VERY-RARE CANCERLiver CancerWHO 5th Edition Classification

Fibrolamellar Hepatocellular Carcinoma (FL-HCC)

Very Rare Malignancy (1–5 cases per 1,000,000 / year) • Clinical Staging, Genomic Targets & Vetted Specialists

A distinct liver cancer of adolescents and young adults that arises in an otherwise healthy, non-cirrhotic liver with no hepatitis or alcohol history. It is defined by the DNAJB1-PRKACA fusion. Because patients are young and well, the diagnosis is frequently delayed.

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Emergent Referral AdvisoryImmediate Action

Certain rare malignancies progress rapidly or carry acute risk of airway obstruction, acute spinal compression, hydrocephalus, or biopsy-seeding. Do not perform needle biopsy or surgery outside of an NCI-designated specialty sarcoma or neuro-oncology unit without multidisciplinary tumor board review.

Report immediately to an emergency department or tertiary oncologist upon:

  • Liver mass in a young patient with a normal AFP and no cirrhosis - test for the fusion
Who It Affects

Adolescents and young adults, median around 25; no cirrhosis, equal sex distribution

Annual Incidence

Approximately 0.02 per 100,000 per year

Clinical Evidence Review

Last audited: 2026-08-13 against NCCN, ESMO, and WHO 5th ed. guidelines.

Clinical Presentation & Hallmark Symptoms

Presenting signs most frequently observed across clinical case series

Vague right upper abdominal pain or fullness
A palpable abdominal mass
Weight loss, nausea and fatigue
Rarely jaundice, unlike conventional liver cancer
Alpha-fetoprotein is characteristically normal, which can falsely reassure

Genomic Profiling & Defining Molecular Lesions

Critical diagnostic fusions, somatic mutations, and therapeutic targets

Rare malignancies frequently depend on distinct oncogenic drivers rather than conventional environmental carcinogens. Comprehensive Next-Generation Sequencing (NGS comprehensive panel) and FISH/IHC are mandatory to establish the true diagnosis and screen for basket trial agents.

DNAJB1-PRKACA fusion (near-universal)CD68 and CK7 co-expression by IHC

Standard-of-Care Treatment Protocol

Frontline and multimodal strategies established under international consensus guidelines

1

Complete surgical resection with lymphadenectomy - the only curative treatment

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

2

Repeat resection or metastasectomy for recurrence, which is often worthwhile

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

3

Liver transplantation in highly selected cases

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

4

Systemic therapy in unresectable disease - limited standard options, trials preferred

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

5

Locoregional therapy for liver-dominant disease

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

Clinical Trial Advisory: For rare and ultra-rare malignancies, enrollment in an active clinical trial or expanded-access program is widely considered the preferred standard of care by ASCO and NCCN panels.

Prognosis & Disease Trajectory

Objective clinical outlook without false reassurance

Better than conventional hepatocellular carcinoma when completely resected, with five-year survival around 60-70%. Recurrence is common but often slow and amenable to further surgery. Lymph node involvement and unresectability are the main adverse factors.

Note: Statistics reflect cohort averages. Individual outcomes depend heavily on performance status, resectability, biomarker expression, and timely access to specialized tertiary care.

Active Research, Biomarkers & Clinical Trials

Novel investigational agents, phase I/II trials, and international rare disease consortia

Direct targeting of the DNAJB1-PRKACA fusion kinase, along with mTOR and immune approaches, is the central research effort; the Fibrolamellar Cancer Foundation maintains a patient registry and tissue bank.

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Expert Clinicians

Verified Specialists for Fibrolamellar Hepatocellular Carcinoma

Browse All Oncologists

Dr. Milind Javle

Medical Oncologist

20+ yrs exp

MD Anderson

Houston, USA

Hepatobiliary OncologyFL-HCCTargeted Therapy
Vetted DirectoryConsult Specialist

Dr. Pierce Chow

Hepatobiliary Surgeon

25+ yrs exp

NCCS/NHCS

Singapore, Singapore

Hepatobiliary SurgeryFL-HCCLiver Tumor Board
Vetted DirectoryConsult Specialist

Prof. Philip Johnson

Hepatologist

30+ yrs exp

University College London

London, United Kingdom

HepatologyFL-HCC RegistryManagement Guidelines
Vetted DirectoryConsult Specialist

Dr. Shripad Banavali

Medical Oncologist

30+ yrs exp

Tata Memorial

Mumbai, India

Medical OncologyRare Liver TumorsFL-HCC
Vetted DirectoryConsult Specialist
Hospital Network

Designated Cancer Centers with Dedicated Programs

Search All 72 NCI Centers

Memorial Sloan Kettering Cancer Center

NY

NCI-Designated Comprehensive Cancer Center

World-leading rare tumor board & pediatric solid tumor protocols

Proton TherapyCAR-T Cell TherapyRobotic Surgery
1,000+ Active Clinical TrialsView Center Profile

University of Texas MD Anderson Cancer Center

TX

NCI-Designated Comprehensive Cancer Center

Largest specialized rare cancer and sarcoma multidisciplinary program

Proton TherapyCAR-T Cell TherapyCyberKnife SBRT
1,200+ Active Clinical TrialsView Center Profile

Dana-Farber / Harvard Cancer Center

MA

NCI-Designated Comprehensive Cancer Center

Pioneering genomic molecular tumor boards & rare histologies

Proton TherapyCAR-T Cell TherapyPhase I Unit
1,100+ Active Clinical TrialsView Center Profile

Mayo Clinic Comprehensive Cancer Center

MN

NCI-Designated Comprehensive Cancer Center

High-volume surgical oncology & rare endocrine/neuroendocrine expertise

Proton TherapyCAR-T Cell TherapyCyberKnife SBRT
600+ Active Clinical TrialsView Center Profile

Frequently Asked Clinical Questions

Authoritative guidance on diagnosis, tumor boards, genomic markers, and care options

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Independent Tumor Board Review

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