S3423 From Mirizzi to Malignancy: A Case of Lynch Syndrome-Associated Distal Cholangiocarcinoma Masquerading as Mirizzi Syndrome

Introduction: Mirizzi syndrome and cholangiocarcinoma are 2 distinct causes of biliary obstruction that can present with overlapping clinical and radiologic features, often making early diagnosis challenging. The presence of gallstones often leads to an initial assumption of a benign etiology; however, such findings should not exclude the possibility of an underlying malignancy. We present a case initially suspected to be Mirizzi syndrome that was ultimately diagnosed as distal cholangiocarcinoma and later found to be associated with Lynch syndrome. Case Description/Methods: A 68-year-old man with a history of diabetes, hyperlipidemia, and bipolar disorder presented with progressive jaundice, pruritus, dark urine, and pale stools. Laboratory workup revealed a cholestatic pattern of liver injury with elevated total bilirubin (11.5 mg/dL), ALT (942 U/L), AST (501 U/L), and CA 19-9 (40 U/mL). Imaging showed cholelithiasis and a 1.4 cm mass at the junction of the cystic and common hepatic ducts, initially raising concern for Mirizzi syndrome. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a compressive cystic duct stone with biliary sludge. Due to persistent obstruction, repeat ERCP with SpyGlass cholangioscopy was performed, revealing a distal biliary stricture. Biopsies confirmed invasive adenocarcinoma of the common hepatic duct. Tumor molecular profiling revealed microsatellite instability-high (MSI-H) status and pathogenic mutations in PMS2 and MSH3, suggestive of Lynch syndrome. PET/computed tomography showed no evidence of metastatic disease. The patient was referred for neoadjuvant chemotherapy followed by planned Whipple resection. Discussion: This case emphasizes the importance of maintaining a high index of suspicion for malignancy in cases of persistent biliary obstruction in presence of Mirizzi syndrome. Advanced endoscopic techniques such as SpyGlass cholangioscopy can aid in timely diagnosis. This case also highlights a rare presentation of cholangiocarcinoma potentially associated with Lynch syndrome, supporting the need for molecular evaluation in select patients.