Significance of microcystic, elongated, and fragmented glandular-like features in intraductal papillary mucinous neoplasm of the pancreas

Microcystic, elongated, and fragmented (MELF) glandular features are associated with epithelial-mesenchymal transition, invasion, and progression in endometrioid adenocarcinoma of the uterus. Similar histological features are also observed at the periphery of pancreatic intraductal papillary mucinous neoplasms (IPMNs). However, the clinicopathological significance of MELF-like features-particularly whether they represent regenerative or truly neoplastic conditions-in IPMNs remains unclear. We assessed a total of 152 surgically resected IPMNs. Fifty cases exhibited MELF-like features, including 26 cases of IPMNs with accompanying adenocarcinomas and 24 cases of IPMNs without accompanying adenocarcinomas. MELF-like features were more frequently observed in IPMN cases with accompanying adenocarcinomas, larger tumors, main-duct type, and non-gastric histologic subtype. A positive correlation between the presence of MELF-like features and high-grade dysplasia was observed in IPMNs without accompanying adenocarcinomas. Moreover, DPC4 loss and p53 overexpression in MELF-like glands were more commonly observed in IPMNs with high-grade dysplasia. IPMN patients with MELF-like features had worse overall and disease-specific survival by univariate analyses. Our observations suggest that MELF-like features in some IPMNs with high-grade dysplasia could be related to stromal invasion. Hence, when MELF-like features are observed in IPMNs, pathologists should carefully evaluate the results of microscopic examinations to identify the invasive components; and, immunohistochemical staining for DPC4 and p53 could help clarify its clinicopathological significance.