埼玉医科大学雑誌 第35巻 第1号別頁 (2008年12月) T9-T22頁 ◇論文(図表を含む全文)は，PDFファイルとなっています．
PDF (4.2 MB)
医学博士 乙第1065号 平成19年10月26日 （埼玉医科大学）
Histopathological and Immunohistochemical Study of Intraductal Papillar y Mucinous Neoplasm of the Pancreas with Special Reference to Its Histologic Subtypes
【Background and Aims】Intraductal papillary mucinous neoplasm (IPMN) is one of major cystic neoplasms of the pancreas, uniquely developing in the ductal system. IPMNs have been classified into some subtypes according to their histology and mucin phenotypes. However, the pathologic features of IPMNs in terms of their histologic subtypes have not been fully investigated. The aims of this study were: 1) to reevaluate the histologic subtypes and mucin profiles of IPMNs, 2) to clarify the pathologic features of IPMNs with regard to their histologic subtypes, and 3) to investigate differential expression of some tumor-related factors among the histologic subtypes of IPMNs. 【Design】91 cases of surgically resected IPMNs of the pancreas were subjected to examination. Formalin-fixed and paraffin-embedded sections of each lesion were cut for hematoxylin and eosin staining (HE) and immunohistochemistry. Pathologic features of each lesion were evaluated on HE slides. Immunohistochemistry for representative sections of each lesion were performed for mucins (MUC1, MUC2, MUC5AC, and MUC6), c-erbB-2, COX-2, and cyclin D1, using ENVISION system, and the results were evaluated semiquantitatively. 【Results】 The IPMNs were classified into the following histologic subtypes: (1) 50 cases of Gastric type (showing some resemblance to gastric foveolar epithelium), (2) 30 cases of Intestinal type (showing a colorectal villous tumor-like appearance), (3) 4 cases of Gastric＋Intestinal type (coexistence of Gastric type area and Intestinal type area), and (4) 7 cases of Oncocytic type (arborizing nodular growth of oncocystic epithelium). The mucin phenotype of Gastric type was mostly MUC5AC＋/MUC2−, whereas that of Intestinal type was MUC5AC＋/MUC2＋. Furthermore, histopathologic features were different in many respects between Gastric type and Intestinal type. However, an obvious difference was not determined with respect to the expression of c-erbB-2, COX-2, or cyclin D1. Oncocytic type showed a distinctive mucin phenotype, i.e. MUC1＋ and MUC6＋ in addition to MUC5AC＋. IPMN-derived invasive carcinoma was observed in 7 out of 30 Intestinal type IPMNs (23％) and one out of 50 Gastric type IPMNs (2％). The histologic type of IPMN-derived invasive carcinoma included mucinous carcinoma and conventional type invasive ductal carcinoma. In Intestinal type IPMN-derived invasive carcinoma, MUC2 expression was preserved in mucinous carcinoma in contrast to the conventional type invasive ductal carcinoma. 【Conclusions】IPMNs of the pancreas are classified into several histologic subtypes. The major subtypes are Intestinal type and Gastric type, which show distinctive pathologic features, possibly reflecting different biological behaviors. With regard to IPMN-derived invasive carcinoma, mucinous carcinoma seems to be unique as Intestinal type IPMN-derived invasive carcinoma. Oncocytic type represents a distinctive feature, whereas it is possible that it is related to Gastric type. Histologic subtypes should be considered in the diagnosis and clinical management of IPMNs of the pancreas.