Uterine Carcinosarcomas - Diagnosis and Management.

Uterine carcinosarcomas are rare tumors that account for less than 5% of all uterine malignancies. These tumors (previously called malignant mixed Müllerian tumors) are dedifferentiated carcinomas that comprise carcinomatous and sarcomatous elements and arise from a single malignant clone. They are considered a high-risk variant of endometrial adenocarcinoma because carcinosarcomas share more similarities in epidemiology, risk factors, and clinical behavior with endometrial carcinoma than with uterine sarcomas. The clinical features, diagnosis, staging, and treatment of uterine carcinosarcoma will be discussed in this review.

Breast Cancer is Common in Women With Ovarian Malignant Mixed Mullerian Tumors.

BACKGROUND: Ovarian malignant mixed Mullerian tumors (MMMTs) are uncommon cancers. The purpose of the study was to determine the rate of metachronous or synchronous breast cancer as well as the rate of truncating germline BRCA1 and/or BRCA2 mutations in a series of women with these uncommon tumors. MATERIALS AND METHODS: Records were reviewed to identify all women with MMMTs treated by the gynecologic oncology service. The stage, grade, histology, survival, and rate of coexistent breast cancer were determined. Tumor and/or peripheral blood was tested for BRCA1 and BRCA2 truncating mutations. RESULTS: Twenty-four patients with MMMTs were found. Tumor and paired peripheral blood was available on 20 patients and 4 more patients had only peripheral blood available. Family pedigrees were available on all 24 patients. Fifteen of 24 (62.5%) patients were found to have metachronous or synchronous breast cancers with 9 of 15 (60%) having bilateral breast cancer. No BRCA1 or BRCA2 mutations were found (somatic or germline) in this cohort. CONCLUSIONS: Although an uncommon tumor, MMMTs are often found in women with breast cancer. Despite this finding, BRCA1 or BRCA2 germline mutations are not common in this population. PRECIS: Ovarian MMMTs are frequently found in women with cancer but are not frequently associated with defects in BRCA1 or BRCA2.

Uterine carcinosarcoma/malignant mixed Mullerian tumor incidence is increased in women with breast cancer, but independent of hormone therapy / 부인종양

No abstract available.

[Carcinosarcomas in female genital tracts: general review]. / Carcinosarcomes gynécologiques: revue générale et principes de prise en charge.

Carcinosarcoma, also known as mixed mesodermal tumor or malignant mixed Mullerian tumor (MMMT) is a pathological entity combining a sarcomatous and a carcinomatous component. Found in thoracic, digestive, genitourinary, liver or skin locations, the most common location is the female genital tract. In gynecological tumors, carcinosarcoma accounts for about 2-5% of endometrial cancers, and 1% of ovarian cancers. To date, there is no consensus on the therapeutic strategy. It relies mostly on maximum cytoreductive surgery. Adjuvant therapy remains controversial, and few prospective studies investigating its interest. Retrospective studies show the benefits of adjuvant chemotherapy based on platinum in most cases. Radiation therapy has a place in the adjuvant situations of endometrial and cervical carcinosarcoma. A more detailed pathological knowledge, and the use of targeted therapies may be promising in this histological subtype whose prognosis remains very poor. The objective of this study is to present the main principles of carcinosarcoma management in female genital tracts, describing pathological and prognostic features at the same time.

The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Tumor mülleriano mixto maligno: la experiencia de un único centro con 43 casos de 1990-2006 / Mixed malignant Mullerian tumours: the experience of a single centre with 43 cases from 1990-2006

