S3370 A Case of IgG4-Related Cholangiopathy and Pancreatopathy Mimicking Cholangiocarcinoma

Introduction: IgG4-related disease (IgG4-RD) is a rare, slowly progressive fibroinflammatory disorder that can affect multiple organs. Its diagnosis is often challenging, as clinical and radiologic features may mimic other conditions. In the gastrointestinal tract, it frequently resembles cholangiocarcinoma or pancreatic cancer. We present a case of IgG4-related sclerosing cholangitis (IgG4-SC) with autoimmune pancreatitis (AIP) mimicking cholangiocarcinoma. Case Description/Methods: A 73-year-old man presented with progressive jaundice, abdominal pain, acholia, choluria, and a 40 lb weight loss over 4 months. Physical exam was notable for jaundice and epigastric tenderness. Initial workup revealed cholestatic liver enzyme elevation, and the ultrasound showed a 1.3 cm common bile duct, intrahepatic ductal dilation, and heterogeneous pancreatic texture. Following magnetic resonance cholangiopancreatography confirmed diffuse pancreatic induration and biliary dilation. Endoscopic ultrasound (EUS) revealed mass-like thickening of the common bile duct and enlarged porta hepatis nodes. Endoscopic retrograde cholangiopancreatography (ERCP) showed multiple strictures; Fine needle aspiration from the common bile duct and nodes was negative for malignancy. Despite features concerning for malignancy, including CA19-9 of 2239 U/mL, elevated IgG4 (319 mg/dL) keeping IgG4-RD high in the differential, and prednisone 40 mg daily was initiated. The patient responded clinically with significant biochemical improvement, including reduction of CA19-9. On repeat EUS, the common bile duct mass resolved, and FNA again showed no malignancy. The pancreas remained lobulated and enlarged; biopsy revealed chronic pancreatitis with lymphoplasmacytic infiltrate and up to 18 IgG4+ plasma cells/hpf, confirming IgG4-RD. Discussion: IgG4-RD is a multisystem, immune-mediated disease with nonspecific symptoms and insidious onset, often mimicking malignancy. Its presentation may resemble pancreatic cancer, PSC, or cholangiocarcinoma. Our patient had features of IgG4-SC with AIP, including pancreatic enlargement, biliary strictures, and steroid response, but also findings concerning for malignancy, such as mass-like common bile duct thickening and CA19-9 >2000. The HISORt criteria guide diagnosis based on histology, imaging, serology, other organ involvement, and response to therapy. Serum IgG4 >300 mg/dL and elevated bile IgG4 levels can help distinguish IgG4-SC from cancer. CA19-9 <85 U/mL has been proposed to support AIP over malignancy, and normalization after treatment in our case further favored a benign etiology. Recognition of overlapping features is critical to avoid misdiagnosis and unnecessary surgical intervention.