Ide Tetsuya, Moriyama Akiko, Uchida Kazuyuki, Chambers James K, Okazaki Takanobu, Kobayashi Kinji, Nakatsuji Shunji, Matsumoto Masahiro
Drug Safety Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura, Kagoshima 891-1394, Japan.
J Toxicol Pathol. 2016 Jul;29(3):191-4. doi: 10.1293/tox.2016-0011. Epub 2016 Apr 21.
A male cynomolgus monkey (Macaca fascicularis) of 5 years and 11 months of age from the vehicle control group of a 4-week repeated oral dose toxicity study had a spontaneously occurring mass lesion directly attached to the proximal part of the left trigeminal nerve. Histologically, the mass was characterized by a multifocal nodular appearance. Nodular zones showed low to moderate cellularity and were composed of small round cells exhibiting nuclear uniformity. On the other hand, inter-nodular zones were composed of nerve fiber containing septa and closely aggregated highly pleomorphic cells. Immunohistochemically, the small round cells were strongly immunopositive for synaptophysin, neuN, and class III beta-tubulin, while the highly pleomorphic cells were weakly immunopositive for neuN and occasionally immunopositive for class III beta-tubulin and doublecortin, suggesting that the tumor had originated from a neuronal lineage cell. Based on these findings, the mass was diagnosed as a neuroblastoma at the trigeminal nerve.
在一项为期4周的重复口服给药毒性研究的车辆对照组中,一只5岁11个月大的雄性食蟹猴(猕猴)在左三叉神经近端直接出现了一个自发的肿块病变。组织学上,该肿块的特征是多灶性结节状外观。结节区域细胞密度低至中等,由核形态一致的小圆形细胞组成。另一方面,结节间区域由含有隔膜的神经纤维和紧密聚集的高度多形性细胞组成。免疫组织化学分析显示,小圆形细胞对突触素、神经元核抗原(neuN)和III类β微管蛋白呈强免疫阳性,而高度多形性细胞对neuN呈弱免疫阳性,偶尔对III类β微管蛋白和双皮质素呈免疫阳性,这表明肿瘤起源于神经谱系细胞。基于这些发现,该肿块被诊断为三叉神经母细胞瘤。