Mesonephric-like adenocarcinoma of the endometrium: detailed molecular characterization of the first case showing a morphological continuum from mesonephric-like metaplasia and atypical mesonephric-like hyperplasia to adenocarcinoma.

Abstract

Mesonephric-like adenocarcinoma is a rare subtype of endometrial cancer, characterized by its histological and molecular overlap with mesonephric carcinoma of the uterine cervix. This study presents a unique case of mesonephric-like adenocarcinoma in the endometrium, accompanied by adjacent mesonephric-like hyperplasia and atypical mesonephric-like hyperplasia. Histologically, the transition from mesonephric metaplasia to adenocarcinoma was evident, and molecular analysis revealed shared mutations, including KRAS (p.G12D) in both atypical hyperplasia and adenocarcinoma, and a novel BCOR mutation (p.A1314Nfs*49) in the adenocarcinoma. These findings suggest a Müllerian origin of mesonephric-like adenocarcinoma via mesonephric transdifferentiation, challenging the traditional understanding of mesonephric histogenesis. The identification of these mutations underscores the potential for targeted therapies, particularly in cases with BCOR and KRAS mutations. This study is the first to document preneoplastic lesions in mesonephric-like adenocarcinoma, offering new insights into its pathogenesis and therapeutic implications.