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Differentiating main-duct IPMN from chronic pancreatitis using next-generation sequencing of main pancreatic duct fluid: a pilot study

Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distingu...

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Main Authors: Schmitz, Daniel (Author) , Prax, Stefan (Author) , Kliment, Martin (Author) , Gocke, Felix (Author) , Kazdal, Daniel (Author) , Allgäuer, Michael (Author) , Penzel, Roland (Author) , Kirchner, Martina (Author) , Neumann, Olaf (Author) , Sültmann, Holger (Author) , Budczies, Jan (Author) , Schirmacher, Peter (Author) , Bergmann, Frank (Author) , Ritz, Jörg-Peter (Author) , Hinze, Raoul (Author) , Grassmann, Felix (Author) , Rudi, Jochen (Author) , Stenzinger, Albrecht (Author) , Volckmar, Anna-Lena (Author)
Format: Article (Journal)
Language:English
Published: 5 August 2025
In: Diagnostics
Year: 2025, Volume: 15, Issue: 15, Pages: 1-12
ISSN:2075-4418
DOI:10.3390/diagnostics15151964
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/diagnostics15151964
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2075-4418/15/15/1964
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Author Notes:Daniel Schmitz, Stefan Prax, Martin Kliment, Felix Gocke, Daniel Kazdal, Michael Allgäuer, Roland Penzel, Martina Kirchner, Olaf Neumann, Holger Sültmann, Jan Budczies, Peter Schirmacher, Frank Bergmann, Jörg-Peter Ritz, Raoul Hinze, Felix Grassmann, Jochen Rudi, Albrecht Stenzinger and Anna-Lena Volckmar

MARC

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520 |a Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm on EUS during the period of 1 June 2017 to 30 April 2024 were prospectively analysed in this single-centre study, with EUS-guided MPD fluid aspiration performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Twenty-two known gastrointestinal cancer genes, including GNAS and KRAS, were analysed by deep targeted (dt) NGS. The results were correlated with resected tissue, biopsy, and long-term follow-up. Results: A total of 164 patients with a dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with 1 patient having a minor complication (3.3%). Twenty-two patients (mean MPD diameter of 12.4 (7-31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Only a fish-mouth papilla, which was present in 3 of 12 (25%) MD-IPMNs, could reliably differentiate between the two diseases, with history, symptoms, diffuse or segmental MPD dilation, presence of calcifications on imaging, cytology, and CEA in the ductal fluid failing to achieve differentiation. However, GNAS mutations were found exclusively in 11 of the 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. 
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