Cholangiocarcinoma Clinical Features
Clinical Presentation
Cholangiocarcinoma presents differently based on anatomic location: intrahepatic tumors typically cause nonspecific symptoms (fever, weight loss, abdominal pain) without jaundice, while extrahepatic tumors characteristically present with obstructive jaundice. 1
Intrahepatic Cholangiocarcinoma
- Nonspecific symptoms predominate: fever, weight loss, and abdominal pain 1
- Biliary obstruction symptoms are uncommon 1
- Often detected incidentally as an isolated intrahepatic mass on imaging 1
- Early-stage disease is typically asymptomatic 1
Extrahepatic Cholangiocarcinoma
- Jaundice is the hallmark presenting symptom, followed by evidence of biliary obstruction on imaging 1
- Perihilar tumors (Klatskin tumors) may cause unilateral biliary obstruction, resulting in lobar atrophy without initial jaundice 2
- Abrupt worsening of jaundice, pain, fatigue, pruritus, or liver biochemistries should raise suspicion 3
Risk Factors
Established High-Risk Conditions
Primary sclerosing cholangitis (PSC): lifetime risk 5-15%, the most common predisposing factor in the UK 1
Age: 65% of patients are over 65 years old, making advanced age a significant independent risk factor 1, 4
Choledochal cysts: approximately 5% lifetime malignancy risk, increasing substantially with age 1, 5
Chronic intraductal gallstones 1
Caroli's disease: 7% lifetime risk 1
Liver fluke infections (Opisthorchis viverrini, Clonorchis sinensis): particularly common in Southeast Asia 1, 6
Additional Risk Factors
- Bile duct adenoma and biliary papillomatosis 1
- Hepatitis C virus infection (associated with intrahepatic cholangiocarcinoma) 1, 6
- Hepatitis B virus 6
- Smoking (particularly in association with PSC) 1
- Cirrhosis, diabetes, obesity, and non-alcoholic fatty liver disease 7, 6
- Chronic typhoid carriers (sixfold increased risk of hepatobiliary malignancy) 1
Laboratory Abnormalities
Liver Function Tests
- Hyperbilirubinemia with cholestatic enzyme pattern (elevated alkaline phosphatase, GGT) 2
- Liver function tests should be included in initial workup 1
Tumor Markers
- CA 19-9: elevated in 69% of cholangiocarcinoma cases 5
- CEA: frequently elevated but not specific for cholangiocarcinoma 1, 2
- Both markers should be measured but are not specific for cholangiocarcinoma 1, 5
Imaging Findings
Initial Imaging Approach
- Delayed-contrast CT/MRI is the recommended imaging modality for both intrahepatic and extrahepatic cholangiocarcinoma 1
- Contrast-enhanced MRI with MRCP provides superior visualization of bile duct anatomy, masses, and cyst characterization 5
Key Imaging Features
For Intrahepatic Cholangiocarcinoma:
- Characterization of primary tumor and relationship to major vessels and biliary tree 1
- Assessment for satellite lesions and distant liver metastases 1
- Evaluation of lymph node involvement 1
- Chest imaging required to assess for distant metastases 1
For Extrahepatic Cholangiocarcinoma:
- Assessment of liver, major vessel, and lymph node involvement 1
- Cholangiography (preferably MRCP) to evaluate hepatic and biliary tumor invasion 1
- MRCP is preferred as it is noninvasive 1
Anatomic Distribution
- 20-25% are intrahepatic 1
- 50-60% are perihilar tumors (including Klatskin tumors at the bifurcation) 1
- 20-25% are distal extrahepatic tumors 1
- Approximately 5% may be multifocal 1
Critical Clinical Pitfalls
- Multidisciplinary review of imaging by experienced radiologists and surgeons is mandatory to accurately stage disease and determine resectability 1
- Early surgical consultation with a multidisciplinary team is recommended as part of initial workup 1
- Laparoscopy may be performed in conjunction with surgery if no distant metastasis is found 1
- Most tumors are adenocarcinomas (>90%) and can be classified as mass-forming, periductal, or intraductal types 1
- Mortality rates from intrahepatic cholangiocarcinoma have risen steeply over the past 30 years, with prognosis remaining very poor 1