大腸鋸歯状ポリープの分類・診断と発育進展

Classification, Diagnosis and Development of Serrated Polyp of the Colorectum

要旨　鋸歯状ポリープ（SP）には，過形成性ポリープ（HP）/化生性ポリープ（MP），鋸歯状腺腫（SA），および鋸歯状腺腫内癌（Ca in SA）あるいは由来癌（SA-deriv Ca）が含まれる．SAに関しては，Longacre and Fenoglioによってまとめられたものがわれわれの頭に入力されているが，最近，米国・カナダの研究者より，hyperplastic polyposis（HPP）の研究をもとに，発癌のリスクのあるHP類似病変として，無茎性鋸歯状ポリープ（SSP）/無茎性鋸歯状腺腫（SSA）なる概念が提出され注目されている．また，HPとの組織学的鑑別点も提案されている．本稿では，米国・カナダの研究者が用いているSPの分類を示し，筆者の立場からコメントを加えた．SSP/SSAには内容に幅がありそうなので，わが国できちんとした診断基準を作るべきであると思った．次いで，筆者の基準でSA成分が含まれていると判断した108個の表在性病変について，SAの臨床病理学的特徴を示した．癌合併率は8％であった．大きなSA，特に右側結腸の扁平（IIa様）なSAは注意する必要がある．さらに，SAを通してのSPの発育進展経路を考察した．最後に，SPの癌化には，従来のadenoma-carcinoma sequenceとは異なる，いわばserrated pathwayが存在し，これにはBRAF遺伝子の変異やhypermethylationがからんでいることを紹介した．

　In a series of serrated polyps (SP), hyperplastic polyp (HP)/metaplastic polyp (MP), serrated adenoma (SA), and carcinoma in adenoma (Ca in SA) or carcinoma derived from serrated adenoma (Ca deriv SA) are included. Concerning diagnosis of SA, we are much influenced by the criteria given by Longacre and Fenoglio. Recently, an entity, "sessile serrated polyp (SSP)" or "sessile serrated adenoma (SSA)", has been presented by researchers as a lesion at risk of cancer development compared with ordinary HP. The researchers were from the US and Canada, and their findings are based on the investigation of hyperplastic polyposis. They have also proposed histological criteria to differentiate it from ordinary HP. In this paper, we firstly introduced the classification of SP, recently used among researchers in the US and Canada. Then we pressented some comments about the classification. Concerning SSP/SSA, however, we feel that there is some ambiguity in the criteria. Thus, it would be better to establish as soon as possible solid criteria for this condition in Japan. Secondly, using 108 lesions in which one of the authors (YK) judged the presence of the SA component in at least some part of the lesion, we investigated clinicopathological characteristics of SA. Carcinoma was found in 9 lesions (8 ％). In endoscopic examination, attention should be paid to larger lesions, particularly to IIa-like lesions located in the proximal colon. 3 lesions showed loss of DNA mismatch repair protein[loss of MLH1 in 2, loss of MSH2 in 1 (HNPCC)]. The loss in two of the lesions was strongly suspected to be due to methylation. In addition, we considered several routes of the development of SP. Finally, we introduced what is called "serrated pathway", a different pathway from the previous adenoma-carcinoma sequence. In this pathway, mutation of BRAF gene and methylation of CpG island are fairly closely related to colorectal carcinogenesis, particularly carcinogenesis in the right side colon.