Mixed Mesodermal Tumor Research Articles

Mesodermal mixed tumor of the uterine cervix associated with retroperitoneal lymph node metastasis

Mesodermal mixed tumor of the uterine cervix associated with retroperitoneal lymph node metastasis

Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (A Gynecologic Oncology Group Study)

A phase II trial of ifosfamide (isophosphamide, NSC 109724) and mesna (2-mercaptoethane sodium sulfonate, NSC 113891) in women with advanced or recurrent mixed mullerian tumors of the uterus was conducted by the Gynecologic Oncology Group. The starting dose of ifosfamide was 1.5 gm/m 2 daily, intravenously, for 5 days. The starting dose of ifosfamide was reduced 1.2 gm/m 2 daily in patients who had received prior radiotherapy. Mesna was given intravenously immediately and at 4 and 8 hours after the administration of ifosfamide. Each mesna dose was 20% of the total daily dose of ifosfamide. Twenty-nine patients are evaluable for toxicity, and 28 patients are evaluable for response. Twenty-one patients had received prior abdominal hysterectomy, and eight patients had prior radiotherapy. Thirteen tumors were homologous and 15 heterologous. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in seven (25%) patients and two (7.1%) had grade 3 or 4 thrombocytopenia. Two patients (7.1%) had grade 3 or 4 neurotoxicity. One patient experienced lethargy and confusion that responded to discontinuation of the ifosfamide. A second patient developed progressive cerebellar dysfunction, left hemiparesis, and coma. This patient died after 3 days of therapy. Complete responses were seen in five (17.9%) patients and partial responses occurred in four (14.3%) patients for a total response rate of 32.2%. These results indicate that ifosfamide is an unusually active drug in patients with advanced or recurrent mixed mullerian tumors of the uterus. Studies with combination regimens incorporating ifosfamide are warranted. The toxicity of ifosfamide in Gynecologic Oncology Group studies is being evaluated retrospectively.

Fallopian tube carcinoma: A clinicopathological study of 17 cases

From 1969 through 1986, 17 patients with primary adenocarcinoma of the fallopian tube were treated at the Loma Linda University Medical Center. Stages I, II, and III of the disease were present in 6, 5, and 6 patients, respectively. The mean age of the patients was 59.9 years. Vaginal bleeding or discharge (57%), followed by abdominal pain or discomfort (29%), was the most common symptom in our patients. A palpable pelvic mass was detected in two-thirds of the patients. One case of carcinosarcoma, one case of mixed mesodermal tumor, and one case of endometrioid carcinoma are included. No patient in this series had a correct preoperative diagnosis. Therapy consisted of surgical resection, usually followed by various combinations of adjuvant radiation therapy and/or chemotherapy. The overall 5-year survival rate was 31%. Five patients (29%) are alive without evidence of disease. This study supports the need for collaboration among large centers to define the optimal adjuvant therapy of this disease. In the absence of the desired treatment protocols, such lesions should be approached in a manner similar to that used for ovarian cancers.

Platinum-based combination chemotherapy for malignant mixed mesodermal tumors of the ovary

Although considerable clinical data are available to guide treatment decisions for patients with ovarian epithelial malignancies, therapy for the rare malignant mixed mesodermal (mullerian) tumor (MMMT) of the ovary is poorly studied. Ten untreated patients diagnosed with primary ovarian MMMT were managed with cis-platinum-based combination chemotherapy from 1980 to 1985. Six of the 10 patients were stage III suboptimal with evaluable residual disease; 4 of these 6 had CRs with a median duration of response of 13 months. The remaining 2 patients had PRs, of 2 and 11 months duration. Four patients had stage III optimal disease; 1 progressed at 7 months, 1 progressed at 16 months and the other 2 patients have no clinical evidence of diease at 12+ and 22+ months. Despite impressive initial response rates, survival overall was poor, with a median survival for all 10 patients of 16+ months.

