[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Liver and gallbladder](https://durgical.com/en/general-pathology/areas/liver/) › Hepatocellular carcinoma

# Hepatocellular carcinoma

- Lesion

Hepatocellular carcinoma is the main primary liver cancer; it usually grows in a liver scarred by hepatitis, alcohol or fat.

Updated Nov 12, 2026

## Key points

- Main risk factors: chronic HBV and HCV, alcohol, MASLD, hemochromatosis, A1AT deficiency, tyrosinemia, aflatoxin B1.
- Aflatoxin B1 (from Aspergillus on stored grains) causes a characteristic TP53 codon 249 mutation.
- Precursors: large cell change, small cell change (more dangerous), low- and high-grade dysplastic nodules.
- Drivers: TERT promoter (most common), CTNNB1, TP53.
- Morphology: trabeculae thicker than normal plates, loss of reticulin, sinusoids lined by CD34-positive endothelium; vascular invasion of the portal vein is typical.
- Fibrolamellar carcinoma: young adults, normal liver, large eosinophilic cells in lamellar collagen, DNAJB1-PRKACA fusion; better outcome.

## 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.

## Memory aid

HCC grows where the liver has long been rebuilt: cirrhosis is the soil, HBV, HCV, alcohol and fat are the seeds, TERT is the first sprout.

## 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.

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## Connections

## Related 8

- [Cirrhosis: morphology](https://durgical.com/en/general-pathology/cirrhosis-morphology/)
- [Hepatocellular adenoma: the molecular subtypes and their risks](https://durgical.com/en/general-pathology/hepatocellular-adenoma-the-molecular-subtypes-and-their-risks/)
- [Hepatitis B and D](https://durgical.com/en/general-pathology/hepatitis-b-and-d/)
- [Hepatitis C: why it becomes chronic, and its extrahepatic disease](https://durgical.com/en/general-pathology/hepatitis-c-why-it-becomes-chronic-and-its-extrahepatic-disease/)
- [Chemical carcinogens: initiation, promotion and the table to know](https://durgical.com/en/general-pathology/chemical-carcinogens-initiation-promotion-and-the-table-to-know/)
- [Oncogenic viruses and H. pylori: the table to know](https://durgical.com/en/general-pathology/oncogenic-viruses-and-h-pylori-the-table-to-know/)
- [Tumour markers: serum and tissue, and what each one is for](https://durgical.com/en/general-pathology/tumour-markers-serum-and-tissue-and-what-each-one-is-for/)
- [Multistep carcinogenesis: the adenoma–carcinoma sequence](https://durgical.com/en/general-pathology/multistep-carcinogenesis-the-adenoma-carcinoma-sequence/)

## Related conditions 7

- [Hepatocellular carcinoma](https://durgical.com/en/conditions/hepatocellular-carcinoma/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Viral hepatitis](https://durgical.com/en/conditions/viral-hepatitis/)
- [Hereditary hemochromatosis](https://durgical.com/en/conditions/hereditary-hemochromatosis/)
- [α1-antitrypsin deficiency](https://durgical.com/en/conditions/1-antitrypsin-deficiency/)
- [Metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD)](https://durgical.com/en/conditions/metabolic-dysfunction-associated-steatotic-liver-disease/)
- [Tyrosinaemia type I (hepatorenal)](https://durgical.com/en/conditions/tyrosinaemia-type-i/)

## Microorganisms 2

- [Hepatitis B virus](https://durgical.com/en/microbiology/hepatitis-b-virus/)
- [Hepatitis C virus](https://durgical.com/en/microbiology/hepatitis-c-virus/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://www.ncbi.nlm.nih.gov/books/NBK559177/) (StatPearls (NCBI Bookshelf), 2023); [Primary Liver Cancer Treatment (PDQ®) - NCI](https://www.cancer.gov/types/liver/hp/adult-liver-treatment-pdq) (National Cancer Institute, 2026).

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Source: https://durgical.com/en/general-pathology/hepatocellular-carcinoma/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/hepatocellular-carcinoma/