S3504 IgG4-Related Sclerosing Cholangitis Masquerading as Cholangiocarcinoma: A Diagnostic Challenge

Introduction: IgG4-related sclerosing cholangitis (IgG4-SC) is a rare autoimmune biliary disease linked to IgG4-related disease (IgG4-RD), often presenting with obstructive jaundice. While most cases are associated with autoimmune pancreatitis, isolated IgG4-SC lacks pancreatic involvement and mimics conditions like PSC or cholangiocarcinoma, complicating diagnosis. We report a case initially misdiagnosed as cholangiocarcinoma, later correctly identified as isolated IgG4-SC, preventing unnecessary treatment. Case Description/Methods: An 80-year-old man presented with a 1-week history of jaundice and fatigue associated with pale stools and dark urine. He also reported unintentional weight loss of approximately 20 kg and loss of appetite over the past year. Labs showed cholestatic liver enzyme elevation and high CA19-9 (920 U/mL). Imaging revealed intrahepatic bile duct strictures with abrupt obstruction at the liver hilum without extrahepatic involvement. Endoscopic retrograde cholangiopancreatography (ERCP) showed malignant-appearing strictures in the left and right intrahepatic branches, biliary stenting led to liver function test improvement, but cytology was inconclusive. Initial diagnosis was cholangiocarcinoma and the patient was deemed ineligible for surgical resection given his locally advanced disease. He was planned for chemotherapy with possible radiation therapy. However, PET/computed tomography was negative for FDG-avid lesions, prompting further work-up. Elevated serum IgG4 (1011 mg/dL) and liver biopsy showed storiform fibrosis and IgG4-positive plasma cells confirmed IgG4-related sclerosing cholangitis. He improved with corticosteroid therapy. Discussion: IgG4-SC is a rare fibroinflammatory disease that mimics cholangiocarcinoma and primary sclerosing cholangitis, making diagnosis challenging—especially in isolated cases without pancreatic involvement. Most IgG4-SC cases are associated with autoimmune pancreatitis, with isolated disease accounting for less than 10%. Diagnostic criteria include the HISORt and Japan Biliary Association guidelines, incorporating imaging, serology, histology, and steroid response. Elevated serum IgG4 supports the diagnosis but lacks specificity. ERCP with IDUS, POCS, and bile duct biopsy are key to distinguishing IgG4-SC from malignancy. Histology shows IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Corticosteroids are the mainstay of treatment, often yielding rapid remission. Our case underscores the importance of early recognition and steroid initiation to avoid misdiagnosis and unnecessary oncologic therapy.