The impact of targeted next-generation DNA sequencing on the diagnostic accuracy of endoscopic ultrasound-guided tissue sampling of focal pancreatic lesions.

[BACKGROUND] Accurate diagnosis of pancreatic lesions remains challenging. This study evaluated the diagnostic value of targeted DNA-based next-generation sequencing (NGS) of tissue obtained by endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) and its contribution to pancreaticobiliary multidisciplinary tumor board (MDTB) discussions.

[METHODS] A retrospective analysis was conducted using a prospectively maintained database at Ghent University Hospital (March 2021-September 2024). Only patients undergoing targeted DNA NGS on EUS-FNA/FNB samples were included and reviewed during MDTB meetings. Diagnostic performance and influence on management were compared with final diagnoses established by clinical follow-up and/or surgical pathology.

[RESULTS] The final cohort comprised 120 focal pancreatic lesions. Ninety-one percent of solid masses (50/55) were malignancies. Cytopathology alone identified pancreatic cancer (PC) or high-grade dysplasia (HGD) in 27 cases (sensitivity 54%), whereas NGS alone identified 42 (sensitivity 84%). Combined cytopathology and NGS detected 45/50 malignancies (90%). Only two samples were non-diagnostic, yielding an overall diagnostic success of 96% (53/55). NGS was technically successful in 33/65 (51%) cystic lesions. Surgery was undertaken in 20 patients, with HGD or carcinoma confirmed in 11 (55%). Molecular profiling combined with cytopathology guided surgical decision-making in 6/11 patients (54%) compared with 3/11 (27%) with cytopathology alone.

[CONCLUSION] Targeted NGS improves diagnostic accuracy in solid pancreatic lesions and supports surgical decision-making for cystic lesions. Integration of molecular findings into MDTB discussions enhances precision and timeliness of pancreatic cancer treatment.