Focal b-catenin mutation identified on formalin-fixed and paraffin-embedded inflammatory hepatocellular adenomas

Abstract

The identification of hepatocellular adenoma (HCA) with mutation in exon 3 of the CTNNB1 gene encoding for b-catenin is clinically relevant due to higher risk of malignant transformation. Inflammatory HCA (IHCA) can exhibit b-catenin activation (b-IHCA). We report 2 cases with multiple IHCA in which focal b-catenin activation has been found in one of the IHCA. In both cases, the diagnosis of IHCA was confirmed on the resected nodules by routine stains, immunohistochemical detection of C-reactive protein (CRP), and molecular biology on frozen material. An additional molecular analysis was performed on formalin fixed paraffin embedded (FFPE) material that showed focal glutamine synthetase (GS) staining, the surrogate marker of b-catenin activation. In case one, it was a 1.8 cm area within the 7.5 cm IHCA, and in case two, a small 0.3 cm area within a 1.8 cm resected IHCA located close to a larger IHCA, negative for GS. In both cases, nuclear beta-catenin expression and decreased reticulin network were observed in the GS expressing foci, together with cholestasis and diffuse CD34 expression in case one. Molecular analysis by pyrosequencing on FFPE material using the GS stained slides as reference to select areas with/without positive staining revealed a CTNNB1 exon 3 mutation restricted to the areas exhibiting both positive GS and CRP expression, whereas wild-type CTNNB1 was found in areas showing only CRP staining. These 2 cases illustrate focal b-catenin activation that can occur within IHCAs. Additional data are needed to tell if b-catenin mutation is a secondary event in IHCA.

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