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Pathogenesis of cholangiocarcinoma
Last reviewed: 06.07.2025
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Cholangiocarcinoma often develops at the confluence of the cystic and common hepatic ducts or the right and left hepatic ducts at the porta hepatis and invades the liver. It causes complete obstruction of the extrahepatic bile ducts, accompanied by dilation of the intrahepatic ducts and enlargement of the liver. The gallbladder collapses, and the pressure in it decreases. If cholangiocarcinoma affects only one hepatic duct, biliary obstruction is incomplete and jaundice does not develop. The lobe of the liver drained by this duct undergoes atrophy; the other lobe hypertrophies.
Cholangiocarcinoma of the common bile duct is a solid nodule or plaque; it results in a ring-shaped stricture that may ulcerate. The tumor extends along the bile duct and through its wall.
Local and distant metastases are detected only in about half of cases, even at autopsy. They are found in the peritoneum, in the lymph nodes of the abdominal cavity, in the diaphragm, liver, or gall bladder. Invasion of blood vessels is rare; spread beyond the abdominal cavity is not typical of this tumor.
Histologically, cholangiocarcinoma is usually a mucin-producing adenocarcinoma composed of cuboidal or columnar epithelium. Tumor dissemination along nerve trunks is possible. Tumors in the hilum area are accompanied by sclerosis and have a well-developed fibrous stroma. Distally located tumors are nodular or papillary.
Changes at the molecular level
In cholangiocarcinoma, point mutations in the 12th codon of the K-ras oncogene have been detected. In this tumor, especially when located in the middle and lower thirds of the bile ducts, the p53 protein is expressed. In cholangiocarcinoma of the liver porta,aneuploidy (a violation of the normal number of chromosomes) is detected, combined with invasion into nerve trunks and low survival.
Cholangiocarcinoma cells contain somatostatin receptor RNA, and cell lines contain specific receptors. Somatostatin analogues inhibit cell growth. Cholangiocarcinoma can be detected by radionuclide scanning with a labeled somatostatin analogue.
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