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

This is a non-final version of an article published in final form in Karasaki, Hidenori ; Mizukami, Yusuke ; Tokusashi, Yoshihiko ; Koizumi, Kazuya ; Ishizaki, Akira ; Imai, Kouji ; Yoshikawa, Daitaro ; Kino, Shuichi ; Sasajima, Junpei ; Tanno, Satoshi ; Matsumoto, Kakuya ; Miyokawa, Naoyuki ; Kono, Toru ; Kohgo, Yutaka ; Furukawa, Hiroyuki, Pancreas, 40(4), 588-594.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

【分枝型IPMNの外科治療戦略】 ムチン発現形質と壁在結節の有無からみたIPMNの切除適応

著者最終原稿版IPMNのムチン発現形質によるサブタイプ別予後、組織学的な異型度と壁在結節(MN)の関係に着目して、新たな切除適応の可能性について検討した。MUC2陽性型は最も予後が良好で、MNの有無と異型度に相関傾向を認めることから、MNが形成されるまでは経過観察が可能であると考えられた。MUC1陽性型もMNの有無と異型度に相関傾向を認めるものの、早期に浸潤を開始する可能性があるため、MNの有無にかかわらず切除適応と考えられた。一方、MUC1、2陰性型ではMNの有無と異型度に相関がなく、MNのないことが臨床的な安全性の高さを示すことにはならない。この型には経過観察が可能と思われる良性病変と、悪性度の高い病変が混在している可能性がある。MNの有無にかかわらず浸潤性管状腺癌の発生がみられることがあるため、経過観察において最も注意を要すると考えられた