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.

Mesodermal mixed tumor primary in the fallopian tube

Mullerian mixed tumors, as a group, are uncommon. Only 27 cases of this tumor of the fallopian tube have been reported to date. We report the 28th case of mixed mesodermal tumor, originating in the fallopian tube. A 79-year-old woman had mistaken a bloody vaginal discharge for hematuria. Various examinations showed no evidence of malignancy. However, computerized tomography revealed an intrapelvic tumor. Laparotomy was performed, with a suspicion of tubal malignancy. The final pathologic diagnosis was mixed mesodermal tumor, originating in the fallopian tube. Postoperatively, the patient was placed on oral adjuvant chemotherapy for 34 months. At present, she is doing well. Though no definite conclusions regarding the best method of therapy can be reached, an aggressive mode of therapy is recommended. The primary therapy is surgery; however, surgery followed by chemotherapy may have a potential benefit.

Mixed mesodermal tumors of the ovary: A clinicopathologic study of 14 cases

Fourteen cases of mixed mesodermal tumor of the ovary are presented. The actuarial survival of patients with these tumors was 2.5 months. Eighty-six percent of patients were stage III or IV at the time of diagnosis. The stromal or carcinomatous component of the tumor could not be correlated with survival. Both our two longest survivors, 14 and 27 months, were treated with surgery and radiotherapy, one patient with and one without chemotherapy.

Clinicopathologic features of ovarian mixed mesodermal tumors and carcinosarcomas

Over a 27-year period there were 15 patients treated at the University of Michigan Medical center for carcinosarcomas or mixed mesodermal tumors of the ovary. Overall median survival was 11 months. Median survival was 4 months in patients with carcinosarcomas and 13 months in patients with mixed mesodermal tumors (P = 0.066). Patients with a chondrosarcomatous element had a significantly longer median survival than patients with mixed mesodermal tumors lacking cartilaginous differentiation (P = 0.031). The presence of a rhabdomyosarcomatous element did not affect survival. The size of the primary tumor, presence of ascites, FIGO stage, and degree of initial resection (optimal versus suboptimal) did not affect survival. There was no difference in survival between patients receiving postoperative chemotherapy and patients undergoing postoperative irradiation.

Management of malignant, mixed mesodermal tumors of the uterus

Forty-two patients with malignant, mixed mesodermal tumors of the uterus were identified by retrospective chart review. Only 2 patients were premenopausal at the time of diagnosis. Six of the patients had previously received pelvic radiotherapy. Surgical/pathologic findings were inconsistent with clinical staging in 17 of the patients. Patients with stage I tumors were found to have extrauterine extension of tumor in 39% of the cases. Overall, 2- and 5-year actuarial survival rates were 40 and 18%, respectively. The surgical extent of disease was a major prognostic factor in patient survival (P = 0.006). Patients with tumors showing no invasion or invasion limited to the inner two-thirds of the myometrium also demonstrated a significant survival advantage as compared to those with deeper myometrial invasion (P = 0.02). However, no statistically significant relationship was demonstrated between survival and patient age, the nature of the sarcomatous element (homologous or heterologous), or the presence of cervical involvement. Patients with recurrent or persistent disease did poorly; only 4 patients have survived more than 1 year after documentation of recurrent disease. Two patients had prolonged disease stabilization with radiotherapy and cisplatin. Another patient with pulmonary metastases had a 6-month, complete response to cisplatin.

Collagen type III formation and distribution in the uterus: effects of hormones and neoplasm development.

