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Differentiating Main-Duct IPMN from Chronic Pancreatitis Using Next-Generation Sequencing of Main Pancreatic Duct
Daniel Schmitz1,2, Stefan Prax1, Martin Kliment1
1Department of Gastroenterology and Infectiology, Helios Kliniken Schwerin, University Campus of Medical School Hamburg, 19055 Schwerin, Germany.
Abstract:
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.
Insights
GNAS gene mutations detected in pancreatic duct fluid can help distinguish main-duct IPMNs from chronic pancreatitis. This molecular testing aids in surgical decision-making for patients with a dilated main pancreatic duct.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Diagnostics
Background:
- Distinguishing between main-duct intraductal papillary mucinous neoplasms (MD-IPMN) and chronic pancreatitis (CP) is challenging due to overlapping features like a dilated main pancreatic duct (MPD) ≥ 5 mm.
- Accurate differentiation is crucial as MD-IPMN and CP require different treatment strategies.
Purpose of the Study:
- To evaluate the utility of cell-free DNA (cfDNA) analysis, specifically GNAS and KRAS mutations, in MPD fluid for differentiating MD-IPMN from CP.
- To assess the diagnostic performance of molecular testing in conjunction with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).
Main Methods:
- Prospective analysis of 164 patients with MPD dilation ≥ 5 mm, with 30 undergoing EUS-FNA for MPD fluid collection.
- Deep targeted next-generation sequencing (dtNGS) of 22 gastrointestinal cancer genes, including GNAS and KRAS, in MPD fluid.
- Correlation of molecular findings with surgical resection, biopsy, and long-term follow-up data.
Main Results:
- GNAS mutations were identified in 91.6% of MD-IPMN cases but were absent in chronic pancreatitis (p < 0.01).
- KRAS mutations were found in both MD-IPMN and CP, offering less discriminatory power.
- Traditional methods like imaging, cytology, and CEA levels in ductal fluid were insufficient for differentiation, unlike a fish-mouth papilla observed in some MD-IPMN cases.
Conclusions:
- GNAS mutation testing via dtNGS in EUS-FNA-derived MPD fluid is a promising biomarker for differentiating MD-IPMN from CP.
- This molecular approach can aid clinicians in making informed decisions regarding surgical resection for patients with dilated MPDs.
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