Carcinosarcoma (CS) of the female genital tract, also known as malignant mixed müllerian tumor (MMMT), is a rare aggressive malignant tumor. It accounts for approximately 1-2% of all malignant tumors in the gynecologic tract. Although it may occur in the ovary, fallopian tube or cervix; the most common site is the uterus. Patients’ age is ranged from 23 to 87 years with a mean of 65 years; it is therefore more commonly seen in postmenopausal women. A prior history of tamoxifen and radiation therapy are well-known risk factors for the development of CS. The clinical manifestations of CS are mainly vaginal bleeding and/or spotting, and abnormal findings on Pap smear. Molecular studies have shown that the tumor is monoclonal in origin rather than a collision tumor. The same epigenetic alterations, including alterations in PT53, gain-of-functional mutations in PIK3CA or KRAS, overexpression of TGF-beta (epithelial to mesenchymal transition pathway) and others, have been detected in both the carcinomatous and sarcomatous component. Based on the molecular profile, the sarcomatous component of CS is now considered a derivative of the carcinomatous component. In addition, there are significant genetic overlaps between uterine high-grade serous carcinomas and CSs. The current World Health Organization classification of the gynecologic tract neoplasms classifies CS as a form of endometrial carcinoma. CS behaves very aggressively, with a five-year survival rate < 30%, in the comparison with endometrial carcinomas. The optimal therapy for CS patients has not been clearly defined. The CS patient is commonly treated with surgical resection of the tumor followed by chemo- and radiation-therapy, based on the tumor stage and histomorphological feature. The morphological evaluation and molecular tests of the tumor are important for the personalized therapy.
Gross examination of the tumor reveals a polypoid mass. Histologically, the tumor is composed of epithelial (carcinoma) and mesenchymal (sarcoma) elements. Adenocarcinoma is the most common epithelial component, however, squamous cell carcinoma or a mixture of adenocarcinoma and squamous cell carcinoma may be seen. The sarcomatous component of the tumor may be of the homologous (elements derived from uterine tissue, i.e. smooth muscle, stroma and connective tissue) and/or heterologous type (elements derived from non-uterine tissue, i.e. skeletal muscle, cartilage and bone). The homologous type refers to features of leiomyosarcoma, stromal sarcoma or anaplastic sarcoma; and the heterologous type refers to features of rhabdomyosarcoma, osteosarcoma or chondrosarcoma. Tumor cells of adenocarcinoma component resemble those of endometrial adenocarcinoma or those of high-grade serous carcinoma. Tumor cells may be arranged in three-dimensional or papillary clusters with large hyperchromatic nuclei, coarse chromatin, irregular nuclear membrane and prominent nucleoli. The sarcomatous cells are usually seen as scattered individual cells with elongated nuclei and abundant cytoplasm. Spindle cells may also form loose clusters or aggregates. Heterologous elements (most commonly rhabdomyosarcoma and/or chondrosarcoma), are associated with a more aggressive course of disease and poor prognosis. However, the sarcomatous component is only noted in less than one third of cases in Pap test slides. Cell block preparations can be made from liquid-based Pap tests for immunohistochemical studies. The epithelial/glandular component is positive for cytokeratin, whereas, the sarcomatous component is positive for desmin, myoD1, myoglobin and sarcomeric actin (for rhabdomyosarcoma), and S100 (for cartilaginous element). P53, WT-1 and p16 can be diffusely positive in both epithelial and sarcomatous components.