Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas

Abstract

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucin-producing cells arising in the main duct (MD) and/or branch ducts (BD) of the pancreas. Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity. IPMN lacks ovarian-type stroma, unlike mucinous cystic neoplasm, and is defined as a grossly visible entity (≥ 5 mm), unlike pancreatic intraepithelial neoplasm. With the use of high-resolution imaging techniques, very small IPMNs are increasingly being identified. Most IPMNs are solitary and located in the pancreatic head, although 20%-40% are multifocal. Macroscopic classification in MD type, BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications. Based on cytoarchitectural atypia, IPMN is classified into low-grade, intermediate-grade and high-grade dysplasia. Based on histological features and mucin (MUC) immunophenotype, IPMNs are classified into gastric, intestinal, pancreatobiliary and oncocytic types. These different phenotypes can be observed together, with the IPMN classified according to the predominant type. Two pathways have been suggested: gastric phenotype corresponds to less aggressive uncommitted cells (MUC1 -, MUC2 -, MUC5AC +, MUC6 +) with the capacity to evolve to intestinal phenotype (intestinal pathway) (MUC1 -, MUC2 +, MUC5AC +, MUC6 - or weak +) or pancreatobiliary /oncocytic phenotypes (pyloropancreatic pathway) (MUC1 +, MUC 2-, MUC5AC +, MUC 6 +) becoming more aggressive. Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises (about 40% of IPMNs), except in some cases of minimal invasion. The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer. Once resected, they must be extensively sampled or, much better, submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.

Keywords: Mucinous pancreatic cysts; Intraductal papillary mucinous neoplasm; Main duct intraductal papillary mucinous neoplasm; Branch duct intraductal papillary mucinous neoplasm; Mucins

Core tip: The authors review the main pathological features of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, including diagnostic criteria and relevance of macroscopic (i.e., main duct, branch duct and mixed or combined) and microscopic (i.e., gastric, intestinal, pancreatobiliary and oncocytic) IPMN classification. Different pathways, mucin immunophenotypes and invasive carcinoma related to IPMN are addressed. Differential diagnosis with pancreatic intraepithelial neoplasm, mucinous cystic neoplasm and other mucinous and non-mucinous pancreatic cystic lesions are also included.