Gene Fusion Events Are Markers of Fibrolamellar Carcinoma

In recent years, researchers have identified several factors, including tumor size, surgical resectability, and genetic alterations, that may influence the prognosis and overall survival of patients with fibrolamellar carcinoma, guiding treatment decisions and follow-up strategies.

Surgical resectability, which refers to the ability to remove the tumor through surgical intervention, has been identified as a significant predictor of survival in fibrolamellar carcinoma. Complete surgical removal of the tumor is essential for achieving optimal outcomes, as it provides the best chance of eliminating the cancerous cells and preventing disease recurrence.

It is important to note that not all fibrolamellar carcinomas are surgically resectable. Tumors that are too large, involve critical blood vessels or have metastasized to distant organs may not be amenable to surgery alone. In such cases, alternative treatment modalities, such as chemotherapy and targeted therapies, may be considered to manage the disease.

The genetic abnormalities that contribute to the development of fibrolamellar carcinoma are not yet fully understood. However, recent research has identified a characteristic genetic alteration known as a DNAJB1-PRKCA fusion. This fusion event involves the fusion of two separate genes, DNAJB1 and PRKCA, resulting in the formation of a fusion protein.

The DNAJB1-PRKCA fusion event is considered a hallmark of fibrolamellar carcinoma and is believed to play a key role in the development and progression of the disease.

Now that we’ve learned about the unique genetic fusion behind fibrolamellar carcinoma, let’s dive into what exactly fibrolamellar carcinoma is and how it affects the body.

What is fibrolamellar carcinoma? 

Fibrolamellar carcinoma (FLC) is a rare form of liver cancer that primarily affects adolescents and young adults without underlying liver disease. It is characterized by the presence of a large tumor mass that contains cancerous cells and a fibrous component. FLC is distinct from other forms of liver cancer, such as hepatocellular carcinoma, in terms of its clinical presentation, histology, and genetic alterations.

Unlike most liver cancers that are associated with liver disease, FLC typically occurs in individuals with normal liver function. It is often diagnosed in patients under the age of 40. FLC tumors are typically single large tumors with dense fibrotic bands forming a central scar in about 75% of cases

Causes of fibrolamellar carcinoma

Fibrolamellar carcinoma (FLC) is a rare type of liver cancer. The exact cause of FLC is still not fully understood, and further research is needed to determine the underlying mechanisms. Here are some factors that may be associated with the development of fibrolamellar carcinoma.

1. Genetic Factors: Some studies suggest that there may be genetic factors involved in the development of fibrolamellar carcinoma. A specific genetic mutation, known as a DNAJB1-PRKACA fusion gene, has been identified in most FLC cases. This fusion gene is not inherited but rather arises spontaneously within liver cells.

2. Environmental Exposures: Some research suggests that certain environmental exposures may increase the risk of developing fibrolamellar carcinoma. However, the specific environmental factors or toxins that may be linked to FLC are not well-defined at this time.

3. Liver Health: Fibrolamellar carcinoma typically occurs in individuals without a background of liver inflammation, fibrosis, or cirrhosis. Unlike other forms of liver cancer, FLC often develops in otherwise healthy liver tissues.

Having explored the causes of fibrolamellar carcinoma, let’s now shift our focus to understanding how this rare liver cancer is diagnosed and identified in individuals.

Diagnosis of fibrolamellar carcinoma

1. Medical History and Physical Examination: The healthcare provider will begin by taking a detailed medical history and conducting a physical examination. 
2. Imaging Studies: Imaging techniques are crucial for diagnosing fibrolamellar carcinoma. Imaging studies commonly used include:

• Ultrasound: Ultrasonography can help identify the presence of a mass or abnormality in the liver.
• CT Scan: Computed tomography (CT) scans provide cross-sectional images of the liver, allowing for an assessment of the tumor’s size, location, and extent.
• MRI Scan: Magnetic resonance imaging (MRI) may be utilized to provide detailed images of the liver, aiding in the characterization of the tumor and detecting any potential metastases.

3. Liver Biopsy: A biopsy is the definitive diagnosis for fibrolamellar carcinoma. During a biopsy, a small sample of liver tissue is extracted either through a needle or during surgery. This sample is then examined under a microscope by a pathologist to confirm the presence of fibrolamellar carcinoma.
4. Genetic Testing: Genetic testing may also be performed to detect the presence of the DNAJB1-PRKACA fusion gene, which is strongly associated with fibrolamellar carcinoma

Risk factors associated with fibrolamellar carcinoma

Risk factors associated with fibrolamellar carcinoma (FLC) based on the search results are:

1. Environmental Exposures: There is some evidence suggesting that environmental exposures may be a risk factor for fibrolamellar carcinoma. The presence of aryl hydrocarbon receptors on tumor cells has been observed, indicating a potential link between environmental exposures and FLC development.
2. Cirrhosis: Unlike other types of liver cancer, fibrolamellar carcinoma is often not associated with underlying liver disease, such as cirrhosis

Treatment options for fibrolamellar carcinoma

The current treatment options for fibrolamellar carcinoma (FLC) primarily revolve around surgical interventions. The following treatment approaches are commonly used:

1. Surgical Resection: Complete surgical resection, which involves removing the tumor and surrounding healthy tissue, is considered the mainstay of treatment for fibrolamellar carcinoma. Surgical resection is the primary treatment option and remains the only potentially curative option for FLC.

