da Fonseca LG, Araujo RLC. Fibrolamellar hepatocellular carcinoma: Advances, challenges and opportunities in a rare malignancy. World J Gastrointest Surg 2025; 17(10): 109107 [PMID: 41178855 DOI: 10.4240/wjgs.v17.i10.109107]
Corresponding Author of This Article
Raphael L C Araujo, MD, PhD, Adjunct Professor, FACS, Department of Surgery, Universidade Federal de São Paulo, No. 715 Rua Napoleão de Barros, São Paulo 04024-002, Brazil. raphael.l.c.araujo@gmail.com
Research Domain of This Article
Surgery
Article-Type of This Article
Minireviews
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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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Surg. Oct 27, 2025; 17(10): 109107 Published online Oct 27, 2025. doi: 10.4240/wjgs.v17.i10.109107
Fibrolamellar hepatocellular carcinoma: Advances, challenges and opportunities in a rare malignancy
Leonardo Gomes da Fonseca, Raphael L C Araujo
Leonardo Gomes da Fonseca, Department of Medical Oncology, Instituto do Câncer do Estado de São Paulo, University of São Paulo, São Paulo 01246-000, Brazil
Raphael L C Araujo, Department of Surgery, Universidade Federal de São Paulo, São Paulo 04024-002, Brazil
Raphael L C Araujo, Department of Surgery, Hepato-Pancreato-Biliary Service, Atrium Health Carolinas Medical Center, Charlotte, NC 28204, United States
Author contributions: Da Fonseca LG and Araujo RLC contributed to the study conception, data preparation, data interpretation, and critical writing.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Raphael L C Araujo, MD, PhD, Adjunct Professor, FACS, Department of Surgery, Universidade Federal de São Paulo, No. 715 Rua Napoleão de Barros, São Paulo 04024-002, Brazil. raphael.l.c.araujo@gmail.com
Received: April 30, 2025 Revised: May 26, 2025 Accepted: August 7, 2025 Published online: October 27, 2025 Processing time: 178 Days and 5.4 Hours
Abstract
Fibrolamellar hepatocellular carcinoma is a rare and unique subtype of primary liver cancer that predominantly affects adolescents and young adults who do not have underlying liver disease or cirrhosis. Representing less than five percent of all liver tumors, it poses significant diagnostic and therapeutic challenges due to its uncommon occurrence, vague clinical symptoms, and absence of standardized treatment protocols. This review summarizes the current understanding of the disease, covering its epidemiology, clinical presentation, imaging characteristics, histopathologic features, molecular biology, and treatment approaches. Patients often present with nonspecific abdominal symptoms, and typical tumor markers, such as alpha-fetoprotein, are usually absent. Imaging may show a central scar and calcifications, while histology reveals large eosinophilic tumor cells separated by fibrous bands. A defining molecular hallmark is the DNAJB1-PRKACA fusion gene, found in the majority of cases. Surgical resection remains the primary curative treatment for localized disease, although recurrence rates are high. Liver transplantation may be an option for selected patients with non-resectable, liver-confined tumors. Treatment options for advanced disease are limited, with some benefit observed from chemotherapy and targeted agents. Recent developments in molecular therapies and immunotherapy offer promise, but further research and clinical trial participation are essential to improve outcomes in this challenging malignancy.
Core Tip: Fibrolamellar hepatocarcinoma is a rare subtype of primary liver cancer characterized by unique histological, clinical, and molecular features. Although surgical resection remains the cornerstone of curative treatment, advances in molecular biology and identifying specific genetic alterations hold promise for developing targeted therapies, potentially improving outcomes for patients with this rare disease.
