S3580 When Histology Isn’t Enough: BiliSeq Points to Early Ampullary Adenocarcinoma Missed on Biopsy

Introduction: Diagnosing biliary tract malignancies remains a challenge. Historically, up to 75% of indeterminate extrahepatic biliary strictures are reported to be malignant on sampling. BiliSeq is a novel next-generation sequencing (NGS) 28 cancer-associated gene assay with an improved sensitivity (∼73%) and specificity (100%) in detecting malignant lesions. Here, we describe a patient with a biopsy-negative ampullary lesion in whom NGS identified a TP53 mutation leading to a pancreaticoduodenectomy with a final diagnosis of a pT1aN0 invasive ampullary adenocarcinoma. Case Description/Methods: An 86-year-old man with atrial fibrillation and polymyalgia rheumatica was evaluated for a transient elevation in liver enzymes (alkaline phosphatase 335 IU/L, AST 52 IU/L, and ALT 69 IU/L). Computed tomography scan showed dilated common bile and pancreatic ducts without an obvious mass. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) confirmed a 14 mm dilated pancreatic duct with a possible 9 by 15 mm hypoechoic ampullary mass. EUS biopsies were negative. ERCP showed an atypical appearing ampulla. common bile duct brushing and biopsies were negative. Ampullary biopsy was inconclusive, showing rare, highly atypical glands. However, NGS test detected an increased expression of p53, concerning for underlying malignancy. Patient was referred to surgical oncology and underwent a laparoscopic pancreaticoduodenectomy. Final pathology revealed a 0.4 cm well-differentiated, pancreaticobiliary subtype invasive ampullary adenocarcinoma (pT1an0) with negative margins and no lymph node involvement. A month after surgery, the patient was doing well and opted for surveillance over chemotherapy. Discussion: This case demonstrates the utility of NGS in risk stratification for what was essentially an indeterminate biliary stricture. The patient and surgeon opted for surgery in part based on the genetic mutation results. Early-stage diagnosis is clinically significant, as long-term survival following pancreaticoduodenectomy strongly correlates with early tumor stage and complete resection. This case provides proof-of-concept for clinicians to utilize BiliSeq results when pathology is inconclusive.