Clinicopathologic spectrum of primary uveal melanocytic lesions in an animal model

Background: Currently, there are no animal models of primary uveal melanoma in an eye large enough to allow documentation of the clinical evolution of the lesion by either funduscopy or fundus photography. Methods: The authors induced primary uveal melanocytic lesions in the eyes of Dutch (pigmented) rabbits using a two-stage carcinogenesis protocol involving initiation with 4 weekly topical applications of 10 μl of a 1 % solution of 7,12-dimethyl-benz[a]anthracene (DMBA) in acetone (21 eyes) followed by 12 weekly topical applications of a 10 μl solution of either 0.25% or 0.5% croton oil in acetone. They also investigated the effect of initiation with DMBA without promotion and the effects of chronic topical exposure to acetone and proparacaine. Results: Exposure to DMBA followed by promotion with croton oil in either concentration was the most effective means of inducing clinically detectable fundus lesions. Histologically, a spectrum of melanocytic proliferations developed including benign nevi, nevi with varying grades of cytologic atypia, and clusters of confluent atypical melanocytes that may represent early melanomas. Although clinical regression of fundus lesions was noted in eight eyes after promotion had been stopped, five of these eyes showed unequivocal histologic evidence of a residual uveal melanocytic lesion. Chronic ocular irritation is capable of inducing cytologically benign subclinical uveal melanocytic proliferations. Conclusions: The conventional classification of human uveal melanocytic lesions includes only nevi and melanomas, but a comparison of the results of this study with descriptions of human uveal melanocytic nevi suggests the existence of a spectrum of intermediate atypical precursor lesions in humans.