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We herein report the case of a 69-year old woman presenting with an abdominal mass, who was found to have a mixed mesodermal tumor (MMT) of the cecum. Imaging studies and endoscopic investigations were consistent with the diagnosis of a nonepithelial malignant tumor of the cecum. On laparotomy, a knuckle-sized firm mass involving the cecum was noticed. As a result, a right hemicolectomy was performed. Pathological examinations, including immunohistochemical staining, resulted in the diagnosis of mesodermal mixed tumor, homologous type. The patient was advised to undergo postoperative chemotherapy but she did not comply. She has been followed up as an outpatient and is still alive 1.5 years after the operation.
A case of mesodermal mixed tumor arising in the uterus of a 57-year-old woman is presented. The tumor was a mixture of adenocarcinoma with occasional squamous metaplasia, stromal sarcoma, myxosarcoma and chondrosarcoma. Light and electron microscopic examinations of the tumor revealed close transition between stromal sarcomatous component and each of other sarcomatous and carcinomatous component. The histogenesis of mixed mesodermal tumor was discussed and it was concluded that the tumor might be derived from endometrial stromal cell which possessed the pluripotency to differentiate toward various epithelial and mesenchymal tissues including the heterologous mesenchymal tissue.
Frequency and characteristics of mixed mesodermal tumors (MMT) and some terminology disparities in the comparatively scarce literature are discussed. The low frequency of MMT described and difficulties in diagnosing have been pointed out. A final diagnosis can be made on operative material only, since curettage contains one (more often the epithelial) of the components of biphase tumorous. The authors emphasize on guided attention to MMT, as well as the necessity of serial sections. The most important factor is depth of invasion.
OBJECTIVE: Mixed mesodermal tumors of the uterus are highly malignant. The purpose of our present study was to investigate possible roles of insulin and insulin-like growth factors I and II (IGF-I and IGF-II) in the growth and development of these tumors. METHODS: Specific binding and growth effects of insulin, IGF-I, and IGF-II were studied in SK-UT-1 cells, derived from a human mixed mesodermal tumor of the uterus. The receptors were further characterized by competitive binding and chemical cross-linking studies. RESULTS: Binding studies with 125I-insulin, 125I-IGF-I, and 125I-IGF-II revealed the presence of specific binding sites for these three growth factors. Specificity studies revealed that the binding sites for IGF-I and IGF-II are distinct. Binding of IGF-II was much higher than insulin and IGF-I binding. Scatchard analysis of the binding data revealed that the cell line has a higher number of IGF-II receptor (100,000 sites per cell) than insulin (1400 sites per cell) and IGF-1 (1200 sites per cell) receptors. The effect of these growth factors on cell growth was studied by monitoring the cell number and incorporation of [3H] thymidine into the DNA of the cells. Insulin-like growth factor-II was potent in stimulating the growth of these cells, but IGF-I did not have any effect. Insulin stimulated DNA synthesis only at pharmacologic concentrations. CONCLUSION: These results indicate that IGF-II is mitogenic to mixed mesodermal tumors of the uterus. Insulin-like growth factor II may be involved in the growth regulation of mixed mesodermal tumors of the uterus.
Malignant mixed mesodermal tumors of the ovary occur in less than 1% of cases of ovarian cancer. They have a dismal prognosis and the most effective type of therapy is still not known. All cases of malignant mixed mesodermal tumor of the ovary between January 1, 1985 and May 1, 1994 operated on by the gynecologic oncology service are the subject of this report. Data were obtained from the hospital and office records of the patients. Nine patients who had their primary surgery by the gynecologic oncology service were found to have the diagnosis of malignant mixed mesodermal tumor of the ovary. Homologous tumors were found in five patients and heterologous tumors in four. Homologous tumors (mean survival 15.2 months) showed a better survival than heterologous tumors (mean survival 6.5 months; P = 0.001). An elevated estrogen receptor status was shown to correspond to longer survival (P < 0.0001). Six specimens were considered to be estrogen receptor positive and three were receptor negative. The mean survival in those patients who had a positive estrogen receptor status, 13.7 months, with a median of 7.5 months was significantly higher than those who were not positive, 6.7 months (P = 0.019) with a median of 6.25 months. All specimens were progesterone receptor negative. Malignant mixed mesodermal tumors of the ovary have a dismal prognosis, no effective therapy, and controversial prognostic indicators. Increasing estrogen receptor status appeared to correlate with longer mean survival. Larger, multi-institutional studies need to be done to determine the overall significance of these findings.
Mixed mesodermal tumor (MMT) arising from the ovary is very rare, but we recently encountered two cases of this tumor. The tumors were examined histologically using hematoxylin-eosin, alcian blue, periodic acid-Schiff (PAS), and toluidine blue staining, as well as immunohistochemical staining for S-100 protein. The two patients were postmenopausal women aged 68 and 58 years, respectively. The carcinomatous region of the mixed tumor was endometrioid carcinoma in Patient 1 and serous cystadenocarcinoma in Patient 2, while the sarcomatous region was chondrosarcoma in both patients. The chondrosarcoma tissue was positive for PAS, alcian blue, toluidine blue, and S-100 protein.
Four cases of mixed mesodermal tumor (MMT) of uterine origin were histologically and cytologically studied. In the case of occurrence of rhabdomyosarcoma, the cells in the aspiration smear appeared independently and sporadically and were relatively large in size and polyhedral in shape. The cell margins were not clearly distinguishable, and the cytoplasm was non-uniformly and heavily stained light green in general except for some pale red eosinophilic areas. The swollen and elliptical nuclei had a high N/C ratio. The chromatin showed a densely stained coarse granular pattern, and the nuclear margin was expanded. On the imprint smear, the cells contained abundant cytoplasm with amoeboid protrusions. The cytoplasm was light green in general, was filled with granules of various sizes which were non-uniformly and heavily stained. The chromatin showed coarse granulation, and a large nucleolus was observed.
