Undifferentiated endometrial carcinoma arising in the background of high-grade endometrial carcinoma - Expanding the definition of dedifferentiated endometrial carcinoma.

ABSTRACT

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.