatous components were focal positive for S-100 protein, chromogranin, neuron specific enolase, synaptophysin and Leu-7. Electron microscopy revealed membrane-bound neurosecretory granules in the cytoplasm of some glandular epithelial cells. Histologically, the tumor involved the left adnexa, abdominal peritoneum, surface of the bladder dome, omentum and left external iliac lymph node (stage IIIc).

Krishnan, E. and R. E. Coleman (1998). "Malignant mixed mullerian tumours of gynaecological origin: chemosensitive but aggressive tumours." Clin Oncol (R Coll Radiol) 10(4): 246-9.

We report the clinical management and outcome of 11 patients with a histological diagnosis of mixed mullerian tumour of gynaecological origin who were treated at Weston Park Hospital, Sheffield during the period 1991 to 1996. Case note review provided the data on the patients, their disease and the treatment given. In six patients, the primary site was the ovary and in four it was the uterus; in the remaining patient, the tissue of primary origin was uncertain. The median age at diagnosis was 53 years (range 48-84). Seven patients had heterologous tumour histology. All but one underwent surgical removal or debulking of disease. Seven patients were treated with platinum-based chemotherapy. There were four complete responders and three partial responders. The median survival was 18 months. Three patients remain alive, two of them disease-free. Mixed mullerian tumours are initially chemosensitive but have an aggressive clinical course, typically with early relapse after treatment and a poor long-term prognosis. Collaborative Phase III studies are required to improve the management of this uncommon cancer.

Molpus, K. L., S. Redlin-Frazier, et al. (1998). "Postoperative pelvic irradiation in early stage uterine mixed mullerian tumors." Eur J Gynaecol Oncol 19(6): 541-6.

PURPOSE OF INVESTIGATION: To review our management experience with uterine mixed mullerian tumors (MMTs) in order to evaluate potential prognostic indicators, and assess the efficacy of various treatment modalities. METHODS: A retrospective, clinicopathologic evaluation of 43 patients presenting for treatment of uterine MMTs between 1982 and 1992 was conducted. Diagnostic criteria for inclusion was the presence of both a malignant glandular or squamous epithelial component, and a homologous or heterologous stromal component. RESULTS: Overall 2- and 5-year cancer related Kaplan-Meier survival estimates with 95% confidence intervals were 44 (.28, .59) and 26% [.12, .39], respectively. Survivals were 83 [.62, .99] and 58% [.31, .85] when disease was confined to the uterus, and 22 [.03, .41] and 7% [.01, .20] when disease extended beyond the uterus. Clinical staging was often inaccurate, with 29% of clinical stage I or II disease being upstaged at laparotomy. A significant survival advantage was found in patients with stage I or II disease treated with surgery plus pelvic irradiation (p = 0.001), as compared to those treated with surgery alone. The prognosis after disease recurrence was poor, irrespective of secondary therapy, with a median survival of 11 months. CONCLUSIONS: A therapeutic advantage may be gained from postoperative pelvic irradiation in the treatment of surgical stage I or II uterine MMT.

Piura, B., A. Rabinovich, et al. (1998). "Primary sarcoma of the ovary: report of five cases and review of the literature." Eur J Gynaecol Oncol 19(3): 257-61.

Primary ovarian sarcomas are rare and usually behave very aggressively. Over a ten-year period (1987-1996) five cases of primary ovarian sarcoma were managed at the Soroka Medical Center, Beer-Sheva, Israel. Four patients had malignant mullerian-mixed mesodermal tumor (MMMMT): two had Stage IIIC tumor with chondrosarcoma being the predominant sarcomatous element, one had Stage IIIC tumor with high-grade endometrioid stromal sarcoma (ESS) being the predominant sarcomatous element and one had Stage IC tumor with rhabdomyosarcoma being the predominant sarcomatous element. One patient had Stage IA leiomyosarcoma (LMS). All four patients with MMMMT received postoperative adjuvant chemotherapy, whereas the patient with LMS did not. The four patients with MMMMT died of their disease 10, 10, 13 and 25 months, respectively, after initial surgery. The patient with LMS died of intercurrent disease 21 months after initial surgery. It is concluded that most patients with primary ovarian sarcoma present with extraovarian disease and the prognosis is poor. The mainstay of treatment is debulking surgery consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy and extirpation of tumor masses. The benefit of postoperative adjuvant chemotherapy and/or radiotherapy is still a subject of debate and has yet not been established.

Huang, H. Y. and W. J. Chen (1997). "Malignant thymoma: a review of 44 cases." Changgeng Yi Xue Za Zhi 20(3): 174-80.

BACKGROUND: Malignant thymomas are rare neoplasms. Factors affecting prognosis and survival of patients with this neoplasm have been intensively discussed, but the results vary among different studies. To find possible prognostic factors, we designed this retrospective study. METHODS: Forty-four cases of malignant thymomas diagnosed and treated in Chang Gung Memorial Hospital, Kaohsiung, from 1986 to 1996 were reviewed. RESULTS: Of the 44 cases, 24 were male and 20 were female (M:F = 1.2:1). Patient age ranged from 25 to 73 years (median 48 years). Thirty-four cases (77%) belonged to type I malignant thymoma (invasive thymoma) and 10 cases (23%) belonged to type II malignant thymomas (thymic carcinoma). The most frequent histologic type was predominantly epithelial (43%), followed by mixed lymphoepithelial (27%). Six patients had myasthenia gravis. Eleven (25%) patients, including 4 cases of invasive thymoma and 7 cases of thymic carcinoma, showed tumor metastasis to lung, bone, liver, spleen and omentum. The 5-year survival was 73% for patients who underwent total tumor excision and 18% for those who received partial tumor excision or biopsy only. The influence of histologic types on prognosis is not statistically significant (P = 0.434). CONCLUSION: Completeness of tumor excision at initial operation is the most important prognostic factor. Predominantly epithelial and mixed lymphoepithelial types are more aggressive forms with a higher tendency to invasion.

Mwinyoglee, J., N. Simelela, et al. (1997). "Non-puerperal uterine inversions. A two case report and review of literature." Cent Afr J Med 43(9): 268-71.

Chronic non-puerperal uterine inversions are rare but the occasional case has to be managed without previous experience. Of the 77 cases reported, 75 (97.4%) were tumour produced and 20% of these tumours were malignant. The importance of taking biopsies from tumours before definitive surgery is highlighted. Adequate surgical management requires experience in vaginal surgery.

Yuan, Y., W. H. Kim, et al. (1997). "Establishment and characterization of cell lines derived from uterine malignant mixed Mullerian tumor." Gynecol Oncol 66(3): 464-74.

OBJECTIVE: We report the establishment and characterization of three new cell lines derived from uterine malignant mixed mullerian tumor (MMMT). METHODS: Three uterine MMMT cell lines from primary tumors of Korean patients were cultured and the involved cell morphology, growth properties, DNA profiles, immunohistochemical properties, tumor-associated antigen secretion, and genetic alterations of related oncogenes and tumor suppressor genes were studied as well. RESULTS: Three MMMT cell lines were successfully established including one homologous tumor SNU-539 and two heterologous tumors SNU-685 and SNU-1077. All lines showed substrate adherence and high viability and were proven by DNA fingerprinting analysis to be unique. Contamination by mycoplasma and bacteria was excluded. SNU-539 and SNU-1077 cells stained positively for both epithelial and mesenchymal antigens, while SNU-685 cells only stained positively for mesenchymal antigens. The level of secretion of tumor-associated antigens, CA125 and CEA, was shown to be undetectable in all three lines. One missense mutation from AAC to GAC at codon 239 of exon 7 in the p53 gene was identified in SNU-539. CONCLUSIONS: These newly established and characterized permanent uterine MMMT cell lines might be regarded as valuable resources for a multitude of in vitro investigations, which should be used for clarifying the obscure histogenetic origin and understanding the biological behavior of this aggressive tumor.

Buchwalter, C. L., E. L. Jenison, et al. (1997). "Pure embryonal rhabdomyosarcoma of the fallopian tube." Gynecol Oncol 67(1): 95-101.

Rhabdomyosarcoma is a neoplasm of childhood which commonly arises in the genitourinary tract. Reported locations include the bladder, prostate, paratestis, vagina, uterus, cervix, and ovary. Rhabdomyosarcomas have been reported to occur in the fallopian tube only as a component of a malignant mixed mullerian tumor. We present a case of pure embryonal rhabdomyosarcoma of the fallopian tube in a 17-year-old. The diagnosis was confirmed by immunohistochemical stains. The strongest evidence for the primary location of this pure embryonal rhabdomyosarcoma was the gross appearance of the tumor at laparotomy. Additionally, rhabdomyosarcomas arising from adjacent organs have never been reported to grow into the fallopian tubes.

Emoto, M., H. Iwasaki, et al. (1997). "Characteristics of rhabdomyosarcoma cell lines derived from uterine carcinosarcomas." Virchows Arch 431(4): 249-56.

Rhabdomyosarcoma (RMS) is occasionally found in the female genital tract, and mostly appears as one of the heterologous mesenchymal components in uterine carcinosarcoma designated as malignant mixed mullerian tumour (MMMT). We examined the biological properties of a pure rhabdomyosarcoma (RMS) cell line designated FU-MMT-3, which was newly established from a surgical specimen taken from a patient with uterine MMMT. We also evaluated c-myc and MYCN gene amplification in three RMS cell lines (including FU-MMT-3) derived from three MMMTs by Southern blot analysis. FU-MMT-3 cells were propagated continuously for 57 serial passages over a 2-year period in vitro. FU-MMT-3 was able to produce tumours demonstrating pure RMS in athymic nude mice. Cytogenetically, FU-MMT-3 showed a triploidy pattern, with complex karyotypic abnormalities including trisomy of chromosome 8. All three RMS cell lines, including FU-MMT-3, showed amplification of the c-myc gene (approximately fourfold to eightfold), while no cell lines demonstrated MYCN gene amplification. FU-MMT-3 is considered to provide a useful system for the study of the biological behaviour of RMS in MMMTs. Extra copies of chromosome 8 and c-myc gene amplification may be associated with the rhabdomyoblastic differentiation in MMMT.

Remmelink, M., I. Salmon, et al. (1997). "In vitro characterisation of soft tissue tumor chemosensitivity." Anticancer Res 17(3C): 2009-17.

BACKGROUND: The benefit of performing chemotherapy on soft tissue sarcomas remains controversial. The present study deals with the in vitro characterisation of the influence of 3 antitumoral agents on the growth of 8 sarcoma cell lines. MATERIALS AND METHODS: Cell growth was monitored by means of the MTT colorimetric assay, which was further validated by a direct cell counting method. The three drugs tested included doxorubicin (ADR), cisplatin (DDP) and dacarbazine (DTIC). ADR was tested at 10(-5) M, 10(-6) M and 10(-7) M; DDP at 10(-5) M, 10(-6) M and 10(-7) M; and DTIC at 10(-3) M, 10(-4) M and 10(-5) M. A combination of the three drugs was also tested in order to ascertain whether a synergistic effect on cell growth inhibition could be obtained. A potential antineoplastic agent-induced influence on cell growth was determined 3 days after the addition of the diverse drug(s) to the culture media. The cell concentration was specifically adapted to each cell line. The 8 cell lines included 3 leiomyosarcomas, 1 malignant mixed Mullerian tumour, 3 rhabdomyosarcomas and 1 fibrosarcoma. RESULTS: The results show that of the three drugs tested, ADR was the most efficient in terms of the level of cell growth inhibition obtained and the number of cell lines whose growth was significantly inhibited. Of the three drugs, the least active was DDP. A significant synergistic effect was observed when the three drugs were added together to the culture medium. This synergistic effect was evident at the lowest doses tested for each drug. Whatever the histopathological type, the 8 cell lines exhibited a wide range of response to chemotherapy. CONCLUSIONS: The present study shows that the inhibition induced by 10(-7) M ADR, 10(-7) M DDP and 10(-5) M DTIC on sarcoma cell line growth is significantly more efficient than if each agent is tested individually. The in vitro methodology used here fits in with clinical reality because it enables sarcoma cell heterogeneity to be taken into account.

Shibahara, H., E. Wakimoto, et al. (1997). "A case of a patient diagnosed with malignant mixed Mullerian tumor of the ovary who conceived after conservative surgery and adjuvant chemotherapy." Gynecol Oncol 65(2): 363-5.

A case of successful pregnancy after treatment of stage Ia malignant mixed Mullerian tumor of the ovary is described. This tumor is very rare and usually occurs in postmenopausal women. cis-platinum-based chemotherapy following the primary operation in the early stage is the most effective treatment, although most of the tumors have been found in the advanced stage. In this patient, treatment with unilateral salpingo-oophorectomy to preserve fertility was performed and followed by cis-platinum-based chemotherapy for 5 years. Two years after completion of the chemotherapy, she spontaneously conceived and the course of the pregnancy has been uneventful to this point.

Dubey, P., C. S. Ha, et al. (1997). "Localized primary malignant lymphoma of bone." Int J Radiat Oncol Biol Phys 37(5): 1087-93.

PURPOSE: A single institution's experience with the treatment of localized primary malignant lymphoma of bone (PLB) was analyzed to identify major prognostic factors, toxicity, and optimal treatment for this rare malignancy. METHODS AND MATERIALS: A retrospective analysis of 45 previously untreated patients with Ann Arbor stage IE and IIE PLB from 1967 to 1992 was undertaken. All histopathologic material was reviewed. Irradiated patients received at least 40 Gy. Systemic chemotherapy was generally doxorubicin based. Overall survival (OS), progression free survival (PFS), and disease-specific survival (DSS) were calculated actuarially. RESULTS: Histologically, there were 41 diffuse large cell, 2 diffuse mixed cell, 1 lymphocytic, and 1 lymphoblastic lymphomas. International Index scores were assessed on 43 patients. Thirty-six patients were treated with chemotherapy and radiation (CMT), five patients were treated with radiation only, and four patients were treated with chemotherapy only. Univariate analysis revealed significantly improved 5-year OS for those patients who had International Index scores of 0 vs. scores of 1 or 2 (85 vs. 53%, respectively, p = 0.004). Analysis failed to demonstrate a difference in OS, PFS, or DSS when comparing radiotherapy alone versus CMT, stage IE vs. stage IIE, or axial skeleton involvement vs. extremities. CONCLUSION: The outcome of patients with PLB is relatively favorable in the era of CMT. Doses of radiation in the range of 46 Gy provide optimal local control with an acceptable rate of complications. The International Index is a valid prognostic tool for PLB.

Fleury, A., F. Menegoz, et al. (1997). "Descriptive epidemiology of cerebral gliomas in France." Cancer 79(6): 1195-202.

BACKGROUND: Descriptive epidemiology of cerebral gliomas has recently been the subject of several studies, indicating a possible increase in brain tumor rates, particularly in the elderly population. METHODS: Between 1983 and 1990, 1376 registered patients with diagnoses of malignant astrocytomas, low grade astrocytomas, oligodendrogliomas - mixed oligoastrocytomas, and tumors without histologic confirmation were reviewed in 6 French cancer registries. The incidence rates by histologic type, age, and gender were calculated. The variation of the incidence between 1983 and 1990 was also analyzed. RESULTS: The highest incidence was observed in the malignant astrocytoma group (2.38/100,000/year) followed by the low grade astrocytoma group (0.54/100,000/year) and the oligodendroglioma - mixed oligoastrocytoma group (0.25/100,000/year). A significant male predominance was observed in the malignant astrocytoma group (male/female [M/F] ratio of 1.59; P < 0.001) and in the group without histologic confirmation (M/F ratio of 2.6; P = 0.008). Between 1983 and 1990, an increasing trend of 5% per year was observed in the incidence of malignant astrocytomas in the population older than 65 years. CONCLUSIONS: These data confirm the observation made in other countries that the incidence of primary brain tumors (particularly malignant astrocytomas) is increasing in elderly patients.

Ariad, S., D. B. Geffen, et al. (1997). "Myasthenia gravis associated with malignant mixed Mullerian tumor of the uterus." Gynecol Oncol 64(3): 510-5.

Myasthenia gravis is a neurologic disorder characterized by intermittent muscle weakness which improves after anticholinesterase medication. The pathogenesis of myasthenia gravis is associated with production of autoantibodies to nicotinic acetylcholine receptor in the motor end plate. Most patients do not have an underlying neoplasm, but in 10-15% of the cases, a thymoma may be detected. Apart from thymoma, no other tumor type or organ has consistently been associated with myasthenia gravis. We describe an unusual case of myasthenia gravis in a patient with malignant mixed Mullerian tumor of the uterine corpus. Initial histology revealed malignant mixed Mullerian tumor of a predominant carcinomatous element. At that time, there were no symptoms of muscle weakness. Intraabdominal metastases were detected later, concommitantly with symptoms of muscle weakness and the diagnosis of myasthenia gravis. Histology of the metastases disclosed an exclusive mesenchymal element with striated muscle differentiation. To the best of our knowledge this case is the first report of myasthenia gravis in a patient with malignant mixed Mullerian tumor of the uterine corpus. We propose that the mechanism contributing to myasthenia gravis in this patient was closely associated with the evolving histology and with the nature of the tumor, so that antibodies produced to muscle-like epitopes exposed by malignant cells could have cross-reacted with acetylcholine nicotinic receptors and caused myasthenia gravis.

Hsiao, C. H., C. J. Cheng, et al. (1997). "Immunohistochemical and ultrastructural study of malignant plasmacytoid myoepithelioma of the maxillary sinus." J Formos Med Assoc 96(3): 209-12.

Myoepithelioma is a rare salivary gland tumor which is composed exclusively of myoepithelial cells. Histologically, it can be divided into three cell types: spindle, plasmacytoid and mixed type. Malignant myoepithelioma is characterized by invasive growth. In March 1995, a 60-year-old man presented with a left cheek tumor which he had first noted 2 years previously. Computed tomography revealed a large expansile tumor in the maxillary sinus with invasion into the surrounding soft tissue. Partial resection of the tumor was performed because of extensive involvement of the surrounding tissue. The patient died due to spread to the brain 5 months after surgery. Histologically, the tumor was composed exclusively of plasmacytoid cells, with bone destruction. Immunohistochemically, these cells were negative for immunoglobulin light chains (kappa and lambda) and heavy chains (Ig G, A, M) but positive for S-100, cytokeratin, actin and vimentin.Ultrastructurally, the tumor cells contained numerous randomly oriented actin-like microfilaments in the cytoplasm, and had desmosomes on the cell membrane. Malignant plasmacytoid myoepithelioma of the maxillary sinus was diagnosed. In addition to our case, only five cases of pure plasmacytoid myoepithelioma have been reported. Plasmacytoid myoepithelioma tends to occur in the minor salivary glands and has more aggressive behavior than spindle cell myoepithelioma. Morphologically, it is very difficult to differentiate plasmacytoid myoepithelioma from plasmacytoma and immunohistochemical staining is necessary to make a correct diagnosis.

Feroze, M., K. P. Aravindan, et al. (1997). "Mullerian adenosarcoma of the uterine cervix." Indian J Cancer 34(2): 68-72.

Two cases of mullerian adenosarcoma with heterologous elements which occurred in uterine cervix and had a gross appearance of sarcoma botyroides are reported. Histologically, the tumours were composed of an admixture of benign appearing glands and a sarcomatous stroma, with heterologous elements consisting of skeletal muscle, bone and cartilage. No malignant epithetial components were observed. Indications are that, the prognosis of these tumours are much better than the usual malignant mixed mullerian tumours.

Gansler, T. S., W. Hardman, 3rd, et al. (1997). "Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival." Hum Pathol 28(6): 686-92.

Certain cancers exhibit derangement of de novo fatty acid biosynthesis, manifested as overexpression and hyperactivity of the lipogenic enzyme fatty acid synthase (FAS). Correlation of elevated FAS with high tumor grade and advanced stage in primary breast, prostate, and colorectal cancers has drawn attention to the enzyme as a possible marker of poor prognosis. To find a similar utility of FAS in ovarian neoplasms, we compared FAS expression in 68 ovarian tumors with their histological features and clinical outcome. Immunohistochemical localization of FAS was observed in 48 (71%) cases in which staining was either focal (defined as positive staining in 1% to 20% of cells) or multifocal/diffuse (positive staining in >20% of cells). Most (83%) of the 48 cases were represented by endometrioid, serous, or mucinous carcinomas and malignant mixed mullerian tumors (MMMTs). In contrast, ovarian adenomas and tumors of low malignant potential (LMPs) contained little or no FAS. Association between FAS expression and histological diagnosis was statistically significant. The extent of FAS immunostaining was also predictive of prognosis. Among all patients with ovarian malignancies (including LMPs), median survival was 64.8 months, when their tumors exhibited no or focal immunostaining for FAS, as opposed to 31.2 months, when staining was multifocal/diffuse (P = .005). Similar median survival values were obtained when cases were limited to endometrioid, serous, and mucinous carcinomas. Short-term survival at 1 and 2 years was significantly higher in patients whose tumors showed no or focal expression of FAS compared with multifocal/diffuse expression. Thus, elevated FAS may serve as an independent marker for predicting poor clinical outcome in patients with ovarian cancer.

Rose, P. G., M. Rodriguez, et al. (1997). "Malignant mixed mullerian tumor of the female peritoneum: treatment and outcome of three cases." Gynecol Oncol 65(3): 523-5.

Three cases of malignant mixed mullerian tumor of the peritoneum are presented. One patient had a complete clinical and pathologic response and remains disease-free 42 months following diagnosis. As with peritoneal carcinoma and ovarian sarcoma, aggressive surgical cytoreduction and postoperative chemotherapy appear indicated.

Ventura, L., P. Leocata, et al. (1997). "Mullerian adenosarcoma of the uterus." J Exp Clin Cancer Res 16(2): 221-6.

A case of adenosarcoma of the uterus in a 59-year-old woman is here reported. Adenosarcoma is a low malignant potential tumor with a benign glandular and a malignant stromal component. The treatment is usually hysterectomy with bilateral salpingo-oophorectomy. Debated is the usefulness of adjuvant chemotherapy, while radiation treatment is not beneficial. Long term follow-up is necessary for these patients because of high recurrence risk, mostly in cases with myometrial invasion.

Grossniklaus, H. E., D. M. Albert, et al. (1997). "Clear cell differentiation in choroidal melanoma. COMS report no. 8. Collaborative Ocular Melanoma Study Group." Arch Ophthalmol 115(7): 894-8.

OBJECTIVE: To describe 2 enucleated eyes of patients enrolled in the Collaborative Ocular Melanoma Study that contained primary choroidal melanoma with clear cell features. METHODS: During a 9-year period, 1493 eyes enucleated as part of the Collaborative Ocular Melanoma Study routinely processed for histologic examination were evaluated by the pathology review committee (H.E.G, D.M.A, and W.R.G). Two eyes with unusual variants of choroidal melanoma were identified and immunostained for S100 protein and HMB 45. Portions of the tumors were processed for electron microscopic examination. RESULTS: Results of electron microscopic examination of both tumors displayed malignant melanoma (mixed cell type with many malignant cells with clear cytoplasm). The cytoplasm of the clear cells stained with periodic acid-Schiff and failed to stain when pretreated with diastase. Results of immunohistochemical stains in both tumors were positive for S100 protein and HMB 45 in the tumor cells. Results of electron microscopic examination showed that the cytoplasm of the clear cells contained scattered glycogen granules, premelanosomes, and melanosomes. CONCLUSION: These cases represent a clear cell variant of malignant melanoma of the choroid. This tumor should not be confused with metastatic clear cell carcinoma to the choroid.

Hashimoto, K., C. Azuma, et al. (1997). "Loss of H19 imprinting and up-regulation of H19 and SNRPN in a case with malignant mixed Mullerian tumor of the uterus." Hum Pathol 28(7): 862-5.

In several human cancers, it has been recently reported that abnormally altered status of genomic imprinting is related to oncogenesis. In this study, we investigated the expression of three imprinted genes in a case with malignant mixed Mullerian tumor of the uterus (MMMT). In the tumor, expression of H19 showed marked upregulation (6.3-fold) with biallelic expression compared with that in the corresponding normal myometrium. The 5'-promoter region of H19 was hypomethylated in the tumor, whereas it was hemimethylated in the myometrium. Expression of the small nuclear ribonucleoprotein polypeptide N gene (SNRPN) was also upregulated by 1.9-fold. However, the insulin-like growth factor II gene (IGF2) was expressed at low levels in both myometrium and MMMT. The overexpression of H19 is caused by reactivation of the repressed allele of H19 due to demethylation of CpG islands within its 5'-promoter region. Whether upregulation of SNRPN is caused by its biallelic expression remains undetermined because restriction fragment length polymorphisms (RFLP) sites were not informative in SNRPN and IGF2. In conclusion, H19 and SNRPN may play significant roles in the tumorigenesis of MMMT and H19 may have tumor-promoting activity in addition to its known tumor-suppressing activity, probably depending on the tissue and the local milieu.

Rubenchik, I., N. Sneige, et al. (1997). "In search of specimen adequacy in fine-needle aspirates of nonpalpable breast lesions." Am J Clin Pathol 108(1): 13-8.

Pathology-related medical malpractice claims frequently concern fine-needle aspirations (FNAs) of breast lesions, and diagnostic errors have been attributed in part to the inadequacy of the specimens. Cytologic criteria for adequate FNA specimens, specifically in cases without malignancy, have not been clearly defined. From January 1988, to August 1995, 669 ultrasonographic-guided FNAs of nonpalpable, solid breast lesions with subsequent histologic examination were performed at our institution. From these, 54 cases with cytologic diagnoses of insufficient or nonspecific benign findings were identified. All aspirates were reviewed, and the number and size of the epithelial cell groups were quantitated in each case. By using criteria for adequate aspirates of palpable breast lesions (six or more epithelial cell groups per case with a minimum of 5-10 cells per group), 23 of the 54 aspirates were deemed inadequate and 31 adequate. Eleven (48%) of the inadequate aspirates and 17 (55%) of the adequate aspirates were from histologically confirmed carcinomas (ductal carcinoma in situ, 6; invasive carcinoma, 22, of which 12 were ductal, 7, lobular, and 3, mixed ductal and lobular). For the mammographic diagnoses "probably benign," "indeterminate," and "suggestive of malignancy or malignant," the probability of malignancy in aspirates of adequate cellularity (eg, > 6 epithelial groups) was 9%, 40%, and 93%, respectively. These findings indicate that a significant proportion of breast aspirates still may yield false-negative results despite adequate to high cellularity. Although a definition of adequacy based on cellularity is useful in reducing false-negative results, cellularity alone cannot be relied on in the management of nonpalpable lesions. For mammographic findings that are indeterminate or suggestive of malignancy or malignant, nonspecific FNA findings should be followed by core or excisional biopsy to exclude carcinoma.

Tazawa, S., K. Marumo, et al. (1997). "[Epidemiological evaluation of mycobacteria isolates in one city hospital: reports from the hospital microbiology laboratory]." Kekkaku 72(7): 435-42.

The frequency of mycobacteria isolated from patient's specimens at Showa University Fujigaoka Hospital was investigated. By fitting a polynominal curve (degree = 3) of the annual frequency of culture-positive Mycobacterium tuberculosis (1977 through 1995), it was noted that the frequency had not changed since 1977. The patients in the 40s or older and 60s or older comprised 74 and 38%, respectively. Of 104 patients diagnosed as tuberculosis (between 1993 and 1995), 43 (41%) were compromised hosts with the following underlying diseases: kidney disease; diabetes mellitus; malignant tumor; respiratory disease; Behcet's disease; ophthalmosarcoidosis; multiple arthritis; Hashimoto's disease. This suggested that these compromised hosts are at high risk of onset and relapse of tuberculosis, and occasionally the doctor's or patient's delay was seen during the diagnostic process. By fitting a polynominal curve (degree = 3) of the annual frequency of culture-positive atypical mycobacteria (1977 through 1995), it was noted that the frequency had increased since 1981. The patients in the 40s or older and 60s or older comprised 88 and 60%, respectively. Between 1982 and 1994, we encountered 46 cases of atypical mycobacteriosis of the lung: 37 M. avium complex (MAX) diseases; 7 M. kansasii diseases; one M. chelonae disease; one unidentified disease involving Runyon Group II mycobacterium. Eight involved patients with bronchiectasia (5 cases), diabetes mellitus (2 cases), or leukaemia (one case). Haemophilus influenzae, Pseudomonas aeruginosa, and Moraxella catarrhalis at more than 10(7) CFU per ml of sputum were isolated from 6 patients diagnosed with MAC or M. kansasii lung diseases, suggesting the possibility of mixed infections. M. tuberculosis and atypical mycobacterium (15 cases), and two different atypical mycobacteria (16 cases) were isolated from the same or different specimens of the same patients at the same or different times. However, the pathogenicity of these mycobacteria remained unknown, because atypical mycobacteria are non-pathogenic in many cases. The above findings suggested that the environment fit for the mycobacteria growth in human body has gradually been formed associating with aging, lung-lesion, and decline of immune capacity.

Fehmian, C., J. Jones, et al. (1997). "Adenosarcoma of the uterus with extensive smooth muscle differentiation: ultrastructural study and review of the literature." Ultrastruct Pathol 21(1): 73-9.

Four cases of Mullerian adenosarcoma were studied by light and electron microscopy and immunohistochemistry. All 4 cases showed the histologic characteristics of adenosarcoma with benign endometrial glands and a malignant stroma. Ultrastructurally, the epithelial component in all cases had the appearance of proliferative endometrial glands, and the malignant mesenchymal cells showed features of endometrial stroma. A distinct basal lamina separating glands from stroma was present. In addition, 2 of the cases showed extensive smooth muscle differentiation which was associated with sarcomatous overgrowth. The smooth muscle features were confirmed by immunohistochemistry. Multiple theories of the histogenesis of this tumor are discussed.

Garden, A. S., A. K. el-Naggar, et al. (1997). "Postoperative radiotherapy for malignant tumors of the parotid gland." Int J Radiat Oncol Biol Phys 37(1): 79-85.

PURPOSE: To update our experience using postoperative irradiation in selected patients with carcinomas of the parotid gland. Outcomes of treatment with a focus on the effectiveness of the two primary techniques of radiation used for treating these tumors were evaluated. METHODS AND MATERIALS: A retrospective analysis of 166 patients with parotid gland malignancies treated in the Department of Radiotherapy at the University of Texas M. D. Anderson Cancer Center between 1965-1989 was performed. All patients were treated following surgery and did not have macroscopic disease at the time of their radiation. The most common histologies were mucoepidermoid carcinoma (28%) and adenocarcinoma (27%). Pathologic features constituting indications for postoperative radiotherapy included: inadequate margins, 104 (63%) cases; extraglandular disease extension, 82 (49%); perineural invasion 57 (34%); and nodal disease 43 (26%). Radiation was delivered through an ipsilateral field of predominantly high energy electrons in 142 patients (86%). Wedged paired 60Co fields were used to treat 19 patients. The median dose was 60 Gy, typically delivered at 2 Gy per fraction. The median follow-up time for surviving patients was 155 months. RESULTS: Forty-seven (29%) patients had disease recurrence, of whom 15 (9%) had disease recur locally and 10 (6%) regionally (neck). There was no association between the dose of radiation and local failure, except for a trend for patients with positive margins and/or named nerve involvement to have improved local control if they received doses > 60 Gy. There was no difference in failure rates in patients treated with wedged pair techniques or ipsilateral fields, but there was a higher complication rate in the former. Overall, 37 patients (22%) developed chronic sequelae attributed to radiation. Twelve patients developed decreased hearing, and 15 patients developed soft tissue or bone necrosis or exposure. CONCLUSIONS: Local and regional control rates for high risk patients with parotid gland carcinomas treated with radiation following surgery were excellent. The technique of using an ipsilateral field encompassing the parotid bed and treated with high energy electrons often mixed with photons was effective with minimal severe late toxicity. The moderate complication rate experienced in this series can be further reduced using modern techniques as described.

Jacques, S. M., F. Qureshi, et al. (1997). "Tumors of the uterine isthmus: clinicopathologic features and immunohistochemical characterization of p53 expression and hormone receptors." Int J Gynecol Pathol 16(1): 38-44.

Five (3%) of 161 endometrial cancers treated surgically between 1988 and 1992 were classified as primary isthmic tumors, and their clinicopathologic features, p53 expression, and hormone receptor status were evaluated. Three were endometrioid adenocarcinomas with squamous differentiation, one was a mixed serous and clear cell carcinoma, and one was a malignant mullerian mixed tumor; all five were high grade, invaded the entire thickness of the myometrium, and exhibited lymphatic space invasion. Four of the five patients had extrauterine metastases identified at the time of hysterectomy. All five patients died due to progressive disease with the survival time ranging from 1 to 23 months. Abnormal p53 gene expression was identified immunohistochemically in three of the five isthmic tumors. Weak positivity for estrogen and progesterone receptors was demonstrated in one case, with the remaining four being negative. Tumors arising in and confined to the uterine isthmus are unusual and, in our series, were uniformly aggressive with an unfavorable prognosis. The histopathologic features and biologic behavior of the isthmic tumors appeared similar to those of other high-grade endometrial cancers arising in the uterine corpus.

Shimizu, M. and M. Nakayama (1997). "Endometrial ossification in a postmenopausal woman." J Clin Pathol 50(2): 171-2.

A case of endometrial ossification in a 62 year old woman is reported. The patient presented with increased vaginal discharge. On transvaginal ultrasonography, a hyperechoic area within the uterine cavity, suggestive of an intrauterine foreign body, was noted. Histological examination of the endometrial curettage showed mature bone with neutrophilic infiltration. There was no evidence of malignancy. Endometrial ossification in postmenopausal women is very rare; most women presenting with this condition are between 20 and 40 years of age. Therefore, clinicians should consider the possibility of endometrial ossification as a differential diagnosis of intrauterine foreign body on ultrasound, even in older patients. In addition, pathologists should be aware of this rare entity to avoid a misdiagnosis of malignant mixed mullerian tumor in the endometrial curettage specimen, which may result in unnecessary hysterectomy.

Abeln, E. C., V. T. Smit, et al. (1997). "Molecular genetic evidence for the conversion hypothesis of the origin of malignant mixed mullerian tumours." J Pathol 183(4): 424-31.

The origin of malignant mixed Mullerian tumours (MMMTs) has long been debated, due to the indefinite relationship between epithelial and mesenchymal malignant cells. In order to obtain insight into the clonal relationship between the two components of these tumours, molecular genetic changes were investigated at the level of loss of heterozygosity (LOH) in both cells types. LOH was studied in a series of six cases with 74 polymorphic microsatellite markers mapping to 19 different chromosomes. The epithelial and the mesenchymal neoplastic cells were separately microdissected from formalin-fixed, paraffin-embedded tissue, prior to DNA isolation. LOH was observed for 35 different markers mapping to chromosomes 3, 6, 8, 11, 15, 16, 17, 18, 21, and X. The most frequently involved chromosomes were 17p, 17q, 11q, 15q, and 21q. LOH was observed in five out of six cases and identical alleles were lost in the epithelial and in the mesenchymal cells. No genetic differences were observed between the two cell types for any of the informative markers. Immunohistochemistry (IHC) and TP53 mutation analysis revealed involvement of TP53 in all cases. Mutations were identified in five MMMTs. In four tumours, of which three had a missense mutation, strong nuclear staining for p53 was observed. In the remaining two cases, the mutation resulted in a stop codon, with no nuclear staining for p53 by IHC. The results support a monoclonal origin of MMMTs, with the absence of genetic changes uniquely associated with either of the phenotypes. The latter finding is compatible with current opinion that these neoplasms should be considered as metaplastic carcinomas and supports the conversion hypothesis.

Bendel, A. E., Y. Shao, et al. (1997). "A recombinant fusion toxin targeted to the granulocyte-macrophage colony-stimulating factor receptor." Leuk Lymphoma 25(3-4): 257-70.

Human granulocyte-macrophage colony stimulating factor (GMCSF) and its high affinity receptor function to regulate the proliferation and differentiation of myeloid lineage hematopoietic cells, and may participate in the pathogenesis of many malignant myeloid diseases. We have used genetic engineering based on the elucidated molecular structures of human granulocyte-macrophage colony-stimulating factor and diphtheria toxin (DT) to produce a recombinant fusion toxin, DTctGMCSF, that targets diphtheria toxin to high affinity GMCSF receptors expressed on the surface of blast cells from a large fraction of patients with acute myeloid leukemia (AML). DTctGMCSF was specifically immunoreactive with antidiphtheria toxin and anti-GMCSF antiseras, and exhibited the characteristic catalytic activity of diphtheria toxin, catalyzing the in vitro ADP-ribosylation of purified elongation factor 2. The cytotoxic effects of DTctGMCSF were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium (MTT) bromide assay of cell viability and in vivo assays of protein synthesis inhibition. DTctGMCSF were specifically cytotoxic to human leukemia cell lines bearing high affinity receptors for human GMCSF with IC50 of 10(-9) to 10(-11) M. It was not toxic to mammalian hematopoietic cell lines lacking human GMCSF (hGMCSF) receptors. In receptor positive cells, cytotoxicity can be specifically blocked by a large excess of hGMCSF, confirming that its cytotoxicity is mediated through the hGMCSF receptor. THough DTctGMCSF inhibited granulocyte-macrophage colony formation by committed myeloid progenitor cells (CFU-GM), it did not significantly affect erythroid burst formation by committed erythroid progenitor cells (BFU-E), or mixed granulocyte-erythroid-macrophage-megakaryocyte colony formation by pluripotent multilineage progenitor cells (CFU-GEMM). DTctGMCSF holds promise for the treatment of myeloid lineage malignancies, and is a useful reagent to study hematopoiesis.

Moll, U. M., F. Valea, et al. (1997). "Role of p53 alteration in primary peritoneal carcinoma." Int J Gynecol Pathol 16(2): 156-62.

Although the clinicopathologic features of primary peritoneal carcinoma (PPC) in women are relatively well defined, the molecular pathogenesis of the disease has not been examined. The object of this study was to assess the biological significance of p53 alterations in PPC. Twenty-nine PPCs studied for p53 protein accumulation with monoclonal antibody DO-7 consisted of 26 serous carcinomas, one clear cell carcinoma, one tumor with endometrioid features, and one malignant mixed mullerian tumor. P53 was overexpressed in 83% of all PPCs and in 81% of the serous PPCs. Among eight immunopositive tumors with at least two distinct anatomic sites sampled, six tumors showed concordance, whereas two tumors showed discordance for p53 immunopositivity. The latter two tumors support the concept of a multifocal origin of PPC. This is the first report to suggest that loss of p53 function plays an important role in the development of PPC and might contribute to the poor prognosis of this disease. Parallels to serous papillary carcinomas of the uterus and ovary are discussed.

Cormio, G., A. Colamaria, et al. (1997). "Central nervous system involvement secondary to metastatic mixed mullerian tumor of the uterus." Gynecol Obstet Invest 44(3): 214-6.

The central nervous system is traditionally considered an uncommon site for metastatic disease from female genital tract tumors. We report the case of a 48-year-old woman with malignant mixed mullerian tumor of the uterus, who developed spinal cord compression by epidural metastasis a few days after the diagnosis of the uterine malignancy. Emergency decompressive laminectomy was performed and a good recovery of the neurological function was achieved. In the following days, while submitted to extensive staging for the uterine malignancy, the patient complained of headache, confusion and visual disturbance. CT scan revealed multiple brain metastases. No other site of metastatic disease could be detected. The patient refused any further treatment and died 1 month later from progressive cerebral disease. Attention should be paid to the possibility of unusual distant metastases associated to uterine sarcoma in order to treat these patients promptly.

Ibanez-Manlapaz, I. G., D. M. Coy, et al. (1997). "Malignant Mixed Mullerian Tumor of the Extra-genital Coelomic Epithelium: Report of Two Cases." Pathol Oncol Res 3(2): 130-134.

Malignant mixed mullerian tumors of the extra-genital coelomic epithelium (female peritoneum) are rare. Since the first case report in 1955, only nineteen have been described. In our Case 1 a 58 year-old G3P3 (gravidity = 3; parity = 3) white female with mixed mullerian tumor, homologous type, involving the abdominal peritoneum was treated with surgery and chemotherapy (doxorubicin hydrochloride and cis-platinum). She died of the disease 20 months after initial surgery. Case 2 is a 75 year-old G0P0 (gravidity = 0; parity = 0) white female with mixed mullerian tumor containing heterologous elements involving the pelvic peritoneum who was treated with surgery and chemotherapy (ifosfamide with mesna). She relapsed 6 months after surgery and refused any further treatment. She died 2 weeks later. These cases support the fact that malignant mixed mullerian tumor of the female peritoneum is rare and usually affects elderly females. It has poor prognosis and among the 15 reported cases with follow-up indicating after initial surgery.

Tsavaris, N., C. Baxevanis, et al. (1996). "The prognostic significance of immune changes in patients with renal cancer, melanoma and colorectal cancer, treated with interferon alpha 2b." Cancer Immunol Immunother 43(2): 94-102.

In the present study we evaluated the response rate and the immunorestorative properties of interferon alpha 2b (IFn alpha 2b) administered to patients with advanced renal cell carcinoma (RCC), melanoma (MEL) or colorectal cancer (CC). We studied the immune status and correlated it with clinical responses. Thirty-five patients with advanced RCC, and 14 with MEL were treated with recombinant INF alpha 2b. The dose was increased progressively from 5 x 10(6) IU/day in the first week (three times every week) to 10 x 10(6) IU/day in the second week and thereafter to 15 x 10(6) IU/day subcutaneously. In patients with CC INF alpha 2b was given at 5 x 10(6) IU/day every other day (three times every week); these patients also received (together with INF) leucovorin 200 mg m-2 day-1 in a 1-h i.v. infusion every week, and mid-infusion 400 mg/m2 5-FU was administered as an intravenous bolus every week. The response rate was as follows: for RCC, 6 patients achieved partial response (PR), 10 stable disease (SD), and 21 progressed (PD); for MEL, 5 patients achieved PR and 9 PD; for CC, 6 achieved PR, 5 SD, and 9 PD. In all patients blood was withdrawn prior to INF alpha 2b treatment and then monthly. T lymphocytes, after isolation from peripheral blood, were tested for proliferation in the autologous mixed-lymphocyte reaction and allogeneic mixed-lymphocyte reaction, interleukin-2 (IL-2) production, expression of IL-2 receptors during the allogeneic-mixed-lymphocyte reaction, and the production of IL-1 by peripheral blood monocytes. Striking increases were demonstrated in all parameters 2 months after treatment with INF alpha 2b. In comparison to normal controls, all patients with the malignant neoplasms presented decreased (> 45%) mean values of the immunological parameters under investigation (P 0.0001). Responders (patients with RCC, MEL, and PR) presented lower mean values of all the parameters studied than did non-responders (P 0.0001). Patients with CC presented the lowest mean values of the parameters than did the other patients (RCC, MEL) (P 0.0001). After therapy with INF alpha 2b, patients with RCC experiencing PR showed a mean increase of more than 30% (P 0.0001). Patients with SD showed a mean increase of about 20% (P 0.0001), and those with PD showed a 6% increase in the immunological parameters under investigation. Patients with MEL experiencing PR showed a mean increase of more than 30% and patients with PD a decrease of more than 10% (P 0.0001). All patients, regardless of the clinical response, achieved an increase of more than 60% (P 0.0001). Administration of IFN alpha 2b resulted in a marked potentiation of a deficient cellular immune response in vitro in those patients with RCC and MEL who responded to the treatment. On the other hand, non-responders demonstrated a decrease in the examined parameters and, in some, deterioration of the already depressed immunological functions was observed. This observation can have prognostic significance regarding clinical response of INF. In contrast, our findings show that the immune stimulation associated with INF alpha treatment in all our CC patients did not predict an improved clinical outcome. There are several theoretical explanations for this discrepancy.

Suster, S. (1996). "Gastrointestinal stromal tumors." Semin Diagn Pathol 13(4): 297-313.