Objetivo: Se realiza un estudio descriptivo de las pacientes con diagnóstico de tumor mülleriano mixto maligno (TMMM) en términos de epidemiología, diagnóstico, tratamiento, seguimiento, recurrencias y supervivencia. Material y método: Se revisaron los archivos anatomo-patológicos y las historias médicas de las pacientes tratadas durante el período 1.990-2.006. Las supervivencias se analizan mediante las curvas de Kaplan-Meier. Se emplea un análisis de regresión logística en el estudio uni y multivariable.Resultados43 pacientes son incluidas en esta revisión. El tratamiento inicial fue quirúrgico en el 79% de los casos. El 34,9% de las pacientes se diagnosticaron en estadio I; 16,3% en estadio II; 34,9% en estadio III y 9,3% en estadio IV. Se alcanzó una respuesta completa en el 60,4%. La enfermedad persistió en el 39,6%. La supervivencia libre de enfermedad a los 2, 5 y 10 años fue del 50%, con una mediana de 15 meses (IC 95% 6-32). La tasa de recurrencia fue del 42,3% con un tiempo medio de 8,4 meses. La supervivencia total a los 2, 5 y 10 años fue del 26% con una mediana de 7 meses (IC 95% 1-44). En el análisis univariante el tamaño tumoral, la invasión linfovascular, el estadio y la radioterapia pélvica adyuvante son factores pronósticos. En el análisis multivariante la invasión linfovascular, el estadio y la radioterapia son factores pronósticos independientes. Conclusión: Los TMMM son tumores de comportamiento clínico extremadamente agresivo con un pronóstico pobre. Los factores pronósticos que afectan la supervivencia son el estadio, la invasión linfovascular y la radioterapia pélvica (AU)

Objective: Malignant mixed Müllerian tumours (MMMT) patients were retrospectively evaluated in terms of epidemiology, diagnosis, treatment, follow-up, recurrent disease and survival. Methods: Medical and histopathology records were reviewed during the 17-year period 1990-2006. Survival rates were analysed by means of the Kaplan-Meier technique. The Cox proportional hazards regression model was used in uni- and multivariate analysis. Results: A total of 43 patients were included in this study. First-line treatment was surgery in 79% of cases. Stage I, II, III and IV were identified in 34.9%, 16.3%, 34.9% and 9.3%, respectively. A complete response was achieved in 60.4% of patients. The disease was progressive in 39.6%. Event–free survival at 2, 5 and 10 years was 50% for all, with a median time of 15 months (95% CI,6-32). There was a 42.3% recurrence-rate with a mean time to recurrence of 8.4 months. The 2, 5 and 10-years overall survival was 26% with a median time of 7 months (95% CI, 1-44). In the univariate analysis tumour size, lymphovascular infiltration, stage and pelvic radiotherapy are prognostic factors. In the multivariate analysis lymphovascular infiltration, stage and radiotherapy were found to have an independent influence on overall survival. Conclusions: MMMT are tumours of aggressive clinical behaviour with a poor prognosis. Stage, lymphovascular infiltration and adjuvant radiotherapy are the dominant prognostic factors (AU)

[Malignant mixed mullerian tumors--case report].

Malignant Mixed Mullerian Tumors (MMMT) are part of the malignant neoplasms of the uterus. They have aggressive growth and bad prognosis. Usually at the time of diagnosis the disease is already too advanced. Almost all of these tumors occur after the menopause and the most frequent presenting symptom is vaginal bleeding. A few cases of patients who underwent surgery at Second Gynecology Clinic at the University Hospital of Obstetrics and Gynecology "Maichin dom"-Sofia are presented.

Primary peritoneal carcinoma in a UK cancer center: comparison with advanced ovarian carcinoma over a 5-year period.

The relative incidence of primary peritoneal carcinoma (PPCa) and advanced (FIGO stage III or IV) ovarian serous carcinoma (AOSCa) was assessed over 5 years at a UK cancer center, and the sociodemographic, clinical, and survival data were compared. There were 23 women with PPCa and 55 with AOSCa. The ratio of PPCa:AOSCa was higher than previously reported. No statistical difference was found between the two groups with regard to age (mean 64.43 vs 64.07 years, P= 0.9), parity (1.6 vs 1.8, P= 1.0), personal/family history of another malignancy (although five patients with AOSCa but none with PPCa had personal histories of breast cancer), or serum CA125, CA19.9, and carcinoembryonic antigen (CEA) levels. Similar numbers in both groups had malignant ascites, although 5.8% of patients with AOSCa but none with PPCa had negative cytology. Tumor grade, stage, treatment, and survival were similar (median 586 vs 641 days, P= 0.66). This analysis of the largest published UK series of patients with PPCa does not support previous reports that patients with PPCa are older than those with AOSCa and have a worse prognosis; it suggests that both groups have similar sociodemographic characteristics, clinical profiles, and survival.

Is tamoxifen associated with high-risk endometrial carcinomas? A retrospective case series of 196 women with endometrial cancer.

