Fibrolamellar carcinoma (FLC) is a rare form of liver cancer that stands apart from more common liver malignancies. Unlike most liver cancers, which often develop in individuals with pre-existing liver damage from conditions like cirrhosis or viral hepatitis, FLC typically affects younger individuals, including adolescents and young adults, who generally have healthy livers. This distinction highlights its unique biological and clinical characteristics within the spectrum of liver cancers.
Understanding Fibrolamellar Carcinoma
Fibrolamellar carcinoma is an extremely rare form of liver cancer, accounting for less than 1% of all primary liver tumors. It is estimated to occur in about one in five million people in the United States. The name “fibrolamellar” refers to the distinctive fibrous bands of tissue that are observed in a layered pattern when tumor tissue is examined under a microscope.
A defining feature of FLC is the unique DNAJB1-PRKACA fusion gene. This fusion occurs when a segment of chromosome 19 breaks and reattaches incorrectly, joining the DNAJB1 gene with the PRKACA gene. This genetic alteration is found in nearly all FLC cases and drives tumor development, leading to the constant activation of the PRKACA protein, a type of signaling protein called a kinase. While FLC tends to grow slowly, it can metastasize, or spread, to other parts of the body, including regional lymph nodes, lungs, and peritoneum.
Diagnosis and Treatment Pathways
Diagnosing fibrolamellar carcinoma often begins with imaging techniques, such as computed tomography (CT) scans or magnetic resonance imaging (MRI), which are used to assess the tumor’s size, location, and potential spread. CT scans are particularly useful for staging FLC and detecting regional lymph node metastases. However, a definitive diagnosis requires a biopsy, where a small tissue sample is taken from the tumor and examined by a pathologist.
Once diagnosed, accurate staging of FLC is important for guiding treatment decisions. Surgical resection, which involves removing the tumor and a portion of the liver, is considered the primary treatment and the only potentially curative option for FLC. In some cases, a liver transplant may be considered for eligible patients. While chemotherapy and radiation therapy have been used, their effectiveness in FLC remains less consistent compared to surgical approaches, with FLC often showing less responsiveness to chemotherapy than conventional hepatocellular carcinoma. Targeted therapies and immunotherapy are also being explored, with ongoing research into agents that might specifically target the DNAJB1-PRKACA fusion protein or enhance the body’s immune response against the cancer. Multidisciplinary teams of specialists typically collaborate to develop individualized treatment plans for patients with FLC.
Factors Influencing Prognosis
Several factors influence the prognosis for individuals diagnosed with fibrolamellar carcinoma. The stage of the cancer at diagnosis plays a substantial role, with localized disease generally having a more favorable outlook than metastatic disease, where the cancer has spread beyond the liver. Many FLC cases are diagnosed at an advanced stage, partly due to the lack of specific early symptoms. The completeness of surgical resection, known as an R0 resection (meaning no detectable cancer cells at the surgical margins), is a primary factor for improved prognosis.
Tumor recurrence also impacts the long-term outlook. FLC has a high rate of recurrence, even after successful surgical removal, with rates reported between 33% and 100%. Younger age at diagnosis and the absence of large vessel invasion or thrombosis are also associated with a better prognosis following surgery. The patient’s overall health and their response to various treatment modalities, especially in cases where surgery is not possible or for recurrent disease, contribute to the individual prognosis.
Survival Statistics and Outlook
Survival statistics for fibrolamellar carcinoma are challenging to report precisely due to its rarity and variability in individual outcomes. For patients who undergo surgical resection, reported 5-year survival rates range from 44% to 68%. In contrast, for individuals who receive other treatments without surgery, 5-year survival rates are considerably lower, ranging from 2% to 17%. Studies indicate the 5-year overall survival rate for all FLC patients is around 40.3%, increasing to 60.7% for those eligible for surgical resection.
For patients with unresectable or advanced metastatic disease, median survival can be around 10 to 14 months. While FLC generally has a better prognosis than conventional hepatocellular carcinoma, recurrence rates remain high, even after complete surgical removal. Research is exploring new therapeutic strategies, including targeted therapies and immunotherapy, often focusing on the DNAJB1-PRKACA fusion protein. Clinical trials are underway to evaluate the safety and effectiveness of new treatments, including peptide vaccines designed to stimulate an immune response against FLC cells. Specialized care centers with multidisciplinary teams are important for FLC patients, offering a comprehensive approach to diagnosis, treatment, and ongoing management.