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Why is this rare cancer so difficult to diagnose? Discover the hidden symptoms and diagnostic challenges of fibrolamellar carcinoma!
Fibrolamellar carcinoma (FLC) is a relatively rare type of cancer that primarily affects young adults. The lesion is characterized microscopically by lamellar fibrous layers interspersed between tumor cells. Approximately 200 new cases are diagnosed globally each year, but with recent insights into its molecular characterization, this number may actually be ten times higher. Fibrolamellar carcinoma usually occurs in younger people with normal liver function and no known risk factors, making it different from the more common hepatocellular carcinoma (HCC).
Many studies have confirmed that the DNAJB1-PRKACA gene fusion is present in all fibrolamellar carcinomas examined, suggesting that this gene fusion is critical in fighting this cancer.
Cause of disease
According to a 2014 study, the DNAJB1-PRKACA fusion gene has been found in all (15/15) fibrolamellar carcinomas examined. By using CRISPR/Cas9 technology to create this 400kb somatic deletion in mouse livers, it was demonstrated that the formation of this gene fusion is a key factor in the generation of fibroblast carcinoma.
Pathological features
The histopathological features of fibrolamellar carcinoma include lamellar fibrous layers and tumor cells with abundant cytoplasm and a relatively low ratio of nuclear cells to cells. In contrast to traditional hepatocellular carcinoma, this tumor is usually unencapsulated but has well-defined borders.
Diagnostic Challenges
Due to the lack of clear symptoms, fibrolamellar carcinoma is often not diagnosed until it has reached a considerable size. General symptoms include vague abdominal pain, nausea, abdominal fullness, fatigue, and weight loss. For many patients, liver function markers detected (eg, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase) tend to be normal or slightly elevated. In some cases, patients may have elevated plasma neuropeptide levels, but this information is not generally useful for diagnosis.
Compared with traditional hepatocellular carcinoma, tumor markers such as alpha-fetoprotein (AFP) are often not elevated in fibrolamellar carcinoma, making early diagnosis more difficult.
Currently, diagnosis usually relies on imaging studies (imaging ultrasound, computed tomography, or magnetic resonance imaging) and biopsy. However, even among biopsies, disagreements often arise about the diagnosis. With the recognition of the DNAJB1-PRKACA gene fusion, reliable diagnosis can be made through molecular characterization, including polymerase chain reaction (PCR) to detect the fusion gene or genome sequencing.
Treatment pathways
Fibrolamellar carcinoma can usually be treated by surgical resection, with liver resection being the optimal option because the disease has a high recurrence rate and may require multiple surgical interventions. Depending on whether the tumor can be surgically resected and whether it has distant metastasis, a variety of systemic therapies are currently used for treatment, but there is no unified standard treatment plan.
While radiation therapy has been used, data are relatively limited. The Fibrolamellar Cancer Registry is a medical registry run by patients and families that collects data on more than 250 patients. Its research provides important information for understanding patient prognosis and the effectiveness of immune checkpoint inhibitors.
Epidemiological background
Fibrolamellar carcinoma accounts for 1% to 10% of primary liver cancers. This cancer, compared with traditional hepatocellular carcinoma, usually occurs in younger patients. The age range of patients identified based on molecular testing ranged from 10 to 40 years, with an average age of 21 years, showing significant differences from other forms of liver cancer.
Historical review
This disease was first described by Hugh Edmondson in 1980 and named fibrolamellar hepatocellular carcinoma. It was not until 2010 that the World Health Organization recognized it as an independent cancer. With the rise of social media, patients and their families began to explore the molecular basis of fibrolamellar carcinoma and used this information to advance their research, forming their own medical registration platform.
This research work not only promotes the understanding of fibrolamellar carcinoma, but also makes it a key example of customized medicine, attracting widespread attention from the medical community.
With the high recurrence rate of fibrolamellar carcinoma, patients' five-year survival rates vary significantly and can vary between 40% and 90%, depending on whether and how far the cancer has spread. This has triggered people's thinking about the hopes and challenges of future treatment of the disease?
