Precursor lesions of pancreatic cancer

Pancreatic ductal adenocarcinoma (a.k.a. PDAC) is a disease of near-uniform lethality. Multiple lines of evidence suggest that PDAC does not arise de novo. Several distinct subtypes of non-invasive precursors of PDAC have been identified in the past two decades, including the microscopic Pancreatic intraepith-elial neoplasia (PanIN), which is by far the most common precursor lesion, f-ollowed by the macroscopic (cystic) precursor lesions, comprised of Intraductal Papillary Mucinous Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN). In this review, we discuss the diagnostic features for each of these PDAC precursor subtypes, and present the salient molecular alterations underlying their path-ogenesis and progression to invasive neoplasia. Finally, the translational implications of identifying PDAC precursor lesions are discussed, particularly in the context of early detection of PDAC in at-risk populations.