Stromal tumors of the gastrointestinal tract represent relatively rare lesions that are thought to arise from connective tissue elements located along the entire length of the gut. For many years these tumors have been the subject of much controversy and debate in the literature regarding their histogenesis, criteria for diagnosis, prognostic features, and nomenclature. Only a minority of these lesions, mainly those confined to the esophagus and rectum, have been shown to correspond to mature, well-differentiated types of neoplasms such as leiomyoma or leiomyosarcoma of the conventional type. The majority of stromal tumors of the gastrointestinal tract correspond to a heterogeneous group of lesions that have as their common denominator an immature proliferation of epithelioid or spindle cells arising from its muscle layer and showing partial or incomplete myoid, neural, ganglionic, or mixed features of differentiation. This review will attempt to summarize our current knowledge and understanding of these lesions based on review of the literature and the author's personal experience, with an analysis of the criteria for distinguishing between benign and malignant tumors, and a proposal for a working classification for these lesions.

Bednar, B. (1996). "[Typing of malignant mantle zone lymphomas]." Cesk Patol 32(2): 60-5.

Principles derived from a group of 46 ML of the mantle zone are presented: Mantle pattern of a ML and its cytological structure are mostly sufficient for positive basic diagnosis. Diffuse mantle zone ML need detection of BCL-1 and CD5 hyperexpression which are characteristic for small-cell and centrocytoid forms when compared with BCL-2 positive centrofollicular lymphomas. B monocytoid lymphomas from the parafollicular subgroup as well as plasmacytoid ML from the marginal subgroup retain faint BCL-1 positivity but lose CD5 positivity. That may results in attempt of problematic narrowing of mantle zone definition because of existence of the mixed cellularity forms of mantle zone ML. Nodular mantle zone ML are clinically recognized late and are unsensitive to treatment which is opposite to the original idea of their relative benignity. M-coding of mantle zone ML is very defective because the codes do not separate nodular (perifollicular) and diffuse variants.

Kitagawa, K., A. Murata, et al. (1996). "Epithelial-mesenchymal transformation of a newly established cell line from ovarian adenosarcoma by transforming growth factor-beta1." Int J Cancer 66(1): 91-7.

We report on 2 cell lines (designated OVAK-I and OVAK-II) established from an adenosarcoma, a rare variant of a malignant Mullerian mixed tumor, of the ovary. OVAK-I was not tumorigenic in nude mice and showed no responsiveness to transforming growth factor (TGF)-beta1, whereas OVAK-II was tumorigenic and had various biological properties. Light- and electron-microscopic studies showed that the morphology of the cells was converted from an epithelial to a mesenchymal form by TGF-betaI. Furthermore, the protein and mRNA expressions of the epithelial marker carcinoembryonic antigen and the mesenchymal marker vimentin were down- and up-regulated, respectively, by TGF-beta1. These findings suggested that TGF-beta1 plays a role in epithelial-mesenchymal transformation and support the single-stem-cell theory which explains the origin of malignant Mullerian mixed tumors: that the epithelial and mesenchymal components of these tumors are of common stem-cell origin.

Emoto, M., H. Iwasaki, et al. (1996). "Tissue polypeptide antigen production in a uterine carcinosarcoma cell line in a serum-free culture." Gynecol Oncol 60(3): 443-9.

Carcinosarcomas (malignant mixed Mullerian tumors, MMMT) of the female genital tract are uncommon neoplasms, most of which show a highly aggressive behavior. However, the biological characteristics of MMMT, especially the producibility of tumor-related substances in vitro, have yet to be clarified. Using a serum-free culture model system which was newly established from an FU-MMT-2 cell line originating from an MMMT of the human uterus, the biological and immunocytochemical characteristics of MMMT cells were examined in vitro. As a control model, the uterine fibroblasts were also cultured in the same conditions. Moreover, several tumor markers were also measured by a radioimmunoassay in the serum of five patients with MMMT. FU-MMT-2 produced and secreted tissue polypeptide antigen (TPA), a tumor marker closely related to the keratin family, under serum-free culture conditions. Moreover, TPA was also immunocytochemically demonstrated in carcinoma cells as well as sarcoma cells in FU-MMT-2. On the other hand, the uterine fibroblasts showed no detectable producibility of the substances examined in vitro. An elevation of the serum TPA levels was also detected in four of five (80%) patients with MMMT. This is the first serum-free culture study of MMMT, which appears to provide a useful model for further studies of the tumor biology in MMMT of the female genital tract. An evaluation of the serum TPA level thus appears to be useful in determining the optimum management of patients with MMMT. In addition, the demonstration of TPA in sarcoma cells of FU-MMT-2 in vitro supports both the theory of a single cell origin and the current concept of MMMT as a "metaplastic carcinoma," as substantiated in our previous study.

Shokeir, M. O., S. M. Noel, et al. (1996). "Malignant mullerian mixed tumor of the uterus with a prominent alpha-fetoprotein-producing component of yolk sac tumor." Mod Pathol 9(6): 647-51.

We describe a case of a 64-year-old woman with a malignant mullerian mixed tumor of the uterus containing a prominent component of yolk sac tumor, which was associated with high serum levels of alpha-fetoprotein. The neoplasm pursued an aggressive course and the patient died 2 months postoperatively. This is the first case of this type and only the ninth alpha-fetoprotein-secreting endometrial cancer in the literature.

Djian, V., E. Menu, et al. (1996). "Immunoactive products of placenta. V. Immunoregulatory properties of a low molecular weight compound obtained from human placental cultures." Am J Reprod Immunol 36(1): 11-24.

PROBLEM: We have previously shown that supernatants from short-term cultures of human placental explants (HPS) are immunosuppressive in vitro as well as in vivo. They contain a low M.W. factor endowed with immunoregulatories activities (Filtrate of such with a 5 kDa cut off). In this paper, we wanted to assess whether this low M.W. material accounts for most, if not all, of the immunosuppressive properties of crude HPS and begin to investigate its mode of action. RESULTS: The filtrate is active across species barrier and inhibits human and murine PHA driven lymphocyte proliferation, Mixed Lymphocyte Reaction, and Natural Killer activity as did crude HPS. It does not affect CTL lytic function at effector stage. Its cross species activity allowed us to study its effects in vivo. It corrects resorbtions in the CBA x DBA/2 murine spontaneous abortion model, and suppresses local and general GVH reactions in a model (A cells into irradiated A x B Fls) relevant to a clinical use e.g., bone marrow transplantation. To ensure that such survival of the recipients was due to donor cells in the latter, surviving experimental animals were analysed by FACS for repopulating lymphocytes phenotype, which was indeed of donor origin. To elucidate the mechanism(s) of action of the active HPS moiety, we first tested various malignant cell lines for the minimal incubation time required for maximal lymphocyte inhibition. In the same vein, we verified that lymphocytes stimulated by PHA and simultaneously treated with filtrate were unresponsive to a second PHA challenge. The effects of the material was reversible if cells were washed out of it early enough before otherwise entering a cycle leading ultimately to cell death in vitro. Finally, we tested several second messenger pathways, none of which were modified. CONCLUSION: These data suggest that the filtrate contains an entity that represents the main, if not all, the immunosuppressive molecules present in HPS. In addition, they suggest that the material acts only on activated T cells and requires to be present early in the replication activation cycle. Altogether, the in vitro data strongly suggest that the material is acting by inducing clonal deletion in activated (T) cells.

Costa, M. J. and J. Walls (1996). "Epidermal growth factor receptor and c-erbB-2 oncoprotein expression in female genital tract carcinosarcomas (malignant mixed mullerian tumors). Clinicopathologic study of 82 cases." Cancer 77(3): 533-42.

BACKGROUND. Epidermal growth factor receptor (EGFR) and c-erbB-2 (also known as HER-2/neu) oncoprotein (p185erbB-2) are members of the subfamily of tyrosine kinase, transmembrane receptors often implicated in human carcinogenesis. We hypothesize that expression of EGFR and p185erbB-2 adds useful prognostic and histogenetic information regarding female genital tract carcinosarcomas (FGTCSs). METHODS. Paraffin sections from 82 FGTCS (61 endometrium, 14 ovary, 5 cervix, and 2 fallopian tube), 56% of which exhibited heterologous elements, were stained using anti-EGFR (clone 31G7, Triton Diagnostics, Alameda, CA) and anti-p185erbB-2 (clone CB11, Novocastra Labs, UK). RESULTS. EGFR reactivity was present in 11 (13.4%) FGTCSs (55% carcinomatous component [CC] only, 18% sarcomatous component [SC] only, and 27% in both). EGFR was associated with adenosquamous histology of the CC (P < 0.05) and heterologous rhabdomyosarcomatous differentiation in the SC (P < 0.05); no other histopathologic features were correlated. p185erbB-2 reactivity was present in 79 (87.8% strong [S], 78% membrane [M], and 8.5% weak) FGTCSs (1% CC only, 0% SC only, and 99% in both). p185erbB-2 did not correlate with histopathologic features or EGFR. Seventy-seven patients had clinical follow-up for longer than 12 months. Approximately 49.3% and 72.3% of patients had recurrent disease by 12 and 80 months, respectively; all but 1 were dead from disease. 27% of patients were disease free after 15 to 307 months (median, 77 months; mean, 92 months). EGFR, but not p185erbB-2 expression predicted disease recurrence (P < 0.05). Recurrent disease was associated with Stage greater than I (P < 0.0001), vascular space invasion in resection specimens (P < 0.01), and deep myometrial invasion in hysterectomies (P < 0.05). EGFR was associated with Stage greater than I and did not help predict recurrence in good prognosis groups. CONCLUSIONS. p185erbB-2 overexpression in both CC and SC of FGTCS suggests a common carcinogenic mechanism for both components and supports the conversion-histogenesis hypothesis implicating a dominant role for the CC with the SC arising as a metaplastic change from the CC. EGFR may be expressed in either component and indicates aggressive biologic behavior; however, its prognostic utility is limited by its low predictive value for recurrence (40.3%), inability to foretell recurrence in good prognosis groups, and dependence on stage. High frequency of overexpression and dismal prognosis make FGTCS patients good candidates for trials of therapeutic strategies involving the p185erbB-2 receptor manipulations.

Ferri, C., L. La Civita, et al. (1996). "Chronic hepatitis C and B-cell non-Hodgkin's lymphoma." Qjm 89(2): 117-22.

Hepatitis C virus (HCV), a hepatotropic and lymphotropic virus, is the major causative agent of nonA-nonB chronic hepatitis; moreover, it is frequently associated with benign and malignant lymphoproliferative disorders such as mixed cryoglobulinaemia and B-cell non-Hodgkin's lymphoma (NHL). We investigated the clinical and virological features of B-cell NHL complicating chronic hepatitis C in a series of 10 patients (M/F 1/9; mean age 63 +/- 6SD years). The malignancy appeared after median 8 +/- 4SD years from onset and was low-grade in six patients, intermediate in three, and high-grade in one. 'One-tube nested' PCR detected serum HCV RNA and viral ongoing replication in both fresh and cultured peripheral lymphocytes in all ten. Analysis of HCV genotypes showed a relatively higher prevalence of 2a/III type compared with unselected chronic hepatitis C (50% vs. 15%). In one patient, HCV RNA was also found in the neoplastic bone marrow and lymph-node specimens. B-cell NHL can complicate chronic hepatitis C and affect the overall prognosis of the disease. The increasing frequency of chronic hepatitis C worldwide suggests that the actual prevalence of this complication may be underestimated. Careful clinical work-up at diagnosis and during follow-up is particularly recommendable.

Nola, M., D. Babic, et al. (1996). "Prognostic parameters for survival of patients with malignant mesenchymal tumors of the uterus." Cancer 78(12): 2543-50.

BACKGROUND: Malignant mesenchymal uterine neoplasms are the most aggressive type of primary uterine tumors, with most patients dying within a few years of diagnosis. Thus, it would be very important to define prognostic factors for predicting the malignancy potential of at least some of their subtypes. METHODS: Flow cytometric cell cycle analysis (proliferative activity, DNA ploidy, and DNA index) was performed on archival paraffin embedded blocks from 80 patients with malignant mesenchymal uterine neoplasms (endometrial stromal sarcomas, malignant smooth muscle tumors, and malignant Mullerian mixed tumors). The Cox proportional hazards regression model was used to assess relative effects of the following factors on patient survival: clinical stage, mode of therapy, DNA+proliferative activity, DNA index, histologic type, cellularity, degree of atypia, mitotic activity, and depth of myometrial invasion. RESULTS: There were 9 low grade stromal sarcomas, 17 high grade stromal sarcomas, 8 smooth muscle neoplasms with uncertain malignant potential, 23 leiomyosarcomas, and 16 homologous and 7 heterologous malignant Mullerian mixed tumors. In univariate analysis for stromal sarcomas, statistical significance was found for DNA ploidy+proliferative activity (P < 0.001), histologic type (P = 0.005), and DNA index (P < 0.001). In multivariate analysis, DNA index appeared to be the only significant parameter influencing patient survival (P = 0.005). In univariate analysis for malignant smooth muscle neoplasms, statistical significance was detected for mitotic activity (P = 0.049) and International Federation of Gynecology and Obstetrics classification (P = 0.021), but in multivariate analysis, clinical stage appeared to be the only significant parameter influencing patient survival (P = 0.032). In univariate analysis for malignant Mullerian mixed tumors, statistical significance was found for the depth of myometrial invasion (P = 0.039), DNA index (P = 0.037), and clinical stage (P = 0.013), but in multivariate analysis, only the depth of myometrial invasion (P = 0.036) and clinical stage (P = 0.025) were of statistical significance. CONCLUSIONS: The most powerful prognostic indicator for stromal sarcomas was the DNA index, for malignant smooth muscle neoplasms it was the clinical stage, and for malignant Mullerian mixed tumors it was the depth of myometrial invasion.

Illert, B., M. Sailer, et al. (1996). "[Primary extragenital manifestation of a malignant mixed Mullerian tumor of the major omentum]." Chirurg 67(12): 1273-5.

Malignant mixed Mullerian tumours (MMMT) are tumours of the female genital tract which rarely occur in extragenital sites. We report a case of a 46-year-old female with MMMT with primary occurrence in the greater omentum. Only 19 cases of primary extragenital manifestations of this tumour are described in literature. The clinical appearance, diagnosis, therapy, histological evaluation and histogenesis are discussed.

Patel, S. R., N. E. Papadopoulos, et al. (1996). "Phase II study of paclitaxel in patients with previously treated osteosarcoma and its variants." Cancer 78(4): 741-4.

BACKGROUND. Patients with osteosarcoma and its variants who did not respond to standard chemotherapy including doxorubicin, ifosfamide, cisplatin, and high dose methotrexate were treated with paclitaxel so that its therapeutic activity in these patients could be determined. METHODS. We conducted a Phase II study of paclitaxel in patients with conventional osteosarcoma (10), malignant fibrous histiocytoma of the bone (3) and dedifferentiated chondrosarcoma (2) whose disease had progressed after prior standard chemotherapy including doxorubicin, cisplatin, ifosfamide, and high dose methotrexate. Paclitaxel was administered at a starting dose of 175 mg/m2 as a 24-hour infusion with standard premedication every 21 days or upon hematologic recovery (absolute granulocyte count [AGC] > 1500/microliters, platelets > 100,000/microliters). Neupogen was not used routinely. The study was conducted based on a two-stage design. A total of 17 patients were entered into the protocol. Two were ineligible since they had Ewing's sarcoma. Responses were assessed radiographically and pathologically when feasible, using standard criteria. RESULTS. Fifteen eligible patients were treated in the first stage of the study. Median age of the patients was 31 years (range, 19-61 yrs). There were 8 females and 7 males with a Zubrod performance status of 0 or 1. One patient achieved a mixed response and 14 developed progressive disease. Median AGC nadir was 0.3, on Day 13, lasting 5 days. Median platelet nadir was 134, on Day 8. There were no Grade III or IV nonhematologic toxicities and no deaths related to treatment. CONCLUSIONS. Paclitaxel, at this dose and schedule, is well tolerated but inactive in this patient population.

Nasu, K., Y. Kawano, et al. (1996). "Immunohistochemical study of c-erb B-2 expression in malignant mixed mullerian tumors of the female genital tract." J Obstet Gynaecol Res 22(4): 347-51.

OBJECTIVE: To study the expression of c-erb B-2 in gynecologic malignancies, especially in malignant mixed mullerian tumors (MMTs). METHODS: Using immunohistochemical techniques, we examined 6 cases of primary MMT, 6 cases of leiomyosarcoma (LMS), 7 cases of endometrial adenocarcinomas, and 10 cases of normal endometria. RESULTS: The expression of c-erb B-2 was observed in the carcinomatous area of all 6 cases of MMT (100%), the sarcomatous area of 5 of 6 cases of MMT (83.3%), in 1 of the 6 cases of LMS (16.7%), in all 7 cases of adenocarcinoma (100%), and in all cases of normal epithelial cells (100%), but was not observed in any of the cases of normal stromal cells (0%). CONCLUSION: The results suggest that the carcinomatous and sarcomatous elements of MMT are similar in their expression of c-erb B-2. MMT differed immunohistochemically from pure sarcoma cells and normal stromal cells, but resembled pure carcinoma cells and normal epithelial cells of the female genital tract.

Hasturk, S., I. Tastepe, et al. (1996). "Combined chemotherapy in pleurectomized malignant pleural mesothelioma patients." J Chemother 8(2): 159-64.

A phase II clinical trial of 20 cancer patients who presented with malignant pleural mesothelioma (MPM) between November 1991 and April 1993 was conducted. Of the histologically proven cases, 16 (80%) were epitheloid and 4 (20%) were mixed type MPM. Patients were treated with mitomycin C, cisplatin, and alpha interferon after pleurectomy. Our schedule consisted of 10 mg/m2 mitomycin C i.v. infusion, 50 mg/m2 cisplatin i.v. infusion, 10 mil Ur-alpha interferon i.m. and 10 mil Ur-alpha interferon i.v. infusion on the first day of treatment. Patients were given a mean of 4.5 chemotherapy cycles (range: 2-6). None of the patients showed complete or partial response. Stable disease was observed in 15 patients, while 5 patients had progressive courses. The overall median survival time after chemotherapy was 12 months (range: 3-31 months). Median survival after chemotherapy was 15 months (range: 4-31 months) in the stable disease group (n:15, 75%), and 5 months (range: 3-13 months) in progressive cases (n:5, 25%). The overall survival rates were 55% [95% Confidence Interval (CI):43%-88.8%] at one year and 15% (95% CI:5%-39.1%) at 2 years. Five patients had grade 3 alopecia, three had grade 2 vomiting and nausea, two had grade 2 leukopenia, one had grade 2 cardiotoxicity and another had discoloration on his fingernails. In our multimodal therapy protocol, we found no difference in survival and relapse rates between our combined modal therapy and other single modal therapies in the literature.

Miyoshi, L. M., S. Tamiya, et al. (1996). "Primary jejunal malignant mixed tumor in a patient with von Recklinghausen neurofibromatosis." Am J Gastroenterol 91(4): 795-7.

A rare case of primary jejunal malignant mixed tumor arising in a 49-64-old Japanese male with von Recklinghausen's disease is reported. The patient, who had a past history of partial gastrectomy due to duodenal ulcer, was admitted with a complaint of epigastric pain. Upper gastrointestinal examinations showed a huge polypoid tumor located in the efferent loop of the gastrojejunostomy site. Because the tumor was strongly suggestive of leiomyosarcoma on histological examination of biopsy specimens, laparotomy was performed. The resected tumor measuring 10 X 7 X 7 cm was composed of adenocarcinoma admixed with various sarcomatous components, including rhabdomyosarcoma, osteosarcoma, and other sarcomas. Immunohistochemical analysis also supported this diagnosis. The features of this tumor closely resembled malignant mixed mullerian tumor of heterologous type that develops in female genital organs. It is well known that patients with von Recklinghausen neurofibromatosis have an increased incidence of mesenchymal tumors and malignant neoplasias, and therefore, it seems that there is a possible relationship between the histogenesis of this peculiar tumor and the genetic abnormality in this patient.

Phillips, K. A., J. P. Scurry, et al. (1996). "Alpha-fetoprotein production by a malignant mixed mullerian tumour of the uterus." J Clin Pathol 49(4): 349-51.

A case of alpha-fetoprotein production by a uterine malignant mixed mullerian tumour is described. The patient was a 68 year old woman who developed intraabdominal recurrence of a stage 1 uterine tumour which had been treated surgically seven years previously. Her serum alpha-fetoprotein was raised at 21,000 micrograms/l (normal < 10 micrograms/l) and staining with immunoperoxidase confirmed that the tumour was the site of alpha-fetoprotein production. The patient was treated with combination chemotherapy but died two weeks after the first course. This is believed to be only the second such case reported.

Antoine, J. M., T. Andre, et al. (1996). "[Mulleroblastoma of the uterus. Role of chemotherapy. A case report]." J Gynecol Obstet Biol Reprod (Paris) 25(1): 53-5.

A case of mulleroblastoma, a malignant mixed Muller tumour, of the uterine body was observed in a 51-year-old patient. This is a rare but severe tumour. Clinically, there is a long latence period and early haematogenous metastases leading to failure of radiotherapy and surgical treatment. Recent data, particularly from immunohistochemistry studies, would suggest that the epithelial component plays a major role in pathogenesis. A therapeutic approach combining surgery, aggressive chemotherapy and radiotherapy allows improved prognosis.

Horn, L. C., C. Werschnik, et al. (1996). "Diagnosis and clinical management in malignant Mullerian tumors of the fallopian tube. A report of four cases and review of recent literature." Arch Gynecol Obstet 258(1): 47-53.

Four out of 42 cases of primary tubal malignancy diagnosed in our histopathological laboratory were malignant mixed Mullerian tumors (MMMT). All four patients were postmenopausal with a mean age of 66.5 years at diagnosis. A correct preoperative diagnosis was made only in one case. Tumor staging (FIGO) revealed stage IIa, IIIc and IV. One patient died of postoperative pulmonary embolism, a second patient of an unknown cause five month after surgery and a third patient died of disease after 11 months with secondary deposits in pelvic peritoneum, omentum and paraaortic lymph nodes. The fourth patient is still alive. One patient received chemotherapy alone, one by radiation and chemotherapy and two patients by radiation alone. Tumor spread at the time of diagnosis and the residual tumor volume were the most important prognostic factors. All tumors were histologically the homologous type of MMMT (carcinosarcomas). No heterologous elements were found. Metastatic tumors showed only sarcomatous elements.

Komatsu, M., T. Ehara, et al. (1996). "Cervical Castleman's disease associated with benign M-proteinemia: report of a case." Surg Today 26(3): 213-6.

We report the unusual case of a 77-year-old man with cervical Castleman's disease associated with benign M-proteinemia. The patient was found to have an anterior cervical tumor during a follow-up examination after surgery for early gastric cancer, at which time blood biochemistry tests revealed M-proteinemia at the position of beta-globulin with a high level of IgG and low levels of IgA and IgM. Serum protein immunoelectrophoresis revealed M-protein consisting of the IgG-k chain, and urine protein immuno-electrophoresis demonstrated Bence Jones protein consisting of the chain. No abnormalities were noted in bone marrow aspiration or bone scintigram. The results of imaging and fine-needle aspiration biopsy of the tumor led to a pre-operative diagnosis of cervical malignant lymphoma with suspected M-proteinemia derived from this disease, and resection of the anterior cervical tumor with bilateral neck dissection was performed. Histopathological examination subsequently demonstrated four mixed-type tumors of Castleman's disease. The pathogenesis of Castleman's disease remains unknown; however, we speculate that the complication of benign M-proteinemia in this patient was not incidental, but caused by an underlying immunological abnormality of the B cells.

Leveque, J., V. Paumier, et al. (1996). "[Mullerian mixed tumors. Experience of the Rennes Regional University Hospital]." Chirurgie 121(3): 198-202.

Seventeen cases of mixed Muller tumours (tumours of the uterus with malignant epithelial and mesenchymal components) are presented. These recently described tumours are rare and occur in menopaused women. Bloody discharge is the usual clinical manifestation, together with an increase of the volume of the uterus. Pathology examination of the surgical specimen is required for diagnosis using immunolabeling to distinguish between homologous tumours (the sarcomatous component occurs in the primary mesenchyma) and heterologous tumours (the mesenchymatous component results from a metastasis). Prognosis, usually poor, depends on the stage of the tumour. Overall survival at 5 years is about 30%. Survival in early stage I and state II tumours is no greater than 50% at 5 years. Treatment is based on radiosurgical techniques in less advanced tumours and requires radiochemotherapy in more advanced stage tumours. Recurrence is usually seen within 2 years, involving the pelvis alone in 10% of the cases and metastasis in most of the others. Because of their rapid development and poor prognosis, these tumours should be identified separately as a separate entity within a larger group of mixed mesodermic tumours.

Jeffers, M. D., J. A. Richmond, et al. (1995). "Overexpression of the c-myc proto-oncogene occurs frequently in uterine sarcomas." Mod Pathol 8(7): 701-4.

Overexpression of the c-myc proto-oncogene occurs in carcinoma of the ovary, endometrium, and cervix, and is associated with an adverse prognosis, but little is known about the pattern of c-myc expression in uterine sarcomas. This study investigates the expression of c-myc in uterine smooth muscle tumors and malignant mixed mullerian tumors. Twenty-three leiomyosarcomas, 10 leiomyomas, and 9 malignant mixed mullerian tumors were examined for c-myc overexpression by immunohistochemistry. Differences in mitotic rate and in survival were compared in c-myc positive and negative cases of leiomyosarcoma. Overexpression of c-myc was seen in 6/12 leiomyomas, 11/23 leiomyosarcomas, and 9/9 malignant mixed mullerian tumors. Positive staining was restricted to a perinuclear location in all of the leiomyomas and one leiomyosarcoma. Diffuse cytoplasmic staining was seen in the remaining 10 positive leiomyosarcomas. Positive staining was seen in both epithelial and stromal elements of malignant mixed mullerian tumors, including homologous and heterologous areas of stromal differentiation. There was no significant difference in mitotic rate or in survival between c-myc positive and negative cases of leiomyosarcoma. Overexpression of c-myc occurs in many uterine leiomyosarcomas and the majority of malignant mixed mullerian tumors. Overexpression of c-myc also occurs in benign uterine smooth muscle tumors but with a different pattern than that seen in malignant tumors. This overexpression does not correlate with survival and the significance of overexpression of c-myc in these tumors is unclear.

Sinha, S. K., N. Basu, et al. (1995). "Malignant mixed muellerian tumour of uterus." J Indian Med Assoc 93(9): 363.

Fuzesi, L., B. Gunawan, et al. (1995). "Endometrial stromal sarcoma with clonal chromosomal aberrations and mixed phenotype." Cancer Genet Cytogenet 84(1): 85-8.

We report a case of a moderate-grade endometrial stromal sarcoma with the following chromosomal complement based on the evaluation of 43 metaphases: 47,XX,der(3)t(3;6)(q29;p21.1),der(6) t(3;6)(q21;q27), + 19. Immunohistochemically, the paraffin-embedded tumor tissue displayed positive vimentin reactivity and lack of cytokeratin expression, indicating a mesenchymal origin. Interestingly, the cultivated tumor cells revealed a co-expression of vimentin and different subtypes of cytokeratin. Therefore, the cytogenetically monoclonal tumor cells which showed co-expression of epithelial and mesenchymal phenotypes suggest that the endometrial stromal sarcoma can be interpreted as a monophasic variant of the malignant mixed Mullerian tumor.

Muntz, H. G., M. A. Jones, et al. (1995). "Malignant mixed mullerian tumors of the ovary: experience with surgical cytoreduction and combination chemotherapy." Cancer 76(7): 1209-13.

BACKGROUND. The role of surgical cytoreduction and combination chemotherapy for malignant mixed mullerian tumors (MMMT) of the ovary was evaluated. METHODS. A retrospective review of 27 women with ovarian MMMT treated from 1980 to 1990 was performed. RESULTS. The International Federation of Gynecology and Obstetrics stages for the 27 women were 1 Stage I, 3 Stage II, 17 Stage III, and 6 Stage IV. Only 10 of the 23 patients with Stage III or IV disease were cytoreduced optimally. With respect to postoperative therapy, 3 women received no treatment, 6 were treated with whole abdomen radiotherapy, 1 received melphalan, and 17 received chemotherapy incorporating a platinum agent (3), doxorubicin (4), or both (10). The significant prognostic factors were stage (P < 0.001) and, for women with Stage III or IV disease, the feasibility of cytoreductive surgery (P = 0.03). The four patients in Stages I or II remained disease free after an interval of at least 5 years. The median and 5-year survival rates for patients with Stages III or IV disease was 18 months and 8%, respectively. Patients in Stage III or IV for whom optimal cytoreduction was not possible had a 2-year survival of 14%, whereas optimal cytoreduction was associated with a 52% 2-year survival. Median survival for the 14 women with Stage III or IV ovarian MMMT treated with combination chemotherapy was 25 months and nine women achieved progression free intervals of greater than 18 months. CONCLUSIONS. Aggressive surgical cytoreduction followed by combination chemotherapy may result in improved progression free intervals for women with advanced ovarian MMMT. However, a major improvement in prognosis for this rare malignancy has not yet been achieved.

Clement, P. B., R. H. Young, et al. (1995). "Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component." Am J Surg Pathol 19(10): 1158-71.

Eight mesonephric adenocarcinomas of the uterine cervix, four of which had a malignant spindle-cell component, occurred in women aged 34 to 71 (median 43, mean 54.5) years, bringing to 14 the number of cervical mesonephric carcinomas in the literature. The tumors with a malignant spindle-cell component ("malignant mesonephric mixed tumors") are, with one possible exception, the first reported examples at this site. The patients, almost all of whom presented with vaginal bleeding, underwent hysterectomy; five also had a pelvic lymph node dissection. The tumors were all stage IB, although microscopic lymph node metastases were found in two cases. Gross examination revealed an invasive cervical mass in each case. On microscopic examination, seven tumors were adjacent to mesonephric hyperplasia, which in five cases was florid and focally atypical; in the remaining case, occasional non-neoplastic mesonephric tubules were found only within the tumor. The adenocarcinomas typically exhibited a variety of patterns, including a ductal pattern resembling endometrioid adenocarcinoma, a small tubular pattern, a retiform pattern, a solid pattern, and a sex-cord-like pattern. These disparate patterns frequently caused diagnostic difficulty. The spindle-cell component generally resembled endometrial stromal sarcoma or a nonspecific spindle-cell sarcoma; one tumor also contained multiple foci of osteosarcoma and another, a single chondroid focus. Immunohistochemical staining for a variety of antigens failed to reveal a distinctive profile, although all the carcinomas were immunoreactive for vimentin. Follow-up in six cases revealed three patients to be alive without evidence of recurrence at postoperative intervals of 2 to 3 years. Recurrent tumor developed in a fourth patient 1 year after hysterectomy; she was treated with chemotherapy and was alive and free of disease at 2 years. Another patient had intra-abdominal recurrences (including liver metastases) at 9 and 11 years and was alive with tumor at 13 years. Death at 8.5 months in a final patient was probably due to an independent stage IIc ovarian clear-cell carcinoma. These and prior observations in the literature suggest that malignant mesonephric tumors of the cervix may be more indolent than their mullerian counterparts, from which they should be distinguished. Mesonephric carcinomas in this site should also be distinguished from florid mesonephric hyperplasia, with which they are usually associated.

Garcia-Rostan y, P. e. G. M., R. G. Troyas, et al. (1995). "Mullerian adenosarcoma of the cervix: differential diagnosis, histogenesis and review of the literature." Pathol Int 45(11): 890-4.

A new case is reported of mullerian adenosarcoma, presenting as a 'benign cervical polyp' protruding through the vulva of a 44 year-old woman admitted with abnormal vaginal bleeding. This report emphasizes the importance of a careful examination of the stroma and special features of the entrapped glands in order to contribute to an earlier and proper diagnosis. The literature is reviewed and the probable histogenesis of this tumor and differential diagnosis with embryonal rhabdomysarcoma (sarcoma botryoides), adenofibroma, malignant mesodermal tumor and carcinosarcoma is discussed.

Mira, J. L., C. M. Fenoglio-Preiser, et al. (1995). "Malignant mixed mullerian tumor of the extraovarian secondary mullerian system. Report of two cases and review of the English literature." Arch Pathol Lab Med 119(11): 1044-9.

OBJECTIVE--To report two cases of malignant mixed mullerian tumor of the extraovarian secondary mullerian system and to identify cases reported in the English literature. DESIGN--Two cases are described and discussed along with cases reported previously in the English literature. SETTING--The University of Cincinnati Medical Center. PATIENTS--(1) A 62-year-old woman with a bilateral ovarian poorly differentiated endometrioid adenocarcinoma with multiple peritoneal metastasis and a malignant mixed mullerian tumor with heterologous elements arising from the pelvic peritoneum. (2) An 83-year-old woman with a malignant mixed mullerian tumor with heterologous elements arising from the cecal peritoneum. RESULTS--Seventeen previously reported cases were identified in the English literature. CONCLUSIONS--The malignant mixed mullerian tumor of the extraovarian secondary mullerian system is a rare disease with only 17 cases reported to date to our knowledge. The prognosis is poor. Of 12 patients with follow-up information available, 10 died within 1 year and 2 within 2 years after diagnosis. The histogenesis of the tumor remains unclear; however, data exist that support transformation of epithelial neoplastic cells into sarcomatous cells (metaplastic theory) and origin from a single totipotential cell. It is possible that both situations may occur.

Berho, M., C. A. Moran, et al. (1995). "Malignant mixed epithelial/mesenchymal neoplasms of the lung." Semin Diagn Pathol 12(2): 123-39.

The existence of biphasic neoplasms occurring primarily in the lung is a well-known albeit rare event. The spectrum of malignant tumors displaying a mixed epithelial/mesenchymal growth pattern is rather narrow when these tumors occur primarily in the lung. The two most often encountered neoplasms showing features of epithelial and mesenchymal differentiation are carcinosarcomas and pulmonary blastomas. Tumors with analogous features are of ubiquitous distribution in the human body and have been described in numerous other organs, including the gastrointestinal tract, the genitourinary tract, and the endocrine system. Although the histopathologic features of these tumors may seem simple in most cases, there appear to be numerous pitfalls in their diagnosis; gray areas still remain in the characterization of these tumors, because a certain degree of overlap may be encountered with these two conditions. Such problems are understandable because the incidence of these tumors in the general population is very rare. Therefore, one is expected to find divergent points of view regarding these neoplasms. It is of importance, however, to unify criteria not only for diagnostic purposes, but also to determine the prevalence and behavior of these neoplasms, because such information may provide a rationale for adjustment and improvement in the treatment and diagnosis of these unusual neoplasms. We will review past and current concepts regarding these unusual tumors, as well as their more salient histopathologic features.

Bicher, A., C. Levenback, et al. (1995). "Ovarian malignant mixed mullerian tumors treated with platinum-based chemotherapy." Obstet Gynecol 85(5 Pt 1): 735-9.

OBJECTIVE: To characterize the clinical course of patients diagnosed with ovarian malignant mixed mullerian tumors treated with platinum-based chemotherapy. METHODS: Thirty-six patients received this treatment at The University of Texas M. D. Anderson Cancer Center in the period 1979-1993. The mean age was 59 years. Stage distribution was as follows: stage IA, one (3%) patient; stage IIIB, two (5.5%); stage IIIC, 21 (58%); and stage IV, two (5.5%). Ten (28%) patients were unstaged. Chemotherapy regimens included cisplatin, doxorubicin, and cyclophosphamide in 16 patients; cisplatin-ifosfamide in five; cisplatin-cyclophosphamide in four; carboplatinum in three; cisplatin-doxorubicin in three; and various other combinations in the remaining five. RESULTS: Of 16 patients evaluated for clinical response, seven (44%) had a complete response and four (25%) had a partial response, for a total clinical response rate of 69%. Nine patients were evaluated for surgical response: five (56%) had a complete response and one (11%) had a partial response, for a total surgical response rate of 67%. The median survival for the cohort was 18 months. At the time of this analysis, five (14%) patients were alive and disease-free, 25 (69%) had died of disease, five (14%) were alive with disease, and one had been lost to follow-up. CONCLUSION: This study suggests that the clinical course of patients with ovarian malignant mixed mullerian tumors treated with platinum-based chemotherapy is similar to the clinical course experienced by patients with high-grade epithelial carcinoma of the ovary.

Huang, K. G., T. C. Chang, et al. (1995). "Malignant mixed mullerian tumor of the uterine corpus--analysis of 12 cases." Changgeng Yi Xue Za Zhi 18(1): 27-35.

Clinical and histopathological features of 12 patients with malignant mixed mullerian tumor of the uterine corpus presenting to Chang Gung Memorial Hospital from January 1988 to September 1993 were retrospectively investigated. The age distribution ranged from 43 to 76 years with a median of 56, and post-menopausal bleeding was the most common symptom in these patients. There was 60% (6/10) of discrepancy in histologic diagnosis between the specimens of dilatation and curettage and that of hysterectomy. All patients received total hysterectomy and bilateral salpingo-oophorectomy, and 10 with retroperitoneal lymph node dissection. Nine patients received cisplatin based chemotherapy, one received radiation only, one received sequential chemotherapy and irradiation, and one underwent concurrent chemoradiation as adjuvant. Two-year survival in patients with stage I-II was 70% (95% C.I.: 34%, 100%) and that of stage III, 25% (95% C.I.: 0.67%). There was 42% (5 of 12) progression/recurrence rate, all developed within 2 years. An effective adjuvant chemotherapy after comprehensive surgery including a total abdominal hysterectomy, bilateral salpingo-oophorectomy and lymph node dissection may be needed for a satisfactory improvement in the patients' survival.

Sasco, A. J., F. Raffi, et al. (1995). "Endometrial mullerian carcinosarcoma after cessation of tamoxifen therapy for breast cancer." Int J Gynaecol Obstet 48(3): 307-10.

The aim of this report is to draw the attention of clinicians to the possible occurrence of endometrial cancers of rare histological type among women currently undergoing or having in the past undergone tamoxifen therapy, in particular for breast cancer. We report a case of heterologous mixed malignant muller tumor occurring in an 80-year-old woman. At 69, she had been diagnosed with breast cancer and received tamoxifen for a total of 55 months over a 6-year period. In the 5th year after cessation of tamoxifen therapy, an endometrial carcinosarcoma was diagnosed. Although the association between tamoxifen use and endometrial cancer is recognized, only a few reports of occurrence long after cessation of therapy exist. We believe ours is the second for this particular histological type. Tamoxifen may have played a role in the occurrence of this tumor although it is also known that this type of tumor may arise de novo in elderly women. The etiologic hypothesis obtained from this case description will now be tested in a formal epidemiological investigation which hopefully will provide more definitive evidence.

Paloheimo, L. I. and J. F. Rehfeld (1995). "Quantitation of procholecystokinin and its products in plasma by processing-independent analysis." Clin Chim Acta 238(1): 21-33.

A procedure for processing-independent quantitation of procholecystokinin (proCCK) and its products has been applied to plasma. The procedure is based on tryptic cleavage after Lys61 and Arg71 with subsequent monospecific radioimmuno-analysis of fragment 62-71 of human proCCK, which again corresponds to fragment 1-10 of CCK-22. The detection limit of the analysis was 0.2 pmol/l. Plasma was extracted with ethanol. In plasma from 13 healthy volunteers the basal concentration with the above-mentioned radioimmunoassay was 1.1 +/- 0.1 pmol/l (mean +/- S.E.M.) before, and 13.7 +/- 0.6 pmol/l after, incubation with trypsin. Two hours after ingestion of a mixed meal, the plasma concentration was 2.0 +/- 0.1 pmol/l before, and 21.7 +/- 1.2 pmol/l after tryptic cleavage. With a conventional CCK radioimmunoassay specific for the C-terminally amidated and O-sulfated bioactive epitope, the concentration was 1.0 +/- 0.1 pmol/l in the basal state and 4.2 +/- 0.4 pmol/l 2 h after a meal. Tryptic cleavage did not increase the concentrations of amidated, bioactive CCK peptides. In plasma from 37 patients with the carcinoid syndrome, the basal concentration of proCCK and its products was 14.1 (2.8-150.4) pmol/l (median (range)), compared with 0.3 (0-18.8) pmol/l for carboxyamidated CCK. Only two patients had significantly elevated CCK concentrations. We conclude that processing-independent analysis is useful for quantitation of proCCK and its products in plasma, since it quantitates CCK cell secretion more accurately than conventional CCK assays.

Modzelewski, J. R., J. F. Silverman, et al. (1995). "Serous effusion cytology in gynecologic malignant mixed mullerian tumors." Diagn Cytopathol 12(4): 309-12.

We reviewed 51 serous effusions (50 peritoneal/one pleural) from 38 patients with uterine (30 cases) and ovarian (eight cases) malignant mixed Mullerian tumors (MMMT). There were 16 patients (42%) with positive effusion cytology specimens; 13 cases (81%) were diagnosed as adenocarcinoma with three cases (19%) interpreted as having a sarcomatous component. Eight of 16 positive effusion specimens had cell block material available for immunoperoxidase (IP) study that included cytokeratin (AE1/3), vimentin, muscle specific actin (HHF) and S-100 protein to determine if unsuspected mesenchymal components were present in the cases originally diagnosed as carcinoma (six cases), or sarcomas (two cases). In the six cases originally interpreted as carcinoma, three were diagnosed as adenocarcinoma and three as poorly differentiated carcinoma. All three of the cases considered adenocarcinoma and two of those diagnosed as poorly differentiated carcinoma reacted only with AE1/3 and vimentin. The remaining case, considered a poorly differentiated carcinoma, stained only with vimentin. In the two cases having cell blocks interpreted as having a sarcomatous component, only vimentin was positive in one while AE1/3, vimentin, HHF, and S-100 were positive in the other. The case where all immunohistochemical stains were reactive contained both carcinomatous and sarcomatous components. In the three cases considered sarcomatous, the cytomorphologic features helpful in the recognition of a mesenchymal component included a dissociated smear pattern of pleomorphic round to oval cells and/or spindle cells. In retrospect, the IP stains did not alter any of the original diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Evans, M. J., N. E. Langlois, et al. (1995). "Is there an association between long-term tamoxifen treatment and the development of carcinosarcoma (malignant mixed Mullerian tumor) of the uterus?" Int J Gynecol Cancer 5(4): 310-313.

A cluster of five patients with endometrial carcinosarcoma (malignant mixed Mullerian tumor) occurred at our center during 1993; four of these had been prescribed long-term tamoxifen for breast carcinoma. Searching the archives for the 9-year period 1983-1992 revealed two further cases of uterine carcinosarcoma occurring in patients prescribed tamoxifen, from a total of 16 cases of this tumor. Five of the six patients diagnosed with carcinosarcoma who had been taking tamoxifen had been maintained on the drug for at least 6 years, while the other had a 3-year history of tamoxifen therapy. From these data we raise the question of an association between long-term tamoxifen treatment and development of endometrial carcinosarcoma, following the dramatic increase in the prescribing of this drug after 1984.

Siriaunkgul, S., K. M. Robbins, et al. (1995). "Ovarian mucinous tumors of low malignant potential: a clinicopathologic study of 54 tumors of intestinal and mullerian type." Int J Gynecol Pathol 14(3): 198-208.

We have reviewed 44 mucinous intestinal (MI) and 10 mucinous mullerian (MM) tumors of low malignant potential (LMP) seen at The George Washington University Medical Center. As previously reported by Rutgers and Scully, MMLMP tumors occurred in younger women, were generally smaller and more frequently bilateral, had a papillary rather than multicystic appearance, and lacked goblet cells. All patients with MMLMP tumors were recurrence-free at last follow-up, including three whose tumors were microinvasive. Patients with MILMP tumors also all did well regardless of tumor grade, with the exception of a single patient with bilateral grade 1 ovarian tumors, an appendiceal villous adenoma, and pseudomyxoma peritonei. Microinvasion was also seen in four of these tumors, none of which recurred. Review of the literature suggests that MILMP tumors without stromal invasion but with either prominent cell stratification or marked nuclear atypia may have a worse prognosis than those lacking these features, but probably largely because of a correlation with higher stage disease. We believe that tumors of this sort should not be diagnosed as "noninvasive carcinomas," but should be sectioned more extensively for evidence of stromal invasion and subjected to careful staging. If the tumor is still noninvasive and in stage I after these procedures, the likelihood of treatment failure appears to be in the range of 1-3%.