The amount and location of interstitial collagen in the endometrial stroma and the uterine wall as well as the effects of hormonal stimulation and neoplastic transformation were studied by light and electron microscopy and immunohistochemical methods using specific antibodies to aminoterminal propeptide type III procollagen (PIIIP). The results showed collagen deposition in atrophic mucosae and in the proliferative endometrium with a decrease in the secretory endometrium. In cystic glandular hyperplasia and adenomatous hyperplasia, PIIIP deposits were abundant. In well-differentiated endometrial adenocarcinoma, dense collagen type III aggregates were found in subepithelial positions, disintegrating with advancing malignancy and decreasing in hormonal-treated morphologically well-differentiated neoplasms. The even distribution of PIIIP around muscle cells and bundles in leiomyomas was disturbed and partly absent in leiomyosarcomas, and surrounded epithelial islets in mixed mesodermal tumors.

Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcoma and mixed mesodermal tumors

Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcoma and mixed mesodermal tumors

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.

Collagen type III in ovarian tumors. Histological, immunohistochemical and ultrastructural findings

The occurrence and location of interstitial collagen amino-terminal propeptide type III procollagen (PIIIP) and fibronectin was studied in 123 ovarian tumors of different types and related to the histological type and clinical behavior of the neoplasm. The purpose was to further our understanding of the development and classification of these tumors and to determine characteristics of diagnostic and prognostic significance. PIIIP-positive fibers were common in the stroma of all types of neoplasms, condensation of fibres occurred at the epithelial-stromal interface of surface epithelial tumors, and disintegration and discontinuation of fibers around invasive epithelial islets and in stroma of undifferentiated epithelial carcinomas. The PIIIP-positive stromal meshwork surrounded individual cells in thecomas, while it was virtually absent in diffuse granulosa cell tumors and distinctly developed in malignant stromal neoplasms, being seen mainly around epithelial islets in mixed mesodermal tumors.

Treatment of advanced ovarian mixed mesodermal tumors with postoperative doxorubicin and cis-platinum based chemotherapy

Treatment of advanced ovarian mixed mesodermal tumors with postoperative doxorubicin and cis-platinum based chemotherapy

Mixed mesodermal tumor of the ovary histological and electron microscopic observations.

Mixed mesodermal tumor of the ovary is very rare, only 10 cases having been reported to date in Japan. We recentry experienced a case of this type of tumor and studied it cytologically and electron microscopically. The patient was a 61-year-old housewife (gravida 2, para 2) who had experienced menopause at the age of 51 years. She received medical examination because of a lower abdominal mass. Ultrasonography and CT revealed a large intrapelvic tumor and ascites. Since the CA 125 level was 704 U/ml, a malignant ovarian tumor was suspected, and bilateral adnexectomy, total hysterectomy, resection of the intestinal area adhering to the tumor plus end-to-end anastomosis, and omentectomy were performed. After 5 courses of chemotherapy, the CA125 level was restored to normal. The patient is now being followed up on an outpatient basis. The resected specimen, the size of a small newborn head, was a soft tumor with a necrotic appearance which adhered to and infiltrated the sigmoid colon. There was about 600 ml of hemorrhagic ascites. Touch smear cytology demonstrated isolated sarcoma cells and endometrioid adenocarcinoma cells showing an accumulated ductal arrangement. Histologically, the tumor was considered to be carcinosarcoma showing a mixture of endometrioid adenocarcinoma and sarcoma. Since transmission electron microscopy of the sarcoma element disclosed thick and thin intracytoplasmic filaments in some tumor cells, the cytoplasm, those were diagnosed as rhabdomyosarcoma cells. By scanning and transmission electron microscopy of adenocarcinoma cells on the same touch smears, grape-like aggregates of tumor cells, bearing dense or sparse microvilli, were evident. Also, there were nucleoli in the marginal areas of large nuclei, intercellular junction complex, and unclear organelles. The histogenesis of this tumor was discussed on the basis of the above findings and the related literature.

