Fibrolamellar hepatocellular carcinoma (FLC) represents a rare form of liver cancer that stands apart from more common liver malignancies. This distinct disease primarily affects adolescents and young adults, often presenting in individuals without the typical risk factors associated with other liver cancers. Its unique characteristics set it apart as a specific entity requiring specialized understanding and management.
What is Fibrolamellar Hepatocellular Carcinoma?
Fibrolamellar hepatocellular carcinoma is a distinct subtype of liver cancer, differing significantly from conventional hepatocellular carcinoma (HCC). Unlike HCC, which frequently arises in livers damaged by conditions like cirrhosis, FLC typically develops in an otherwise healthy liver. Its unique cellular appearance, characterized by lamellar fibrosis and large, eosinophilic tumor cells, gives it its name.
A defining feature of FLC is the DNAJB1-PRKCA gene fusion. This fusion occurs when parts of two different genes, DNAJB1 and PRKCA, abnormally join together. This genetic change is considered a hallmark of FLC, playing a role in tumor development and progression.
This rare liver cancer predominantly affects adolescents and young adults, typically between the ages of 10 and 35 years. Patients diagnosed with FLC usually do not have a history of chronic liver disease, viral hepatitis, or excessive alcohol consumption, which are common risk factors for HCC. The absence of these traditional risk factors highlights the unique biological pathways involved in FLC.
Identifying Symptoms and Diagnosis
Recognizing fibrolamellar hepatocellular carcinoma can be challenging because its initial symptoms are often vague and resemble those of many other conditions. Patients might experience persistent abdominal pain, a sensation of fullness, or unexplained weight loss. Fatigue is also common, and some individuals may notice a palpable mass in their upper abdomen. Jaundice, a yellowing of the skin and eyes, occurs less frequently but can indicate advanced disease.
The diagnostic process typically begins with imaging studies to detect any abnormalities in the liver. Ultrasound is often the first step, followed by more detailed scans such as computed tomography (CT) or magnetic resonance imaging (MRI). These advanced imaging techniques help visualize the liver mass, assess its size, location, and relationship to surrounding structures, and look for any signs of spread. Imaging can also show the characteristic appearance of FLC, which often includes a central scar within the tumor.
A definitive diagnosis of FLC requires a tissue biopsy, usually performed as a core needle biopsy. During this procedure, a small sample of the liver mass is extracted, often guided by ultrasound or CT imaging. Pathologists then examine the tissue under a microscope to identify the characteristic fibrolamellar cells and confirm the diagnosis. Blood tests, such as liver function tests, may show some abnormalities, but tumor markers like alpha-fetoprotein (AFP), which are often elevated in other liver cancers, are typically within normal limits or only mildly elevated in FLC patients.
Treatment Options
Surgical resection is the primary and most effective treatment option for fibrolamellar hepatocellular carcinoma. The goal is complete removal of the tumor, along with a margin of healthy liver tissue. For tumors confined to the liver and fully resectable, surgery offers the best chance for long-term survival. The extent of surgery depends on the tumor’s size, location, and the overall health of the liver.
If the tumor is too large, has spread extensively, or is unsafe to remove completely, surgery may not be an immediate option. Unlike other liver cancers, FLC has shown limited responsiveness to conventional systemic therapies. Chemotherapy and radiation therapy are generally not effective against FLC and are reserved for palliative care or specific circumstances. Targeted therapies and immunotherapies have also shown limited consistent efficacy in FLC, although research continues.
Given the rarity and unique characteristics of FLC, a multidisciplinary team approach is beneficial for patient management. This team typically includes liver surgeons, oncologists, radiologists, and pathologists who collaborate to develop an individualized treatment plan. For patients with advanced or recurrent disease, or those not candidates for surgery, participation in clinical trials exploring newer therapeutic agents may be considered. These trials provide access to investigational treatments.
Prognosis and Follow-Up Care
The prognosis for individuals with fibrolamellar hepatocellular carcinoma varies considerably, influenced by several factors. Key factors include the cancer’s stage at diagnosis, whether the tumor was completely removed surgically, and if it has spread to other parts of the body. Patients who undergo successful complete surgical resection generally have a more favorable outlook.
Long-term follow-up care and surveillance are important for all FLC patients, even after successful surgery. Regular monitoring is necessary due to the high rate of recurrence. Follow-up typically involves periodic imaging studies, such as CT or MRI scans of the abdomen, to detect any signs of tumor regrowth or new lesions. Blood tests, including liver function tests, are also part of routine surveillance.
Managing FLC, particularly in cases of recurrence, presents ongoing challenges. Treatment strategies for recurrent disease may involve repeat surgery if feasible, or other localized therapies depending on the extent and location of the recurrence. Research into FLC biology and more effective systemic therapies continues. Patient support groups and organizations offer resources and community for affected individuals and families.