Glutamine Synthetase Immunoreactivity in Peritumoral Hyperplasia in Liver: Case Report of a Metastatic Paraganglioma With Focal Nodular Hyperplasia-Like Changes and Review of an Additional 54 Liver Masses

Am J Clin Pathol. 2016 Aug;146(2):254-61. doi: 10.1093/ajcp/aqw056. Epub 2016 May 31.


Objectives: Focal nodular hyperplasia (FNH) and peritumoral hyperplasia in the liver exhibit increased immunoreactivity for glutamine synthetase (GS). We observed FNH-like changes with map-like GS staining surrounding a metastatic paraganglioma and sought to determine how often such changes occur around primary and metastatic liver lesions.

Methods: We performed GS immunohistochemistry in liver cases of 20 metastatic neuroendocrine carcinomas (NECs), 21 metastatic colon carcinomas (CCs), seven hepatocellular carcinomas (HCCs), and six FNHs and assessed lesions for size, degree of fibrosis (scored 1-3), and peritumoral hyperplasia.

Results: Most NEC or CC cases had few peritumoral hyperplastic features. Three NECs, two CCs, and one HCC (13%) had patchy GS staining at the periphery of the lesions. One CC case had both histologic and immunohistochemical peritumoral hyperplasia.

Conclusions: Peritumoral hyperplasia or FNH-like changes are uncommon findings around primary or metastatic lesions in the liver. GS immunohistochemistry assists in distinguishing true peritumoral hyperplasia from mass effect.

Keywords: Focal nodular hyperplasia; Glutamine synthetase; Liver metastasis; Mass effect; Paraganglioma; Peritumoral hyperplasia.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / secondary
  • Adult
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / secondary
  • Colonic Neoplasms / pathology
  • Diagnosis, Differential
  • Female
  • Focal Nodular Hyperplasia / diagnosis*
  • Glutamate-Ammonia Ligase / analysis
  • Glutamate-Ammonia Ligase / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / secondary*
  • Paraganglioma, Extra-Adrenal / diagnosis*
  • Paraganglioma, Extra-Adrenal / secondary


  • Biomarkers, Tumor
  • Glutamate-Ammonia Ligase