Final Diagnosis -- Mixed Müllerian Tumors

FINAL DIAGNOSIS:

1. Poorly differentiated carcinosarcoma (Malignant Mixed Mullerian tumor with papillary serous carcinoma and rhabdomyosarcomatous component) arising from the posterior wall of endometrium (6.0 cm.) invading myometrium.
2. Extensive angiolymphatic invasion by papillary serous carcinoma present.
3. Multiple leiomyomas (largest 11 cm.) with angiolymphatic invasion by papillary serous carcinoma.
4. T3aN1M1 (FIGO stage IVB).

AUTOPSY FINDINGS: Extensive metastatic papillary serous carcinoma to thoracic and abdominal lymph nodes, multiple small intestinal, peri-biliary and splenic capsular metastases.

Mixed Müllerian tumors (MMT) or carcinosarcomas comprise 2-3 % of all uterine malignancies occurring in older post-menopausal women. They are tumors in which both the epithelial and non-epithelial components are histologically malignant. They are further subdivided into homologous and heterologous types. The most common presenting symptom is post- menopausal uterine bleeding. Other symptoms include lower abdominal pain, abdominal distention, and a palpable abdominal mass are also frequent presenting complaints. Many patients have clinical evidence of extensive extrauterine disease at initial presentation.

Grossly, carcinosarcomas present as a large, soft, friable polypoid tumors, involving endometrium and myometrium, and usually fill the endometrial cavity. Many of them are so large that they protrude through the external os. The surface is often smooth and the cut surface is more fleshy, variegated, hemorrhagic and necrotic.

MMT of the endometrium extends to the endocervix in about a quarter of cases. MMT may also arise in the cervix, where it growth as a polypoid neoplasm. Cervical MMT, compared to their counterparts in the corpus, are more commonly confined to the uterus at presentation, may have a better prognosis, and frequently have a nonglandular epithelial component.

Microscopically the tumor is composed of admixture of malignant epithelium (carcinomatous) and sarcomatous stroma, with latter usually predominating. The carcinoma component can include the full range of histologic variants. An adenocarcinoma of endometrioid type and poorly differentiated (often papillary serous) endometrial carcinoma usually predominant. The epithelial component of the tumor usually shows the most capability for invasion and metastases.

The sarcomatous component can be either homologous or heterologous. The homologous sarcomatous component is usually high grade and may consist of spindle cells, round cells or giant cells. Sometimes the stromal component resembles fibrosarcoma or leiomyosarcoma. The heterologous are those that contain chondrosarcoma, osteosarcoma or rhabdomyosarcoma.

Immunohistochemical staining for cytokeratin and epithelial membrane antigen (EMA) highlights the epithelial component. There is a generalized immunoreactivity for vimentin in the mesenchemal component. Occasionally mesenchymal components of MMT exhibit patchy positive staining with antibodies to cytokeratin and EMA, but this staining is less intense than is observed in the epithelial component of the tumor. Myoglobin is the most specific marker of rhabdomyoblastic differentiation but is also less sensitive. Immunoreactivity with desmin or muscle specific actin is also indicative of rhabdomyosarcoma. Foci of chondrosarcomatous differentiation are positive for S-100 protein.

The prognosis is extremely poor. Metastases occur early. Some studies suggest that having only homologous stroma elements have a slightly better prognosis than those with heterologous elements. Other studies suggest that there is no significant difference in prognosis. The prognosis is far more outweighed by the surgical pathological stage of disease and the stage is the single most significant prognostic factor. Positive peritoneal cytology is associated with unfavorable prognosis and shows extrauterine spread.

Total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy is the treatment of choice. The response to radiation therapy and chemotherapy has been generally poor. The most common sites of recurrence are lung and abdominal cavity.

REFERENCES:

1. Clement PB, et al. Malignant müllerian mixed tumors of the uterine cervix. Int J Gynecol Pathol 1998 Jul; 17(3): 211-22.
2. Iwasa Y, et al. Prognostic factors in uterine carcinosarcoma: a clinicopathologic study of 25 patients. Cancer 1998 Feb 1; 82(3); 512-9.
3. Sartori E, et al. Carcinosarcoma of the uterus: a clinicopathological multicenter CTF study. Gynecol Oncol 1997 Oct; 67(1): 70-5.
4. Sreenan JJ, et al. Carcinosarcoma of the female genital tract. A pathologic study of 29 metastatic tumors: further evidence for the dominant role of the epithelial component and the conversion theory of histogenesis. Am J Surg Pathol 1995 Jun; 19(6): 666-74.
5. de Brito PA, et al. Carcinosarcoma (malignant mixed müllerian (mesodermal) tumor) of the female genital tract: immunohistochemical and ultrastructural analysis of 28 cases. Hum Pathol 1993 Feb; 24(2): 132-42.
6. Costa MJ, et al. Carcinoma (malignant mixed müllerian [mesodermal] tumor) of the uterus and ovary. Correlation of clinical, pathologic and immunohistochemical features in 29 cases. Arch Pathol Lab Med 1991 Jun; 115(6): 583-90.
7. Silverberg SG, et al. Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group study of 203 cases. Int J Gynecol Pathol 1990; 9(1): 1-19.
8. Blaustein's Pathology of the female genital tract, forth edition 1994 (514-518)
9. Tumors of the uterine corpus and gestational trophoblastic disease, AFIP 1991 (166-179).

Contributed by Irina Pushkar, MD and Uma NM Rao, MD