Hepatocellular carcinoma
- Lesion
Hepatocellular carcinoma is the main primary liver cancer; it usually grows in a liver scarred by hepatitis, alcohol or fat.
What it is
Hepatocellular carcinoma (HCC) is a malignant tumour of hepatocytes and one of the leading causes of cancer death worldwide. Most arise in cirrhosis from chronic hepatitis B or C, alcohol or MASLD; HBV and aflatoxin can cause HCC without cirrhosis. Cancer develops stepwise from dysplastic foci and nodules, with driver mutations in TERT, CTNNB1 and TP53. Fibrolamellar carcinoma is a distinct variant of young people with no underlying liver disease.
Structure
- Gross: a single large mass, multiple nodules, or diffuse infiltration; soft, pale or bile-stained green; tumour thrombus in the portal vein.
- Micro: well to poorly differentiated hepatocyte-like cells in thick trabeculae, pseudoglands with bile, or sheets; bile production proves hepatocellular origin.
- Fibrolamellar: large polygonal oncocytic cells with prominent nucleoli and pale bodies, separated by parallel bands of collagen.
Step by step
- Chronic injury and regeneration in cirrhosis expose hepatocytes to inflammation and oxidative stress.
- Telomere shortening and TERT promoter mutation allow unlimited replication.
- Clones with growth advantage form dysplastic foci (small cell change) and dysplastic nodules.
- CTNNB1, TP53 and other mutations accumulate; nodules gain unpaired arteries.
- Invasion of stroma and portal vein branches marks carcinoma; intrahepatic spread follows.
- Metastasis to lungs, bones and lymph nodes occurs late.
Classic hepatocellular carcinoma vs fibrolamellar carcinoma
| Feature | Classic HCC | Fibrolamellar carcinoma |
|---|---|---|
| Patients | Older adults, more men | Adolescents and young adults, both sexes |
| Background liver | Cirrhosis or chronic disease in most | Normal |
| AFP | Often raised in advanced disease | Usually normal |
| Molecular hallmark | TERT, CTNNB1, TP53 mutations | DNAJB1-PRKACA fusion |
| Outlook | Poor unless found early | Better, often resectable |
Markers
- Arginase-1
- HepPar-1
- Glypican-3
- Serum alpha-fetoprotein
- CD34 (diffuse sinusoidal)
Clinical notes
- Often silent until advanced: pain, weight loss, sudden decompensation of cirrhosis.
- Surveillance of people with cirrhosis (and some HBV carriers) by ultrasound detects early tumours; prevention by HBV vaccination and HCV cure.
Test yourself
Think of the answer, then tap the question to see it.
Which mycotoxin causes HCC with a specific TP53 mutation?
Aflatoxin B1, from Aspergillus contaminating stored grains and nuts, which causes a codon 249 TP53 mutation.
Which premalignant hepatocyte change carries the higher risk: large cell change or small cell change?
Small cell change, which is more closely linked to progression to carcinoma.
What gene fusion defines fibrolamellar carcinoma?
DNAJB1-PRKACA, from a deletion on chromosome 19.
Which vessel does HCC typically invade?
The portal vein, forming tumour thrombus; hepatic vein invasion also occurs.
Connections
Microorganisms2
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hepatocellular Carcinoma (StatPearls (NCBI Bookshelf), 2023); Primary Liver Cancer Treatment (PDQ®) - NCI (National Cancer Institute, 2026).
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Representative model, for educational purposes only.