Localization of the Most Severely Dysplastic/Invasive Lesions and Mucin Phenotypes in Intraductal Papillary Mucinous Neoplasm of the Pancreas

Objective: The aim of this study was to define the relevance of mural nodules (MNs) as a "direct" indicator of malignancy of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Methods: Thirty-nine surgically resected IPMNs excluding obviously invasive carcinomas were examined. The distribution of the most severely dysplastic lesions was mapped on specimens. Immunohistochemical analysis for MUC1 and MUC2 was performed on sections containing the histologically predominant lesions and the most severely dysplastic areas. Results: The presence of MNs correlated well with the histological grade of IPMN (P < 0.01); however, the most severely dysplastic lesions were associated with a flat/nonelevated area rather than MNs (78.9%). In the MUC1-positive subgroup, minimally invasive carcinoma was colocalized to MNs, whereas most severely dysplastic foci including minimally invasive carcinoma with components of mucinous and tubular adenocarcinoma were observed in the areas apart from MNs in the MUC2-positive and MUC1/2-negative subgroups, respectively. Conclusions: Although our data support the concept that MNs represent areas of higher-grade dysplasia within IPMN, development of invasive lesions from MNs may be limited to cases that are MUC1-positive. Careful attention should be paid to the emergence of invasive IPMN from flat foci in MUC2-positive and MUC1/2-negative cases.