Update on pancreatic intraepithelial neoplasia

Abstract

Pancreatic intraepithelial neoplasia (PanIN) is a histologically well-defined precursor to invasive ductal adenocarcinoma of the pancreas. PanINs are remarkably common lesions, particularly in the elderly population. Molecular studies have helped establish the progression of PanIN to invasive cancer, and recently genetically engineered mouse models have been generated that recapitulate the entire spectrum of lesions from precursor to invasive pancreatic cancer. Some PanIN lesions produce lobulocentric atrophy of the pancreatic parenchyma, and, when multifocal, this lobulocentric atrophy may be detectable using currently available imaging techniques such as endoscopic ultrasound. The association of acinar-ductal metaplasia with PanIN lesions has led some to hypothesize that PanINs develop from acinar cells that undergo acinar-ductal metaplasia.

Keywords: Pancreatic cancer; epigenetics; genetics; intraepithelial neoplasm; metaplasia.

Figure 1

The progression from normal ducts (A) to pancreatic intraepithelial neoplasia (PanIN) (B-D) is associated with both architectural and cytological changes. In PanIN-1 the nuclei are uniform and basally oriented (B). The nuclei in PanIN-2 are slightly larger, more basophilic and there is some loss of nuclear polarity (C). The nuclear pleomorphism in PanIN-3 can be significant (D).

Figure 2

Model for the histological and genetic progression from normal cells (far left) through PanIN lesions (center), to invasive pancreatic cancer (far right). (Reprinted, with permission, from Annual Review of Pathology: Mechanisms of Disease. 2008;3:157–188 © by Annual Reviews. www.annualreviews.org).