Diagnostic impact of nuclear DNA content and proliferative activity in benign and malignant melanocytic lesions

Nuclear DNA content was assessed, using image cytometry, in adult melanocytes in normal skin and in 20 intradermal naevi, 60 junction naevi, 107 compound naevi, 61 dysplastic naevi, 17 melanomas in situ and 101 primary malignant melanomas. Proliferation was estimated using mitotic counting and immunohistochemical staining by anti-Ki-67 (clone MIB1) monoclonal antibodies. All normal adult melanocytes; and intradermal naevi (97% junction naevi, 98% compound naevi, 66% dysplastic naevi) were diploid. Thirty-four percent of the dysplastic naevi, 88% of the melanomas in situ and 96% of the malignant melanomas were clearly aneuploid. Proliferation, as assessed by mitotic counting and MI81 index, was significantly higher in aneuploid invasive malignant melanomas than in aneuploid dysplastic naevi (P<0.0001). The results indicate that histomorphologically defined entities of melanocytic lesions are characterized by typical DNA distribution patterns. Distinct aneuploidy combined with high proliferation rates generally seem to be well correlated to an increased malignancy potential of the lesion. In dysplastic naevi, the clonic expansion of aneuploid naevus cells may be limited by host defence mechanisms. Thus, DNA aneuploidy seems to indicate increased risk of malignant transformation, but has to be combined with other data, such as proliferation, in order to differentiate more precisely between different melanocytic lesions.