Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2021; 13(4): 393-410
Published online Apr 27, 2021. doi: 10.4254/wjh.v13.i4.393
Pathologic and molecular features of hepatocellular carcinoma: An update
Mukul Vij, Julien Calderaro
Mukul Vij, Department ofPathology, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
Julien Calderaro, Department of Pathology, Groupe Hospitalier Henri Mondor, Creteil F-94010, France
Author contributions: Vij M and Calderaro J conceptualized and designed the study, performed literature review and drafting of the manuscript; both authors approved the manuscript for publication.
Conflict-of-interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Mukul Vij, MD, PDCC, Senior Consultant Pathologist, Department of Pathology, Dr Rela Institute and Medical Center, #7, CLC Works Road, Chromepet, Chennai 600044, Tamil Nadu, India.
Received: December 20, 2020
Peer-review started: December 20, 2020
First decision: January 7, 2021
Revised: January 27, 2021
Accepted: March 31, 2021
Article in press: March 31, 2021
Published online: April 27, 2021

Morphological diversity and several new distinct pathologic subtypes of hepatocellular carcinoma (HCC) are now well-recognized. Recent advances in tumor genomics and transcriptomics have identified several recurrent somatic/genetic alterations that are closely related with histomorphological subtypes and have therefore, greatly improved our understanding of HCC pathogenesis. Pathologic subtyping allows for a diagnosis which is clinically helpful and can have important implication in patient prognostication as some of these subtypes are extremely aggressive with vascular invasion, early recurrence, and worst outcomes. Several targeted treatments are now being considered in HCC, and the reporting of subtypes may be quite useful for personalized therapeutic purpose. This manuscript reviews the recently identified histomorphological subtypes and molecular alterations in HCC.

Keywords: Pathology, Hepatocellular carcinoma subtypes, Macrotrabecular massive, Steatohepatitic, Fibrolamellar, Molecular alterations

Core Tip: We summarize several new distinct histologic subtypes of hepatocellular carcinoma (HCC) and recurrent molecular alterations in HCC. Major histologic subtypes like macrotrabecular massive, fibrolamellar HCC, steatohepatitic HCC, scirrhous HCC, lymphoepithelioma-like HCC, and combined hepatocellaular-cholangiocarcinoma are discussed in detail. Rare and provisional histological variants are also discussed.