Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Citations
Citations to this article as recorded by
Burden of Liver Disease Among Individuals With Turner Syndrome and Klinefelter Syndrome: A Comprehensive Perspective Mohamad Jamalinia, Amedeo Lonardo, Ralf Weiskirchen Chronic Diseases and Translational Medicine.2026; 12(1): 39. CrossRef
The natural history of hepatocellular adenoma: long-term outcomes from a large tertiary centre Evangelia Florou, Anushka Jindal, Mohammad Reza Fattahi, Nigel Heaton, Parthi Srinivasan European Journal of Gastroenterology & Hepatology.2026;[Epub] CrossRef
PET/MRI evaluation of hepatobiliary tumors Joseph FRANKL, Naveen RAJAMOHAN, Jaewon YANG, Robert C. SIBLEY The Quarterly Journal of Nuclear Medicine and Molecular Imaging.2025;[Epub] CrossRef
Diagnosis and Management of Benign Liver Tumors Yeonjung Ha The Korean Journal of Gastroenterology.2025; 85(3): 314. CrossRef
Hepatocellular adenomas Hans-Christian Pommergaard, Henning Grønbæk, Eva Fallentin, Nikolaj Skou, Nicolai Aagaard Schultz, Mette Bak Nielsen, Gro Linno Willemoe Ugeskrift for Læger.2025; : 1. CrossRef
Focal Hyperechoic Hepatic Lesions in Northern Region of Saudi Arabia: Prevalence, Radiologic Features, and Clinical Relevance Fatimah M. Alonzi, Mohammed J. Alsaadi, Khaled Said Karam, Essa M. Alanzi, Noura K. Alhathal, Maram F. Alreshidi, Abdulrahman M. Alfuraih Journal of Clinical Medicine.2025; 14(19): 6987. CrossRef
Focal nodular hyperplasia combined with hepatocellular carcinoma with bone metastasis: a case report and literature review Yuliang Zhang, Xiyue Deng, Kaiyue Cao, Yang Li Frontiers in Oncology.2025;[Epub] CrossRef
Variation in the management of benign liver tumors: A European survey and case vignette study Martijn P.D. Haring, Robbert J. de Haas, Frederike G.I. van Vilsteren, Joost M. Klaase, Evelien W. Duiker, Hans Blokzijl, Koert P. de Jong, Vincent E. de Meijer, Frans J.C. Cuperus, Y.S. de Boer, R.A. de Man, C.M. den Hoed, J.P.H. Drenth, M.G. Garcovich, Clinics and Research in Hepatology and Gastroenterology.2023; 47(3): 102094. CrossRef
Hepatocellular Neoplasm of Uncertain Potential of Malignancy or Well-Differentiated Hepatocellular Carcinoma Arising within Hepatocellular Adenoma Elisabete Campos, Roberto Silva, Sara Rodrigues, Marinho de Almeida, Joanne Lopes, Marisa Aral, Humberto Cristino, Luís Graça, Elisabete Barbosa, Neil Donald Merrett Case Reports in Surgery.2023; 2023: 1. CrossRef
Desmoplastic small round cell tumor of the liver: diagnosing a rare case on liver biopsy Xiao Feng, Jing Tao, Qiang Zhou, Yi-Dan Qiao, Le-Jian He, Nan Zhang Diagnostic Pathology.2023;[Epub] CrossRef
Pedunculated Focal Nodular Hyperplasia: When in Doubt, Should We Cut It Out? Christos Tsalikidis, Athanasia Mitsala, George Pappas-Gogos, Konstantinos Romanidis, Alexandra K. Tsaroucha, Michail Pitiakoudis Journal of Clinical Medicine.2023; 12(18): 6034. CrossRef
Significance of hepatocyte atypia in liver fine needle aspiration Susan Shyu, Syed Z. Ali Diagnostic Cytopathology.2022; 50(4): 186. CrossRef
Senescence markers in focal nodular hyperplasia of the liver: pathogenic considerations on the basis of immunohistochemical results Helmut Denk, Daniela Pabst, Peter M. Abuja, Robert Reihs, Brigitte Tessaro, Kurt Zatloukal, Carolin Lackner Modern Pathology.2022; 35(1): 87. CrossRef
Preneoplastic lesions in the liver: Molecular insights and relevance for clinical practice Elvire Desjonqueres, Claudia Campani, Fabio Marra, Jessica Zucman‐Rossi, Jean‐Charles Nault Liver International.2022; 42(3): 492. CrossRef
