Cholangiocarcinoma
Cholangiocarcinoma is a malignant tumor arising from cholangiocytes in the biliary tree. It tends to have a poor prognosis and high morbidity. It is the second most common primary hepatic tumor, with intrahepatic cholangiocarcinomas (ICCs) accounting for 10-20% of primary liver tumors.
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Epidemiology
Although overall cholangiocarcinoma is rare, there are significant regional variations in incidence with much higher rates seen in south-east Asia and the Middle East 2.
Incidence is usually in the elderly; mean age is 65 years 7. There may be a slight male predilection. In the United States, incidence had been on the rise over the last 40 years, with 2000-3000 new cases each year.
Risk factors
A number of risk factors for cholangiocarcinoma have been identified including 1-2,9:
-
primary sclerosing cholangitis (PSC)
- major risk factor in western countries
-
recurrent pyogenic cholangitis (hepatolithiasis)
- major risk factor in endemic areas
- choledocholithiasis more than cholelithiasis 10,11
- Asian liver flukes
- Opisthorchis viverrini
- Clonorchis sinensis (clonorchiasis)
-
Caroli disease / choledochal cysts
- lifetime risk of 10-15% 2
- toxins
- thorotrast
- dioxin
- polyvinyl chloride
- heavy alcohol use
- viral infection(s)
Clinical presentation
Typically the presentation is with painless jaundice.
Pathology
Macroscopically cholangiocarcinomas have a number of different growth patterns (see below), and their macroscopic appearance will reflect this. In general, they are sclerotic masses without hemorrhage or macroscopic necrosis 2.
Histologically, cholangiocarcinomas are divided into well, moderately and poorly differentiated adenocarcinomas 2. In specimens of bile ducts from patients with hepatolithiasis, biliary intraepithelial neoplasia (BilIN) is a common finding and is considered to be a precursor lesion of cholangiocarcinoma. It is typically a microscopic lesion with a flat or micropapillary dysplastic epithelium. It is synonymous with carcinoma in situ 2.
In general, the active tumor is at the periphery, with the central portions having been replaced by fibrosis, accounting for the capsular retraction which may be seen in intrahepatic tumors.
Growth patterns/types
Cholangiocarcinomas can be either intrahepatic or extrahepatic. They are also classified according to macroscopic growth pattern 2:
- intrahepatic (20% of diagnosed cases)
- extrahepatic (80%)
Mass-forming
Intrahepatic exophytic nodular (peripheral) tumors are most commonly of the mass-forming type 3. They demonstrate variable amounts of central fibrosis, usually marked.
Periductal infiltrating
Periductal infiltrating intrahepatic tumors are most common at the hilum (comprise over 70% of hilar-perihilar cholangiocarcinomas), where they are known as Klatskin tumors 3 but can also be seen in combination with mass-forming tumors within the liver. Growth along the walls of the duct may narrow or dilate the duct.
Intraductal
Intraductal tumors comprise 8-18% of resected cholangiocarcinomas 3 and a much smaller number of all cholangiocarcinomas (as most are inoperable). They are characterized by alterations in duct caliber, usually duct ectasia with or without a visible mass. If a mass is visible it may be mural or polypoid in shape 2. The duct dilatation is thought to be due to abundant mucin production. This entity is thought to be similar to the pancreatic intraductal papillary mucinous neoplasms (IPMN).
Extrahepatic/large duct
There is much confusion in the literature as to the definition of extrahepatic cholangiocarcinomas, and there is thus some overlap.
The distribution of large duct (hilar and extrahepatic) tumors 3 is as follows:
- intrahepatic large ducts: 15%
- hilum/proximal third of CBD: 50%
- middle third CBD: 17%
- distal third CBD: 18%
These tumors are most commonly infiltrating, although both exophytic (mass-forming) and polypoid (intraductal) types are identified. They have similar appearances to their intrahepatic counterparts 3.
Staging
Staging depends on the growth pattern/type of cholangiocarcinoma.
See: Cholangiocarcinoma staging
Radiographic features
Ultrasound
The appearance will vary according to the growth pattern.