Crouzier, R., T. Martin, et al. (1995). "Monoclonal IgM rheumatoid factor secreted by CD5-negative B cells during mixed cryoglobulinemia. Evidence for somatic mutations and intraclonal diversity of the expressed VH region gene." J Immunol 154(1): 413-21.

Mixed cryoglobulinemia is usually considered to be a nonmalignant human B cell proliferation that produces a monoclonal IgM rheumatoid factor (RF). Important immunologic similarities and differences were described between the monoclonal B cells during mixed cryoglobulinemia and during malignant chronic lymphocytic leukemia (CLL):high frequency of the same VH and V kappa gene usage by both types of monoclonal B cells producing IgM with RF activity, apparent intraclonal homogeneity, but different expression of the pan T cell CD5 Ag. The description of an unusual CD5-negative B cell CLL case secreting a mutated IgM RF led the authors to suggest that the usage of non-mutated germline Ig genes is a property of cells derived from the CD5 lineage or stage of differentiation, rather than an intrinsic property of CLL or of IgM RF-producing cells in general. Because mixed cryoglobulinemia cells are usually CD5-negative, it was of interest to test for the existence of mutations in the VH and V kappa regions, as well as for the intraclonal homogeneity of the expressed Ig genes. In this study, we used the PCR technique to analyze the monoclonal rheumatoid factor (mRF) V genes from a patient with mixed cryoglobulinemia. We show that the CD5-negative monoclonal B cells express a slightly mutated V kappa 3 gene, but a more mutated VH1 gene whose genomic counterpart was shown to be the 51p1 germline gene. The sequence analysis of several independent clones shows some degree of intraclonal diversity, suggesting the existence of a clonal filiation. These results are discussed in terms of the origin of the monoclonal B cell during mixed cryoglobulinemia and CLL.

George, E., T. J. Lillemoe, et al. (1995). "Malignant mixed mullerian tumor versus high-grade endometrial carcinoma and aggressive variants of endometrial carcinoma: a comparative analysis of survival." Int J Gynecol Pathol 14(1): 39-44.

To ascertain whether uterine malignant mixed mullerian tumors are biologically distinct from high-grade endometrial carcinomas (FIGO grade 3), we compared patient survival in 32 and 39 cases, respectively. The Cox proportional hazard model was employed to determine whether tumor type was an independent predictor of survival. The survival of patients with MMMT was also compared to that of patients with serous adenocarcinoma and clear cell carcinoma. The 5-year overall and disease-free survival were significantly lower for malignant mixed mullerian tumors (25% and 11%) than for high-grade endometrial carcinomas (64% and 56%). Using the Cox proportional hazard model, tumor type (MMMT vs. high-grade endometrial carcinoma) was a statistically significant predictor of survival after other important prognostic variables such as pathologic stage, depth of myometrial invasion, and vascular invasion had been taken into account. The increased aggressiveness of MMMT appears most attributable to their tendency to reach a more advanced stage by the time of clinical presentation and to their greater propensity for upper abdominal dissemination. The survival of patients with MMMT was also lower than that of patients with the special histologic variants of endometrial carcinoma, serous adenocarcinoma and clear cell carcinoma, which are recognized for their unusually aggressive clinical behavior. These results indicate that uterine malignant mixed mullerian tumors are clinically more aggressive than high-grade endometrial carcinomas and should continue to be recognized as a distinct entity.

Mount, S. L., K. R. Lee, et al. (1995). "Carcinosarcoma (malignant mixed mullerian tumor) of the uterus with a rhabdoid tumor component. An immunohistochemical, ultrastructural, and immunoelectron microscopic case study." Am J Clin Pathol 103(2): 235-9.

A case of uterine carcinosarcoma (malignant mixed mullerian tumor) of the uterus containing a rhabdoid tumor element is described. In addition to a malignant glandular component and anaplastic sarcomatous areas, this tumor had multiple foci with histologic and ultrastructural features of malignant rhabdoid tumor. Vimentin positivity by immunohistochemistry was confirmed by immunoelectron microscopy. Although three malignant rhabdoid tumors of the uterus have been previously described, in addition to rhabdoid differentiation in an endometrial stromal sarcoma, to our knowledge this is the first report of rhabdoid tumor differentiation occurring within a uterine carcinosarcoma.

Shin, D. M., F. V. Fossella, et al. (1995). "Prospective study of combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin for unresectable or metastatic malignant pleural mesothelioma." Cancer 76(11): 2230-6.

BACKGROUND. This study was designed to determine the efficacy and side effects of a combination of cyclophosphamide (C), doxorubicin (D), and cisplatin (P) in patients with inoperable, unresectable, or metastatic malignant pleural mesothelioma. METHODS. Twenty-three patients with unresectable or metastatic malignant pleural mesothelioma were entered onto the study. The median age was 62 years (range, 42-74 years); there were 20 males and 3 females; the median performance status was 1 (Zubrod's scale). The histologic types included epithelial (14 patients), sarcomatoid (4 patients), unclassified (4 patients), and mixed type (1 patient). Twenty patients were known to have been exposed to asbestos and 3 were not. All patients were treated with the following starting dose of chemotherapy: a cycle comprised of C, 500 mg/m2 intravenously, day 1; D, 50 mg/m2 intravenously, day 1; and P, 80 mg/m2 intravenously, day 1 every 3 weeks. The cisplatin dose was reduced to 50 mg/m2 for the subsequent courses. For the assessment of tumor response, all patients had computed tomography scans of the chest after each three cycles of chemotherapy. RESULTS. Overall, 7 of 23 patients (30%) had partial responses (durations of responses [weeks]: 158+, 91+, 70+, 41+, 40, 39, 25), three had minor responses, and 14 had stable or progressive disease. One partial responder later underwent surgical resection and no viable tumors cells were found in the pathologic specimen. All patients have stopped treatment, and eight are still alive. The most common side effect was granulocytopenia (grade 4, 52%; grade 3, 17%). Other hematologic side effects were modest. Nonhematologic side effects included mild to moderate nausea and vomiting, neutropenic fever (three patients), peripheral neuropathy (one patient), and congestive heart failure (one patient). The overall median duration of survival was 60 weeks. CONCLUSION. Combination chemotherapy with CDP was well tolerated and had significant activity against unresectable or metastatic malignant pleural mesothelioma. The median duration of responses was 60 weeks; however, the survival rate was far from satisfactory. Continued development of new approaches including the biologic understanding of tumor development and testing new agents is warranted.

Tornos, C., E. G. Silva, et al. (1995). "Endometrioid carcinoma of the ovary with a prominent spindle-cell component, a source of diagnostic confusion. A report of 14 cases." Am J Surg Pathol 19(12): 1343-53.

Fourteen endometrioid carcinomas of the ovary with a prominent component of spindle-shaped epithelial cells are reported. Eleven were initially misdiagnosed as sexcord stromal tumors, malignant mesodermal mixed tumors, tumors of probable wolffian origin, or metastatic carcinomas. All of the tumors, however, had one or more features establishing them as endometrioid carcinomas, including (a) glands typical of endometrioid adenocarcinoma, (b) foci of squamous differentiation, and (c) an adenofibromatous component. Six cases were examined immunohistochemically, and the epithelial nature of the spindle cells was supported by immunostaining for keratin and epithelial membrane antigen. The patients ranged in age from 42 to 89 years (mean, 61). Four cases were stage I, five stage II, and three stage III. Follow-up information was available in seven cases. Five patients were free of disease at 8, 11, 32, 56, and 103 months, and two patients were alive with disease at 10 and 20 months. The age of the patients, clinical presentation, tumor stage, and gross appearance were similar to those of typical endometrioid carcinomas. It is important that this tumor be distinguished from other ovarian neoplasms with a spindle-cell component because of differences in treatment and prognosis.

Anderson, D., J. B. Bishop, et al. (1995). "Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks." Mutat Res 330(1-2): 115-81.

Cyclophosphamide (CP) is used to treat a wide range of neoplastic diseases as well as some non-malignant ones such as rheumatoid arthritis. It is also used as an immunosuppressive agent prior to organ transplantation. CP is, however, a known carcinogen in humans and produces secondary tumors. There is little absorption either orally or intravenously and 10% of the drug is excreted unchanged. CP is activated by hepatic mixed function oxidases and metabolites are delivered to neoplastic cells via the bloodstream. Phosphoramide mustard is thought to be the major anti-neoplastic metabolite of CP while acrolein, which is highly toxic and is produced in equimolar amounts, is thought to be responsible for most of the toxic side effects. DNA adducts have been formed after CP treatment in a variety of in vitro systems as well as in rats and mice using 3H-labeled CP. 32P-postlabeling techniques have also been used in mice. However, monitoring of adducts in humans has not yet been carried out. CP has also been shown to induce unscheduled DNA synthesis in a human cell line. CP has produced mutations in base-pair substituting strains of Salmonella tryphimurium in the presence of metabolic activation, but it has been shown to be negative in the E. coli chromotest. It has also been shown to be positive in Saccharomyces cerevisiae in D7 strain for many endpoints but negative in D62.M for aneuploidy/malsegregation. It has produced positive responses in Drosophila melanogaster for various endpoints and in Anopheles stephensi. In somatic cells, CP has been shown to produce gene mutations, chromosome aberrations, micronuclei and sister chromatid exchanges in a variety of cultured cells in the presence of metabolic activation as well as sister chromatid exchanges without metabolic activation. It has also produced chromosome damage and micronuclei in rats, mice and Chinese hamsters, and gene mutations in the mouse spot test and in the transgenic lacZ construct of Muta Mouse. Increases in chromosome damage and gene mutations have been found in the peripheral blood lymphocytes of nurses, pharmacists and female workers occupationally exposured to CP during its production or distribution. Chromosome aberrations, sister chromatid exchanges and gene mutations have been observed in somatic cells of patients treated therapeutically with CP. In general, there is a maximum dose and an optimum time for the detection of genetic effects because the toxicity associated with high doses of CP will affect cell division. In germ cells, CP has been shown to induce genetic damage in mice, rats and hamsters although the vast majority of such studies have used male mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Sun, M., T. Shioya, et al. (1995). "[Two autopsy cases of malignant mixed mullerian tumor of the uterus with metastasis to alimentary tract and liver]." Nippon Ika Daigaku Zasshi 62(4): 391-5.

Two autopsy cases (69 and 87-year-old women) of malignant mixed mullerian tumor (MMMT) following radiation therapy for uterine cervical cancer sixteen and twenty years ago respectively were reported. They were admitted due to abdominal pain and diagnosed as ileus. In the first case, CT examination revealed a tumor measuring about 8 x 10 cm in size in the uterine posterior wall. Recurrence of the uterine cancer was suspected and hysterooophorectomy combined with sigmoidectomy was performed. In the second case, artificial anus formation was performed because of sigmoid stricture by the invasion of the tumor. Histologically, tumors in both cases were composed of carcinomatous and sarcomatous components including heterologous elements such as cartilage. The patients died of extensive spreads and metastasis in the liver and alimentary tract.

Mainkhard, K., S. Raicheva, et al. (1995). "[Malignant Mullerian mixed tumors of the female genitalia]." Akush Ginekol (Sofiia) 34(2): 39-41.

Morphological features and clinical data of 27 malignant mixed Mullerian tumors of uterus and ovaries are represented. These neoplastic entities have been systematized and controversial problems of terminology, nature and origin, as well as macroscopic and histopathological features have been discussed. Based on our own experience and on references to literature on this subject, clinicopathological correlation have been analyzed in order to point out reliable criteria for differential diagnosis, prognosis for therapeutic response and biological behavior of these tumors.

Emoto, M., H. Iwasaki, et al. (1994). "Primary osteosarcoma of the uterus: report of a case with immunohistochemical analysis." Gynecol Oncol 54(3): 385-8.

Primary osteosarcoma of the uterus is an extremely rare neoplasm, and its immunohistochemical characteristic is unknown. We report a case of osteosarcoma occurring primarily in the uterine corpus of a 67-year-old woman with lower abdominal pain. The excised tumor showed bony inconsistency and histologically displayed a "pure" osteosarcoma of the uterus. Immunocytochemically, the tumor cells were positive for vimentin but negative for epithelial markers. The patient died 4 months after surgery because of developed local recurrence and pulmonary metastases. In conclusion, uterine osteosarcoma differs from malignant mixed Mullerian tumor (MMMT) in biological behavior, macroscopic and histologic features, and immunohistochemical profile. Osteosarcoma shows more aggressive behavior than MMMT, and displays nonpolypoid feature in appearance and no evidence of epithelial differentiation.

Choong, S. Y., J. P. Scurry, et al. (1994). "Extrauterine malignant mixed mullerian tumor of primary peritoneal origin." Pathology 26(4): 497-8.

The case of an extrauterine heterologous malignant mixed mullerian tumor (MMMT) of primary peritoneal origin occurring in a 63 yr old woman is presented. The tumor was a 19 cm, soft, friable mass arising from the serosa of the sigmoid colon and spreading to adjacent pelvic peritoneum. The uterus, tubes and ovaries were uninvolved. It was composed of sarcomatous areas showing cartilaginous and rhabdomyoblastic differentiation and sharply demarcated carcinomatous areas showing endometrioid and serous differentiation. This is the thirteenth reported case of an extragenital MMMT. It demonstrates the pluripotentiality of female pelvic peritoneum to differentiate into tumors resembling those of the genital tract.

Goertchen, R., A. Seidenschnur, et al. (1994). "[Clinical pathology of inverted papillomas of the urinary bladder. A complex morphologic and catamnestic study (2)]." Pathologe 15(5): 279-85.

The histopathology, ultrastructure, pathological status and clinical course are described in a total of 29 cases of inverted papilloma of the urinary bladder (IP). The IP was isolated in 16 cases and occurred in combination with a papillary urothelial carcinoma in 13 cases. Histologically, a trabecular, a glandular and a mixed type can be differentiated. The trabecular form predominates in a ratio of 4:1. The glandular form is further subdivided into a cystic form and an adenomatous form containing cylindrical cells. Contrary to earlier assumptions, dysplasia and malignant transformation also occur in IP. Amongst the 16 isolated IP observed, four showed slight and four showed moderate dysplasia. One isolated IP was malignant and invasive. In IP in combination with papillary urothelial carcinomas, malignant transformation is somewhat more frequent. Four malignant IP and up to 85% dysplasias were found among the 13 cases. The ultrastructure of IP reveals two cell types: a light cell form which corresponds to a slightly dysplastic urothelium and a darker cell form with or without microvilli which is observed in the glandular type. A frequent characteristic is a thickening of the basement membrane besides abundant "tight junctions". The immunohistochemistry is relatively uncharacteristic. This also applies to the blood group isoantigens, which showed irregular and relative uninformative results in the SCRA test. IP is observed in all age groups and the sex ratio (M/F) is 3:1. The average age of manifestation is 56 years, about 10 years earlier than bladder carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

To, W. W. and H. Y. Ngan (1994). "Malignant mixed Mullerian tumors of the uterus." Int J Gynaecol Obstet 47(1): 39-44.

OBJECTIVE: To review the prognostic factors of Chinese women with mixed Mullerian tumors of the uterus. METHOD: A retrospective review of 21 cases of malignant mixed Mullerian tumors of the uterus treated during the 10-year period from 1980 to 1990. RESULTS: All patients except one were postmenopausal. The incidence of previous pelvic irradiation was 9.5%. The most common presenting symptom was abnormal vaginal bleeding. One-third of patients yielded an abnormal cervical smear. Treatment included surgery, chemotherapy and radiotherapy in the majority of patients. Prognosis was poor with only three long-term survivors, all with stage-I homologous tumors with superficial myometrial invasion. The survival rate for stage-I and -II disease at 2 years was 50% and for more advanced disease extending beyond the uterus was 0%. The survival rate for all stages at 5 years was 14.3%, and the cumulative probability of survival at 5 years was 0.165. CONCLUSION: The most important prognostic factors appear to be the extent of tumor involvement at the time of diagnosis and the depth of myometrial invasion.

Munkarah, A., D. M. Gershenson, et al. (1994). "Salvage surgery for chemorefractory ovarian germ cell tumors." Gynecol Oncol 55(2): 217-23.

This study was undertaken to determine whether secondary surgical debulking is beneficial for patients with malignant ovarian germ cell tumors (OGCT). Twenty patients with OGCT treated at our institution between 1975 and 1992 were retrospectively identified and analyzed. Survival was analyzed using the life-table methods of Kaplan and Meier and the statistical significance of various perioperative factors was tested by both the log-rank and the Wilcoxon tests. Histologic tumor type included 8 immature teratomas, 6 mixed tumors, 5 endodermal sinus tumors, and 1 dysgerminoma. After primary surgery, all patients received chemotherapy--non-platinum-based in 12 patients, platinum-based in 5, and both types in 3 patients. Treatment failure was classified as progression in 14 patients, persistence in 3, and recurrence in 3. Salvage surgery consisted of exploratory laparotomy and tumor debulking in 18 patients, inguinal lymphadenectomy in 1, and thoracotomy and wedge resection in 1. Sixteen patients subsequently received salvage chemotherapy. At the time of analysis, 11 patients were alive disease-free, 1 was alive with tumor, 6 had died of tumor progression, and 2 had died of treatment-related complications. Survival of patients with immature teratoma who underwent salvage surgery was significantly better than survival of those with other tumor cell types (P = 0.006). In conclusion, although the role of secondary debulking in chemorefractory OGCT remains undetermined, it may have some benefit for a select group of patients, particularly those with immature teratoma.

Amin, M. B., J. Y. Ro, et al. (1994). "Lymphoepithelioma-like carcinoma of the urinary bladder." Am J Surg Pathol 18(5): 466-73.

We report the cases of 11 patients who were treated for undifferentiated carcinoma of the urinary bladder with a prominent lymphoid stroma (lymphoepithelioma-like carcinoma [LELC]). The chief complaint of all 11 patients was hematuria. Their ages ranged from 52 to 79 years (mean of 67). All tumors except one invaded the muscle wall and showed the typical syncytial growth pattern of undifferentiated cells with ill-defined cytoplasmic borders, prominent nucleoli, and numerous mitoses. A significant lymphocytic reaction was an essential component of all these tumors. There were three pure LELC tumors without concurrent invasive transitional-cell carcinoma (TCC) or TCC in situ; these cases morphologically simulated large-cell lymphoma. The remainder were mixed TCC and LELC (five predominant and three focal LELC). The tumor cells were immunoreactive for keratin and showed negative results for leukocyte common antigen. The lymphoid population was an admixture of T cells and B cells with a predominance of T cells. Seven patients (four with predominant and three with focal LELC) were treated with various therapeutic methods. Four patients (three with pure and one with predominantly LELC) received only chemotherapy after transurethral resection of the tumor, and follow-up found no evidence of disease for 9-72 months (mean of 38 months). Awareness of an LELC component in a urinary bladder tumor is also important in order to avoid misinterpreting these tumors as malignant lymphoma or severe chronic cystitis. Our data suggest that the pure LELC tumor appears to be morphologically and clinically different from TCC and that it merits recognition as a separate clinicopathologic entity. In addition, there is strong suggestive evidence that it responds to chemotherapy and therefore there is the potential of salvaging bladder function.

Prendiville, J., D. Murphy, et al. (1994). "Carcinosarcoma of the ovary treated over a 10-year period at the Christie Hospital." Int J Gynecol Cancer 4(3): 200-205.

Carcinosarcomas (previously termed malignant mixed Mullerian tumors) are highly malignant but rare tumors of the ovary. Most patients have been treated according to a wide variety of protocols for soft tissue sarcoma or for epithelial ovarian carcinoma and as a result the optimal treatment for this neoplasm is unknown. We describe here 20 patients with this ovarian tumor (15 with heterologous sarcomatous elements and five with homologous sarcomatous elements) referred to our institute. Five patients were treated with surgery alone, two patients with chemotherapy alone and 13 patients with a combination of surgery and chemotherapy. A variety of chemotherapeutic regimens were used reflecting the 10-year time span it took to accrue these patients. Forty-five per cent of all patients died within 1 year of initial surgery and there was a median survival of 14 months. Two patients achieved a complete remission following treatment with 10 cycles of intravenous cyclophosphamide and are still alive at 103 and 106 months follow-up. We suggest that a chemotherapy regimen combining cyclophosphamide and a platinum analog may be useful for the management of patients with carcinosarcoma of the ovary requiring further therapy following surgery.

Donat, E. E., J. M. McCutcheon, et al. (1994). "Malignant mixed mullerian tumor of the ovary. Report of a case with cytodiagnosis by fine needle aspiration." Acta Cytol 38(2): 231-4.

An elderly woman with a history of a total hysterectomy underwent fine needle biopsy of an ovarian lesion during laparotomy. The cytologic findings demonstrated adenocarcinomatous and heterologous sarcomatous cells and were reported as a malignant mixed mullerian tumor. A histologic examination confirmed this diagnosis.

Cheung, A. N., H. Y. Ngan, et al. (1994). "Clinicopathologic study of 16 cases of primary tubal malignancy." Int J Gynecol Cancer 4(2): 111-118.

Sixteen cases of primary carcinoma of the fallopian tube were diagnosed and treated at Queen Mary Hospital, Hong Kong from July 1972 to June 1992 constituting 0.26% of the total gynecologic malignancies seen during that period. The average age was 61 years and the most common presenting symptom was abnormal vaginal bleeding. Preoperative diagnosis is difficult; in only one case was a diagnosis of malignancy made by cervical smear. An adnexal mass was detected in 13 of the cases (81.3%) either by clinical examination and/or ultrasonography. Therapy consisted of surgical resection, usually followed by various combinations of adjuvant radiation therapy and chemotherapy. The cumulative survival was 62%. In addition to the typical form of adenocarcinoma, one case of squamous cell carcinoma and a case of multifocal endometrioid adenocarcinoma were observed. One case of an apparently usual form of adenocarcinoma recurred as a heterologous malignant mixed Mullerian tumor 2 years after diagnosis. This series further emphasises the wide range of differentiation possible in the Mullerian system and the variety of neoplasms which may arise from it.

Westra, W. H., B. O. Anderson, et al. (1994). "Carcinosarcoma of the spleen. An extragenital malignant mixed mullerian tumor?" Am J Surg Pathol 18(3): 309-15.

A 55-year-old woman with painful splenomegaly underwent surgical exploration and resection of the spleen. Pathologic examination revealed a neoplasm of the spleen exhibiting malignant stromal and epithelial components with mullerian features. In the absence of a recognized neoplasm elsewhere, the carcinosarcoma most likely arose as a primary splenic tumor and may represent an extrauterine malignant mixed mullerian tumor arising in the spleen.

Silva, E. G., C. S. Tornos, et al. (1994). "Malignant neoplasms of the uterine corpus in patients treated for breast carcinoma: the effects of tamoxifen." Int J Gynecol Pathol 13(3): 248-58.

We reviewed the clinical history and pathology material of 72 patients seen at the M. D. Anderson Cancer Center who developed malignant neoplasms of the uterine corpus after being treated for breast carcinoma with either tamoxifen or other therapeutic regimens. The purpose of this study was to investigate the type of malignant tumors seen in the uterus, their association with endometrial polyps or hyperplasia, and their possible relationship to tamoxifen treatment. This study shows that in patients treated for breast carcinoma, the uterine malignancies are characterized by several features: (a) a previously unreported high incidence of clear cell carcinoma (14 cases) and leiomyosarcoma (12 cases); (b) seven of 12 leiomyosarcomas with unusual features, such as epithelioid (5), tubular (1), and myxoid features (2); (c) a higher incidence of serous carcinoma (45% in patients treated for > or = 12 months); (d) endometrial polyps associated with carcinoma more often than endometrial hyperplasia.

Boucher, D. and B. Tetu (1994). "Morphologic prognostic factors of malignant mixed mullerian tumors of the ovary: a clinicopathologic study of 15 cases." Int J Gynecol Pathol 13(1): 22-8.

Fifteen ovarian malignant mixed mullerian tumors (MMMT) of the ovary are reported in an attempt to identify morphologic factors of prognostic interest. Several features were correlated to survival: histologic subtype and nuclear and histologic grades of the epithelial component; histologic subtype, grade, and mitotic rate of the mesenchymal component; necrosis and epithelial-to-mesenchymal ratio. The epithelial component was mainly of endometrioid (four cases) and serous (four cases) types. The mesenchymal component was largely heterologous, of which five were of chondromatous and five of rhabdomyoblastic differentiation. This latter differentiation was further demonstrated by electron microscopy (two cases) and immunohistochemistry (four cases). Ten tumors showed hyaline droplets that stained for alpha 1-antitrypsin in two cases. Eight patients died of their disease, 13 days to 32 months after diagnosis (median, 5 months). Seven were alive 3 to 49 months (median, 10 months) after initial therapy. No morphologic factor was found to correlate with survival, but a tendency was observed for ovarian MMMTs with a high epithelial nuclear grade, a predominance of the mesenchymal component, or a rhabdomyoblastic mesenchymal component to be associated with more aggressive behavior. The histologic appearance of metastases did not correlate with prognosis.

Hackett, T. E., P. Kaminski, et al. (1994). "Tissue distribution of TAG-72 in malignant mixed mullerian tumors of the uterus." Gynecol Oncol 52(2): 165-71.

Malignant mixed mullerian tumors are the most frequent sarcomas arising from the uterus. Since these tumors are traditionally associated with a poor prognosis, tumor-associated antigens may be useful in the evaluation and follow-up of affected patients. The purpose of this study was to determine the frequency and tissue distribution of TAG-72, an antigen frequently expressed in endometrial carcinomas, and to compare it to CA 125 and CA 19-9 expression in malignant mixed mullerian tumors of the uterus. Consecutive, paraffin-embedded sections from 35 tumors were immunohistochemically evaluated using primary antibodies directed against the tumor-associated antigens. These antigens were demonstrated in the neoplastic glandular epithelium and not in the sarcomatous portion of the tumor. The degree of antigen expression was unrelated to the nature of the sarcomatous element present (homologous vs heterologous). Positive staining (> or = 5% of the glandular epithelium) for TAG-72 was present in 66% of the tumors; another 6% of the tumors contained focal staining (< 5% of the glandular epithelium) for TAG-72. Although cytoplasmic and intraluminal staining were present, cell surface staining was the most prominent feature of TAG-72 expression. Tumors were more likely to be positive for TAG-72 than either CA 125 (P = 0.046) or CA 19.9 (P = 0.004). The extent of TAG-72 expression was unrelated to the extent of disease (intrauterine vs extrauterine) and overall patient survival. However, antigen expression was correlated with the differentiation of the glandular component present.(ABSTRACT TRUNCATED AT 250 WORDS)

Woodruff, J. M. and G. Perino (1994). "Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation, with emphasis on the malignant Triton tumor." Semin Diagn Pathol 11(1): 69-81.

Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation can be divided into three groups. Group I consists of tumors with only sarcomatous differentiation. Included in this group are malignant mesenchymoma, dedifferentiated chondrosarcoma, and the dedifferentiated retroperitoneal liposarcoma. Epithelial or Sertoli-Leydig cell elements represent the second component of tumors in group II. The best known tumor in this group is the malignant mullerian mixed tumor, but other well described tumors with rhabdomyosarcomatous differentiation are the carcinosarcoma, mullerian adenosarcoma, Sertoli-Leydig cell tumor, mammary cystosarcoma, and blastomas. Most of the tumors in groups I and II are derived from mesenchymal tissue. A neuroectodermal origin is shared by all tumors in group III. This includes the medulloblastoma, retinoblastoma and, most frequently, the malignant Triton tumor. The tumors in all three groups are clinically malignant to a varying degree.

Bulun, S. E., K. Economos, et al. (1994). "CYP19 (aromatase cytochrome P450) gene expression in human malignant endometrial tumors." J Clin Endocrinol Metab 79(6): 1831-4.

C19 steroids are converted to estrogens in a number of human tissues by the aromatase enzyme complex, which consists of aromatase cytochrome P450 (P450arom; product of the CYP19 gene) and NADPH-cytochrome P450 reductase. Aromatase activity has been previously demonstrated in endometrial tumors. In the present study, we investigated CYP19 gene expression and its regulation in endometrial tumor samples (n = 9). Using a specific method of competitive polymerase chain reaction after reverse transcription, varying levels of P450arom transcripts were detected in all endometrial adenocarcinomas (n = 8) and one mixed Mullerian tumor studied. No correlations were observed between P450arom transcript levels and histological type of the tumor, grade, myometrial invasion, stage of the disease, or patient age. We have recently demonstrated that the tissue-specific regulation of CYP19 gene transcription is in part the consequence of alternative promoter use. The use of each promoter gives rise to a P450arom transcript with a unique untranslated 5'-end. We analyzed the untranslated first exons in 5'-terminals of P450arom transcripts in endometrial adenocarcinomas using a specific reverse transcription-polymerase chain reaction/Southern hybridization method we recently developed. Our findings indicated the gonadal-type (promoter II) and one of the adipose stromal cell-type (I.3) promoters were primarily used for P450arom expression in adenocarcinomas. On the other hand, distribution of transcripts specific for I.3, I.4 (another adipose-type promoter), and promoter II in one mixed Mullerian tumor was uniform. Placental promoter (I.1)-specific P450arom transcripts were not detected in endometrial tumors. As P450arom transcripts were detected in all endometrial malignancies studied, whereas they were not demonstrable in the disease-free endometrium, activation or failure of inhibition of aromatase expression in these tumors may serve to promote neoplastic proliferation.

Mourad, W. A., N. Sneige, et al. (1994). "Fine-needle aspiration cytology of recurrent and metastatic mixed mesodermal tumors." Diagn Cytopathol 11(4): 328-32.

We report the cytological and clinical findings of 16 fine-needle aspirates (FNAs) performed on recurrent (n = 6) and metastatic (n = 10) mixed mesodermal tumors (MMMTs). The median interval between the primary diagnosis and FNA was 16 mo. Primary sites were the endometrium (n = 11), the ovary (n = 3), the cervix (n = 1), and pelvic soft tissue (n = 1). Primary tumors showed carcinoma with homologous mesenchymal components in 13 cases and focal heterologous elements in three (two chondrosarcomas and one rhabdomyosarcoma). The FNAs showed carcinoma in all 16 cases, with adenocarcinoma differentiation in three. Mesenchymal elements were identified in aspirates of three recurrent and two metastatic lesions. They were all homologous. aspirates. We conclude that mesenchymal components in FNAs of MMMTs are less likely to be seen in metastatic lesions, and that heterologous mesenchymal components are rarely seen in these aspirates even in recurrent disease. These findings confirm that the epithelial component is responsible for the malignant behaviour of MMMTs, and suggest that these lesions may need to be classified as sarcomatoid carcinomas rather than true carcinosarcomas.

Vaideeswar, P., M. S. Desai, et al. (1994). "Malignant mixed mesodermal (Mullerian) tumour of ovary." Indian J Pathol Microbiol 37 Suppl: S21-2.

Garamvoelgyi, E., L. Guillou, et al. (1994). "Primary malignant mixed Mullerian tumor (metaplastic carcinoma) of the female peritoneum. A clinical, pathologic, and immunohistochemical study of three cases and a review of the literature." Cancer 74(3): 854-63.

BACKGROUND. Malignant mixed mesodermal tumors (malignant mixed Mullerian tumors [MMMT]) occur rarely in extragenital sites. METHODS. The authors analyzed the clinical, pathologic, and immunohistochemical features of three cases of primary MMMT of the female peritoneum. RESULTS. The neoplasms occurred in 60-, 64- and 84-year-old women and arose from pelvic peritoneum. Two patients died with disseminated disease 8 and 24 months postoperatively. The third died of cardiac failure 12 months postoperatively with questionable metastatic disease. Microscopically, two tumors were of the heterologous type, containing foci of rhabdomyosarcomatous (case 1) and chondrosarcomatous (case 3) differentiation. Immunohistochemically, coexpression of keratin and vimentin was observed focally in both carcinomatous and sarcomatous components in all three neoplasms, whereas coexpression of low molecular weight cytokeratin, vimentin and actin was observed focally in case 2. Rhabdomyosarcomatous areas were positive with desmin and actin, and chondrosarcomatous areas for S-100 protein. Both epithelial and mesenchymal components were positive for alpha-1 antichymotrypsin in all cases. CONCLUSIONS. On the basis of the present cases and a review of 15 reports from the literature, primary MMMT of the female peritoneum proved to be a rare but highly malignant neoplasm occurring in elderly postmenopausal women. Of 15 patients with available follow-up, 12 died with disease, mostly within 1 year, regardless of the initial tumor stage, histology (homologous versus heterologous MMMT) or treatments attempted. The tumor developed within pelvic peritoneum in half the cases. Histogenetically, peritoneal MMMT are thought to represent "metaplastic" carcinomas originating from the secondary Mullerian system.

Wanke-Jellinek, C., S. M. Missaghi, et al. (1994). "[Hypercapnia and mixed acidosis as the only sign of malignant hyperthermia (MH)?]." Anaesthesist 43(8): 553-6.

CASE REPORT. A 34-year-old male (190 cm/100 kg) was scheduled for surgery of the nasal septum. He had had uneventful anaesthesia for appendicectomy 14 years earlier: following 600 mg thiopentone, 180 mg suxamethonium and up to 2 vol.% halothane for 20 min had been used and no symptoms of malignant hyperthermia (MH) were recorded. Following oral premedication with 2 mg flunitrazepam at 7.00 a.m. anaesthesia was induced with a priming dose of atracurium at 8.45 a.m. followed by 0.2 mg fentanyl, 500 mg thiopentone, and 100 mg suxamethonium. Endotracheal intubation was accomplished easily, and the patient was ventilated manually in a semi-closed circle system until spontaneous ventilation resumed. Enflurane (1.5% for 5 min, 1.0% for 10 min, and 0.8% until the diagnosis of MH was suspected) was given in 33% O2/66% N2O. Seventy minutes after induction it was noted that the spontaneous respiratory rate and minute volume had risen continuously from 10/min and 6 l/min, respectively, to 20/min and 12 l/min. Attempts at deepening anaesthesia with repeated doses of fentanyl up to a total dose of 0.95 mg failed to reduce the hyperventilation. In spite of a high fresh gas flow of 6 l/min and assisted manual ventilation, the FIO2 started to fall from 0.34 to 0.28 at 10:20 a.m. The O2/N2O ratio was changed to 1:1, but the FIO2 remained at 0.3. MH was suspected, enflurane was discontinued, and an arterial blood gas analysis was done (Table 2). When marked acidosis and hypercarbia were found, dantrolene 2.5 mg/kg was given, the operation was terminated, and the patient's trachea was extubated and he was monitored closely in the intensive care unit for 24 h. Vital signs were stable (Table 3) and no further complications were observed. The patient did not mention pain or uneasiness postoperatively. About 6 months later, a muscle biopsy was done according to the European MH Protocol and the patient was found to be MHEh. DISCUSSION. In this case five main reasons for the hypercarbia and mixed acidosis must be considered (Table 1). Firstly, hypoventilation does not seem to be reasonable as the patient was ventilated with 8 to 12 l/min, which is within the range of 80-120 ml/kg.min. Secondly, we can exclude shock and hypoperfusion because the patient had a normal blood pressure and heart rate (within 65-90 beats/min), his fingertips and skin were well perfused, his body temperature was 37 degrees C, and there was no sign of muscle rigidity. Thirdly, a defect of the CO2 absorber as well as CO2 admixture to the N2O and O2 ventilation gases can cause hypercarbia. We use two absorbers in sequence of which one is changed every day, and found neither a change in colour of the indicator nor an abnormally raised temperature of the absorbers. A postoperative check of the ventilator showed no defect in the O2/N2O supply and a correctly functioning anaesthesia apparatus. A malfunction of both CO2 absorbers resulting in intraoperative hypercarbia could not explain a postoperative mixed acidosis lasting for more than 6 h. Anaesthesias performed at the same time using soda lime from the same canisters were totally uneventful. CONCLUSION. It is concluded that the hypercarbia and mixed acidosis were caused by hypermetabolism. A thorough postoperative examination by an internist did not reveal any thyroid, pulmonary, endocrine, or circulatory reason for our intra- and postoperative findings. Iatrogenic factors like superficial anaesthesia or systemic side effects of adrenaline admixture to local anaesthetics can cause hypermetabolism without striking clinical signs, but they do not cause mixed acidosis lasting longer than 6 h (Table 2). The most suitable explanation in this case is an abortive form of MH. Even patients who are MHS positive on muscle biopsy do not necessarily go through an MH crisis every time they have stress or undergo anaesthesia. The diagnosis of a fulminant MH crisis is a clinical one. Therefore, we are aware that there is no direct scientific ev

Benda, J. A., A. Veronezi-Gurwell, et al. (1994). "An unusual extrauterine variant of adenosarcoma with multiple recurrences over 16 years." Gynecol Oncol 53(1): 131-7.

An unusual extrauterine (pelvic) variant of adenosarcoma is presented. A benign-appearing epithelium resembling fallopian tube epithelium is integrally mixed with malignant stroma that in all areas sampled is low-grade leiomyosarcoma. The tumor has behaved as a low-grade malignancy with four local recurrences over a 16-year period. Extrauterine adenosarcomas have rarely been reported in the literature; and one in which the stromal component is histologically all of smooth muscle differentiation is more unusual.

Zorlu, C. G., O. Cobanoglu, et al. (1994). "Malignant mixed mullerian tumor of the fallopian tube." Acta Obstet Gynecol Scand 73(4): 352-4.

Primary malignant mixed mullerian tumor of the fallopian tube is uncommon. Only 37 cases of malignant mixed mullerian tumor of the fallopian tube have been reported to date and of these only 16 contained heterologous components (mesodermal mixed tumor). This rarity made us report a case of malignant mixed mullerian tumor of the fallopian tube containing heterologous components which was operated on in our gynecologic oncology department. Postoperatively the patient was placed on six courses of adjuvant chemotherapy consisting of cis-platinum, adriamycin and cyclophosphamide (PAC). Second look laparotomy was performed after completion of chemotherapy. Presently, she is doing well, at two months follow-up, with no evidence of disease.

Magliocco, A. M. and M. H. Brilliant (1994). "Genome scanning detects genetic alterations in human ovarian carcinoma." Hum Mutat 4(2): 141-9.

Genome scanning, originally used to detect mouse mutations, is a technique which can rapidly identify differences between genomic DNA samples. The procedure is essentially a high resolution Southern analysis using a probe that hybridizes to a medium copy number (1000-2000 copies per haploid genome) repetitive element naturally dispersed throughout the genome. This technique detects genetic changes (primarily large scale genetic changes, e.g., amplifications and deletions) as differences in hybridization band intensity. The use of a probe derived from an endogenous human retroviral-like repetitive sequence, the RTVL-H element, has made genome scanning in humans feasible. In this report, the genome scanning technique was used to evaluate genomic DNA extracted from 14 frozen ovarian tumors. These included 8 high grade serous cystadenocarcinomas, 2 endometrioid carcinomas, one malignant mixed mullerian tumor, 2 Krukenberg tumors, and one tumor where histological classification was unavailable. Band amplifications were identified in 11 cases, with the most prominent amplifications observed in the high grade serous cystadenocarcinomas. In some of the cases, the amplifications involved bands of identical molecular size suggesting that similar underlying changes occurred in different tumors and are potentially associated with specific histological tumor types or clinical behavior. Band deletions were also observed in one endometrioid tumor where blood leukocyte genomic DNA was available from the same patient, allowing a direct comparison.

Chadwick, D. E., L. F. Jean, et al. (1993). "Differential sensitivity of human myeloma cell lines and normal bone marrow colony forming cells to a recombinant diphtheria toxin-interleukin 6 fusion protein." Br J Haematol 85(1): 25-36.

The cytotoxicity of a recombinant interleukin 6 (IL-6)-diphtheria toxin (DT) fusion protein towards human myeloma cell lines was investigated. DAB389-IL-6 inhibited protein synthesis and methylcellulose colony formation by U266 myeloma cells. In the clonogenic assay, the fusion protein approached the level of cytotoxicity achieved by native DT. The specificity of killing by DAB389-IL-6 was demonstrated by inhibition of cytotoxicity by a molar excess of free rhIL-6. The effect of DAB389-IL-6 on colony formation by six OCI-My cell lines was assessed. Similar to U266 cells, colony growth by the OCI-My 5 and -My 2 cell lines was inhibited in a simple dose dependent manner. However, a biphasic effect was observed for the IL-6 dependent OCI-My 4 cells; DAB389-IL-6 stimulated colony formation at low (< or = 10(-11) M) concentrations, yet was inhibitory at higher doses. Three other cell lines whose growth was not altered by IL-6 were relatively unaffected by DAB389-IL-6, despite their sensitivity to native DT. Flow cytometric analysis for IL-6 receptor expression using phycoerythrin-conjugated IL-6 demonstrated specific binding sites on both DAB389-IL-6 sensitive and certain insensitive cell lines, suggesting that other factors in addition to the expression of IL-6 receptors are involved in killing by the fusion toxin. Despite evidence for a role of IL-6 in myeloid cell development, normal bone marrow was insensitive to the IL-6 fusion toxin. In cultures containing both normal bone marrow and U266 cells DAB389-IL-6 effectively inhibited the growth of U266 myeloma colonies but had little effect on normal bone marrow erythroid, granulocyte and mixed erythroid/granulocyte colony growth. From these experiments we conclude that DAB389-IL-6 is specifically cytotoxic towards a subset of IL-6-responsive human myeloma cell lines and may be useful, in some cases, in the selective elimination of tumour cells from mixed populations of normal and malignant cells.

Iqbal, J. B. and J. W. Ironside (1993). "Cerebral metastasis from a malignant mixed mullerian tumour of the uterus." Histopathology 23(3): 277-9.

Liesveld, J. L., S. Rush, et al. (1993). "Phenotypic characterization of the human fibrous histiocytoma giant cell tumor (GCT) cell line and its cytokine repertoire." Exp Hematol 21(10): 1342-52.

The pleiotropic nature of malignant fibrous histiocytomas (MFH) is manifested as mixed cellular infiltrates consisting of myofibroblasts, histiomonocytes, and neutrophils. We detail in this report the phenotypic characteristics of the human fibrous histiocytoma giant cell tumor (GCT) cell line that establish its mesenchymal origin. The latter is underscored by the ability of GCT cells to express mRNA for transforming growth factor beta (TGF-beta) as well as both A and B chains of platelet-derived growth factor (PDGF). GCT cells also support the binding of CD34+ cells, but less efficiently than do normal marrow stromal cells. Since cytokines elaborated by MFH may mediate in part the recruitment of monocytes and neutrophils into tumor-infiltrated tissues, we have determined the cytokine repertoire of the GCT cell line, already known for its ability to elaborate colony-stimulating factors (CSFs) and interleukin-1 (IL-1). GCT cells express IL-1 alpha, IL-1 beta, IL-6, macrophage colony-stimulating factor (M-CSF or CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and IL-8. No detectable mRNA for IL-3, IL-4, IL-7, and tumor necrosis factor-alpha (TNF-alpha) was detected in GCT cells by polymerase chain reaction (PCR). Expression of cytokine mRNAs was responsive to agents such as dexamethasone (dex), 12-O-tetradecanoyl phorbol 13-acetate (phorbol diester or TPA), and TNF-alpha. Thus, this cell line provides a useful model for understanding the pathobiology of MFH and hematopoietic progenitor interactions with mesenchymal/stromal cells.

Fornage, B. D., M. H. McGavran, et al. (1993). "Imaging of the skin with 20-MHz US." Radiology 189(1): 69-76.

