Yoshitomi K, Elwell M R, Boorman G A
Department of Pathology, Tsukuba Research Institute, Sandoz Pharmaceuticals Ltd, Ibaraki, Japan.
Toxicol Pathol. 1995 Jan-Feb;23(1):16-25. doi: 10.1177/019262339502300103.
A total of 121 spontaneous amelanotic melanomas of the skin were identified in 70 of 11,171 male and 51 of 10,927 female Fischer-344/N rats in 63 2-yr carcinogenicity studies conducted by the National Cancer Institute's Carcinogenicity Testing Program/National Toxicology Program. Amelanotic melanomas had characteristic anatomical locations and histologic features distinguishable from Schwann cell tumors. Of the 121 tumors, 84, 19, 10, and 8 cases occurred in the pinna, eyelid, scrotum, and perianal region (anus and tail), respectively. Amelanotic melanomas originated from the dermis and consisted of spindle cells arranged in an interlacing fascicular pattern often with a perivascular orientation; epithelioid cells were rarely seen. Only the tumors arising in the pinna metastasized to the lung and/or mandibular lymph nodes. The metastatic rate was 19% (16/84) of the tumors and was clearly increased with an increase in tumor size. Most metastasizing tumors had focal areas consisting of anaplastic spindle cells with an increased number of mitosis. The tumor cells stained positive for S-100 protein but negative for melanin. Ultrastructurally, the tumors were diagnosed as amelanotic melanomas based on the identification of numerous, intracytoplasmic premelanosomes without melanin formation in the tumor cells which were not enveloped by pericytoplasmic basal laminae. One localized amelanotic melanoma of the pinna was successfully transplanted to the subcutaneous tissue in the flank of 3 Fischer-344/N rats.
在美国国立癌症研究所致癌性测试项目/国家毒理学项目开展的63项为期两年的致癌性研究中，在11171只雄性和10927只雌性Fischer-344/N大鼠中，分别有70只雄性和51只雌性大鼠身上共发现了121例自发性皮肤无色素性黑色素瘤。无色素性黑色素瘤具有特征性的解剖位置和组织学特征，可与施万细胞瘤相区分。在这121例肿瘤中，分别有84例、19例、10例和8例发生于耳廓、眼睑、阴囊和肛周区域（肛门和尾部）。无色素性黑色素瘤起源于真皮，由呈交错束状排列且常呈血管周围排列方向的梭形细胞组成；很少见到上皮样细胞。只有发生于耳廓的肿瘤转移至肺和/或下颌淋巴结。转移率为肿瘤的19%（16/84），且明显随肿瘤大小增加而升高。大多数发生转移的肿瘤有由间变梭形细胞组成的局灶区域，有丝分裂数量增加。肿瘤细胞S-100蛋白染色呈阳性，但黑色素染色呈阴性。在超微结构上，根据在肿瘤细胞中识别出大量未形成黑色素的胞质内前黑素体，且这些前黑素体未被周细胞质基膜包裹，这些肿瘤被诊断为无色素性黑色素瘤。1例局限性耳廓无色素性黑色素瘤成功移植到3只Fischer-344/N大鼠胁腹的皮下组织。
