Clinicopathological features of pancreatic intraepithelial neoplasias and their relationship to intraductal papillary-mucinous tumors

Abstract

Pancreatic intraepithelial neoplasia (PanIN) is a recently proposed nomenclature for putative precursor lesions of pancreatic cancer, which are designated as PanIN-1 through -3 according to their increasing grade of dysplasia. A stepwise progression model of PanINs has been proposed, and multistep genetic alterations in PanINs are being investigated. PanIN-1A and PanIN-1B may remain unchanged for a long period. PanIN-3 potentially progresses toward invasive ductal carcinoma (IDC), and there are several case reports suggesting such progression. In these reported patients, PanIN-3 was found in specimens from partial pancreatectomies, and IDC manifested in the pancreatic remnant 17 months to 29 years after the surgery. We describe herein a patient with PanIN-3, in whom IDC manifested in the distal remnant pancreas 69 months after segmental pancreatectomy. Of the reported cases, including the present one, four of the patients were male and three were female, and the age at the first operation ranged from 46 to 70 years. Intraductal papillary-mucinous tumor (IPMT) is an entity that is distinct from PanIN. However, IPMTs of small size resemble PanINs morphologically. Loss of Dpc4 expression has been reported in the invasive component of IPMT, as well as in PanIN-3 and IDC. Analysis of mucin expression patterns has been reported, suggesting that, in practice, MUC1-positive MUC2-negative IPMTs may not be distinguishable from PanINs. There may be overlapping lesions between PanINs and IPMTs. Should the paradigm of the ductal origin of IDC be accepted, PanINs and a fraction of IPMTs would represent precursors of IDC.