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