病理組織からみたcolitic cancerの初期病変

Histopathological Analysis of Ulcerative Colitis-related Cancers（Colitic Cancers）with Reference to Their Histogenesis

要旨　外科的に切除された潰瘍性大腸炎（UC）関連colitic cancer 10症例13病変の主病変部および周囲粘膜の病理組織学的所見に基づき，colitic cancerが組織レベルでどのように生じてくるのかについて検討した．7症例（10病変）では，細胞質の好酸性が一様に目立つ低異型度腺管やdystrophic goblet cellを含む杯細胞に富む低異型度不規則腺管の領域を伴っており，一部は鋸歯状変化も伴っていた．主病変の浸潤癌部の腫瘍上皮がこれらの低異型度上皮に類似した異型度を呈している例がみられたことや，これらの腺底部から微小浸潤癌が生じている所見を認めたことから，このような低異型度腺管領域はcolitic cancerの発生母地として重要と考えられた．これらは上皮の増殖・分化異常を示し，一部はp53が強陽性を呈しており，しばしばhuman gastric mucin（45M1）が陽性であった．他の3症例では平坦な萎縮粘膜内に進展した高異型度腺管領域から浸潤癌が生じていた．そのうちの1例では粘液豊富な絨毛状の低異型度上皮も認められたがp53強陽性であり，これも注意すべき所見と考えられた．colitic cancerの早期診断のためには，colitic cancerの発生に関連するとみなされる，これらの低異型度上皮・腺管領域を認識する努力が重要と思われる．一方，散発性腺腫と同様の組織像を呈する小ポリープ病変を伴うUC非手術例9例（平均経過期間5.8年）では，手術例のようなcolitic cancerおよび関連した所見が生じた例は認められなかった．

　To investigate the histogenesis of colitic cancers, we performed histopathological analysis of surgically resected ulcerative colitis-related cancers from 10 ulcerative colitis patients, with particular focus on the associated surrounding mucosal changes of the 13 main cancer lesions. In seven patients, with 10 of the main cancer lesions, the surrounding mucosal changes included eosinophilic and/or goblet cell-rich irregular glands with dystrophic goblet cells, and a partly serrated appearance, generally showing and low-grade atypia. Given that some of the main invasive cancers comprised low-grade neoplastic epithelia similar to those in the associated surrounding mucosa, and that some minute invasive cancers arose from the bases of glands with low-grade atypia as mentioned above, the presence of these glands showing low-grade atypia is an important stage in the development of colitic cancers. These glands showed abnormal proliferation and maturation through the crypt axis, some were strongly positive for p53, and many were positive for human gastric mucin（45M1）. In the other three patients, the main cancer lesions showed proliferation of glands with high-grade atypia in the atrophic flat mucosa, which in one case included an area of mucin-rich villous epithelium with low-grade atypia strongly positive for p53, indicating another significant lesion related to colitic cancers. In contrast, the above-mentioned lesions were not observed in nine non-operative ulcerative colitis cases with sporadic adenoma-like polypoid lesions during a mean follow-up period of 5.8 years. The identification of low-grade atypia in mucosal glands could be a vital step in the early diagnosis of colitic cancers.