Liver & intrahepatic bile ducts

Hepatocellular carcinoma

Clear cell variant

Topic Completed: 1 February 2012

Minor changes: 11 June 2021

Copyright: 2002-2021,, Inc.

PubMed Search: Clear cell hepatocellular carcinoma[TI]

Deepali Jain, M.D.
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Cite this page: Jain D. Clear cell variant. website. Accessed December 4th, 2021.
Definition / general
  • Predominant appearance of neoplastic hepatocytes with abundant clear cytoplasm
  • Predominant in 5 - 16% of cases but some clear cells present in 20 - 40% of cases
  • Clear cytoplasm is due to cytoplasmic fat or glycogen
  • May need to hunt for typical hepatocellular carcinoma to rule out metastatic tumor
Clinical features
Microscopic (histologic) description
  • Trabecular, pseudoacinar, solid or mixed patterns of large number of neoplastic hepatocytes with abundant clear cytoplasm (glycogen or lipid) and round nuclei
  • May have bland nuclear features
  • May have intracytoplasmic bile (5 - 33%)
  • Usually no intratumoral fibrosis except in areas of hemorrhage and necrosis
  • Must distinguish from HCC variant with foamy histiocytes (Case Rep Gastroenterol 2010;4:286)
Microscopic (histologic) images

Contributed by Jaime A. Mejía, M.D.

Clear cell hepatocellular carcinoma

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Various images

Positive stains
Negative stains
  • EMA and LeuM1 (positive in clear cell renal cell carcinoma)
Differential diagnosis
  • Balloon cell melanoma: S100+, HMB45+, MelanA+, HepPar1-, pCEA-
  • Clear cell neuroendocrine tumors: chromogranin+, synaptophysin+, MOC31+
  • Epithelioid angiomyolipoma: HMB45+, SMA+
  • Metastatic renal (PAX2+, EMA+), adrenal (inhibin+, MelanA+, calretinin+) or ovarian carcinoma: no classic hepatocellular carcinoma present
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