Mass-forming intrahepatic: tumors will be a homogeneous mass of intermediate echogenicity with a peripheral hypoechoic halo of compressed liver parenchyma. They tend to be well delineated but irregular in outline and are often associated with capsular retraction 2 which, if present, is helpful in distinguishing cholangiocarcinomas from other hepatic tumors.
Periductal infiltrating intrahepatic: tumors typically are associated with altered caliber bile duct (narrowed or dilated) without a well-defined mass.
Intraductal: tumors are characterized by alterations in duct caliber, usually duct ectasia with or without a visible mass. If a polypoid mass is seen, it is usually hyperechoic compared to surrounding liver 2.
Contrast-enhanced ultrasound may aid with the diagnosis of cholangiocarcinoma 8:
- arterial phase
- peripheral irregular rim-like enhancement
- heterogeneous central hypoenhancement
- portal venous phase / delayed phase
- decreased echogenicity relative to background liver ("wash out")
CT
Mass-forming cholangiocarcinomas: are typically homogeneously low in attenuation on noncontrast scans, and demonstrate heterogeneous minor peripheral enhancement with gradual centripetal enhancement 2-3. The rate and extent of enhancement depend on the degree of central fibrosis 2. Again, capsular retraction may be evident. The bile ducts distal to the mass are typically dilated.
Although narrowing of the portal veins - or less frequently, hepatic veins - is seen, unlike HCC, cholangiocarcinoma only rarely forms a tumor thrombus 2.
Lobar or segmental hepatic atrophy is usually associated with vascular invasion 6.
Periductal infiltrating: intrahepatic tumors appear as regions of duct wall thickening or of the periductal parenchyma, with altered caliber of the involved duct (usually narrowed). These are most common at the hepatic hilum. They tend to be longer than benign strictures (i.e. approximately 20 mm in length) and show contrast enhancement. There is usually some proximal (i.e. peripheral) dilatation of the biliary tree.
Intraductal tumors: are characterized by alterations in duct caliber, usually duct ectasia with or without a visible mass. If a polypoid mass is seen it is hypoattenuating on pre-contrast imaging and demonstrates enhancement 2.
MRI/MRCP
MRI is the imaging modality of choice, as it can best visualize all three the tumor itself, the biliary ducts and the blood vessels, all of which are essential for determining resectability (see below). Appearances on MR are similar to those described above for CT, except that MR is more sensitive to contrast enhancement 3 and bile duct visualization.
- DWI/ADC: a peripherally hyperintense "target" appearance on DWI favours cholangiocarcinoma over hepatocellular carcinoma
Direct cholangiography
Direct cholangiography is a blanket term for any imaging obtained with intra-biliary tree contrast and includes:
- PTC
- ERCP
- CT IVC
- MRCP
All these modalities not only allow evaluation of the biliary tree but are invaluable in planning treatment as assessing for resectability.
Radiology report
The following reporting checklist pertains to hilar/perihilar cholangiocarcinoma, as it is anatomically close to the large bile ducts and blood vessels, crucial to the determination of resectability:
- bile ducts (see Bismuth-Corlette classification)
- tumor confined to the common or hepatic bile duct?
- extension to right or left hepatic duct or both?
- does tumor involve second-order radicles and on which side?
- portal vein: does tumor abut/encase main/right/left portal vein and to what extent?
- hepatic artery
- common hepatic artery/hepatic artery proper involved and to what extent?
- right/left hepatic artery involved and to what extent?
- variant arterial anatomy, if any
- lymph nodes: enlarged regional (N1) or distant (N2) lymph nodes?
- assess for distal metastases
Treatment and prognosis
The most important factor in prognosis is whether or not the tumor can be resected. Unfortunately, when discovered, most cases are too advanced for curative resection. Even with resection, the prognosis is poor with a five-year survival of only 10-44% 4, with prognosis favouring extrahepatic tumors (around 30% five-year survival vs. 15% for intrahepatic tumors).