PURPOSE: The authors clinically evaluated a new high-frequency ultrasound (US) scanner to determine the value of US for dermatologic applications. MATERIALS AND METHODS: A 20-MHz US scanner was used to visualize normal skin at eight sites in 10 healthy volunteers and to evaluate 200 skin lesions (45 malignant, 155 benign). RESULTS: In normal skin, the dermis was markedly echogenic and sharply demarcated from hypoechoic subcutaneous fat. The epidermis was not resolved except on the palm and sole. Only three superficial lesions were not identified with US; evaluation of another three was limited by shadowing. Thickness of the lesions visualized was 0.2-26.0 mm (mean, 1.9 mm +/- 2.6). Most lesions (77%) were hypoechoic, 9% were anechoic, 12% had mixed echogenicity, and 2% were isoechoic or hyperechoic. CONCLUSION: The diagnostic role of high-frequency US appears limited. It did not help differentiate benign from malignant lesions, but it did enable accurate delineation of deep margins of lesions and allowed noninvasive measurement of thickness. These features may help in the preoperative evaluation of skin tumors and in monitoring the response to therapy for certain inflammatory conditions.

Hamaguchi, H., Y. Nakamura, et al. (1993). "Philadelphia-chromosome-positive, monosomy 7 biphenotypic acute mixed lineage leukemia in adults: a pluripotent stem cell disorder." Leukemia 7(11): 1752-8.

Two adult patients with acute mixed lineage leukemia (AMLL) having combined Philadelphia chromosome (Ph1) positivity and monosomy 7 are presented. The phenotypes of leukemic blasts from both cases were almost same (early B-lymphoid lineage and myeloid lineage); CD10+, CD13+, CD19+. HLA-DR+, and dual-color analysis showed simultaneous expression of CD10 (CD19) and CD13 antigens in individual blasts (biphenotypic) in both cases. On molecular analysis, the leukemic blasts showed rearrangement in the first intron of the BCR gene with breakpoint just outside of 3' end of m-BCR-2 (bcr 3) in case 1, and in the M-BCR in case 2. Immunoglobulin heavy chain gene (IgH) rearrangement was noted in both cases, but rearrangement of the T-cell receptor beta-chain gene (TCR beta) was detected only in case 1. Clinically, both cases achieved complete remission by the combination chemotherapy consisting of L-asparaginase, doxorubicin, vincristine, and prednisolone (L-AdVP). In remission, all these molecular abnormalities disappeared in both patients. These results suggest that the Ph1-positive and monosomy 7 AMLL in adults is de novo acute leukemia with both early B-lymphoid and myeloid phenotypes and may arise from malignant transformation of pluripotent stem cell, and expresses a heterogenous rearrangement pattern of the BCR gene.

Reymundo, C., M. Toro, et al. (1993). "Hyaline globules in uterine malignant mixed mullerian tumours. A diagnostic aid?" Pathol Res Pract 189(9): 1063-6.

In order to evaluate the presence of hyaline globules (HGs) in uterine malignant mixed mullerian tumours (MMMT), and its possible diagnostic value in haematoxylin & eosin stained sections, a retrospective microscopic study of 38 cases (13 homologous and 25 heterologous) was carried out. Intra- and extracellular HGs were found in 31 MMMT (81.6%), 8 homologous (61.5%) and 23 heterologous (92%). In addition, strong alpha-1-antitrypsin immunoreactivity was also noted in the HGs of 10 cases out of 13 investigated. In initial diagnostic curettage material, HGs were observed in 18 of 22 cases (81.8%), 6 of 9 homologous (66.7%) and 12 of 13 heterologous (92.3%). In view of the high incidence of HGs in curettage specimens, their finding in haematoxylin & eosin stained sections could orientate a histopathologic preoperative diagnosis of MMMT, specially of heterologous type, and may be considered a diagnostic tool in order to indicate an early, planned therapy and staging in these neoplasms of poor prognosis.

Mourad, W. A., B. Mackay, et al. (1993). "Clear cell melanoma of the bladder." Ultrastruct Pathol 17(3-4): 463-8.

Primary malignant melanoma of the urinary bladder is a rare tumor. A case in a 34-year-old man who presented with gross hematuria is reported. Cystoscopic biopsy showed a mixed spindle cell and clear cell neoplasm with focal pigmentation. The tumor cells were immunoreactive for S-100 protein and HMB-45. The patient did not have a history of melanoma, and clinical and radiologic work-up did not reveal other lesions, so a partial cystectomy and pelvic lymphadenectomy were performed. The tumor formed an ulcerated mass that extended into the perivesicular fat. Microscopically, the tumor was composed predominantly of clear cells in sheets or small nests. A solitary metastatic focus was present in 1 of 25 pelvic lymph nodes. Ultrastructurally, the tumor cells were characterized by irregular nuclear contours, complex nucleoli, abundant cytoplasmic glycogen, and premelanosomes.

Emoto, M., H. Iwasaki, et al. (1993). "Characteristics of cloned cells of mixed mullerian tumor of the human uterus. Carcinoma cells showing myogenic differentiation in vitro." Cancer 71(10): 3065-75.

BACKGROUND. To elucidate the relationship between the epithelial and mesenchymal elements of malignant mixed Mullerian tumors (MMMT), the authors examined the biologic properties of two clones of different cell types (designated as FU-MMT-2-C1 and FU-MMT-2-S1) established from a uterine MMMT cell line (FU-MMT-2), which they previously have reported. METHODS AND RESULTS. By morphologic and immunocytochemical analyses, FU-MMT-2-C1 exhibited features of adenocarcinoma cells, whereas FU-MMT-2-S1 showed characteristics of sarcoma cells with myogenic differentiation. Some FU-MMT-2-C1 cells at confluence differentiated spontaneously into myogenic mesenchymal cells in vitro. In addition, transitional-type cells between epithelial cells and sarcomatous cells were observed in the areas of mesenchymal differentiation in FU-MMT-2-C1 by light and electron microscopic study. Ultrastructurally, the transitional-type cells represented biphasic morphologic characteristics consisting of epithelial and myogenic features, which proved to coexpress epithelial, mesenchymal, and muscle markers by double immunoenzymatic staining. However, no epithelial differentiations were apparent in the sarcoma clone FU-MMT-2-S1. FU-MMT-2-C1 produced tumor in nude mice, the histologic study of which showed a mixture of adenocarcinoma and myogenic sarcomatous elements that resembled the original tumor. Cytogenetic studies demonstrated that these two clones were monoclonal in origin because of the presence of common karyotypic abnormalities in both cells. In addition, the amplified (approximately fourfold to eightfold) c-myc oncogene was found in the cloned cells and the original tumor cells. CONCLUSIONS. The current results strongly support the theory of single cell origin in uterine MMMT and suggest that the mesenchymal elements originated from primitive Mullerian epithelial cells capable of differentiating into epithelial, mesenchymal, or both elements.

Yamashita, Y., M. Takahashi, et al. (1993). "Contrast-enhanced MR imaging of malignant mixed mullerian tumor of the uterus." AJR Am J Roentgenol 160(5): 1150-1.

Magriples, U., F. Naftolin, et al. (1993). "High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients." J Clin Oncol 11(3): 485-90.

PURPOSE: Several reports have associated tamoxifen administration with endometrial carcinoma. A retrospective study of the histologic features of uterine cancer in patients with a history of breast carcinoma was undertaken to determine the effect of treatment with tamoxifen. MATERIALS AND METHODS: A computer search of the Yale-New Haven Hospital Tumor Registry from 1980 to 1990 identified 53 patients with a history of breast carcinoma who subsequently developed a malignant tumor of the uterine corpus. RESULTS: Fifteen patients received tamoxifen for breast carcinoma and 38 did not. The mean ages of the two groups were not significantly different. The mean interval between detection of breast and endometrial cancers was 5 years in the tamoxifen group and 12 years in the nontreated group (P = .0023). Sixty-seven percent of patients in the tamoxifen group had poorly differentiated endometrioid carcinomas (including adenosquamous carcinoma) or carcinomas associated with poor outcome (eg, uterine papillary serous carcinoma, clear-cell carcinoma, or mixed mullerian tumor), as compared with 24% in the nontreated group (P = .03). Patients in the tamoxifen group were much more likely to die of endometrial cancer (33.3% v 2.6% of the nontreated group, P = .005). CONCLUSION: From this retrospective study, it appears that women receiving tamoxifen as treatment for breast cancer who subsequently develop uterine cancer are at risk for high-grade endometrial cancers that have a poor prognosis. These findings also indicate that tamoxifen-associated uterine cancers may have a different basis from those associated with steroidal estrogen treatment.

Numata, K., K. Tanaka, et al. (1993). "Flow characteristics of hepatic tumors at color Doppler sonography: correlation with arteriographic findings." AJR Am J Roentgenol 160(3): 515-21.

OBJECTIVE. We studied benign and malignant hepatic tumors with color Doppler sonography and arteriography in order to correlate color Doppler flow characteristics with tumor hemodynamics (vascularity, arteriovenous shunting, and portal vein involvement) shown by arteriography. We also evaluated the usefulness of color Doppler flow characteristics in discriminating between tumor types. SUBJECTS AND METHODS. We performed color Doppler sonography and hepatic arteriography in 58 patients with 72 hepatic lesions larger than 2.0 cm in diameter. Differences in pulsatile flow (peritumoral or intratumoral) and the highest systolic peak flow velocities reached were evaluated on color Doppler sonograms and compared with arteriographic findings. RESULTS. Color flow sonograms were obtained in 43 of 45 hepatocellular carcinomas, 15 of 16 cholangiocellular carcinomas or hepatic metastases, and six of 11 hemangiomas. Mixed peritumoral and intratumoral pulsatile flow was shown by arteriography in highly vascular tumors. The mean peak systolic flow velocity seen in hepatocellular carcinomas (0.52 m/sec) significantly exceeded the velocity seen in hemangiomas (0.16 m/sec), but not the velocity seen in other malignant hepatic tumors (0.51 m/sec). Six hepatocellular carcinomas, one cholangiocellular carcinoma, and two hepatic metastases with peak systolic flow velocities greater than 0.80 m/sec were each proved arteriographically to have arteriovenous shunting or portal vein involvement. CONCLUSION. Color Doppler sonography was useful for evaluating hepatic tumor hemodynamics as seen at arteriography, and peak systolic velocity may be useful in differentiating malignant hepatic tumors from hemangiomas.

Shy, S. W., W. H. Lee, et al. (1993). "Malignant mixed mullerian tumor of the ovary: report of a case and review of the literature." Zhonghua Yi Xue Za Zhi (Taipei) 51(6): 468-73.

Malignant mixed Mullerian tumors (MMMTs) have been reported to occur in the female genital tract, especially in the uterine corpus. However, MMMT of the ovary is very rare and to best knowledge, no previous case has been reported in the literature of Taiwan. A 63-year-old female, with unique MMMT of the ovary, is described as having tumor with both carcinomatous and sarcomatous elements. The carcinomatous component was mainly composed of undifferentiated carcinoma. Small foci of glandular or papillary differentiation could be found. The sarcomatous component was composed of islands of atypical cartilaginous elements. Immunohistochemical studies revealed carcinomatous and heterologous sarcomatous elements respectively. Carcinomatous elements were cytokeratin and epithelial membrane antigen (EMA) positive, whereas heterologous sarcomatous elements were vimentin and S-100 positive. The patient received a left salpingo-oophorectomy and omentectomy without further chemotherapy or radiotherapy. The patient, already in the advanced stage, expired one month after the initial diagnosis.

Bystryn, J. C., E. Hodak, et al. (1993). "A paraneoplastic mixed bullous skin disease associated with anti-skin antibodies and a B-cell lymphoma." Arch Dermatol 129(7): 870-5.

BACKGROUND--The full spectrum of bullous diseases associated with underlying cancers remains to be fully defined. OBSERVATION--We describe a patient with a mixed bullous disease exhibiting combined features of cicatricial pemphigoid and pemphigus and associated with a B-cell lymphoma producing an IgM paraprotein to intercellular antigens in human skin. The patient had the clinical features of cicatricial pemphigoid and the histologic and immunofluorescence abnormalities of both cicatricial pemphigoid and pemphigus. These included oral and cutaneous erosions; ocular scarring; subbasal and acantholytic intraepidermal bullae; and circulating and tissue-fixed basement membrane zone and intercellular antibodies. The antibodies were directed to a 140-kd antigen in dermal extracts of skin split with 1 mol/L of sodium chloride and to antigens with approximate molecular weights of 150, 180, 230, and 285 kd in the dermal extract. In contrast to paraneoplastic pemphigus, the intercellular antibodies did not react to mammalian bladder. The intercellular antibodies were of the IgM class and were associated with the paraprotein produced by the malignant B cells. CONCLUSIONS--We believe that this condition represents a novel bullous disease, which we refer to as paraneoplastic mixed bullous disease. This condition illustrates that distinct bullous diseases are associated with paraneoplastic syndromes and that at least one possible mechanism for such eruptions is the production of anti-skin antibodies by malignant B cells.

Carlson, J. A., Jr., B. L. Ackerman, et al. (1993). "Malignant mixed mullerian tumor of the fallopian tube." Cancer 71(1): 187-92.

BACKGROUND. Malignant mixed mullerian tumor (MMT) of tubal origin is rare and optimal therapy is unknown. METHODS. Five new cases of MMT of the fallopian tube are presented, and the previous literature is reviewed. RESULTS. Eight of 10 patients disease-free at 36 months had long-term cancer-free survival. Surgery alone was inadequate therapy even for those with apparent Stage I disease. Five of six treated postoperatively with radiation and chemotherapy have lived disease-free for at least 45 months. CONCLUSIONS. Combination radiation and chemotherapy may offer improved outcome.

de Brito, P. A., S. G. Silverberg, et al. (1993). "Carcinosarcoma (malignant mixed mullerian (mesodermal) tumor) of the female genital tract: immunohistochemical and ultrastructural analysis of 28 cases." Hum Pathol 24(2): 132-42.

In an attempt to clarify the histogenesis of carcinosarcoma (malignant mixed mullerian tumor) of the female genital tract, 20 uterine and eight ovarian tumors were studied by light microscopy, transmission electron microscopy, and immunohistochemistry. Cytokeratins (MAK-6 and AE1:AE3) and epithelial membrane antigen were detected in the epithelial component of all tumors and in the stromal component of 15 cases (55%). Vimentin was detected in the stromal component of all cases and was focally positive in the epithelial component of 18 cases (69%). Tumors showing rhabdomyosarcomatous or chondrosarcomatous differentiation were positive for myoglobin and S-100 protein, respectively. At the ultrastructural level epithelial cells were observed in tight clusters (usually surrounded by a basal lamina), in loose aggregates, and singly (sometimes spindle shaped), and were surrounded by cells displaying variable differentiation. The closest examples of "hybrid" epithelial/stromal cells were those with a prominent rough endoplasmic reticulum, cytoplasmic projections, poorly formed intercellular junctions, and an incomplete basal lamina. The observations support the view that carcinosarcomas of the female genital tract could represent examples of biphasic (metaplastic) carcinomas.

Kawakami, S., K. Togashi, et al. (1993). "Primary malignant tumor of the fallopian tube: appearance at CT and MR imaging." Radiology 186(2): 503-8.

Primary malignancy of the fallopian tube is a rare entity. To determine the radiologic characteristics of the tumor, 10 patients with pathologically confirmed fallopian tube malignancy (nine with adenocarcinoma and one with mixed mullerian tumor) underwent magnetic resonance (MR) imaging and computed tomography (CT). With both CT and MR imaging, the lesion appeared relatively small, solid, and lobulated when not associated with hydrosalpinx. At CT, the lesion had an attenuation equal to that of other nonspecific soft-tissue masses and enhanced less than myometrium. On T1-weighted MR images the tumor was usually hypointense, and on T2-weighted images the tumor was most often homogeneously hyperintense. Associated CT and MR imaging findings were peritumoral ascites (four cases), intrauterine fluid collection (two cases), and hydrosalpinx (one case). MR findings allowed the lesion to be distinguished from uterine leiomyoma in three cases in which pelvic examination, ultrasound, and CT findings were equivocal.

al-Nafussi, A. I., D. E. Hughes, et al. (1993). "Hyaline globules in ovarian tumours." Histopathology 23(6): 563-6.

Hyaline eosinophilic globules have so far been described in a restricted variety of tumour types. We have noted their presence in a variety of gynaecological malignancies, in particular mixed Mullerian tumours and other epithelial ovarian tumours. We therefore studied their incidence and distribution in a series of malignant, borderline and benign epithelial ovarian tumours, and endometrial and endocervical adenocarcinomas. Hyaline eosinophilic globules were found in all 30 mixed Mullerian tumours from various sites in the female genital tract, 22 of 30 clear cell carcinomas, seven of 30 serous, two of 30 mucinous, and one of 30 endometrioid carcinomas examined, and were also seen in metastases from these tumours. They were present in only two of 25 borderline serous, one of 25 borderline mucinous tumours, and in four of 50 benign serous and one of 50 benign mucinous tumours. The globules were not found in any of 25 Brenner tumours examined, nor in 30 endometrial or 30 endocervical adenocarcinomas. The globules were periodic acid-Schiff positive after diastase, stained positively with PTAH, and were immunoreactive for alpha-1-antitrypsin. This study therefore demonstrates that eosinophilic globules are not specific for any particular tumour. However, their frequency in malignant mixed Mullerian tumours suggests that this diagnosis should be carefully excluded whenever these globules are present in epithelial tumours of the female genital tract.

Clarke, M. R. (1993). "Uterine malignant mixed mullerian tumor in a patient on long-term tamoxifen therapy for breast cancer." Gynecol Oncol 51(3): 411-5.

A case of malignant mixed mullerian tumor of the uterus, heterologous type, in an 83-year-old woman on tamoxifen (TAM) therapy for 9 years for breast cancer is presented. Benign endometrial polyps were diagnosed on endometrial curettings for postmenopausal bleeding after the patient had been on TAM for 5 years. Recurrent postmenopausal bleeding developed 4 years later. Endometrial curettings and hysterectomy revealed a 10-cm polypoid malignant mixed mullerian tumor (MMMT) and endometrial polyps. There was no invasion of the myometrium or endocervix and no evidence of metastatic tumor in 13 pelvic lymph nodes, peritoneal washings, or omentum. TAM has been associated with the development of endometrial polyps, hyperplasia, and adenocarcinoma possibly mediated through its agonistic estrogenic properties. Only one other case of MMMT arising in patients on TAM therapy has been previously reported, but may also be a consequence of the estrogenic effects of TAM therapy.

Dass, K. K., C. V. Biscotti, et al. (1993). "Malignant mixed mullerian tumors of the ovary. An analysis of two long-term survivors." Am J Clin Oncol 16(4): 346-9.

Long-term survival following the diagnosis of ovarian malignant mixed mullerian tumor (MMMT) is unusual. This report analyzes two such long-term survivors. One patient presented with a FIGO Stage III, homologous MMMT treated initially with a combination of surgery and chemotherapy. Residual disease, present at the time of initial operation, responded to the chemotherapy; however, the tumor recurred 2 1/2 years postoperatively. This recurrence responded to a combination of surgery and chemotherapy, including continuous adjuvant chemotherapy. This patient is alive, on maintenance chemotherapy, and without evidence of disease, approximately 7 years after the recurrence and 9 years after the initial presentation. The other patient presented with a FIGO Stage III heterologous MMMT treated initially with combined surgery and chemotherapy. Residual disease was present at the time of initial operation. Persistent pelvic disease led to exploratory laparotomy, excision of an 8-cm diameter pelvic mass, and postoperative radiation therapy. The tumor recurred in the left supraclavicular lymph nodes 2 years later (3 years after the initial presentation). This recurrence responded to radiation therapy. This patient was last seen 2 years later (5 years after the initial presentation). At that time, she was without evidence of recurrence. She died 7 1/2 years after her initial presentation. These two patients represent examples of the unusual occurrence of patients with advanced-stage ovarian MMMT experiencing long-term survival following surgical and adjuvant therapy.

Fox, H. (1993). "Primary neoplasia of the female peritoneum." Histopathology 23(2): 103-10.

Primary neoplasms of the female peritoneum may be mesothelial or Mullerian in nature. Primary mesotheliomas may be cystic, benign papillary or diffuse malignant. Primary Mullerian tumours of the peritoneum are thought to arise within the secondary Mullerian system: the overwhelming majority are serous in nature and probably develop from pre-existing endosalpingiosis. Primary peritoneal serous tumours of borderline malignancy are identical histologically to the peritoneal 'implants' found in association with ovarian serous tumours of borderline malignancy, whereas primary peritoneal serous adenocarcinomas are histologically identical to ovarian serous adenocarcinomas. The recognition of a primary peritoneal serous neoplasm of borderline malignancy rests on the presence of either normal ovaries, ovaries containing only a fully benign neoplasm or ovaries showing only minimal surface involvement. The diagnosis of a primary peritoneal serous adenocarcinoma is made if the ovaries are of normal size with either no tumour or only minimal surface involvement: in some cases normal ovaries will have previously been prophylactically removed because of a family history of ovarian cancer. The differential diagnosis between a primary serous adenocarcinoma and a diffuse malignant mesothelioma can be difficult and is often not resolved by either electronmicroscopy or immunocytochemistry.

Weber, A. M., W. F. Hewett, et al. (1993). "Malignant mixed mullerian tumors of the fallopian tube." Gynecol Oncol 50(2): 239-43.

Malignant mixed mullerian tumors of the female genital tract are rare and occur least commonly in the fallopian tube. A case is reported and 51 other cases in the literature are reviewed. The mean age at diagnosis is 59 years. Abdominal pain is the most common presenting complaint. A pelvic or abdominal mass is present in 75% of patients. The diagnosis is not usually established until surgery, with the most common preoperative diagnosis being ovarian malignancy. Seventy-five percent of cases had tumor extension beyond the fallopian tube at the time of surgery. Treatment has focused on surgery with postoperative radiation and/or chemotherapy. Prognosis is poor, with fewer than half of patients surviving 2 years. Recent reports suggest improved outcome with platinum-based chemotherapy but data are limited.

Andreassi, S., L. Manente, et al. (1993). "[A case of malignant mixed Mullerian tumor]." Minerva Ginecol 45(4): 199-213.

A case of malignant mixed mullerian tumor of the uterus is reported. Clinical, microscopic and immunohistochemical findings are compared with those described in the literature.

Kempson, R. L. and M. R. Hendrickson (1993). "Miscellaneous types of surface epithelial neoplasms. The well-differentiated end of the morphologic spectrum of endometrioid, clear-cell, and Brenner tumors and mixed epithelioid tumors of low malignant potential of mullerian type." Pathology (Phila) 1(2): 335-65.

Benign ovarian neoplasms with endometrioid or clear-cell differentiation are rare, but benign Brenner tumors are not unusual. A subgroup of endometrioid, clear-cell, and Brenner neoplasms, characterized by morphologic features intermediate between benign and malignant, has been labelled by various investigators as borderline, of low malignant potential (LMP), or proliferating. This chapter reviews the definition of each of these cell types, evaluates the significance of the LMP category, and concludes with a discussion of well-differentiated ovarian neoplasms with mixed differentiation of the mullerian type.

Nimaroff, M., D. Gal, et al. (1993). "Extragenital malignant mixed mullerian tumor." Eur J Gynaecol Oncol 14(1): 23-7.

A malignant mixed mullerian tumor, originating from the serosa of the sigmoid colon was found in an 82-year-old female. The reproductive organs were normal. There was no evidence of endometriosis. The patient's clinical course deteriorated rapidly and she succumbed to her disease despite aggressive surgery and chemotherapy. Only twelve cases with extragenital malignant mixed mullerian tumors have been described in the past. Pathogenesis is discussed and the literature is reviewed.

Umbas, R., J. A. Schalken, et al. (1992). "Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer." Cancer Res 52(18): 5104-9.

E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.

Imachi, M., N. Tsukamoto, et al. (1992). "Malignant mixed Mullerian tumor of the fallopian tube: report of two cases and review of literature." Gynecol Oncol 47(1): 114-24.

Malignant mixed Mullerian tumors are usually found in the endometrium, vagina, cervix, and ovary. It is extremely rare for this tumor to arise in the fallopian tube, and to date only 37 tubal cases have been reported. We recently experienced 2 such cases. The clinical features, pathologic findings, diagnosis, therapy, and outcome of these 39 cases were reviewed. The clinical features and diagnosis were similar to those of primary carcinoma of the fallopian tube. Correct preoperative diagnosis was difficult. Histologically, 18 patients had homologous elements and 21 had heterologous elements in the sarcomatous components. The most common type of heterologous element was cartilage, followed by striated muscle and bone. The clinical stage (FIGO staging of ovarian carcinoma) was stage I in 15 cases, stage II in 11 cases, stage III in 8 cases, stage IV in 3 cases, and unknown in 2 cases. In all the patients except 1, the tumor was surgically removed. Postoperatively, radiotherapy was given to 9 patients, chemotherapy to 9 patients, and both to 2 patients. Sixteen patients died of the disease, after a mean period of 16.1 months. Of the 15 stage I patients, 10 survived more than 12 months. The most important prognostic factor was spread of the tumor at diagnosis.

Messing, M. J., D. M. Gershenson, et al. (1992). "Primary treatment failure in patients with malignant ovarian germ cell neoplasms." Int J Gynecol Cancer 2(6): 295-300.

Between 1970 and 1990, 160 patients with malignant non-dysgerminomatous ovarian germ cell tumors have been treated at our own institution. Primary therapy failed in 42 of these patients, who constitute the basis for this study. Seventeen patients had stage I disease, 5 stage II, 17 stage III, and 3 stage IV. Histologic type included 13 immature teratomas, 8 endodermal sinus tumors, and 21 mixed germ cell tumors. Primary therapy for 14 patients was surgery alone, for 23, surgery plus chemotherapy, for 2, surgery plus radiotherapy and for 3, all three modalities. Median progression-free survival from initial diagnosis lasted 6.8 months (range, 0.9-24 months). Thirty-four patients received chemotherapy as part of salvage; 5/11 (45%) who received VAC are disease-free, and 6/11 (55%) who received cisplatin combinations are disease-free. When primary VAC failed, 3/7 (43%) were salvaged with cisplatin combinations. When primary cisplatin combinations failed, 2/5 (40%) were salvaged. Twelve of the 42 patients (29%) are currently alive disease-free. Primary treatment failure was attributed to surgery alone for 14 patients (7 because of misdiagnosis), radiotherapy for 5, and toxicity for 1. Of the 22 patients who failed chemotherapy, 12 did so because of a suboptimal regimen, 3 because of possible dose-intensity problems, one because of non-compliance, and 6 for unexplained reasons. Patients with ovarian germ cell tumors have an excellent probability of cure with aggressive primary therapy, but successful salvage may be difficult when primary treatment fails.

Moore, D. T., M. M. Taslimi, et al. (1992). "Malignant mixed mullerian tumor of the fallopian tube of the heterologous type." J Tenn Med Assoc 85(11): 513-4.

Glass, J., F. H. Hochberg, et al. (1992). "The treatment of oligodendrogliomas and mixed oligodendroglioma-astrocytomas with PCV chemotherapy." J Neurosurg 76(5): 741-5.

Malignant oligodendrogliomas have been shown to be responsive to chemotherapy. The authors administered systemic chemotherapy to seven patients with oligodendroglioma or anaplastic oligodendroglioma, and to 14 with mixed oligodendroglioma-astrocytoma. Fourteen patients underwent chemotherapy before and seven after irradiation. The PCV (procarbazine, methyl-1-(2-chloroethyl)-1-nitrosourea (CCNU), and vincristine) chemotherapy was administered every 6 weeks (42-day cycles) for two to five cycles as follows: CCNU, 110 mg/sq m on Day 1; procarbazine, 60 mg/sq m/day on Days 8 to 21; and vincristine, 1.4 mg/sq m/day on Days 8 and 29. Complete or partial (greater than 50% reduction in tumor mass) responses at 20 to 100+ weeks after treatment were noted in 11 (79%) of the 14 patients treated before irradiation, including two with anaplastic oligodendroglioma and nine with mixed tumors. Complete responses were seen in two patients, one with anaplastic oligodendroglioma and one with a mixed tumor. Partial responses were seen in three of seven patients treated after radiotherapy. Stabilization of tumor growth followed PCV chemotherapy in four patients (two treated before and two after radiotherapy). Tumor growth progressed in two patients during therapy despite an initial response and in two patients despite therapy. The authors conclude that mixed oligodendroglial tumors as well as anaplastic oligodendrogliomas are responsive to PCV chemotherapy.

Martin, T. and J. L. Pasquali (1992). "CD5 negative IGM rheumatoid factor B cells in B-chronic lymphocytic leukemia and benign mixed cryoglobulinemia." Leuk Lymphoma 7(1-2): 55-62.

IgM-RF B cell precursors are abnormally overrepresented in "well differentiated" lymphoid monoclonal proliferations while data on less mature lymphoid malignancies are still awaited. This nevertheless suggests that RF activity plays a role in the transforming process perhaps by inducing constant stimulation of the precursor B cells. Despite the preferential use of similar VH and VL genes with little or no somatic hypermutations in both malignant B-cell CLL and nonmalignant mixed cryoglobulinemia, these proliferations do differ in CD5 membrane expression and in their clinical evolution. One possibility could be that CD5 glycoprotein is lost during maturation of the lymphocyte into a secreting cell as suggested by data on Waldenstrom's disease and the LES-CLL and by in vitro studies. Alternatively, CD5 expression could play an additional direct role in malignant transformation as suggested by recent data on the CD5 receptor ligand. Further data on the proliferating cells in both situations as well as on the genetic control of CD5 expression in B cells and its physiology should shed additional light on the mechanisms of B-cell malignancy.

Muntz, H. G. and E. Brown (1992). "Lactic acidosis and hypoglycemia: a metabolic complication of advanced gynecologic malignancy." Int J Gynecol Cancer 2(3): 163-167.

Refractory lactic acidosis and hypoglycemia characterize a paraneoplastic syndrome observed in advanced gynecologic cancer, as illustrated by a patient with a large malignant mixed Mullerian tumor. Massive infusions of sodium bicarbonate and glucose failed to reverse her metabolic abnormalities, and the patient suffered a rapidly fatal course. The biochemical basis for this metabolic complication is reviewed, including how medical intervention can lead to iatrogenic exacerbation of the metabolic imbalance.

Sreekantaiah, C., U. N. Rao, et al. (1992). "Complex karyotypic aberrations, including i(12p), in malignant mixed mullerian tumor of uterus." Cancer Genet Cytogenet 60(1): 78-81.

We report the cytogenetic findings in a malignant mixed mullerian tumor of the uterus in a 59-year-old woman. Karyotypic analysis of short-term cultures revealed two abnormal clones of cells characterized by extensive structural and numerical rearrangements. An i(12p) maker chromosome was present in addition to other changes in both clones. This marker, characteristically associated with testicular germ cell tumors in males, has recently been reported in ovarian germ cell tumors, a mediastinal germ cell tumor and in a mixed mullerian tumor of the ovary.

Antela Lopez, A., J. Antunez Lopez, et al. (1992). "[Association of sarcoidosis, diffuse centroblastic-centrocytic lymphoma and IgM monoclonal gammapathy in the same female patient]." Med Clin (Barc) 98(9): 342-4.

A case illustrating the infrequent association of sarcoidosis and lymphoma which was also a secretor of a monoclonal IgM paraprotein is described in a 68 year old woman. The first entity manifested by dyspnea corresponded with a bilateral interstitial pneumopathy with restrictive syndrome and was diagnosed by bronchoalveolar lavage and transbronchial biopsy and biopsy prescalenic fat. The lymphoma presented three years later followed by lymphadenopathies and a monoclonal IgM peak being diagnosed by biopsy of an axillary lymph node. In order to relate both entities it has been suggested that prolonged stimulation of the lymphocytes peculiar to the sarcoidosis would cause its malignant transformation.

Bur, M. E., C. Perlman, et al. (1992). "p53 expression in neoplasms of the uterine corpus." Am J Clin Pathol 98(1): 81-7.

It has been recognized that mutations in tumor suppressor genes may have an important oncogenic role. Although abnormalities of the p53 tumor suppressor gene have been reported in tumors from various organ systems, p53 expression has not been studied in neoplasms of the uterine corpus. Using a monoclonal antibody to the p53 product, frozen sections of 56 uterine tumors (40 endometrioid endometrial adenocarcinomas, 7 serous endometrial carcinomas, 4 mixed Mullerian tumors, 2 endometrial stromal sarcomas, 1 leiomyosarcoma, 2 leiomyomas) and 2 normal endometria were stained using the immunoperoxidase technique. Staining was evaluated by light microscopic examination; in carcinomas with strong/diffuse reactivity, evaluation was by digitized image analysis. p53 staining of adenocarcinomas was compared statistically to the histologic type, grade, surgical stage, and clinical follow-up. Specific staining was present in the nucleus of malignant tumor cells only. Benign cells did not stain. Strong/diffuse staining was seen in 14 adenocarcinomas and in 2 mixed Mullerian tumors. Weak/focal staining was observed in 14 adenocarcinomas. Serous carcinomas showed strong positivity more frequently than endometrioid endometrial carcinomas. Staining patterns correlated with histologic grade and stage. Image analysis of immunostained p53 correlated with type of adenocarcinoma, but not with grade or stage in the cases measured. p53 was expressed strongly in tumors of five of eight patients who died of adenocarcinoma but in none of five patients with no evidence of disease and a minimum follow-up of 24 months. In addition, 3 of 12 patients with persistent or recurrent disease showed tumors that strongly expressed p53. It is concluded that abnormal expression of p53 occurs frequently in malignant uterine tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Clement, P. B. and R. E. Scully (1992). "Endometrial stromal sarcomas of the uterus with extensive endometrioid glandular differentiation: a report of three cases that caused problems in differential diagnosis." Int J Gynecol Pathol 11(3): 163-73.

Three cases of endometrial stromal sarcoma (ESS) with prominent glandular differentiation within the primary or recurrent tumors are described. Each case posed a problem in diagnosis and classification. The patients, who ranged in age from 41 to 47 years, presented with abnormal uterine bleeding, a pelvic mass, or a combination thereof. All the patients underwent hysterectomy with or without bilateral salpingo-oophorectomy. There was no evidence of extrauterine spread of tumor in any case. Polypoid tumors involved the endometrium in two cases, and in one of them, tumor deeply invaded the myometrium. The tumor in the third case was an infiltrative mass that was confined to the myometrium and its vessels. On microscopic examination, the tumors were low-grade ESSs that contained large numbers of endometrioid glands, which were benign appearing in two cases, and in the third varied from atypical to carcinomatous. In one of the cases in the first group, the glandular component was present only in recurrent tumor excised 10 years after hysterectomy; prominent foci of sex-cord-like differentiation were also present in the recurrent tumor. This patient was clinically free of tumor 27 months later; follow-up in the other two patients was uneventful. ESSs with prominent numbers of benign-appearing glands should be distinguished from adenomyosis, endometriosis, ESSs arising in adenomyosis or endometriosis, ESSs with sex-cord-like differentiation, and mullerian adenosarcomas. ESSs with carcinomatous glands should be distinguished from endometrial adenocarcinomas and malignant mullerian mixed tumors (carcinosarcomas). Extrauterine lesions that have been designated "aggressive endometriosis" may be examples of extrauterine ESS with prominent glandular differentiation.

Jiang, Z. M. (1992). "[Sarcomas of the uterus: immunohistochemical characterization and diagnosis]." Zhonghua Bing Li Xue Za Zhi 21(6): 336-8.

Pathologic findings and immunohistochemical characterizations of 18 cases of uterine sarcomas were studied. In endometrial stromal sarcoma (ESS), 5 out of 10 cases had ovarian sex cord-like pattern and 4 out of 10 cases had smooth muscle differentiation. Immunohistochemical findings showed vimentin, desmin and cytokeratin positive in 9/10, 6/10, 2/10 cases respectively which reflects that ESS may differentiate into both epithelium and muscle components morphologically. In malignant mixed Mullerian tumors (MMT), its carcinomatous structure may be positive about vimentin, and its sarcomatous structure may be positive to the epithelium markers, which indicates that both the sarcoma and carcinoma structures have possibly a common origin. It is considered to be of value for the diagnosis of MMT, if the tumor has differentiated both epithelium and mesoderm components or to be positive to myoglobin, NSE* in immunoreaction, accompanying with the morphologic characterizations of the tumor.

Emoto, M., H. Iwasaki, et al. (1992). "Two cell lines established from mixed mullerian tumors of the uterus. Morphologic, immunocytochemical, and cytogenetic analyses." Cancer 69(7): 1759-68.

To clarify the cellular origin and characteristics of malignant mixed mullerian tumor (MMMT), the authors investigated two cell lines (designated as FU-MMT-1 and FU-MMT-2) established from two patients with heterologous MMMT of the uterus. Both cell lines propagated continuously for 83 and 55 serial passages over 1.5 years, respectively. Morphologically, FU-MMT-2 was a mixture of carcinoma cells and sarcoma cells with predominance of carcinoma cells; FU-MMT-1 only had a sarcomatous element with distinct rhabdomyoblastic differentiation. Immunocytochemically, the sarcoma cells of each cell line expressed, not only myogenic and mesenchymal antigens (desmin, myoglobin, and vimentin), but also epithelial antigens, including epithelial membrane antigen and keratin. The carcinoma cells in FU-MMT-2 were positive for the epithelial antigens and vimentin and negative for desmin and myoglobin. Both lines had abnormal karyotypes; the modal chromosome numbers of FU-MMT-1 and FU-MMT-2 were 47 and 80, respectively. In addition, FU-MMT-1 had trisomy 8, and FU-MMT-2 had complex structural abnormalities. When transplanted into nude mice, FU-MMT-1 reproduced and maintained the characteristics of the original tumor. These cell lines and xenografts appear to provide a useful system for studying the biologic behavior, cytogenetic features, and histogenesis of MMMT. In conclusion, the presence of epithelial antigens in the sarcomatous and carcinomatous elements seemed to support the hypothesis that both elements are derived from a common stem cell.

Kataoka, A., T. Nishida, et al. (1992). "[Immunohistochemical studies of recessive oncogene p53 and N-myc oncogene expression in 7, 12 dimethylbenz (a) anthracene-induced rat ovarian tumors]." Nippon Sanka Fujinka Gakkai Zasshi 44(4): 391-6.

In the present study, the expressions of p53 and N-myc gene were analyzed immunohistochemically in rat ovarian tumors induced by 7,12 dimethylbenz (a) anthracene (DMBA). 1) p53 could be seen in the nucleolei of tumor cells. The positive rates were: adenomas 17%, adenocarcinomas 37%, sarcomas 0%, mixed mullerian tumor 0% and epidermal cysts 100%. Neither the serial-allografted tumor nor DMBA-OC-1 was positive. 2) N-myc could be seen in the cytoplasm and perinuclear cytoplasm of tumor cells. The positive rates were: adenomas 33%, adenocarcinomas 77%, sarcomas 100%, mixed mullerian tumors 100% and epidermal cysts 100%. Both the serial-allografted tumor and DMBA-OC-1 were positive. 3) The positive rates in both p53 and p21 were: adenocarcinoma 20% and epidermal cysts 100%. The positive rates in both N-myc and p21 at the were: adenoma 17%, adenocarcinoma 50%, sarcoma 33%. Both the serial-allografted tumor and DMBA-OC-1 were positive. Only two cases were positive for p53, N-myc and p21. p53 was detected in most of the adenomas. 4) The positive rate for both N-myc and p21 was higher than that for both p53 and p21. This was similar to other reports. The results suggested that p53 plays a role in precancerous tumor as a recessive oncogene. It was supposed that tumors with N-myc gene expression were had malignant growth characteristics.

Costa, M. J., C. Tidd, et al. (1992). "Cervicovaginal cytology in carcinosarcoma [malignant mixed mullerian (mesodermal) tumor] of the uterus." Diagn Cytopathol 8(1): 33-40.

We examined the cervicovaginal cytology (PAP) findings in a series of 21 endometrial and 2 cervical carcinosarcomas (CS) [malignant mixed mullerian (mesodermal) tumors] (MMMT). Initial cytology diagnosis was positive for cancer in 14 of 23 cases (sensitivity of 61%); however, CS was correctly identified only 2 times. The remaining 12 cancer diagnoses were carcinomas: 10 adenocarcinomas (4 endometrial, 1 cervical, and 5 adenocarcinomas not otherwise specified), 1 squamous carcinoma, and 1 poorly differentiated carcinoma. Seventeen smears were available for review, all 8 false negative, one unsatisfactory, and 8 of 14 true positive smears. One false negative smear showed rare clusters diagnostic of adenocarcinoma. The remaining 7 false negative smears showed 3 high grade squamous dysplasias (two with additional findings: one showed atypical spindle cells and the other showed endometrial stromal cells), 2 extensive repair changes, and 2 negatives. The unsatisfactory smear showed atypical spindle cells. Review of the 8 true positive smears confirmed malignant spindle cells in the two cases originally identified as CS by cytology and in 3 other cases originally identified as adenocarcinoma. Of 9 smears positive for cancer available for review, 4 showed only carcinoma cells. PAP positive for cancer was associated with high stage at presentation (P less than .025) and recurrent disease (P less than .001) (even among stage I or II patients, P less than .025). PAP positive for cancer showed no association with depth of myometrial invasion, size, grade, or histologic type of carcinosarcoma. The results of this study demonstrate the importance of consultative cytology reporting in which recommendations for appropriate biopsy are included in the report.(ABSTRACT TRUNCATED AT 250 WORDS)

Repique, C. J., J. D. Kettering, et al. (1992). "Immunosuppression derived from human B-lymphoblastoid and melanoma cell lines." Cancer Invest 10(3): 201-8.

Previous work conducted by the authors, using a murine model, suggested that soluble factors secreted by tumor cells suppress lymphocyte responses. To apply this premise to human tumors, the effects of UC729-6 (lymphoblastoid B-cell) and M21-HPB (malignant melanoma) conditioned media (CM) on normal lymphocyte proliferation, as well as on tumor cell growth in autologous CM was studied. The CM was collected at 2-5 day intervals from cultures of UC729-6 and M21-HPB cells in serum-free media. Phytohemagglutinin- and concanavalin A-stimulated mononuclear peripheral blood cells from healthy human donors showed decreased [3H]thymidine ([3H]Tdr) uptake in the presence of each CM when compared with controls. In assays using 100% CM, mitogen stimulation was 68-85% less than that of controls and 40-50% less using 50% CM. The suppression was more pronounced with UC729-6 CM than with M21-HPB CM. In mixed lymphocyte cultures (MLC), addition of 50% CM from either tumor cell line resulted in 40-50% reduction in [3H]Tdr uptake by lymphocytes. Incubation of UC729-6 cells in 5% to 100% of UC729-6 fCM (filter-concentrated) produced a decrease in [3H]Tdr uptake which was directly proportional to the amount of fCM present. In contrast, M21-HPB cell growth in autologous fCM was dependent on cell number, as well as on the amount of fCM used. Treatment of the UC729-6 fCM using acid (pH 4.5), trypsin (100 micrograms/ml), and heat (56 degrees C) did not restore mitogen-stimulated lymphoproliferation. However, the inhibition observed with UC729-6 fCM was partially reversed after dialysis with membranes having M(r) limits of 2.5 x 10(4), 1.5 x 10(4), or 1 x 10(4).

Valente, P. T., H. D. Schantz, et al. (1992). "Peritoneal cytology of uncommon ovarian tumors." Diagn Cytopathol 8(2): 98-106.

Peritoneal cytology has been well established as a diagnostic and staging tool in the management of the common epithelial tumors of ovary. Germ cell, mesenchymal, and sex-cord stromal tumors are much less frequently encountered in peritoneal specimens, often with cytologic features that may pose problems in differential diagnosis. This report presents the cytomorphology of the ascitic fluid in cases of endodermal sinus tumor, dysgerminoma, and Sertoli-Leydig-cell tumor, and peritoneal washings in a case of ovarian malignant mixed mullerian tumor. The cytologic features of Sertoli-Leydig-cell tumors have not been well described. Careful correlation of peritoneal cytologic findings, cell-block preparations, and immunocytochemistry with the cytohistologic features of these tumors is crucial for correct tumor classification.

Bruner, J. M., H. Saya, et al. (1991). "Immunocytochemical detection of p53 in human gliomas." Mod Pathol 4(5): 671-4.

