Multiple Melanomas on Speckled Lentiginous Nevus: A Systematic Review and a Case Report.

Speckled lentiginous nevus (SLN), also known as nevus spilus (NS), is a variant of congenital melanocytic nevus. Although historically considered to have low malignant potential, recent studies have reported melanoma arising within SLN. This study presents a systematic review of multiple melanomas occurring in association with SLN and includes a representative clinical case. We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar was performed from 1957 to 2025 using the terms "melanoma" and "nevus spilus" or "speckled lentiginous nevus." Filters were applied for original reports, case series, and case reports. Studies were selected based on predefined criteria, with data independently extracted by two reviewers. A case of a 66-year-old male with three melanomas (two within and one outside SLN) over nine years is also presented. Because the evidence base consisted almost exclusively of case reports and small series, meta-analysis and formal risk-of-bias assessment were not feasible; findings were therefore synthesized qualitatively. We first describe an illustrative case of a 66-year-old male who developed three melanomas (two within and one outside SLN) over a nine-year period, underscoring the challenges of diagnosis and long-term monitoring. In the systematic review, we identified 41 eligible publications describing 51 patients, and in our illustrative case, we identified a total of 52 with melanoma on SLN; 9/52 (17.3%) developed multiple melanomas (24 total), and in our illustrative case, we identified a total of 52. Most were male (seven of nine), with the first melanoma diagnosed at a mean age of 52.4 years. The majority (21/24) occurred within SLNs ≥5 cm and were of the superficial spreading type (16/17 where specified). Of 24 tumors, 19 (79.2%) were synchronous, and among the 16 invasive melanomas, the mean Breslow thickness was 1.17 mm (median 0.95 mm, IQR 0.56-1.40 mm). Large or segmental SLNs may carry a clinically relevant risk for developing multiple melanomas. Regular full-body skin examinations and dermoscopic monitoring are recommended for early detection and management. As the synthesis is based mainly on case reports and small series, these conclusions are necessarily descriptive and exploratory, providing a qualitative mapping of the available evidence rather than definitive risk estimates.