Histopathological Subtypes and PD-L1 Expression in Primary Urethral Adenocarcinoma: A Series of 5 Cases

Urethral adenocarcinoma is a rare disease with poor prognosis that can display multiple histologic patterns and has an unclear histogenesis. Radical surgery with extensive periurethral resection is the preferred therapeutic approach. Both chemotherapy and radiotherapy have been used as complementary treatment options. Due to the tendency of these tumors to recur, treatment-associated complications, and the limited choice of therapeutic options, patient management can be difficult. Given the lack of literature regarding immunotherapy in urethral adenocarcinoma, our objective was to explore the expression of programmed death receptor-ligand 1 (PD-L1) throughout the different histological subtypes of primary urethral adenocarcinoma.

We reviewed all primary urethral adenocarcinomas diagnosed at our hospital between 1965 and 2019, performed immunohistochemical assays on the tissue blocks, classified them according to their histology and origin, and performed PD-L1 (22C3) immunohistochemistry assays in all cases.

We found a total of 5 cases of primary urethral adenocarcinoma. All of the patients were women. One of the cases was a cribriform adenocarcinoma, 2 were columnar-mucinous adenocarcinomas, and 2 were clear cell adenocarcinomas. One of the clear cell adenocarcinomas strongly expressed PD-L1. In addition, a profuse inflammatory infiltration constituted by CD3-positive and CD8-positive T lymphocytes within tumor cells was observed in this case. None of the other cases showed PD-L1 expression.

In conclusion, some urethral adenocarcinomas may strongly express PD-L1 and thus could potentially allow the use of immunotherapy in selected cases of advanced or recurrent adenocarcinoma.