September 2022 – Gynecological Pathology

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.

Figure 1: HE Low Power
Figure 2: HE High Power
Figure 3: KRT7
Figure 4: Desmin
Figure 5: Myogenin
Figure 6: MyoD1

What is the most likely diagnosis?

  • Dedifferentiated endometrioid carcinoma
  • Corded and hyalinized endometrial adenocarcinoma
  • Mullerian adenosarcoma
  • Endometrial carcinosarcoma

The correct answer is ...

Endometrial carcinosarcoma.

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

  • Dedifferentiated carcinoma: These are uncommon tumors and are characterized by an undifferentiated epithelial component, which is formed by sheets of medium-to-large discohesive round cells that can occur in isolation or in combination with areas of well-differentiated endometrioid adenocarcinoma. There is frequently a sharp demarcation between both components and hence can be mistaken for a carcinosarcoma, as the undifferentiated carcinoma can be misinterpreted as an undifferentiated sarcoma. However, in dedifferentiated endometrioid carcinoma the epithelial component is low-grade while in carcinosarcoma the epithelioid component, when endometrioid is typically high-grade. Immunohistochemical stains can be helpful as the undifferentiated epithelial component formed by non-cohesive cells are focally positive for cytokeratins and EMA. These tumors are also associated with mismatch repair abnormalities, while carcinosarcomas are not.1
  • Corded and hyalinized endometrioid adenocarcinoma: These are low- to intermediate- grade adenocarcinomas with areas of hyalinized stroma containing corder epithelioid and spindled cells. Metastatic osteoid can be present. These features can be mistaken for a malignant stromal component with heterologous differentiation. In contrast to carcinosarcoma, this variant often occurs at a younger age group, is associated with a low- to intermediate-grade, glandular component, and lacks the high-grade pleomorphic malignant stromal component seen in carcinosarcoma.1
  • Mullerian adenosarcoma: This is a mixed epithelial and stromal tumor. The epithelial component, usually endometrioid has a benign appearance, may have a phyllodes like growth pattern. The stromal component shows a “tufting” pattern of hypercellularity beneath the glandular epithelium. The stromal atypia varies from mild to severe. These tumors are usually low-grade but high-grade variants exist.1


  1. McCluggage, W.G., A practical approach to the diagnosis of mixed epithelial and mesenchymal tumours of the uterus. Mod Pathol. 2016;29 Suppl 1:S78-91.
  2. McCluggage, W.G., N. Singh, C.B. Gilks. Key changes to the World Health Organization (WHO) classification of female genital tumours introduced in the 5th edition (2020). Histopathology. 2022;80(5):762-778.
  3. Chen, X., et al., Uterine Carcinosarcomas: Clinical, Histopathologic and Immunohistochemical Characteristics. Int J Gynecol Pathol. 2017;36(5):412-419.
  4. Matsuzaki, S., et al., Uterine carcinosarcoma: Contemporary clinical summary, molecular updates, and future research opportunity. Gynecol Oncol. 2021;160(2):586-601.

Luisa Maria Ricaurte Archila, M.D.

Resident, Anatomic and Clinical Pathology
Mayo Clinic

Gary Keeney, M.D.

Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.