A Case Report of Uterine Dedifferentiated Mesonephric-Like Adenocarcinoma With Comprehensive Molecular Profiling.

Abstract

Mesonephric-like adenocarcinoma (MLA) of the uterus is a rare, aggressive malignancy of presumed Müllerian origin that was recently included in the 2020 World Health Organization (WHO) Classification of Female Genital Tumours. MLA is challenging to diagnose given its rarity and morphologic heterogeneity. The recently published first case report of MLA that underwent dedifferentiation via TP53 mutation expands the morphologic spectrum of dedifferentiated carcinoma. In here, we describe a second case of an endometrial MLA with dedifferentiation from a 41-yr-old woman who presented with bilateral ovarian masses, peritoneal carcinomatosis, and hypercalcemia. A diagnosis of small cell carcinoma of the ovary, hypercalcemic type, was initially rendered at an outside institution from an omental biopsy, which only showed the undifferentiated component. The subsequent endometrial curettings performed at our institution showed both the MLA and undifferentiated components, each of which demonstrated distinct immunophenotype with the immunoreactivity to epithelial markers, GATA3 and TTF1 limited to the MLA component and the aberrant nuclear expression of beta catenin, global loss of expression of SMARCA4 and loss of expression of SMARCA2 limited to the undifferentiated component. Molecular studies on the undifferentiated component from the omental biopsy identified not only a mutation in KRAS, gene mutation commonly seen in MLA, but also mutations in SMARCA4 and CTNNB1. In summary, we describe a second case of dedifferentiated MLA with dedifferentiation driven by various genetic alterations, including SMARCA4 and CTNNB1 gene mutations, novel gene alterations that have never been described in dedifferentiated MLA.