Page 458 - Concise Pathology for Exam Preparation ( PDFDrive )

15 Diseases of the Hepatobiliary System and Pancreas 443

Q. Write briefly on the aetiology, clinical features and morphology
of hepatocellular carcinoma (HCC)/hepatoma.
Ans. Salient Features
• HCC accounts for 80–90% of all liver cancers.
• Occurs more often in men than women; presents with abdominal pain, malaise, weight
loss and palpable/radiologically detected lesion.
• Most common in Africa and South-East Asia which show a high rate of chronic HBV
infection. HCC in these countries occurs earlier (20–40 years) and in half the cases there
is no evidence of background cirrhosis. In the Western countries, increase in the inci-
dence of HCC is attributed to hepatitis C; it manifests after 60 years and in 90% cases
shows background cirrhosis.

Predisposing Factors

• Chronic hepatitis B and C infections
• Aflatoxin toxicity (a fungal toxin present in moulds and grains and produced by the
fungus Aspergillus flavus)
• Alcoholic cirrhosis
• Primary biliary cirrhosis
• NAFLD and metabolic syndrome
• Haemochromatosis
• a-1 antitrypsin deficiency
• Wilson disease
• Anabolic steroids, thorotrast and arsenic
• Oestrogens and androgens
Note: Aflatoxin and alcohol synergize with HBV and HCV and even cigarette smoking to
increase the risk of HCC.

Pathogenesis
Presence of structural/numerical chromosomal aberrations in HCC possibly attributed to:
1. Repeated cycles of death, inflammation and active hepatocyte replication (regeneration)
in chronic hepatitis induce genomic instability in hepatocytes.
2. Point mutation or overexpression of cellular genes, ie, b-catenin and loss of heterozygos-
ity of tumour suppressor genes, ie, P53. Recent studies indicate that IL-6/JAK/STAT
pathway may have a role (IL-6 is shown to suppress hepatocytic differentiation and in-
crease their proliferation by enhancing the function of the transcription factor HNF-a).
3. Defects in DNA repair.
4. HBV-X gene may have some oncogenic potential.
Precursor lesions of HCC
(a) HCC is thought to arise from mature hepatocytes and progenitor cells called
ductular cells and oval cells.
(b) Dysplasias in the liver can be classified as small cell change (cells show high nu-
clear–cytoplasmic ratio, nuclear hyperchromasia and pleomorphism) and large cell
change (large pleomorphic cells which may show multiple nuclei). The former is
thought to be directly premalignant whereas the latter is considered directly pre-
malignant only in the presence of hepatitis B and is otherwise just identified as a
marker for increased risk of HCC.
(c) High-grade dysplastic nodules are definitely premalignant and show cytological
atypia. The premalignant potential of low-grade dysplastic nodules is uncertain
though they have been shown to be clonal. They do not show cytological or archi-
tectural atypia.

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