Since previous published studies of astrocytomas have shown alterations in the short arm of chromosome 17, and this chromosomal location is that which encodes the p53 protein, we used a monoclonal antibody and immunocytochemistry to detect this protein in a series of brain biopsies. The normal p53 protein has a short half-life and is not detectable using this method. Expression of an altered p53 protein was detected in 29 of 71 brain biopsies, but only in those that showed astrocytic features. p53 expression was detected in 20/32 glioblastomas, 5/12 anaplastic astrocytomas, and 3/5 mixed anaplastic oligo-astrocytomas, but only in astrocytic cells. It could not be detected in any other histologic types of primary brain neoplasms, either benign or malignant. The protein was detected in only 1/11 biopsies interpreted as showing gliosis, but this was in a patient who had previously had a resection for glioblastoma, and may have represented unrecognized infiltrating astrocytoma cells. The p53 protein was also expressed in the nuclei of the two human astrocytoma cell lines examined, U251MG and D54MG. These results are in general agreement with previous detailed chromosomal analyses that have found loss of heterozygosity in up to 60% of malignant astrocytic gliomas.

Smith, J. W., 2nd, W. J. Urba, et al. (1991). "Phase I evaluation of recombinant tumor necrosis factor given in combination with recombinant interferon-gamma." J Immunother 10(5): 355-62.

In light of in vitro and preclinical animal model data suggesting potential additive or synergistic antitumor effects from the combined use of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), we conducted a phase I study employing escalating doses of each agent in 36 patients with solid tumors to determine the maximum tolerated dose (MTD). Patients were given an intramuscular (i.m.) injection of IFN-gamma, followed 5 min later by an i.m. injection of TNF-alpha, each agent in different sites, every other day for ten doses over 20 days. Patients received 10, 50, or 100 micrograms/m2 of each agent throughout the treatment course. No dose modifications were made. Patients suffering serious toxicity had therapy stopped and were considered to be off-study. All patients experienced fatigue, and 36% spent over half their time in bed on treatment days. Fever and chills were nearly universal. Mild to moderate elevations in serum transaminase levels were noted in 44% of patients, and 44% developed transient microscopic hematuria. Although 81% of patients had anorexia, only 17% of patients lost more than 3 kg of body wt during the 3 weeks of therapy. Because two of three patients receiving 100 micrograms/m2 of both agents developed serious toxicity (one fever greater than 105 degrees F, one thrombocytopenia 43,000/mm3), the MTD was established to be 100 micrograms/m2 of IFN-gamma plus 50 micrograms/m2 of TNF-alpha. The use of aspirin did not significantly alter the toxic effects of the agents. One patient with melanoma had a mixed response and one patient with mesothelioma transiently cleared his ascites of malignant cells.

Garde, J. R., M. A. Jones, et al. (1991). "Extragenital malignant mixed mullerian tumor: review of the literature." Gynecol Oncol 43(2): 186-90.

A case of extragenital malignant mixed mullerian tumor (MMMT) of the heterologous type 11 years after treatment of a Stage I ovarian neoplasm in a 65-year-old patient is described. There was no evidence of a histologic relationship between these two neoplasms. This case represents the 10th report of an extragenital MMMT. The medical literature and histogenesis of this rare tumor are discussed.

Ullrich, S. E. (1991). "Photoinactivation of T-cell function with psoralen and UVA radiation suppresses the induction of experimental murine graft-versus-host disease across major histocompatibility barriers." J Invest Dermatol 96(3): 303-8.

Bone marrow transplantation is employed in the treatment of a number of hematologic and malignant diseases. A major complication is the induction of graft-versus-host disease. Whereas removal of T lymphocytes from the donor marrow effectively reduces the incidence of graft-versus-host disease, the incidence of graft failure often increases when T cells are depleted from the transplanted marrow. In the current study, photoinactivation of the donor cells with 8-methoxypsoralen coupled with exposure to long-wavelength ultraviolet radiation (PUVA therapy) was used to inactivate the response of the donor T cells against the host. PUVA therapy suppressed the ability of spleen cells to respond to alloantigen in the in vitro mixed lymphocyte reaction. The induction of acute graft-versus-host disease across complete major histocompatibility barriers in lethally X-irradiated mice was significantly suppressed after bone marrow transplantation with photoinactivated bone marrow cells. Long-term survivors demonstrated allogeneic reconstitution and partial restoration of T-cell function. Because PUVA therapy had no inhibitory effect on hematopoiesis, these data suggest that using phototherapy to inactivate the alloreactivity of T cells may provide an alternative to purging T cells from the donor marrow, thus suppressing both the incidence of graft-versus-host disease and the incidence of graft failure.

Costa, M. J., R. Khan, et al. (1991). "Carcinoma (malignant mixed mullerian [mesodermal] tumor) of the uterus and ovary. Correlation of clinical, pathologic, and immunohistochemical features in 29 cases." Arch Pathol Lab Med 115(6): 583-90.

We examined the histologic, immunohistochemical, and clinical features of a series of 23 endometrial, five cervical, and one ovarian carcinosarcomas (malignant mixed mullerian [mesodermal] tumors) and nine associated distant peritoneal metastases. The primary tumors all showed epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) of the carcinomatous component, while sarcomatous areas showed epithelial differentiation in all but one case. The metastases showed uniform staining for cytokeratin (eight of eight cases) and epithelial membrane antigen (eight of eight cases), including the spindle cell component that was present in four of nine cases. Desmin significantly changed the interpretation of rhabdomyosarcoma differentiation by refuting putative rhabdomyoblasts in two cases and identifying rhabdomyoblasts in two other cases where they were unrecognized on hematoxylineosin staining. S100 protein was positive in all five cases with chondrosarcoma differentiation. Muscle-specific actin and vimentin were positive in the sarcomatous component of all cases and in the carcinomatous component of seven and 10 cases, respectively. After immunostaining, heterologous elements were present in 18 of 29 cases (11 cases of rhabdomyosarcoma, three cases of chondrosarcoma, three cases of mixed rhabdomyosarcoma and chondrosarcoma, and one case of liposarcoma). Only six of 27 patients with follow-up were disease free for 12 months or longer (associated with stage I or II disease, smaller size, no lymphatic invasion in the resection specimen, and no invasion of the outer two thirds of myometrium). Presence and type of heterologous elements, grade of sarcomatous or carcinomatous components, histologic type of carcinomatous component, gross appearance, presence of necrosis, or use of chemotherapy or radiotherapy did not affect outcome. Carcinosarcomas are clinically aggressive distinctive mixed epithelial-stromal neoplasms with histologic and immunohistochemical features that overlap with metaplastic carcinoma in many cases.

Garcia, C. R., M. Toro Rojas, et al. (1991). "Uterine mullerian adenosarcoma with histiocytic (xanthomatous) mesenchymal component." Histol Histopathol 6(3): 363-7.

We present an endometrial Mullerian adenosarcoma in which the sarcomatous component showed prominent nests of foamy cells that accounted for 50% of the neoplastic mesenchyma. Such foamy cells showed occasional cytological atypias and immunohistochemical features of histiocytic (macrophagic differentiation in the absence of changes that could substantiate the presence of an inflammatory infiltration of foamy histiocytes. These facts suggest histiocytic differentiation from neoplastic mesenchymal cells. Such differentiation has been reported in association with malignant mixed mesodermal tumor, but not in Mullerian adenosarcoma.

Osborne, B. M. and J. J. Butler (1991). "Clinical implications of nodal reactive follicular hyperplasia in the elderly patient with enlarged lymph nodes." Mod Pathol 4(1): 24-30.

In older persons, the humoral immune response, as reflected morphologically by proliferation and expansion of germinal centers, is relatively subdued in comparison with the florid reactive follicular hyperplasia (RFH) which may be observed in younger age groups. The presence of RFH in lymph node biopsies in patients 60 yr or older, which we have regarded with concern since 1972, appears to represent an imbalance of the immune system, in some patients, on the background of which predominantly non-Hodgkin's malignant lymphoma (NHL) may be present or will develop. Fifty-eight patients 60 yr old or more who presented with enlarged lymph nodes exhibiting inappropriate RFH for age were identified during the interval from 1969 to 1989. An apparent etiology was initially identified for the reactive follicular hyperplasia in only 12 cases: five with documented rheumatoid arthritis; one each with a history of trauma, positive monospot test, and combination of thrombophlebitis and fungal skin infection, and two each with elevated Epstein-Barr virus (EBV) titers and human immunodeficiency virus type 1 (HIV-1) seropositivity. While most were alive or died of nonlymphomatous causes and one was lost to follow-up, 18 (31%) patients either had concurrent lymphoma or subsequently developed diffuse NHL. There were ten diffuse interfollicular (I-Foll) lymphomas (six concurrent), two diffuse mixed cell lymphomas (DMCL), one diffuse large cell lymphoma (DLCL), one diffuse immunoblastic sarcoma (DIBS), two diffuse small noncleaved cell lymphomas (DSNCL), one unclassified NHL, and only one Hodgkin's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Sternberg, C. N. (1991). "[Chemotherapy in the treatment of advanced urothelial tumors]." Urologe A 30(1): 33-44.

Progress has been made in the management of patients with advanced metastatic and muscle-invasive urothelial tract tumors. Combination chemotherapy has proved effective, and, in those who attain complete remission it prolongs survival. Chemotherapy alone or combined with radiotherapy and TURB may now make less aggressive surgery and bladder conservation possible in selected patients. Improvements in perioperative care, coupled with surgical, radiotherapeutic and diagnostic achievements, have led to substantial progress. Recombinant DNA technology has led to the availability of sufficient quantities of hematopoietic factors, which are now available for clinical trials. Today, CSFs can complement therapy and ameliorate the myelosuppression and mucositis associated with chemotherapy, permitting safer administration of therapy and increased dose intensity of treatment programs. Investigations of the biology of bladder cancer aimed at defining the malignant and metastatic potential of an individual tumor are very promising. Immunohistochemistry of cell surface antigens, such as blood group antigens, monoclonal antibody technology, and assessment of the chromosomal complement or DNA content will have increasing importance for this aim in the future. Future trials will need to consider the biology of bladder cancer and more sophisticated prognostic variables than performance status. Mixed-histology tumors are probably less responsive. Why certain tumors metastasize and others remain restricted to the bladder or nodes is still a matter of conjecture. Hopefully, future studies will throw some light on these still-unexplained areas.

Chang, H. C., S. Hsueh, et al. (1991). "Malignant mixed mullerian tumor of the fallopian tube. Case report and review of the literature." Changgeng Yi Xue Za Zhi 14(4): 259-63.

Malignant mixed mullerian tumor of the fallopian tube is extremely rare, with less than 50 cases recorded in the English literature. Another case is reported and discussed. This 66-year-old female patient complained of profuse watery vaginal discharge for one month. Vaginal cytology was positive for malignancy while the endometrial curettage and cervical biopsy were both negative. Gynecologic sonography revealed a left adnexal mass of 6 cm in diameter. She underwent exploratory laparotomy after complete oncologic survey. The main tumor was confined to one tube but the peritoneal washing cytology was positive for adenocarcinoma cells. She tolerated the maximal debulking surgery very well but refused to receive adjuvant chemotherapy. Pathology proved that the tumor was composed of poorly differentiated adenocarcinoma and sarcoma. There were focal areas of rhabdomyoblastic differentiation with cross striation in immunoperoxidase stain. Carcinomatosis peritonii occurred 12 months after primary surgery and she expired one month later.

Nogales, F. F., A. Ayala, et al. (1991). "Myxoid leiomyosarcoma of the ovary: analysis of three cases." Hum Pathol 22(12): 1268-73.

The first three cases of myxoid leiomyosarcoma occurring in the ovary are reported. Two cases in stage III were found in postmenopausal patients and a further case was found in stage I in a 32-year-old. All masses were large and gelatinous with cystic change, necrosis, and hemorrhage, but both uteri and ligaments and contralateral adnexa appeared normal. Microscopically, the tumors showed a predominantly reticular meshwork of elongated cells surrounded by abundant basophilic material. While electron microscopy proved inconclusive due to nondifferentiation, the use of monoclonal antibodies against smooth muscle actin demonstrated a smooth muscle type of differentiation. The differential diagnosis of this rare ovarian condition includes other myxoid ovarian lesions, such as ovarian edema, myxoma, endodermal sinus tumors, and the sarcomatous component of malignant mixed mullerian tumor and carcinosarcoma, as well as lymphovascular tumors. Since mitotic count due to decreased cellular density is unusually low in myxoid leiomyosarcoma, capsular rupture and clinical stage seem to be more reliable prognostic markers. The highly aggressive behavior of myxoid leiomyosarcoma parallels that of typical ovarian leiomyosarcoma. Two of the three patients in this series died of tumor at 13 and 24 months after diagnosis; the other patient is free of disease at 3 years after diagnosis.

Chiou, Y. K., I. J. Su, et al. (1991). "Malignant mixed mullerian tumor of the fallopian tube." J Formos Med Assoc 90(8): 793-5.

Malignant mixed Mullerian tumor (MMMT) of the fallopian tube is an extremely rare neoplasm with a poor prognosis. To date, only 37 cases have been reported. The primary treatment for this tumor is surgery. Chemotherapy has been used with some success. The role of radiotherapy is less clear. A case of malignant mixed Mullerian tumor of the fallopian tube occurring in a 63- year- old woman, presenting with postmenopausal vaginal spotting for 7 months, is reported.

Tokunaga, T., K. Miyazaki, et al. (1991). "Pathology of the fallopian tube." Curr Opin Obstet Gynecol 3(4): 574-9.

Tubal carcinoma and serous adenocarcinoma of the ovary are remarkably similar in biologic characteristics and tumor markers, which suggests that the management for tubal carcinoma would be based on that for ovarian carcinoma. The cases with rare histologic features, including endometrioid carcinoma, mixed mullerian tumor, and malignant fibrous histiocytoma have been reported. In the genesis of tubal pregnancy, microscopic evidence of silent inflammation has attracted special interest recently. With the development of sophisticated diagnostic tests and the progress of medical management, it has become possible to treat unruptured tubal pregnancies by pharmacologic approaches, laparoscopy, or transvaginal sonographic control. This review briefly outlines the conspicuous pathologic and etiologic features of neoplasms, ectopic pregnancy, and abnormality of the fallopian tube, and discusses some recent observations regarding these disorders.

Pasquali, J. L., C. Waltzinger, et al. (1991). "The majority of peripheral blood monoclonal IgM secreting cells are CD5 negative in three patients with mixed cryoglobulinemia." Blood 77(8): 1761-5.

The mixed cryoglobulinemia is considered to be a nonmalignant human B-cell proliferation that frequently produces a monoclonal IgM with anti-IgG activity (rheumatoid factor). Using murine monoclonal anti-idiotypic antibodies specific for private or minor idiotopes on monoclonal IgM from three patients suffering from nonmalignant mixed cryoglobulinemia, we investigated the presence of the CD5 antigen on the monoclonal IgM producing cells in these patients. It is shown by two-color cytofluorometric analysis that the majority of the peripheral blood monoclonal IgM rheumatoid factor secreting cells is CD5 negative in these three patients. One of the monoclonal rheumatoid factor K variable regions was sequenced at the protein level and belongs to the human VK III group, as a high proportion of monoclonal rheumatoid factors and some B-cell chronic lymphocytic leukemia (CLL) membrane bound Igs. Thus, despite the preferential use of similar VK genes and the absence of somatic mutation affecting these variable regions in both malignant B-cell CLL and nonmalignant mixed cryoglobulinemia, these proliferating B cells differ in the CD5 membrane expression.

Jones, M. A., R. H. Young, et al. (1991). "Endometrial adenocarcinoma with a component of giant cell carcinoma." Int J Gynecol Pathol 10(3): 260-70.

We report six high-grade endometrial adenocarcinomas with a malignant giant cell component. The patients ranged in age from 43 to 85 years (mean 65); five were postmenopausal. All the patients presented with vaginal bleeding. The tumors all had a giant cell component that was composed of poorly cohesive sheets and nests of bizarre multinucleated giant cells admixed with an approximately equal number of mononucleate tumor cells. A sarcomatoid pattern and a marked inflammatory infiltrate were each present in three cases. All the tumors contained at least focal areas of endometrial adenocarcinoma of one of the usual types. Occasional malignant giant cells were positive for cytokeratins (AE1/AE3 or CAM 5.2) and epithelial membrane antigen in all three tumors tested. Three tumors were in stage I, one stage III and two stage IV. Two of the patients with stage I disease (each with superficial myometrial invasion) were alive and well 6 and 2 years later. Of the remaining four patients, three died of disease 2.5 years, 6 months, and 5 months after presentation, and one was alive with extensive abdominal disease after 1 year. Giant cell carcinoma of the endometrium is an aggressive tumor that should be distinguished from other endometrial tumors with a prominent giant cell component, including trophoblastic tumors, certain primary sarcomas, and malignant mixed mullerian tumors. It is imperative that malignant giant cells and non-neoplastic giant cells not be confused, as is possible in a curettage or biopsy specimen.

Pfeiffer, P., M. Hardt-Madsen, et al. (1991). "Malignant mixed mullerian tumors of the ovary. Report of 13 cases." Acta Obstet Gynecol Scand 70(1): 79-83.

Thirteen patients with verified malignant mixed Mullerian tumor of the ovary treated in Denmark during the 7-year period 1981-87 were reviewed. Two patients had homologous and 11 patients had heterologous tumors. Four patients with early stage disease underwent radical surgery; 9 patients had stage III disease. Median survival for all 13 patients was 12 months. Six patients received platinum-containing cytotoxic therapy; 2 of these patients without measurable disease became long-term survivors (survival times 42+ and 92+ months, respectively) and 3 of the 4 remaining patients with evaluable disease obtained an objective remission.

Hano, H., M. Endo, et al. (1990). "Malignant mixed mullerian tumor of the ovary. Report of a case studied by immunohistochemistry." Acta Pathol Jpn 40(11): 845-50.

A case of malignant mixed mullerian tumor of the ovary in a 57-year-old woman is reported along with the results of an immunohistochemical study. The tumor, measuring 16 x 10 x 9 cm, was composed predominantly of adenocarcinoma with a smaller amount of anaplastic carcinoma as an epithelial component and chondrosarcoma, liposarcoma, fibrosarcoma and rhabdomyoblasts as mesenchymal elements. Immunohistochemistry using paraffin sections demonstrated cytokeratin (CK) and epithelial membrane antigen (EMA), generally regarded as epithelial markers, not only in the epithelial component but also in chondrosarcoma cells. Vimentin and desmin, generally regarded as mesenchymal markers, were exhibited partly in carcinoma cells as well as in mesenchymal elements. Positive staining for S-100 protein was obtained not only in chondrosarcoma and liposarcoma cells, but also partly in adenocarcinoma cells. This intricate immunohistochemical picture reflected the histologic findings. It is noteworthy that both carcinoma cells and chondrosarcoma cells demonstrated simultaneous expression of CK, EMA, vimentin, desmin and S-100 protein. This somewhat unusual antigen expression by tumor cells may indicate a change in the nature of tumor cells due to microenvironmental factors.

Milatovich, A., N. A. Heerema, et al. (1990). "Cytogenetic studies of endometrial malignancies." Cancer Genet Cytogenet 46(1): 41-53.

Thirty cases of endometrial malignancy were successfully studied cytogenetically. Twenty-four of the cases were endometrial adenocarcinomas. Twenty-three of these were stage I tumors, and the twenty-fourth was a stage IV tumor. Fourteen of the stage I adenocarcinomas had abnormal chromosomes, and nine had apparently normal chromosomes. No two tumors had an identical chromosomal rearrangement. Trisomy 1q was common however; 10 of the 14 tumors with abnormal chromosomes had a chromosome 1 abnormality. Clinical and pathologic data were available for 17 of these patients. There appeared to be no relationship between prognostic indicators and the tumor karyotype except for uterine size. Six cases of endometrial malignant mixed mullerian tumor (MMMT) of the homologous type were also analyzed cytogenetically. Three of these tumors had very abnormal karyotypes, and the remaining three had apparently normal chromosomes. Structural abnormalities of chromosome 1, 3, and 5 were present in all three tumors with abnormal karyotypes, but identical breakpoints or rearrangements were not observed.

Seraj, I. M., A. King, et al. (1990). "Malignant mixed mullerian tumor of the oviduct." Gynecol Oncol 37(2): 296-301.

Malignant mixed mullerian tumor is an uncommon gynecologic neoplasm, especially in the oviduct, where fewer than 30 have been described. We report two additional cases which clinically mimicked carcinoma of the oviduct. Both patients were postmenopausal and had the chief complaint of abdominal pain associated with increased abdominal girth. Presurgical vaginal cytologies were negative and both diagnoses were made only with histologic examination of tissues removed at surgery. As most of the cases from the literature involved low-parity women, the high parity of these women is unusual. Unfortunately both presented with stage III disease and died of recurrent disease 18 and 12 months following surgery.

Fedorchenko, S. V., A. D. Vovk, et al. (1990). "[Delta hepatitis as a mixed infection]." Vrach Delo(3): 5-8.

Radioimmunoassay of 247 patients revealed in their sera 8 cases of anti-delta agents. On the basis of testing of HBV infection markers the authors revealed three cases of coinfection and five cases of delta superinfection. A fatal case of fulminant hepatitis with development of acute liver dystrophy was observed in one patient with coinfection. In two other patients the course of the disease was severe but ended in recovery. Superinfection with delta agent resulted in a progression of the disease with early formation of chronic active hepatitis. This form chronic disease was characterized by a malignant course and proved resistant to immunosuppressive therapy. The clinical and biochemical signs of coinfection and delta superinfection are discussed.

Ballance, W. A., J. Y. Ro, et al. (1990). "Pleomorphic adenoma (benign mixed tumor) of the breast. An immunohistochemical, flow cytometric, and ultrastructural study and review of the literature." Am J Clin Pathol 93(6): 795-801.

Pleomorphic adenoma (or benign mixed tumor) of the breast is a rare benign neoplasm that might be misinterpreted both clinically and pathologically as a malignant tumor. The authors present an additional case of this unusual lesion studied by immunohistochemistry, electron microscopy, and flow cytometry. A 77-year-old white woman presented with a 2-cm, nontender, mobile, calcified, right subareolar mass suggestive of a fibroadenoma. Microscopically, the tumor resembled a pleomorphic adenoma occurring in salivary glands. Positive immunostaining for S-100 protein, cytokeratin, and muscle-specific actin, as well as the ultrastructural presence of intermediate filaments with dense bodies and intercellular junctions, supported the predominant myoepithelial cell differentiation within the tumor, whereas the epithelial cell component stained only with cytokeratin and contained formed lumina with surface microvilli. The DNA pattern was diploid. The patient is alive and well 14 months after surgery. The authors' findings confirm that pleomorphic adenoma of the breast is a benign neoplasm in which myoepithelial cell proliferation plays a major role in tumorigenesis.

Ishizaki, A., M. Shinozaki, et al. (1990). "[A clinical study of death in profound mental retardation with motor disturbance]." No To Hattatsu 22(4): 357-63.

Among 848 cases of profound mental retardation with motor disturbance admitted to Metropolitan Medical Center of Severely Handicapped in the last 20 years, 98 died. The 94 cases whose cause of death was determined were clinically investigated. There was no difference in sex, and 72% of the patients died before the age of 15 years. Half of the patients died of pneumonia; sudden death occurred in 9, and ileus in 8. These three were thought to be the most important and characteristic causes of death in severely handicapped patients. In recent years, deaths due to pneumonia have decreased and those due to ileus have disappeared, but deaths due to malignant neoplasm have begun to be recognized. There were also some deaths from intracranial hemorrhage in young children, and some deaths from tracheal bleeding in those who had tracheal tubes. These two were also important causes of death in the patients. Sudden death had certain characteristics: most cases were adolescent or young patients with mixed quadriplegia who were sensitive to environmental changes and often showed marked hypertonia by athetosis, and in addition, all of their acute changes occurred between 5 and 8 a.m. or between 6 and 9 p.m.

Meis, J. M. and W. D. Lawrence (1990). "The immunohistochemical profile of malignant mixed mullerian tumor. Overlap with endometrial adenocarcinoma." Am J Clin Pathol 94(1): 1-7.

The distinction between malignant mixed mullerian tumor (MMMT) of the female genital tract and poorly differentiated endometrial adenocarcinoma (EA) is sometimes difficult and arbitrary. Although several studies have described the immunohistochemical profile of MMMT and EA, the results have varied, and controversy regarding the histogenetic relationship between them remains. The authors examined the histologic characteristics and immunohistochemistry of 31 formalin-fixed paraffin-embedded MMMTs from a variety of female genital tract sites with a panel of monoclonal and polyclonal antibodies using the avidin-biotin-peroxidase complex (ABC) method. Eighteen neoplasms were homologous and 13 were heterologous; the average patient age was 67 years. In all cases the epithelial component stained for keratin (K), whereas the stromal component stained in 48%; vimentin (V) was detected in the epithelial component in 35% and the stromal component in 81%. Myoglobin (M) detected rhabdomyoblasts in three of five cases tested; desmin (D) was found in five of six and actin (A) in all six cases with skeletal muscle. Overall, A stained the stromal components in 45% of cases, whereas none of the epithelial components stained. The coexpression of K and V in the epithelial component of 35% of cases and in the stromal component of 48% of cases led the authors to conclude that the immunoprofile of MMMT broadly overlaps with that of EA and, independent of morphologic findings, it is often not reliable or useful in distinguishing between the two. Furthermore, the variable immunoprofile suggests that MMMT may be a histogenetically heterogeneous group of neoplasms, including both carcinomas (metaplastic, sarcomatoid) as well as true carcinosarcomas. Although A detected rhabdomyoblasts in all cases, it also stained neoplastic mesenchymal elements in eight more cases, suggesting the presence of smooth muscle or myofibroblasts in the stroma of some MMMTs.

Nakamura, M., T. Hachisuga, et al. (1990). "[A case of an unusual mixed mullerian tumor in the lower uterine segment]." Gan No Rinsho 36(8): 959-63.

A unique case of a mixed mullerian tumor in a 33-year-old woman is presented. On gross examination of the hysterectomized specimen, well-circumscribed nodules, the largest measuring 3 cm in diameter, were found in the lower uterine segment. Microscopic examination revealed that the lesion was composed of a malignant glandular epithelium and a spindle cell stroma containing a smooth muscle. The atypical gland had deeply infiltrated into the normal myometrium and showed a squamous differentiation. This tumor should be differentiated from a benign mixed mullerian tumor, including an atypical polypoid adenomyoma, an adenofibroma, and an adenomyoma.

Nishida, T., N. Nagasue, et al. (1990). "Cisplatin, adriamycin and ifosfamide-based combination chemotherapy for gynecological cancers derived from the extended mullerian system." Nippon Sanka Fujinka Gakkai Zasshi 42(2): 193-8.

Their histogenetic similarity suggests that a group of malignant tumors may have a common sensitivity to a cytotoxic chemotherapy. Seventy patients with a variety of gynecological cancers arising from the uterine cervix, endometrium, ovary and pelvic peritoneum were treated with a combination of cisplatin, adriamycin and ifosfamide (PAI). As schedule modifications, PAI plus bleomycin for cancers containing squamous components and PAI plus etoposide for nonepithelial malignancies were recommended. In twenty-five evaluable cases, including 12 recurrent tumors after previous radiation therapy or PAC (cisplatin, adriamycin and cyclophosphamide) chemotherapy, the total response rate was 95% for epithelial cancers (vaginal cancer: 1/1, cervical: 9/10, endometrial: 2/2, ovarian: 6/6 and peritoneal: 2/2), and 100% for nonepithelial malignancies including one uterine leiomyosarcoma, one uterine mixed Mullerian tumor and one extragonadal mixed Mullerian tumor. The survival rates of patients with non measurable lesion were 100% for cervical cancer (the observation period: 65-879 days), 92.9% for endometrial cancer (96-975 days) and 88.9% for ovarian cancer (148-976 days). The hematological toxicity of this treatment was severe but acceptable. The results obtained indicate that a wide range of gynecological cancers originating in the primary and secondary Mullerian tissues (extended Mullerian system) must have a similar sensitivity to cytotoxic treatment with a PAI-based combination chemotherapy.

Kirby, G. M., M. Stalker, et al. (1990). "Expression of immunoreactive glutathione S-transferases in hepatic neoplasms induced by aflatoxin B1 or 1,2-dimethylbenzanthracene in rainbow trout (Oncorhynchus mykiss)." Carcinogenesis 11(12): 2255-7.

The expression of immunoreactive glutathione S-transferase (GST) was examined in hepatic neoplasms induced in rainbow trout by aflatoxin B1 (AFB) or 1,2-dimethylbenzanthracene (DMBA). Tumors were induced in adult trout by continuous dietary exposure to 8 p.p.b. AFB1 for 12 months or embryo bath exposure to DMBA (5 p.p.m. for 24 h, 3 times with 12 h intervals between exposures). Polyclonal antiserum specific for the two major trout hepatic GST subunits in trout liver was produced by immunizing rabbits with affinity-purified trout GST. Hepatocellular, cholangiolar and mixed neoplasms as well as foci of hepatocellular alteration were examined for GST immunoreactivity by the PAP technique. The majority of lesions were GST-deficient (AFB treated, 67%; DMBA treated, 54%), whereas GST expression was induced in 21% (AFB treated) and 31% (DMBA treated) of altered hepatic foci. The GST-induced foci were consistently small (AFB treated, 0.07 +/- 0.05 mm2; DMBA treated, 0.02 +/- 0.01 mm2) and none had progressed beyond the altered focus stage. The majority of larger advanced lesions (adenomas and carcinomas) were GST deficient (AFB treated, 2.33 +/- 0.35 mm2; DMBA treated, 2.95 +/- 0.59 mm2). These studies demonstrate that induced GST expression occurs in some small populations of hepatocytes, but not in larger advanced stages of malignant progression of aflatoxin- or PAH-induced hepatic neoplasms in rainbow trout.

Marth, C., A. Koza, et al. (1990). "[Prognostically relevant factors in malignant mixed Mullerian tumor]." Geburtshilfe Frauenheilkd 50(8): 605-9.

In a retrospective analysis of 429 endometrial carcinoma and 29 malignant mixed Mullerian tumour (MMMT) patients, the prognostic factors were evaluated. More than 80% of endometrial carcinomata were staged as I or II, whereas about 30% of MMMT's already in stage III or IV (p less than 0.05). MMMT patients were 10 years older than the carcinoma group (73a vs 63a; p less than 0.001). The risk factors parity, adipositas, and diabetes were equally distributed in the two groups, the survival was worse in MMMT (p less than 0.0001). Applying univariate analysis stage, grading, myometrial invasion and type of therapy significantly affected the survival of endometrial carcinoma patients. After a Cox regression, only stage and grading remained significantly associated with the prognosis. For MMMT's, the survival was also influenced by stage, myometrial invasion, and kind of therapy. Moreover, the parity was found to affect markedly the course of disease. Cox regression of our data excluded all but stage and parity. The beneficial influence of parity on the prognosis of MMMTs, despite a latency of more than 20 years from the last birth to tumour appearance, is unique in oncology.

Takahashi, H., N. Tsuda, et al. (1990). "Non-Hodgkin's lymphoma of the major salivary gland: a morphologic and immunohistochemical study of 15 cases." J Oral Pathol Med 19(7): 306-12.

A total of 15 cases of Japanese salivary gland lymphoma was analysed by conventional histology and also by immunoperoxidase staining of paraffin sections. The initial sites included: parotid gland (14 cases, 93%) and submandibular gland (1 case, 7%). The mean age was 59 yr, with a male to female ratio of 2.8:1. The only one patient (Case 9) with clinical evidence of Sjogren's syndrome showed the development of intrasalivary malignant lymphoma. Each lymphoma was classified according to the Working Formulation for Clinical Usage. The Working Formulation grades were 20% low, 67% intermediate, and 13% high. These neoplasms fell into six categories: follicular, small cleaved type (1 case); follicular, mixed small cleaved and large cell type (2 cases); follicular, large cell type (2 cases); diffuse, mixed small and large cell type (1 case); diffuse, large cell type (7 cases); and large cell, immunoblastic type (2 cases). Fifteen tumors were studied using a indirect immunoperoxidase method. A selected antibody panel was used, including B-cell markers (immunoglobulins, Ki-B3, L26), T-cell markers (UCHL-1 and MT1) and histiocytic markers (lysozyme, alpha 1-antitrypsin and cathepsin D). Eleven cases reacted with pan-B-marker (Ki-B3 and L26) and eight of them showed the presence of monoclonal cytoplasmic immunoglobulin (C-Ig). Following rigid criteria, monoclonal C-Ig of M kappa was demonstrated in one case of follicular, small cleaved cell type, one follicular, large cell type and two diffuse, large cell type; M lambda was demonstrated in one diffuse, large cell type; and G lambda was demonstrated in one follicular, mixed small cleaved and large cell type, and two diffuse, large cell type.(ABSTRACT TRUNCATED AT 250 WORDS)

van Haaften-Day, C., P. Russell, et al. (1990). "Two homologous mixed mullerian tumor lines of the ovary and their characteristics." Cancer 65(8): 1753-61.

Two cell lines, NF and JoN, derived from human ovarian carcinosarcomas, were established in tissue culture and in nude mice. Both lines, growing in monolayers, showed morphologic features of adenocarcinoma cells (NF being aneuploid with a modal number of 53, and JoN being pseudodiploid with a modal number of 44). Intermediate filaments were demonstrated immunohistochemically; the JoN line expressed keratin, but not vimentin or desmin, whereas the NF line expressed vimentin and desmin, but not keratin. Plasminogen activator activity was found in both lines. It is concluded that both of these lines are potentially useful models for studying the diverse characteristics of malignant mixed Mullerian tumors.

Liang, W. W., Y. N. Lin, et al. (1990). "Malignant mixed mullerian tumor of fallopian tube. Report of a case and review of literature." Zhonghua Yi Xue Za Zhi (Taipei) 45(4): 272-5.

This is a case of malignant mixed Mullerian tumor arising primarily from the fallopian tube. The tumor was distant metastasis to the omentum and the serosa of the sigmoid colon. Literatures published in the last two decades are reviewed and discussed.

Ehrmann, R. L., N. Weidner, et al. (1990). "Malignant mixed mullerian tumor of the ovary with prominent neuroectodermal differentiation (teratoid carcinosarcoma)." Int J Gynecol Pathol 9(3): 272-82.

We report a unique carcinosarcoma of the ovary having an organoid growth pattern that resembled immature teratoma. The tumor contained both adenocarcinoma and squamous carcinoma (focally sebaceous) admixed with chondrosarcoma, rhabdomyosarcoma, and malignant neuroectodermal components. The neuroectodermal components were prominent, resembling ependymoblastoma, medulloepithelioma, ganglioneuroblastoma, glioblastoma multiforme, and pigmented neuroectodermal tumor. Immunohistochemical studies dramatically revealed carcinoma and rhabdomyosarcoma admixed with malignant neuroectodermal tumor. Implants of papillary serous carcinoma (with psammoma bodies) were present in the opposite ovary, uterine serosa, omentum, and appendiceal serosa. Although a variant not previously described in the ovary, this ovarian carcinosarcoma closely resembled nasopharyngeal tumors described as teratoid carcinosarcoma or terato-carcinosarcoma.

Kaspareit-Rittinghausen, J. and F. Deerberg (1990). "Spontaneous malignant mixed mullerian tumors and rhabdomyosarcoma of the uterus in rats." Toxicol Pathol 18(3): 417-22.

Five malignant mixed mullerian tumors and one rhabdomyosarcoma were observed in LEWIS rats. Heterologous mullerian neoplasms (cases 1-4) consisted of epithelial and mesenchymal elements including squamous epithelium, glandular epithelium and sarcomatous, rhabdomyosarcomatous, cartilaginous as well as osseous parts. All the heterologous tumors revealed undifferentiated areas with an anaplastic appearance. The homologous mullerian tumor (case 5) was composed of glandular epithelium embedded in sarcomatous tissue. The rhabdomyosarcoma (case 6) consisted of bundles of elongated strap-like cells mixed with cells resembling rhabdomyoblasts.

Schweizer, W., R. Demopoulos, et al. (1990). "Prognostic factors for malignant mixed mullerian tumors of the uterus." Int J Gynecol Pathol 9(2): 129-36.

This study examined factors affecting the survival of 28 consecutive patients with malignant mixed Mullerian tumors diagnosed at New York University Medical Center from 1971 through 1985. The cumulative 5-year survival for all patients was 38%. Patients with pedunculated tumors (18/25) had a significantly improved 5-year survival of 53% compared with patients having a tumor with a broad-based attachment (7/25), all of whom died within 1 year (p less than 0.01). Eleven patients whose tumors demonstrated vascular invasion had a worse prognosis compared with 14 patients without demonstrable vascular invasion (18% versus 53% 5-year survival; p less than 0.05). Interestingly, patients with pedunculated tumors persisted in having an improved survival even after correcting for vascular invasion, compared with patients having broad-based tumor attachment. Small tumor size (less than or equal to 7 cm) also proved to be a significant and independent prognostic indicator for improved survival. Advanced stage, heterologous sarcomatous elements, and deep myometrial invasion (greater than one-third invasion) tended to be associated with decreased survival, but not with statistical significance. Patient age and grade of the carcinoma element did not appear to affect survival.

Lu, Y. M., H. C. Chang, et al. (1989). "Mullerian adenosarcoma of uterus--a case report." Changgeng Yi Xue Za Zhi 12(3): 174-8.

A rare case of Mullerian adenosarcoma occurred in the uterine endometrium of a 40-year-old woman. Histologically, the tumor was composed of an admixture of benign-appearing glands and a sarcomatous stroma. This neoplasm appears to have a relatively low malignant potential in contrast to the more aggressive form of malignant mixed Mullerian tumor. Our case was treated with hysterectomy and radiation. She was well after two and a half years.

Gagne, E., B. Tetu, et al. (1989). "Morphologic prognostic factors of malignant mixed mullerian tumor of the uterus: a clinicopathologic study of 58 cases." Mod Pathol 2(5): 433-8.

Sixty-one patients with malignant mixed mullerian tumor (MMMT) of the uterus were seen at L'Hotel-Dieu de Quebec between 1950 and 1986, and the histopathologic material was available for review in 58 cases. Of the morphologic parameters studied, the histologic grade of both epithelial and mesenchymal components correlated with the initial stage. Patients with stages I and II disease had a significantly better survival rate than those with stages III and IV (P less than 0.006). Twenty-five patients with a minimum follow-up of two years were initially stage I or II. All six patients of this subgroup with an epithelial component of serous carcinoma type were dead of their disease at 2 yr. Although not statistically significant, tumor necrosis, the mode of tumor invasive (pushing and infiltrative), and the ratio of epithelial to mesenchymal components tended to influence the outcome. The mitotic rate, the type of mesenchymal components, and vascular and myometrial invasion were of no prognostic significance. We conclude that the outcome of patients with uterine MMMT is mainly influenced by the initial stage and the type of epithelial component. The influence of tumor necrosis, the ratio of epithelial to mesenchymal component, and the mode of tumor invasion deserve further studies.

Ozaki, Y., K. Amemiya, et al. (1989). "A case of mixed mullerian tumor, usefulness of 67Ga-citrate scintigraphy." Kaku Igaku 26(9): 1207-12.

Mixed Mullerian Tumor (M.M.T.) is a rare malignant neoplasm usually arising from uterine body in postmenoposal woman, and imaging diagnosis for the tumor has not been established. A 45-year-old female with pathologically confirmed M.M.T. was evaluated by 67Ga-citrate scintigraphy and CT on the basis of imaging diagnosis. 67Ga-citrate scintigraphy detected correctly not only primary lesions but also metastatic and recurrent-foci. The findings of 67Ga-citrate scintigraphy were confirmed to be correspond to autopsy findings. Generally, detectability of 67Ga-citrate scintigraphy for genito-urinary tract neoplasm was not appreciated, but in our case 67Ga-citrate scintigraphy was useful for detection of the primary lesion, metastatic and recurrent foci. The cellular components and grade of cell-differentiation of this tumor seemed to be responsible for good detection of the tumor. Thus, 67Ga-citrate scintigraphy was considered to be useful diagnostic imaging modality of M.M.T.

Dupuy, P., M. Bagot, et al. (1989). "Synthetic retinoids inhibit the antigen presenting properties of epidermal cells in vitro." J Invest Dermatol 93(4): 455-9.

The clinical efficacy of retinoids in benign and malignant skin diseases involving immune mechanisms suggests that they affect the immunologic functions of the epidermis. However, these effects have yet to be demonstrated. The action of vitamin A (retinol) and the synthetic retinoids, isotretinoin, etretinate, acitretin, and arotinoid-free acid have been studied on the lymphocyte proliferation induced by phytohemagglutinin (PHA), by the mixed lymphocyte reaction (MLR), and the mixed epidermal cell-lymphocyte reaction (MECLR). The results for PHA-induced proliferations were highly variable for all the retinoids. However, in MECLR, the synthetic retinoids consistently reduced the proliferation by 20%-30%. This occurred at therapeutic drug concentrations of about 10(-7)M. In MLR, a minor decrease of 10%-15% was only found for higher concentrations (10(-5)M). Retinol induced no effect in either reaction. Further analysis of acitretin on MECLR showed that it reduced lymphocyte proliferation in a dose-dependent fashion. This reduction was combined with a decrease in cytotoxic T-lymphocyte induction (CTL). Addition of 10(-6)M acitretin at various times also revealed that its presence at cell culture initiation was necessary to inhibit proliferation significantly. Furthermore, cell treatments prior to MECLR showed that exposure of epidermal cells to acitretin was essential to produce this inhibition, suggesting that it acts directly on epidermal cells. Consequently, it is suggested that the specific inhibitory effect of synthetic retinoids on lymphocyte activation in MECLR may partly account for their therapeutic action on the skin.

Nakajima, H., S. Mabara, et al. (1989). "Malignant lymphomas of follicular centre cell origin in 14 pigs." Zentralbl Veterinarmed A 36(8): 621-30.

Malignant lymphomas of follicular centre cell (FCC) origin in 14 pigs are described. Seven cases were classified as abdominal type according to the distribution of the neoplastic lesions and the residual cases were of the general type. Most cases were composed of mixed populations of large and medium-sized neoplastic cells and the growing pattern varied from partially follicular to diffuse. The neoplastic cells often showed necrosis, to which macrophages reacted. A part of the neoplastic cells had cytoplasmic immunoglobulin M (CIgM) or cytoplasmic immunoglobulin G (CIgG). The histological features of swine FCC lymphomas are discussed.

Itaya, T., J. G. Judde, et al. (1989). "Genotypic and phenotypic evidence of clonal interactions in murine tumor cells." J Natl Cancer Inst 81(9): 664-8.

The stability of mixed tumor cell populations has been described in terms of phenotypic characteristics such as metastatic potential, immunogenicity, and drug resistance. We have extended these analyses to the molecular level in a model that uses transfection of the hemagglutinin antigen (HA) gene of influenza virus into murine CT-26 colorectal carcinoma cells. Transfection was followed by fluorescence-activated cell sorting (FACS) to select a parent population with expression of high levels of HA. We characterized this population (FACS-3) and four derived clones (5, 6, 9, and 18) over time with regard to phenotypic characteristics: immunogenicity and cross-protection against tumor challenge, cell surface expression of HA, evidence of HA gene amplification, and levels of HA mRNA. During 6 months in culture, the FACS-3 parent cells remained stable, but the individual clones varied for all of the parameters assessed. Among the clones, all possible molecular variations occurred, including changes in HA gene copy number (increased in clone 5 and decreased in clone 18), gene rearrangement (clone 5), decrease in HA mRNA (clones 6, 9, and 18), increase in HA mRNA (clone 5), and an abnormality in translational control or a posttranslational error. In all cases, the molecular changes correlated with cell surface HA expression, immunogenicity, and cross-protective potential. We conclude that in vitro clonal interactions play a role in stabilizing heterogeneity in this system. These studies show that even in the absence of selection, clonal interactions may alter the phenotype of tumors by increasing malignant progression or impeding tumor growth.

Kan-Mitchell, J., M. S. Mitchell, et al. (1989). "Characterization of uveal melanoma cell lines that grow as xenografts in rabbit eyes." Invest Ophthalmol Vis Sci 30(5): 829-34.

