Cholangiocarcinoma Imaging

Updated: Jul 19, 2023
  • Author: Mahesh Kumar Neelala Anand, MBBS, DNB, FRCR; Chief Editor: John Karani, MBBS, FRCR  more...
  • Print

Practice Essentials

Cholangiocarcinoma is a slow-growing malignancy of the bile duct. It is the most frequent malignant tumor of the biliary tract and is the second most common primary hepatic tumor after hepatoma. Intrahepatic cholangiocarcinoma constitutes about 15% of all primary liver tumors. According to the World Health Organization classification, there are 2 subtypes of intrahepatic cholangiocarcinoma, small duct (SD) and large duct (LD), each with distinct clinicopathologic features. SD has been shown to develop more frequently in patients with chronic viral hepatitis without precursor lesions, whereas LD lesions have been found more frequently in patients with chronic bile duct disease. [1, 2, 3, 4, 5]  

On the basis of the site of origin, cholangiocarcinoma can be classified as intrahepatic (arising proximally to the second-order bile ducts, in the context of liver parenchyma), perihilar (originating between second-order bile ducts and the insertion of the cystic duct into the common bile duct), and extrahepatic or distal (below the insertion of common bile duct). [6]

Main international guidelines recommend computed tomography (CT) and/or magnetic resonance imaging (MRI) as the principal imaging modalities for the diagnosis of intrahepatic cholangiocarcinoma. [7, 8, 9]  Surgical resection is the only potentially curative therapy for intrahepatic cholangiocarcinoma, resulting in a 5-year survival rate of 15-40%; overall 5-year survival is estimated at 8-18%. [10]

The cause of bile duct cancer is unclear. Results of epidemiologic studies have implicated bacteria-induced carcinogens derived from bile salts (eg, lithocholate) as a causative factor in the pathogenesis of cholangiocarcinomas. Biliary ductal calculi occur in 20-50% of patients with cholangiocarcinoma; however, the association of gallstones with cholangiocarcinoma is less marked than with carcinoma of the gallbladder. Computed tomography (CT) and magnetic resonance imaging (MRI) remain the primary imaging tools. The most common cause of malignant biliary obstruction is pancreatic adenocarcinoma. Gallbladder carcinoma is 9 times more common than bile duct malignancy. Cholangiocarcinoma is one of the more difficult tumors to treat, and to date, surgery remains the only definitive curative treatment. [1, 2]

High-risk groups for cholangiocarcinomas include patients with the following [2] :

  • Parasitic disease of the biliary tract with either Clonorchis sinensis or Opisthorchis viverrini infestation (C sinensis infestation is the most common cause worldwide)

  • Congenital choledochal cysts

  • Inflammatory bowel disease (Risk is increased 10 times. The incidence of cholangiocarcinoma in patients with ulcerative colitis is 0.4-1.4%, with a latent period of 15 years)

  • History of other malignancy (10% of cases)

  • Previous surgery for choledochal cyst or biliary atresia

  • Gallstones (20-50% of cases, probably coincidental)

  • Papillomatosis of the bile ducts

  • Thorotrast exposure

  • Chronic typhoid carrier status

Imaging modalities

Cholangiocarcinoma presents as 3 separate morphologic subtypes: mass forming, periductal infiltrating, and intraductal growing. Each subtype has distinct imaging characteristics, as well as a variety of benign and malignant mimics, making accurate diagnosis of cholangiocarcinoma through imaging challenging. Although histopathologic examination is required to arrive at a definitive diagnosis, radiologists must be cognizant of these entities and must be able to provide reasonable differential diagnoses because these can greatly impact patient management decisions. [11]

The first-line investigation in a patient with jaundice or right upper quadrant pain is ultrasonography (US). Biliary duct dilatation is easily demonstrated with US, but US seldom localizes the tumor mass. [12, 13]

Computed tomography may reveal the tumor if the malignancy is nodular and masslike, but tumors of the diffuse sclerosing variety are difficult to detect on CT. [14, 15]

Compared with other techniques, endoscopic retrograde cholangiopancreatography (ERCP) more definitively depicts the periampullary tumor. However, with the advent of magnetic resonance cholangiopancreatography (MRCP), easy visualization of stricture-causing tumors is possible. [16] Disadvantages of MRCP include its inability to distend the duct and equivocal findings because of long segments and minimal narrowing in diffuse sclerosing tumors. Celiac axis arteriography is required to assess the vascular supply and the potential for resectability.

Magnetic resonance angiography has shown promising results, with sensitivity similar to that of conventional angiography in demonstrating the mesenteric circulation.