Tamoxifen therapy is associated with an increased risk of endometrial cancer. There is controversy regarding the incidence of high-grade endometrial malignancies associated with tamoxifen therapy. This retrospective study assesses pathological features of endometrial malignancy in patients with and without a history of tamoxifen therapy. This is a retrospective case analysis from a district general hospital. The cases were identified from the pathology database and the medical notes reviewed. The period of the study was January 1994 to December 2001. One hundred and ninety six women with endometrial cancer were identified. 20 patients had a history of breast cancer being treated with adjuvant tamoxifen therapy and developed subsequently endometrial cancer. The histology in women who had not taken tamoxifen showed: adenocarcinoma (97.1%), 1.7% had mixed mullerian tumour. Women in the tamoxifen-treated group had: adenocarcinoma (85%), sarcoma (5%), mixed mullerian tumour (5%). In this study the tamoxifen-treated group of patients developed endometrial malignancies with a higher incidence of poor prognostic malignancies (p = 0.01). Further research is needed to analyse the precise tumour types and pathophysiology.

Does tamoxifen use affect prognosis in breast cancer patients who develop endometrial cancer?

OBJECTIVE: The use of tamoxifen to prevent breast cancer and decrease recurrence is not controversial. However, the effect that tamoxifen may have in women with a history of breast cancer in whom endometrial cancer develops is unclear. The purpose of this study was to estimate whether a history of tamoxifen use is a prognostic factor for such patients. METHODS: Between 1990 and 2002, patients seen at The University of Texas M. D. Anderson Cancer Center with a history of breast cancer who developed endometrial cancer were identified. Medical records were reviewed to identify clinical, pathologic, and outcome information. RESULTS: Eighty-nine patients with a history of breast cancer in whom endometrial carcinoma developed were identified. Fifty-two percent (46/89) had a history of tamoxifen use (median duration 48 months; range 2-120 months). There were no significant differences in the clinical or pathologic features between tamoxifen users and nonusers. A history of tamoxifen use was associated with a shorter interval from breast cancer to endometrial cancer diagnosis (77.2 versus 121.3 months for nonusers; P =.01). There was no significant difference in overall survival between tamoxifen users and nonusers (39.2 months versus 48.3 months, P =.27), and there was no difference in endometrial cancer-specific survival duration between tamoxifen users and nonusers (55.7 versus 51.0 months, P =.92). CONCLUSION: Among tamoxifen users, the interval from breast cancer to endometrial cancer diagnosis was significantly shorter than that in nonusers. In this cohort, a history of tamoxifen use was not associated with a worse overall or disease-specific survival.

Malignant mixed Mullerian tumours of the uterus--a ten-year experience.

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

Tumores müllerianos mixtos. Revisión bibliográfica. A propósito de tres casos de localización diferente: vaginal, uterina y ovárica / Müllerian mixed tumours. A literature review. Three case studies with different localizations: vaginal, uterine, and ovarian

Los tumores müllerianos mixtos son neoplasias cuyo origen son las células estromales primitivas que originariamente derivan del mesodermo mülleriano. Reciben el nombre de mixtos porque están constituidos por elementos glandulares malignos y estromales sarcomatosos (AU)

No disponible

Hormone replacement therapy and risk of epithelial ovarian cancer.

It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case-control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32-4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% CI 1.54-5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours.

Cluster of uterine mullerian adenosarcoma in the Washington, DC metropolitan area with high incidence of sarcomatous overgrowth.

Mullerian adenosarcoma is an uncommon variant of uterine sarcoma. Twelve uterine adenosarcomas were diagnosed during a 42-month period at the Washington Hospital Center in Washington, DC. Based on estimated incidence data derived from the US Department of Defense beneficiary population, an estimated relative risk of 15.4 (95% confidence interval, 7.7-31.0) was calculated, indicating a significantly increased incidence of adenosarcoma in the population studied (p<0.0000001). Among 10 patients who underwent hysterectomy, six (60%) of their tumors had sarcomatous overgrowth. In comparison with the previously reported proportion of adenosarcomas with sarcomatous overgrowth, approximately 16%, the proportion with sarcomatous overgrowth was significantly higher than expected (p<0.01). Mullerian adenosarcoma with sarcomatous overgrowth was first described in 1989 and suggests that the cluster of adenosarcomas reported herein may be due in part to the current classification of some uterine tumors as adenosarcoma with sarcomatous overgrowth that previously would have been classified as other types of uterine sarcoma. Nonetheless, even after reviewing and updating the classification of all sarcomas diagnosed at the Washington Hospital Center from 1985 to 1998, the ratio of adenosarcomas to uterine adenocarcinomas during the 1994-1998 period was 4.7 times (p<0.005) that of the 1985-1993 period, suggesting a more modest but real increase in the occurrence of this tumor. Correct classification of mullerian adenosarcomas with sarcomatous overgrowth is important because the limited available data suggest that the prognosis is notably worse than that for adenosarcomas without sarcomatous overgrowth.

