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Treatment of patients with sarcoma of the uterus.

In the present series of 156 patients with sarcomas of the uterus the therapeutic modalities employed were evaluated. The 5-year survival rate of 51.3% was obtained for this series including 41.2% for leiomyosarcomas, 57.1% for endometrial stromal sarcomas, 50.0% for mixed mesodermal tumors and 40.0% for carcinosarcomas. The prognostic significance of the extent of disease, histological type and the age of patients is emphasised. Clinical features of uterine sarcomas specific for different histological types were shown: leiomyosarcomas were characterized by a rapid tumor growth while uterine bleeding in the background of neuroendocrine disturbances similar to those observed in endometrial carcinomas were related to endometrial stromal sarcomas and mixed mesodermal tumors. In respect to early diagnosis of sarcomas an ultrasonic pelvic examination and studies of aspirate specimens taken from the uterine cavity are recommended to be performed for the groups at high risk. An individual treatment policy was developed for each sarcoma patient depending on the histological type, the stage of disease and general condition of the patient. Surgical approach varied ranging from a total hysterectomy and adnexectomy, done for leiomyosarcomas, to an extended hysterectomy and pelvic lymphadenectomy for mixed mesodermal tumors and endometrial stromal sarcomas. Postoperative distant and/or endovaginal radiation are indicated for all histological types of sarcomas excepting leiomyosarcomas. Application of adjuvant chemotherapy with carminomycin or adriamycin improves the results of treatment.

Carcinosarcoma↗

Patterns of metastasis in uterine sarcoma. An autopsy study.

The autopsy findings of 73 patients with uterine sarcoma were studied to determine the sites and possible modes of metastasis. Homologous mixed mesodermal tumors were the most frequent (41%) followed by leiomyosarcoma (26%), heterologous mixed mesodermal tumor (18.3%), stromal sarcoma (12%), and endolymphatic stromal myosis (3%). The peritoneal cavity and omentum were the most frequently involved sites (59%), followed by the lung (52%), pelvic lymph nodes (41%), paraaortic lymph nodes (38%), and liver parenchyma (34%). The presence of lung metastasis was not associated with pelvic or paraaortic node metastasis or intraperitoneal disease. Metastasis to other distant sites including the brain, heart, kidney, and bone were independent of pelvic and paraaortic nodal metastasis or intraperitoneal disease. Metastatic sites were not different among various histologic types. Distant metastatic sites were statistically associated with lung metastasis. Hematogenous metastasis best explains this metastatic pattern and adjuvant systemic therapy seems indicated.

Adult↗

[Abnormalities of chromosome involving 1q in uterine endometrial carcinomas].

Cytogenetic studies were performed on endometrial specimens from four patients with hyperplasia, six with adenocarcinoma and one with mixed mesodermal tumor. Except for one cell, all 65 cells from the hyperplastic specimens had a normal female karyotype. However, a total of 92 cells from the 5 adenocarcinoma specimens had chromosomal abnormalities, though all 20 cells from a specimen of a well differentiated adenocarcinoma showed a normal karyotype. The chromosome number and morphology of the aneuploid cells had minimal changes. The modal number of chromosomes was pseudodiploid in one case and hyperdiploid in four. Three kinds of structural abnormalities involving chromosomes 1q were identified as of clonal origin: del. 1 (p21) in 2 cases, t. dic (1;16) (p21;q24) in one case and i (1q) markers in 2 cases. Since the carcinoma cells had two chromosomes 1 of normal morphology, the presence of the marker chromosome led to a partial trisomy or tetrasomy of the long arm of a chromosome 1. This involvement of the long arm of chromosome 1, therefore, may be assumed to represent a karyotypic change in the characteristics of adenocarcinoma of the endometrium. Complex karyotypes with many rearranged chromosomes were observed in cells from the mixed mesodermal tumor. The karyotypic differences between endometrial carcinoma and the mixed mesodermal tumor suggest that the genesis (and its mechanism) of the former may differ from that of the latter.

Adenocarcinoma↗

[Malignant mesodermal (Mullerian) mixed tumor of the ovary: histologic, immunohistochemical and cytologic study].

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

Adult↗

Primary sarcoma of the adult vagina: a clinicopathologic study.

