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Liver and intrahepatic bile ducts - tumor

Other malignancies

Combined hepatocellular carcinoma - cholangiocarcinoma

Reviewers: Nat Pernick, M.D. (see Reviewers page)
Revised: 5 January 2013, last major update August 2012
Copyright: (c) 2004-2013, PathologyOutlines.com, Inc.


● Tumor with unequivocal, intimately mixed elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (ChC) (WHO)
● Must distinguish from separate HCC and ChC arising in same liver, which are either separated or intermixed (“collision tumor”)
● Includes "transitional" types with primarily features intermediate between hepatocellular carcinoma and cholangiocarcinoma (Am J Surg Pathol 2002;26:989)
● < 5% of primary hepatic carcinomas
● Aggressive, with 5 year survival of 18% overall and 24% after resection (worse than pure hepatocellular carcinoma or cholangiocarcinoma, Clin Med Pathol 2008;1:43)
● Poor prognosis and high rate of tumor recurrence after liver transplantation (Liver Transpl 2011;17:934)
Laboratory: serum alpha-fetoprotein usually normal, usually negative for Hepatitis B and C serum markers

Case reports

● 53 year old man with Hepatitis B and weight loss (Cases J 2009;2:6789)

Gross description

● 3-16 cm, solitary or multiple tumor nodules
● Pale-tan to bile stained, variably fibrotic and hemorrhagic or necrotic

Gross images

Poorly circumscribed mass with extensive necrosis

Micro description

● Intimate admixture of tumor cells with features of unequivocal hepatocellular carcinoma and cholangiocarcinoma (cuboidal / columnar cells with amphophilic cytoplasm, inconspicuous nucleoli, gland formation and mucin)
● May have sarcomatoid component or cirrhosis
● Transitional tumors have no distinct hepatocellular or cholangiocarcinoma-like areas; usually no cirrhosis; areas with “antler-like” morphology in 33% (irregular thin branching columns of hepatoid cells separated by broad desmoplastic stromal bands), rarely papillary

Micro images

Various images

Left: H&E; right: CK7

Positive stains

● Albumin mRNA by ISH (96%); cytokeratin, EMA and mucicarmine in glandular areas

Differential diagnosis

Hepatocellular carcinoma with pseudoglandular spaces but not true glands
● Undifferentiated carcinoma: features suggestive but not diagnostic of both tumor types, may represent metastatic diseases

End of Liver and intrahepatic bile ducts - tumor > Other malignancies > Combined hepatocellular carcinoma - cholangiocarcinoma

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