Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria

Histopathology. 2021 Jul;79(1):23-33. doi: 10.1111/his.14330. Epub 2021 Apr 12.


Aims: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey.

Methods and results: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, β-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) β-catenin-activated HCAs, three (6%) β-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the β-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the β-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases.

Conclusion: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that β-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

Keywords: atypical hepatocellular neoplasm; hepatocellular adenoma; hepatocellular carcinoma.

MeSH terms

  • Adenoma, Liver Cell / classification*
  • Adenoma, Liver Cell / pathology*
  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Child
  • Female
  • Humans
  • Liver Neoplasms / classification*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Turkey
  • World Health Organization
  • Young Adult


  • Biomarkers, Tumor