Hepatocellular carcinoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]


The exact pathogenesis of hepatocellular carcinoma (HCC) is not fully understood. It is thought that HCC is mediated by either HBV infection, HCV infection, underlying cirrhotic liver disease, inflammation, necrosis, and fibrosis. On microscopic histopathological analysis, large polygonal tumor cells with granular eosinophilic cytoplasm or layered dense collagen bundles are characteristic findings of hepatocellular carcinoma.



Major molecular events in the pathogenesis of HCC
Genomic alterations
Epigenetic modifications
Growthfactor pathway alterations
Gene Mutations
Gene Amplification
DNA methylation micro RNA
Micro RNA
Major Signaling pathways
TERT promoter
Tyrosine kinase pathways

To review the pathogenesis of HBV infection, click here.

To review the pathogenesis of HCV infection click here.

To review the pathogenesis of hepatic cirrhosis, click here.


  • As of now there is no significant manifestation of an ordered cycle of genomic events leading to hepato-carcinogenesis. The pattern of genomic transformations exhibit huge variations often between two different HCCs from a single patient.
  • Hepatocellular carcinoma is most commonly implicated with underlying chronic hepatitis and cirrhosis, however different genes have been associated with the pathogenesis of the HCC, which are further divided into four major groups:[2][24]
  • Genes involved in the pathogenesis of hepatocellular carcinoma include:

Associated Conditions

The associated conditions with hepatocellular carcinoma are

Microscopic Pathology

  • On microscopic histopathological analysis, large polygonal tumor cells with granular eosinophilic cytoplasm or layered dense collagen bundles are characteristic findings of hepatocellular carcinoma.

Gross Pathology

On gross pathology, hepatocellular carcinoma has the following characteristic findings:[55]

  • The nodular type may be unifocal (large mass) or multifocal (when developed as a complication of cirrhosis). Tumor nodules are round to oval, grey or green (if the tumor produces bile), well circumscribed but not encapsulated.
  • In about fifty percent of the cases, the tumors are multifocal where as some authors have suggested it to be around 75 percent.
  • The portal vein is infiltrated by the poorly circumcised diffused type and the hepatic veins are rarely infiltrated.
  • Pale in relation to surrounding liver or green (due to bile secretion)

Microscopic Pathology

On microscopic histopathological analysis, hepatocellular carcinoma has the following characteristic findings:

  • Large polygonal tumor cells with:
  • Granular eosinophilic cytoplasm
  • Low NC ratio
  • Layered dense collagen bundles [56]



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