There is a poorly recognized and characterized group ofatypical hepatocellular neoplasms that fall between the WHOclassifications of hepatocellular adenoma and carcinoma.Joseph et al. examined 27 hepatocellular neoplasms (14carcinomas and 13 atypical neoplasms) showing diffuseglutamine synthetase staining (surrogate marker for activatedβ-catenin). Capture-based next-generation sequencing wasperformed across the samples to assess genomic alterationsthat might support further classification of the samplesbetween hepatocellular adenoma and hepatocellularcarcinoma. Alterations in WNT pathway genes (CTNNB1, APC,AXIN1) were seen in 81% of cases. Non-WNT pathwaymutations in TP53, TSC1, DNMT3A, CREBBP or various copynumber alterations were present in 56% of atypicalhepatocellular neoplasms irrespective of presence or degreeof cytoarchitectural atypia. TERT promoter mutations andcopy-number alterations were restricted to hepatocellularcarcinoma (21%). The group proposes that this additionalgenomic analysis is supported when, by themselves,glutamine synthetase staining and morphology are unable tofully support definitive classification.
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