Short-term cultures of four malignant mixed mesodermal tumors of the ovary were cytogenetically analyzed. The primary tumor was examined in three cases, whereas in one case the sample was obtained from a residual tumor mass after chemotherapy. The tumor sampled after cytostatic treatment had a relatively simple karyotype with numerical changes that included pentasomy 12 and an i(1)(q10) as the only structural abnormality. Karyotypic analysis of the three primary tumors revealed extensive structural as well as numerical aberrations, i.e., a picture similar to that seen in the few malignant mixed mesodermal tumors with karyotypic anomalies described previously. Rearrangements of chromosome 1, leading to loss of distal 1p, and homogeneously staining regions have so far been the most frequent cytogenetic changes in this tumor type. Malignant mixed mesodermal tumors of the ovary thus seem to be karyotypically identical to the more numerous mixed mesodermal tumors of uterine origin, and they do not differ substantially in this respect from pure ovarian carcinomas.
Malignant mixed mesodermal tumors (MMMT) are the most malignant neoplasms known to occur in the uterus. The most important prognostic factors are the extent of tumor at diagnosis, depth of myometrial invasion, and, as regarded by some authors, the sarcomatous component. We report on a retrospective analysis in 83 patients with MMMT. By univariate analysis survival was dependent on stage, depth of myometrial invasion, kind of therapy, age at menopause, and parity. However, the sarcomatous component did not significantly influence survival. Using the multivariate Cox regression analysis stage and parity or depth of myometrial invasion and parity were found to independently predict prognosis. Despite an interval of more than 20 years from the last childbirth to tumor appearance a beneficial influence of parity on the prognosis of MMMT was identified. This is unique in oncology. Especially patients with more than three children formed a subgroup of long-term survivors. It is interesting to note that parity was found by means of a Cox regression analysis to be statistically independent, and no correlation with other classical prognostic factors was detected.
Uterine malignant mixed mesodermal tumors (MMMT) are highly malignant tumors containing both malignant glands and stroma, while adenosarcomas (AS) are less aggressive tumors composed of malignant stroma and benign glands. Immunohistochemistry was used to grade overexpression of p53 protein, HER-2/neu protein, epidermal growth factor receptor (EGFR), and Ki-67 antigen in both the glands and stroma of tissue from 20 women with MMMT and 6 women with AS. EGFR was overexpressed in 2 AS and 9 MMMT, and was more commonly found in the sarcomatous component than the carcinomatous component in MMMT (P = 0.03). p53 was not found in any AS samples and was strongly present in 6 MMMT samples with a random distribution between the malignant components. HER-2/neu protein was not overexpressed in any AS or primary MMMT. Ki-67 antigen, a marker of cell proliferation, was found at higher levels in MMMT than AS samples (P = 0.03) and high Ki-67 antigen expression correlated with a decreased survival in patients with MMMT (P = 0.004). Independent characterization of oncogene proteins in the malignant components of these heterogeneous tumors may provide insight into the histogenesis and behavior of these malignancies.
The mixed mesodermal tumor is a very uncommon malignancy. The aggressiveness of this lesion is illustrated by extremely poor prospects for afflicted patients: postoperative survival is usually shorter than 24 months. According to the literature, malignant mixed tumor of the ovary is rather rare and its occurrence with other malignancy is exceptional. We report here a case of a 62-years old woman with serous cystadenocarcinoma in the right ovary and a heterologous malignant mixed mesodermal tumor in the left one. Both tumors expressed cytokeratins, while only the mesodermal tumor expressed S-100 and focal NSE.
Malignant mixed mesodermal tumors rarely occur in extragenital sites. An 80-year-old patient presented with a malignant mixed mesodermal tumor, consisting of papillary serous adenocarcinoma and chondrosarcomatous components. The patient refused further treatment following surgery and died of disease 2.5 months later. Based on the present case and a review of the literature, primary extragenital malignant mixed mesodermal tumors prove to be rare but highly malignant neoplasms. Further data is yet to be gathered in order to determine the exact origin and behavior of these tumors.
Early diagnosis of malignant mixed mesodermal tumors of the ovary is very difficult because of the rarity and the insidious onset. The purpose of this report is to review the magnetic resonance imaging features of an ovarian malignant mixed mesodermal tumor, which occurred in a 52-year-old woman, aiding in the differential diagnosis.
OBJECTIVE: To review the experience at Women & Infants Hospital and Hartford Hospital of patients with malignant mixed mesodermal tumors of the ovary, and to review the pertinent literature. METHODS: Fourteen cases of malignant mixed mesodermal tumors of the ovary at the two hospitals over a 5-year period were identified through their tumor registries. Demographic data, pathology, treatment, and survival rates were reviewed. RESULTS: The median survival of the patients in our series was 7 months, with 64% dead of disease in 1 year. A review of the pertinent literature indicated median survivals of 6-12 months, with more than 70% of the patients dead of disease at 1 year, despite treatment. CONCLUSION: Further investigation is needed to determine the proper management for malignant mixed mesodermal tumors of the ovary. Meanwhile, current treatment strategies should recognize the present therapeutic limitations, so as not to diminish any further the quality of life for women with this malignancy.
Malignant mesodermal mixed tumor comprised of epithelial and nonepithelial components is rarely encountered in the urological field. Only 6 cases of malignant mesodermal mixed tumor of the ureter have previously been reported in the literature. We recently encountered a 7th case of malignant mesodermal mixed tumor of the ureter and describe the case in detail. The etiology of malignant mesodermal mixed tumor is also discussed.
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.
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.