Over-expression of glutamine synthase in focal nodular hyperplasia (part 1): Early stages in the formation support the hypothesis of a focal hyper-arterialisation with venous (portal and hepatic) and biliary damage

Neither fibrotic scars nor hepatocytic nodules surrounded by fibrosis with a ductular reaction were observed in the sections studied. Most sections generally displayed preserved architecture. The glutamine synthase-positive hepatocyte areas were wider than those observed in non-tumoural surrounding liver, and they tended to extend outwards. Portal tracts bordering the nodule were more fibrotic, with an absence of portal veins and ducts and with arterial proliferation often in proximity with large draining veins; isolated arteries were present and hepatic veins were rare in the nodule. These features appeared prior to the identification of other major criteria characteristics of FNH, thus supporting the "hypothesis of Wanless".The findings confirm that in FNH there is a portal tract injury leading to local portal vein injury. This leads to a cascade of events, including arterial venous shunts, ductular reaction, and scar formation.The estimated prevalence of focal nodular hyperplasia(FNH) is 0.4 to 3% in a non-selected autopsy series and 0.3% in a clinical series. Most FNH cases are diagnosed by chance, but some are symptomatic. In contrast to hepatocellular adenomas, imaging techniques are sufficient for diagnosis in 70% of FNH cases. Histopathological examination is required for diagnosis in the few cases that have non-diagnostic imaging features [1,2]. In about two-thirds of cases, the FNH lesion is solitary. The typical histopathological features of classic FNH include a firm, well-delimited but not encapsulated lesion composed of hepatocellular nodules, a central scar, and radiating fibrous cords. The fibrous regions typically contain large dystrophic arteries and ductular reaction, usually associated with a lymphocytic infiltrate. FNH can be diagnosed from a liver biopsy. However, in some cases of FNH, the histopathological diagnosis may still be difficult, even in a resected specimen; this is because the definitive histopathological features may be absent, inc