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Liver and intrahepatic bile ducts - tumor

Hepatocellular carcinoma

Clear cell variant

Reviewers: Deepali Jain, M.D. (see Reviewers page)
Revised: 9 January 2013, last major update February 2012
Copyright: (c) 2004-2013, PathologyOutlines.com, Inc.


● 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

● Elevated serum AFP (92%), may have hypoglycemia or hypercholesterolemia
● Similar prognosis as classic hepatocellular carcinoma (World J Gastroenterol 2010;16:764)

Micro 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)

Micro images

Tumor cells with clear cytoplasm     With central focus of typical hepatocellular carcinoma

With cirrhosis and hemochromatosis   CEA and Mallory bodies   HepPar1

Renal cell carcinoma:
Tumor cells with clear cytoplasm     EMA, LeuM1 and pan-keratin

Various images

Positive stains

● Polyclonal CEA (canalicular pattern, 63%), HepPar1 (82-97%, Mod Pathol 2000;13:874)
● ISH for albumin mRNA (93%, Am J Surg Pathol 2000;24:177)
● Ubiquitin (for Mallory bodies)

Negative stains

● EMA and LeuM1 (positive in clear cell renal cell carcinoma)

Differential diagnosis

● Metastatic renal (PAX2+, EMA+), adrenal (inhibin+, MelanA+, calretinin+) or ovarian carcinoma: no classic hepatocellular carcinoma present
● Balloon cell melanoma: S100+, HMB45+, MelanA+, HepPar1-, pCEA-
● Clear cell neuroendocrine tumors: chromogranin+, synaptophysin+, MOC31+
Epithelioid angiomyolipoma: HMB45+, SMA+

End of Liver and intrahepatic bile ducts - tumor > Hepatocellular carcinoma > Clear cell variant

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