New histopathological terminology for well-differentiated hepatocellular lesions in unusual clinico-pathological scenarios: HCA-like and FNH-like
Year: 2026
Type: review
Abstract: 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.
Source: JHEP Reports
Authors: Christine Sempoux, Venancio AF. Alves, Johanna Arola, Charles Balabaud, Paulette Bioulac-Sage, Romano Colombari, James M. Crawford, Amar P. Dhillon, Luca di Tommaso, Linda D. Ferrell, Ryan M. Gill, Maria Guido, Bilal Hameed, Kenichi Harada, Prodromos Hytiroglou, Yasuni Nakanuma, Valérie Paradis, Pierre-Emmanuel Rautou, Neil D. Theise, Swan Thung, Wilson MS. Tsui, Dale Snover, Ashley Stueck, Arief Suriawinata, Dirk J. van Leeuwen, Alberto Quaglia
Institutions: Centre Hospitalier Universitaire Vaudois, University of Lausanne, Universidade de São Paulo, University of Helsinki, Helsinki University Hospital, Université de Bordeaux, Inserm, Northwell Health, University College London, Humanitas University, IRCCS Humanitas Research Hospital, University of California, San Francisco, University of Padua, Kanazawa University, Aristotle University of Thessaloniki, Shizuoka Cancer Center, Université Paris Cité, Hôpital Beaujon, Assistance Publique – Hôpitaux de Paris, Centre de Recherche sur l'Inflammation, New York University, Icahn School of Medicine at Mount Sinai, Caritas Medical Centre, Fairview Southdale Hospital, Dalhousie University, Dartmouth–Hitchcock Medical Center, Dartmouth College, Royal Free London NHS Foundation Trust, The Royal Free Hospital
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,110
Funders: Helsingin Yliopisto, Dartmouth College, Royal Free London NHS Foundation Trust, Kanazawa University, Northwell Health, York University, Institut National de la Santé et de la Recherche Médicale, Dalhousie University, Università degli Studi di Padova, Universidade de São Paulo, Université de Lausanne, Centre Hospitalier Universitaire Vaudois, Humanitas University, Humanitas Research Hospital, School of Medicine, New York University, University of California, San Francisco, Audrey and Theodor Geisel School of Medicine at Dartmouth, Department of Medicine, University of California, San Francisco
Award: G7221727713
OpenAlex ID: W7128166884