HPV-associated Endocervical Adenocarcinoma In Situ (AIS) With an ER+/Vimentin+/CEA− immunophenotype Mimicking Tubo-endometrioid Metaplasia

HPV-associated endocervical adenocarcinoma in situ (AIS) is typically ER−, vimentin−, and CEA+. By contrast, tubo-endometrioid metaplasia (TEM), a well-known mimicker of AIS, is typically ER+, vimentin+, and CEA−. Both AIS and TEM express p16, with block-positive expression in AIS and predominantly patchy expression in TEM; however, TEM may also exhibit p16 expression that is extensive enough that it borders on block-like expression. Here we share 2 cases of endocervical AIS that showed an endometrioid immunophenotype (ER+, vimentin+, and CEA−). The AIS in these cases also had a second population of pale p40− epithelioid cells resembling the ciliated cells of TEM; no true cilia were seen. High-risk human papillomavirus (HPV) in situ hybridization (HR-HPV ISH) testing was positive in both cases of AIS, establishing their HPV association. Despite the lack of true cilia, the morphology and immunophenotype of the AIS in these cases resulted in a very TEM-like picture. Given the aforementioned propensity of TEM to show a high degree of p16 expression, we share these cases as a reminder that an endometrioid-like immunophenotype by ER, CEA, and vimentin IHC does not unequivocally establish a benign diagnosis.