Clinical Impact of Molecular Biomarkers in the Management of Patients with Pancreatic Cysts

Background: Pancreatic cysts are common and often discovered incidentally. Accurate differentiation is essential to guide management, as some cysts may progress to malignancy. Common pancreatic cyst includes intraductal papillary mucinous neoplasms, pseudocysts, neuroendocrine tumors, serous cystadenoma, and mucinous cystic neoplasms. Current diagnostic approaches, including magnetic resonance imaging, endoscopic ultrasound, biochemical assays, and cytopathology, have an accuracy of approximately 70% in distinguishing benign from precancerous lesions. Molecular analysis of intracystic fluid, particularly KRAS and GNAS mutations, increases the diagnostic accuracy by up to 90%. These mutations are indicative of mucinous cystic lesions; however the efficacy of nextgeneration sequencing in routine clinical practice remains poorly studied. Methods: This retrospective study included 85 patients who underwent EUS-guided fine-needle aspiration for pancreatic cysts at a single center between 2014 and 2021. Clinical data, EUS features, cytopathological results, and molecular testing (KRAS/GNAS mutations) were analyzed. Results: Among the patients (mean age 63, 39% male), 73% of cysts were discovered incidentally. The most common type of cyst was intraductal papillary mucinous neoplasm (58%). KRAS and/or GNAS mutations were present in 16 patients with mucinous lesions, including 12% of the cases without elevated carcinoembryonic antigen. KRAS/GNAS mutations had 94.4% specificity but 23.7% sensitivity for mucinous differentiation. Surgery revealed high-grade dysplasia or cancer in 11 of the 25 operated cases. Conclusions: This study found that molecular analysis enhances the classification of pancreatic cysts but does not improve the detection of malignancy. Further research is needed to characterize the role of molecular biomarkers in pancreatic cyst management.