Last updated:
12/15/2025
Years published: 2018, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for the preparation of this report.
Fibrolamellar carcinoma is a rare type of liver cancer. Unlike most cancers of the liver, it often affects teenagers and young adults who are otherwise healthy. Many people have no symptoms for a long time. When symptoms do appear, they may include abdominal (belly) pain, unplanned weight loss, or feeling tired and unwell (malaise). Treatment is usually surgery to remove the tumor (resection). When surgery is not possible or does not work, other therapies may be tried. Even after successful surgery, the cancer can sometimes come back (recurrence). The exact underlying cause of this disorder is unknown.
The term fibrolamellar comes from the way this cancer looks under the microscope. The tumor tissue has thick, fibrous bands that occur in a unique “lamellar” pattern.
Fibrolamellar carcinoma was first reported by doctors in medical literature in 1956 as a different type of liver cancer from the more common kind of liver cancer, hepatocellular carcinoma (HCC). Most people with HCC have serious liver damage, often from conditions such as hepatitis or long-term alcohol use, which cause scarring of the liver (cirrhosis). Most people with fibrolamellar carcinoma do not have an underlying liver disease and do not have cirrhosis. For this reason, many physicians now consider fibrolamellar carcinoma to be a distinct form of liver cancer.
The signs and symptoms often appear only after the disease has advanced. For many years, a person may have no noticeable signs or symptoms (also known as asymptomatic) because they are otherwise healthy. Early symptoms are usually vague (nonspecific) and can look like many other medical conditions. Every person is unique, and how this disorder affects one person can be different from how it affects another person. This cancer may grow slowly over many years in some people, or it may progress quickly in others, sometimes spreading to nearby areas or other parts of the body (metastasizing).
When symptoms do develop, they often include:
Additional symptoms can include:
Less common symptoms:
As with many forms of cancer, the exact, underlying cause of fibrolamellar carcinoma is unknown. Researchers speculate that several factors, including genetic (related to our DNA, or deoxyribonucleic acid) and environmental ones, play a role in how it develops. Current research suggests that abnormalities (changes, or mutations) of DNA, which is the carrier of the body’s genetic code, are the underlying basis that causes cells to become malignant.
Researchers have determined that many people with fibrolamellar carcinoma have the same underlying genetic abnormality (change) called a DNAJB1-PRKACA fusion gene. This genetic abnormality is highly specific to fibrolamellar carcinoma, meaning it is not found in healthy liver tissue or in other organs.
Normally, genes provide the instructions for making (encoding) proteins, which carry out important jobs in the body. In fibrolamellar carcinoma, a small piece of genetic material is missing (deletion) on chromosome 19. This loss causes two genes, the DNAJB1 and PRKACA genes, to join together into one new gene (see figure below). This new “fused” gene called a “chimeric” gene, makes an abnormal protein that combines parts of both original proteins (see figure below). Researchers believe that the abnormal protein created by this chimeric gene may cause liver cells to grow and divide too much, which can lead to tumor development. However, the exact reason why the loss of genetic material and fusion of these two genes happens is not fully understood. The exact way that the fusion protein causes the cells to grow excessively as cancer is also not fully understood.
Figure: FLC fusion gene and protein
Other types of liver cancer are usually associated with underlying liver disease (e.g. hepatitis) or damage (e.g. scarring [cirrhosis]) to the liver. Generally, individuals with fibrolamellar carcinoma do not have any identified or proven risk factors other than the presence of the DNAJB1-PRKACA chimeric gene. Researchers are studying the disorder to try and determine where there are specific environmental risk factors, or any additional genetic risk factors.
FLC is an ultra-rare form of liver cancer. Because it is so uncommon, there is limited information about how many people are affected. It is estimated to make up 1% to 5% of all liver cancers. FLC affects both men and women and is thought to occur in about one in five million people in the U.S. It affects both men and women and affects approximately 1 in 5 million people in the U.S.
Cancer rates in the U.S. are tracked through the Surveillance, Epidemiology, and End Results (SEER) Program, which estimates that FLC occurs in about 0.02 out of every 100,000 people per year. However, in a more recent study, researchers carefully analyzed electronic medical records and national insurance data and found that FLC may be five to eight times more common than previously thought. They estimated that approximately 602 new cases of FLC occur annually in the United States, or about 0.185 per 100,000 people.
Fibrolamellar carcinoma occurs with greater frequency among young adults with a median age of diagnosis of 25. It is found all over the world, and the rate of occurrence can vary geographically. The disorder accounts for about 1% of all people with primary liver cancer in the United States, but accounts for about 5.8 percent of all people with primary liver cancer in Mexico.
Doctors diagnose fibrolamellar carcinoma by looking at a person’s symptoms, detailed medical history, thorough physical exam, and results from a variety of specialized tests.
Diagnosing this cancer can be challenging because its symptoms are often vague (nonspecific) and can look like those of many other conditions. Since fibrolamellar carcinoma tends to affect young adults who are otherwise healthy, doctors may not suspect cancer at first. It is often considered only after more common health problems have been ruled out.
