Etiology and risk factors
Hepatocellular carcinoma exhibits marked geographical variations in prevalence, which is directly related to dietary habits and endemic infections in the population. The vast majority of affected individuals (70–80%) are men.
Key factors triggering tumor development:
- Viral hepatitis: chronic infection with hepatitis B (HBV) and C (HCV) viruses, as well as prolonged carriage of the surface antigen HBsAg.
- Liver cirrhosis (LC): serves as the primary background condition. The tumor develops in 70–80% of patients with LC (predominantly the macronodular form, including those of viral etiology).
- Aflatoxins: specific metabolic products of the mold Aspergillus flavus. Infection occurs through the ingestion of contaminated grain and plant 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 dense 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 (frequently encountered, represented by one or more well-defined nodes).
- Massive.
- Diffuse-infiltrative.
On cross-section, the tumor is pale brown. Sometimes the nodes acquire a distinct green hue due to the ability of carcinoma cells to produce bile.
Histological structure
The microscopic appearance of HCC is diverse, but the trabecular architectural variant is the most typical. Tumor cells form double-, triple-, or multilayered cords (trabeculae), between which sinusoidal vessels and bile canaliculi are located.
Cytological features:
- 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 variant, glandular, acinic (pseudoglandular), and compact (solid) structural variants are also observed. Areas of necrosis, hemorrhage, and intrahepatic cholestasis are constantly detected within the tumor tissue. With low differentiation grade, anaplasia increases, and giant multinucleated atypical cells appear.
Growth, metastasis, and staging (TNM)
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 seeding frequently localized within the liver itself.
Primary tumor extent classification (T):
- T1: Solitary cancerous nodule less than 2 cm in diameter, with no evidence of blood vessel invasion.
- T2: Includes three possible scenarios: a solitary nodule up to 2 cm with vascular invasion; a solitary 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 cancerous nodules that invade major branches of the portal or hepatic vein.
Briefly: answers to topical questions
What molecular genetic mutations are characteristic of hepatocellular carcinoma?
Hepatocellular carcinoma is characterized by secondary genetic alterations arising as a result of the integration of hepatitis B virus DNA into the human genome.
- Deletions — cause the loss of chromosomal integrity in hepatocellular carcinoma.
- Translocations — movements of chromosomal segments.
General genomic instability and mutations arising against the background of aberrant hepatocyte regeneration under conditions of liver cirrhosis also contribute to tumor development.
What clinical (paraneoplastic) syndromes accompany hepatocellular carcinoma?
Hepatocellular carcinoma may be accompanied by Trousseau syndrome—phlebothrombosis in malignant diseases as a paraneoplastic syndrome. HCC can also be the cause of Budd-Chiari syndrome, which is an acute, subacute, or chronic occlusion of the hepatic veins.
To remember the main risk factors for HCC, use the "AVP" rule: Aflatoxins, Viral hepatitis, Liver cirrhosis (Cirrhosis).
Class and exam questions
Which laboratory marker indicates the development of hepatocellular carcinoma?
The primary marker is serum $\alpha$-fetoprotein. In 85% of patients, its concentration exceeds 10 ng/mL.
Why do tumor nodules in the liver sometimes have a green color?
The green color is due to the fact that hepatocellular carcinoma cells can retain their functional activity and produce bile.
How often and by what pathway does this tumor metastasize?
Metastases occur in 50% of cases. The main route of spread is hematogenous, characterized by the appearance of metastatic nodules within the liver itself and invasion into veins.
What else to study on this topic
- Cholangiocellular adenocarcinoma: morphological differences from HCC
- Rare mesenchymal liver tumors: angiosarcoma and hepatoblastoma
- Morphogenesis and types of liver cirrhosis as a precancerous condition
- Pathogenesis of progressive liver failure in tumors
- Mechanism of the carcinogenic action of aflatoxins on hepatocytes
Master the entire topic in the "Pathological Anatomy" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Hepatocellular carcinoma" and another 4,414 pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 153 video lessons on the subject
Other topics in the section "Diseases of the Liver, Biliary System, and Exocrine Pancreas"
Free video lessons: pathological anatomyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.