Review

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

Address of Corresponding Author

Pancreatology 2007;7:9-19 (DOI: 10.1159/000101873)

  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 survival of pancreatic cancer rests upon early detection of this neoplasm 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 adenocarcinoma: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. We also discuss two clinical scenarios of emerging importance, namely asymptomatic pancreatic cysts ('pancreatic incidentalomas') and the significance of precursor lesions in familial pancreatic cancer kindreds. Results: Pancreatic intraepithelial neoplasias are the microscopic precursor lesions of pancreatic adenocarcinomas, while intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are macroscopic, cystic precursor lesions. All three noninvasive entities demonstrate a multistep morphologic and genetic progression that culminates in frank invasive adenocarcinoma. Despite these commonalities, each precursor lesion harbors a unique repertoire of clinicopathologic and genetic characteristics that has an impact on natural history and prognosis of these lesions. Due to improvements in radiological techniques, asymptomatic pancreatic cysts are being increasingly discovered in the general population; intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are the most common underlying histology in resected incidentalomas of the pancreas. Pancreatic asymptomatic cysts present an enormous challenge in terms of accurate diagnosis and management stratification. Incorporating 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 pancreatic cancer precursors in these high-risk individuals, preventing 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 ameliorate pancreatic cancer survival.

Copyright © 2007 S. Karger AG, Basel and IAP

  Author Contacts

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

  Article Information

Published online: April 18, 2007
Number of Print Pages : 11
Number of Figures : 2, Number of Tables : 0, Number of References : 100