Two cell lines, OCM-1 and OCM-2, were established from biopsied specimens of choroidal melanomas of spindle B and mixed cell type morphologies. Both cell lines were phenotypically malignant. Karyotypic analyses revealed human chromosomes with a modal number of 95 and 85, respectively. These cell lines have been passaged for over 2 years and are essentially immortal. The cells grew without contact inhibition as monolayers in liquid culture or as clones in soft agar. Electron microscopy revealed melanoma cells containing premelanosomes and cultures free from contamination by fibroblasts. To categorize the morphologies of these cultured cells better by the Callender classification, they were grown as xenografts in the anterior chambers of rabbits immunosuppressed with daily i.m. doses of Cyclosporin A (10 mg/kg). Tumor plaques were detected after 10 days. The eyes were enucleated and fixed in formalin and stained with hematoxylin and eosin for histopathological evaluation. The xenograft from OCM-1 was found to consist predominantly of spindle B-type melanoma cells. In contrast, the xenograft from OCM-2 contained epithelioid, spindle B and clear cell ("balloon") melanoma cells. The ability of these cell lines to grow as xenografts confirmed their neoplastic origin. In fact, the types of the uveal melanoma cells in the xenografts resembled those in the original biopsied tumors. This suggests that the morphology of human uveal melanoma cells is an inherited trait and may be genetically fairly stable.

Zhiri, M. A., A. Hamdouch, et al. (1989). "[Mixed Mullerian tumors. Apropos of a new case with a review of the literature]." Rev Fr Gynecol Obstet 84(5): 447-50.

The authors report a new case of a Mullerian mixed tumor with malignant double composition with homologous tissue. They are uncommon, probably sometimes unrecognised. These tumors have the same clinical expression but their prognosis is linked to their benign or malignant composition. The treatment proposed by different authors is radical even for benign tumors in the fear of malignant evolution. The number of cases is not sufficient to propose a more economic treatment tested on patients.

Andersen, W. A., D. E. Young, et al. (1989). "Platinum-based combination chemotherapy for malignant mixed mesodermal tumors of the ovary." Gynecol Oncol 32(3): 319-22.

Although considerable clinical data are available to guide treatment decisions for patients with ovarian epithelial malignancies, therapy for the rare malignant mixed mesodermal (mullerian) tumor (MMMT) of the ovary is poorly studied. Ten untreated patients diagnosed with primary ovarian MMMT were managed with cis-platinum-based combination chemotherapy from 1980 to 1985. Six of the 10 patients were stage III suboptimal with evaluable residual disease; 4 of these 6 had CRs with a median duration of response of 13 months. The remaining 2 patients had PRs, of 2 and 11 months duration. Four patients had stage III optimal disease; 1 progressed at 7 months, 1 progressed at 16 months and the other 2 patients have no clinical evidence of disease at 12+ and 22+ months. Despite impressive initial response rates, survival overall was poor, with a median survival for all 10 patients of 16+ months.

Axelrod, J. H., D. R. Herbold, et al. (1989). "Carcinosarcoma of the fallopian tube." Gynecol Oncol 32(3): 398-400.

A patient with Stage III fallopian tube carcinosarcoma treated with cisplatin, doxorubicin, and cyclophosphamide, surviving 31 months disease-free after diagnosis, is presented. Review of the literature revealed this is the 28th case report of malignant mixed Mullerian tumor of the fallopian tube, and fifth instance in which chemotherapy was used as a primary therapy. Modern chemotherapy appears to have improved survival.

Mi, C. (1989). "[Clinicopathologic and immunohistochemical study on 8 cases of malignant mixed mullerian tumor]." Zhonghua Bing Li Xue Za Zhi 18(2): 141-2.

The clinico-pathological features of eight cases of malignant mixed mullerian tumor, a rare neoplasm composed of an admixture of epithelial and stromal elements, are reported. Four of the tumors located in the endometrium, three in the cervix and one in the ovary. Microscopically, the epithelial elements ranged from poorly to well differentiated adenocarcinoma. Homologous stromal sarcoma cells were present in six tumors and heterologous elements were also seen in the other two tumors. Immunohistochemical studies showed diffuse cytoplasmic staining of keratin in the epithelial elements of all the eight cases. Sarcomatous cells were positive focally for keratin in four spindle cell sarcoma cases. Desmin immunoreaction was moderately positive in the sarcomatous element of four neoplasms. Follow-up result was available in 7 patients of whom 3 survived and 4 died from recurrence or metastasis. Immunohistochemical findings support the stem cell origin of this tumor.

Falk, S., I. Papaikonomou, et al. (1989). "[Malignant mixed Mullerian tumors of the uterus. Clinical, morphologic and immunohistochemical findings]." Geburtshilfe Frauenheilkd 49(7): 630-4.

Clinical and morphological findings in four patients with mixed mullerian tumors of the uterus showed, that these highly aggressive neoplasms are derived from the undifferentiated mullerian epithelium. Immunohistochemically, each component exhibits characteristic differentiation markers. The presence of cytokeratins or desmin signals an epithelial viz. rhabdomyosarcomatous differentiation, whilst the detection of vimentin in the absence of other markers demonstrates an undifferentiated mesenchymal component. This component appears to be responsible for the aggressive biological behavior of mixed mullerian tumors.

Evinger-Hodges, M. J., J. A. Spinolo, et al. (1989). "Detection of minimal residual disease in acute myelogenous leukemia by RNA-in situ hybridization." Bone Marrow Transplant 4 Suppl 1: 13-5.

Several proto-oncogenes have been reported to be expressed in normal and malignant hematopoietic cells. Since these studies have been done almost exclusively by Northern and dot-blot analyses using mixed populations of cells, any conclusions concerning quantitative changes in gene expression are difficult to document. We have developed a rapid and sensitive RNA-in situ hybridization technique permitting detection of as few as 5 copies of mRNA per individual cell. Using this technique we have studied the expression levels of several oncogenes including MYC, SIS, FMS, p53, FOS and RAF in both normal hematopoietic cells and bone marrow (BM) cells obtained from acute myelogenous leukemia (AML) patients at presentation, at relapse and in complete remission (CR). Two of these oncogenes, MYC and SIS, are expressed at levels at least 2-5-fold higher in hematopoietic cells obtained from leukemia patients than in any normal hematopoietic cell examined, including cells obtained from regenerating bone marrow. The proportion of abnormal cells correlated well with the percentage of blast cells determined by morphological examination. In 7 out of 10 AML patients in morphological remission, a subpopulation of cells is detectable with abnormally high levels of MYC and/or SIS mRNA. These high levels of MYC expression are similar to those found in BM cells obtained from AML patients at presentation or relapse, but the percentage of cells with this abnormality is generally much lower. Continued follow-up of these patients has shown that 5 of them relapsed within 8 months. At this time, none of the 3 patients which were negative for MYC overexpression has relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)

Oster, W., R. Mertelsmann, et al. (1989). "Role of colony-stimulating factors in the biology of acute myelogenous leukemia." Int J Cell Cloning 7(1): 13-29.

A high proportion of acute myeloid leukemias (AML) recently investigated for their capacity to synthesize biologically active bioregulatory molecules was found to accumulate messenger (m) RNA and to produce membrane-bound or -secreted forms of stimulating factors for granulocyte, macrophage and mixed granulocyte-macrophage colony growth. Blast cells have also been found to secrete interleukin 1, tumor necrosis factor-alpha, interleukin 6, and to express receptors for various growth factors as well. However, growth factors like interleukin 2 and interleukin 3 have not been identified as AML products, and several other factors including interleukin 4, interleukin 5, etc. need further evaluation. Responsiveness of clonogenic leukemic cells to exogenous growth-promoting factors in vitro suggests a possible role of these biomolecules in the course of these disorders. Important evidence for the crucial role of growth factors, at least in some subtypes of AML, has been provided by demonstrating constitutive growth factor production by leukemic cells and their autonomous in vitro growth which is dependent on autocrine secretion of a specific growth factor. The concert of mechanisms providing stimulatory and inhibitory signals for hematopoiesis, which is adapted to the various physiological requirements of the organism, may have multiple defects in AML. This leads to successive steps of malfunctioning of cells, which finally express a fully malignant phenotype. In addition, these derangements also lead to defects in accessory cells on the level of mediator communication. However, there is evidence for autonomous growth promotion of AML blast by constitutive production of growth factors active in an autocrine fashion (GM-CSF, G-CSF, interleukin 6) and by recruitment of accessory cells to increase CSF supply (GM-CSF, G-CSF) via molecules such as interleukin 1 and TNF-alpha in a paracrine fashion. Molecular analysis of transformed hematopoietic cells has revealed changes of the genome, e.g., insertion of viral genetic information or cytogenetic fractures at DNA sites controlling growth factor gene activation. These events appear to be crucial in the induction of uncontrolled growth factor expression promoting oncogenic transformation of hematopoietic progenitor cells.

Thomas, C. Y., V. K. Buxton, et al. (1989). "Phenotypic heterogeneity of spontaneous lymphomas of CWD mice." Blood 73(1): 240-7.

Animals of the inbred mouse strain, CWD, express endogenous murine leukemia viruses early in life and have a high incidence of spontaneous neoplasms. We found that approximately one half of these animals died of malignant lymphoma by the age of 16 months. Splenic enlargement was seen in all mice, but thymic involvement was unusual. One half of the CWD tumors were diffuse lymphoblastic or immunoblastic lymphomas while the remainder were large cell, small cell, or mixed cell lymphomas. Analysis of DNAs from 12 tumors for immunoglobulin and T-cell receptor gene rearrangements revealed that all six of the lymphoblastic and immunoblastic lymphomas were of T-cell origin, as was one tumor of small cleaved cells. Four of the others were clonal B-cell lymphomas and one was of uncertain lineage. Assays of a limited number of tumors for the expression of the Thy 1.2 and IgM molecules confirmed the diversity in the cellular phenotype. The results indicate that CWD mice develop primarily splenic lymphomas with an unusual degree of heterogeneity in the tumor cell phenotypes as compared with the thymic lymphomas found in other high leukemia strains. The CWD strain is a useful new model for studies of retroviral leukemogenesis and the relationship between the histopathology and immunophenotype of malignant lymphomas.

Podczaski, E. S., C. A. Woomert, et al. (1989). "Management of malignant, mixed mesodermal tumors of the uterus." Gynecol Oncol 32(2): 240-4.

Forty-two patients with malignant, mixed mesodermal tumors of the uterus were identified by retrospective chart review. Only 2 patients were premenopausal at the time of diagnosis. Six of the patients had previously received pelvic radiotherapy. Surgical/pathologic findings were inconsistent with clinical staging in 17 of the patients. Patients with stage I tumors were found to have extrauterine extension of tumor in 39% of the cases. Overall, 2- and 5-year actuarial survival rates were 40 and 18%, respectively. The surgical extent of disease was a major prognostic factor in patient survival (P = 0.006). Patients with tumors showing no invasion or invasion limited to the inner two-thirds of the myometrium also demonstrated a significant survival advantage as compared to those with deeper myometrial invasion (P = 0.02). However, no statistically significant relationship was demonstrated between survival and patient age, the nature of the sarcomatous element (homologous or heterologous), or the presence of cervical involvement. Patients with recurrent or persistent disease did poorly; only 4 patients have survived more than 1 year after documentation of recurrent disease. Two patients had prolonged disease stabilization with radiotherapy and cisplatin. Another patient with pulmonary metastases had a 6-month, complete response to cisplatin.

Shimizu, K., K. Hara, et al. (1989). "Relationship between immunophenotype and the development of second primary neoplasms in patients with non-Hodgkin's lymphoma." Nippon Ketsueki Gakkai Zasshi 52(1): 71-9.

We reviewed the records of 107 patients with non-Hodgkin's lymphoma (NHL) to evaluate the relation between second primary neoplasms and the NHL immunophenotype. The incidence of second primary neoplasms was 3.7%. There were one case of hepatocellular carcinoma and 3 cases of gastric adenocarcinoma including one patient who had a history of metachronous malignant lymphomas. Three patients had B cell lymphoma with monoclonal IgM kappa phenotype, and one patient had follicular mixed cell type lymphoma with serum monoclonal IgM kappa. The dominant immunophenotype of B cell lymphomas in Japanese patients is IgM lambda. We believe that the association of the uncommon phenotype of IgM kappa with second primary neoplasms, especially gastric cancer, reflects an underlying genetic predisposition. NHL patients with IgM kappa phenotype should be evaluated carefully for second primary neoplasms.

Oosterhuis, J. W., S. M. Castedo, et al. (1989). "A malignant mixed gonadal stromal tumor of the testis with heterologous components and i(12p) in one of its metastases." Cancer Genet Cytogenet 41(1): 105-14.

A malignant mixed gonadal stromal tumor with mesenchymal heterologous elements of the testis is presented. This entity has been described in the ovary, but not hitherto in the testis. Karyotyping and ploidy measurement was done of the primary tumor and of an inguinal and lung metastases. The DNA ploidy and modal chromosome numbers were in agreement with each other in all samples. The most significant cytogenetic finding was the presence of the metacentric germ cell tumor marker i(12p) in an inguinal metastasis. This marker has been demonstrated in testicular and ovarian germ cell tumors and in a mixed Mullerian tumor, which raises the question of a possible relationship between the pluripotency of these tumors and the presence of i(12p).

Ohmori, T. (1989). "Immunohistochemical study of a case of malignant mullerian mixed tumor in comparison with the activity of normal uterine tissue." Histol Histopathol 4(2): 123-8.

A case of malignant Mullerian mixed tumor of the uterus, exhibiting a histology of heterologous osteosarcomatous differentiation, is presented. Special emphasis is placed on the characteristic immunohistochemical reactivity of the tumor tissue in comparison with that of normal uterine tissue in the proliferative phase. Keratin, cytokeratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (HCG) were found only in the carcinomatous element. However, neuron specific enolase (NSE), S-100 protein (S 100) and vimentin were identified in almost all tumor tissue elements. Desmin and actin were not stained in any elements. Myoglobin was only detected weakly in the squamous carcinomatous element. Undifferentiated cell element, composed of small, round, spindle, or polygonal cells showed positive reactions to NSE and S 100, but not to any other antibodies. As compared to the reactivities of the normal proliferative endometrium, the glandular epithelial cells were positive with NSE, S 100, vimentin and CEA, but the stromal cells were only positive with vimentin. Such a multitudinous and concomitant expression of antigenicity to the different tumor elements indicates a close relationship to its mesodermal Mullerian origin, and NSE, S 100 and vimentin might be most adequate indicators of these types of tumors.

Fetissof, F., B. Arbeille, et al. (1989). "[Malignant mesodermal mixed tumor of the ovary with neuro-ectodermic differentiation]." Ann Pathol 9(3): 204-8.

A striking ovarian tumour was observed in a post-menopausal, 54-year-old woman. Most of the tumour shows histologic features of a malignant mesodermal (mullerian) mixed tumour. However, this tumour harbours a peculiar component suggesting neuroectodermal neoplasia. Histochemical and immunohistochemical studies demonstrate focal pheochromocytomatous (or paraganglionic) and ganglionic differentiations. Several types of cells could be identified: ganglion cells (NSE +, neurofilaments +), pheochromocytes or paraganglion cells (chromogranin +), Schwann cells (S 100 protein +), and neuroblastomatous elements (NSE +). This neoplastic component could be compared with compound tumours such as pheochromocytomaganglioneuroblastoma or gangliocytic paraganglioma. This type of tumour has not been reported in ovary, notably in association with a mesodermal mixed tumour. Such observation prompts us to consider tumours of somatic origin containing germ cell-type elements, with a review of the literature.

Gersell, D. J., D. A. Duncan, et al. (1989). "Malignant mixed mullerian tumor of the uterus with neuroectodermal differentiation." Int J Gynecol Pathol 8(2): 169-78.

A case of malignant mixed mullerian tumor of the uterus with neuroectodermal differentiation is reported. The most notable feature of the tumor was its large component of central nervous system tissue containing both glial and neuronal elements. The islands of neural tissue were admixed with more conventional carcinomatous and sarcomatous elements typically found in tumors of this type. The neuroectodermal component was conspicuous in the residual uterine tumor removed after radiotherapy, but not in the initial biopsy specimens. The patient died after developing local recurrence and distant metastases, which were treated with chemotherapy.

Michel, G., F. Pfeiffer, et al. (1989). "[Sarcoma of the uterus. A clinical study apropos of 50 surgically treated cases at the Gustave Roussy Institute. Review of the literature]." J Gynecol Obstet Biol Reprod (Paris) 18(8): 1024-30.

From 1970 to 1987 fifty patients with uterine sarcoma who have been operated at the G. Roussy Institute (IGR) were studied. The histological material was reviewed according to the W.H.O. classification and the Hendrickson and Kempson's criteria. Staging was done on surgical and histological findings according to the pTNM classification of the UICC for endometrial carcinoma. There were 22 cases of heterologous malignant mixed mullerian tumor (MMT), 5 cases of homologous MMT, 20 cases of leiomyosarcoma (LS), 1 high grade stromal sarcoma, 1 low grade stromal sarcoma (stromal myosis (SM], 1 adenosarcoma. There were 22 cases of stage T1 T2, 23 cases of stage T3 T4 and 5 TX (first surgery outside IGR). Total hysterectomy with bilateral salpingo-oophorectomy was performed in 86% of the cases. Radiation therapy was performed in 26 cases mostly external pelvic irradiation associated with endobrachytherapy. "Cyvadic" combination chemotherapy was used in 16 cases associated with platinum in few cases. There were 2 postoperative deaths, 11 cases of progression and 37 cases of complete remission (CR). Of the 37 cases of CR, 10 patients are alive with NED 6 months to 10 years after diagnosis in 2 cases of MMT. 27 patients presented recurrence or metastasis. Of the 22 patients with pelvi-abdominal recurrence, 10 had debulking surgery (one total pelvic exenteration (PE), three posterior PE). Among them five are alive 14 to 78 months later (3 LS, 1 AS, 1 SM). Thirty percent of the patients developed lung metastasis. The overall five-year survival was 42 +/- 16% (28 patients) (Kaplan-Meier's method), similar to literature data.(ABSTRACT TRUNCATED AT 250 WORDS)

Strong, L. C., W. R. Williams, et al. (1989). "Genetic analysis of childhood sarcoma." Princess Takamatsu Symp 20: 151-7.

A survey of cancer in 159 3-year survivors of childhood soft tissue sarcoma and their relatives revealed a cancer excess in first-degree relatives primarily due to cancers occurring before the age of 35 years and a highly significant excess in relatives of patients with second malignant neoplasms. Tumors of soft tissue and bone, breast, and brain were in excess in relatives and as second malignant neoplasms in patients. To determine the most likely explanation for the observed cancer distribution, we applied segregation analysis under a unified version of the mixed model. The observed data were most compatible with a rare autosomal dominant gene with high penetrance (gene carriers had a 50% probability of cancer by age 30, increasing to 90% by age 60) as compared with a chance occurrence or a multifactorial explanation. We contrasted the relative odds of observing each pedigree under a sporadic, multifactorial, or major gene model, and identified 11 pedigrees in which familial clustering of cancer was significant, with the distribution of cancer strongly favoring a major gene in 9 pedigrees. The tumors in these kindreds have been associated with alterations in specific genetic loci by tumor-specific genetic analysis. In particular, we observed soft tissue sarcoma, osteosarcoma and premenopausal ductal breast carcinoma tumors, perhaps attributable to loss of the Rb-1 suppressor gene on chromosome 13q, in the same patients and families. Study of the cancer predisposition segregating in 10 families by genetic linkage with markers of chromosome 13q and the Rb-1 gene have to date given negative LOD scores at 0 = 0 of Z = -1.2 to -13.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissot, R. G., C. W. Beattie, et al. (1989). "The swine leucocyte antigen (SLA) complex and Sinclair swine cutaneous malignant melanoma." Anim Genet 20(1): 51-7.

Cutaneous malignant melanoma of Sinclair swine (SSCM) is an inherited neoplasm present at birth in a majority of affected animals. We have characterized the swine leucocyte antigen (SLA) complex of the Sinclair herd at Texas A & M University using a one-way mixed lymphocyte test and found that one particular haplotype, arbitrarily identified as haplotype B, is associated with the expression of SSCM. Only a single dose of the B haplotype is required for a dominant allele at a 'tumour initiator' locus to be fully penetrant. In addition, swine homozygous for haplotype B develop more primary tumours between birth and weaning than those heterozygous for the B haplotype. Taken together, these findings indicate that tumour initiation, in utero, and expression between birth and weaning may involve different mechanisms.

White, V. A., C. V. Fanning, et al. (1988). "Osteosarcoma and the role of fine-needle aspiration. A study of 51 cases." Cancer 62(6): 1238-46.

Fifty-one patients were evaluated by fine-needle aspiration (FNA) as part of the diagnosis, staging, and management of osteosarcoma. All patients had histologic confirmation of osteosarcoma. Five patients underwent two aspirations each; thus, the total number of aspirates reviewed was 56. Aspirations were performed by interventional radiologists using fluoroscopic guidance. The cytologic features of osteosarcoma were divided into five groups: (1) pleomorphic (malignant fibrous histiocytoma-like); (2) epithelioid; (3) chondroblastic; (4) small cell; and (5) mixed. Although osteoid-like material was seen, it could not be distinguished readily from dense collagen. The chondroid matrix of chondroblastic osteosarcoma was recognized as a granular film with scattered clear bubbles. Fine-needle aspiration was diagnostic of sarcoma in 45 of 56 aspirates (80.4%). In eight aspirates, the cellularity of the smears was insufficient for diagnosis due to extensively osteoblastic tumors (six), necrotic tumor (one), and undetermined causes (one). In three aspirates, failure was attributed to poor cellular preservation due to unknown factors. The authors conclude that FNA is a useful tool in the multidisciplinary diagnosis and management of osteosarcoma. Aspirates should only be evaluated with full knowledge of the clinical and radiographic findings. The most significant limitation of FNA is the inability to detect osteoid.

Clement, P. B. and R. E. Scully (1988). "Uterine tumors with mixed epithelial and mesenchymal elements." Semin Diagn Pathol 5(2): 199-222.

The clinical and pathologic features and the differential diagnosis of uterine tumors containing mixed epithelial and mesenchymal elements are reviewed. The malignant mullerian mixed tumor (MMMT) is the most common neoplasm in this group, which also includes the mullerian adenofibroma and adenosarcoma, endometrial stromal neoplasms with focal epithelial differentiation, uterine tumors resembling ovarian sex cord tumors, and adenomyomas, including the atypical polypoid adenomyoma.

Maiman, M., J. C. Remy, et al. (1988). "Uterine rupture secondary to a malignant mixed mesodermal (mullerian) tumor: a case report." Gynecol Oncol 30(1): 137-42.

A case of uterine rupture resulting from tumor penetration of the myometrium in a patient with malignant mixed mesodermal tumor is described; the first in the literature known to the authors. Notable features include rapid progression of disease, hemoperitoneum, and diffuse intraoperative bleeding controlled by radiographic embolization.

Chang, S. Y., T. S. Lin, et al. (1988). "[Malignant mixed mullerian tumor of uterus--report of 3 cases]." Changgeng Yi Xue Za Zhi 11(2): 128-33.

Scioscia, A. L., M. J. Merino, et al. (1988). "Malignant mixed mullerian tumor of the uterus arising in association with a viable gestation." Obstet Gynecol 71(6 Pt 2): 1047-50.

Malignant mixed mullerian tumors of the uterus are rare neoplasms occurring predominantly in postmenopausal women. We report the prenatal course and diagnosis of a stage III malignant mixed mullerian tumor at cesarean section in a 35-year-old woman. Despite aggressive radiation and chemotherapy, the patient died 14 weeks after diagnosis and initial surgical therapy. The premature infant had an uneventful course.

Chen, C. J., H. C. Liu, et al. (1988). "[Malignant mixed mullerian tumor of the fallopian tube--a case report]." Zhonghua Yi Xue Za Zhi (Taipei) 42(1): 75-80.

Chen, K. T. and R. W. Wolk (1988). "Extragenital malignant mixed mullerian tumor." Gynecol Oncol 30(3): 422-6.

A case of extragenital malignant mixed mullerian tumor that appeared to represent a second primary tumor in a patient previously treated for disseminated ovarian serous papillary carcinoma is reported and compared with other reported cases of extragenital malignant mixed mullerian tumor.

Han, C. P., K. C. Chao, et al. (1988). "Malignant mixed mullerian tumor of uterine corpus." Zhonghua Yi Xue Za Zhi (Taipei) 42(1): 53-8.

Evinger-Hodges, M. J., J. Bresser, et al. (1988). "myc and sis expression in acute myelogenous leukemia." Leukemia 2(1): 45-9.

Several oncogenes have been reported to be expressed in normal and malignant hematopoietic cells. Since these studies have almost exclusively been done by Northern and dot blot hybridization techniques using mixed populations of cells, any conclusions concerning quantitative changes in gene expression are difficult to document. We have developed a rapid and sensitive RNA-in situ hybridization technique permitting detection of as few as five copies of mRNA per cell. Using this technique we have studied the expression of two genes, c-myc and c-sis, in acute leukemia patients as well as hematologically normal individuals. We have found that expression levels of myc and often sis are higher (greater than 5-fold) in hematopoietic cells obtained from leukemia patients than in normal hematopoietic cells. In regenerating marrow, there is a dramatic increase in the frequency of cells expressing myc at the level of five to 10 copies without the presence of any cells expressing myc at the high levels found in acute leukemia. This is completely different from leukemic remission marrow in which we find a subpopulation of cells which express myc at very high levels. At this time, the leukemic origin of this abnormal cell population is likely because of the close correlation we find between gene overexpression and leukemic phenotype as identified by double-labeling experiments. It appears that gene overexpression may be a more sensitive or an earlier marker for leukemic cells and that such an assay could be used in the detection of residual disease.

Kato, T., S. Teshima, et al. (1988). "The increasing trend in Japan of mullerian mixed tumor of endometrium." Jpn J Clin Oncol 18(4): 303-8.

An increasing trend in Japan of Mullerian mixed tumor (MMT) of the endometrium has been suspected from both the Annual Pathological Autopsy Records in Japan (APARJ) and an analysis of surgical cases from the National Cancer Center Hospital (NCCH). One hundred and four MMT cases were recorded in APARJ during the period, 1965-1984, which constituted 1.1% of all malignant uterine tumors. The number of MMT cases in the past 10 years (87 cases during the period, 1975-1984) increased more than fivefold over that of the previous 10 years (17 cases during the period, 1965-1974). The proportion among malignant uterine tumors also increased from 0.5 to 1.5%. Eighteen patients with MMT underwent surgery in the NCCH during the period, 1963-1986, which accounted for 4.3% of endometrial malignant tumor cases. Of these only one was resected during the 12-year period, 1963-1974, while there were 17 surgically resected cases during the 12 years from 1975 to 1986. These represented 0.8 and 5.7%, respectively of malignant tumors of the endometrium during the two periods. In five out of 18 cases, MMT occurred as a second primary malignancy, and in all cases the histology was one of mesodermal mixed tumor. It was suggested that its occurrence as a second primary malignancy would be contributing to the recent increase of MMT in Japan.

Nozaki, H., K. Tanaka, et al. (1988). "B-cell malignant lymphoma associated with monoclonal macroglobulinemia and cryoglobulinemia." Tokai J Exp Clin Med 13(4-5): 245-51.

A 55-year-old man was admitted to our hospital with fever, ascites, generalized lymphadenopathy and hepatosplenomegaly. A cervical lymph node was biopsied and diagnosed as a diffuse mixed cell type B-cell malignant lymphoma with positive cytoplasmic IgM in plasmacytoid lymphocytes and immunoblasts. Serum protein electrophoresis disclosed a monoclonal peak and immuno-electrophoresis identified the abnormal protein as IgM kappa(k). Serum immunoquantitation revealed an IgM level of 1470 mg/dl. Bence-Jones protein of the k type was positive in the urine. Cryoglobulin with the characteristics of IgM was present in the serum. In peripheral blood, hemoglobin was 12.4 g/dl, WBC 26,500/microliters with increased abnormal cells and the platelet count 2.2 x 10(4)/microliters. Low fibrinogen and high FDP levels indicated the existence of disseminated intravascular coagulation (DIC). Gabexate mesilate (FOY) was administered at a dose of 1,000 mg/day for the DIC with very good response. After one course of combination chemotherapy (vincristine, cyclophosphamide, prednisolone, adriamycin), he achieved complete remission. However, three months later, he showed icterus and anorexia again with high levels of serum GOT and GPT and positive HBs antigen. On the 117th hospital day, he became abruptly developed right hemiplegia and coma. Cranial CT demonstrated massive thalamic bleeding in the left hemisphere with ventricular rupture, and he died on the same day.

Auerbach, H. E., V. A. LiVolsi, et al. (1988). "Malignant mixed Mullerian tumors of the uterus. An immunohistochemical study." Int J Gynecol Pathol 7(2): 123-30.

Malignant mixed mullerian tumors (MMMT) of the uterus have been subdivided into two types: those with heterologous sarcomatous elements (e.g., rhabdomyosarcoma, and chondrosarcoma) and those with only homologous elements (e.g., stromal sarcoma). The distinction, which may have prognostic significance, was based on the identification by light microscopy of cells that exhibited definite cross-striations, cartilage, or osteoid production. We studied 32 cases of uterine MMMT to assess the value of immunohistochemical markers in delineating the sarcomatous and epithelial components. Of 32 cases, 11 showed heterologous sarcoma (6, rhabdomyosarcoma, and 5, chondrosarcoma), and the remaining 21 were homologous MMMT. Six antigens--desmin, myoglobin, S-100, alpha 1-antichymotrypsin (ACT), epithelial membrane antigen (EMA), and monoclonal cytokeratin (AE1 and AE3), (to test for possible myogenic, chondroid, fibrohistiocytic, and carcinomatous differentiation)--were analyzed by the avidin-biotin-peroxidase method. EMA was found in neoplastic cells in all cases; 31 of 32 cases showed keratin. Desmin reactivity was detected in 14 of 32 cases, whereas myoglobin was present in 10 of 32. Three cases exhibited S-100 positivity (two in areas of chondrosarcoma, and one in some stromal sarcoma cells). Twenty-two cases (69%) exhibited ACT reactivity. Several cases displayed a malignant fibrous histiocytoma pattern. These demonstrated ACT positivity in both the neoplastic spindle and giant cells. We conclude that immunohistochemical staining for the above mentioned antigens is a useful diagnostic aid in delineating the sarcomatous and carcinomatous elements in MMMT.

Barbazza, R., D. Infantolino, et al. (1988). "Malignant mixed mullerian tumor of the endometrium. Report of a case with cytological diagnosis." Eur J Gynaecol Oncol 9(5): 381-5.

A case is reported of malignant mixed mesodermal tumor of the uterus in a postmenopausal 56 year-old woman presenting vaginal bleeding and who was cytologically diagnosed with an endometrial aspirate. The cytologic examination of smears showed the presence of two different cellular types: adenocarcinomatous and sarcomatous (some with evident cross striations). The patient underwent total hysterectomy with lymphadenectomy. Histologically, a malignant mixed Mullerian tumor was confirmed. Cytological, histological, histochemical and immunohistochemical features are described in detail together with the main differential diagnosis.

Deligdisch, L., S. Plaxe, et al. (1988). "Extrauterine pelvic malignant mixed mesodermal tumors. A study of 10 cases with immunohistochemistry." Int J Gynecol Pathol 7(4): 361-72.

Ten cases of extrauterine malignant mixed mesodermal tumors (MMMTs), nine ovarian, and one pelvic, are presented. One patient had a purely epithelial primary ovarian tumor and MMMT in her recurrent tumors. All the other patients had MMMT in their primary and recurrent tumors. Eight patients had heterologous MMMT including cartilage, striated muscle, and adipose tissue in one case. Two patients had homologous MMMT. All cases presented with metastases involving abdominal organs that were either MMMT or epithelial neoplasms and MMMT. Five patients had recurrent tumors, one extensively involving the spleen. In all recurrent tumors, the mesenchymal components were considerably more abundant than in the primary tumors. Immunohistologic studies of intermediate filaments were performed in seven cases, revealing cytokeratin-positive epithelial structures, vimentin-positive mesenchymal (including cartilaginous) structures, as well as coexpression of cytokeratin and vimentin in anaplastic and giant tumor cells in some cases. Some anaplastic spindle cells, which on routine stains were suggestive of stromal cells, stained positive for cytokeratin, thus identifying their epithelial nature. Desmin staining performed in five cases showed positive staining of rhabdomyoblasts in only one case. Myoglobin staining performed in seven cases was positive in four. The histogenesis from primitive mullerian structures and the natural history of these uncommon neoplasms are discussed in light of the pathological and immunohistochemical data presented.

Engdahl, E. and U. Wolfhagen (1988). "Carcinofibroma--a rare variant of mixed mullerian tumor." Acta Obstet Gynecol Scand 67(1): 85-8.

We report a case of an endometrial neoplasm of Mullerian origin, consisting of a malignant epithelial component and a benign stromal component. Only 3 similar cases have been described previously. By comparative study of other, more common mixed Mullerian tumors, we have tried to determine the behavior and management of this neoplasm.

Nishida, T., T. Obuchi, et al. (1988). "Extragenital malignant mixed Mullerian tumor: a case report." Kurume Med J 35(4): 201-5.

Rodriguez-Escudero, F. J., M. Martin Mateos, et al. (1988). "Malignant mixed mullerian tumor of the cervix in a 12-year-old girl." Eur J Gynaecol Oncol 9(5): 365-9.

The Authors present the first known case of Malignant Mixed Mullerian Tumor arising in the cervix of a 12-year-old girl. This tumor is rare, and the histogenesis uncertain. The most common localization is in the uterine corpus. The size of the tumor is presented and also the most relevant microscopic characteristics. The course followed by the disease and the treatments performed are also discussed.

Schroder, H., K. B. Jensen, et al. (1987). "Lack of correlation between methotrexate concentrations in serum, saliva and sweat after 24 h methotrexate infusions." Br J Clin Pharmacol 24(4): 537-41.

1 Methotrexate (MTX) concentrations were studied in serum, mixed saliva and sweat during and after 24 h continuous MTX infusions (0.5-6 g m-2) in 14 patients with various malignant diseases. 2 The serum-MTX concentrations declined in a biphasic manner, but the MTX elimination in saliva and sweat varied to a much greater extent. 3 Saliva/serum and sweat/serum ratios during the MTX infusion were 2.3% and 0.55% respectively. The ratios had increased significantly 20 and 44 h postinfusion. 4 No correlations were demonstrated between salivary- and serum-MTX concentrations during the MTX infusion or 20 and 44 h later. 5 Markedly delayed renal MTX excretions were demonstrated in two patients. In one of them the salivary MTX elimination was also retarded, whereas this was not seen in the other one. 6 We conclude that measurements of MTX concentrations in mixed saliva cannot substitute for serum-MTX determinations in the monitoring of patients after 24 h MTX infusions.

Buchino, J. J. (1987). "Malignant mixed mullerian tumor of the fallopian tube." Arch Pathol Lab Med 111(4): 386-7.

Malignant mixed mullerian tumor of the fallopian tube is an extremely rare neoplasm, with less than 30 cases reported. Clinical signs and symptoms are usually nonspecific and include lower abdominal pain, fever, and vaginal bleeding. The age at diagnosis varies from 14 to 76 years, with a mean of 55 years. Prognosis is poor, with only one woman surviving more than five years. Surgery is the treatment of choice, although chemotherapy may be of some benefit.

Agdal, N. and C. Wilken-Jensen (1987). "Adenosarcoma uteri." Acta Obstet Gynecol Scand 66(2): 183-4.

Adenosarcoma of the uterus is a rare tumor of low-grade malignancy. It belongs to the family of mixed mesodermal (Mullerian) tumors. It is a biphasic tumor with benign epithelium and malignant stromal components. A case in a 76-year-old woman is presented.

Carson, D. A., P. P. Chen, et al. (1987). "Rheumatoid factor and immune networks." Annu Rev Immunol 5: 109-26.

Rheumatoid factors represent a normal component of the immune network. The autoantibodies promote complement fixation and clearance of immune complexes. They amplify the avidity of polyclonally induced IgG. Genes related to the primary structure of rheumatoid-factor light chains are widely distributed in the human population and have been conserved during the evolution and dispersion of the species. Products of these genes may be detected with anti-idiotypic antibodies against synthetic peptides corresponding to individual hypervariable regions on rheumatoid-factor light chains. Such anti-peptide antibodies provide unique reagents for analyzing the genetics of immunoglobulins in outbred populations. Precursors of rheumatoid factor are abundant among immature B lymphocytes. Some of these cells may tend to localize to mucosal surfaces, where they are stimulated directly by pathogenic microorganisms with polyclonal B cell-activating properties. Synthesis of rheumatoid factor regularly accompanies all secondary immune responses but is usually transient. Production of the autoantibody is T-cell dependent. The T cells may recognize antigen in an IgG-antigen immune complex that is processed and presented by B-cell precursors of rheumatoid factor. Rheumatoid factor-associated light-chain idiotypes are rare in serum IgG and on IgG myeloma proteins. They are common among monoclonal IgM proteins and on the surface of the malignant B cells from patients with chronic lymphatic leukemia. The rheumatoid factors that are produced by patients with mixed cryoglobulinemia, or primary Sjogren's syndrome can share idiotypic antigens with monoclonal rheumatoid factors. Rheumatoid factor synthesis in the diseases may reflect an abnormal proliferation of B-cells that is not antigen-driven and that can degenerate into malignancy. The rheumatoid factors in patients with rheumatoid arthritis are diverse and almost certainly represent the outcome of antigen-induced, T cell-dependent mechanisms. The antigens that drive the T cells have not been identified but could represent exogenous microorganisms, self components, or idiotypic antigens that fortuitously interact with rheumatoid factors.

Fetissof, F., B. Arbeille, et al. (1987). "[Malignant mixed mesodermal tumor with endocrine cells of the corpus uteri]." Ann Pathol 7(4-5): 311-4.

A case of uterine malignant mixed mesodermal tumor harboring endocrine cells is reported. Endocrine cells were immunocharacterized as serotonin, somatostatin and pancreatic polypeptide cells. This variety of mixed mullerian tumor is added to other endocrine cells-containing neoplasms of the uterus.

Mukherji, B., A. L. Nashed, et al. (1986). "Regulation of cellular immune response against autologous human melanoma. II. Mechanism of induction and specificity of suppression." J Immunol 136(5): 1893-8.

The cytotoxic immune response in the peripheral blood lymphocytes (PBL) against an autologous malignant melanoma cell line, PJ-M, was found to be down-regulated in in vitro co-culture (IVC) selectively by unfractionated resident lymph node lymphocytes (derived from a lymph node infiltrated with the PJ-M melanoma cells) and T4+ as well as T8+ fractions of the resident lymph node-derived lymphocytes. In this study, the mechanism involved in, and the specificities of, cytotoxic immune response in this autologous system were examined at population and clonal levels. Resident lymph node lymphocytes were isolated from both involved and uninvolved lymph nodes from the same patient. Resident lymphocytes from both sources regulated the generation of cytotoxic immune response when both types of resident lymph node lymphocytes were further sensitized against the PJ-M cells in IVC and were expanded in interleukin 2 (IL 2). An IL 2-dependent homogeneous lymphocyte line (I-10:1) bearing the phenotype of a helper T cell (T4+) and a T4+ clone (I-10.3) of the I-10:1 line, established by limiting dilution culture, also down-regulated the generation of cytotoxic immune effector cells in the PBL in IVC against the PJ-M targets. The IL 2-dependent T4+ inducer line I-10:1 generated a functionally differentiated T8+ suppressor population(s) that, in turn, could abrogate cytotoxic response in fresh PBL in IVC against PJ-M cells. The inducer line I-10:1 and its subclone I-10.3 suppressed the generation of cytotoxic effector cells in the PBL in IVC selectively against the autologous PJ-M cells. Generation of cytotoxic allo-response in IVC was unaffected by the inducer lines. These results provide further evidence for the involvement of the regulatory network in cytotoxic immune response in an autologous human tumor system, and suggest a potential explanation for cytotoxic unresponsiveness against autologous melanoma cells.

Matsui, Y., D. E. Staunton, et al. (1986). "Comparison of MHC antigen expression on PHA- and MLC-induced T cell lines with that on T and B lymphoblastoid cell lines by cell cycle dependency." Hum Immunol 15(3): 285-301.

Although it is well known that the expression of major histocompatibility complex (MHC) antigens on the surface of lymphoblastoid cell lines are cell cycle dependent, the way in which the MHC antigen expression on activated T cells varies with cell cycle phase has not previously been described. Using 11 lymphoblastoid cell lines from malignant and nonmalignant tissues (B cells, T cells, and myeloid cells) and five activated T cell lines (two cell lines activated by phytohemagglutinin and three alloreactive T cell clones), MHC antigen expression was quantitatively studied by dual-beam flow cytometry. Correlated measurements of surface antigen quantity (immunofluorescence), DNA content (Hoechst 33342), and cell size (light scatter), uninfluenced by induction synchrony and cell fixation, were performed. The data indicate that cell surface antigen quantity and cell surface area demonstrate specific values at each phase of the cell cycle when the cells are in logarithmic growth. Examining cells in logarithmic growth, it was confirmed, for all lymphoblastoid cell lines, that the quantity of MHC antigens on G2 (S + G2 + M) cells was greater than that on G1 cells. In addition, it was found, by analyzing antigen quantity and surface area, that class I antigen density in the G2 phase is 17% less than that in the G1 phase in leukemic T cell lines, and that both class I and class II antigen densities in the G2 phase were 21% less than that in the G1 phase in lymphoblastoid B cell lines. In activated T cells, class I antigen density in the G2 phase was 11% less than that in the G1 phase, while class II antigen density in the G2 phase was 12% greater than that in the G1 phase. We describe four important observations in this report. In both G1 and G2 phases, activated T cells express: quantitatively fewer class I antigens than lymphoblastoid B cell lines; similar quantity of class I antigens as that of leukemic T cell lines; and similar quantity of class II antigens as that of lymphoblastoid B cell lines. Also, class II antigens are expressed in greater density in the G2 phase than in the G1 phase in activated T cells. In contrast, lymphoblastoid B cell lines express greater density of class II antigens in the G1 phase than in the G2 phase of the cell cycle. These findings differ from previous reports, suggesting that G1 phase cells may have a more significant role than G2 phase cells as target cells for MHC restricted cytotoxic cells.

Kajino, T., K. Kanazawa, et al. (1986). "[Effect of oncofetal antigen-I (OFA-I) on lymphocyte response in pregnant women]." Nippon Sanka Fujinka Gakkai Zasshi 38(6): 845-52.

OFA-I, a membrane antigen on human malignant melanoma cells, was reported to be also found on a fetal brain tissue and to have a highly immunogenic effect on a pregnant woman. The aim in this study is to analyse an immunologic activity of OFA-I on in vitro response of lymphocytes from pregnant women. OFA-I was prepared from M-14 cells which are an in vitro cell line originating in a human malignant melanoma and purified by affinity column chromatography using the antibodies which were prepared from ascites of an embryonal carcinoma patient and exhibited anti-OFA-I activity in immune adherence test. The results obtained were as follows: No significant effect of OFA-I was found on PHA-induced lymphocyte response. A suppressive effect of OFA-I was observed on an unidirectional mixed lymphocyte culture (MLC) between a wife and husband when OFA-I was added at a concentration of more than 0.1 micrograms/ml. It was also suggested that the effect was attributable to inhibition in an initial phase of MLC. A suppressive effect of OFA-I was observed on Ig production of PWM-stimulated lymphocytes at a final concentration of more than 0.25 micrograms/ml. There was no significantly difference between the effect in pregnant and non-pregnant women. Furthermore, the effect was demonstrated to be mediated with macrophages in the culture system. From these findings, it was implied that OFA-I might play an important role in maternal immune recognition in the feto-placental unit.

Geszler, G., C. A. Szpak, et al. (1986). "Prognostic value of peritoneal washings in patients with malignant mixed mullerian tumors of the uterus." Am J Obstet Gynecol 155(1): 83-9.

