Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2019; 25(14): 1653-1665
Published online Apr 14, 2019. doi: 10.3748/wjg.v25.i14.1653
Update on hepatocellular carcinoma: Pathologists’ review
Tony El Jabbour, Stephen M Lagana, Hwajeong Lee
Tony El Jabbour, Hwajeong Lee, Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, United States
Stephen M Lagana, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States
Author contributions: El Jabbour T and Lee H drafted the manuscript; Lagana SM and Lee H contributed to the editing of the manuscript; El Jabbour T and Lagana SM provided the microscopic images; Lagana SM contributed to critical review of the manuscript; El Jabbour T, Lagana SM, and Lee H gave final approval of the version to be published and is agreeable to be accountable for all aspects of the work in ensuring that questions that arise are investigated and the information is accurate.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: Hwajeong Lee, MD, Associate Professor, Department of Pathology and Laboratory Medicine, Albany Medical College, 47 New Scotland Ave., MC81, Albany, NY 12208, United States.
Telephone: +1-518-2626254 Fax: +1-518-2623663
Received: February 12, 2019
Peer-review started: February 14, 2019
First decision: March 5, 2019
Revised: March 12, 2019
Accepted: March 24, 2019
Article in press: March 25, 2019
Published online: April 14, 2019

Histopathologic diversity and several distinct histologic subtypes of hepatocellular carcinoma (HCC) are well-recognized. Recent advances in molecular pathology and growing knowledge about the biology associated with distinct histologic features and immuno-profile in HCC allowed pathologists to update classifications. Improving sub-classification will allow for more clinically relevant diagnoses and may allow for stratification into biologically meaningful subgroups. Therefore, immuno-histochemical and molecular testing are not only diagnostically useful, but also are being incorporated as crucial components in predicting prognosis of the patients with HCC. Possibilities of targeted therapy are being explored in HCC, and it will be important for pathologists to provide any data that may be valuable from a theranostic perspective. Herein, we review and provide updates regarding the pathologic sub-classification of HCC. Pathologic diagnostic approach and the role of biomarkers as prognosticators are reviewed. Further, the histopathology of four particular subtypes of HCC: Steatohepatitic, clear cell, fibrolamellar and scirrhous - and their clinical relevance, and the recent consensus on combined HCC-cholangiocarcinoma is summarized. Finally, emerging novel biomarkers and new approaches to HCC stratification are reviewed.

Keywords: Hepatocellular carcinoma, Subtype, Classification, Review, Update

Core tip: We summarize the updated classifications of hepatocellular carcinoma. Immunohistochemistry and molecular pathology are becoming crucial components of prognostication and theranostics. Pathologic and molecular features of clinically relevant subtypes to include steatohepatitic, clear cell, fibrolamellar and scirrhous hepatocellular carcinomas are reviewed. Recent consensus on the combined hepatocellular carcinoma-cholangiocarcinoma, a controversial pathologic entity, is summarized.