Endometrial endometrioid carcinomas associated with Ewing sarcoma/peripheral primitive neuroectodermal tumor

Area of Science:

• Gynecologic Pathology
• Oncology
• Molecular Diagnostics

Background:

• Uterine tumors can present with complex histology, challenging accurate diagnosis on initial biopsy.
• Ewing's sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is rare in the uterus, often misdiagnosed.
• Distinguishing ES/pPNET from other small round cell tumors is critical for appropriate patient management.

Observation:

• Three cases of concurrent endometrioid carcinoma and ES/pPNET are presented.
• ES/pPNET components were initially misidentified as high-grade homologous sarcomas on endometrial biopsies.
• Immunohistochemical analysis revealed focal neuron-specific enolase, diffuse vimentin, and strong CD99 (O13) membrane positivity in the ES/pPNET.
• EWS/FLI-1 fusion transcript was detected, confirming the ES/pPNET diagnosis.
• CD99 (O13) immunoreactivity was absent in 40 cases of malignant mixed mullerian tumors (MMMT).

Findings:

• CD99 (O13) membrane positivity is a key diagnostic indicator for ES/pPNET in uterine round cell sarcomas.
• The EWS/FLI-1 fusion transcript confirms the diagnosis of ES/pPNET.
• ES/pPNET can be overlooked in endometrial biopsies, necessitating examination of hysterectomy specimens.

Implications:

• CD99 (O13) immunohistochemistry can serve as an important diagnostic clue for ES/pPNET in uterine sarcomas.
• Accurate diagnosis of co-occurring ES/pPNET and endometrioid carcinoma is essential for treatment planning.
• This study highlights the utility of molecular testing (EWS/FLI-1) for definitive diagnosis.