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World J Gastrointest Oncol. Jun 15, 2022; 14(6): 1103-1114
Published online Jun 15, 2022. doi: 10.4251/wjgo.v14.i6.1103
Fibrolamellar hepatocellular carcinoma: A rare but unpleasant event
Walaa Abdelhamed, Mohamed El-Kassas
Walaa Abdelhamed, Department of Endemic Medicine, Sohag University, Sohag 14322, Egypt
Mohamed El-Kassas, Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
Author contributions: Both authors put the idea, planned the structure of the review and wrote the draft, then critical revision, editing, and approval of the final version of the manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Mohamed El-Kassas, MD, Full Professor, Department of Endemic Medicine, Faculty of Medicine, Helwan University, Helwan, Cairo 11795, Egypt.
Received: January 15, 2022
Peer-review started: January 15, 2022
First decision: March 13, 2022
Revised: March 19, 2022
Accepted: May 8, 2022
Article in press: May 8, 2022
Published online: June 15, 2022

Fibrolamellar carcinoma (FLC) is a rare variant of hepatocellular carcinoma (HCC), comprising 1%–9% of all HCCs. FLC is a poorly understood malignancy, which seems to be more prevalent in young patients with no underlying liver diseases. The term “fibrolamellar” is derived from thick fibrous collagen bands surrounding the tumor cells. Unlike HCC, cirrhosis and viral hepatitis infection are not predisposing to FLC, and it is not associated with elevations in serum alpha-fetoprotein. FLC patients often present with vague abdominal pain, nausea, malaise, and weight loss. Most cases present are at an advanced stage at the time of initial diagnosis. However, curative treatment options can still be offered to up to 70% of patients. Surgery (resection/liver transplantation) is the mainstay of treatment and the only potentially curative option. FLCs have been less chemo-responsive than the conventional HCC, however, in advanced cases, multimodality treatments can be effective. Recent advances in molecular studies of FLC have found a unique DNAJB1–PRKACA fusion transcript in most of the cases studied. The review aims to describe clinical characteristics, diagnostic methods, and therapeutic modalities for this rare tumor to raise awareness among clinicians and surgeons.

Keywords: Fibrolamellar carcinoma, Hepatocellular carcinoma, Hepatitis, Cirrhosis, Viral hepatitis infection

Core Tip: Fibrolamellar carcinoma (FLC) is a rare liver cancer that displays unique features in behavior and clinical findings from conventional hepatocellular carcinoma (HCC). No certain underlying trigger is detected in FLC. Alpha-fetoprotein levels are normal, unlike in traditional HCC. Surgery (resection/liver transplantation) is the current mainstay of treatment and remains the only curative option. FLCs have been less chemo-responsive than the conventional HCC. Controlled trials evaluating checkpoint inhibitors in FLC are lacking. In this review, we collect and summarize current evidence and clinical experience of conversion therapy, highlight remaining problems and challenges for further research.