Combined hepatocellular-cholangiocarcinoma

Definition

About 5% of primary liver tumours combine hepatocellular and glandular features. There is a lack of agreement on the exact definition of a combined tumour. The WHO classification requires unequivocal elements of both hepatocellular and cholangiocarcinoma2. However, a broader definition covers a number of possible morphological and immunohistochemical combinations:

areas of definite pure hepatocellular carcinoma and areas of definite pure cholangiocarcinoma - apparent "collision tumours"4.
tumours in which there is a clear transition from hepatocellular carcinoma to cholangiocarcinoma, through zones of intermediate differentiation4.
morphological hepatocellular carcinomas with immunohistochemical evidence of biliary differentiation, principally in the form of cytokeratin expression, in areas morphologically suggestive of biliary differentiation3 or in morphologically pure hepatocellular carcinoma5.
Fibrolamellar type hepatocellular carcinoma with areas of mucin-producing pseudoglandular differentiation4.

Clinical features

In the West but not in the Far East , a background of hepatitis B or C, and/or cirrhosis is less common than in pure hepatocellular carcinoma1. Serum AFP is generally lower1.

Macroscopic appearances

Tumours vary from pale tan to green and may be haemorrhagic. The fibrosis may be apparent grossly.

Histopathology

Hepatocellular areas consist of sheets or trabeculae of cells with variable degrees of sinusoidal development. Fibrosis is lacking. Well differentiated tumour cells have abundant eosinophilic cytoplasm.
Glandular ares consist of cuboidal to low columnar cells forming glands. There is usually a prominent fibrotic or desmoplastic stroma.
Transition areas variably show hepatoid cells within a glandular architecture or within abundant fibrotic stroma. In the latter case, the hepatoid cells may form thin branching "antlers"1.

Immunohistochemistry

This is a large study of combined tumours. Information from studies with a few cases are to be found on the page "Hepatocellular carcinoma v cholangiocarcinoma v metastatic adenocarcinoma".

	pure hepatocellular carcinomas	combined tumours		pure cholangiocarcinomas
	pure hepatocellular carcinomas	hepatoid areas	glandular areas	pure cholangiocarcinomas
AE1	0/121	20/221	21/221	7/71
CK7	2/121	13/251	20/251	7/71
CK19	3/121	14/241	20/241	7/71
CK20	5/121	3/251	7/251	5/71
EMA	1/121	21/251	24/251	6/71
Cam5.2	12/121	21/211	21/211	7/71
AFP	5/121	4/171	2/171	0/71
p-CEA (canalicular)	10/121	11/251	0/251	0/71
Albumin mRNA	12/121	22/231	18/231	0/71

Prognosis

Metastases may occur more readily than in pure hepatocellular carcinoma3,5, with inferior survival1.

References

1Tickoo, S. K., S. Y. Zee, et al. (2002). "Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study." Am J Surg Pathol 26(8): 989-97.

2Ishak KG, Anthony PP, Sobin LH. Histologic typing of tumors of the Liver. World Health Organisation: International Histologic Classification of Tumours, 2nd edition, Berlin: Springer Verlag, 1994.

3Maeda, T., E. Adachi, et al. (1995). "Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features." Hum Pathol 26(9): 956-64.

4Goodman, Z. D., K. G. Ishak, et al. (1985). "Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study." Cancer 55(1): 124-35.

5Wu, P. C., J. W. Fang, et al. (1996). "Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications." Am J Pathol 149(4): 1167-75.

This page last revised 28.12.2003.