Over-expression of glutamine synthetase in focal nodular hyperplasia: a novel easy diagnostic tool in surgical pathology

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. 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. 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'. 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.