Etiology and Risk Factors
Hepatocellular carcinoma shows marked geographical variations in prevalence, directly related to dietary habits and endemic infections. The vast majority of affected individuals (70–80%) are men.
Key factors provoking tumor development:
- Viral hepatitis: chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV), as well as prolonged carriage of the surface antigen HBsAg.
- Liver cirrhosis: the primary underlying condition. The tumor forms in 70–80% of patients with cirrhosis (predominantly macronodular forms, including viral etiology).
- Aflatoxins: specific metabolic products of the mold Aspergillus flavus. Contamination occurs through the ingestion of infected grains and plant raw materials.
Clinical Presentation and Gross Pathology
The disease often manifests with a sudden deterioration in the patient's general condition. Pain appears in the right upper quadrant of the abdomen, and progressive liver failure worsens. In some cases, a firm tumor mass is palpable.
Macroscopically, the liver is markedly enlarged, and its mass can reach 2000–3000 grams. There are three main growth patterns:
- Nodular (frequent, presenting as single or multiple distinct nodes).
- Massive.
- Diffuse-infiltrative.
On cross-section, the tumor has a pale brown color. Sometimes the nodes acquire a distinct green hue because carcinoma cells are capable of producing bile.
Histological Structure
The microscopic appearance of HCC is diverse, but the most typical is the trabecular pattern. Tumor cells form two-, three-, or multi-layered cords (trabeculae), between which sinusoidal vessels and bile canaliculi are located.
- Cells are significantly larger than normal hepatocytes.
- Cytoplasm is abundant and eosinophilic.
- Nuclei demonstrate marked cellular atypia.
- Specific intracellular inclusions are found: Mallory bodies and $\alpha_1$-antitrypsin granules.
In addition to the trabecular pattern, glandular, acinus (pseudoglandular), and compact (solid) variants are observed. Areas of necrosis, hemorrhage, and intrahepatic cholestasis are constantly identified within the tumor tissue. With low differentiation, anaplasia increases, and giant multinucleated atypical cells appear.
Growth, Metastasis, and TNM Staging
Hepatocellular carcinoma is characterized by invasive growth with early invasion into the venous system. This frequently leads to a severe complication: portal vein thrombosis. Metastasis occurs predominantly via the hematogenous route (observed in 50% of cases), with tumor implants frequently localized within the liver itself.
Primary Tumor (T) Staging Classification:
- T1: Solitary cancer nodule less than 2 cm in diameter, without signs of blood vessel invasion.
- T2: Includes three possible scenarios: a single nodule up to 2 cm with vascular invasion; a single nodule greater than 2 cm without invasion; multiple small nodules (up to 2 cm) within a single lobe without invasion.
- T3: Single large tumor (greater than 2 cm) OR multiple invasive neoplasms in a single lobe (each $\le$ 2 cm).
- T4: Multiple cancer nodes that invade major branches of the portal or hepatic vein.