髄様型大腸低分化腺癌の病理学的特徴

Clinicopathologic Characteristics of Medullary-type Poorly Differentiated Colorectal Adenocarcinoma

要旨　大腸低分化腺癌の中に比較的予後良好な群が存在することは古くから指摘されており，近年，髄様型低分化腺癌として認識されつつある．この腫瘍は，組織学的に比較的よく揃った類円形核と，豊富な好酸性胞体を有する細胞から構成され，膨張性に増殖し，腫瘍辺縁や内部に炎症細胞浸潤を高率に伴うという特徴がある．これらの組織学的特徴に基づき，低分化腺癌84例を髄様型50例と非髄様型34例に亜分類し，臨床病理学的に検討した．その結果，髄様型癌は高齢，女性，右側結腸発生，肉眼型2型優位，低脈管侵襲，低リンパ節転移，比較的予後良好という臨床病理学的特徴を示すことが明らかになった．分子病理学的には，hMLH1プロモーター領域のメチル化，hMLH1蛋白発現減弱，マイクロサテライト不安定性が高率に認められ，髄様型低分化腺癌は特異な発癌経路により発生する腫瘍と考えられた．この腫瘍は高齢者では低分化腺癌の約2/3を占め，特に女性の右側結腸に発生した低分化腺癌はまず髄様型であることを疑って鑑別診断を進める必要がある．さらに，現規約の低分化腺癌の亜分類（por1，por2）は，上記の疾患概念に基づいた髄様型・非髄様型に改めるべきと考える．

　It is well known that there is a poorly differentiated colorectal carcinoma with a favorable prognosis. According to cellular findings including nuclear atypia and cytoplasmic features, poorly differentiated adenocarcinomas were divided into two groups : medullary type and non-medullary type. Pathology and microsatellite status were examined in 84 poorly differentiated colorectal adenocarcinomas（50 medullary type and 34 non-medullary type）as well as hMLH1 promoter methylation and hMLH1 expression. Medullary-type carcinomas were significantly linked to older age, female predominance, proximal location, low incidence of lymph-node metastasis, less frequent lymphatic and venous permeation and a favorable prognosis. Molecular pathology demonstrated frequent hMLH1 promoter methylation with loss of hMLH1 expression and microsatellite instability in the medullary-type carcinoma. Medullary-type carcinomas accumulate with advancing age, especially in women. Furthermore, subclassification of poorly differentiated adenocarcinoma in the present version of the general rules should be revised because medullary-type carcinoma clinicopathologically shows a distinct entity.