Current topics on precursors to pancreatic cancer

Prognosis of invasive pancreatic ductal adenocarcinoma is bleak and the vast majority of patients with pancreatic cancer die of their disease. The detection and treatment of the non-invasive precursor lesions of pancreatic cancer offer the opportunity to cure this devastating disease and therefore great efforts are being made to identify the precursors to pancreatic cancer. Several distinct precursor lesions have been identified. Mucinous cystic neoplasms (MCNs), intraductal papillary mucinous neoplasms (IPMNs), and pancreatic intraepithelial neoplasias (PanINs) all harbor varying degrees of dysplasia and stepwise accumulation of genetic alterations, suggesting progression of these lesions from benign toward malignant neoplasms. MCNs have a characteristic ovarian-type stroma. About one-third of MCNs are associated with invasive carcinoma of ductal phenotype. IPMNs are recently established clinical entity with characteristic features of mucin hypersecretion and duct dilatation. Some IPMNs are associated with invasive carcinoma and IPMNs are recognized precursors to pancreatic cancer. PanINs are microscopic proliferative lesions arising from any parts of the pancreatic duct system. Low grade PanINs are commonly found in pancreatic ducts of elder individuals, while high grade PanINs, previously called carcinoma in situ/severe ductal dysplasia, may eventually give rise to invasive pancreatic cancer. Appropriate clinical managements are requisite for patients with MCNs, IPMNs and PanINs. Further investigation of these precursor lesions is expected to reduce the mortality from pancreatic cancer.