Peritoneal washings from 36 women with all pathologic stages of mixed mullerian tumors of the uterus (27 homologous stroma, nine heterologous stroma) were reviewed in a blinded retrospective fashion for the presence and type of malignant cells collected. Malignant tumor cells were demonstrated in the washings of 16 patients; 13 contained adenocarcinoma only, two contained adenocarcinoma and sarcoma, and one contained sarcoma cells only. Cox's logistic regression analysis showed that cytologic examination of peritoneal washings when combined with pathologic staging provides a statistically significant discriminant of disease-free survival. Patients with a favorable prognosis (pathologic Stage I and peritoneal washings free of malignancy) had sevenfold increased disease-free survival compared with survival of the patients with an unfavorable prognosis (pathologic Stages II, III, or IV or malignant cells present in peritoneal washings). Three of the 18 patients with pathologic Stage I disease manifested malignant tumor cells in the peritoneal washings and all three patients died of disease in less than 1 year. The presence of malignant cells in peritoneal washings in patients with mixed mullerian tumor apparently limited to the uterus suggests a clinical course that is similar to that of those with more advanced disease.

Spanos, W. J., Jr., L. J. Peters, et al. (1986). "Patterns of recurrence in malignant mixed mullerian tumor of the uterus." Cancer 57(1): 155-9.

Of 120 patients treated definitively at University of Texas System Cancer Center, M. D. Anderson Hospital for malignant mixed mullerian tumor of the uterus, 67 had their tumors recur. These patients were analyzed for recurrence pattern and response of recurrence to treatment. The most frequent sites of recurrence were the lung and abdomen, accounting for 66% of all first-site recurrences and 80% of all first-site distant metastases. Locoregional recurrences were much less frequent, accounting for 18% of recurrences. There was no apparent change in recurrence pattern with the addition of adjuvant chemotherapy. The effect of adjuvant radiation could not be assessed, because 95% of patients treated surgically received adjunctive radiation. The survival after treatment of recurrence was shortest for patients with bone, brain, or liver metastases (median, 4 months). There were four long-term survivors (more than 36 months). Patients with resectable recurrences had the highest response rates. Response to chemotherapy alone was uniformly poor (6% response rate).

Chumas, J. C., L. Thanning, et al. (1986). "Malignant mixed mullerian tumor arising in extragenital endometriosis: report of a case and review of the literature." Gynecol Oncol 23(2): 227-33.

A primary malignant mixed Mullerian tumor (MMMT) was found in the wall of the rectum of a 67-year-old female. The uterus, fallopian tubes, and ovaries had been previously excised for benign disease. The tumor was associated with foci of benign endometriosis. A literature review of extragenital MMMTs indicates that these are extremely rare tumors. This case supports the theory that endometriosis may serve as a progenitor to extraendometrial malignancy.

Young, R. H. and R. E. Scully (1986). "Testicular and paratesticular tumors and tumor-like lesions of ovarian common epithelial and mullerian types. A report of four cases and review of the literature." Am J Clin Pathol 86(2): 146-52.

Three new and eleven previously reported testicular or paratesticular tumors that resembled ovarian tumors of common epithelial type are discussed. The 14 tumors occurred in patients ages 11-68 (average 47) years of age. The exact location for 12 of the tumors is known; 5 involved primarily the testicular parenchyma, 3, the tunica vaginalis, and 4, paratesticular tissue. Five tumors were serous, four of which were in the borderline category. Four tumors were Brenner tumors, admixed in one case with an adenomatoid tumor. Single examples of mucinous cystadenoma, mucinous cystadenocarcinoma, endometrioid adenoacanthoma, clear cell adenocarcinoma, and a benign tumor of mixed cell types complete the list. Follow-up of from 3 months to 14 years is available in eight cases; only one tumor, the clear cell adenocarcinoma, is known to have been clinically malignant. A fourth lesion in this article was a paratesticular mass composed of endometrial glands and stroma and bundles of smooth muscle. It arose in an 82-year-old man who had been treated with estrogens for prostatic adenocarcinoma.

Liao, S. Y. and B. H. Choi (1986). "Expression of glial fibrillary acidic protein by neoplastic cells of mullerian origin." Virchows Arch B Cell Pathol Incl Mol Pathol 52(2): 185-93.

Immunocytochemical studies of malignant mixed Mullerian tumors revealed the presence of neoplastic cells showing strong immunoreactivity for glial fibrillary acidic protein, a protein specific for astrocytes, in 9 of 13 cases. Undifferentiated malignant tumor cells of endometrial stromal sarcoma and astrocytes in glioma of the uterus also demonstrate GFAP immunoreactivity. GFAP immunostaining in these neoplastic cells is highly specific and shows no cross-reactivity with cytokeratin, actin, myoglobin, epithelial membrane antigen or factor VIII. It is postulated that the GFAP immunostaining within neoplastic cells of Mullerian origin may be a reflection of the phenotypic diversity of intermediate filament proteins that can be expressed by malignant neoplastic cells, that the polypeptides of GFAP may be heterogeneous, that there may be an ontogenic relationship between the cells of Mullerian origin and neuroectodermal cells, or that this may represent neometaplasia of Mullerian cells.

Sugai, S., S. Shimizu, et al. (1986). "Lymphoproliferative disorders in Japanese patients with Sjogren's syndrome." Scand J Rheumatol Suppl 61: 118-22.

Fourteen Sjogren's syndrome (SS) patients with monoclonal gammopathy (MG), 4 SS patients with malignant lymphoma (ML) and one with pseudolymphoma (PL) were described. Among the 14 MG patients, the IgG class was found in 3, IgA in 6, IgM in 3, and 2 M proteins (IgM/IgG and IgA/IgG) were found in 2 patients. The monoclonal rheumatoid factor (RF) was found in 4 patients (3 IgA and one IgM). Idiotypes (Id) of M proteins were studied in 11 out of 14 patients. The histology of ML showed the diffuse, large cell, medium-sized cell and follicular, mixed cell type. The monoclonal surface membrane Ig (SmIg) and/or cytoplasmic Ig (CIg) were identified (3 IgM and one IgG). A review of the Japanese literature on lymphoproliferative disorders (LPD) in SS patients disclosed additional 15 MG patients (3 IgG, 5 IgA, 6 IgM and one Bence Jones protein) and 22 LPD patients (14 non-Hodgkin's ML, 4 PL, 2 plasmacytomas and 2 thymomas). The literature was also reviewed on LPD in non-Japanese SS patients; 26 patients with MG (4 IgG, 2 IgA, 19 IgM and one Bence Jones protein) and 104 patients with LPD (59 non-Hodgkin's ML, 4 Hodgkin's lymphomas, 23 PL, 5 thymomas, 4 immunoblastic lymphadenopathies (IBL), 2 Lennert's lymphomas and 7 others) were found. These results indicate that non-IgM class MG was more dominant in Japanese than in non-Japanese SS patients and that there was a higher incidence of MG in primary than in secondary SS patients, and also that B cell lymphomas (9 in Japanese and 11 in non-Japanese) were more common in SS patients.

Kawagoe, K. (1985). "A case of mixed mesodermal tumor of the uterus with alpha-fetoprotein production." Jpn J Clin Oncol 15(3): 577-83.

A case of mixed mesodermal tumor of the uterus with alpha-fetoprotein (AFP) production in a postmenopausal woman is reported, with special reference to its histogenesis. Judging from the serum AFP levels, the AFP content of the tumor and immunohistochemical localization of AFP in the tumor, AFP was produced by the tumor. The observation that in this patient AFP existed exclusively in carcinoma cells strongly supports the hypothesis that malignant transformation of Mullerian epithelial and stromal cells in mixed mesodermal tumors of the uterus occurs independently after the primitive mesenchymal cells have differentiated towards epithelial and stromal components.

Press, M. F. and R. E. Scully (1985). "Endometrial "sarcomas" complicating ovarian thecoma, polycystic ovarian disease and estrogen therapy." Gynecol Oncol 21(2): 135-54.

Unopposed endogenous and exogenous estrogenic stimulation has been considered by most investigators to have a role in the pathogenesis of carcinoma of the endometrium. Although a few cases of "sarcomas" of the endometrium that had developed in an estrogenic setting have been reported, a clear-cut association between estrogenic stimulation and these forms of endometrial cancer has not been established. We report six cases of endometrial sarcomas complicating ovarian thecomas, polycystic ovarian disease, or prolonged estrogen therapy. Three ovarian thecomas, which are considered to be estrogenic tumors, were associated with endometrial malignant mullerian mixed tumor, mullerian adenosarcoma, and low-grade stromal sarcoma in postmenopausal women. Polycystic ovarian disease, a condition characterized by unopposed estrinism due to the peripheral conversion of excessive androstenedione to estrone, was found in a 27-year-old infertile woman with an endometrial malignant mullerian mixed tumor. A pure osteogenic sarcoma of endometrial stromal origin developed in a 28-year-old woman with gonadal dysgenesis (Turner's syndrome) who had received estrogens for 18 years. The sixth woman, with an empty sella turcica after radiation therapy of a pituitary adenoma, had an endometrial mullerian adenosarcoma at the age of 40 years after 16 years of estrogen therapy. None of these patients had had pelvic radiation therapy. The evidence from this series of cases and from six additional cases identified in the literature suggests that the risk of endometrial sarcomas may be increased by estrogen therapy or endogenous disorders that lead to unopposed estrogenic stimulation of the uterus.

de Jong, A. S., M. van Kessel-van Vark, et al. (1985). "Skeletal muscle actin as tumor marker in the diagnosis of rhabdomyosarcoma in childhood." Am J Surg Pathol 9(7): 467-74.

Immunoaffinity-purified and tissue-specific antibodies against carp skeletal muscle actin have been assessed for their usefulness in diagnosing rhabdomyosarcoma. Routinely processed formaldehyde-fixed tissue and the avidin--biotinyl--peroxidase complex technique were used. Thirty-six tumors of patients varying in age from less than 1 year to 17 years were diagnosed as rhabdomyosarcoma on the basis of routine histological stains or electron microscopy, and on clinical grounds. Among them were 20 poorly differentiated tumors. All moderately and well-differentiated rhabdomyosarcomas and the majority of the poorly differentiated tumors (13 of 20) showed positive immunostaining for actin. Positive staining was observed in all three types of rhabdomyosarcoma, i.e., embryonal, alveolar, and pleomorphic. Besides rhabdomyosarcomas, the only other positive neoplasms were those that contained rhabdomyoblastic differentiation such as malignant "triton" tumors and malignant mixed mullerian tumors. Our results indicate that antibodies against skeletal muscle actin are a powerful tool for diagnosing rhabdomyosarcoma and that they can be used to distinguish the poorly differentiated forms from other types of small round cell tumors in childhood such as neuroblastoma, Ewing's sarcoma, and malignant lymphoma. The results are discussed in the light of the embryogenesis of cross-striated skeletal muscle.

Ulbright, T. M. and L. M. Roth (1985). "Metastatic and independent cancers of the endometrium and ovary: a clinicopathologic study of 34 cases." Hum Pathol 16(1): 28-34.

Twenty-one of 34 simultaneous cancers involving the endometrium and ovary were classified as endometrial primary tumors with ovarian metastases. The criteria for this classification were either a multinodular ovarian pattern (major criterion) or two or more of the following minor criteria: small (less than 5 cm) ovary(ies), bilateral ovarian involvement, deep myometrial invasion, vascular invasion, and tubal lumen involvement. Twelve cancers were classified as independent neoplasms, primarily by the absence of the above criteria. Although they were classified as independent, the histologic features of the endometrial and ovarian tumors were the same in 11 of these 12 cases. Only one case represented an ovarian primary tumor with an endometrial metastasis. Both the group believed to have endometrial primaries with ovarian metastases and that with independent primaries showed high incidences of associated endometrial hyperplasia, supporting the belief that the endometrium is a primary site in both groups. The cancers classified as metastatic, with no known spread outside the endometrium-myometrium and ovary, were found to involve other sites significantly (P less than 0.01) more frequently than those classified as independent. Grade 3 endometrioid carcinoma, adenosquamous carcinoma, and malignant mixed mullerian tumors occurred only in the metastatic group, whereas the independent group had a variety of endometrioid and nonendometrioid tumors.

Nouwen, E. J., D. E. Pollet, et al. (1985). "Human placental alkaline phosphatase in benign and malignant ovarian neoplasia." Cancer Res 45(2): 892-902.

In benign and malignant ovarian tumor patients, human placental alkaline phosphatase (HPLAP) was determined in serum and extracts from surgical tumor biopsies using a highly specific enzyme-antigen immunoassay based on a mouse monoclonal antibody (E6) to HPLAP. Serum HPLAP levels greater than or equal to 0.1 unit/liter were found in 58% of ovarian cancer patients. Serum carcinoembryonic antigen levels were positive (greater than 5.4 ng/ml) in 17% of these patients. HPLAP was detected in extracts from 13 of the 14 tumors investigated (range, 2.4 to 557 milliunits/g). Only the mixed heterologous Mullerian sarcoma was negative. The highest HPLAP content of normal ovarian tissue was 1.1 milliunits/g. The amount of heat-stable and L-p-bromotetramisole-insensitive alkaline phosphatase was in all cases much higher than the fraction recognized by E6. The neoplastic origin of HPLAP was confirmed immunohistochemically on paraffin sections by an indirect avidin-biotin-peroxidase staining procedure using E6. The staining pattern was compared to the histochemical distribution of total alkaline phosphatase on adjacent sections. A consistency was found between the amount of HPLAP in tissue extracts and its immunohistochemical distribution. In all the tumors, staining for HPLAP was observed mainly on the plasma membranes of carcinoma cells. In 9 of the 10 carcinomas, the histological distribution of HPLAP and also of total alkaline phosphatase was heterogeneous. HPLAP staining, present in one of five normal ovaries, was restricted to germinal inclusion cysts. The present results support the hypothesis that serous ovarian tumors originate from these cysts.

Robins, E. J., A. S. Breathnach, et al. (1985). "Ultrastructural observations on the effect of azelaic acid on normal human melanocytes and a human melanoma cell line in tissue culture." Br J Dermatol 113(6): 687-97.

Azelaic acid has been shown clinically to have a cytotoxic effect on the abnormally active and malignant human melanocyte, but it has no apparent effect upon normal melanocytes. This difference in reactivity between normal and abnormal cells in vivo is further examined here in vitro. The disodium salt of azelaic acid (C(9)2Na) was added to pure and mixed cultures of normal human melanocytes and to cultured human melanoma cells, at 10(-3) M, 10(-2) M, 5 X 10(-2) M, and 10(-1) M for 1 and 6 h. Control cultures and cultures exposed to the same concentrations of the disodium salt of adipic acid (C(6)2Na) were also examined. No damage to cells of any line was observed with diacids at 10(-3) M or 10(-2) M up to 6 h. At 5 X 10(-2) M some mitochondria of melanoma cells appeared swollen. With C(6)2Na at 10(-1) M for I and 6 h, minimal swelling of mitochondria was observed in some cells of all lines. Pure normal melanocytes and melanocytes of mixed cultures exhibited greater swelling of mitochondria with 10(-1) M C(9)2Na at 1 and 6 h, but the mitochondria of the malignant melanocytes were massively swollen with destruction of cristae. Plasma and nuclear membranes and membranes of rough endoplasmic reticulum were intact, but Golgi membranes exhibited vesiculation. These results provide further evidence that azelaic acid damages the human malignant melanocyte and that one of its targets is the mitochondrion. Damage to normal melanocytes, found here, may be due to the fact that, in culture, they are more active than in intact epidermis.

Stenback, F. and V. M. Wasenius (1985). "Basement membrane structures in tumors of the ovary." Eur J Obstet Gynecol Reprod Biol 20(6): 357-71.

The location and amount of the basement membrane (BM) components collagen IV and laminin were studied in ovarian epithelial, sex cord-stromal and germ cell tumors. BM structures were found in the epithelial stromal interface of benign surface epithelial tumors and, though discontinuous, around well-differentiated tumor islets, being less well developed in invasive undifferentiated neoplasms. The stromal components in Mullerian mixed tumors had less distinct BM structures, a finding useful for the classification of these neoplasms. Thecomas and fibromas had scanty collagen IV and laminin; granulosa cell tumors contained large amounts of BM material. A fine diffuse BM-positive pattern occurred in dysgerminomas and endodermal sinus tumors; BM structures in cystic teratomas were distinct. Collagen IV and laminin were well-developed in benign and slow-growing tumors with epithelial components and in their metastases, but less distinct in stromal tumors and highly malignant undifferentiated tumors, showing the usefulness of this method for the clinical and biological classification of such tumors.

Chen, K. T. (1985). "Rhabdomyosarcomatous uterine adenosarcoma." Int J Gynecol Pathol 4(2): 146-52.

A case of rhabdomyosarcomatous adenosarcoma of the uterine cervix is described and the literature reviewed. This variant of adenosarcoma does not appear to be more malignant than other adenosarcomas. It can and should be differentiated from embryonal rhabdomyosarcoma and malignant mixed mullerian tumor because of the different prognostic implications and therapeutic approaches.

Bale, P. M. (1984). "Sacrococcygeal developmental abnormalities and tumors in children." Perspect Pediatr Pathol 8(1): 9-56.

Lesions from the SC region of children examined histologically at the RAHC were: 1. Malformations almost always associated with spina bifida aperta or occulta: 183 myelomeningocele (MM), 32 meningocele (M), 35 lipoMM and lipoma, 19 dermoid cyst, six occult meningocele, two Pacinian hamartoma, one short filum, four hindgut cysts or sinuses, two tailgut cysts, and two epithelial heterotopia. 2. Neoplasms, usually without spina bifida: 56 teratomas (11 malignant), five ependymomas (two purely subcutaneous), and 14 miscellaneous primary malignancies, (most neuroblastoma and rhabdomyosarcoma). Distinction between MM with glial tissue and M without glial tissue is important as M had a much better prognosis, less than a third developing hydrocephalus, and 77% walking unaided. Of those with glial tissue, the eight without Arnold-Chiari malformation were myelocystocele associated with cloacal exstrophy (six), caudal regression syndrome (one), and microcephaly (one). Postsacral glial tissue without paraplegia may occur with a subcutaneous vestige of filum terminale, or with herniation of the nonfunctioning half of a diplomyelia. Of postsacral "lipomas" and dermoids, 70% had an intraspinal connection through an occult spina bifida. This posterior vertebral defect is easily overlooked as the arches normally may not ossify until after 6 years. Therefore, the pathologist receiving a postsacral specimen may wish to alert the clinician to the high incidence of late effects from an occult intraspinal component or tethering of the spinal cord. Transsacral hindgut herniations and cysts probably result from ectoendodermal adhesions. Presacral multicystic malformations with mixed squamous and mucus cell lining are probably tailgut remnants or anorectal duplications, and may be mistaken for dermoid or teratoma. In SC teratoma in infants, contrary to some reports on ovarian teratoma in adults, immature tissues do not indicate a worse prognosis. Malignancy is virtually confined to teratomas including a carcinomatous or "yolk sac" component. It is more common in predominantly presacral examples and rare before the age of 4 months. SC ependymoma differs from ependymoma elsewhere in that it may be primary outside the craniospinal cavity (presacral or postsacral), may have a myxopapillary pattern special to the region, and although low-grade and slow growing, is more likely to metastasize beyond the central nervous system. Postsacral examples arise from vestiges of the filum terminale which are normal in the subcutis there. Combinations of all these lesions occur with vertebral defects and with each other.(ABSTRACT TRUNCATED AT 400 WORDS)

Okamura, J., M. Letarte, et al. (1984). "Augmentation of mixed lymphocyte response. Stimulatory activity by phorbol ester." J Clin Immunol 4(3): 228-34.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a variety of phenotypic changes on normal and malignant cells. In chronic and acute lymphocytic leukemia we have observed a marked augmentation in mixed lymphocyte reaction stimulatory capacity (MLRs) following pretreatment of leukemia blasts with TPA. We have now characterized the effects of TPA on MLRs utilizing the non-T, non-B lymphoblastic leukemia-cell line, HOON. Following pretreatment with TPA (optimal concentration, 1.6 X 10(-10) M), but not with other phorbol esters, there was a marked increase in MLRs, particularly at lower stimulator-cell concentrations. This effect was maximal following a 44-hr preincubation period and the enhancement in MLRs was not accompanied by changes in levels of Ia expression. This cell line provides a model for determining the molecular basis for the TPA-induced augmentation of stimulatory capacity in the mixed lymphocyte reaction.

Jong, A. S., M. van Vark, et al. (1984). "Myosin and myoglobin as tumor markers in the diagnosis of rhabdomyosarcoma. A comparative study." Am J Surg Pathol 8(7): 521-8.

Antibodies against the myosin heavy chain of adult chicken pectoral muscle and heart muscle which cross-react with myosin of human fast type II fibers ( antifast myosin) and slow type I fibers ( antislow myosin), respectively, and antibodies against human myoglobin have been assessed for their usefulness in diagnosing rhabdomyosarcoma. Formaldehyde-fixed and paraffin-embedded tissue and the avidin-biotinyl-peroxidase complex technique were used. Of 23 rhabdomyosarcomas studied, 20 were positive with antifast myosin and 11 with antimyoglobin . All tumors were negative with antislow myosin. Positive staining was observed in all three types of rhabdomyosarcoma, i.e., embryonal, alveolar, and pleomorphic, regardless of the antiserum used. Staining with antimyoglobin was generally limited to the cytoplasm-rich tumor cells. Besides rhabdomyosarcomas, the only other positive neoplasms were those which contained rhabdomyoblastic differentiation such as malignant Triton tumors and malignant mixed mullerian tumors. Our results indicate that antibodies against the fast myosin heavy chain are a useful tool for diagnosing rhabdomyosarcoma and that they can be used to distinguish that tumor from other small round cell tumors in childhood. The results are discussed in the light of the embryogenesis of skeletal muscle.

Morrow, C. P., G. d'Ablaing, et al. (1984). "A clinical and pathologic study of 30 cases of malignant mixed mullerian epithelial and mesenchymal ovarian tumors: a Gynecologic Oncology Group study." Gynecol Oncol 18(3): 278-92.

Between November 1971 and June 1980, thirty patients with primary malignant mixed mullerian tumors of the ovary were entered into a Gynecologic Oncology Group registry and treatment protocol. The mean age of the patients is 60.4 years. Six were Stage II, twenty-three were Stage III, and one patient had Stage IV disease. Among the 30 cases, 15 were designated carcinosarcomas (CS) and 15 were mixed mesodermal sarcomas (MMS). Twenty-three of the thirty study patients died from 1 to 16 months following their initial surgery. Two of the seven living patients have persistent cancer at 11 and 54 months. Four patients were alive and well at 6, 11, 22, and 32 months at the close of the study. Of the 12 patients receiving vincristine, dactinomycin, and cyclophosphamide (VAC) with (8 cases) or without (4 cases) radiation therapy (RT), there were two clinical complete responses; both died with disease at 6 and 16 months. One of the six patients receiving adriamycin had a complete response (CR). She is alive with disease at 11 months. There was no apparent difference in the survival or stage distribution among the cases with CS and MMS. Survival was somewhat better for the patients with earlier stage disease or smaller residual tumor burden.

Zhu, R. L. (1984). "[An analysis of 29 cases of malignant mixed mullerian tumor]." Zhonghua Fu Chan Ke Za Zhi 19(3): 155-7, 191.

Spanos, W. J., Jr., J. T. Wharton, et al. (1984). "Malignant mixed Mullerian tumors of the uterus." Cancer 53(2): 311-6.

One hundred and eight patients with a diagnosis of malignant mixed mullerian tumors of the uterus treated at the M.D. Anderson Hospital from 1948 through 1977 were analyzed. Pathology was reviewed and subdivided according to the sarcomatous element. No difference in pattern of recurrence or survival could be demonstrated between homologous, heterologous, or undifferentiated sarcomatous elements. Nine patients were treated with only palliative intent due to advanced local disease combined with poor medical condition. Of the remaining 99 patients, 87% had minimum surgical procedures of total abdominal hysterectomy. All but two of these patients had adjunctive radiation either preoperatively or postoperatively. The 5-year survival rate was 38%. There was frequent upstaging at surgery in all stages except IA. Patients with tumor confined to the uterus at the time of surgery had a 5-year disease-free survival of 52%. When there was extension outside of the uterus, the 5-year disease-free survival dropped to 28%. The locoregional recurrence rate was 17%.

Hasiuk, A. S., R. O. Petersen, et al. (1984). "Extragenital malignant mixed Mullerian tumor. Case report and review of the literature." Am J Clin Pathol 81(1): 102-5.

The second case of extragenital malignant mixed Mullerian tumor, heterologous type, occurring in the posterior peritoneum, and confirmed at autopsy, is presented. The histogenesis of this tumor is discussed.

Iwai, M., I. Konishi, et al. (1984). "[A light and electron microscopic studies of mullerian adenofibroma of the uterus]." Nippon Sanka Fujinka Gakkai Zasshi 36(1): 44-8.

Mullerian adenofibroma composed of both histologically benign epithilia and benign mesenchyme is considered to be a rare entity of mixed mullerian tumor. A case of mullerian adenofibroma of the uterus was studied by light and electron microscopy. Light microscopically, the cleft-like glands lined by single-layered columnar or cuboidal epithelial cells were distributed in the proliferation of surrounding fibroblast-like mesenchymal cells. Mitotic figures of mesenchymal cells were less than 1--2 in 10 high power fields, and no nuclear atypia or heterologous elements were observed. Electron microscopically, the epithelial cells had well-developed mitochondria, r-ERs, tonofilaments in the cytoplasm, and short microbilli or cilia protruding into the lumen. In the mesenchyme, two types of cells were observed. One was spindle-shaped cells resembling fibroblasts, and the other was cells resembling immature smooth muscle cells. The histological and ultrastructural features of mullerian adenofibroma were felt to resemble those of mullerian adenosarcoma, which may pursue a clinically malignant course. These findings suggest that mullerian adenofibroma and adenosarcoma may be in the common spectrum of mixed mullerian tumor.

Yonemitsu, N., M. Nakahara, et al. (1984). "[A case of Mullerian adenosarcoma of the uterus]." Gan No Rinsho 30(1): 105-9.

A case of Mullerian adenosarcoma of the uterus is reported. This is a low-grade malignant tumor situated between fibroadenomas and carcinosarcomas in the mixed mesodermal tumors. A 69-year-old woman complaining of an abdominal mass, underwent surgical resection of a tumor of the uterus. The tumor was divided into two parts, i.e. polypoid tumor in the endometrial cavity and nodular tumor in the myometrium. The 2 tumor types showed continuity. Microscopically, it was a so-called mixed tumor consisting of a glandular element of benign epithelial cells and an undifferentiated sarcoma; it was diagnosed as adenosarcoma.

Yamasaki, T., J. Yamashita, et al. (1984). "[Effects of TCGF (T-cell growth factor) on experimental malignant glioma-specific killer T-cell]." No Shinkei Geka 12(2): 141-50.

The immunoregulatory effects of TCGF (T-cell growth factor) on the generation and growth of syngeneic murine malignant glioma (20-methylcholanthrene-induced 203-glioma)-specific killer T-cell were investigated in C57BL/6 adult mice in order to clarify the immunopotential usefulness for anti-tumor local adoptive immunotherapy against malignant brain tumor. TCGF was prepared and assayed. Briefly, 5 x 10(6) ml mouse spleen cells were cultured with 2 microgram/ml concanavalin A in RPMI-1640 medium supplemented with 2% fetal calf serum for 24 hours. Culture supernatants were concentrated by ammonium sulphate precipitation (55 to 80% saturation) and purified by gel filtration (Sephadex G-100, a molecular weight from 30 to 36,000 daltons) and ion exchange chromatography (DEAE-cellulose, elution with 0.15 M in NaCl at ph 7.4). The purified TCGF had no IFN activity. Assays for TCGF was performed for quantitative analysis using 203-glioma-specific killer T cell clone (G-CTLL), which was obtained by limiting dilution method (0.3 cells/well in 96 well microtiter plate) and maintained for over 6 months in the presence of TCGF. Titer (U/ml) of TCGF was defined as the quantity of TCGF required to obtain one-half of the maximal stimulation of G-CTLL proliferation assay. It was confirmed that the specific killer T-cell against 203-glioma was generated in mice after intracranial as well as subcutaneous inoculation of the tumor cells. The killer T-cell activity of spleen cells, however, began to be severely impaired 2 weeks after intracranial inoculation concurrently with the increased intracranial pressure due to developing the tumor growth. Sensitized lymphocytes obtained from intracranial and subcutaneous tumor-bearing mice were assessed for CTL (cytotoxic T-lymphocyte) activity in MLTC (mixed lymphocyte-tumor cell culture) for 18 hours by microcytotoxicity assay. The specific cytotoxicity against 203-glioma cells was enhanced when sensitized lymphocytes from intracranial and subcutaneous tumor-bearing mice were pre-cultured with optimal TCGF (20 U/ml) for over 5 days. After the treatment of sensitized lymphocytes with anti-Thy-1 monoclonal antibody and complement, however, the specific cytotoxicity of sensitized lymphocytes was eliminated almost completely. Therefore, it was thought that TCGF possesses immunoregulatory effects of enhancement of killer T-cell activity. On the contrary, TCGF had no influence on normal T lymphocytes and the growth of 203-glioma cells in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)

Berneman, Z. N., R. Mathijs, et al. (1984). "IgD plasma cell leukemia and uterine malignant mixed Mullerian tumor." Acta Haematol 72(1): 52-6.

The case of a 74-year-old female with an IgD kappa plasma cell leukemia is presented. In contrast to the majority of the cases in the literature, this patient responded rather well to melphalan and prednisolone and survived for 20 months after starting treatment. Another remarkable feature was the simultaneous occurrence of a double uterine neoplasm, a malignant mixed Mullerian tumor of the homologous variety (also called carcinosarcoma).

Dallenbach-Hellweg, G. (1984). "On the histogenesis and morphology of ovarian carcinomas." J Cancer Res Clin Oncol 107(2): 71-80.

The modern classification of ovarian tumors based on histogenetic principles is clinically important in the evaluation of prognosis and differential therapy. Ninety percent of malignant ovarian tumors belong to the category of "common carcinomas." All of these tumors originate from the coelomic epithelium at any of various stages of its differentiation into the derivatives of the Mullerian duct, giving rise to a large group of tumors that can be subdivided into serous papillary cyst-adenocarcinomas arising from surface-like epithelium, mucinous cystadenocarcinomas arising from endocervical-like epithelium, endometrioid carcinomas from endometrium-like epithelium, clear-cell carcinomas from endocervical or endometrium-like epithelium, malignant cystadenofibromas from undetermined pluripotent Mullerian epithelium, and (malignant) Brenner tumors from heterotopic epithelium resembling Wolffian differentiation, as seen in the urothelium. The well differentiated stages of these carcinomas can be readily distinguished by comparing them with the derivates of the Mullerian epithelium. The poorly differentiated types, on the other hand, may provide no criteria for comparison, but can still be classified as belonging to the group of common epithelial tumors. Adenocarcinomas of one type may also contain portions of another related type, e.g., serous papillary carcinomas may contain mucinous glands or groups of clear cells and vice versa. Serous papillary carcinomas form the largest group containing about 50% of all ovarian carcinomas. The endometrioid carcinomas comprise roughly 20%, the mucinous carcinomas 10%, and the VXGHb-cell carcinomas roughly 10%. Five percent of all carcinomas are unclassifiable and the remaining 5% constitute the group of rare ovarian carcinomas: the malignant cystadenofibromas, adenosarcomas, malignant mesenchymal mixed tumors, and malignant Brenner tumors. The three main groups can be histologically subdivided into three grades: those of high, moderate and poor differentiation. In addition, a borderline tumor representing a pre-stage of invasion and metastasis has been recognized. The prognosis with serous papillary carcinomas is poor, with an overall 5-year survival rate of 20%; the 5-year survival rate for mucinous carcinomas is 40%-60%, for endometrioid carcinomas 55%, and for clear-cell carcinomas 40%. Statistically significant data for predicting the prognosis for rare carcinomas are not available.

Wechsler, J., J. Diebold, et al. (1984). "[Lymph node localization of epidermotropic T malignant lymphomas (mycosis fungoides and Sezary's syndrome)]." Bull Cancer 71(2): 89-99.

In this paper are reported the different histological variants of Mycosis Fungoides (M.F.) observed in 48 lymph node positive biopsies providing from 98 lymph nodes obtained from 94 patients with M.F. A partial destruction of the lymphoid architecture was required for attesting M.F. involvement. The remaining 50 lymph nodes demonstrated dermopathic non specific lesions. A partial lymph node involvement is often observed with a persistent sinusal pattern and residual germinative follicles (39 from 48 cases or 80%). The tumoral infiltration begins in the deep cortex and in the interfollicular areas. Some reactive lesions of dermopathic lymphadenopathy are frequently associated. The main histological feature is the cellular pleomorphism. Nevertheless 4 cytological variants may be described according to the predominant proliferating cells: a small cell variant, a large cell variant, a mixed cell variant comprising an equivalent proportion of small medium and large-sized cells, an immunoblastic variant with majority of immunoblasts and some Sternberg-like tumoral cells. Any form may be associated with granuloma which increase polymorphism. In some histological variants, so-called Lutzner cells are numerous and facilitate the diagnosis of epidermotropic malignant T lymphoma. Nevertheless, some cases may be discussed with centrocytic or centroblastic centrocytic lymphomas, with Pinkus multilobulated T lymphoma or with convoluted lymphoblastic lymphoma. More difficult is the distinction from Lennert T - zone lymphomas and from adult T-cell lymphoma/leukemia described in Japan. The immunoblastic variant may be mistaken with some high-grade malignant non-Hodgkin lymphoma, with an angio-immunoblastic lymphadenopathy, even with a metastatic carcinoma. The evidence of granuloma with numerous eosinophiles frequently observed in the Hodgkin-like variant is a cause of confusion with Hodgkin's disease. A good help would be supplied by the discover of some Lutzner cells among the granuloma. No correlation was found between these histological variants and the M.F. evolution. Evidence of reactive inflammatory cells do not interfere with the prognosis.

Kikuchi, M., T. Mitsui, et al. (1983). "Macroglobulinemia and chronic B-cell type lymphocytic leukemia in japan--study of autopsy cases." Jpn J Clin Oncol 13(3): 607-22.

Autopsy cases of Waldenstrom's macroglobulinemia (WM) and chronic lymphocytic leukemia of B-cell type (B-CLL) were examined to determine the geographical distribution and histological characteristics of these diseases in Japan. Both diseases occurred primarily at 50 to 60 years of age with a predominance of males and were distributed throughout Japan with a population slightly lower than that of T-CLL in southwestern Japan. Histologically WM (31 cases) consisted mainly of small cell type malignant lymphoma with plasmacytic differentiation (27 cases) according to the Japanese Classification (LSG) and cytoplasmic immunoglobulins with a monoclonal pattern of immunoglobulin M (IgM) (lambda 12; kappa seven). The bone marrow involvement (27 cases) was follicular, mixed (follicular and diffuse) or diffuse. B-CLL (58 cases) also showed principally a small cell type histology (48 cases) and 16 of the cases showed plasmacytic differentiation as in WM. Cytoplasmic immunoglobulins with a monoclonal pattern were found in 10 (six of IgG, two of IgM, one of IgG and M, and one of IgA). Bone marrow involvement (56 cases) revealed the same histological pattern as WM. According to the growth pattern of the tumor cells in the bone marrow and lymph nodes, both diseases may be categorized as bone marrow-based lymphoma.

Sugai, S., T. Takiguchi, et al. (1983). "B-cell malignancy and monoclonal gammopathy, and idiotype of cell surface and serum immunoglobulin." Jpn J Clin Oncol 13(3): 533-42.

We studied cell surface membrane immunoglobulins (SmIg), intracytoplasmic Ig (CIg) and monoclonal Ig (M protein) in patients with the B-cell series malignancies; malignant lymphoma, chronic lymphocytic leukemia (CLL), Waldenstrom's macroglobulinemia (WM), multiple myeloma (MM), and monoclonal gammopathy (MG) associated with Sjogren's syndrome (SS). The patients were examined for idyotype (Id) determinants on the cell surface and in the cytoplasm of malignant cells as well as serum M proteins. Twenty-two patients had malignant lymphoma with monoclonal SmIg. The malignant cells of 11 patients contained CIg; four of these 11 patients had a small amount of serum M protein. SmIg of the IgM class was most frequent (12/22) and the lambda type light chain was predominant (kappa/lambda ratio = 4/8). By means of rabbit anti-Id antisera prepared against M proteins, Id determinants were demonstrated on the cell surface and in the cytoplasm of malignant cells as well as in the serum M proteins, indicating that the malignant cells proliferated monoclonally producing monoclonal IgM on the cell surface and in the cytoplasm and secreting it to the serum. Six CLL patients were included in our series; one manifested monoclonal IgM in the serum. The Id determinants of M protein was detected on the cell surface and in the cytoplasm of pathologic cells in the peripheral blood. Eight of ten WM patients were examined for SmIg; all had monoclonal SmIg on the surface of cells from peripheral blood or bone marrow. Id determinants were detected on the cell surface and in the cytoplasm of malignant cells in four WM patients. There were 42 patients with MM; 10 of them were examined for SmIg and three of these had monoclonal SmIg on plasma cells derived from the bone marrow. By immunofluorescent and mixed rosette methods, Id-bearing B (0-20%) and T cells (0-2%) were identified in the peripheral blood of MM patients who had no plasma cells in the peripheral blood. Our findings suggest that a monoclonal change may occur at the B-cell level and that Id-bearing T cells may exist as regulatory T cells. Ten SS patients had M proteins. Non-IgM class M proteins (2 IgG and 4 IgA) were more frequent than the IgM class (3 IgM). Four M proteins with rheumatoid factor (RF) activity were found among these 10 M proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Chumas, J. C., W. J. Mann, et al. (1983). "Malignant mixed Mullerian tumor of the endometrium in a young woman with polycystic ovaries." Cancer 52(8): 1478-81.

A 19-year-old female with Stein-Leventhal syndrome and polycystic ovaries was found to have a malignant mixed Mullerian tumor (MMMT) of the uterus with superficial myometrial invasion. This patient is the youngest reported with MMMT of the endometrium. The association of endometrial malignancies and polycystic ovaries is reviewed. The tumor was found to have above normal levels of estradiol and progesterone receptors. A possible role of estrogen stimulation in the genesis of some MMMTs is suggested.

Suzuki, A., H. Tahara, et al. (1983). "Hysteroscopic diagnosis of malignant mixed mullerian tumor of the corpus uteri." Gynecol Oncol 15(3): 350-6.

Hysteroscopic findings of two cases with homologous type of malignant mixed mullerian tumor of the corpus uteri are described. On hysteroscopic examination, not only were nodular or polypoid lesions with fairly smooth surfaces found but also lesions with rough uneven surfaces and dilated vessels resembling the figures of endometrial carcinoma were observed. The blood vessels of lesions with fairly smooth surfaces were not dilated. Under hysteroscopy, each lesion with a smooth surface seemed to be more closely related to a benign lesion, such as an endometrial polyp or submucous myoma. The lesions with smooth surfaces corresponded to the histologically sarcoma-dominant areas and the lesions with uneven surfaces and dilated vessels were equivalent to the sites where adenocarcinoma was noted. Thus, hysteroscopic findings of this tumor well reflected the histology near the surface of the endometrium.

Waxman, M., J. S. Waxman, et al. (1983). "Heterologous malignant mixed Mullerian tumor of the cervical stump." Gynecol Oncol 16(3): 422-8.

A 76-year-old woman presented with vaginal bleeding 37 years following supracervical hysterectomy for a benign disease. Extensive malignant mixed Mullerian tumor was found in the remaining uterine cervix. This appears to be the first documented case of the malignant mixed Mullerian tumor arising in a cervical stump. Possibility of derivation of this tumor from endometriosis notwithstanding, the cervical Mullerian neoplastic potential parallels that of the endometrium because of the developmental kinship of the two. This potential has been fully retained and expressed as a tumor in the cervical stump in this case.

Kahanpaa, K. V., R. Laine, et al. (1983). "Malignant mixed Mullerian tumor of the fallopian tube: report of a case with 5-year survival." Gynecol Oncol 16(1): 144-9.

The literature reveals a total of only 25 cases of malignant mixed Mullerian tumor of the fallopian tube. Another case is presented; the patient is well and without evidence of disease more than 5 years after the operative treatment. She also received postoperatively adjuvant cytostatic treatment with cyclophosphamide, vincristine, adriamycin, and external radiation therapy. An aggressive mode of treatment is recommended in this rare disease due to the usually very poor prognosis.

Czernobilsky, B., J. J. Gillespie, et al. (1982). "Adenosarcoma of the ovary. A light- and electron-microscopic study with review of the literature." Diagn Gynecol Obstet 4(1): 25-36.

This is a light- and electron-microscopic study of a large ovarian adenosarcoma in a 50-year-old woman as well as a review of the literature. The tumor showed a variety of mullerian type epithelia and a spectrum of stromal patterns including nonspecific fibroblastic, and endometrial type stroma. The latter ranged from normal-appearing to low-grade sarcoma. This study emphasizes the relationship of ovarian adenosarcoma to cystadenofibroma, on the one hand, and to malignant mixed mullerian (mesodermal) tumor, on the other. It appears that the mitotic count which is used as the primary means for the classification of smooth muscle and stromal tumors of the uterus, has less value in the assessment and prognostication of ovarian adenosarcomas.

Evans, H. L. (1982). "Endometrial stromal sarcoma and poorly differentiated endometrial sarcoma." Cancer 50(10): 2170-82.

U.T.M.D. Anderson Hospital cases filed as endometrial sarcoma were reviewed. Malignant mixed Mullerian tumors, Mullerian adenosarcomas, and poorly differentiated sarcomas of uncertain origin were excluded, and a minimum of 36 months follow-up was required. On pathologic examination, the remaining cases fell into two distinct groups: endometrial stromal sarcoma (11 cases) and poorly differentiated endometrial sarcoma (seven cases). The former were characterized histologically by small to medium-sized uniform cells and distinctive arterial vasculature resembling the spiral arteries to the normal endometrium; they were thus considered to exhibit endometrial stromal differentiation. The latter showed topographic configurations indicative of endometrial origin but did not demonstrate endometrial stromal differentiation; they were composed of generally larger cells with nuclear hyperchromatism and pleomorphism and had no distinctive vascular pattern. The mitotic rate was usually low in endometrial stromal sarcoma and high in poorly differentiated endometrial sarcoma, although two examples of the former had more than 20 mitoses per 10 high-power fields. All but one of the patients with endometrial stromal sarcoma were less than 50 years of age, whereas all of those with poorly differentiated endometrial sarcoma were older than 50 years. One patient with endometrial stromal sarcoma died of tumor, two were living with tumor at latest follow-up, and eight were clinically tumor-free. By contrast, six of those with poorly differentiated endometrial sarcoma died of tumor, all within 34 months. The extent of tumor was the major prognostic factor in both groups; the three patients with endometrial stromal sarcoma who were dead or living with tumor all had extrauterine extension at the time of hysterectomy (only one of the other eight did so) and all six who died with poorly differentiated endometrial sarcoma had myometrial invasion (the one survivor had a tumor limited to the endometrium). Other pathologic factors, including mitotic rate, had no prognostic significance in either category; of particular interest was that both patients who had endometrial stromal sarcomas with high mitotic rates were tumor-free. It is concluded that endometrial stromal sarcoma is a distinct tumor entity whose diagnosis should not depend on mitotic rate, and it is suggested that poorly differentiated endometrial sarcoma is closely related to malignant mixed Mullerian tumor, in view of clinical and pathologic similarities.

Waxman, M., J. G. Boyce, et al. (1982). "Concurrence of malignant and benign heterologous mixed tumors of the uterus." Am J Clin Pathol 77(5): 631-7.

