Immunobiology of melanoma. Gross and ultrastructural studies in a new melanoma model: the Sinclair swine.

Work with the Sinclair swine began about 5 years ago when certain animals were noted to have an unusually large number of pigmented tumors (1) (Fig. 1). Initial analysis of these animals was done in a 2-year study of the evolution of these tumors, (2) which characterized the tumors in several stages that paralleled the life cycle of human melanocyte nevi (3). It appeared then that all lesions progressed through all these stages, from flat macules-Stage I, to smooth noduWes-Stage II, to florid exophytic tumors-Stage III, and then slowly regressed in Stages IV and V (Fig. 2). A significant finding of this study was the striking generalized depigmentation seen with tumor regression in some animals (Fig. 3). It was apparent in the preliminary studies that not all lesions progressed from Types I-V and that more than one type of lesion was present in these animals. About 2 years ago we began to study these animals with the following objectives: (1) To characterize the types of pigmented lesions and determine their human correlates; (2) to determine the chronology of the lesions with particular reference to the processes of depigmentation and malignant degeneration; (3) to begin selective breeding to increase the incidence of tumors; (4) to examine these lesions at the ultrastructural level. Ultrastructural study was necessary since on initial light-microscopy studies melanin was so abundant that even after bleaching the exact separation of melanocyte and melanophage was not possible (Fig. 4). Many of these lesions have now been evaluated and characterized. One example of malignant degeneration resulting in death of the animal was seen during the study. The types of pigmentary disorders seen in animals include: vitiligo, blue nevus, junctional nevus, compound nevus, congenital or bathing trunk nevus, Sutton's halo nevus, and melanoma (5). Selective breeding has dramatically increased the number of pigmented lesions present at birth and early life (Fig. 5). The rate of regression and incidence of depigmentation is currently being evaluated. From initial studies it appeared that the rate of malignant degeneration was less than 10%. This needs to be reevaluated. With the new genetic makeup from in-