Madalena Pimenta, MD

Cholangiocarcinoma is an adenocarcinoma that arises from the intra- and extrahepatic bile duct epithelium. It is a relatively common liver cancer, the second most prevalent after hepatocellular carcinoma.

The exact cause of cholangiocarcinoma is unknown and most cases occur sporadically. Some biliary diseases are known to be risk factors. These include intrahepatic stone disease, choledochal cyst, Caroli disease, and primary sclerosing cholangitis.

 Cholangiocarcinomas tend to grow slowly and to infiltrate duct walls, dissecting along tissue planes. Tumors may extend locally into the liver, porta hepatis, and regional lymph nodes of the celiac and pancreaticoduodenal chains.

Cholangiocarcinoma may arise at any portion of the bile duct epithelium, from terminal ductules (canals of Hering) to the ampulla of Vater, as well as the peribiliary glands. Intrahepatic cholangiocarcinoma is subdivided into peripheral or hilar disease (Klatskin tumor), on the basis of its site of origin.

Perihilar tumors occur where the right and left hepatic ducts bifurcate, and are the most common type of cholangiocarcinoma. Intrahepatic tumors (located peripheral to the secondary confluence) are the least common. Extrahepatic tumors are located from the upper border of the pancreas to the ampulla. The tumor is located distal to the cystic duct takeoff, leading to augmentation of the gallbladder (Figure 1).

Three types of cholangiocarcinoma have traditionally been regarded as distinct disease entities clinically, therapeutically, and radiologically. This classification scheme is controversial, though.

The Liver Cancer Group of Japan proposed a classification scheme for primary liver cancer that divided intrahepatic cholangiocarcinoma into three types based on macroscopic appearance: exophytic or mass-forming, periductal infiltrating, and intraductal or polypoid.

 Most-but not all-intrahepatic peripheral cholangiocarcinomas are mass-forming.

Periductal infiltrating growth is typically observed in the hilar and extrahepatic areas. Intraductal intrahepatic cholangiocarcinoma is morphologically similar to papillary cholangiocarcinoma of the large bile duct in the hepatic hilum and extrahepatic area. This type of malignancy is characterized by superficial mucosal spreading and is associated with a better prognosis than other types of cholangiocarcinoma.

Many different multislice CT protocols can be used in the diagnosis of cholangiocarcinoma. We use a combination of oral contrast (750 to 1000 mL) and intravenous contrast (120 to 150 mL, delivered at 3 to 5 mL/sec). Imaging is performed at 120 kVp with a tube current of 200 to 250 mA in the late arterial phase after IV contrast administration (40 sec), the venous phase (60 to 70 sec), and the parenchymal phase (five to 10 min). Collimation is 1.25 to 2.5 mm for arterial imaging, and 2.5 to 5 mm when visualizing venous anatomy.

Contrast-enhanced CT can detect intrahepatic bile duct tumors, the level of biliary obstruction, and the presence of liver atrophy with good sensitivity. CT may also visualize nodal metastasis.

 A triple-phase spiral CT scan will detect all cholangiocarcinomas that are greater than 1 cm in diameter.

Dynamic CT can establish resectability in only about 60% of patients. Dynamic CT may still, however, provide more information on resectability than MRI. 

 Both imaging methods are similarly capable of showing tumor enhancement and biliary ductal dilatation, though the relationship of the tumor to vessels and surrounding organs is evaluated more easily using CT.

The appearance of cholangiocarcinoma on MSCT depends on biological behavior. This varies according to the tumor's location, size at the time of diagnosis, and macroscopic growth type, as described above.

Mass-forming cholangiocarcinoma. This kind of macroscopic growth is the most common among intrahepatic cholangiocarcinomas. Masses are generally large, lobulated, and well-defined, but they can also be irregular. The mass is typically hypodense on MSCT with stippled or punctate hyperattenuating foci within the tumor (Figure 2).

Dynamic MSCT of mass-forming cholangiocarcinomas shows rim-like or thick, incomplete peripheral contrast enhancement at the early parts of both arterial and portal venous phases with progressive and concentric filling of contrast at the delayed phase.

