Cystic Neoplasia of the Pancreas: Pathology and Biology

In contrast with solid tumors, most of which are invasive ductal adenocarcinoma with dismal prognosis, cystic lesions of the pancreas are often either benign or low-grade indolent neoplasia. Those that are mucinous, namely, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), constitute the most important category, not only because they are the most common, but more importantly because they have well-established malignant potential, representing an adenomacarcinoma sequence. While many are innocuous adenomas — in particular, those that are small and less complex, and in the case of IPMN, those that are branch-duct type are more commonly benign, some harbor or progress into in situ or invasive carcinomas. For this reason, pancreatic cysts with mucinous differentiation ought to be evaluated carefully, preferably by experts familiar with subtle evidences of malignancy in these tumors. In the past few years, the definition of IPMNs and MCNs has become more refined. The presence of ovarian-type stroma has now almost become a requirement for the diagnosis of MCN, and when defined as such, MCN is seen almost exclusively in women of perimenopausal age group as thick-walled multilocular cystic mass in the tail of the pancreas in contrast with IPMN which afflicts an elder population, both genders in almost equal numbers, and occur predominantly in the head of the organ. While mucinous lesions have well-established pre-malignant properties, most of the entities that fall into the nonmucinous true cyst category such as serous tumors, lymphoepithelial cysts, congenital cysts, and squamoid cyst of ducts have virtually no malignant potential. In contrast, the rare cystic tumors that occur as a result of degenerative/necrotic changes in otherwise solid neoplasia such as the rare cystic ductal adenocarcinomas, cystic endocrine neoplasia, and most importantly, solid-pseudopapillary tumor (SPT) in which cystic change is so common that it used to be incorporated into its name (“solid-cystic,” “papillary-cystic”) are malignant neoplasia, albeit variable degrees of aggressiveness. SPT holds a distinctive place among pancreatic neoplasia because of its highly peculiar characteristics, undetermined cell lineage, occurrence almost exclusively in young females, association with β-catenin pathway, and also by being a very low-grade curable malignancy. In conclusion, cystic lesions in the pancreas constitute a biologically and pathologically diverse category most (but not all) of which are either benign or treatable diseases; however, a substantial subset, especially mucinous ones, has malignant potential that requires careful analysis.