Human melanocytic neoplasms and their etiologic relationship with sunlight

Abstract

Two hypotheses have been presented. The first states that melanomas commonly evolve from normal melanocytes by a tumor progression pathway from a banal nevus to a nevus with dysplasia, to a micro-invasive, and then to a fully evolved, tumorigenic, primary melanoma which has competence for metastasis. It is important to note that not all melanomas follow this complete pathway. As Foulds noted long ago, tumors may bypass any of the stages of tumor progression. Thus, many melanomas do not, apparently, arise in nevi, and melanomas may evolve "fully formed" as pure tumorigenic nodules. However, from the biological point of view, study of the benign potential precursors (nevi and, especially, dysplastic nevi as well as microinvasive melanomas) may well reveal mechanisms of progression that are applicable to all melanomas, and perhaps to other solid tumors as well. From a clinical viewpoint, follow-up and education of patients at increased risk for melanoma, and early diagnosis of melanomas in their curable, microinvasive stages may result in a reduction of mortality from the disease, even without influencing its overall incidence. The melanomas that occur on plantar and palmar (acral) skin appear to progress through a microinvasive stage similar to that of other cutaneous melanomas. However, the significance of precursor and marker lesions (if any exist) in acral melanoma remains to be elucidated by clinicopathologic and epidemiologic studies. The possibility of etiologic agents other than UV light, such as chemical carcinogens and/or viruses, should be investigated in these cases. The second hypothesis presented here, that UV light is etiologic for the common cutaneous melanoma of white populations, has support from clinical, epidemiologic, and biologic observations. From a biologic viewpoint, ultraviolet light has all of the properties that might enable it to act as a complete carcinogen, and to enhance tumor progression in melanocytic "potential-precursor" lesions. Clinically, it seems appropriate to encourage patients (and members of the general population, as well) to adopt sensible attitudes to sun exposure. By such means, it is possible that some melanomas might be prevented, or that the rate and incidence of progression to more-advanced stages might be inhibited.