消化管内分泌細胞腫瘍の病理学的特徴―下部消化管（小腸・大腸）を中心に

Endocrine Cell Tumor of the Colorectum and Appendiceal Goblet-cell Carcinoid: A Problem of Pathologic Diagnostic Classification of Neuroendocrine Neoplasms

要旨　消化管内分泌細胞腫瘍は臨床病理学的特徴からカルチノイド腫瘍と内分泌細胞癌に分類される．WHO分類（2010年）は，腫瘍細胞の核分裂数とKi-67指数のみを組み合わせた組織学的分類で，神経内分泌腫瘍（NET G1/G2）と神経内分泌癌（NEC）に分類される．下部消化管のカルチノイド腫瘍の多くが直腸に発生し，悪性度の指標としては，腫瘍径，深達度，中心陥凹・潰瘍形成，核分裂像，脈管侵襲，およびKi-67指数が有用である．核分裂数とKi-67指数のみを組み合わせたWHO分類では，神経内分泌腫瘍（NET）の悪性度を推定するのは難しい．高悪性度癌である内分泌細胞癌は高率に腺癌を伴うが，WHO分類によれば腫瘍成分の割合によっては腺神経内分泌癌（MANEC）ではなく腺癌と診断されるため，呼称に真の悪性度が反映されない危険性をはらんでいる．虫垂の杯細胞カルチノイドの生物学的態度は，5年以上経過観察された8例中6例が5年以内に癌性腹膜炎で死亡していたことなどから，従来考えられている以上に十分な悪性性格を有しており，カルチノイドの1variantとするには特徴的組織像からも予後の点からも問題がある．

　Gastrointestinal endocrine cell tumors are classified in a carcinoid tumor and an endocrine cell carcinoma by a clinicopathologic characteristic. The WHO 2010 classification of neuroendocrine neoplasms is the histologic grading classification that is only based on mitotic count and Ki-67 index, and neuroendocrine neoplasms are classified in NET（neuroendocrine tumor）G1/G2 and NEC（neuroendocrine carcinoma）. Most of carcinoid tumor of the large intestine occurs in rectum. The findings of tumor size, depth of invasion, central depression and/or ulceration, mitotic index, vascular invasion, and Ki-67 index are useful predictive criteria in the assessment of the malignant nature of carcinoid tumor. In the WHO classification that is combined in only the number of mitoses and Ki-67 index, it is difficult to estimate a malignant potential of NET. Endocrine cell carcinoma is a kind of high-grade carcinoma and is frequently associated with an overlying adenoma or adenocarcinoma. According to the WHO classification, a mixed tumor may be diagnosed as an adenocarcinoma, not as MANEC（mixed adenoneuroendocrine carcinoma）, by a ratio of tumor component. So a true malignant potential is not reflected in the name called of this tumor. Among the 8 cases of appendiceal goblet-cell carcinoid followed up for over 5 years, six patients died of carcinomatous peritonitis within 5 years after the first operation. It shows that a biological behavior of a goblet-cell carcinoid of appendix is sufficiently malignant than it was thought. It has a problem that a goblet-cell carcinoid is a variant of carcinoid tumor from a characteristic histology and a poor prognosis.