In the majority of cases, CCA is clinically silent, with symptoms only developing at an advanced stage. Once symptomatic, the clinical presentation depends on tumor location and growth pattern. Ninety percent of patients with extrahepatic ductal CCA present with painless jaundice, and 10% of patients present with cholangitis.77,78 Unilobar biliary obstruction with ipsilateral vascular encasement results in atrophy of the affected lobe and hypertrophy of the unaffected lobe.79 Upon physical examination, this “atrophy–hypertrophy complex” phenomenon presents as palpable prominence of one hepatic lobe. Intrahepatic mass-forming CCA presents with symptoms typical for hepatic masses, including abdominal pain, malaise, night sweats, and cachexia. The tumor markers CA-125 and CEA can be elevated in CCA; however, they are nonspecific and can be increased in other gastrointestinal or gynecologic malignancies or cholangiopathies. 80 CA 19-9 is the most commonly used tumor marker for CCA.81 Its sensitivity and specificity for detection of CCA in PSC are 79% and 98%, respectively, at a cutoff value of 129 U/mL. Other investigators have identified a higher cutoff of >180 U/mL to achieve this degree of specificity.82 A change from baseline of >63 U/L has a sensitivity of 90% and specificity of 98% for CCA.83 In patients without PSC, its sensitivity is 53% at a cutoff of >100 U/L and its negative predictive value is 76% to 92%.84 CA 19-9 can also be elevated in bacterial cholangitis and other gastrointestinal and gynecologic neoplasias; patients lacking the blood type Lewis antigen (10% of individuals) do not produce this tumor marker