Diffuse glutamine synthetase overexpression restricted to areas of peliosis in a β-catenin-activated hepatocellular adenoma: a potential pitfall in glutamine synthetase interpretation

Virchows Arch. 2014 Aug;465(2):241-5. doi: 10.1007/s00428-014-1620-8. Epub 2014 Jul 6.

Abstract

Hepatocellular adenomas have recently been classified into four subtypes based on molecular findings: hepatocyte nuclear factor 1α (HNF1α) inactivated, inflammatory/telangiectatic, β-catenin activated, and unclassifiable. β-catenin-activated adenomas have the potential for malignant transformation and are thus important to recognize. Diffuse glutamine synthetase immunohistochemical positivity has been shown to be a reliable surrogate marker for β-catenin activation, though variations in staining patterns may be difficult to interpret. We report a case of a peliotic adenoma that was morphologically consistent with a β-catenin wild-type hepatocellular adenoma but harbored a β-catenin mutation by molecular analysis. The tumor lacked nuclear β-catenin positivity and demonstrated a hitherto undescribed pattern of glutamine synthetase overexpression restricted to areas of peliosis with mostly negative staining in non-peliotic areas. This pattern was initially interpreted as physiologic and may represent a potential pitfall in glutamine synthetase interpretation.

Publication types

  • Case Reports

MeSH terms

  • Adenoma, Liver Cell / diagnosis
  • Adenoma, Liver Cell / epidemiology
  • Adenoma, Liver Cell / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Comorbidity
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glutamate-Ammonia Ligase / biosynthesis*
  • Hepatectomy
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver / surgery
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / metabolism*
  • Middle Aged
  • Mutation / genetics
  • Peliosis Hepatis / epidemiology
  • Peliosis Hepatis / metabolism*
  • Up-Regulation
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • beta Catenin
  • Glutamate-Ammonia Ligase