【大腸】Superficially serrated adenoma（SuSA）と鋸歯状病変全体像

Superficially serrated adenoma: a proposal for a novel subtype of colorectal serrated lesion

Modern Pathology volume 31, pages1588–1598(2018)
Taiki Hashimoto, Yusaku Tanaka, Reiko Ogawa, Taisuke Mori, Hiroshi Yoshida, Hirokazu Taniguchi, Nobuyoshi Hiraoka, Motohiro Kojima, Yasuhiro Oono, Yutaka Saito & Shigeki Sekine

Abstract
We describe a series of colorectal polyps characterized by mixed adenomatous and serrated features, herein referred to as superficially serrated adenomas. Twenty superficially serrated adenomas were obtained from 11 female and 9 male patients aged 62-87 years. Most lesions endoscopically appeared as small sessile polyps, but larger lesions were plaque-like (2-20 mm; median, 5 mm). Eighteen lesions (90%) were located in the sigmoid colon or rectum. They consisted primarily of straight, adenomatous glands but showed serration confined to the superficial layer. Immunohistochemistry revealed CK20 expression in the upper layer. Proliferating cells, determined by their expression of Ki-67, were localized to the middle to bottom layers. Genetic analyses identified KRAS mutations in 19 lesions and a BRAF mutation in one lesion. Furthermore, RSPO fusions and/or overexpression were observed in 18 lesions and truncating APC mutations were observed in the two remaining lesions. Consistent with the presence of WNT pathway gene alterations, all superficially serrated adenomas showed focal or diffuse nuclear β-catenin accumulation. Since concurrent KRAS mutations and RSPO fusions are reportedly common in traditional serrated adenomas, we reviewed 129 traditional serrated adenomas and found 15 lesions (12%) that were associated with superficially serrated adenoma components. Remarkably, all but one superficially serrated adenoma-associated traditional serrated adenoma exhibited concurrent KRAS mutations and RSPO fusions/overexpression. The present study suggests that superficially serrated adenoma is a morphologically and molecularly distinct type of colorectal serrated polyp that is histogenetically related to traditional serrated adenoma.

Superficially serrated adenoma: a proposal for a novel subtype of colorectal serrated lesion

【SANOTIC SUMMARY】
SuSA は
（１）表面鋸歯状、深部は管状腺腫様を示す新規疾患単位
（２）KRAS 変異＋RSPO 融合遺伝子or過剰発現を示す
（３）KRAS 変異陽性の TSA の前駆病変
（４）増殖帯（Ki-67陽性細胞）は中層付近に分布

💡鋸歯状病変の癌化経路

上記は国立がんセンター中央病院から 2018 年に発表された論文で、鋸歯状病変の癌化経路に関して非常に大きなインパクトがあったが、新 WHO 分類の改定にはまだ内容が反映されていない。次回の改定では間違いなく反映されると思う。

従来、TSA には KRAS 変異群と BRAF 変異群があることが知られていた。BRAF 変異群は SSA/P 由来と考えられ、SSA/P 由来と考えられる TSA では病変基部に SSA/P 様成分が少量あるが、基本的には 0-Ip 型病変を示す。一方、本論文から、KRAS 変異 TSA は SuSA 由来と考えられ、基部に広い SuSA 病変が広がっており、0-IIa+Ip 型病変を示す。

TSA の前駆病変は２種類（SSA/P と SuSA）
　👉 SSA/P-TSA 経路は BRAF 系：0-Ip 型
　👉 SuSA-TSA 経路は KRAS 系：0-IIa+Ip 型

【鋸歯状病変と管状腺腫の癌化経路の概略図】

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