Occurring less frequently, alterations of p53 present late events in PanIN and IPMN, which are associated with a high grade of dysplasia (20,23–26) Furthermore, loss of Smad4/DPC4 is an abundant observation in high grade PanIN lesions (25,27). The gene discussed is SMAD4; the disease is pancreatic intraductal papillary-mucinous neoplasm.