[Familial endometrial adenocarcinoma: MSH6 variant of unknown significance in the presence of phenocopy, what should be done?]

Abstract

Endometrial cancer (EC) is the second most common tumor in women with Lynch syndrome, and can be its first manifestation. It may exhibit negative immunostaining for DNA mismatch-repair proteins and/or microsatellite instability. We present the case of a woman with EC in which a MSH6 variant of unknown significance was identified. To establish the pathogenicity of the variant, the family study was extended, identifying her healthy sister as a carrier while her aunt, with EC, was not. In the latter, the histopathology of a first tumor block did not identify the pathway of carcinogenesis, but its repetition in a second tumor block suggested the possibility of it being a phenocopy. The multidisciplinary approach in the study of this family allowed a correct diagnosis of the different adenocarcinomas, adequate family genetic counselling and the correct assignment of pathogenicity to a variant in MSH6.

Keywords: Adenocarcinoma de endometrio; Endometrial adenocarcinoma; Heterogeneidad somática; Inestabilidad de microsatélites; Microsatellite instability; Mismatch repair proteins; Proteínas reparadoras; Somatic heterogeneity.