 This delayed enhancement is due to the fibrotic component within this type of cholangiocarcinoma causing slow diffusion into the tumor's interstitial spaces (Figure 3).

Secondary signs that are often associated with cholangiocarcinoma include focal dilatation and thickening of the peripheral intrahepatic bile ducts around the tumor, capsular retraction, segmental or lobar atrophy associated with the tumor, vascular encasement, and central scars (Figure 2).

 Peripheral cholangiocarcinomas are usually large at the time of diagnosis because they are rarely symptomatic early in their course.

It is important to note that the pattern of peripheral enhancement and delayed filling is not specific for cholangiocarcinoma. A similar enhancement pattern can be seen with metastatic liver tumors.

Cholangiocarcinomas in hilar and extrahepatic regions that grow in a similar way to peripheral cholangiocarcinoma are referred to as exophytic hilar cholangiocarcinoma. These present as large, low-attenuating masses with peripheral rim enhancement. This type of macroscopic growth is uncommon in the hilar area.

Infiltrative cholangiocarcinoma. This type of cholangiocarcinoma exhibits infiltrative growth along the ductal wall. Infiltrative cholangiocarcinoma is usually an undifferentiated or poorly differentiated ductal adenocarcinoma.

It is the most common type of hilar and extrahepatic cholangiocarcinoma. This type of growth is uncommon in the intrahepatic area, but it is not unheard of. Cases of periductal infiltrating intrahepatic cholangiocarcinoma can be found peripheral to the secondary confluence. These are very small fibrotic tumors that cause segmental bile duct dilatation and liver parenchyma atrophy.

Infiltrative cholangiocarcinoma produces a focal stricture of the bile duct on MSCT. Ill-defined focal wall thickening is observed without an identifiable mass. Dynamic MSCT shows rim-like or thick tumor wall enhancement. Early enhancement may be seen, followed by progressive and concentric contrast filling at the later phase, sometimes 15 minutes after injection.

Bile duct dilation that suddenly disappears is a frequent finding. The lumen is replaced by a small focal stricture encircled by a high-attenuation mass. The duct distal to the mass regains its normal diameter. These masses are small and images should be scrutinized carefully (Figure 4).

Although hilar and extrahepatic cholangiocarcinoma are clinically and radiologically similar, hilar cholangiocarcinoma has been subsumed under the heading of intrahepatic cholangiocarcinoma. Hilar cholangiocarcinoma (Klatskin tumor) arises from the hepatic duct or near its bifurcation. It is in a critical location, causing early jaundice or cholangitis. This tumor is usually very small when it is diagnosed.

In extrahepatic cholangiocarcinoma, the bile ducts proximal to the tumor will be dilated. The severity of this dilation depends on the degree and duration of the obstruction. The tumor's location distal to the cystic duct takeoff causes the gallbladder to be augmented (Courvoisier sign), as mentioned earlier.

Intraductal intrahepatic/papillary cholangiocarcinoma. This intraluminal polypoid mass, infrequently found in both the intra- and extrahepatic ducts, causes a filling defect on cholangiography.

 MSCT reveals an intraductal, soft-tissue mass that is hypointense relative to hepatic parenchyma within the dilated bile duct.

 Extensive superficial spreading, resulting in diffuse involvement, is common. The true extent of the tumor is consequently difficult to determine.

CT shows papillary tumor and bile duct stones as high- or low-attenuation soft tissue masses. Precontrast CT can be used to differentiate between the two. A tumor attached to the wall of the bile duct will be enhanced, whereas detached tumor fragments and stone will not.

In conclusion, imaging has a key role to play in the diagnosis of cholangiocarcinoma and treatment monitoring. A variety of radiologic manifestations may be observed owing to the malignancy's diverse growth patterns, histologic types, and locations. Cholangiocarcinoma is associated with some pathological conditions that should therefore be monitored closely so that cholangiocarcinoma can be promptly diagnosed. A variety of diseases, including liver metastases, may resemble cholangiocarcinoma, making differential diagnosis particularly important.

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Cholangiocarcinoma is an adenocarcinoma that arises from the intra- and extrahepatic bile duct epithelium.

Madalena Pimenta, MD

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