Normal histology	Histopathology	Pathological basis of disease	Clinical findings	
Tissue architecture:
•	The hepatocytes are arranged into lobules which are bounded by thin septa of collagenous supporting tissue.
•	The hepatic lobules are hexagonal in shape.
•	Terminal branches of the hepatic artery & hepatic portal vein are located at the angles of the lobule boundaries in portal tracts.
•	Blood from the portal tracts converges upon a terminal hepatic venule (centrilobular venule) of each lobule via sinusoids which pass between plates of hepatocytes.
•	The terminal hepatic venules drain to the hepatic vein. 

Cellular characteristics:
•	Hepatocytes are large polyhedral cells with large round nuclei (polypoid), dispersed chromatin & prominent nucleoli.
•	Hepatocytes store glycogen & lipids.
•	The cytoplasm is strongly eosinophilic due to numerous mitochondria with a fine basophilic granularity due to extensive free ribosomes.
•	Sinusoid lining cells: flattened condensed nuclei & poorly stained cytoplasm.
•	Kupffer cells: scattered among endothelial cells are large plump phagocytic cells with ovoid nuclei.	Abnormal histology:
•	Tumor may form a unifocal mass, multifocal nodules, or a diffusely infiltrative cancer with massive liver enlargement.
•	Occurs more often in cirrhotic livers.
•	Malignant foci are pale pink-yellow or bile-stained.

Lesions:
•	Well-differentiated: hepatocytes arranged in trabecular or acinar pseudoglandular patterns.
•	Poorly-differentiated: markedly pleomorphic giant cells; small, completely undifferentiated cells.
•	Hepatocytes may contain cytoplasmic inclusions resembling Mallory bodies. 	Incidence:
•	Constitute 90% of primary liver cancers.
•	Arises in the middle to late decades of life.
•	Male to female ratio: 3 to 4:1.
•	Strong casual relationship between hepatotropic viral infection & hepatocellular carcinoma.
•	Represents 40% of all cancers in high-incidence locales: Africa & Southeast Asia.

Causes:
•	Chronic HBV & HCV infection.
•	Cirrhosis
•	Iatrogenic carcinogens: aflatoxin B1 & Thorotrast.

Pathogenesis:
•	Integration of HBV DNA into host genome at random sites, which induces genomic host instability.
•	Possible oncogenic transformation events.	•	Hepatomegaly
•	Right upper quadrant pain
•	Weight loss
•	Elevated serum levels of -fetoprotein & 1-antitrypsin.
•	Rapid clinical progression with average survival from diagnosis being around six months.