Sarcomatous Transformation in Undifferentiated/Dedifferentiated Endometrial Carcinoma: An Underrecognized Phenomenon and Diagnostic Pitfall

Undifferentiated/dedifferentiated carcinoma is an aggressive endometrial carcinoma which remains underrecognized but may account for up to 9% of all endometrial malignancies. We describe 3 cases in which the undifferentiated component was associated with sarcomatous differentiation, characterized by spindled cells in 2 cases and heterologous malignant cartilage in 1 case. Two of the 3 cases demonstrated mismatch repair deficiency by immunohistochemistry. This phenomenon has not previously been formally reported and increases the likelihood of misdiagnosis, especially within biopsy samples; differential diagnoses may include endometrial stromal sarcoma and grade 3 endometrioid adenocarcinoma with spindled morphology. We review the current literature and provide strategies for resolving the differential diagnoses, with a suggested panel of antibodies which includes EMA, E-cadherin, and mismatch repair proteins as approximately 50% of cases show loss of mismatch repair expression.