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Summary.-Evidence is presented which indicates that S-(1,2,3,4-tetrahydro-2-hydroxy-l-naphthyl)-L-cysteine (THN-cysteine), formed by the reaction of 1,2-epoxy-THN with cysteine, can be incorporated into protein. The position of incorporation of THN-cysteine into protein would depend on whether the epoxide of THN reacts with cysteinyl-tRNACYs or with cysteine. In both cases, the mechanism of incorporation of THN-cysteine into protein is the same as for the natural amino acids. For example, the incorporation of THN-cysteinyl-tRNACYs is stimulated by Poly-UG, the code for tRNACys, and would be expected to be substituted for cysteine in protein being synthesized, whereas THN-cysteine not previously esterified to tRNA is activated by the isoleucyl-and valyl-RNA synthetases, and its incorporation is stimulated by Poly-AU and Poly-UG, respectively. Consequently, in this case, THN-cysteine would substitute for isoleucine and valine during protein synthesis.

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IMPORTANCE Little evidence exists to guide the management of moderately dysplastic nevi excisionally biopsied without residual clinical pigmentation but with positive histologic margins (hereafter referred to as moderately dysplastic nevi with positive histologic margins). OBJECTIVETo determine outcomes and risk for the development of subsequent cutaneous melanoma (CM) from moderately dysplastic nevi with positive histologic margins observed for 3 years or more. DESIGN, SETTING, AND PARTICIPANTS A multicenter (9 US academic dermatology sites) retrospective cohort study was conducted of patients 18 years or older with moderately dysplastic nevi with positive histologic margins and 3 years or more of follow-up data collected consecutively from January 1, 1990, to August 31, 2014. Records were reviewed for patient demographics, biopsy type, pathologic findings, and development of subsequent CM at the biopsy site or elsewhere on the body. The χ 2 test, the Fisher exact test, and analysis of variance were used to assess univariate association for risk of subsequent CMs, in addition to multivariable logistic regression models. To confirm histologic grading, each site submitted 5 random representative slide cases for central dermatopathologic review. Statistical analysis was performed from MAIN OUTCOMES AND MEASURES Development of CM at a biopsy site or elsewhere on the body where there were moderately dysplastic nevi with positive histologic margins. RESULTS A total of 467 moderately dysplastic nevi with positive histologic margins from 438 patients (193 women and 245 men; mean [SD] age, 46.7 [16.1] years) were evaluated. No cases developed into CM at biopsy sites, with a mean (SD) follow-up time of 6.9 (3.4) years. However, 100 patients (22.8%) developed a CM at a separate site. Results of multivariate analyses revealed that history of CM was significantly associated with the risk of development of subsequent CM at a separate site (odds ratio, 11.74; 95% CI, 5.71-24.15; P < .001), as were prior biopsied dysplastic nevi (odds ratio, 2.55; 95% CI, 1.23-5.28; P = .01). The results of a central dermatopathologic review revealed agreement in 35 of 40 cases (87.5%). Three of 40 cases (7.5%) were upgraded in degree of atypia; of these, 1 was interpreted as melanoma in situ. That patient remains without recurrence or evidence of CM after 5 years of follow-up. CONCLUSIONS AND RELEVANCEThis study suggests that close observation with routine skin surveillance is a reasonable management approach for moderately dysplastic nevi with positive histologic margins. However, having 2 or more biopsied dysplastic nevi (with 1 that is a moderately dysplastic nevus) appears to be associated with increased risk for subsequent CM at a separate site.