The most common tumour of the intrahepatic bile ducts is intrahepatic cholangiocarcinoma. A much rarer entity, cystadenoma/cystadenocarcinoma, may also occur.
Bile duct tumours occur within the liver and in the extrahepatic bile ducts. They are considered separately.
Cholangiocarcinoma is the second most common malignancy of the liver, making up about 1 in 6 of those diagnoses. It is very rare in Australia (incidence 0.2 per 100,000 compared with 1.7 per 100,000). It occurs in older patients and there is no sex difference.
From a more global perspective, people living in northern Laos and Thailand may be chronically infected with Opisthorchis viverrini, a liver parasite. In these populations, intrahepatic cholangiocarcinoma makes up close to 90% of liver malignancies with an incidence of 85 per 100,000. In the Far East, chronic infection with Clonorchis sinensis also conveys an increased risk of cholangiocarcinoma.
As mentioned above, the liver fluke Opisthorchis is an important pathogen in Indochina and Clonorchis in the Far East. These pathogens are through to induce malignancy through several means, including nitrosamine production, chronic inflammation and proliferation of the bile duct epithelium.
Other causes include hepatolithiasis, inflammatory bowel disease and primary sclerosing cholangitis. Historically, patients exposed to Thoratrast in the 1930s and 40s had an increased risk of intrahepatic cholangiocarcinoma.
Natural History and Patterns of Spread
The stage at which the tumour is detected is highly dependent on the location within the biliary tree. Distal lesions of smaller bile ducts may cause minimal symptoms until the tumour has progressed to a large size, whereas those arising more proximally in the central bile ducts may cause early jaundice and sepsis.
Tumours invade the liver parenchyma locally as well as the extrahepatic bile ducts. They may metastasise within the liver to set up multiple deposits. Lymphovascular invasion is frequent and lymph node metastases are common. Haematogenous spread to the lungs is most common.
Lesions located in the distal bile tree are less likely to cause jaundice and other common symptoms than those that infiltrate the main bile ducts; they are also more likely to be larger at presentation.
Most patients have upper abdominal pain and weight loss. If there is occlusion of the large bile ducts then cholangitis may occur. Occlusion of the common bile duct leads to jaundice and liver failure.
Patients may have a palpable liver (depending on the size of the tumour). Unlike hepatocellular carcinoma which has a tendency to invade the portal vein, ascites and splenomegaly are less common except when liver failure occurs.
Elevated CA 19-9 levels are usually present and AFP is not elevated (in contrast to hepatocellular carcinoma). Liver function tests are variably deranged depending on the extent of biliary obstruction and hepatic failure.
Ultrasound and CT imaging may show a heterogenous lesion with central fibrosis. The bile ducts distal to the lesion are usually dilated (in contrast to hepatocellular carcinoma which rarely invades bile ducts). These changes may also be visible on cholangiopancreatography (either MRCP or ERCP).
An uncommon variant is the intraductal papillary cholangiocarcinoma which demonstrates minimal invasion but grows along multiple bile ducts. These may appear as a grossly dilated bile duct. Cholangiography demonstrates multiple filling defects due to the papillary nature of growth.
Most tumours show a tubular architecture in the early stages, with more advanced lesions becoming less differentiated and simply showing features of adenocarcinoma. Mucin is present either on H&E staining or with immunohistochemistry. The stroma is characteristically dense and fibrous, usually more so in the central part of the tumour. Papillary growth patterns can occur less frequently with less invasion beyond the bile duct.
The trabecular pattern seen in hepatocellular carcinoma is very infrequently seen allowing for easy distinguishing between the two tumours.
The hepatocyte antigen is not expressed by cholangiocarcinoma, also allowing for differentiation of the two tumours.
RAS and TP53 mutations are most common, particularly in Western cohorts.
Staging is via TNM. The staging is different from hepatocellular carcinoma
T1: Single tumour without vascular invasion
T2a: Single tumour with vascular invasion
T2b: Multiple tumours
T3: Extrahepatic invasion or penetration through visceral peritoneum
T4: Periductal invasion / growth pattern
N1: Regional nodes involved
- R) liver regional nodes are hilar, periduodenal and peripancreatic
- L) liver regional nodes are hilar and gastrohepatic
M1: Distant metastases
Cystic Bile Duct Tumours
This rare category includes cystadenoma (benign) and cystadenocarcinoma (malignant). The benign form is seen more commonly in women. Tumours contain multiple cysts, although cystoadenocarcinoma may contain a mass lesion as well.
Prognosis is typically better than cholangiocarcinoma.