The role of endoscopic and intraductal US in the management of these tumors remains to be defined. Furthermore, determination of the preferred examination is complex in the presence of a predisposing condition such as primary sclerosing cholangitis (PSC). Study findings have shown the potential role of positron emission tomography (PET), which improves the depiction of cholangiocarcinoma superimposed on PSC.

Plain radiographs usually have no diagnostic value. Calcifications occur in 18% of intrahepatic cholangiocarcinomas. They may appear on plain radiographs when they are large, nodular, and located in the right upper quadrant. Extrahepatic tumors may cause an extrinsic impression, with indentation or infiltration of the stomach or duodenum on an upper gastrointestinal barium series.

Angiographic features of cholangiocarcinoma include arterial encasement, obstruction, and neovascularity and focal encasement of the portal vein. Angiographic findings alone are poor in confirming a diagnosis of cholangiocarcinoma because features may occur in both hepatocellular and pancreatic malignancies.


Cholangiocarcinoma tumors are classified as extrahepatic (87-92%) and intrahepatic (8-13%). [17]

Extrahepatic tumors are divided into proximal, middle, and distal ductal tumors. Tumors located at the confluence of the right and left hepatic ducts with the proximal common hepatic duct are called Klatskin tumors.

Intrahepatic tumors arise from the small ducts and are often diffuse and multicentric; satellite nodules occur in about 65% of patients.

Solitary well-demarcated tumors are difficult to differentiate from primary hepatocellular carcinomas (HCCs). [18] The diffuse sclerosing and scirrhous types are densely fibrotic and have annular long strictures. Compared to other tumors, they are less cellular and have relatively few well-differentiated carcinoma cells in a dense connective tissue stroma. They generally are confined to the proximal ducts.

The nodular variety is also called the papillary type. These tumors are nodular on intraluminal and extraluminal surfaces, and they form irregular strictures. They are most commonly seen in the distal duct and in the periampullary region.

Papillary tumors are friable and vascular and tend to bleed easily, causing hemobilia.

Intrahepatic tumors have a special predilection for perineural spread. Hematogenous spread to the liver, peritoneum, or lung is extremely rare.

Lymphatic spread is common and occurs in cystic and common bile duct (CBD) nodes in about 32% of extrahepatic tumors and 15% of intrahepatic tumors.

Extrahepatic tumors spread to the celiac nodes in about 16% of cases and to the peripancreatic and superior mesenteric nodes. Infiltration of adjacent liver occurs in 23% of cases, and peritoneal seeding occurs in 9%.

(See the image below.)

Bismuth classification for perihilar cholangiocarc Bismuth classification for perihilar cholangiocarcinoma. Shaded areas represent tumor location.

Criteria for assessing unresectability by imaging

Imaging is an important link in the decision-making process at multidisciplinary meetings seeking to determine resectability. Surgical colleagues depend vastly on imaging in case selection.

Major determinants of resectability include the following:

  • Extent of tumor within the biliary tree

  • Amount of hepatic parenchyma involved

  • Vascular invasion

  • Hepatic lobar atrophy

  • Metastatic disease

Determination of resectability is most challenging for patients with Klatskin tumors. About half of patients with Klatskin tumors that are determined preoperatively to be resectable are found intraoperatively to have unresectable disease.

(See the image below.)

Three-dimensional treatment planning uses CT scan Three-dimensional treatment planning uses CT scan slices to reconstruct the patient as a volume. Shown here is the display for planning external-beam radiotherapy to the cholangiocarcinoma (green structure). A biliary catheter (red tube) runs through the tumor volume and was used to deliver brachytherapy, which was given in addition to external-beam radiotherapy. Such technology has assisted greatly in the delivery of high doses to the tumor, while sparing vital normal structures, such as the kidney and spinal cord

Radiologic criteria for defining unresectability in patients with hilar tumors are shown below. [19]

Local tumor invasion

Criteria for local tumor invasion include the following:

  • Bilateral hepatic duct involvement up to secondary biliary radicles

  • Encasement or occlusion of the main portal vein

  • Unilateral tumor extension to secondary biliary radicles with contralateral portal vein or hepatic artery encasement or occlusion

  • Hepatic lobar atrophy with contralateral portal vein or hepatic artery encasement or occlusion

  • Hepatic lobar atrophy with contralateral tumor extension to secondary biliary radicles

  • Insufficient predicted hepatic reserve following extended hepatectomy

Metastatic disease

Following are characteristics of metastatic disease.

