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.

Tumores müllerianos mixtos malignos uterinos / Uterine malignant mixed mullerian tumors

Los tumores müllerianos mixtos malignos o carcinosarcomas son neoplasias poco frecuentes y altamente agresivas que suelen presentarse en pacientes mayores de 60 años, generalmente en forma de metrorragia posmenopáusica y/o presencia de masas uterinas. Entre los factores de riesgo reconocidos está descrita la historia de irradiación previa del área pélvica. Presentamos 3 casos clínicos de pacientes diagnosticadas y tratadas de tumores müllerianos mixtos uterinos malignos, existiendo en todos ellos el antecedente de neoplasias que habían precisado radioterapia pélvica como parte de su tratamiento.

The malignant Mullerian mixed tumors are rare and highly aggressive, these tumors usually occur in women over 60 years and the most common clinical appearance is that of postmenopausal vaginal bleeding or the presence of uterine mass. As a risk factor is described the history of prior irradiation of the pelvic area. We reported the case of three patients with mullerian mixed tumors, in all these cases the patients have a history of cancer who required pelvic radiation as part of their treatment.

[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.

Irradiation-induced uterine malignant mixed müllerian tumor.

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.

Post-irradiation carcinosarcoma of uterus--a case report.

The carcinosarcoma (malignant mixed mullerian tumour) of uterus is an aggressive neoplasm composing of malignant glands in the malignant stroma showing biphasic appearance. A 55 year old woman presented with discharge per vaginum of one month duration. Earlier she was given radiotherapy for squamous cell carcinoma of vulva, six years back. Abdominal examination was insignificant. USG suggested presence of post-radiation effect with uterine mass. Panhysterectomy was done and on histopathology, the diagnosis of carcinosarcoma (heterologous variant) was made. The case is being reported and discussed.

Ureteral mullerian carcinosarcoma (mixed mullerian tumor) associated with endometriosis occurring in a patient with a concentrated soy isoflavones supplementation.

Malignant transformation and particularly malignant mixed mullerian tumor arising in extragenital endometriosis is extremely rare and occurs in the majority of cases after estrogen replacement therapy. We present a case of a 75-year-old woman who developed a ureteral malignant mullerian carcinosarcoma in a context of florid endometriosis. The patient had a history of total hysterectomy with bilateral salpingo-oophorectomy 30 years earlier for extensive endometriosis. Since 5 years, the patient has been on phytoestrogen supplementation consisting of 72 mg/day of superconcentrated soy isoflavones. This is the first case of ureteral mullerian carcinosarcoma arising in endometriosis foci after extensive phytoestrogen supplementation. Our data suggest that phytoestrogens at least in concentrated form may play a role not only in maintenance of endometriosis but also in its malignant transformation. Given the extraordinary popularity and availability of these dietary supplements, several studies are indispensable regarding their safety particularly in women with extensive endometriosis.

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.

Müllerian adenosarcoma of vagina arising in persistent endometriosis: report of a case and review of the literature.

BACKGROUND: Primary adenosarcoma arising in vaginal endometriosis poses a diagnostic challenge, especially in superficial vaginal biopsies. CASE: A 56-year-old woman, with a prior diagnosis of ovarian endometriosis, presented with a rapidly enlarging mass of the vaginal vault. Two prior biopsies were benign and showed endometriosis. The third vaginal biopsy revealed benign endometriotic glands cuffed by a cellular stroma with moderate cytologic atypia, a histological appearance diagnostic of Müllerian adenosarcoma. A 16-cm vaginal mass that had infiltrated the pelvic structures was resected. CONCLUSIONS: Close clinical follow-up of extrauterine endometriosis and clinical-pathologic correlation is necessary. Histological features such as cellular stromal cuffing around benign endometriotic glands are critical in arriving at a timely diagnosis of adenosarcoma in patients with persistent extrauterine endometriosis, even in superficial vaginal biopsies.

Extragenital mullerian adenosarcoma with sarcomatous overgrowth arising in an endometriotic cyst in the pouch of Douglas.

Mullerian adenosarcoma is a neoplasm composed of benign mullerian epithelium and a sarcomatous stroma. This tumor classically occurs in the endometrium of postmenopausal women and less frequently in the extrauterine genital tract. Rare cases of extragenital adenosarcoma have been reported. We present the case of a 23-year-old female who presented with an extragenital adenosarcoma arising in an endometriotic cyst in the pouch of Douglas. The patient was treated with local excision, chemotherapy and radiotherapy. At 2 years follow-up she was disease-free. The literature on extragenital adenosarcoma is reviewed. These tumors are clinically more aggressive than their uterine counterparts. Surgical excision is the initial treatment modality for these patients. Little information is available regarding the efficacy of adjuvant chemotherapy or radiotherapy. This is an area that requires further study.

Endometrial mixed Müllerian tumor with heterologous elements following tamoxifen therapy for breast cancer: a case report and literature review.

CASE: A 67-year-old multiparous woman received 20mg tamoxifen daily for four years after surgical treatment of breast cancer. She presented with vaginal bleeding. Uterine curettage revealed a uterine MMT with heterologous elements. She was treated surgically with adjuvant radiotherapy. Tumor cells were found to be estrogen receptor negative and progesterone receptor positive. Uterine MMT may be linked to long term use of tamoxifen. A mechanism in developing MMT other than estrogen receptor pathway may be possible.

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)

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Heterologous mullerian mixed tumor after whole body irradiation because of Hodgkin's disease in stage IV.

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

Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors.

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

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.

Endometrial müllerian carcinosarcoma after cessation of tamoxifen therapy for breast cancer.

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