Multifocal β-catenin activated hepatocellular adenomas (HCA) with malignant transformation in hepatocellular carcinoma (HCC) after abuse of anabolic steroids

N Waldburger; N Habbe; F Schulze; H Lindenmaier; F Ulrich; WO Bechstein; P Schirmacher; T Longerich

doi:10.1055/s-0033-1360983

Zeitschrift für Gastroenterologie, Table of Contents

Multifocal β-catenin activated hepatocellular adenomas (HCA) with malignant transformation in hepatocellular carcinoma (HCC) after abuse of anabolic steroids

N Waldburger ¹, N Habbe ², F Schulze ³, H Lindenmaier ¹, F Ulrich ², WO Bechstein ², P Schirmacher ¹, T Longerich ¹

¹Ruprecht-Karls-Universität, Institute of Pathology, Heidelberg, Germany
²Johann Wolfgang Goethe-Universität, Department of General and Visceral Surgery, Frankfurt, Germany
³Johann Wolfgang Goethe-Universität, Institute of Pathology, Frankfurt, Germany

Abstract

Introduction: Hepatocellular adenoma (HCA) is a benign neoplasm of the non-cirrhotic liver mainly affecting young women with use of oral contraceptives. Based on genetic, pathological and clinical features HCAs are divided into four subgroups: HNF1α-mutated, β-catenin-activated, inflammatory, and unclassified. Especially the β-catenin-activated subgroup harbors a higher risk of malignant transformation and is characterized by overexpression of glutamine synthetase. Case presentation: A 28-years old male bodybuilder abusing anabolic steroids presented with acute abdomen and massive abdominal pain in the emergency department. Abdominal computed tomography (CT) showed a ruptured subcapsular haematoma with signs of active bleeding into the left liver lobe and a cystic lesion in segment 5. Consecutively, left hemihepatectomy was performed. Macroscopically, the liver resection specimen showed seven, partially ruptured nodules with areas of necrosis and hemorrhage. Histological examination revealed multiple highly differentiated hepatocellular neoplasms with areas of architectural and cytological atypia arising in a non-cirrhotic liver. Immunohistochemistry revealed overexpression of glutamine synthetase, heat shock protein 70 and nuclear overexpression of β-catenin in absence of glypican-3 positivity. Only few tumor cells were positive for serum amyloid A. Three different β-catenin mutations (p.G34E, p.G34R, p.S33C) were identified in 3 nodules by Sanger sequencing, respectively. Based on clinical, molecular, and pathological findings we diagnosed multifocal β-catenin-activated hepatocellular adenomas (HCA) with independent malignant transformation in hepatocellular carcinoma (HCC). Conclusion: The detection of three different β-catenin mutations strongly argues for both multifocal genesis of adenomas and multifocal malignant transformation driven by abuse of anabolic steroids.