Fibrolamellar carcinoma is a rare and distinct form of primary liver cancer. Its name is derived from the unique appearance of the tumor tissue under a microscope, which shows characteristic fibrous bands, known as lamellae, layered between the cancer cells. This cancer was first described in medical literature in 1956.
Unlike the more common hepatocellular carcinoma (HCC), which often develops in the context of chronic liver disease, fibrolamellar carcinoma arises in a liver that is otherwise healthy. This cancer accounts for less than 1% of all primary liver cancers in the United States. While it is classified as a subtype of hepatocellular carcinoma, its unique clinical and molecular features set it apart.
Unique Characteristics and Risk Factors
A defining feature of fibrolamellar carcinoma (FLC) is the population it affects. It predominantly occurs in adolescents and young adults, with a median age of onset around 21 to 22 years old. This stands in stark contrast to hepatocellular carcinoma (HCC), which is more commonly diagnosed in older individuals with a history of underlying liver conditions. Patients with FLC almost always have a healthy, non-cirrhotic liver.
There are no known environmental or lifestyle risk factors associated with the development of FLC. The disease is not linked to alcohol consumption, viral hepatitis infections, or other common causes of liver damage that predispose individuals to other liver cancers. This lack of identifiable external triggers points toward an internal, genetic origin for the disease.
Research has identified a specific genetic alteration that is the signature event in FLC. In the vast majority of cases, a small piece of chromosome 19 is deleted, causing two genes, DNAJB1 and PRKACA, to fuse. This fusion creates a new chimeric gene, DNAJB1-PRKACA, which produces an abnormal protein that drives the uncontrolled growth of the cancer cells.
The presence of this fusion gene is so consistent that it is now used to help confirm the diagnosis. The resulting fusion protein leads to the overactivation of an enzyme called protein kinase A (PKA), which is required for the tumor to grow and survive. This makes it a focus of ongoing research for targeted therapies.
Symptoms and Diagnostic Process
In its early stages, fibrolamellar carcinoma often produces no noticeable symptoms. As the tumor grows larger, individuals may begin to experience non-specific complaints. These often include vague abdominal pain, which can sometimes radiate to the back or shoulder, a feeling of fullness in the abdomen, or the sensation of a palpable mass. Unexplained weight loss, a general feeling of being unwell (malaise), fatigue, and nausea are also commonly reported.
Because the initial symptoms are often subtle, the cancer is frequently at an advanced stage by the time a diagnosis is made. The diagnostic process begins when these symptoms prompt a visit to a doctor, who may then order imaging studies. Technologies like computed tomography (CT) scans and magnetic resonance imaging (MRI) are used to visualize the liver, identify the tumor’s size and location, and check if the cancer has spread.
Blood tests are also performed, but they often show normal or only slightly elevated liver enzymes. A distinguishing factor from other liver cancers is that the alpha-fetoprotein (AFP) tumor marker, often elevated in hepatocellular carcinoma, is normal in individuals with FLC. Some patients may have elevated levels of other substances, such as neurotensin or vitamin B12 binding globulin, but these are not universally present.
While imaging and blood tests can strongly suggest FLC, a definitive diagnosis requires a biopsy. During this procedure, a small sample of tissue is removed from the liver tumor using a needle. A pathologist then examines the tissue under a microscope to identify the characteristic laminated fibrous bands that confirm the diagnosis.
Primary Treatment Modalities
The most effective treatment for fibrolamellar carcinoma is the complete surgical removal of the tumor, a procedure known as surgical resection. This approach offers the only potential for a cure and is the standard of care for patients with resectable disease. Due to the young age of patients and the absence of underlying cirrhosis, major liver resections are often feasible even when tumors are large. More than 70% of patients may require a major hepatectomy.
For some patients, surgeons may recommend chemotherapy before surgery, known as neoadjuvant therapy, to shrink the tumor and make it easier to remove. In other cases, chemotherapy might be given after surgery as an adjuvant treatment to address any remaining cancer cells and reduce the chance of recurrence. The effectiveness of these chemotherapy approaches can vary.
When the tumor is confined to the liver but cannot be surgically resected due to its size or location, a liver transplant may be an option. This procedure involves removing the entire liver and replacing it with a healthy donor liver. Liver transplantation can offer high survival rates for select patients, though finding a suitable donor organ can be a significant challenge.
For individuals with advanced disease that has spread beyond the liver or for tumors that cannot be removed surgically, other treatments are considered. These are not curative but are used to control the cancer’s growth and manage symptoms. Options include:
- Systemic chemotherapy, though FLC is often not highly responsive to it
- Trans-arterial chemoembolization (TACE), which delivers chemotherapy directly to the tumor
- Targeted therapies
- Enrollment in clinical trials investigating new drugs
Prognosis and Long-Term Management
The prognosis for fibrolamellar carcinoma is directly linked to whether the tumor can be completely removed through surgery. If a complete resection is successful, the outlook is better than for other types of advanced liver cancer. However, even after a successful surgery, the disease has a high rate of recurrence, affecting more than two-thirds of patients.
This high probability of recurrence makes long-term surveillance a fundamental part of post-treatment care. Patients who have undergone surgery must adhere to a lifelong follow-up plan to monitor for any signs of recurrence. This surveillance involves regular appointments and periodic imaging scans, such as CT or MRI, to check for new tumor growth.
The median time for recurrence to occur falls within the first few years after surgery, between 10 and 33 months. While most recurrences happen within this timeframe, the cancer can return many years later. This underscores the necessity for extended, long-term surveillance, as patients are not entirely free from the risk of a late recurrence.
For patients whose cancer does recur, surgical resection of the new tumors may again be a viable option and is associated with improved survival. For those with unresectable disease, either at initial diagnosis or upon recurrence, the prognosis is less favorable.