CLINICAL UTILITY OF NEXT-GENERATION SEQUENCING FOR DIFFERENTIATING MAIN-DUCT INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM AND CHRONIC PANCREATITIS AS ETIOLOGY OF PANCREATIC DUCT DILATION

Introduction:
The management of pancreatic duct (PD) dilation is challenging as it may be secondary to both benign and malignant conditions. Next-generation sequencing (NGS) of PD aspirates has emerged as a useful modality for identifying epithelial mucinous lesions with malignant potential and stratifying the risk of progression. We aim to describe the clinical utility of NGS for differentiating main-duct intraductal papillary mucinous neoplasm (IPMN) and chronic pancreatitis as causes of PD dilation.

Methods:
This single-center, retrospective cohort study included adult patients who were evaluated in a high-risk pancreatic lesion clinic between 2016 and 2021 and was approved by the institutional review board. We included only patients referred for evaluation of PD dilation without radiologically evident cysts and had NGS results available. Demographic and clinical variables were abstracted by chart review. The primary outcome was progression to surgery, enrollment in surveillance program, or discharge from clinic. Statistical significance was defined as p<0.05.

Results:
We included a total 27 patients with main PD dilation. The mean age was 68.4 ± 14.0 years with the majority (51.9%) being female. The most common race was White (66.7%). There were no differences in demographic characteristics between those with PD dilation secondary to neoplasia and chronic pancreatitis (Table 1). NGS revealed mutations consistent with mucinous neoplasms in 12 patients (48.1%) leading to a diagnosis of main duct IPMN. Six were enrolled in active surveillance protocols for high-risk lesions, while the remaining 6 underwent surgical resection. Among these patients undergoing surgery, 2 were found to have high-grade dysplasia and 4 were found to have low-grade dysplasia. All 6 of these patients had confirmed IPMN on surgical pathology. One patient exhibited no mutations associated with mucinous neoplasms but had mutations in both TP53 and SMAD4. This patient ultimately underwent surgical resection with a pathologic diagnosis of intraductal tubulopapillary neoplasm with an associated invasive adenocarcinoma. The remaining 14 patients harbored no genomic alterations and PD dilation was attributed to chronic pancreatitis without associated IPMN. One underwent surgery (pathology with chronic pancreatitis and no neoplasm), and the remaining were discharged from clinic, or enrolled in low-risk surveillance protocols (Figure 1).

Conclusion:
The integration of NGS in the evaluation of PD dilation has yielded significant and clinically relevant alterations in patient management. This underscores the importance of routinely considering NGS when assessing patients with PD dilation, as it has the potential to enhance the precision and effectiveness of clinical decision-making.