Combination chemotherapy has dramatically improved the results of treatment for embryonal rhabdomyosarcoma of the vagina in children, but little attention has been directed toward vaginal sarcomas in adults. This report of 17 cases of primary sarcoma of the adult vagina includes ten leiomyosarcomas, four mixed mesodermal tumors, one undifferentiated sarcoma, one stromal sarcoma, and one neurofibrosarcoma. The leiomyosarcomas, mixed mesodermal tumors, and the stromal sarcoma were morphologically similar to their uterine counterparts. Thirty-five percent of the patients had received pelvic irradiation for carcinoma of the cervix. Three of four patients treated by pelvic exenteration are alive and disease free after 84 to 161 months of observation. All 13 patients who received other forms of primary therapy died of recurrence. The pelvis was the first site of recurrence in all treatment failures and the only site of failure in 50%.

Adenocarcinoma↗

Mitoxantrone in the treatment of advanced uterine sarcoma. A phase II trial of the Gynecologic Oncology Group.

Twenty-nine evaluable patients with metastatic or recurrent leiomyosarcoma or malignant mixed mesodermal tumors of the uterus were treated with mitoxantrone 12 mg/m2 every 3 weeks. All patients had good performance status and measurable disease. Nineteen had prior chemotherapy but only five had prior doxorubicin. No complete or partial responses were seen in 12 patients with leiomyosarcoma (95% confidence interval for a response of 0-22%) or 17 patients with mixed mesodermal tumors (95% confidence interval for a response of 0-16%). The median progression-free interval for patients with leiomyosarcoma was 1.4 months and the median survival 4.1 months. The median progression-free interval for patients with mixed mesodermal was 1.4 months and median survival 4.0 months. Mitoxantrone does not appear to be very active against leiomyosarcoma or mixed mesodermal tumors as second-line therapy.

Adult↗

Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma.

OBJECTIVE: To determine the incidence of uterine sarcoma in patients operated on for symptomatic uterine leiomyomas or "rapidly growing" leiomyomas. METHODS: We reviewed the medical records of 1332 women admitted to either of two community hospitals between 1988-1992 for hysterectomy or myomectomy for uterine leiomyomas. The incidence of leiomyosarcoma, endometrial stromal sarcoma, and mixed mesodermal tumor was calculated. Patient ages, admitting symptoms, and operative and pathologic findings were analyzed. The study included 371 women (28%) operated on for rapidly growing leiomyomas. All patients operated on during the same interval and found to have a uterine sarcoma were reviewed. RESULTS: One of the 1332 patients operated on for presumed leiomyoma was found to have a leiomyosarcoma. This women was the only patient found to have a sarcoma among 371 women operated on for rapid growth of the uterus. None of 198 patients who met a published definition of rapid growth had a uterine sarcoma. Two women (0.15%) had endometrial stromal sarcoma, but none had a mixed mesodermal tumor. During the same interval, nine additional patients were found to have uterine sarcomas, and for these women, the preoperative diagnosis was sarcoma in four, endometrial cancer in three, ovarian cancer in one, and prolapsed uterus in one. CONCLUSIONS: The total incidence of uterine sarcoma (leiomyosarcoma, endometrial stromal sarcoma, and mixed mesodermal tumor) among patients operated on for uterine leiomyoma is extremely low (0.23%). The incidence of sarcoma among patients having surgery for "rapidly growing" leiomyoma (0.27%) or among those who met published criteria for rapid growth (0%) does not substantiate the concept of increased risk of sarcoma in these women.

Adult↗

Role of electron microscopy in metastatic endometrial stromal tumors.

Endometrial stromal tumors may pose a problem in diagnosis when they appear as metastatic lesions without a known primary tumor. To determine the usefulness of electron microscopy in identifying them in these situations, optimally fixed low-grade stromal sarcomas (five), normal endometrial specimens (six), and malignant mesodermal mixed tumors (four) were studied. The endometrial stromal sarcomas had a general resemblance to normal proliferative endometrial stroma, being composed of undifferentiated cells, fibroblasts, and myofibroblasts. One stromal tumor showed evidence of partial epithelial differentiation. One of the four malignant mesodermal mixed tumors had a fibrosarcomalike component, but there was insufficient resemblance to normal endometrial stroma to indicate a relationship between the two. Together with a review of the literature, this study indicates that electron microscopy is useful in the diagnosis of low-grade endometrial stromal tumors by demonstrating characteristic cellular findings as well as a lack of features specific for other round cell and spindle cell neoplasms.

