HISTOPATHOLOGY OF REGRESSION IN SINCLAIR SWINE MODEL OF MELANOMA

BACKGROUND: Detailed histopathologic studies of melanomas occurring in neonatal Sinclair miniature swine have demonstrated a remarkable simi larity to human melanoma. A significant difference is the predictable, complete regression of primary and metastatic tumors that occurs in a ll animals by early adulthood (1 to 2 years). Prior histopathologic de scriptions of regression in this model have been incomplete with regar d to the time of onset and chronologic sequence of events. This lack o f data makes it difficult to plan studies of regression mechanisms esp ecially when requiring the harvesting of tumor tissue. EXPERIMENTAL DE SIGN: By routine histologic methods, 94 tumors from 46 piglets were ev aluated for the degree of regression, presence of pigment-laden macrop hages, and presence of lymphocytes. One or more punch biopsies were pe rformed on 51 tumors before excision, for a total of 256 biopsies. RES ULTS: Regression took place in two phases. The first phase began durin g the 4th week after birth; was preceded by a rapid, massive infiltrat ion of pigment-laden macrophages; and was most active during the 2nd m onth. Significant numbers of lymphocytes were rarely seen in tumors du ring this phase of regression. In the vast majority of tumors, this in itial regression activity was followed by regrowth of residual tumor u sually appearing as emerging clones (intralesional transformation). Th e second phase of regression was characterized by asymmetrically distr ibuted lymphocytic infiltration of the residual melanoma, and progress ive regression of tumor over several months. Significant numbers of ly mphocytes were not present in the majority of the tumors until the beg inning of the 4th month. CONCLUSIONS: We conclude that regression of m elanoma in this animal model is a complex event in which the immune sy stem participates differentially during the natural history of the dis ease.