What is Hepatocellular Carcinoma?
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It typically arises in the context of chronic liver disease, particularly in patients with cirrhosis due to hepatitis B or C infection, alcohol abuse, or non-alcoholic fatty liver disease. HCC is characterized by the transformation of hepatocytes, the main functional cells of the liver, into malignant cells.
Histological Features
Under the microscope, HCC can display a wide variety of histological patterns. The most common pattern is the
trabecular pattern, where tumor cells are arranged in thickened cords or plates that are usually more than three cells thick. Other patterns include the pseudoglandular (or acinar) pattern, and the solid pattern.
Cytologically, the tumor cells often have increased nuclear-to-cytoplasmic ratios, prominent nucleoli, and a variable degree of
pleomorphism. Intracytoplasmic bile production and hyaline bodies may also be observed.
Vascular invasion is a common and significant feature indicating a poor prognosis.
Pathogenesis and Risk Factors
Several factors contribute to the development of HCC, including chronic viral hepatitis (B and C), cirrhosis, aflatoxin exposure, and genetic mutations. Chronic liver injury leads to continuous cycles of cell death and regeneration, creating an environment conducive to genetic mutations and cancer development. Mutations in genes such as
TP53 and
CTNNB1 (encoding β-catenin) are commonly associated with HCC.
Diagnosis
The diagnosis of HCC typically involves a combination of imaging techniques and histological examination. Imaging modalities like
ultrasound,
CT scan, and
MRI are often used to identify liver lesions. Histological confirmation is usually obtained via a liver biopsy, where tissue samples are examined for characteristic features of HCC.
Immunohistochemistry can aid in diagnosis by using markers like
HepPar1,
Glypican-3, and
Alpha-fetoprotein (AFP) to distinguish HCC from other liver tumors.
Grading and Staging
The histological grading of HCC is based on the degree of differentiation of the tumor cells. Well-differentiated tumors resemble normal hepatocytes, while poorly differentiated tumors show significant atypia and anaplastic features. The
Edmondson-Steiner grading system is commonly used for this purpose.
Staging of HCC considers the size of the tumor, the extent of liver involvement, vascular invasion, and the presence of metastasis. The
Barcelona Clinic Liver Cancer (BCLC) staging system is one of the most widely used staging systems, guiding treatment decisions and prognosis.
Treatment
Treatment options for HCC depend on the stage of the disease and the liver function status. Early-stage HCC may be treated with surgical resection, liver transplantation, or local ablative therapies like
radiofrequency ablation and
transarterial chemoembolization (TACE). Advanced cases may require systemic therapies such as targeted therapy (e.g., sorafenib) or immunotherapy.
Prognosis
The prognosis of HCC is generally poor, with a 5-year survival rate of less than 20% for advanced-stage disease. Early detection and treatment significantly improve outcomes, highlighting the importance of regular screening in high-risk populations.
