What Is Fibrolamellar Carcinoma?

Introduction

Fibrolamellar Carcinoma (FLC) is a rare type of liver cancer that primarily affects adolescents and young adults. Unlike most other liver cancers, FLC has a unique histological appearance (meaning it can be identified easily when looking under a microscope) and a specific genetic mutation that sets it apart. It is characterized by the presence of large tumour masses that contain fibrous tissue bands, hence the name "fibrolamellar."^1,2 This cancer type tends to occur in individuals without a history of chronic liver disease or traditional risk factors associated with liver cancer, such as hepatitis or cirrhosis. FLC is often diagnosed at an advanced stage due to its subtle and variable symptoms, which can include abdominal pain, weight loss, and malaise. Given its rarity and distinct features, FLC requires specialized diagnostic and treatment approaches.³

Brief overview of liver cancer

Liver cancer is a serious condition where abnormal cells grow in the liver. There are two main types of liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC is common and linked to liver diseases like hepatitis, cirrhosis, and alcohol use. Cholangiocarcinoma is a liver cancer affecting the bile ducts, and it is linked to type II diabetes, obesity and HIV infection. Risk factors include liver diseases, viral hepatitis, alcohol, and obesity. Symptoms include pain, weight loss, jaundice, and fatigue. Diagnosis involves exams, blood tests, imaging, and biopsies. Treatment options range from surgery to chemotherapy based on the cancer stage. Prevention includes managing risks and regular check-ups for early detection.⁴ 

Distinction between FLC and other liver cancers

FLC stands out from other types of liver cancers due to several key distinctions. These include:

• Age of Onset: FLC typically affects adolescents and young adults, while most other liver cancers are more common in older individuals.^4,5
• Risk Factors: Unlike other liver cancers, which often arise from chronic liver diseases (hepatitis B or C, cirrhosis), alcohol abuse, or fatty liver disease, FLC is less associated with these common risk factors.⁵
• Genetic Mutation: FLC has a unique genetic mutation involving the DNAJB1 and PRKACA genes, which is not commonly found in other liver cancers.⁶ 
• Histological Features: FLC tumours have fibrous tissue bands running through them, leading to the name "fibrolamellar." Other liver cancers lack this distinctive histological appearance.⁷
• Symptoms: While symptoms of liver cancers are often similar, FLC can manifest with a variety of symptoms, such as abdominal pain, weight loss, and malaise, but these might not immediately point to liver cancer due to its rarity.³
• Prognosis: FLC has shown a relatively better response to certain treatments, especially if detected early and treated aggressively, in contrast to the generally poor prognosis of many other liver cancers.⁸
• Diagnosis Challenges: Due to its rarity and unique characteristics, FLC can be challenging to diagnose accurately and quickly, often requiring specialized imaging and histological examination.⁹
• Awareness and Research: FLC has historically received less attention in terms of research and awareness efforts compared to more common liver cancers.⁸

In summary, the age group affected, genetic mutation, histological appearance, risk factors, and prognosis of FLC set it apart from other liver cancers, making it a distinct and challenging entity to diagnose and treat effectively.

Age and gender prevalence

FLC displays distinct age and gender prevalence patterns compared to other liver cancers:

Age Prevalence:

FLC primarily affects adolescents, young adults, and occasionally individuals up to their 40s. This stands in contrast to other types of liver cancers that are more commonly diagnosed in older adults, often above the age of 50 or 60. The young age at which FLC develops sets it apart from the typical age range associated with most liver cancers.¹⁰

Gender Prevalence:

FLC tends to occur in both males and females, meaning it occurs slightly more in females. While it affects both genders, the female-to-male ratio is often reported to be higher in FLC cases compared to other liver cancers. However, the exact gender distribution may vary based on different studies and populations.¹⁰

Causes and risk factors

Genetic mutations and their role

• FLC is associated with a specific genetic mutation involving the fusion of the DNAJB1 and PRKACA genes.
• These genetic alterations play a pivotal role in the development of FLC, contributing to the unique characteristics of the tumour.
• The fusion of these genes leads to dysregulation of cell growth and signalling pathways, promoting the formation of FLC tumours.¹¹

