Definition

 • A malignant epithelial neoplasm of the liver derived from hepatocytes.

Epidemiology

 • Common worldwide, but with a wide geographical variation.

• Incidence figures largely parallel rates of infection with HBV, making HCC particularly common in parts of Africa and Asia.

Aetiology

 • HCC usually arises on a background of liver cirrhosis.

 • Chronic hepatitis B and haemochromatosis are particularly carcinogenic substrates.

• Dietary ingestion of aflatoxins produced by Aspergillus fungi which are also known to be potent liver carcinogens.

Carcinogenesis

• Loss of function of tumour suppressor genes, such as TP53, is common.

 • Activating mutations of oncogenes appear to be rare.

 • Hepatitis B X gene product disrupts p53 function and inhibits nucleotide excision repair.

 Presentation

• Presents late with non- specific weight loss and abdominal pain.

 • Known cirrhotics may be diagnosed following investigation of a rising serum alpha- fetoprotein (AFP) or on ultrasound surveillance.

 Macroscopy • expansile tumour mass in the liver, often with satellite deposits (Fig.1).

• tumour may have a green tinge due to the production of bile.

• Distinguishing tumour deposits from dysplastic nodules in cirrhotic livers can be difficult.

 Histopathology

 • Classical HCC is composed of epithelial cells resembling hepatocytes, which typically grow in trabeculae that resemble thickened liver cell plates. Bile production may be seen by the tumour. A very typical feature is the loss of reticulin fibres.

 • HepPar 1 and CD10 staining (to demonstrate canaliculi) can be useful to confirm a tumour as being an HCC.

• Glypican 3 staining is useful especially in poorly differentiated tumours.

 • It is increasingly apparent that many tumours have features of both HCCs and cholangiocarcinomas.

 • A number of histological variants of HCC are now recognized: clear cell, steatohepatitic, scirrhous, macrotrabecular, chromophobe, and fibro-lamellar.

 • Fibrolamellar HCC is a rare, but distinctive, variant which typically arises in young patients without background cirrhosis. Histologically, the tumour is composed of nests of very large neoplastic cells with abundant granular pink cytoplasm separated by dense fibrous bands.

 Prognosis

 • Generally very poor, with 5- year survival rates < 5%. HCCs of stem cell origin are CK19- positive and carry a worse prognosis.

• Fibrolamellar HCC has a slightly better prognosis, with 5- year survival rates ~60%.

Fig1. Liver cell cancer arising in a cirrhotic liver .