Biomarkers in cystic lesions of the pancreas: Controversies and advances

Pancreatic cystic lesions (PCLs) represent a highly heterogeneous category of pancreatic abnormalities with an increasing prevalence due to advances in imaging modalities and an aging population. While the majority of PCLs are benign, a subset harbors a variable risk of malignant transformation. Current guidelines rely primarily on imaging features for risk stratification, but limitations in diagnostic accuracy have led to many unnecessary surgical procedures and conversely, missed opportunities for timely resection in cases that progress to malignancy.Recent advances in biomarker discovery hold great promise for improving the management of PCL. In this review, we focus on comparing the diagnostic efficacy of classical tumor markers, highlighting the controversies and challenges associated with each. In addition, we explore the heterogeneous expression of mucins in different subtypes of intraductal papillary mucinous neoplasms (IPMNs) and review the role of common genetic mutations and next-generation sequencing (NGS) in the genomic assessment of PCLs. Importantly, we summarize the results of several novel gene panels and evaluate their diagnostic performance and clinical potential. Although accurate diagnosis and risk stratification of PCLs remain challenging, advances in biomarkers and molecular techniques continue to reveal their potential in precision medicine, with promising implications for clinical translation.