Intrahepatic clear cell cholangiocarcinoma

Definition

A very rare variant of intrahepatic bile duct carcinoma dominated by a clear cell morphology.

Clinical features

There is no association with cirrhosis.

Macroscopic appearances

The tumour may form a single or multiple masses.

Histopathology

The tumour shows a solid growth or papillary4 pattern. Towards the centre of the tumour, there are fibrotic areas. The tumour cells have clear vacuolated cytoplasm with distinct cell membranes. They have been variously reported as positive3 and negative1 for PAS. There may also be areas composed of cells with eosinophilic cytoplasm, forming glands. There may be an associated bile-duct adenoma like component, which may also be positive for CD56.

Immunohistochemistry

	CK7	3/3(10% to 100% of tumour cells)1, 1/12
	CK8	3/3(20% to 100% of tumour cells)1
	CK18	3/3(100% of tumour cells)1
	CK19	1/31
	CK20	0/31, 0/12
	CD56	3/3(10% to 60% of tumour cells)1
	bcl-2	1/31
	BerEP4	2/31
	pCEA	0/31, 1/12
	EMA	1/31
	p53	1/12
	Vimentin	2/31
	HepPar1	0/31
	AFP	0/31
	Mib-1	2% to 5% of cells1, >50% of cells2
	CD10	0/31
	Chromogranin	0/31
	Synaptophysin	0/31
	Ca19.9	0/31
	Muc1, 2, 5AC	0/31
	TTF-1	0/31

Ultrastructure

The vacuoles are optically empty lipid droplets. There are scanty glycogen granules.

Differential diagnosis

Bile duct adenoma, clear cell type: nuclear pleomoprhism is less marked.
Clear cell hepatocellular carcinoma: shows positivity for HepPar1, canalicular staining for CD10 and pCEA, and may be positive for AFP.
Metastatic clear cell carcinoma from:
- kidney: shows positivity for vimentin and CD10. Rarely may be positive for CD56.
- lung: positive for TTF-1.
- thyroid: positive for TTF-1.
- ovary
- GI tract
Neuroendocrine tumours are positive for CD56 but also for chromogranin and synaptophysin.

Prognosis

These tumours may show aggressively metastatic behaviour.

References

1 Haas S, Gutgemann I, Wolff M, et al. Intrahepatic clear cell cholangiocarcinoma: immunohistochemical aspects in a very rare type of cholangiocarcinoma. Am J Surg Pathol 2007; 31:902-6

2 Albores-Saavedra J, Hoang MP, Murakata LA, et al. Atypical bile duct adenoma, clear cell type: a previously undescribed tumor of the liver. Am J Surg Pathol 2001; 25:956-60

3 Falta EM, Rubin AD,Harris JA. Peripheral clear cell cholangiocarcinoma: a rare histologic variant. Am Surg 1999; 65:592-5

4 Tihan T, Blumgart L,Klimstra DS. Clear cell papillary carcinoma of the liver: an unusual variant of peripheral cholangiocarcinoma. Hum Pathol 1998; 29:196-200

This page last revised 30.6.2007.