S5779 IgG4-Related Sclerosing Cholangitis Mimicking Cholangiocarcinoma: A Case Report Emphasizing the Need for Careful Differential Diagnosis Prior to Surgical Intervention

Introduction: IgG4-related sclerosing cholangitis (IgG4-SC) is a rare, immune-mediated biliary disease characterized by inflammation and fibrosis. It is rarely fatal, with survival rates exceeding 75%–90%. However, without proper application of the HISORt criteria (Histology, Imaging, Serology, Other organ involvement, Response to therapy), IgG4-SC can be difficult to distinguish from malignancies such as cholangiocarcinoma, potentially leading to unnecessary surgical intervention. Case Description/Methods: The patient is a 62-year-old man with a history of metabolic associated steatotic liver disease (MASLD), polymyalgia rheumatica, and mixed connective tissue disease. He had elevated liver chemistries on routine labs, and an MRCP showed intrahepatic bile duct dilation in the left hepatic lobe and periportal lymphadenopathy. An endoscopic ultrasound with node sampling showed atypical cells. An ERCP with biliary duct brushing at the stricture site was negative for malignancy. He underwent an IR-guided biopsy of the biliary stricture, which was inconclusive. After multidisciplinary tumor board discussion and high concern for cholangiocarcinoma, he was referred to transplant surgery for hepatic resection. He underwent resection of segments 1, 2, 3, and 4, cholecystectomy, hepaticojejunostomy, and lymph node removal. Pathology was negative for malignancy; the left lobe showed sclerosing cholangitis with periductal fibrosis and marked lymphoplasmacytic inflammation. Immunostaining of left bile duct tissue showed numerous IgG4-positive plasma cells. CA 19-9 was normal, but serum IgG4 subclass was elevated at 122 mg/dL. After starting steroids for IgG4-SC, the patient’s chemistries and IgG4 levels normalized. Discussion: Diagnosis of IgG4-SC is complex and uses the HISORt criteria, which includes histopathology, imaging, serology, organ involvement, and response to steroid therapy. Serology shows IgG levels greater than 135 mg/dl. Imaging, specifically ERCP typically shows diffuse or segmental strictures on the intrahepatic and extrahepatic bile ducts. Histopathology of liver biopsies show lymphoplasmacytic infiltrates with IgG positive plasma cells and obliteration storiform fibrosis. The primary treatment for IgG4-SC is corticosteroids. A clinical response to treatment with steroids is also part of the diagnosis of the disease. Of note, cholangiocarcinoma can show a brief improvement with steroids as well, which again points to the complexity of diagnosing this disease.