  • Lymph node metastases beyond the hepatoduodenal ligament (N2 lymph nodes) (peripancreatic, periduodenal, periportal, celiac, or superior mesenteric lymph nodes)

  • Distant metastasis (eg, lung, liver, peritoneum)


Computed Tomography

Intrahepatic cholangiocarcinoma cannot be depicted easily with cross-sectional imaging. The mass is predominantly hypoattenuating, with irregular margins, and the tumor may measure 5-20 cm at the time of presentation. The mass is rounded or oval, and images may demonstrate segmental biliary duct dilatation due to obstruction. Intravenous administration of iodinated contrast material may reveal a variable enhancement pattern. No enhancement, minimal peripheral enhancement, or central enhancement may be depicted. [20, 21]

Delayed enhancement with increasing attenuation may be seen on images in as many as 74% of patients. This pattern of enhancement may be useful in differentiating hepatocellular carcinoma (HCC) from cholangiocarcinoma. [22] Hepatocellular carcinoma shows an early peak increase in attenuation with a progressive decrease. The overlying liver capsule may be retracted when lesions are peripheral. A central scar is seen in about 30% of patients. Occasionally, peripheral cholangiocarcinomas are resectable when they do not involve the inferior vena cava or the caudate lobe.

Biliary ducts may show intense enhancement in the early phase because of associated chronic bile duct inflammation. Satellite nodules of masses are seen in 65% of patients with intrahepatic tumor. Regional metastatic lymphadenopathy may be evident in about 15% of cases involving intrahepatic tumor.

Extrahepatic disease is characterized by dilatation of intrahepatic ducts without extrahepatic duct dilatation. The mass within or surrounding the ducts is visible on CT scan in about 40% of cases. Confluence of the right and left ducts may be obliterated with the loss of sharp distinction. Infiltrating tumors, which grow along the duct, and intraluminal polypoidal tumors are difficult to detect with CT and may be defined in only 22-25% of cases. Infiltrating tumors are seen as high-attenuating lesions in 22% of cases. Exophytic tumors are larger, and with thin-section imaging, they are demonstrable in 100% of cases as low-attenuating lesions with lobulation. Morphologic changes may occur late in the disease process, with atrophy of the left lobe of the liver as compared to the right lobe. Left-sided ducts may be more dilated than right-sided ducts.

Differentiating the tumor from HCC, especially the fibrolamellar type of HCC, may be difficult because the alpha-fetoprotein (AFP) level is not increased with either tumor.

Differentiating solitary intrahepatic cholangiocarcinoma from HCC is difficult with the use of CT. The presence of satellite nodules suggests cholangiocarcinoma.


Magnetic Resonance Imaging

The intrahepatic mass is seen as a hypointense lesion relative to normal liver on T1-weighted images. T2-weighted images show predominant isointensity or slight hyperintensity relative to the liver parenchyma in about 64% of cases and marked hyperintensity in 36% of cases. These alterations in signal intensity are seen in the periphery of the tumor mass, with a hypointense area at the center of the mass. [23, 24, 25]

Pathologic correlation with magnetic resonance appearance reveals that isointense or slightly hyperintense areas on T2-weighted images are due to the abundant fibrous content of these tumors and that hyperintense areas on T2-weighted images are due to mucous secretion within the lesion. Intravenous administration of gadolinium-based contrast material results in concentric contrast enhancement. [26]

MRI features suggestive of large duct intrahepatic cholangiocarcinoma include infiltrative contour, diffuse biliary dilatation, no arterial phase hyperenhancement, and vascular invasion. In one study, when 2 or more of these features were combined, according to Park et al, sensitivity was 59.6% (28/47), and specificity was 95.7% (89/93). Overall survival was significantly shorter in patients with 2 or more MRI features. [3]

In a study by Promsorn et al of patients with intrahepatic mass-forming cholangiocarcinoma, patients with tumor size 5 cm or greater on diffusion-weighted imaging had increased intrahepatic and peritoneal metastases, and the number of deaths was significantly higher in patients with diffusion restriction less than one third of the tumor. [27]

Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). This disease has occurred in patients with moderate to end-stage renal disease after they were given a gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

Magnetic resonance imaging shows vascular encasement, focal liver atrophy, or dilatation of intrahepatic ducts in about 70% of cases. Although magnetic resonance features are well correlated with pathologic changes, these appearances are nonspecific for a definitive diagnosis.

Conventional MRI, MRCP (MR cholangiopancreatography), and magnetic resonace angiography have been applied to evaluate malignant biliary obstruction. These techniques can demonstrate the features of cholangiocarcinoma. Clinical application of the data and expertise in the use of MRI alone, compared with application and use of helical CT and endoscopic US, are continuing to evolve.