Clinical Testing and Workup
Doctors may use several imaging tests to help diagnose fibrolamellar carcinoma and to determine if and how far the disease has spread. These may include a CT (computed tomography) scan, MRI (magnetic resonance imaging), or ultrasound.
During CT scanning, x-rays are used to create detailed cross-sectional pictures of the liver and nearby organs.
An MRI uses magnets and radio waves to produce images of soft tissues in the body.
During an ultrasound, reflected sound waves are used to create pictures of internal organs or structures, such as the liver.
A doctor may need to perform a biopsy to confirm a diagnosis. During a biopsy, a doctor will use CT or ultrasound imaging to obtain a sample area in the liver with a needle to examine the tissue under the microscope. Rarely, a small part of tumor must be surgically removed to obtain the sample to study. A biopsy may be necessary to distinguish fibrolamellar carcinoma from benign tumors (like FNH) or other cancers (such as HCC).
After the biopsy, the tissue sample may be tested using a process called immunostaining. During immunostaining, antibodies are applied to a sample of the tumor from a biopsy or from surgical removal. The antibodies test for certain proteins (markers), for example CK7 and CD68, which are often found in individuals with fibrolamellar carcinoma. While these markers do not confirm the diagnosis on their own, they can provide important clues.
Another lab test, called FISH (fluorescence in situ hybridization) can help confirm the diagnosis. This test looks for a genetic change called the DNAJB1-PRKACA fusion, which is specific to fibrolamellar carcinoma. FISH uses a special probe for the PRKACA gene to detect this change. This test uses a break-apart strategy, where a positive result (indicating a fusion) is shown by a separation of the red and green signals of the probe, while a negative result shows the signals are together. FISH is a highly accurate tool for confirming the diagnosis.
Currently, there is no known blood test that can make a diagnosis of fibrolamellar carcinoma. In other forms of liver cancer, such as hepatocellular carcinoma, there are elevated levels of alpha fetoprotein (AFP) in the blood. Physicians may run a blood test to see whether this protein is present. This helps to distinguish fibrolamellar carcinoma from hepatocellular carcinoma.
Treatment
The treatment of fibrolamellar carcinoma is tailored to each person’s situation and symptoms. Because this cancer can be complex, care usually involves a team of specialists, including: physicians with expertise in the diagnosis and treatment of liver disorders (hepatologists), physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), physicians who use radiation to treat cancer (radiation oncologists), physicians who use imaging to perform various interventions (interventional radiologists), surgeons who perform an operation to remove the cancer, and other healthcare professionals. Emotional and social (psychosocial) support for the entire family is also very important.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; presence of cancer in lymph nodes or other areas of the body; tumor size and exact location within the liver; the presence or absence of certain symptoms; an individual’s age and general health; etc. All these factors are taken into consideration when deciding if surgery can be performed.
Similarly, decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; and patient preferences.
Main treatment: Surgery
Surgery to remove the tumor (called a resection) offers the best chance for long-term survival. During surgery, surgeons often remove nearby lymph nodes as well, since the cancer can spread to them. If the tumor can be removed (complete resection), the patient’s prognosis is considered much improved. However, fibrolamellar carcinoma can sometimes come back (recur) even after a successful surgery, and additional surgery may be needed.
Liver Transplantation
In some cases, individuals with fibrolamellar carcinoma may be treated with a liver transplant. This is not considered a standard treatment option and is usually only an option with the tumor cannot be removed surgically (resection), when other treatments have not worked, or when the liver is badly damaged (for example, from cirrhosis). Liver transplantation is only done if the cancer has not spread from the liver to another part of the body. During a liver transplant, the affected liver is removed and replaced by a healthy liver from a donor. This is a major surgical procedure that carries significant risk. After the surgery, patients require lifelong supplemental medications to suppress the immune system (immunosuppressive medications). This is done to minimize the risk of the body rejecting the donated liver and attacking it through the immune system.
Other Treatments and Ongoing Research
Because fibrolamellar carcinoma is very rare, there are no standardized treatment guidelines, and there are no treatment trials that have been tested on a large group of patients. Instead, various treatments, including chemotherapy, have been reported in the medical literature as part of smaller research studies. More research is needed to determine the long-term safety and effectiveness of specific medications and treatments for individuals with fibrolamellar carcinoma.
Researchers are also studying targeted therapies that focus on the unique genetic change in fibrolamellar carcinoma. The identification of the DNAJB1-PRKACA chimeric gene has enabled investigators to research therapies targeted toward this specific gene or the associated protein. Some physicians believe the abnormal protein created by this chimeric gene drive the growth of cancer in people with fibrolamellar carcinoma. Medications are being studied that block or inhibit this protein.
Another area of research is immunotherapy, which helps the body’s own immune system attack cancer cells. For example, the most common form of immunotherapy called PD-1 or PD-L1 blockade releases the “brakes” on the immune system that some cancers use to keep the immune system from attacking them. Researchers are currently studying whether immunotherapy could potentially be used in fibrolamellar carcinoma.
