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

Figure 1

Computerized tomography scan demonstrating massive dilatation of the main pancreatic duct and its branches. Obstructed bile duct is also dilated.

Figure 2

Scheme of macroscopic classification of intraductal papillary mucinous neoplasm.

Figure 3

Macroscopic classification of intraductal papillary mucinous neoplasm. A: Main duct type; B: Branch duct type; C: Combined type.

Figure 4

Different degrees of dysplasia. A: Low-grade (gastric IPMN). See transition with non dysplastic normal duct epithelium (right side); B: Intermediate-grade (intestinal IPMN); C: High-grade (pancreatobiliary IPMN). IPMN: Intraductal papillary mucinous neoplasm.

Figure 5

Gastric intraductal papillary mucinous neoplasm. A: The neoplasm involves branch ducts with a multicystic appearance; B: Columnar cells with basal nucleus and apical mucin. Notice the scattered goblet cells (arrows); C: Immunohistochemical MUC5AC expression (colored brown by diaminobenzidine); D: MUC2 highlighting the goblet cells. MUC: Mucin.

Figure 6

Intestinal intraductal papillary mucinous neoplasm. A: Main duct distended by long papillae; B: Projections of columnar cells with pseudostratified nuclei; C: Immunohistochemical MUC2 expression. MUC: Mucin.

Figure 7

Pancreatobiliary intraductal papillary mucinous neoplasm. A: Intraductal papillary mucinous neoplasm with associated conventional duct carcinoma (upper side); B: Small thin papillae with cuboidal neoplastic epithelium; C: Immunohistochemical MUC1 expression. MUC: Mucin.

Figure 8

Colloid carcinoma. A: Invasive neoplastic cells floating in pools of mucin (upper side) and associated with intraductal papillary mucinous neoplasm (lower side); B: Immunohistochemical MUC2 expression; C: CDX2 nuclear immunoexpression. MUC: Mucin.

Figure 9

Pseudoinvasion. Mucin spillage dissecting into the pancreatic stroma without neoplastic cells.

Figure 10

Mucinous cystic neoplasm. A: An example with papillary projections and surrounded by a thick collagenized band; B: Demonstration of ovarian-type stroma, at least focally, leads to diagnosis.