Malignant transformation of a β-catenin inflammatory adenoma due to an S45 β-catenin-activating mutation present 12 years before

Abstract

In 1984, a 24-year-old woman underwent a right hepatectomy after a 17-cm nodule, diagnosed as a hepatocellular adenoma with some atypia. The resection was incomplete. Follow-up was interrupted. In 1996, a computed tomographic scan revealed a large multifocal hepatocellular carcinoma confirmed on biopsies. The patient died the same year. We reviewed these nodules using immunohistochemistry and gene sequencing. C-reactive protein was overexpressed in the tumor resected in 1984. Glutamine synthetase was heterogeneous in the tumor, with a few tumor nuclei expressing β-catenin. Glypican and heat shock protein 70 were negative. In this β-catenin-activated inflammatory hepatocellular adenoma, S45 β-catenin-activating mutation was detected on fixed tissue, embedded in paraffin without TERT promoter mutation. An identical CTNNB1 mutation was identified in the 1996 liver tumor together with a TERT promoter mutation showing that this hepatocellular carcinoma results from the malignant transformation of the initial β-catenin inflammatory adenoma.

Keywords: Hepatocellular carcinoma; Inflammatory hepatocellular adenoma; S45 β-catenin–activating mutation; TERT promoter mutation; β-Catenin–activated inflammatory hepatocellular adenoma.