Midline teratomas, mullerianosis, the multifariousness of gynaecological neoplasias, and the scrotum. Are they manifestations of a germ-soma barrier?

Empirical evidence and theoretical considerations suggest that there are mechanisms protecting the germ line from untoward somatic influences. In the intraorganismal competition between cell lineages, evolution will give priority for protection to the germ line, which carriers the heritable genes. In embryogenesis, germ cells migrate along the midline as this is an area where developmental influences are lower; exposure to somatic factors may cause inception of teratomas. In order not to hinder the germ line, the female genital tract has a reduced level of cell determination, which results in the multifariousness of gynaecological proliferations, including mullerianosis. The external location of testes reduces somatic constraints on spermatogenesis.

Uterine cancer--the KK Hospital experience.

Kandang Kerbau Hospital saw 165 new cases of uterine cancers over the 4-year period from 1991 to 1994. The median age of presentation was 54.1 years and 10.9% of these cases occurred in those aged less than 40 years, unlike the corresponding figures of 61 years and less than 5%, respectively, which are often quoted for endometrial cancers in standard textbooks. Endometrioid adenocarcinoma was the commonest type of uterine cancer seen in our population (75.2%) as in other series. However, we had fewer cases of adenoacanthoma (1.4%) and adenosquamous carcinoma (1.4%) but more cases of uterine sarcoma (11.5%) than is usually reported. 6.7% of our patients had papillary serous adenocarcinoma and 3.0% had clear cell carcinoma. These 2 sub-types are associated with poorer prognosis and there is a need to increase awareness of their existence in our local population as their management differs from that for the usual endometrioid adenocarcinoma. We had fewer patients with stage I disease (53.3%) but more patients with stage III disease (22.4%). This is most likely due to the use of surgico-pathological staging currently as opposed to the clinical staging used previously which led to the under-staging of a proportion of patients.

Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus.

BACKGROUND: We analyzed data from a population-based, multi-center, case-control study to determine whether the occurrence of histologic types of uterine sarcoma is related to exogenous hormone use and/or to two correlates of endogenous estrogens: excess weight and cigarette smoking. METHODS: One hundred sixty-seven women with newly-diagnosed uterine sarcoma (56 leiomyosarcoma, 85 mixed mullerian tumors, and 26 endometrial stromal sarcomas) were interviewed by telephone regarding possible risk factors for these neoplasms, For comparison, 208 women identified at random from the general population of the study areas were interviewed as controls. RESULTS: Use of oral contraceptives was positively associated with the risk of leiomyosarcoma (odds ratios [OR] = 1.7, 95% confidence interval [CI] = 0.7, 4.1), primarily among women who last used these medications 15 or more years prior to diagnosis. Use of noncontraceptive estrogens was directly associated with the risk of mixed mullerian tumors, but only among recent and long-term users of these medications. Women in the highest quantile of body mass index (> or = 27.5 kg/m2) one year prior to diagnosis were at increased risk of each type of uterine sarcoma (leiomyosarcoma, OR = 2.5, 95% CI = 1.1, 5.7; mixed mullerian tumors, OR = 2.9, 95% CI = 1.3, 6.7; stromal sarcoma, OR = 3.5, 95% CI = 1.1, 10.9). Women who had ever smoked cigarettes were at reduced risk of leiomyosarcoma (OR = 0.6, 95% CI = 0.3, 1.1) and stromal sarcoma (OR = 0.5, 95% CI = 0.2, 1.2), but the relationship was not more pronounced among heavy smokers; no association with smoking was observed with mixed mullerian tumors. CONCLUSIONS: Several of these findings parallel those from studies of endometrial carcinoma and may indicate a role for unopposed estrogen in the etiology of histologic types of uterine sarcoma.