Lack of association with common liver cancer risk factors

FLC stands out due to its unique lack of association with the common risk factors typically linked to other forms of liver cancer.. Instead of being primarily influenced by environmental or lifestyle-related risks, FLC's development appears to be more closely tied to genetic factors, as evidenced by the specific DNAJB1-PRKACA.  Since FLC differs from other cancers in terms of its risk factors, more research needs to be done to understand its causes specifically.^10,11

Current research on potential causes

Currently, ongoing research is being done to understand the genetic causes of FLC further. Scientists are working to understand the factors that lead to the development of these mutations, seeking to shed light on the mechanisms behind FLC. In this pursuit, researchers are investigating a range of possibilities encompassing environmental, genetic, and epigenetic factors that could potentially contribute to the emergence of FLC. A key avenue of exploration involves studying the contrasts between the DNAJB1-PRKACA gene fusion, characteristics of FLC, and the normal functioning of these genes. This analytical approach is expected to offer valuable insights into how these mutations play a role in driving the growth of FLC tumours.^9,11

Furthermore, research is being conducted to understand environmental exposures and FLC when it first develops. By studying whether external factors or developmental stages might influence the initiation or progression of FLC, researchers aim to further understand this disease.. Overall, the ongoing research into the potential causes of FLC aims to understand the overlap between genetic, environmental, and developmental components that contribute to the development of this unique cancer.^9-11

Diagnosis

Imaging techniques (Ultrasound, MRI, CT Scan):

Diagnosing Fibrolamellar Carcinoma (FLC) often begins with advanced imaging techniques, such as ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) scans. These imaging methods allow medical professionals to visualize the liver and surrounding structures, enabling them to detect the presence, size, and location of tumours. Ultrasound offers real-time imaging using sound waves, while MRI and CT scans provide detailed cross-sectional images. These techniques aid in distinguishing FLC from other liver conditions and help in seeing how far the tumour has spread..^12,13

Biopsy and histological examination:

A diagnosis of FLC typically requires a biopsy, where a small sample of tissue is collected from the tumour for analysis. This tissue is then examined under a microscope in a process known as histological examination. Histology reveals the characteristic features of FLC, including the presence of fibrous tissue bands within the tumour. This microscopic analysis also helps differentiate FLC from other types of liver cancers and non-cancerous liver conditions. Additionally, molecular testing may confirm the presence of the DNAJB1-PRKACA gene fusion, which is specific to FLC.¹⁴

Importance of accurate diagnosis for treatment planning:

Accurate diagnosis of Fibrolamellar Carcinoma is crucial for developing an effective treatment plan. Given FLC's unique characteristics and better response to certain treatments when detected early, precise diagnosis enables medical professionals to determine the most appropriate therapeutic approach from the many options available. An accurate diagnosis also helps in assessing the stage of cancer and if surgical removal can be done. Therefore, accurate diagnosis not only confirms the presence of FLC but also guides medical decisions to increase the chances of successful treatment and an overall better outcome after treatment.¹⁵

Treatment approaches

Surgical resection:

Surgical resection is a primary treatment option for FLC if the tumour is localized and operable. During this procedure, the tumour, along with a margin of healthy tissue, is surgically removed from the liver. Surgical resection offers the potential for a complete cure, particularly when FLC is detected in its early stages. However, whether this treatment approach can be chosen depends on factors like tumour size, location, and the overall health of the patient. While surgical resection can provide favourable outcomes, the decision to proceed with surgery is made after careful assessment by a medical team.¹⁶

Liver transplantation:

Liver transplantation may be considered in cases where FLC has spread throughout the liver or surgical resection cannot be carried out due to factors such as tumour size or location. During transplantation, the diseased liver is replaced with a healthy donor liver. Liver transplantation can offer a chance for cure, as it removes the entire liver containing the tumour. However, suitable donor organs and the patient's overall health play significant roles in determining whether this treatment option can be chosen for patients..¹⁷

