A 71-year-old woman with no significant past medical history presented with postmenopausal bleeding of 4 months of duration. Ultrasound revealed a markedly thickened and enlarged endometrium with free pelvic fluid concerning for endometrial malignancy. Hysteroscopy revealed a vascularized protruding mass through the cervical os. Representative H&E sections of the endometrial biopsies are depicted below, along with selected immunohistochemical stains.
The correct answer is ...
This tumor is a carcinosarcoma with heterologous rhabdomyoblastic differentiation. Cytokeratin 7 immunohistochemical stain highlights the high-grade carcinoma component. Myogenin and MyoD1 confirm the rhabdomyoblastic heterologous component.
This is an uncommon, highly aggressive tumor that accounts for less than 5% of uterine malignancies. These tumors usually present in postmenopausal women. It is associated with unopposed estrogens, pelvic irradiation, and prior tamoxifen use. The most common presenting symptom is vaginal bleeding. Some patients present with symptoms related to a pelvic mass or metastatic disease. On gross examination, these tumors are typically large polypoid masses involving the posterior wall, frequently protruding unto the endometrial cavity and may prolapse through the cervical os. Histologically, they are characterized by high-grade malignant epithelial and mesenchymal components of variable proportions and are sharply demarcated. The carcinoma component is high-grade, often serous or endometrioid differentiation, but other components including clear cell and undifferentiated can be seen. The mesenchymal component can be heterologous or homologous. If homologous, this component is frequently high-grade and undifferentiated. The most common heterologous elements are chondrosarcoma followed by rhabdomyosarcoma.
In the appropriate clinical setting, extensive sampling of an undifferentiated sarcoma or pleomorphic rhabdomyosarcoma may reveal areas of epithelial differentiation, rendering the diagnosis of carcinosarcoma. Immunohistochemical stains can aid the diagnosis; however, the epithelial and mesenchymal component should be apparent upon morphological examination. The carcinomatous component is positive for cytokeratins and EMA. The sarcomatous component is positive for vimentin and may show staining for desmin, actin, CD10, and CD34. P16 and p53 are overexpressed in both components. Myogenin and MyoD1 nuclear staining confirms the presence of a rhabdomyoblastic differentiation. Pathologic factors that are associated with poor prognosis include high-grade carcinoma component, heterologous element in the sarcoma component, sarcoma component >50%, increased size (>5 cm), deep myometrial invasion, lymphovascular invasion, malignant peritoneal cytology, lymph node metastasis, as well as local and distant metastatic disease.1-4
Luisa Maria Ricaurte Archila, M.D.
Resident, Anatomic and Clinical Pathology
Gary Keeney, M.D.
Consultant, Anatomic Pathology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science