Aged↗

[Mixed uterine mesodermal sarcoma in the population of southern Israel in the years 1996-1971--clinical and pathological characteristics].

During 1971-1996, 17 patients with mixed mesodermal uterine tumors were treated. Average age at diagnosis was 67.3 years, 12/17 were of European and 5/17 of Afro-Asian extraction. The overall 5-year survival was 21%. 10/17 patients had mixed mesodermal tumors with a heterologous mesenchymal element, and 7/17 had a homologous mesenchymal element (carcinosarcoma). 6/17 had another primary malignancy, including breast cancer (3/17), bilateral metachronous breast tumor (2/17), and malignant lymphoma of the neck region (2/17). All 3 with breast cancer had previously been treated with tamoxifen. I had simultaneous mesodermal tumor and ovarian thecoma. Simultaneous autoimmune manifestations occurred in 2/17, including thrombocytopenic purpura in 1, and myasthenia gravis in another. Mesodermal tumor of the uterus is a relatively rare malignancy with aggressive behavior and poor prognosis. It also had unusual associations with other primary tumors, hormonal treatment, and autoimmune manifestations.

Aged↗

Carcinosarcoma (malignant mixed müllerian (mesodermal) tumor) of the female genital tract: immunohistochemical and ultrastructural analysis of 28 cases.

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

Aged↗

Carcinoembryonic antigen (CEA) and carbohydrate determinant 19-9 (CA 19-9) localization in 121 primary and metastatic ovarian tumors: an immunohistochemical study with the use of monoclonal antibodies.

An immunoperoxidase study, using the Avidin-Biotin-Peroxidase complex method and the monoclonal antibodies, anti-carcinoembryonic antigen (CEA) and anti-carbohydrate determinant 19-9 (CA 19-9), was carried out on 108 common epithelial tumors of the ovary and 13 epithelial tumors metastatic to the ovary. Primary mucinous tumors were positive in 62% of the cases (benign, 15%; borderline, 80%; and carcinomatous, 100%) with anti-CEA. None of the serous tumors were positive with anti-CEA, but 27% (benign, 23%; borderline, 40%; and carcinomatous, 20%) were positive with anti-CA 19-9. With anti-CEA, 30% of the endometrioid carcinomas, 50% of the malignant mesodermal mixed tumors, 14% of the clear cell carcinomas, 36% of the Brenner tumors, and 83% of the metastatic carcinomas from the large intestine were positive. With anti-CA 19-9, 76% of the mucinous, 40% of the endometrioid, 25% of the malignant mesodermal mixed tumors, 57% of the clear cell carcinomas, 45% of the Brenner tumors, and all the metastatic carcinomas from the large intestine were positive. All the undifferentiated carcinomas were unreactive with both antibodies. Although neither CEA nor CA 19-9 is a specific marker for any type of ovarian tumor or for malignancy per se, the presence of the former antigen can be useful in differentiating serous from mucinous tumors. Moreover, demonstration of either antigen in a variety of tumors may indicate its potential value as a serum marker in monitoring the course of the patient.

Adenocarcinoma↗

Marker chromosomes of the long arm of chromosome 1 in endometrial carcinoma.

Cytogenetic studies were performed on endometrial specimens of four patients with hyperplasia, six with adenocarcinoma, and one with a mixed mesodermal tumor. Except for one cell, all 65 cells from the hyperplastic specimens had a normal female karyotype. However, a total of 92 cells from the five adenocarcinoma specimens had chromosome abnormalities, though all 20 cells from a specimen of a well differentiated adenocarcinoma showed a normal karyotype. The chromosome number and morphology of the aneuploid cells had minimal changes. The modal number of chromosomes was pseudodiploid in one case and hyperdiploid in four cases. Three kinds of structural abnormalities involving chromosomes #1 were identified to be of clonal origin: del(1p21) in two cases, tdic(1;16)(p21;q24) in one case, and i(1q) markers in two cases. Because the carcinoma cells had two chromosomes #1 of normal morphology, the presence of the marker chromosome led to partial trisomy or tetrasomy of the long arm of chromosome #1. This involvement may be assumed to represent a karyotypic change characteristic of some adenocarcinomas of the endometrium. Complex karyotypes with many rearranged chromosomes were observed in cells from the mixed mesodermal tumor. The karyotypic differences between endometrial carcinoma and the mixed medodermal tumor suggest that the genesis (and its mechanism) of the former may differ from that of the latter.

Adenocarcinoma↗