Precursor lesions in pancreatic cancer: morphological and molecular pathology

Pancreatic cancer has a dismal prognosis and is the fourth most common cause of cancer related death in Western societies. In large part this is due to its typically late presentation, usually as locally advanced or metastatic disease. Identification of the non-invasive precursor lesions to pancreatic cancer raises the possibility of surgical treatment or chemoprevention at an early stage in the evolution of this disease, when more amenable to therapeutic interventions. Precursor lesions to pancreatic ductal adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN), have been recognised under a variety of synonyms for over 50 years. Over the past decade our understanding of the morphology, biological significance and molecular aberrations of these lesions has grown rapidly and there is now a widely accepted progression model integrating the accumulated morphological and molecular observations. Further progress is likely to be accelerated by improved mouse models of pancreatic cancer and by insight into the cancer genome gained by the International Cancer Genome Consortium (ICGC), in which an Australian consortium is leading the pancreatic cancer initiative. This review also outlines the morphological and molecular features of the other two precursors of pancreatic ductal adenocarcinoma, i.e., intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.