Gastroduodenal Signet-Ring Cell Carcinoma Presenting as IgG4-Related Sclerosing Cholangitis: Not Everything That Glitters Is Gold

Abstract

Introduction: IgG4-related sclerosing cholangitis (IgG4-SC) is a new entity of cholangiopathy and IgG4-related disease, described as dense infiltration of IgG4-positive plasma cells and extensive fibrosis in the bile duct wall. We presented a case of signet-ring cell carcinoma of the duodenum with initial presentation of IgG4-SC. A 75-year-old male presented with gradual-onset painless jaundice and right upper quadrant pain for 3 weeks. He was afebrile, with mild right upper quadrant tenderness, without Murphy’s sign. Labs were pertinent for AST of 142 U/L, ALT of 142 U/L, alkaline phosphatase of 461 U/L, and direct/total bilirubin of 3.5/9.3 mg/dL. MRCP showed intrahepatic biliary dilatation with right hepatic duct strictures and non-visualization of the proximal common hepatic and central common bile ducts, replaced with vague enhancement. Further investigations were significant for negative CA 19-9, CA-125 of 125 U/mL (0-30), and normal gamma immunoglobulin subclasses. EUS showed marked thickening of the extrahepatic bile duct up to the hilum without definite mass lesion. He underwent ERCP for biliary sphincterotomy and biliary stenting. Biopsies of the ampulla and the bile duct showed frequent IgG4-positive plasma cells (30 cells/highpower field). Steroid was initiated for possible IgG4-SC. At 10 days after the index ERCP, he had worsening nausea and vomiting without worsening labs. ERCP for biliary stent exchange showed narrowing of the duodenal bulb and the proximal second portion of the duodenum. Biopsies of the duodenum and the bile duct showed nonspecific inflammatory changes without evidence of malignancy. Over a 4-week follow-up after the index ERCP, he developed worsening clinical gastric outlet obstruction. Repeat ERCP/EUS revealed thickening of the pre-pyloric antrum and proximal duodenum without obvious mass, and diffuse sclerosis of the bile duct, especially the right hepatic duct, and markedly dilated left duct. Duodenal biopsies eventually revealed poorly differentiated signet-ring cell carcinoma. At 2 months, he developed new-onset symptomatic pleural effusion and ascites. Cytology analysis of the fluids showed adenocarcinoma. He died under hospice care at 2 months after initial presentation. IgG4-SC is a new challenging disease that clinicians should consider in the differential diagnosis of cholangiopathy (e.g., cholangiocarcinoma and primary sclerosing cholangitis). This case represents an example of signet-ring cell carcinoma of the stomach and duodenum that presented as IgG4-SC. These could represent separate concurrent disease processes; the latter could result from immune dysregulation secondary to occult malignancy, or represent a nonspecific change.