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Cytogenetic findings in malignant mixed mesodermal tumors of the uterus.

Cytogenetic analyses of four malignant mixed mesodermal tumors (MMMT) of the uterus are reported, of which one was of the homologous type and three of the heterologous. Karyotypic analyses were obtained in two cases from original tumors and in two cases from tumors xenotransplanted into nude mice. The karyotype of the homologous MMMT was normal in three different passages of a nude mice xenograft line established from the primary tumor. The heterologous tumors showed normal karyotype in one case and hyperdiploid and near triploid range with extensive numerical and structural rearrangements in two cases. Deletion of chromosome 1 at p32, and deletion of chromosome 11 at q13 were common markers in anomalous cases. The chromosomes most often involved in structural rearrangements were chromosomes 1, 9, 11, 12, 17, and 19. Double minutes, homogeneously staining regions, and telomeric association were also seen.

Aged↗

A phase II trial of amonafide in patients with mixed mesodermal tumors of the uterus: a Gynecologic Oncology Group study.

Amonafide demonstrated a poor response rate and substantial toxicity in patients who had measurable, advanced mixed mesodermal tumors of the uterus. Amonafide-a drug that acts through intercalation of tumor DNA-was used to treat 16 patients who had measurable, advanced mixed mesodermal tumors of the uterus as part of a Gynecologic Oncology Group (GOG) Phase II study. The starting dose was 300 mg/m2 intravenously over 1 hour for 5 consecutive days every 3 weeks. Severe or life-threatening hematologic toxicity occurred in 50% of the patients. Two patients experienced vomiting requiring hospitalization. Other toxicities were not severe. One patient had a partial response and one had stable disease, each lasting 4 months. This dose schedule was associated with poor response rate and substantial toxicity.

Adenine↗

Incidental finding of malignant mixed mesodermal tumor at hysterectomy for uterine prolapse. A case report.

BACKGROUND: The finding of unanticipated pathology in a uterus after vaginal hysterectomy for prolapse is uncommon. CASE: An incidental small malignant mixed mesodermal tumor was found at vaginal hysterectomy in a 68-year-old woman. CONCLUSION: A MED-LINE search found no other reported cases of malignant mixed mesodermal tumor in a patient undergoing vaginal hysterectomy for uterine prolapse. Unexpected endometrial and cervical lesions will be discovered occasionally after hysterectomy for benign disease.

Aged↗

A phase II trial of ifosfamide and mesna in patients with advanced or recurrent mixed mesodermal tumors of the ovary previously treated with platinum-based chemotherapy: a Gynecologic Oncology Group study.

A phase II trial of ifosfamide and mesna in women with mixed mesodermal tumors of the ovary who had previously received platinum-containing chemotherapy was conducted by the Gynecologic Oncology Group (GOG). The starting dose of ifosfamide was 1.2 g/m2 daily iv for 5 days. Mesna was given intravenously with and at 4 and 8 hr following the administration of ifosfamide. Each dose of mesna was 20% of the total daily dose of ifosfamide. Thirty-two patients were placed on the study; 31 were evaluable for toxicity and 28 for response. Twenty-seven patients (87.1%) had previously undergone surgery and three (9.3%) had received radiotherapy before this trial. GOG grade 3 or 4 granulocytopenia occurred in 11 (35.5%) patients, and one (3.2%) developed grade 4 thrombocytopenia. Two patients (6.4%) had grade 3 neurotoxicity. A complete response was observed in one patient (3.6%) and partial responses in four patients (14.3%) for a total response rate of 17.9% (95% confidence interval = 6.1-36.9%). In conclusion, ifosfamide has activity in previously mixed mesodermal tumors of the ovary.

Adult↗

Simultaneous endometrial malignant mixed mesodermal tumor and ovarian serous adenocarcinoma.

Although simultaneous endometrial and ovarian tumors are observed occasionally, rarely are the two neoplasms histologically disparate. We report a case of simultaneous endometrial malignant mixed mesodermal tumor and ovarian serous adenocarcinoma with a single right external iliac lymph node metastasis. Using immunohistochemical profiles, we demonstrated that the two tumors are separate primary neoplasms and identified the origin of the metastatic deposit as the mixed malignant mesodermal tumor.

Cystadenocarcinoma, Serous↗

Malignant mixed mesodermal tumor in a young woman with polycystic ovary syndrome. A case report.

BACKGROUND: Malignant mixed mesodermal tumors (MMMTs) are uncommon, highly aggressive tumors of the uterus composed of both carcinomatous and sarcomatous elements, both likely to be derived from the same original stem cell. There is a strong association between endometrial adenocarcinoma and polycystic ovary disease. However, only two cases of MMMT occurring in women with polycystic ovaries have been reported. CASE: A 36-year-old woman with polycystic ovary disease developed an MMMT of the endometrium. CONCLUSION: Some cases of MMMT may be estrogen related.

Adult↗

Pelvic malignant mixed mesodermal tumor of uncertain origin: a case report.

