S3247 Caught Yellow-Handed: An Unusual Case of a Klatskin Tumor in a Young Adult

Introduction: Perihilar cholangiocarcinoma (pCCA), or Klatskin tumor, is a rare malignancy arising at the hepatic duct confluence. It typically affects older adults with risk factors such as primary sclerosing cholangitis. Symptoms are often nonspecific, contributing to delayed diagnosis. We present a rare case of aggressive, widely metastatic pCCA in a previously healthy 37-year-old man. Case Description/Methods: A 37-year-old man presented with 2 weeks of painless jaundice, dark urine, and acholic stools. He reported a prior 2-month history of cough, dyspnea, and fatigue, initially treated as pneumonia with doxycycline and prednisone. Jaundice developed shortly thereafter, raising concern for drug-induced liver injury. He later self-administered over-the-counter “liver detox” supplements. Exam revealed jaundice and hepatomegaly. Labs showed total bilirubin 15.0 mg/dL, ALT 361 U/L, ALP 796 U/L, and CA 19-9 >10,000 U/mL. Hepatitis serologies were negative. Imaging revealed a 4.5 cm left hepatic mass with intrahepatic biliary ductal dilation and suspicious pulmonary and osseous lesions. Endoscopic retrograde cholangiopancreatography (ERCP) showed a hilar stricture with poor left ductal filling. Endoscopic ultrasound-guided biopsy confirmed pCCA. Immunostaining was positive for CK7, CK19, and MOC31. Molecular profiling revealed a KRAS G12V mutation and CDKN2A loss. PD-L1 expression was <1%, and tumor mutational burden was low. Despite supportive measures, the patient rapidly declined and later passed due to respiratory failure. Discussion: This case illustrates an atypically aggressive presentation of pCCA in a young adult without known risk factors. Metastatic spread to the lungs and bones is rare at initial diagnosis, and respiratory failure is an uncommon terminal event. Early imaging and specialist referral are essential when evaluating cholestatic liver enzyme elevations in patients with systemic symptoms, regardless of age. This case highlights the need for vigilance in the differential diagnosis of painless jaundice, even in young adults.