 However, it is important to note that recurrence of the tumor after surgery is relatively common.

2. Liver Transplantation: In some cases, liver transplantation may be considered a treatment option. A liver transplant is typically reserved for patients with localized fibrolamellar carcinoma who meet specific eligibility criteria.
3. Embolization Therapy: Embolization therapy, such as transarterial chemoembolization (TACE) or transarterial embolization (TAE), may be used in select cases. This therapy involves blocking the blood supply to the tumor, thereby limiting its growth and potentially reducing symptoms.

The survival rate of fibrolamellar carcinoma

• The overall 5-year survival rate for fibrolamellar carcinoma ranges from 7% to 40%. It is important to note that the survival rate can vary widely depending on the specific study and patient population.
• For patients who undergo surgery, the reported 5-year survival rate is approximately 44% to 68%. Complete surgical removal of the tumor is considered essential for improving survival rates in FLC.

How is it different from other types of hepatocellular carcinoma (liver cancer)? 

Fibrolamellar carcinoma (FLC) is considered a distinct subtype of hepatocellular carcinoma (HCC), which is the most common type of primary liver cancer. 

Here are some ways in which fibrolamellar carcinoma is different from other types of hepatocellular carcinoma:

1. Age and demographics: Fibrolamellar carcinoma typically affects younger individuals, with a peak incidence in the second and third decades of life. In contrast, other types of hepatocellular carcinoma are more commonly seen in older adults.

2. Absence of underlying liver disease: Fibrolamellar carcinoma often occurs in individuals without underlying liver disease, such as cirrhosis or hepatitis, which are commonly associated with other types of hepatocellular carcinoma.

3. Histological features: Fibrolamellar carcinoma has distinct histological features that set it apart from other types of hepatocellular carcinoma. This includes the presence of large, polygonal tumor cells.

4. Alpha-fetoprotein (AFP) levels: Fibrolamellar carcinoma tends to have lower levels of alpha-fetoprotein (AFP) compared to other types of hepatocellular carcinoma. AFP is a tumor marker that can be elevated in hepatocellular carcinoma, but it is often within normal limits or only mildly elevated in fibrolamellar carcinoma.

5. Prognosis and treatment response: Fibrolamellar carcinoma has been associated with better overall survival compared to other types of hepatocellular carcinoma. Additionally, fibrolamellar carcinoma has shown higher rates of response to certain treatments, such as chemotherapy or targeted therapies, compared to traditional hepatocellular carcinoma.

Role of MedicoExperts Tumour Board in Treatment

MedicoExperts Tumor boards are groups of doctors who are experts in different areas of cancer, even rare types like fibrolamellar carcinoma (FLC). These doctors work together and share their knowledge to make sure that FLC is diagnosed correctly and quickly.

Radiological evaluation means looking at detailed pictures of the body using things like CT scans and MRIs. These pictures help find and understand FLC. In the tumor board, there are special doctors called radiologists who know how to read these pictures and spot possible FLC cases.

Histopathological examination is like investigating tiny bits of tissue to confirm if someone has FLC. In the tumor board, there are also doctors known as pathologists. They check the tissue samples and use their expertise to confirm the diagnosis and know which kind of FLC it is.

If you or a loved one suspect you have fibrolamellar carcinoma, it’s important to discuss your case with a tumor board of experts. Their combined knowledge can provide you with a comprehensive evaluation and guide you toward the best possible treatment decisions.

Conclusion 

Further research is needed to improve the understanding and treatment of fibrolamellar carcinoma. Studies have also examined the potential association between fibrolamellar carcinoma and genetic mutations, such as  DNAJB1-PRKCA fusion in cases of fibrolamellar carcinoma.  

Environmental exposures have also been explored as potential risk factors for fibrolamellar carcinoma, but more research is needed to draw definitive conclusions in this regard.

MedicoExperts Tumor Board is like a team of super doctors who work together to help people with fibrolamellar carcinoma. They use their special knowledge to figure out the best ways to find and treat this rare cancer. With these experts working together, they offer personalized strategies for each person, making sure they get the right treatment. The Tumor Board is here to guide and support those facing fibrolamellar carcinoma on their journey to better health.

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Written by Dr Subhamoy Mukherjee, Ph.D. (Oncology).

Dr Subhamoy is a molecular oncologist and worked with genomic profiles of patients. He has 8 years of experience in scientific writing and patient data analysis. He takes strong interest in making people aware of the different diagnostic and treatment approaches of cancer through his informative articles and blogs.