Genomic analysis of focal nodular hyperplasia with associated hepatocellular carcinoma unveils its malignant potential: a case report Caner Ercan, Mairene Coto-Llerena, John Gallon, Lana Fourie, Mattia Marinucci, Gabriel F. Hess, Jürg Vosbeck, Stephanie Taha-Mehlitz, Tuyana Boldanova, Marie-Anne Meier, Alexandar Tzankov, Matthias S. Matter, Martin H. K. Hoffmann, Luca Di Tommaso, Markus Communications Medicine.2022;[Epub] CrossRef
Comparison of the Value of Color Doppler Ultrasound and Multislice Spiral CT in the Differential Diagnosis of Benign and Malignant Nodules in the Liver Peiwan Jia, Ruirong Liu, Yun Liu, Yanyan Wu, Ting Dou, Yuvaraja Teekaraman Contrast Media & Molecular Imaging.2022;[Epub] CrossRef
Magnetic Resonance Imaging Findings of an Intrahepatic Bile Duct Adenoma: A Case Report Jie Yuan, Kun Liu, Mengxiao Liu, Songhua Zhan Cureus.2022;[Epub] CrossRef
Liver Abnormalities in Turner Syndrome: The Importance of Estrogen Replacement Istvan Fedor, Eva Zold, Zsolt Barta Journal of the Endocrine Society.2022;[Epub] CrossRef
Microvascular imaging: new Doppler technology for assessing focal liver lesions. Is it useful? A. Wilson, A.K.P. Lim Clinical Radiology.2022; 77(12): e807. CrossRef
A focalis nodularis hyperplasia multimodális kezelése Damján Pekli, Bálint Kokas, Dávid Bárdos, András Fülöp, Péter Pajor, Oszkár Hahn, Ildikó Illyés, Attila Kovács, Attila Szijártó Orvosi Hetilap.2022; 163(15): 606. CrossRef
CT-Based Radiomics Nomogram: A Potential Tool for Differentiating Hepatocellular Adenoma From Hepatocellular Carcinoma in the Noncirrhotic Liver Pei Nie, Ning Wang, Jing Pang, Guangjie Yang, Shaofeng Duan, Jingjing Chen, Wenjian Xu Academic Radiology.2021; 28(6): 799. CrossRef
Panel of potential lncRNA biomarkers can distinguish various types of liver malignant and benign tumors Olga Y. Burenina, Natalia L. Lazarevich, Inna F. Kustova, Daria A. Shavochkina, Ekaterina A. Moroz, Nikolay E. Kudashkin, Yuriy I. Patyutko, Alexey V. Metelin, Eduard F. Kim, Dmitry A. Skvortsov, Timofei S. Zatsepin, Maria P. Rubtsova, Olga A. Dontsova Journal of Cancer Research and Clinical Oncology.2021; 147(1): 49. CrossRef
Benign hepatocellular lesions and neoplasms: a comprehensive review Luiz Paulo Guido, Monica T. Garcia-Buitrago Diagnostic Histopathology.2021; 27(2): 85. CrossRef
Hepatocellular adenomas: recent updates Haeryoung Kim, Young Nyun Park Journal of Pathology and Translational Medicine.2021; 55(3): 171. CrossRef
Appearance of Focal Nodular Hyperplasia after Chemotherapy in Two Patients during Follow-Up of Colon Carcinoma L. A. de Wert, S. A. Huisman, F. Imani, D. J. de Gooyer, J. M. G. H. van Riel, P. D. Gobardhan, A. M. Rijken, Mario Ganau Case Reports in Surgery.2021; 2021: 1. CrossRef
Scoping review of clinical practice guidelines on the management of benign liver tumours Martijn P D Haring, Frans J C Cuperus, Evelien W Duiker, Robbert J de Haas, Vincent E de Meijer BMJ Open Gastroenterology.2021; 8(1): e000592. CrossRef
Diagnosis and surgical treatment of a rare hepatic angiomyolipoma with internal hemorrhage Mizelle D'Silva, Hee Young Na, Jai Young Cho, Ho-Seong Han, Yoo-Seok Yoon, Hae Won Lee, Jun Suh Lee, Boram Lee, Moonhwan Kim Annals of Hepato-Biliary-Pancreatic Surgery.2021; 25(4): 532. CrossRef
Alpha‐fetoprotein and focal nodular hyperplasia: An unconventional couple Paul Carrier, Anne Guyot, Marilyne Debette‐Gratien, Fabien Fredon, Marie‐Pierre Teissier, François Labrousse, Véronique Loustaud‐Ratti JGH Open.2021; 5(11): 1316. CrossRef
Hepatobiliary MR contrast agents are useful to diagnose hepatocellular carcinoma in patients with Budd-Chiari syndrome Morgane Van Wettere, Luisa Paulatto, Lucas Raynaud, Onorina Bruno, Audrey Payancé, Aurélie Plessier, Pierre-Emmanuel Rautou, Valérie Paradis, Dominique Cazals-Hatem, Dominique Valla, Valérie Vilgrain, Maxime Ronot JHEP Reports.2020; 2(3): 100097. CrossRef