Chemotherapy and targeted therapies:

Chemotherapy and targeted therapies are utilised in cases where surgical options are limited or when FLC has spread beyond the liver. Chemotherapy involves the use of drugs to kill or stop cancer cells from growing. Targeted therapies, on the other hand, focus on specific molecules or pathways involved in cancer growth. While these treatments may not provide a complete cure for FLC, they can help slow down tumour progression, alleviate symptoms, and improve quality of life.¹⁸

Potential for combination therapies:

Due to the rarity of FLC and its unique genetic characteristics, treatment strategies often involve a personalized approach. Researchers are exploring the potential of combining different treatment options, such as surgery, chemotherapy, and targeted therapies, to optimize outcomes. Combining treatments can enhance their effectiveness and potentially improve long-term treatment outcomes.¹⁶

Patient-specific treatment plans:

Each FLC case is unique, and treatment plans are tailored to individual patients based on factors like tumour stage, location, overall health, and patient preferences. A medical team called the multidisciplinary team comprising of surgeons, oncologists, radiologists, and other specialists collaborate to design comprehensive treatment plans. Patient-specific treatment plans aim to strike a balance between achieving optimal disease control and maintaining the patient's quality of life.¹⁵

In summary, treatment approaches for Fibrolamellar Carcinoma encompass a range of options, including surgical interventions, transplantation, chemotherapy, targeted therapies, and the potential for combination therapies. The choice of treatment depends on the specific characteristics of the tumour and the patient's overall health, with the ultimate goal of achieving the best possible outcome.

Contribution to the field of FLC

Ongoing research and challenges:

Ongoing research in the field of fibrolamellar carcinoma (FLC) is aimed at helping understand the genetic, molecular, and environmental factors driving the development of this rare cancer. Scientists are focused on studying the mechanisms behind the DNAJB1-PRKACA gene fusion and its role in tumour growth. Additionally, efforts are being made to identify potential therapeutic targets that could lead to more effective treatments. However, the rarity of FLC poses challenges in terms of obtaining sufficient research data and funding for dedicated studies. Collaborative efforts among researchers, medical professionals, and advocacy groups are essential to advance knowledge and uncover novel treatment avenues.¹⁵

Support and resources:

For patients and families affected by FLC, support and resources play a crucial role. Various patient advocacy groups and organizations are dedicated to raising awareness, providing information, and offering emotional support to those facing FLC. These groups connect patients with medical experts, share research updates, and create a sense of community among individuals navigating this rare cancer. Additionally, specialized medical institutions and centres of excellence offer expertise in diagnosing and treating FLC, contributing to improved patient care. The combined efforts of research, support networks, and medical expertise contribute to enhancing the quality of life and outcomes for individuals affected by FLC.¹⁵

In summary, ongoing research in the field of Fibrolamellar Carcinoma is essential to uncover its underlying mechanisms and develop effective treatments. Challenges stem from its rarity, underscoring the need for collaboration and funding. Support and resources from advocacy groups and medical institutions are invaluable in providing information, emotional support, and expert care for those affected by FLC.

Summary

FLC is a rare and distinctive form of liver cancer that typically affects adolescents and young adults, setting it apart from other liver cancers that usually arise in older individuals. Unlike common liver cancers, FLC is not linked to common risk factors such as chronic hepatitis and cirrhosis. Instead, genetics play a major role in its development through the presence of a specific DNAJB1-PRKACA. Diagnosing the condition involves advanced imaging, biopsies, and molecular testing. In terms of treatment, FLC presents varied options, including surgical resection, transplantation, chemotherapy, and targeted therapies, all carefully tailored to the individual's case. While its prognosis tends to be more favourable compared to other liver cancers, its rarity poses challenges in research and funding. Support networks, advocacy groups, and medical institutions play a critical role in providing resources, information, and emotional support to those affected by FLC. A full grasp of FLC, including its genetic roots, how it's diagnosed, ways to treat it, and the importance of support, all come together to give a complete view of this special kind of cancer.