New histopathological terminology for well-differentiated hepatocellular lesions in unusual clinico-pathological scenarios: HCA-like and FNH-like

The lines defining Hepatocellular Adenoma (HCA) and Focal Nodular Hyperplasia (FNH) can be blurred when they occur outside their prototypical clinico-pathological contexts. A terminology going beyond HCA and FNH with comments on possible malignant potential, the status of the background liver and/or underlying unusual clinical scenario is thereby justified. Indeed, both more sophisticated contrast-enhanced characterization and the identification of specific immunohistochemical and molecular markers for well-differentiated hepatocellular lesions have enabled a greater understanding of their presentation and biology. The traditional concepts of HCA and FNH occurring in livers that are "otherwise histologically normal or near normal" has given way to understanding that these lesions can also occur in livers affected by chronic liver conditions. When this is the case, morpho-molecular overlap exists between the two entities. Hence, it is now necessary to set a new approach for HCA and FNH, considering not only their intrinsic morphologic and molecular features, but also the background liver in which they are arising, and the clinical context in which they are occurring. The dichotomous paradigm of benign vs. malignant also becomes more nuanced. To raise the diagnostic uncertainty in unusual clinico-pathological scenarios, the International Liver Pathology Study Group suggests designating these lesions as well-differentiated hepatocellular lesions, HCA-like (and subtype when applicable) or FNH-like. This nuanced terminology enables pathologists to highlight these outliers to the hepatobiliary multidisciplinary team that will adapt the clinical management accordingly. It also provides a framework for further collaborative studies. In conclusion, we propose a more nuanced terminology, beyond conventional HCA and FNH, to consider, alongside histological and molecular features, abnormalities in the background liver and unusual clinical scenarios.