Hepatocellular Neoplasms Arising in Association With Androgen Use

Sounak Gupta, Bita V. Naini, Richard Munoz, Rondell Graham, Benjamin R. Kipp, Michael Torbenson, Taofic Mounajjed

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13 Scopus citations

Abstract

Correlation between androgen use and hepatocellular neoplasia is well established. However, there are no detailed studies of the histopathology and immunohistochemical/molecular profile of these tumors. We studied 9 patients with androgen-associated hepatocellular neoplasms. In addition to histology, immunostains for liver fatty acid–binding protein, β-catenin, glutamine synthetase, C-reactive protein, and serum amyloid A were utilized for tumor subtyping. Molecular testing using Solid Tumor Targeted Cancer Panel was performed on 3 cases. The neoplasms were predominantly seen in male individuals (7/9). Two patients (22%) had multifocal lesions. All lesions had architectural and 4/9 had cytologic atypia. Cholestasis was present in 6/9 cases. Reticulin was focally disrupted in 5/9 cases. Given the clinical setting, all lesions were classified as well-differentiated hepatocellular neoplasms of uncertain malignant potential. In cases with follow-up (6/9 cases, 67%), there were no recurrences or metastases. On the basis of the immunoprofile, 7 (78%) cases were β-catenin activated (including 1 hepatic adenoma with concurrent hepatocyte nuclear factor 1α inactivation) and 2 (22%) had inflammatory phenotype. Somatic mutations in CTNNB1 were detected in all 3 tested cases (all β-catenin activated by immunostain), all involving exon-3. Our data indicate that androgen-associated hepatocellular neoplasms most often develop in male individuals and always show some degree of atypia and/or focal reticulin disruption. Most are β-catenin activated, often harboring CTNNB1 exon-3 mutations, and a minority is inflammatory type. Although β-catenin and inflammatory pathways likely play a role in pathogenesis, the heterogenous molecular profile suggests there are other (yet to be characterized) primary oncogenic mechanisms in this unique tumor type.

Original languageEnglish (US)
JournalAmerican Journal of Surgical Pathology
DOIs
StateAccepted/In press - Dec 17 2015

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ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

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