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In order to detect possible dysplastic melanocytic naevi (DMN) associated melanoma risk factors and lesion specific differences in the mutation spectrum of dysplastic and congenital melanocytic naevi (CMN), we screened 19 specimens of human sporadic DMN derived from 19 patients for the presence of mutations in five genes, which we had investigated in a former study in 19 CMN 1 and which have been reported to be associated with human cutaneous melanoma (N-ras, 2 p53, 3 CDKN2A, 4 CDK4, 5 and MC1R 7). METHODSDNA was extracted from selected paraffin embedded DMN resection specimens using the QIAamp DNA Mini Kit (Qiagen) according to the recommendations of the supplier. The relative number of atypical melanocytes in the DMN and the histological subtype of the DMN were determined in parallel slides by an experienced dermatologist (Dr Regina Zimmermann) (table 1). The screening strategy for the detection of activating point mutations in the oncogenes N-ras and CDK4 as well as for germline sequence variants in the MC1R gene by combined RFLP-PCR/SSCP analysis, and the screening strategy for the detection of homozygous deletions and point mutations in the tumour suppressor genes p53 and CDKN2A by combined multiplex-PCR/SSCP analysis, have been described previously.1 In order to find out if the SSCP screening system that is used in our laboratory is suitable to detect point mutations in minor cellular subpopulations of the DMN lesions investigated (for example, N-ras point mutations in the atypical melanocyte fraction), we added gradually decreasing amounts of N-ras mutation harbouring genomic DNA (CAA to AAA mutation at one allele) to genomic N-ras wild type DNA before PCR and SSCP analysis. As a result, we could show that the aberrant mutation associated SSCP band is still visible at an admixture of less than 1% of mutation harbouring DNA (fig 1).In the present study we extended our MC1R screening system in order to allow the detection of two additional sequence variants (R151C and R160W), which like V92M and D294H 6 have been reported to be associated with red hair and light skin. 8 For reamplification of the 899 bp MC1R PCR preamplification product 1 with primer pair MC1R4A (5′ TCGCC GTGGA CCGCT ACATC 3′)/MC1R4B (5′ GCGTG CTGAA GACGA CACTG 3′) (120 bp PCR product, suitable for codon 151 and Key points• Nineteen specimens of human sporadic dysplastic melanocytic naevi (DMN) were screened for the presence of mutations in N-ras, p53, p16INK4a, p14ARF, CDK4, and MC1R.• In contrast to human congenital melanocytic naevi, a very low frequency of N-ras mutations seems to be characteristic of DMN.

Eighteen congenital melanocytic naevi (CMN) from 17 patients and 18 dysplastic melanocytic naevi (DMN) from 18 patients were screened for mutations in the BRAF oncogene (present study) and the N-ras oncogene (in the course of two foregoing studies) by single-strand conformational polymorphism (SSCP)/sequencing analysis. BRAF mutations were demonstrated in both types of lesion. As a whole, 17 of 18 CMN (94.4%) and five of 18 DMN (27.7%) harboured either BRAF or N-ras mutations. As the BRAF oncogene is frequently found to be mutated in human cutaneous melanomas, it may constitute a risk factor for melanoma formation within CMN and DMN.

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Five patients with generalized slate-gray discoloration of the skin have been diagnosed histologically as argyria in the last 35 years in the Department of Dermatology and Venereology of Rostock and Halle. Light microscopically, there was visible black pigmentation in histiocytes, fibroblasts, and multinucleated giant cells of the dermis. In the transmission electron microscope (TEM), the authors observed electron-dense deposits inside lysosomes and residual bodies of phagocytes as well as outside the cells in the connective matrix. These deposits were identified by elemental analysis in TEM and electron energy loss spectroscopy (EELS) as well as scanning electron microscope (SEM) and energy dispersive x-ray analysis (EDX) containing silver and sulfur. Therefore, they seem to consist of silver sulfide. Argyria is of low medical relevance and is very rarely induced because of silver-containing drugs. Nevertheless, there are still a lot of silver products on the market, easily available over-the-counter. Therefore, argyria should not be forgotten or missed in the diagnostics of human dermis.