title: 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.
authors.affiliation: Institut Universitaire de Pathologie, Université de Lausanne, CH-1011 Lausanne, Switzerland. Electronic address: christine.sempoux@chuv.ch.
authors.forename: Christine
authors.initials: C
authors.lastname: Sempoux
authors.affiliation: Institut Universitaire de Pathologie, Université de Lausanne, CH-1011 Lausanne, Switzerland. Electronic address: Bettina.Bisig@chuv.ch.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bisig
authors.affiliation: Functional Genomics of Solid Tumors, Inserm, U1162, Université Paris Descartes, Université Paris Diderot, Université Paris 13, 75010 Paris, France. Electronic address: gabrielle.couchy@inserm.fr.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Couchy
authors.affiliation: Université Bordeaux, Inserm U1053, 33076 Bordeaux Cedex, France. Electronic address: charles.balabaud@u-bordeaux.fr.
authors.forename: Charles
authors.initials: C
authors.lastname: Balabaud
authors.affiliation: Functional Genomics of Solid Tumors, Inserm, U1162, Université Paris Descartes, Université Paris Diderot, Université Paris 13, 75010 Paris, France. Electronic address: jessica.zucman-rossi@inserm.fr.
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
authors.affiliation: Université Bordeaux, Inserm U1053, 33076 Bordeaux Cedex, France. Electronic address: paulette.bioulac-sage@u-bordeaux2.fr.
authors.forename: Paulette
authors.initials: P
authors.lastname: Bioulac-Sage
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007120:Immunochemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009154:Mutation; D018365:Neoplasm, Residual; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin
keywords: Hepatocellular carcinoma; Inflammatory hepatocellular adenoma; S45 β-catenin–activating mutation; TERT promoter mutation; β-Catenin–activated inflammatory hepatocellular adenoma