Some individuals have been treated with hepatic artery chemoembolization. Chemoembolization is a way of decreasing blood supply to the tumor site within the liver to control the disease. During this procedure, a catheter is placed into the main artery that supplies blood to the liver (hepatic artery). Chemotherapeutic drugs and drugs that block (occlude) the blood vessels are delivered right near the tumor to block the blood supply to the tumor. This can slow or stop tumor growth and sometimes shrink the size of a tumor.
Radiation therapy is not commonly used for fibrolamellar carcinoma but has been reported in isolated cases of recurrent FLC. In one case series, high-dose radiation resulted in a significant reduction in tumor volume, suggesting potential benefits in select situations.
Since FLC is such a rare disease without established treatment regimens, patients should be referred to tertiary care centers with appropriate expertise.
Because fibrolamellar carcinoma is so rare and treatment options are limited, participation in clinical trials is strongly encouraged. These trials not only provide access to emerging therapies but also help researchers better understand which treatments are most effective for different patient populations.
The Fibrolamellar Registry allows to the linking of the FLC community’s health data with the scientists, physicians, collaborating hospitals and research institutions around the world studying this disease. Their goal is to spur and speed up research, develop a diagnostic test, and ultimately, develop effective treatments.
The National Cancer Institute (NCI) has information about fibrolamellar hepatic carcinoma.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact:
www.centerwatch.com
For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Zack T, Losert KP, Maisel SM, et al. Defining incidence and complications of fibrolamellar liver cancer through tiered computational analysis of clinical data. NPJ Precis Oncol. 2023;7(1):29. Published 2023 Mar 23. doi:10.1038/s41698-023-00371-2.
Smith M, Tomboc PJ, Markovich B. Fibrolamellar Hepatocellular Carcinoma. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 January. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553113/.
Graham RP, Yeh WM, Lam-Himlin D, et al. Molecular testing for the clinical diagnosis of fibrolamellar carcinoma. Mod Pathol. 2018;31:141-149. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758901/
Tomasini MD, Wang Y, Karamafrooz A, et al. Conformational landscape of the PRKACA-DNAJB1 chimeric kinase, the driver for fibrolamellar hepatocellular carcinoma. Sci Rep. 2018;8:720. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768683/
Dinh TA, Vitucci EC, Wauthier E, et al. Comprehensive analysis of The Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma. Sci Rep. 2017;7:44653. https://www.ncbi.nlm.nih.gov/pubmed/28304380
Wahab MA, El Hanafy E, El Nakeeb A, Ali MA. Clinicopathological features and surgical outcome of patients with fibrolamellar hepatocellular carcinoma (experience with 22 patients over a 15-year period). World J Gastrointest Surg. 2017 Feb 27;9(2):61-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329705/
Riggle KM, Turnham R, Scott JD, Yeung RS, Riehle KJ. Fibrolamellar hepatocellular carcinoma: mechanistic distinction from adult hepatocellular carcinoma. Pediatr Blood Cancer. 2016;63:1163-1167. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877189/
Kassahun WT. Contemporary management of fibrolamellar hepatocellular carcinoma: diagnosis, treatment, outcome, prognostic factors, and recent developments. World J Surg Oncol. 2016;14:151. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877801/
Graham RP, Jin L, Knutson DL, et al. DNAJB1-PRKACA is specific for fibrolamellar carcinoma. Mod Pathol. 2015;28:822-829. https://www.ncbi.nlm.nih.gov/pubmed/25698061
Lim II, Farber BA, LaQuaglia MP. Advances in fibrolamellar hepatocellular carcinoma: a review. Eur J Pediatr Surg. 2014;24:461-466. https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0034-1396420
Kaseb AO, Shama M, Sahin IH, et al. Prognostic indicators and treatment outcome in 94 cases of fibrolamellar hepatocellular carcinoma. Oncology. 2013;85:197-203. https://www.ncbi.nlm.nih.gov/pubmed/24051705
Stipa F, Yoon SS, Liau KH, et al. Outcome of patients with fibrolamellar hepatocellular carcinoma. Cancer. 2006;106:13311338. https://www.ncbi.nlm.nih.gov/pubmed/16475212
INTERNET
Kalman RS, Abou-Alfa GK. Epidemiology, clinical manifestations, diagnosis and treatment of fibrolamellar carcinoma. UpToDate, Inc. Oct 20, 2025. Available at: https://www.uptodate.com/contents/epidemiology-clinical-manifestations-diagnosis-and-treatment-of-fibrolamellar-carcinoma Accessed 10/31/2025.
Choti MA. Fibrolamellar Carcinoma Treatment & Management. Medscape Reference. October 17, 2022. Available at: https://emedicine.medscape.com/article/278354-treatment Accessed on 10/31/2025.
Fibrolamellar Carcinoma (FLC/FLHCC). National Cancer Institute. My Part. February 27, 2019. Available at: https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-digestive-system-tumors/fibrolamellar-hepatocellular-carcinoma Accessed on 10/31/2025.
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