Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review Pancreatology 2007;7:9–19 DOI: 10.1159/000101873 Precursor Lesions of Pancreatic Cancer: Molecular Pathology and Clinical Implications Mansher Singh Anirban Maitra Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Md., USA sor lesion harbors a unique repertoire of clinicopathologic and genetic characteristics that has an impact on natural his- tory and prognosis of these lesions. Due to improvements in radiological techniques, asymptomatic pancreatic cysts are being increasingly discovered in the general population; in- traductal papillary mucinous neoplasms and mucinous cys- tic neoplasms are the most common underlying histology in resected incidentalomas of the pancreas. Pancreatic asymp- tomatic cysts present an enormous challenge in terms of ac- curate diagnosis and management stratification. Incorporat- ing molecular signatures of cystic precursor lesions into the diagnostic algorithm will likely become a standard of care for asymptomatic pancreatic cysts. High-risk individuals from familial pancreatic cancer kindreds are another group of individuals where knowledge of precursor lesions has had a therapeutic impact; sensitive imaging technologies have enabled the identification and subsequent resection of pan- creatic cancer precursors in these high-risk individuals, pre- venting the progression to invasive cancer. Conclusions: Precursor lesions of pancreatic adenocarcinomas represent a unique opportunity for diagnosis and intervention for a malignancy with near uniform lethality. Further studies on these precursors will enable the development of rational early detection and therapeutic strategies in order to ame- liorate pancreatic cancer survival. Copyright © 2007 S. Karger AG, Basel and IAP Key Words Intraductal papillary mucinous neoplasm  Mucinous cystic neoplasm  Pancreatic cancer, precursor lesions  Pancreatic intraepithelial neoplasia Abstract Background: Pancreatic cancer is a lethal disease, with near uniform 5-year mortality rates. The key to improving surviv- al of pancreatic cancer rests upon early detection of this neo- plasm at a resectable, and hence potentially curable, stage. Methods: We review the current state of the literature vis-à- vis the three common precursor lesions of pancreatic adeno- carcinoma: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neo- plasm. We also discuss two clinical scenarios of emerging importance, namely asymptomatic pancreatic cysts (‘pan- creatic incidentalomas’) and the significance of precursor le- sions in familial pancreatic cancer kindreds. Results: Pancre- atic intraepithelial neoplasias are the microscopic precursor lesions of pancreatic adenocarcinomas, while intraductal papillary mucinous neoplasms and mucinous cystic neo- plasms are macroscopic, cystic precursor lesions. All three noninvasive entities demonstrate a multistep morphologic and genetic progression that culminates in frank invasive ad- enocarcinoma. Despite these commonalities, each precur- Published online: April 18, 2007 Anirban Maitra, MBBS Room 345, CRB-II Johns Hopkins University School of Medicine, 1550 Orleans Street Baltimore, MD 21231 (USA) Tel. +1 410 502 8191, Fax +1 410 614 0671, E-Mail amaitra1@jhmi.edu © 2007 S. Karger AG, Basel and IAP 1424–3903/07/0071–0009$23.50/0 Accessible online at: www.karger.com/pan