Qureshi S R, Perentes E, Ettlin R A, Kolopp M, Prentice D E, Frankfurter A
Sandoz Pharma Ltd., Drug Safety Assessment/Toxicology, Basle, Switzerland.
Toxicol Pathol. 1991;19(3):280-6. doi: 10.1177/019262339101900311.
During a routine long-term drug safety study, lasting approximately 2 1/2 yr, male Wistar rats, treated with a prolactin-inhibiting compound, developed an excess of Leydig cell tumors (LCTs). Most tumors were typical for the rat but a small number showed an unusual variation and some appeared malignant. The variation consisted of glandular and/or tubular structures within the tumor mass which occasionally anastomosed and contained an eosinophilic periodic-acid Schiff (PAS) positive material. In a few of these variants, malignant features such as cellular atypia, capsular, and lymphatic invasion and necrosis were seen. No metastases were detected. Detailed morphological and immunohistochemical investigations were conducted in order to establish the cell of origin of these variants. Glandular/tubular structures were found to stain with varying intensity for vimentin and cytokeratin, but were always negative for beta-tubulin. The results indicated that the cell of origin of these LCT variants was indeed the Leydig cell and that glandular and/or tubular structures within LCTs represented a form of Leydig cell metaplasia.
在一项为期约两年半的常规长期药物安全性研究中,用一种催乳素抑制化合物处理的雄性Wistar大鼠发生了过量的睾丸间质细胞瘤(LCT)。大多数肿瘤是典型的大鼠肿瘤,但少数表现出异常变异,有些似乎是恶性的。变异包括肿瘤块内的腺管和/或管状结构,这些结构偶尔相互吻合并含有嗜酸性过碘酸希夫(PAS)阳性物质。在其中一些变异体中,可见细胞异型性、包膜侵犯、淋巴管侵犯和坏死等恶性特征。未检测到转移。为了确定这些变异体的起源细胞,进行了详细的形态学和免疫组织化学研究。发现腺管/管状结构波形蛋白和细胞角蛋白染色强度不同,但β微管蛋白始终为阴性。结果表明,这些LCT变异体的起源细胞确实是睾丸间质细胞,LCT内的腺管和/或管状结构代表了一种睾丸间质细胞化生形式。