Extra-uterine, and especially extragenital, malignant mixed mesodermal tumors (MMMT) are very rare. A large intrapelvic tumor resected from a 56-year-old woman was investigated with morphological and immunohistochemical methods. A large, soft and fragile tumor was located in the pelvic space. The tumor showed high cellularity and was biphasic; it consisted of an admixture of adenocarcinoma and various kinds of sarcomas. The latter were comprised of high-grade endometrial stromal sarcoma, pleomorphic sarcoma, and chondrosarcoma. The pleomorphic sarcoma showed a storiform pattern. The periodic acid-Schiff-positive eosinophilic hyaline droplets and globules in multinucleated giant cells revealed a typical ring-like or peripheral staining for alpha-1-antitrypsin and alpha-1 antichymotrypsin. We considered this case to be pelvic MMMT of uncertain origin, heterologous type.

Combined Modality Therapy↗

Phase II evaluation of oral trimetrexate in mixed mesodermal tumors of the uterus: a gynecologic oncology group study.

OBJECTIVES: This is a Phase II group-wide study of the Gynecologic Oncology Group to determine the toxicity and objective response rate of trimetrexate (TMTX) in patients with advanced, persistent, or recurrent mixed mesodermal tumors of the uterus who have failed higher priority treatment protocols. METHODS: TMTX was administered orally at a dose of 5 mg/m(2) BID for 5 days and repeated in 14 days. The maximum total dose was 50 mg/m(2)/week given every other week. The minimum treatment period was one course. Patients who had a complete response, partial response, or stable disease were continued on treatment for at least three courses. RESULTS: Twenty-eight patients were entered into the study. Three patients were ineligible based on review of pathologic materials. Twenty-five patients were evaluable for toxicity, and 21 were evaluable for response, as 4 patients did not complete one course of therapy. Eleven patients had heterologous mixed mesodermal tumor (MMT) and 10 had homologous MMT. Of the 25 evaluable for toxicity, one patient had grade 4 platelet toxicity. No patient had grade 4 neutropenia, while 4 patients had grade 3 decrease in absolute neutrophil count. One patient had grade 3 gastrointestinal toxicity, while 2 had grade 4 toxicity. There were no complete responses noted and only one partial response, for an overall response rate of 4.8%. The duration of the partial response was 15.2 months. CONCLUSION: Oral TMTX has insignificant activity in the treatment of advanced, persistent, and recurrent uterine MMT at the dose and schedule administered.

Administration, Oral↗

A phase II trail of aminothiadiazole in patients with mixed mesodermal tumors of the uterine corpus: a Gynecologic Oncology Group study.

Aminothiadiazole (NSC 4728) is an analog of the thiadiazoles, a group of drugs that stimulated interest because they do not cause significant myelosuppression and have a unique ability to increase uric acid production unrelated to tissue damage. Previous articles have reported results in ovarian cancer, squamous cell cervical cancer, nonsquamous cell cervical cancer, and endometrial cancer. The Gynecologic Oncology Group chose to study aminothiadiazole in patients with mixed mesodermal tumors of the uterus refractory to prior chemotherapy. Twenty-two patients were entered into this study. Eligibility required that patients had histologically confirmed measurable malignancy. All patients received a starting dose of aminothiadiazole of 125 mg/m2 intravenously (30-45 min infusion) repeated at weekly intervals. All patients also took allopurinol, 300 mg orally per day, to prevent hyperuricemia. Subsequent therapy was not given unless the white blood cell count was > 3,000/microliters and platelets were > 100,000/microliters prior to treatment. One patient (5%) in this study had a partial response, which lasted only 1.2 months. The site of this response was a mesenteric mass. Most patients in this study had no toxicity whatsoever, and no life-threatening toxicity was seen. There were no complete responses. Aminothiadiazole in this dose schedule appears to have no utility in previously treated patients with mixed mesodermal tumors of the uterus.

Adult↗

Mixed mesodermal tumor of the ovary: immunohistochemical study with histogenetic consideration.

The clinical, histological and immunohistochemical features of three cases of ovarian mixed mesodermal tumor (MMT) were examined. The epithelial component was serous papillary cystadenocarcinoma in case 1 and 3, and endometrioid adenocarcinoma in case 2. In case 1, undifferentiated adenocarcinoma was also seen. The mesenchymal component was fibrosarcomatous and chondrosarcomatous in case 1 and 2. In case 3, only fibrosarcomatous area was seen. No endometriosis was observed. Immunohistochemically, the epithelial component showed positivity for epithelial membrane antigen in all three cases. S-100 protein was positive in two cases with chondrosarcomatous differentiation. The fibrosarcomatous area showed positivity for vimentin in all three cases. However desmin, myosin and myoglobin were negative. The antibodies thought to be epithelial or mesenchymal markers unexpectedly reacted positively in some cells; for example, EMA was positive in fibrosarcomatous and chondrosarcomatous cells. Therefore, it was speculated that because the undifferentiated tumor cells had a biphasic character, MMT might originate from immature multipotential cells of surface epithelium and subcapsular connective tissue of the ovary.

Aged↗

Ovarian malignant mixed mesodermal tumor producing the free form of the beta-subunit of human chorionic gonadotropin.