Patterns of enhancement in the hepatobiliary phase of gadoxetic acid-enhanced MRI Cathryn L Hui, Marcela Mautone The British Journal of Radiology.2020;[Epub] CrossRef
Focal Nodular Hyperplasia and Hepatic Adenoma Lauren Myers, Joseph Ahn Clinics in Liver Disease.2020; 24(3): 389. CrossRef
OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd‐EOB‐DTPA uptake and correlates with risk of malignancy Amedeo Sciarra, Sabine Schmidt, Alessandro Pellegrinelli, Marco Maggioni, Daniele Dondossola, Jerome Pasquier, Claudia Cigala, Delfina Tosi, Nermin Halkic, Gaetano Bulfamante, Giuseppe Viale, Silvano Bosari, Charles Balabaud, Paulette Bioulac‐Sage, Christ Liver International.2019; 39(1): 158. CrossRef
MicroRNA Expression in Focal Nodular Hyperplasia in Comparison with Cirrhosis and Hepatocellular Carcinoma Gábor Lendvai, Tímea Szekerczés, Benedek Gyöngyösi, Krisztina Schlachter, Endre Kontsek, Adrián Pesti, Attila Patonai, Klára Werling, Ilona Kovalszky, Zsuzsa Schaff, András Kiss Pathology & Oncology Research.2019; 25(3): 1103. CrossRef
Challenging liver lesions in noncirrhotic patients: Report of three cases Tania Franceschini, Deborah Malvi, Lorenzo Maroni, Matteo Ravaioli, Matteo Cescon, Antonia D’Errico, Francesco Vasuri Therapeutic Advances in Gastrointestinal Endoscopy.2019;[Epub] CrossRef
Down-regulation of cell membrane localized NTCP expression in proliferating hepatocytes prevents hepatitis B virus infection Ying Yan, Lena Allweiss, Danli Yang, Jingting Kang, Jianwen Wang, Xiangjun Qian, Ting Zhang, Hui Liu, Lu Wang, Shuhong Liu, Jianhua Sui, Xiangmei Chen, Maura Dandri, Jingmin Zhao, Fengmin Lu Emerging Microbes & Infections.2019; 8(1): 879. CrossRef
Multi-parameter ultrasound based on the logistic regression model in the differential diagnosis of hepatocellular adenoma and focal nodular hyperplasia Meng Wu, Ru-Hai Zhou, Feng Xu, Xian-Peng Li, Ping Zhao, Rui Yuan, Yu-Peng Lan, Wei-Xia Zhou World Journal of Gastrointestinal Oncology.2019; 11(12): 1193. CrossRef
Focal Nodular Hyperplasia in a Young Male as an Incidental Finding Associated With Acute Lithiasic Chronic Cholecystitis. Case Report and Literature Review José J. Gómez-Ramos, María G. Ascencio-Rodríguez, Alejandro Marín-Medina, Moises Alejandro Alatorre Jimenez, Vickramjeet Johal, Eduardo Esteban-Zubero Iberoamerican Journal of Medicine.2019; 1(1): 16. CrossRef
Primary Liver Cancers—Part 1 Kun Jiang, Sameer Al-Diffalha, Barbara A. Centeno Cancer Control.2018;[Epub] CrossRef
Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing Jian Zheng, Eran Sadot, Joana A. Vigidal, David S. Klimstra, Vinod P. Balachandran, T. Peter Kingham, Peter J. Allen, Michael I. D’Angelica, Ronald P. DeMatteo, William R. Jarnagin, Andrea Ventura, Yu-Jia Chang PLOS ONE.2018; 13(7): e0200776. CrossRef
Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma Archana Rastogi World Journal of Gastroenterology.2018; 24(35): 4000. CrossRef
A practical diagnostic approach to hepatic masses Monika Vyas, Dhanpat Jain Indian Journal of Pathology and Microbiology.2018; 61(1): 2. CrossRef
Hepatocellular adenoma: Classification, variants and clinical relevance Paulette Bioulac-Sage, Christine Sempoux, Charles Balabaud Seminars in Diagnostic Pathology.2017; 34(2): 112. CrossRef
Tissue Biomarkers in Hepatocellular Tumors: Which, When, and How Luca Di Tommaso, Massimo Roncalli Frontiers in Medicine.2017;[Epub] CrossRef
Comparison of Subtypes of Hepatocellular Adenoma to Hepatocellular Carcinoma and Non-Neoplastic Liver Tissue in Terms of PTEN Expression Grzegorz Szparecki, T. Ilczuk, N. Gabzdyl, B. Górnicka Folia Biologica.2017; 63(5-6): 202. CrossRef
Leberadenome und andere maligne und benigne Lebertumoren F. Hartmann, A. Tannapfel Der Gastroenterologe.2016; 11(5): 359. CrossRef
First
Prev
