title: Over-expression of glutamine synthetase in focal nodular hyperplasia: a novel easy diagnostic tool in surgical pathology.
abstract: OBJECTIVE
  Glutamine synthetase (GS) is a useful marker in tumour liver pathology, including hepatocellular adenomas and nodules in cirrhosis. We investigated the use of GS as a marker in various clinical situations, in which FNH diagnosis had been firmly established to determine its contribution to diagnosis.
  
  
  METHODS
  Seventy-nine cases of resected FNH, all on normal (or occasionally steatotic) livers, were retrieved from our collection. The control group was composed of hepatocellular adenomas and well-differentiated hepatocellular carcinoma. The following stains: H&E, Masson's trichrome, Gordon-Sweet, PAS, perls and immunostains: CK7 and 19, and GS were carried out. FNH was diagnosed based on traditional pathological techniques. In case of uncertainty, particularly with hepatocellular adenoma, additional immunostainings including liver fatty acid-binding protein, serum amyloid A and beta-catenin were performed.
  
  
  RESULTS
  Glutamine synthetase immunostaining was similar in all FNH cases. Positive GS staining of hepatocytic cytoplasms formed large areas, anastomosed in a 'map-like' pattern, often surrounding hepatic veins, whereas GS was not expressed in hepatocytes close to fibrotic bands containing arteries and ductules. In comparison, hepatocellular adenoma staining was completely different, even in cases of fibrotic bands due to tumour remodelling related to necrosis or haemorrhage. In hepatocellular adenomas or well-differentiated hepatocellular carcinoma presenting beta-catenin mutation, GS was positive but with a completely different pattern that appeared diffuse and not 'map-like'.
  
  
  CONCLUSIONS
  Regardless of the FNH size or steatotic content, GS produced a similar and characteristic pattern and consequently represents a good marker for easily identifying resected FNH from other hepatocellular nodules.
authors.affiliation: Department of Pathology, Hôpital Pellegrin CHU Bordeaux, Bordeaux, France. Paulette.bioulac-sage@chu-bordeaux.fr
authors.forename: Paulette
authors.initials: P
authors.lastname: Bioulac-Sage
authors.forename: Hervé
authors.initials: H
authors.lastname: Laumonier
authors.forename: Anne
authors.initials: A
authors.lastname: Rullier
authors.forename: Gaelle
authors.initials: G
authors.lastname: Cubel
authors.forename: Christophe
authors.initials: C
authors.lastname: Laurent
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: Charles
authors.initials: C
authors.lastname: Balabaud
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000201:enzymology* / Q000473:pathology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D005974:Glutamate-Ammonia Ligase