We report a patient with ovarian malignant mixed mesodermal tumor (MMMT) that produced immunoreactive human chorionic gonadotropin beta-subunit (IR-hCG beta). Qualitative analysis indicated that IR-hCG beta in the patient's serum represented the free form of the beta-subunit of hCG. Immunohistochemical localization of hCG beta in MMMT was observed in the sarcomatous stroma, but not in the adenocarcinoma component. Reverse transcription-polymerase chain reaction (RT-PCR) for hCG subunits revealed that the mRNA transcripts of two of six hCG beta genes (beta-1 and -2) were predominantly expressed in the tumor tissue. The serum level of free hCG beta correlated with disease status and was helpful for monitoring the response to therapy for MMMT in this patient.

Adenocarcinoma↗

MRI findings including gadolinium-enhanced dynamic studies of malignant, mixed mesodermal tumors of the uterus: differentiation from endometrial carcinomas.

Our objective was to evaluate the usefulness of MRI including dynamic study in differentiating malignant, mixed mesodermal tumor (MMMT) from endometrial carcinoma (EC). The MR images were reviewed in 4 patients with histologically confirmed MMMT and 11 patients with EC. Flow voids inside and/or around the tumors were seen in 2 patients with MMMT but not in any EC cases. In dynamic studies, all 4 patients with MMMT showed areas of early and persistent marked enhancement similar to that of the myometrium, mixed with areas of gradual and delayed marked enhancement. The portions showing early and persistent enhancement histologically corresponded to predominantly sarcomatous components with prominent vascularity. Ten of 11 ECs did not show such enhancement and only one showed a rapid enhancement in the early phase which was diminished in the delayed phase. The MR imaging with a gadolinium-enhanced dynamic study seems to be useful in differentiating MMMT from EC.

Aged↗

Coexistent choriocarcinoma and malignant mixed mesodermal tumor of the uterus.

OBJECTIVE: The purpose of this article is to report a case of coexisting uterine choriocarcinoma and uterine malignant mixed mesodermal tumor (MMMT). The relevant literature is reviewed and possible pathogenesis discussed. METHODS: The clinical course and histopathology of the case were reviewed and a Medline literature search for other cases was performed. RESULTS: The patient's uterine tumor contained syncytiotrophoblastic and cytotrophoblastic cells that stained positively for the beta subunit of human chorionic gonadotrophin consistent with uterine choriocarcinoma. Pathology also revealed a second distinct neoplasm composed of adenocarcinoma admixed with sarcoma, compatible with a uterine MMMT. The patient experienced metastatic choriocarcinoma to her lungs, lymph nodes, and brain. She suffered a complicated clinical course and died 7 months after her initial diagnosis. The literature search revealed that various gynecologic and nongynecologic carcinomas with trophoblastic differentiation have been described, but an association with uterine MMMT has not been previously reported. CONCLUSIONS: Trophoblastic differentiation and choriocarcinoma associated with gynecologic and nongynecologic tumors is rare. We document the presence of uterine MMMT coexisting with uterine choriocarcinoma that followed an aggressive clinical course and review the possible pathogenesis of this lesion.

Adult↗

[Malignant mixed mesodermal tumors of the ovary: a clinical analysis of 12 cases].

OBJECTIVE: To explore the clinical characteristics, treatment and prognostic factors of patients with malignant mixed mesodermal tumors of the ovary (MMMTO). METHODS: Clinical data of 12 patients with MMMTO between 1983-1997 were reviewed retrospectively. The median age of the patients was 50.7 years. According to FIGO staging system (1985), there were 4 cases in stage II, 6 in stage III and 1 in stage IV. Staging was unclear in the remaining case. Heterologous and homologous elements were present in the primary ovarian tumors in 4 and 8 of the 12 patients, respectively. All patients received cytoreductive surgery. Eleven of them received postoperative chemotherapy and 3 of these eleven patients received additional radiotherapy of pelvic field. RESULTS: The median survival of this group of 12 patients was 24 months. The 2- and 5-year survival rate was 33.3% (4/12) and 8.33% (1/12), respectively. The 2-year survival rate of stage II and III was 50% and 33.3% respectively. One patent in stage IV died within 1 year. Four of the 8 patients with homologous histology survived over 2 years while all the 4 cases with heterologous histology died within 2 years. Five of the 11 patients (45.5%) received combination therapy died within 1 year while 1 patient treated with surgery alone died within 6 months. CONCLUSIONS: The prognosis of MMMTO is rather poor. Surgery combined with chemotherapy and/or radiotherapy seems to be a better choice of approach. The histological tpyes of tumor and stage of the disease are related to prognosis.

Adult↗

Malignant mixed mesodermal tumor arising in a benign cystic teratoma.

The occurrence of sarcoma in a benign cystic teratoma is very rare. We report the first poorly differentiated, malignant mixed mesodermal tumor with a component of rhabdomyosarcoma to arise in a benign cystic teratoma of the ovary. The tumor was staged as FIGO IC due to capsule invasion. Although combination chemotherapy of cisplatin, ifosfamide and mesna, was instituted, the disease took a rapidly progressive course. After an unusual metastasis to the scapula was detected, the patient deteriorated and died in the forth postoperative month.

Adult↗