Clinicopathological features of malignant mixed mesodermal tumor: analysis of 50 cases

Abstract

Objective: To investigate the clinicpathological, immunohistochemical and molecular genetic features of malignant mixed mesodermal tumor (MMMT) in the female reproductive system. Methods: To analyze its histopathological characteristics, we performed a retrospective review of the MMMT cases diagnosed at PLA General Hospital, Beijing, China during 2005-2019 using its surgical and pathological databases. EnVision immunohistochemical staining was used to detect the expression of ER, PR, p16, p53 and MMR proteins. Results: Fifty cases were conformed to the diagnosis, including 29 cases originated in the uterus, 16 cases in ovary, 4 cases of synchronous occurrence in uterus and ovary, 1 case in cervix. The tumor was histologically composed of two components, namely carcinoma and sarcoma ones, with clear borderline or blend mutually. The proportion of cancer component in the whole tumor ranged from 5%-90%. The proportion of carcinoma was more than 50% in 76% of the cases, and less than 50% in 24% of cases, including 2 cases with<10% of carcinoma. In the cases of primary uterine MMMT, the main carcinoma type was high grade endometrioid carcinoma (55%, 16/29). In ovarian MMMT, the main carcinoma type was serous carcinoma (12/16), while that of cervical MMMT was squamous cell carcinoma. The others were clear cell carcinoma or the undifferentiated carcinoma. There was one carcinoma type in most cases, only 7 cases had two carcinoma types. Homologous sarcomas, including stromal sarcoma, leiomyosarcoma and high-grade spindle cell sarcomas, were more commonly found in uterine MMMT (72.4%, 21/29). While heterogenic sarcomas, including chondrosarcoma, osteosarcoma and rhabdomyosarcoma, were more commonly noted in ovarian MMMT (12/16) than MMMT of other sites. There were 10 cases that consisted of two types of sarcomas. The synchronous MMMT of uterus and ovary had similar morphology and the types of carcinoma and sarcoma. The tumor cells that spread or metastasized to lymph node, omentum, intestinal wall or skin were all carcinoma cells, and were morphologically consistent with the original tumors. Immunohistochemically, ER and PR were both negative (23/25 in uterine, 8/10 in ovarian tumors). p16 was strongly positive (11/11 in uterine tumors, and 6/6 in ovarian tumors), with similar expression patterns in the carcinoma and sarcoma components. p53 showed mutant-type staining (64%, 21/33) and expressed synchronously in carcinoma and sarcoma components. p53 mutation was found in 35% cases of endometrial carcinoma and 46.7% cases of non-endometrial carcinoma. p53 mutation was also found in only 31.8% cases of heterogenic sarcomas, but in 50% of non-heterogenic sarcomas. Twenty-eight cases (28/33, 85%) presented intact mismatch repair proteins, while 5 cases (5/33, 15%) presented deficient mismatch repair proteins. Conclusions: MMMT in female reproductive system is a rare high-grade biphasic tumor with complex and diverse morphology. The immunohistochemical features are characterized by negative ER/PR and strongly positive p16, mostly mutant p53 and proficient mismatch repair proteins. The patients with a high FIGO stage have worse prognosis.