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Home > E. Pathology by systems > Digestive system > Liver and pancreatobiliary system > cholangiocarcinoma


Tuesday 28 August 2007

cholangiocarcinomas; bile duct carcinoma; biliary duct adenocarcinoma


Definition: Cholangiocarcinoma is an adenocarcinoma arising from intrahepatic bile duct epithelial cells.

Cholangiocarcinoma is an adenocarcinoma. Cells have pleomorphic round nuclei, and eosinophilic cytoplasm. It is positive for markers of adenocarcinoma such as MOC-31, and Ber-EP4 and positive for markers suggestive of cholangiocarcinoma: CK7 and CK19.


- Whipple gross specimen common biliary duct adenocarcinoma

Cholangiocarcinoma has a worldwide distribution which accounts for about 10-15% of all cases of primary hepatobiliary malignancy.


- intrahepatic cholangiocarcinoma
- extrahepatic cholangiocarcinoma

Differential diagnosis

- intraductal lesions without high grade dysplasia

  • adenomatosis
  • biliary papillomatosis
  • intraductal adenoma


- Extrahepatic cholangiocarcinoma from in an Intraductal Papillary Neoplasms of the Bile Duct (IPNB / IPNBs )

See also

- bile duct tumors

Risk factors

Although, in the majority of cases, no aetiological factor can be identified, a number of risk factors have been shown to be important in the development of cholangiocarcinoma; most of these factors share long standing inflammation and chronic injury of the biliary epithelium.

Primary sclerosing cholangitis is an uncommon disease, characterized by stricturing, fibrosis and inflammation of the biliary tree which is closely associated with chronic inflammatory bowel disease, particularly ulcerative colitis. It is commonly associated with cholangiocarcinoma and between 10-20% of patients with primary sclerosing cholangitis will go on to develop a cholangiocarcinoma. T

he rare congenital fibropolycystic diseases of the biliary system are associated with increased risks of cholangiocarcinoma, particularly choledochal cysts and Caroli’s disease.

Choledochal cysts are associated with a 10% overall incidence of cholangiocarcinoma: there is a 1% cumulative risk which plateaus after 15-20 years. However, the risk is diminished in children who present under the age of 10 years where the over all risk is 0.7%. This compares with the 14% over all risk of patients presenting over the age of 20 years.

In the Far East, other forms of chronic inflammation associated with cholangiocarcinoma include infestation with liver flukes. Clonorchis sinensis and Opisthorchis viverinni.

Cholangiocarcinoma is also rarely seen in association with cirrhosis and has been weakly linked to hepatitis C infection.


- intrahepatic cholangiocarcinoma
- extrahepatic cholangiocarcinoma

Main features

- Well-differentiated adenocarcinoma forming glandular (tubular) and duct-like structures associated with prominent interstitial fibrosis is common.
- The tumor cells usually are medium-sized to small and cuboidal, with oval to round nuclei without prominent nucleoli, and moderate to scanty eosinophilic to clear cytoplasm.
- Papillary, cribriform, and solid growth patterns may occur. In rare instances, focal or diffuse papillomatosis without significant parenchymal infiltration has been described.
- Proteinaceous secretory material (not bile) may be present within the glandular lumen.
- Variants include the following:

  • Poorly differentiated type, with pleomorphic cells closely packed without associated fibrosis.
  • Signet-ring type, resembling that seen in gastric carcinomas.
  • Mucinous type, with extensive extracellular mucin containing scattered tumor cells.
  • Adenosquamous type, with variable degrees of squamous differentiation.
  • Spindle cell type, with sarcomatous changes.
  • Mucoepidermoid and squamous cell types, exhibiting mucous secretion as well as squamous differentiation.

- Patchy lymphocytic infiltration may be seen in fibrotic regions, these inflammatory cells not oriented towards ducts.
- Microcalcifications may occur.
- Tumor originating within the large and major ducts tends to have a glandular growth pattern consisting of columnar cells sometimes containing abundant mucin.
- Large duct tumors may infiltrate along the submucosa and wall, with minimal parenchymal invasion. There may be prominent atrophy of non-tumor liver distal to the major duct involved.
- Neoplastic cells merge into the sinusoids, not trabecular cords, of non-tumor liver at the border of the lesion. Significant extension of this sinusoidal growth pattern, or compression of non-tumor liver, is infrequent.
- Hilar duct lesions may contain tumor cells that can be single or form small clusters and glands admixed in a prominent fibrous stroma, and are sometimes difficult to differentiate from reactive duct proliferation. Perineural invasion is common and a very helpful diagnostic feature.
- Hilar lesions are often associated with prominent intrahepatic cholestasis and changes of extrahepatic biliary tract obstruction in the distal non-tumor liver.
- Bile may be seen at the edge of the tumor adjacent to trapped hepatocytes; however, the tumor cells themselves do not synthesize or secrete bile.
- The non-tumor liver may show nonspecific changes or may be involved in an underlying liver disease associated with an increased incidence of cholangiocarcinoma (e.g., primary sclerosing cholangitis, recurrent pyogenic cholangiohepatitis with Clonorchis sinensis infection).


- Chapman RW. Risk factors for biliary tract carcinogenesis. Ann Oncol. 1999;10 Suppl 4:308-11. PMID: 10436847