LAUSR

Dedifferentiated endometrial adenocarcinoma (DEC) is defined by the coexistence of undifferentiated carcinoma with low‐grade (FIGO grade 1 or 2) endometrioid carcinoma. Few cases of DEC arising in the background of high‐grade carcinoma (DEC‐HG) have been reported, however, this phenomenon is poorly characterized. In this study we describe the morphologic, immunohistochemical and clinico‐pathologic characteristics of DEC‐HG. 18 DECs were diagnosed at our institution between 2008‐2019, and in 11 (61%), the undifferentiated component was associated with high‐grade carcinoma (8 endometrioid FIGO grade 3, 2 with ambiguous features, 1 serous). The remaining 7 (39%) represented DEC‐LG (3 FIGO grade 1 and 4 FIGO grade 2). 7/11 (64%) patients with DEC‐HG presented with advanced stage (FIGO stage III/IV), whereas most with DEC‐LG (6/7, 86%) were stage I. On follow up, 2 patients in the DEC‐HG group died of disease and 2 had progressive disease within 2 months of surgery. There was only one recurrence in the DEC‐LG, 6 months post‐surgery. The DEC component in both groups showed similar morphology and immunophenotype, with predominantly focal or complete loss of expression of pan‐keratin, EMA, E‐cadherin, CK8/18, PAX8 and ER. The DEC component in the DEC‐HG group had wild‐type p53 expression in 8/11 (73%) cases, loss of MLH1 and PMS2 in 6/11 (55%) and loss of SMARCA4 in 3/9 (33%). Although numbers are small, we show that DEC‐HG is a previously under‐recognized phenomenon, with morphologic and immunophenotypic similarities to DEC‐LG, which supports expanding the definition of DEC to include DEC‐HG. DEC‐HG may be more aggressive than DEC‐LG.