The Increasing Trend in Japan of Müllerian Mixed Tumor of Endometrium

An increasing trend in Japan of Müllerian mixed tumor (MMT) of the endometrium has been suspected from both the Annual Pathological Autopsy Records in Japan (APARJ) and an analysis of surgical cases from the National Cancer Center Hospital (NCCH). One hundred and four MMT cases were recorded in APARJ during the period, 1965-1984, which constituted 1.1% of all malignant uterine tumors. The number of MMT cases in the past 10 years (87 cases during the period, 1975-1984) increased more than fivefold over that of the previous 10 years (17 cases during the period, 1965-1974). The proportion among malignant uterine tumors also increased from 0.5 to 1.5%. Eighteen patients with MMT underwent surgery in the NCCH during the period, 1963-1986, which accounted for 4.3% of endometrial malignant tumor cases. Of these only one was resected during the 12-year period, 1963-1974, while there were 17 surgically resected cases during the 12 years from 1975 to 1986. These represented 0.8 and 5.7%, respectively of malignant tumors of the endometrium during the two periods. In five out of 18 cases, MMT occurred as a second primary malignancy, and in all cases the histology was one of mesodermal mixed tumor. It was suggested that its occurrence as a second primary malignancy would be contributing to the recent increase of MMT in Japan.

Extrauterine Pelvic Malignant Mixed Mesodermal Tumors; A Study of 10 Cases with Immunohistochemistry

Ten cases of extrauterine malignant mixed mesodermal tumors (MMMTs), nine ovarian, and one pelvic, are presented. One patient had a purely epithelial primary ovarian tumor and MMMT in her recurrent tumors. All the other patients had MMMT in their primary and recurrent tumors. Eight patients had heterologous MMMT including cartilage, striated muscle, and adipose tissue in one case. Two patients had homologous MMMT. All cases presented with metastases involving abdominal organs that were either MMMT or epithelial neoplasms and MMMT. Five patients had recurrent tumors, one extensively involving the spleen. In all recurrent tumors, the mesenchymal components were considerably more abundant than in the primary tumors. Immunohistologic studies of intermediate filaments were performed in seven cases, revealing cytokeratin-positive epithelial structures, vimentin-positive mesenchymal (including cartilaginous) structures, as well as coexpression of cytokeratin and vimentin in anaplastic and giant tumor cells in some cases. Some anaplastic spindle cells, which on routine stains were suggestive of stromal cells, stained positive for cytokeratin, thus identifying their epithelial nature. Desmin staining performed in five cases showed positive staining of rhabdomyoblasts in only one case. Myoglobin staining performed in seven cases was positive in four. The histogenesis from primitive müllerian structures and the natural history of these uncommon neoplasms are discussed in light of the pathological and immunohistochemical data presented.

組織学的に異なる2つの間葉成分を有する卵巣Mixed Mesodermal Tumorの検討

組織学的に異なる2つの間葉成分を有する卵巣Mixed Mesodermal Tumorの検討

Uterine rupture secondary to a malignant mixed mesodermal (Mullerian) tumor: A case report

A case of uterine rupture resulting from tumor penetration of the myometrium in a patient with malignant mixed mesodermal tumor is described; the first in the literature known to the authors. Notable features include rapid progression of disease, hemoperitoneum, and diffuse intraoperative bleeding controlled by radiographic embolization.

Malignant mixed mesodermal tumors of the ovary. A report of 13 cases.

The surgical pathology files at Thomas Jefferson University Hospital (TJUH) were reviewed for the period 1973-1984. Thirteen cases of primary ovarian malignant mixed mesodermal tumor (MMT) were found; however, material from only seven of these cases could be obtained for repeat review. No conclusions can be drawn regarding any impact on survival based on the histology. Treatment was highly varied reflecting the mix of physicians rendering treatment and the range of modalities used. Overall, survival was miserable. Six of the 13 patients (46.2%) survived 6 months or less, 10 of the 13 (76.9%) survived 12 months or less. No particular treatment modality seemed to offer enhanced survival unless aggressive cytoreductive surgery was performed. A plea is made for national cooperative groups to develop treatment protocols for this aggressive ovarian cancer.