A large polypoid uterine mas was composed to two distinct and separate parts: a malignant mixed mullerian tumor (MMMT) and a benign mixed mesenchymal tumor (BMMT). It was considered a collision of two neoplasms rather than a malignant degeneration of the BMMT. Malignant transformation of benign mesenchymal uterine tumors is a controversial concept which is difficult to prove or disprove. Concerning the histogenesis of MMMT it appears, at least in some cases, that they originate not from a single multipotential mullerian cell, but rather from two, a stromal cell and an epithelial cell. It is suggested furthermore, that in certain instances presence of one neoplastic component, e.g., adenocarcinoma, can incite proliferation of the second, sarcomatous element of the MMMT.

Nguyen, G. K. (1982). "Cytopathologic aspects of a metastatic malignant mixed Mullerian tumor of the uterus. Report of a case with transabdominal fine needle aspiration biopsy." Acta Cytol 26(4): 521-6.

The cytologic details of a fine needle aspiration biopsy of an intraabdominal metastatic malignant mixed Mullerian tumor of the uterine corpus are presented. Cytologically, the malignant stromal and epithelial elements resembled those in previous histologic materials. Given the aggressive nature of this lesion, the patient may initially present with an inoperable tumor; cytologic examination of an aspiration biopsy may be diagnostic without the need for an exploratory laparotomy.

Sutherland, C. M., S. P. Leong, et al. (1982). "In vivo delayed hypersensitivity reactions to partially purified human melanoma antigens." J Surg Oncol 20(4): 221-6.

Sera from patients receiving autologous cell immunization were shown to contain antibody specific for melanoma cells by immunofluorescence, microcomplement fixation, and mixed hemadsorption. These hyperimmune specific sera were used to define antigens shed into tissue culture media from human malignant melanoma cells. When supernatants from cultured melanoma cells were passed over a Sephadex G-200 column, melanoma antigens were found in Peak 2. The active fraction was further purified by carboxymethylcellulose ion exchanger and found in the 0.4 M NaCl gradient. This fraction has been tested in four immunized patients and in one nonimmunized melanoma patient. All five patients developed lymphocytic vasculitis compatible with delayed hypersensitivity reaction. These antigens should be of benefit in studying delayed hypersensitivity in melanoma patients and as potential agents for specific immunotherapy.

Chen, K. T. and J. M. Vergon (1981). "Carcinomesenchymoma of the uterus." Am J Clin Pathol 75(5): 746-8.

A unique case of intramural uterine tumor composed of malignant epithelium and benign smooth muscle, adipose tissue, and cartilage is reported. This tumor, which the authors designated "carcinomesenchymoma," apparently represents an example of a previously unreported variant of mixed mullerian tumor that is composed of malignant epithelium and benign mesenchymal elements.

Butler, W. H. and V. Hempsall (1981). "Histochemical studies of hepatocellular carcinomas in the rat induced by aflatoxin." J Pathol 134(2): 157-70.

A histochemical study has been done on a group of 18 hepatocarcinomas induced by aflatoxin. One hundred per cent, incidence of hepatocarcinomas is induced by feeding 5 p.p.m. aflatoxin for 6 weeks. The carcinomas were trabecular hepatocarcinomas with a mixed adenomatous pattern and showed considerable variation in histochemical reactions throughout the lesions. There was a patchy distribution of glycogen and glucose-6-phosphate and the membrane ATPase was present along much of the canalicular border of the cells but with an abnormal and tortuous pattern. Aniline hydroxylase was present in varying amounts in both trabecular and adenomatous carcinomas. It is concluded that the histological variants of hepatocarcinoma are all derived from hepatocytes, but no unique changes were observed related to the progress involved in malignant neoplasia. The observations form a basis for comparison with early lesions seen prior to the recognition of carcinoma.

Hall-Craggs, M., C. Toker, et al. (1981). "Carcinosarcoma of the uterine cervix: a light and electron microscopic study." Cancer 48(1): 161-9.

A case of carcinosarcoma of the uterine cervix is presented. Light microscopic and ultrastructural features of the tumor are described. While the epithelial component had the appearance of a carcinoma arising from endocervical epithelium, the stromal component was composed of malignant smooth muscle cells together with some cells having the charactristics of malignant fibroblasts. The tumor is considered to arise from the mullerian tract mesoderm and to be part of the spectrum of tumors which range from the totally benign adenofibroma to the malignant heterologous mixed mesodermal tumor.

Mazur, M. T. (1981). "Atypical polypoid adenomyomas of the endometrium." Am J Surg Pathol 5(5): 473-82.

Five unusual polypoid lesions of the endometrium which we term atypical polypoid adenomyomas are described; these growths occurred in premenopausal women. Each of the polyps was characterized by irregular atypical glands with squamous metaplasia and a cellular, smooth muscle mesenchyme, having a pattern to be distinguished from infiltrating adenocarcinoma or a malignant mixed mullerian tumor. Electron microscopy in one case confirmed the presence of a well-differentiated smooth muscle component. These lesions were focal and noninvasive. Two of the three patients who had hysterectomies has small residual lesions confined to the endometrium. Follow-up from 4 to 24 months showed no recurrence. One patient had a second D & C reported as normal; she subsequently became pregnant. The benign behavior of these unusual polyps suggests that atypical adenomyomas can be managed conservatively in the premenopausal woman without the necessity of a hysterectomy.

Bain, G. O. and A. Belch (1981). "Nodular mixed cell lymphoma with monoclonal gammopathy." Am J Clin Pathol 76(6): 832-7.

Malignant lymphomas are rarely accompanied by a serum M component. Such neoplasms are usually of lymphocytic cell type and, with extremely rare exceptions, of diffuse pattern. A patient with an unusual malignant lymphoma of mixed cell type characterized by follicular structures and vascular proliferation was found to have a serum monoclonal gammopathy (IgM kappa) of over 4 g/dl. Remission accompanied by a pronounced reduction in the M protein was achieved with Chlorambucil. Subsequent relapse was characterized by the emergence of a large cell lymphoma with IgM kappa surface immunoglobulin. No concomitant rise in the serum M component accompanied relapse.

Dietze, O., I. Hopfel-Kreiner, et al. (1981). "[Heterologous Mullerian adenosarcoma of the uterus--a rare tumor. Light- and electron-microscopic findings, biological behavior (author's transl)]." Arch Gynecol 231(1): 75-85.

A case of heterologous Mullerian adenosarcoma of the uterus is presented with emphasis on morphologic differentiation, clinical course, prognosis, and treatment. This tumor was described first by Clement and Scully in 1974. Since that time 36 cases have been reported in the literature. The neoplasm consists of benign epithelial and malignant mesenchymal elements. The latter are composed of tissue with homologous and heterologous differentiation. Our microscopic and ultrastructural studies suggested that the heterologous elements were rhabdomyoblasts with a variable degree of differentiation. According to the literature the prognosis of Mullerian adenosarcoma is better than that of malignant mixed Mullerian tumor. The location of the tumor - whether intrauterine or extrauterine - seems to be more important as regards prognosis than the differentiation of the sarcomatous elements. The clinical course in our patients was not different from those described in the literature. Surgical removal of the tumor remains the treatment of choice. Some authors report a better survival rate when surgical treatment is followed by radiotherapy. Chemotherapy may be useful in cases of local or distant metastasis, and in cases of incomplete excision of the tumor mass.

Chang, W. W., C. B. Boyd, et al. (1980). "An evolution of malignant mixed mullerian tumor." Diagn Gynecol Obstet 2(4): 257-63.

In an unusual example of malignant mixed mullerian tumor, a tumor originated in the uterine corpus as an endometrial carcinoma consisting of ordinary endometrial adenocarcinoma, papillary adenocarcinoma, mucinous adenocarcinoma, and squamous cell carcinoma. Following hysterectomy, the tumor recurred at the vaginal vault as poorly differentiated papillary adenocarcinoma. During the second recurrence as a pelvic tumor about 3 years after hysterectomy, the tumor evolved into a malignant mixed mullerian tumor with predominance of sarcomatous element. The latter included undifferentiated sarcoma, endometrial stromal sarcoma, fibromyxosarcoma, leiomyosarcoma and rhabdomyosarcoma. These findings support the contention of Sternberg et al. that a malignant mixed mullerian tumor may exceptionally originate in an endometrial carcinoma.

Clerc, D., P. Segond, et al. (1980). "[Mixed cryoglobulinaemia and benign monoclonal gammopathy in Sjogren's syndrome (author's transl)]." Sem Hop 56(29-32): 1290-2.

The authors report a case of Sjogren's syndrome associated with Raynaud phenomenon and mixed IgM-IgG cryoglobulinaemia. Three years after the onset of this association:--Immunoelectrophoresis of the serum showed a monoclonal IgM (lambda) protein, --the level of the mixed IgM-IgG cryoglobulinaemia had increased from 28 mcg/ml up to 12 mg/ml and its IgM component was monoclonal (lambda) with anti-IgG activity. Search for amyloidosis and for a malignant lymphoma was negative. Such an association of a benign monoclonal gammopathy, mixed cryoglobulinaemia and Sjogren's Syndrome has only exceptionally been reported in the literature.

Brownstein, D. G. and A. L. Brooks (1980). "Spontaneous endomyometrial neoplasms in aging Chinese hamsters." J Natl Cancer Inst 64(5): 1209-14.

Twenty-one endomyometrial neoplasms among 93 nulliparous noninbred Chinese hamsters were evaluated. The median survival time of the 93 females was 1,040 days. The median age of hamsters with endomyometrial neoplasms was 1,200 days. Neoplasms were classified as carcinoma or malignant mixed mullerian tumors of the endometrium and benign or malignant myometrial neoplasms. There were 13 endometrial adenocarcinomas. Three tumors were mixed adenosquamous carcinomas, which occurred in significantly older Chinese hamsters than did adenocarcinomas. Three malignant mixed mullerian tumors consisted of 2 carcinosarcomas and 1 mixed mesodermal tumor. The 2 myometrial neoplasms were a leiomyoma and a leiomyosarcoma. The classification and relative frequency of these neoplasms were similar to endomyometrial neoplasms of women, which makes Chinese hamsters useful subjects for studies of spontaneous endomyometrial cancers.

Terrell, T. G., D. H. Gribble, et al. (1980). "Malignant lymphoma in macaques: a clinicopathologic study of 45 cases." J Natl Cancer Inst 64(3): 561-8.

Malignant lymphoma was diagnosed in 42 rhesus macaques (Macaca mulatta) and 3 stumptail macaques (M. arctoides) between February 1969 and December 1977. The distribution of tumor masses in the tissues of individual animals varied widely. Solitary tumor masses were present in 14 animals and multiple masses in the remaining 31 animals. Visceral lymph nodes, gastrointestinal tract, heart, and kidneys were most commonly affected. Peripheral lymph nodes were rarely involved. Most malignant lymphomas were of an undifferentiated cell type, although tumors of histiocytic, lymphocytic, poorly differentiated, and mixed lymphocytic and histiocytic cell types were also observed. Concurrent bacterial and/or viral infections were evident in 30 of the 45 macaques with malignant lymphoma. Amyloidosis was present in 9 animals. This high incidence of malignant lymphoma suggested that their immune responses were abnormal. The development of malignant lymphoma in the macaques may have been secondary to or enhanced by immunodeficiency.

Hanjani, P., R. O. Petersen, et al. (1980). "Malignant mixed Mullerian tumor of the fallopian tube. Report of a case and review of literature." Gynecol Oncol 9(3): 381-93.

Matuchansky, C., M. Morichau-Beauchant, et al. (1980). "Nodular lymphoid hyperplasia of the small bowel associated with primary jejunal malignant lymphoma. Evidence favoring a cytogenetic relationship." Gastroenterology 78(6): 1587-92.

A nonimmunodeficient patient with diffuse nodular lymphoid hyperplasia of the small bowel and a jejunal malignant lymphoma of mixed lymphocytic-histiocytic type is reported. Surface marker and immunohistologic studies of the malignant lymphoma and of histologically benign lymphoid nodules proximal to the tumor showed a similar pattern of monoclonality (IgM-kappa) and gave suggestive evidence of a cytogenetic relation of the lymphoma to nodular lymphoid hyperplasia. It is suggested that intestinal nodular lymphoid hyperplasia may be a condition leading to lymphoid malignancy; its exact incidence in patients with both malignant lymphoma of the gut and a primary immunodeficiency syndrome should warrant further consideration.

Mukai, K., J. Varela-Duran, et al. (1980). "The rhabdomyoblast in mixed Mullerian tumors of the uterus and ovary. An immunohistochemical study of myoglobin in 25 cases." Am J Clin Pathol 74(1): 101-4.

Forty per cent of 25 uterine and ovarian mixed mullerian tumors contained stainable myoglobin that was present in the abundant cytoplasm of large rounded tumor cells. Intracytoplasmic cross striations identified rhabdomyoblasts in 32% of the cases, but were difficult to find. The authors believe that the immunoperoxidase technic successfully demonstrates skeletal muscle differentiation in a high proportion of mixed mullerian tumors and may be employed as a suitable diagnostic aid. However, the nonspecific staining of benign and malignant squamous elements should be interpreted with caution.

King, M. E. and E. E. Kramer (1980). "Malignant Mullerian mixed tumors of the uterus: a study of 21 cases." Cancer 45(1): 188-90.

In a study of 21 malignant Mullerian mixed tumors of the uterus seen at The New York Hospital from 1957 to 1977, we found an unexpectedly high incidence (67%) of heterologous tumors which we attribute to an assiduous search for striated cells. Four patients, all of whom had had heterologous tumors, were free of tumor 3 1/2 to 17 years after diagnosis. The tumors were confined to the corpus and exhibited no more than moderate myometrial invasion. The heterologous element was rhabdomyosarcoma in three cases and osteosarcoma in one. Fifteen cases were treated in the last decade as compared with six in the previous decade.

Elbers, J. R. and S. S. Wagenaar (1980). "Malignant mixed mesodermal tumor of the ovary." Eur J Obstet Gynecol Reprod Biol 10(1): 47-53.

Mixed mesenchymal and epithelial tumors are highly malignant neoplasms most commonly found in the uterus. Rarely, histologically identical tumors occur in the ovary. We report a 70-yr-old woman with a malignant mixed Mullerian tumor of the ovary. The tumor contained heterologous foci of immature cartilage and striated muscle, in addition to carcinosarcomatous areas. Postoperative chemotherapy was administered, but she died within 5 mth with recurrent and metastatic tumor. A review of the literature concerning extrauterine malignant mixed Mullerian tumors is added.

Kondo, A., Y. Niitsu, et al. (1980). "[A case of B-cell malignant lymphoma associated with high serum titer of cold haemagglutinin (IgG-IgM mixed type) (author's transl)]." Rinsho Ketsueki 21(1): 46-51.

Bertram, J. S. (1979). "Modulation of cellular interactions between C3H/10T1/2 cells and their transformed counterparts by phosphodiesterase inhibitors." Cancer Res 39(9): 3502-8.

It has been demonstrated previously that nontransformed C3H/10T1/2CL8 mouse embryo fibroblasts (10T1/2) can induce a state of reversible growth inhibition in cocultured malignantly transformed mouse fibroblasts and that this inhibition is modulated by serum concentration. The present study suggests that cyclic nucleotides may be implicated in this intercellular communication. The phosphodiesterase inhibitors theophylline, caffeine, and 3-isobutyl-1-methylxanthine (IBX) at concentrations of 10(-3) M, maintained continuously, were all found to inhibit the expression of 3-methylcholanthrene-induced malignant transformation when added 7 days after removal of carcinogen. IBX was the most potent, causing 100% inhibition at 10(-4) M and 70% inhibition at 10(-5) M. This inhibition was partially reversible in the former case and completely reversible in the latter case by removal of drug. Complete inhibition by 10(-4) M IBX was still observed when treatment was delayed 21 days postcarcinogen. In reconstruction experiments, utilizing confluent monolayers of 10T1/2 cells overlaid with transformed cells, IBX caused a dose-dependent inhibition of colony size of the transformed cells. Adenosine cyclic 2':3'-monophosphoric acid (cAMP) and N6,O2'-dibutyryladenosine cyclic 3':5'-monophophoric acid potentiated this response. The presence of non-transformed 10T1/2 cells was required for this effect, since a concentration of IBX (10(-4) M) inhibitory for the growth of transformed cells in mixed cultures was without effect on the growth rate, plating efficiency, or saturation density of pure cultures of 10T1/2 cells or of their transformed counterparts. Conditioned medium removed from IBX-treated 10T1/2 cells was not growth inhibitory for transformed cells, indicating a requirement for cell-cell contact. IBX caused a dose-dependent increase in intracellular cAMP in confluent 10T1/2 cells and a more pronounced increase in cAMP concentration in the culture medium of these cells. The dose-response effects of IBX on growth inhibition of malignant cells in mixed cultures appear to correlate well with its ability to elevate cAMP levels. Thus, IBX increased the capacity of 10T1/2 cells to cause reversible growth arrest of transformed cells and appears to act in a manner analogous to the previously reported effects of serum.

Sanin, A. V., A. V. Pronin, et al. (1979). "[Immune response of (C57BL/6xA/Sn)F1 mice in mycoplasm-virus infection]." Biull Eksp Biol Med 88(9): 327-9.

Mixed Rauscher leukemia virus (RLV) and M. arthritidis infection of (C57BL/6xA/Sn)f1 mice-hybrids, highly resistant to RLV, was accompanied by a progressive inhibition of rosette-forming cells (RFC) and plaque-forming cells (PFC), resulting in the induction of malignant erythroblastosis identical by cytology to Rauscher leukemia. The mice-hybrids infected with A. laidlawii and RLV developed significant splenomegaly on the 21st day of the infection, and their immune response was almost entirely suppressed, but both RFC and PFC populations as well as the spleen weight returned to the initial level by the 62d day the infection. A possible role of mycoplasm in the induction and development of Rauscher leukemia is discussed.

Pick, A. I., Y. Shoenfeld, et al. (1979). "Plasma cell dyscrasia. Analysis of 423 patients." Jama 241(21): 2275-8.

Present clinical and laboratory diagnostic criteria permit a more accurate diagnosis and closer follow-up of patients with plasma cell dyscrasias. A ten-year follow-up of a group of 423 patients showed that the indications for and the adjustment of treatment are more precise when these criteria are summarized into profiles based on each diagnostic category. M components may be an indication of the presence of another sometimes nonreticular malignant neoplasm. The improvement of the specificity and sensitivity of immunologic methods sheds additional light on mechanisms controlling the synthesis of homogeneous antibodies such as prevalence of IgM-K in mixed cryoglobulinemia and lambda-light chains in IgD myeloma, excretion of lambda-Bence Jones proteins in amyloidosis, and greater IgG-subclass restriction in multiple myeloma as compared with benign monoclonal gammopathy. The activation of additional clones (biclonal gammopathies) was found in 3% of our patients.

Waxman, M. (1979). "Pure and mixed Brenner tumors of the ovary: clinicopathologic and histogenetic observations." Cancer 43(5): 1830-9.

Fifty-six Brenner tumors of 51 patients were analyzed. The incidence of bilaterality was 9.8%. Most tumors were smaller than 2 cm, and constituted incidental finding. Most of the patients were 30-49 years old (mean 49.7, main 44). A high incidence of associated malignant neoplasms was noticed among the patients with Brenner tumor but was considered coincidental. No evidence of hormone secretion by the tumor was found. Out of 31 tumors, 27 occupied the cortex. Urothelial metaplasia of the ovarian surface epithelium was demonstrated in one case, and continuation of the Brenner column with the surface of ovary in another. There were 12 cases of mixed Brenner tumor in this series (21.1%). The most frequent associated constituents of the mixed Brenner tumors are mucinous cystadenomas. These tumors represent a single mixed neoplasm originating in a multipotential celomic cell which proliferates and differentiates into several mullerian forms. The histogenesis of medullary and hilar Brenner tumors can be explained on the basis of celomic metaplasia. Uncertainty persists in explaining the histogenesis of Brenner tumors mixed with mature cystic teratoma.

Bibro, M. C., V. A. LiVolsi, et al. (1979). "Adenosarcoma of the uterus: ultrastructural observations." Am J Clin Pathol 71(1): 112-7.

Mullerian adenosarcoma has been recently described as a distinctive biphasic uterine tumor with benign epithelial and malignant stromal components. The lesion belongs generally to the group of mixed mullerian tumors, but the benignity of the epithelium separates it from the other neoplasms of this type. This entity usually affects postmenopausal patients who follow a protracted course. This paper reports a case fulfilling the original clinical and pathologic description of Clement and Scully and adds ultrastructural observations. Electron microscopic examination confirmed the optical impression of a biphasic neoplasm with benign epithelial and malignant stromal components. The epithelium resembled proliferative endometrium, and the stroma had features of endometrial stromal sarcoma or mixed mullerian tumor. The findings of stromal resemblance to endometrial stromal sarcoma or mixed mullerian tumor and the presence of a variety of mullerian epithelia support the proposed mullerian derivation of this lesion.

Barwick, K. W. and V. A. LiVolsi (1979). "Malignant mixed mullerian tumors of the uterus. A clinicopathologic assessment of 34 cases." Am J Surg Pathol 3(2): 125-35.

We have analyzed clinical and pathologic features of a series of 34 patients with malignant mixed mullerian tumors of the uterus. This study includes 17 homologous and 17 heterologous lesions. The most significant prognostic indicator in our patients was tumor extent (stage) at diagnosis. Of lesser importance were the presence of heterologous elements, especially chondrosarcoma, high grade of carcinoma and tumor size. Survival rates were 52% at 2 years and 36% at 5 years for homologous tumors; and 47% and 14%, respectively, for the heterologous variety.

Barwick, K. W. and V. A. LiVolsi (1979). "Heterologous mixed mullerian tumor confined to an endometrial polyp." Obstet Gynecol 53(4): 512-4.

Mixed mullerian tumors of the uterus, which have been divided into homologous and heterologous types, are considered neoplasms of high malignant potential. In the heterologous variety, the presence of rhabdomyosarcoma has been associated with an especially poor prognosis. We report the first case of a heterologous, malignant mixed mesodermal tumor (adenocarcinoma, stromal sarcoma, and rhabdomyosarcoma) confined to an endometrial polyp. The patient, treated by surgery only, remains clinically free of disease 11 years later. Mixed mullerian tumors of limited extent may not be associated with the dismal prognosis that usually accompanies such lesions.

Perez, C. A., F. Askin, et al. (1979). "Effects of irradiation on mixed mullerian tumors of the uterus." Cancer 43(4): 1274-84.

A retrospective study of 54 patients with histologically proven malignant mixed mullerian tumors of the uterus was undertaken with main emphasis on the evaluation of the effects of irradiation on pelvic tumor control. The tumors were staged according to the FIGO classification for endometrial carcinoma and 24 were classified as Stage I, 10 as Stage II, 13 as Stage III and seven as Stage IV. Patients with Stage I and II were treated with surgery alone (9 patients, three surviving) or preoperative intracavitary irradiation (13 patients, eight surviving) or preoperative combination of intracavitary and external irradiation (12 patients, six surviving). Five patients with Stage III and IV were treated with surgery alone, two were treated with a combination of irradiation and surgery and 11 with radiation alone. None of these patients survived. In seven patients showing no residual tumor in the uterine specimen after irradiation, no pelvic failures were noted, whereas seven of 17 (41.2%) with residual tumor developed pelvic recurrences. In patients with Stage I treated with surgery alone, three out of six recurred in the pelvis whereas only three of 17 (17%) receiving preoperative irradiation developed pelvic recurrences. However, in Stage II six of eight patients treated with preoperative irradiation failed in the pelvis. Correlation with the doses of irradiation given to the uterus or the pelvic lymph nodes indicate that with doses below 5000 rads a significantly higher number of pelvic recurrences take place, whereas these are uncommon with doses over 6000 rads. The difference in pelvic recurrences between dosage levels is not, however, statistically significant. It is suggested that patients with Stage I and II malignant mixed mullerian tumors of the uterus should be treated with preoperative radiation and total hysterectomy with bilateral salpingo-oophorectomy. Patients with more advanced disease have extremely poor prognosis and should be treated with radiation therapy alone. This tumor has a high propensity to spread through lymphatics and hematogenous metastases are seen in approximately 75% of the patients. Because of this dissemination, significant improvements in survival rate will not be seen until effective cytotoxic agents are available.

Syrjanen, K. J. (1979). "A diffuse mixed histiocytic-lymphocytic lymphoma associated with immunological abnormalities." Arch Geschwulstforsch 49(4): 289-98.

A diffuse generalized lymphoma histologically classified as mixed histiocytic-lymphocytic type and associated with profound immunologie abnormalities is reported. The patient had an autoimmune hemolytic anemia, an autoimmune thrombocytopenia, polyclonally increased IgG and IgM, polyclonal secretion of kappa and lamda chains into urine, very low serum complement C3 and antibodies against glomerulus and smooth muscle. When studied with the modern surface-marker techniques, the lesion was found to be composed of entirely lymphoid cells of the B-lymphocyte series. The proper classification of this tumor could be a primitive immunoblastic sarcoma. The relationship of the present tumor to the non-neoplastic angioimmunoblastic lymphadenopathia is discussed. The necessity of applying the surface-marker techniques in the classification of malignant lymphomas is emphasized.

Clement, P. B. and R. E. Scully (1978). "Extrauterine mesodermal (mullerian) adenosarcoma: a clinicopathologic analysis of five cases." Am J Clin Pathol 69(3): 276-83.

Five extrauterine examples (three pelvic and two ovarian) of a distinctive mesodermal (mullerian) mixed tumor previously described to occur in the uterus and designated mullerian adenosarcoma are reported. The tumors were diagnosed during the fifth to eight decades of life. They usually formed very large, partly cystic masses, which had occasionally spread to adjacent organs by the time of operation. On microscopic examination the tumors consisted of benign-appearing neoplastic glands lying in a sarcomatous stroma. The glands were lined by a variety of mullerian epithelial cell types, and the stromal element resembled endometrial stromal sarcoma. Three patients had malignant courses manifested by intrabdominal recurrence, distant metastases, or both. This tumor should be clearly distinguished from the more common forms of mesodermal (mullerian) mixed tumor in which the epithilial as well as the stromal component is malignant and the prognosis is much more grave.

Kim, H., R. F. Dorfman, et al. (1978). "Signet ring cell lymphoma. A rare morphologic and functional expression of nodular (follicular) lymphoma." Am J Surg Pathol 2(2): 119-32.

Nodular lymphomas and diffuse lymphomas of corresponding cellular composition have been shown to arise from follicular center cells. This paper describes a rare functional and morphological expression of malignant lymphomas arising from follicular center cells, namely, immunoglobulin production, an observation for which no detailed description or nanlysis is available in the literature. Furthermore, the unusual signet ring-like appearance of the lymphoma cells, which is due to retention of immunoglobulins within the cytoplasm, may result in an erroneous interpretation of metastatic adenocarcinoma or liposarcoma. Therefore, we are presenting a detailed analysis of light microscopic, histochemical, immunocytochemical, and ultrastructural observations. The lymphomas of all seven patients in our series showed nodular growth patterns; in all but one, diffuse areas were also observed. Five of the lymphomas were classified as poorly differentiated lymphocytic type and two as mixed cell type, according to Rappaport's classification. In four of the seven patients, the majority of the neoplastic cells had a clear vacuolated cytoplasm, and in three of these cases, a few of the neoplastic cells showed immunoperoxidase positivity for monoclonal IgG. This group in particular closely simulated metastatic carcinoma composed of so-called signet ring cells. In the remaining three cases, most of the neoplastic cells contained PAS-positive, Russell body-like monoclonal IgM. Ultrastructurally, the monoclonal IgG appeared as even-sized electron-dense spherules or irregular electron-dense clumps, while the monoclonal IgM appeared as membrane bound, homogeneous, electron-dense material. The implications of these findings and the morphologic features which are helpful in the identification of these lymphomas are discussed.

Leong, A. S., P. A. Cowled, et al. (1978). "Erythroderma, an unusual manifestation of B cell lymphoma." Br J Dermatol 99(1): 99-106.

A case is described in which the initial manifestation of a malignant lymphoma was an erythematous skin rash over the face, scalp and trunk. Immunological surface marker analysis showed the malignant cells to be of B lymphocyte origin with a homogeneous secretion of IgM-K. Repeated skin and lymph node biopsies and finally post mortem documented the progression of the lymphoma from that of a mixed lymphocytic-histiocytic type with a nodular pattern of growth to a diffuse histiocytic lymphoma with frequently bizarre cells. The theory of ecotaxis or homing of lymphocytes to the skin and other non-lymphoid organs of the body is discussed in an attempt to explain the occurrence of cutaneous involvement as a primary manifestation of lymphoma.

Stein, H., C. S. Papadimitriou, et al. (1978). "Demonstration of immunoglobulin production by tumor cells in non-Hodgkin's and Hodgkin's malignant lymphomas and its significance for their classification." Recent Results Cancer Res 64: 158-75.

Combined application of morphologic, immunochemical, and immunologic methods has led to a reinterpretation of non-Hodgkin's lymphomas and to the establishment of the Kiel classification. In the present paper, the main Ig-producing entities are considered. These are: 1. Chronic lymphocytic leukemia of the B-type (B-CLL)--a proliferation of lymphocytes and a few so-called prolymphocytes and lymphoblasts. The mean tissue IgM value is slightly increased; the serum IgM level is normal or reduced. The tumor cells bear SIg, and a majority of them have a receptor for C3d but always lack CIg and are usually devoid of receptors for C3b. 2. Lymphoplasmacytoid immunocytoma--a mixed proliferation of lymphocytes and centrocytes, blast cells, plasma cells, or plasmacytoid cells. The tissue Ig content is most often (91%) and most highly increased in this group, whereas the serum Ig level is increased in only 20% of the cases. The tissue IgM of 17 cases was shown to be monoclonal by IEF. Most tumor cells have SIg and a variable numbear CIg. The tumor cells bear both complement receptor subtypes, only a receptor for C3b, or no complement receptors at all. 3. Centroblastic/centrocytic lymphoma--usually a follicular proliferation of abundant small germinal center cells (centrocytes) and some large germinal center cells (centroblasts). The tumor cells bear SIg and both complement receptor subtypes. The C3b- and C3d-positive cells are located in the follicles, as in nonneoplastic lymphatic tissue. 4. Centrocytic lymphoma--a purebred, diffuse proliferation of the small germinal center cells (centrocytes). These cells bear SIg and receptors for C3b and C3d but usually lack CIg. 5. Centroblastic lymphoma--a proliferation of the large germinal center cells (centroblasts). 6. Lymphoblastic lymphoma of Burkitt's type. 7. Immunoblastic lymphoma--a diffuse proliferation of large basophillic cells resembling immunoblasts. The tissue IgM content is increased in 60% of the cases. It proved to be monoclonal with IEF in all five cases studied. The cells of five cases with increased tissue Ig content bore SIg. Nearly half of the cases studied showed CIg. Besides non-Hodgkin's lymphomas, paraffin sections of 87 biopsies from Hodgkin's disease were investigated for CIg in Hodgkin's and Sternberg-Reed cells. These cells stained positively in 68 cases, most often for IgG, followed by IgD. In five cases of the lymphocyte-depleted type, the staining of the Hodgkin's and Sternberg-Reed cells was restricted to one light chain type.

Manes, J. L. and H. B. Taylor (1976). "Carcinosarcoma and mixed mullerian tumors of the fallopian tube: report of four cases." Cancer 38(4): 1687-93.

We report a 74-year-old woman with malignant mixed mullerian tumor and three women, aged 47, 58, and 76 years, with carcinosarcomas, all primary in the fallopian tube. The tumors grew predominantly intraluminally and were associated with hydrosalpinx. All four patients underwent salpingectomy. Two of them received radiation therapy; one died within 9 months because of the tumor and the second is well 2 years after diagnosis. Of the two women without additional therapy, one is alive with tumor 53 months postoperatively and the other is well 1 year after surgery. Available data suggest that these neoplasms are relatively radioresistant and that their prognosis correlates best with local invasiveness.

Acevedo, H. F., E. A. Campbell, et al. (1976). "Urinary cholesterol. VIII. Its excretion in women with ovarian neoplasms." Cancer 37(6): 2847-57.

The urinary excretion of nonesterified cholesterol (NEC) has been investigated in 57 women with ovarian neoplasms and/or related nonneoplastic diseases. Twelve patients had benign tumors or lesions and 45 had malignant neoplasms of their ovaries. All patients with nonmalignant ovarian tumors or lesions had normal NEC excretion irrespective of the type of tumor or lesion or its degree of extension. In contrast, urinary NEC hyperexcretion occurred with the following frequencies in patients with active malignant ovarian neoplasms: 18 of 19 cystadenocarcinomas of the serous and/or mucinous types; one of one endometrioid carcinoma; four of four malignant granulosa cell tumors; two of two mixed malignant germ cell tumors; and one of one malignant mixed mullerian tumor. Single cases of clear cell carcinoma and of rhabdomyosarcoma had a normal NEC excretion. Urinary hyperexcretion of NEC was also found after surgery in two of seven surviving patients with apparently localized resectable disease according to their staging. It is possible that in these two patients NEC hyperexcretion was due to undetected foci of cancer (wrong staging), since neither omental and peritoneal biopsies, nor cytologic examination of peritoneal washings or free fluid were performed. A normal excretion of urinary NEC has been characteristic of 19 of 21 surviving patients treated by surgery and adjunctive therapy in whom we have performed follow-up NEC determinations. They were 16 of 18 cystadenocarcinomas malignant germ cell tumor. The 94% correlation between the presence of proven active ovarian carcinomas and urinary NEC hyperexcretion is significant. The clinical significance of this investigation is even greater when one considers that cystadenocarcinomas constitute more than 75% of all primary malignant ovarian tumors.

Emura, M., K. Kano-Tanaka, et al. (1976). "Attempts to induce tubular deformations and subsequent mixed tumours from organotypic cultures of mouse renal mesenchyma." Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 85(1): 39-46.

With the aim of expanding knowledge on the pathogenesis of nephroblastomata, an embryological organ culture system (Grobstein, 1956) was tested for its applicability to in vitro carcinogenesis experiments by using murine sarcoma virus (MSV-M) and 3-methylcholanthrene (MCA). Treatment of CBA/H-T6 mouse metanephrogenic mesenchyma with MSV-M at the pretubular stage neither disturbed the glomerulogenesis nor induced rapid malignant transformation. Treatment of the same tissues with MCA considerably inhibited the glomerulogenesis but failed to also reduce rapid malignant transformation. However, one MSV-M, one MCA and two untreated cultures showed malignant transformation after prolonged survival in vitro and produced different histological types of tumours upon transplantation into newborn CBA/H-T6 mice.

Roth, L. M., G. L. Pride, et al. (1976). "Mullerian adenosarcoma of the uterine cervix with heterologous elements: a light and electron microscopic study." Cancer 37(4): 1725-36.

A mullerian adenosarcoma with heterologous elements having the gross appearance of a sarcoma botryoides occurred in the uterine cervix of a 14-year-old girl. Histologically, the tumor was composed of an admixture of benign-appearing glands and a sarcomatous stroma, the latter containing areas of undifferentiated sarcoma and endometrial stromal sarcoma, as well as heterologous elements consisting of rhabdomyosarcoma and hyaline cartilage. No malignant epithelial component was observed. The distribution of benign mullerian-type glands throughout the tumor simulated a malignant mixed mullerian tumor in appearance. Ultrastructural studies of the stromal elements of the neoplasm suggest origin from primitive mullerian stroma, and the glands have features of primitive mullerian epithelium. This study supports the concept that the malignant mixed mullerian tumor and related mullerian sarcomas originate from a common undifferentiated multipotential mullerian stem cell.

Schmidt, J. and K. D. Balz (1976). "[Two malignant uterine tumors of embryonic tissue residues. (Carcinoma of Gartner's ducts, Mullerian mixed tumor)]." Zentralbl Gynakol 98(23): 1456-65.

Report about a Gartnergang-carcinoma of the cervix uteri of a 24 years old woman. The cytological findings as well as the typical histological characteristics are represented. Persisting particles of the Gartnergang have been proved at the right lateral wall of the cervix uteri and in the lower parts of the corpus uteri. Report about a woman of 62 years. A Mullerian mixed tumour of the corpus uteri with myxoedematous parts has been diagnosed. It must be pointed out, that previous radiotherapy of the true pelvis may possible incluence the development of a Mullerian mixed tumour.

Aoki, T., M. Potter, et al. (1975). "Cell populations and known surface antigens of tumors induced by Abelson virus in pristane-primed BALB/c mice: an analysis by immunoelectron microscopy." J Natl Cancer Inst 55(5): 1097-106.

When Abelson murine leukemia virus (MuLV-A) was inoculated into pristane-primed BALB/c mice, either plasmacytomas (PCT), lymphosarcomas, or their mixed form was induced with a shorter latent period than that for PCT induction in mice treated with pristane alone. All 3 neoplasms were designated Abelson's tumors. The morphology of the induced malignant cells and the presence of known surface antigens were analyzed by electron microscopy. The cell surface antigens (CSA) examined were PC1, X.1, Gross (GCSA), and Moloney (MCSA); viral envelope antigens (VEA) were xVEA, x1-VEA, sub-gsVEA, and MVEA. MuLV-A-pristane-induced PCT cells produced markedly fewer intracisternal type-A particles than did mineral oil-induced PCT cells. Most, if not all, mineral oil-induced PCT cells carried PC1 antigen and produced many extracellular type-C viruses carrying xVEA and x1-VEA, whereas Abelson's tumor cells had both a lower incidence and a smaller amount of PC1 and X.1 antigens and xVEA+ virus and lacked x1-VEA+ virus. In addition, most Abelson's tumors and their type-C viruses did not carry MCSA and MVEA ro GCSA and sub-gsVEA. All the macrophages in the PC1+ Abelson's tumors and many macrophages in PC1-Abelson's tumors contained various amounts of PC1 on their cell surfaces. For these reasons, Abelson's tumors were clearly distinct from pristane- or mineral oil-induced BALB/c PCT and from M-MuLV- ro G-MuLV-induced tumors.

Lapin, B. A., L. A. Yakovleva, et al. (1975). "Transmission of human leukaemia to nonhuman primates." Proc R Soc Med 68(3): 141-5.

The experiments described show that inoculation of two monkey species, M. arctoides and P. hamadryas, with human leukaemic blood or its filtrates causes a viral disease with the characteristics of malignant lymphoma of mixed type. The disease was passed in subsequent passages. The virus was isolated and identified as an oncornavirus of C-type by its characteristic morphological appearance and buoyant density (1.16 g/cm3 in sucrose and 1.21 g/cm3 in caesium chloride), and by the presence of 60-70S RNA and RNA-dependent DNA polymerase. There is some evidence that it differs immunologically from other known oncornaviruses of mammals including primates. It is postulated that both horizontal and vertical transmission of this oncornavirus can occur.

Lennert, K., H. Stein, et al. (1975). "Cytological and functional criteria for the classification of malignant lymphomata." Br J Cancer 31 SUPPL 2: 29-43.

The subtle morphology and functional properties of cells are the best parameters to use for their definition. This is also true for the corresponding tumours, especially malignant lymphomata. In studies of 106 cases of malignant lymphoma we therefore applied as morphological methods haematological staining (Giemsa in sections and imprints) and electron microscopic analysis. As functional criteria we used the nonspecific esterase reaction to define tumours of histiocytes and an estimation of the immunoglobulin content of tissue extracts and single cells to define tumours of B lymphocytes and their derivatives. By combining all of these methods it was possible to propose a new classification. Whereas not one histiocytic malignant lymphoma ("reticulosarcoma") was found in the series, at least most of the malignant lymphomata investigated seemed to be derived from the B lymphocyte system. The following types are distinguished: (1) Chronic lymphocytic leukaemia; (2) diffuse germinocytoma (malignant lymphoma, lymphocytic, intermediate); (3) germinoblastoma (follicular, follicular and diffuse, diffuse; sclerotic, nonsclerotic) which can show a transition into germinoblastic sarcoma; (4) immunoblastic sarcoma of the B cell type (previously called reticulo-sarcoma); (5) lymphoplasmocytoid immunocytoma, which may be associated with Waldenstrom's macroglobulinaemia and can show a mixed cellularity; (6) lymphoblastic (paraleukoblastic) sarcoma and leukaemia, which are, at least in most cases, probably neoplasias of germinoblasts. All of these lymphomata can produce immunoglobulins. Sixty-seven cases showed an Ig increase in the tumour. This was mostly IgM, but sometimes IgG, IgA, IgD and/or IgE. A morphological equivalent of even abnormal Ig secretion is the globular positive (diastase resistant) PAS reaction in lymphoid cells (not in the histiocytes) in paraffin sections, which we found in 43 cases. Only 19 of the 63 cases with an IgM increase in the tumour showed an increase of IgM in the serum. Waldenstrom's macroglobulinaemia is a facultative symptom of morphologically different malignant lymphomata and should therefore be considered only as a clinical syndrome and not as a nosological entity.

Kahner, S., A. Ferenczy, et al. (1975). "Homologous mixed Mullerian tumors (carcinosarcomal) confined to endometrial polyps." Am J Obstet Gynecol 121(2): 278-9.

Ritzmann, S. E., D. Loukas, et al. (1975). "Idiopathic (asymptomatic) monoclonal gammopathies." Arch Intern Med 135(1): 95-106.

Asymptomatic forms of monoclonal gammopathies (MG) are recognized with increasing frequency; their recognition and differentiation from the symptomatic forms of MG appear imperative, since the therapeutic approaches are different. Available clinical and laboratory indexes lack specificity required for useful and practical discrimination; presently, we must still rely on the timecourse monitoring of such laboratory values as hemoglobin levels, M-protein concentrations, and presence of Bence Jones proteins. Elucidation of histocompatibility A and W antigenic profiles, as well as the functions and kinetics of B-lymphocytes from such patients, appear most promising. Evidence of the causative role of extrinsic and intrinsic antigenic stimulation in MG production is increasing; segregation into two distinct concentration ranges of M-proteins in the asymptomatic and symptomatic groups suggests two control levels of the expression of immune response (Ir) genes, due to partial or complete derepression of the latent Ir gene function, reflecting "partial" (asymptomatic, benign MG) and "complete" (symptomatic, malignant MG) monoclonal immune responders.

Copeland, D., D. P. Sengar, et al. (1974). "Mixed leucocyte culture blocking factor activity in the plasma of patients with cancer." Oncology 30(5): 393-404.

Plasma samples obtained from 74 patients with malignant disease were assayed for their ability to suppress or block the mixed lymphocyte reactivity of random normal donors. 24 of the 74 patients investigated had evidence of mixed lymphocyte culture blocking factoractivity (MLC-BFA). 19 of 33 patients with disseminated disease had evidence of MLD-BFA whereas in only 5 of 41 patients with localized disease was evidence of BFA found. There was a relationship between a history of previous blood transfusion inthe 6-month period prior to study and the presence of MLC-BFA in patients' plasma. Excluding this group of patients, where previous transfusion might have been responsible for MLC-BFA and excluding, too, that group of patients with a history of past pregnancy,there remained still 11 patients with evidence of BFA in their plasma. Nine of these11 had widely disseminated and progressiv disease. MLC-BFA was found in both IgM and IgG fractions of plasma. Plasma with MLC-BFA was found to suppress normalin vitro lymphocyte responses to mitogens PWM and PHA. The MLC-BFA assay utilized in this work may provide the means of monitoring cancer patients in order to detect 'blocking' antibody.

Wu, J. P., W. S. Tanner, et al. (1973). "Malignant mixed mullerian tumor of the uterine tube." Obstet Gynecol 41(5): 707-12.

Bashour, B. N., K. Mancer, et al. (1973). "Malignant mixed mullerian tumor of the cervix following cyclophosphamide therapy for nephrotic syndrome." J Pediatr 82(2): 292-3.

Silverberg, S. G. (1971). "Malignant mixed mesodermal tumor of the uterus: an ultrastructural study." Am J Obstet Gynecol 110(5): 702-12.

De Queiroz, A. C. and L. M. Roth (1970). "Malignant mixed mullerian tumor of the fallopian tube. Report of a case." Obstet Gynecol 36(4): 554-7.

Hurrell, D. P. and W. G. McCluggage "Uterine leiomyosarcoma with HMB45+ clear cell areas: report of two cases." Histopathology 0(0).