The pattern of metastatic spread includes 1:
- intrahepatic vascular involvement with numerous local metastases
- regional lymph nodes (50% at autopsy)
- haematogenous (50% at autopsy)
- lungs
- bones, especially vertebrae
- adrenals
- brain
Surgical resectability
An increase in margin-negative resection rates and survival can be achieved by resection of the ipsilateral hepatic lobe. In the interest of leaving the patient with a large enough contralateral lobe, portal vein branch embolization of the lobe intended for resection 4-6 before surgery can induce hypertrophy of the contralateral lobe. It should be noted that when attempting resection, tumor size in itself is unimportant.
A hilar-perihilar tumor is considered unresectable in the following cases 12:
- Bismuth type IV: bilateral secondary biliary radicle involvement
- main portal vein encasement/occlusion
- atrophy of a liver lobe with contralateral portal vein or hepatic artery encasement
- atrophy of a liver lobe with contralateral secondary biliary radicle involvement
- involvement of both hepatic arteries
Differential diagnosis
Differential diagnosis depends on whether the tumor is intrahepatic or extrahepatic and on the growth pattern.
For an intrahepatic mass-forming cholangiocarcinoma consider:
-
liver metastases
- central necrosis (high T2 signal) is more common
-
hepatocellular carcinoma (HCC)
- tumor thrombus more common
- capsular retraction uncommon
- may appear very similar
- other primary liver tumors
- hepatic abscess
For a periductal infiltrating cholangiocarcinoma consider:
-
benign stricture
- usually short-segment
- regular margin, but there are exceptions to this
- symmetric narrowing
- no ductal enhancement
- no lymph node enlargement
- no periductal soft-tissue mass
- periportal lymphangitic metastasis 2
For an intraductal cholangiocarcinoma consider:
- intraductal invasion by hepatocellular carcinoma (HCC)
- extraductal mass
-
hepatolithiasis
- no enhancement
- higher attenuation
-
biliary cystadenoma or cystadenocarcinoma
- intratumoural cysts do not communicate with the biliary tree
- benign stricture
Related Radiopaedia articles
Hepatobiliary pathology
- depositional disorders
- infection and inflammation
- liver abscess
- hepatic hydatid infection
- cirrhosis
- hepatitis
- cholecystitis
- cholangitis
- malignancy
- liver and intrahepatic bile duct tumors
- benign epithelial tumors
- hepatocellular hyperplasia
- hepatocellular adenoma
- hepatic/biliary cysts
- benign nonepithelial tumors
- primary malignant epithelial tumors
- hepatocellular carcinoma
- hepatocellular carcinoma variants
- cholangiocarcinoma
- biliary cystadenocarcinoma
- combined hepatocellular and cholangiocarcinoma
- hepatoblastoma
- undifferentiated carcinoma
- primary malignant nonepithelial tumors
- hematopoietic and lymphoid tumors
- primary hepatic lymphoma
- hepatic myeloid sarcoma (hepatic chloroma)
- secondary tumors
- miscellaneous
- adrenal rest tumors
- hepatic carcinosarcoma
- hepatic fibroma
- hepatic Kaposi sarcoma
- hepatic lipoma
- hepatic mesenchymal hamartoma
- hepatic myxoma
- hepatic rhabdoid tumor
- hepatic solitary fibrous tumor
- hepatic teratoma
- hepatic yolk sac tumor
- inflammatory myofibroblastic tumor (inflammatory pseudotumor)
- nodular regenerative hyperplasia
- pancreatic rest tumors
- primary hepatic carcinoid
- benign epithelial tumors
- extrahepatic bile duct tumors
- extrahepatic bile duct cholangiocarcinoma
- hilar cholangiocarcinoma (Klatskin tumor)
- extrahepatic bile duct cholangiocarcinoma
- liver and intrahepatic bile duct tumors
- metabolic
- trauma
- vascular
- portal venous gas
- portal hypertension
- portal vein thrombosis
- arterioportal shunts
- hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
- Budd-Chiari syndrome
- passive hepatic congestion
- hepatic veno-occlusive disease
- hepatic infarction
- peliosis hepatis
- hepatic venous malformations (hemangiomas)