P4445 - When Histology Isn’t Enough: BiliSeq Points to Early Ampullary Adenocarcinoma Missed on Biopsy

Natalie Rosseau, MD¹, Alexandria Iakovidis, MD², Lindsey A. Creech, DO, MBA, MPH³, Aleksey Novikov, MD²
1University of Florida Health Shands Hospital, Gainesville, FL; 2University of Florida College of Medicine, Gainesville, FL; 3University of Florida, Gainesville, FL

Introduction: Diagnosing biliary tract malignancies remains a challenge. Historically, up to 75% of indeterminate extrahepatic biliary strictures are reported to be malignant on sampling1. 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.2 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 male 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 (CT) scan showed dilated common bile and pancreatic ducts without an obvious mass. 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. CBD 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.

Disclosures:
Natalie Rosseau indicated no relevant financial relationships.
Alexandria Iakovidis indicated no relevant financial relationships.
Lindsey Creech indicated no relevant financial relationships.
Aleksey Novikov indicated no relevant financial relationships.

Natalie Rosseau, MD¹, Alexandria Iakovidis, MD², Lindsey A. Creech, DO, MBA, MPH³, Aleksey Novikov, MD². P4445 - When Histology Isn’t Enough: BiliSeq Points to Early Ampullary Adenocarcinoma Missed on Biopsy, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.