MRCP images may show a variety of artifacts and normal variants that mimic cholangiocarcinoma-like lesions. An experienced radiologist should be able to recognize such pitfalls.



Depending on tumor type, the sensitivity of ultrasonography in depicting cholangiocarcinomas is variable, but a more definitive role in demonstrating cholangiocarcinomas with US has been defined. Dilatation of the intrahepatic bile ducts is the most common abnormality among patients with ductal cholangiocarcinoma. [28, 29, 30]

Intrahepatic tumors can present as predominantly homogeneous or heterogeneous lesions, which are hyperechoic in 75% of cases. The mass may be isoechoic (about 10% of cases) or hypoechoic (15% of cases) with irregular borders and satellite nodules. Peripheral tumors are usually hypoechogenic when smaller than 3 cm, but hyperechoic when larger. Peripheral cholangiocarcinoma may be infiltrating or nodular. The infiltrating form may manifest as a simple diffuse abnormality of the liver echotexture. With the nodular type, the mass predominates and appears as a solitary mass with a distinct predilection for the right lobe.

Nearly 100% of extrahepatic tumors with polypoidal intraluminal tumors are depicted on US, whereas US reveals the primary sign of the mass in only 13% of cases involving sclerosing tumors and in only 29% of those involving exophytic masses. Klatskin tumors classically manifest as segmental dilatation and nonunion of the right and left ducts at the porta hepatis.

Newer developments include extension of US techniques via endoscopic routes. Intraportal endovascular US has been used to assess vascular invasion by bile duct tumors. The use of 3-dimensional intraductal US has been investigated for the staging of bile duct cancer. In a group of 8 patients in Japan, this technique enabled accurate assessment of tumor invasion of the arteries in 88% of patients and of the portal vein and pancreatic parenchymal invasion in 100%.

In capable hands, modern high-resolution color Doppler US is highly sensitive in depicting and characterizing cholangiocarcinoma, and in helping the clinician to determine its resectability.

In more than 90% of cases, US is sufficient for adequate imaging and staging. Diffuse tumors may be difficult to see on US. Benign tumors of the bile duct and cholangitis may simulate cholangiocarcinoma. Strictures caused by cholangitis may cause false-positive results. Sclerosing lesions may yield false-negative results.


Nuclear Imaging

Technetium-99m (99mTc) sulfur colloid and 99mTc acetanilide iminodiacetic acid analogues may be used to demonstrate cholangiocarcinoma.

Approximately 85% of the volume of intravenously injected 99mTc sulfur colloid accumulates in the liver because of hepatocyte uptake. Intrahepatic cholangiocarcinomas are seen as cold liver lesions. Appearances on the scan do not suggest a primary diagnosis of cholangiocarcinoma. Cold lesions due to benign disease, trauma, and abscess may be present. This technique helps in localizing lesions when they are larger than 2 cm.

Tc-99m diisopropyl iminodiacetic acid (DISIDA) excreted into the biliary ducts may reveal the site of biliary obstruction. After injection, the common bile duct and the cystic duct usually are visualized within 15 minutes. These ducts might not be visualized, even in healthy patients.

Positron emission tomography (PET) is a noninvasive imaging technique that can be used to assess metabolism through administration of positron-emitting radiolabeled tracers. Fluorodeoxyglucose is one such tracer that has been used in evaluating malignancies. Keiding et al used PET to improve the detection of intrahepatic cholangiocarcinoma in patients with superimposed PSC; their data are promising, although the study group comprised only 20 patients. [31] Larger prospective studies are required to further assess this technique.

In an Italian study, fluorine-18-fluorodeoxyclucose (18F-FDG) and PET or PET/CT were demonstrated to be accurate diagnostic imaging methods for primary tumor evaluation in patients with cholangiocarcinoma. These tools were found to have better diagnostic accuracy for patients with intrahepatic cholangiocarcinoma than for patients with extrahepatic cholangiocarcinoma. [32]

Focal defects on sulfur colloid scans are nonspecific. The point of obstruction revealed on the DISIDA scan may be due to tumor or to benign causes.

Appearance on sulfur colloid and iminodiacetic acid (IDA) scans is nonspecific. These techniques probably are sensitive for larger lesions and may show the level of obstruction. False-positive findings on sulfur colloid scans may occur as the result of benign tumors and other malignant tumors. False-negative findings occur when tumors are smaller than 2 cm and are central in location. False-positive findings on IDA scans may occur because of benign biliary tumors and ductal stones complicated by infection.