Differentiation of MD-IPMN from Chronic Pancreatitis by cfDNA Next Generation Sequencing from Ductal Fluid Using EUS-Guided FNA: A Prospective Controlled Study

Aims A dilated main pancreatic duct (MPD)≥5 mm can be observed in main duct IPMN and chronic pancreatitis (CP) but distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA could help to distinguish MD-IPMN from CP.

Methods All patients with a dilated MPD≥5 mm on EUS were prospectively analyzed from 01/06/2017 to 30/04/2024 in this single-center study. EUS-guided MPD fluid aspiration was performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Fourteen known gastrointestinal cancer genes, including GNAS and KRAS, were analyzed by Deep Targeted (dt) NGS. Results were correlated with resected tissue, biopsy, and long-term follow-up [1] [2] [3] [4] [5] [6] [7] [8] [9].

Results 164 patients with dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with one patient having a minor complication (3.3%). 22 patients (mean MPD diameter of 12.4 (7-31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Neither history, symptoms, diffuse or segmental MPD dilatation, presence of calcifications on imaging, cytology or CEA in the ductal fluid could reliably differentiate between the two diseases, except for a fish-mouth papilla, which was present in only 3 of 12 (25%) MD-IPMNs. However, GNAS mutations were found exclusively in 11/12 (91.6%) patients with MD-IPMN (p<0.01), whereas KRAS mutations were identified in both diseases.

Conclusions GNAS testing by dtNGS in aspirated fluid from dilated MPD obtained by EUS-guided FNA may help differentiate MD-IPMN from CP for surgical resection.

Publication History

Article published online:
27 March 2025

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