Endometrial Carcinosarcomas are Almost Exclusively of p53abn Molecular Subtype After Exclusion of Mimics

Our aim was to assess the molecular subtype(s) and perform a detailed morphologic review of tumors diagnosed as carcinosarcoma in a population-based cohort. Forty-one carcinosarcomas were identified from a cohort of 973 endometrial carcinomas diagnosed in 2016. We assessed immunostaining and sequencing data and undertook expert pathology reviews of these cases as well as all subsequently diagnosed (post-2016) carcinosarcomas of no specific molecular profile (NSMP) molecular subtype (n=3) from our institutions. In the 2016 cohort, 37 of the 41 carcinosarcomas (91.2%) were p53abn, 2 (4.9%) were NSMP, and 1 each (2.4%) were POLE mut and mismatch repair deficiency molecular subtypes, respectively. Of the 4 non-p53abn tumors on review, both NSMP tumors were corded and hyalinized (CHEC) pattern endometrioid carcinoma, the mismatch repair deficiency tumor was a grade 1 endometrioid carcinoma with reactive stromal proliferation, and the POLE mut tumor was grade 3 endometrioid carcinoma with spindle cell growth, that is, none were confirmed to be carcinosarcoma on review. We found 11 additional cases among the 37 p53abn tumors that were not confirmed to be carcinosarcoma on the review (3 undifferentiated or dedifferentiated carcinomas, 5 carcinomas with CHEC features, 2 carcinomas showing prominent reactive spindle cell stroma, and 1 adenosarcoma). In the review of institutional cases reported as NSMP carcinosarcoma after 2016, 3 were identified (1 adenosarcoma and 2 mesonephric-like adenocarcinoma on review). In this series, all confirmed endometrial carcinosarcomas were p53abn. The finding of any other molecular subtype in a carcinosarcoma warrants pathology review to exclude mimics.