Melanoma arising in nevus spilus: a systematic review and report of two new cases.

Nevus spilus (NS) is a melanocytic lesion characterized by multiple darker macules or papules within a lighter-brown background patch. It is generally considered benign, but rarely melanoma may arise within NS. This association is controversial and poorly quantified. We systematically reviewed the literature on melanoma arising in NS and describe two additional reports. Clinical, histopathologic, molecular, and outcome data were extracted from all eligible cases. The aim of our study was to analyze the clinicopathological patterns, risk factors, and management implications. A total of 39 cases met inclusion criteria, suggesting that melanoma arising in NS is rare but not anecdotal. Most cases occurred in large, congenital, zosteriform lesions; the predominant location was the trunk, followed by the lower and upper limbs; the most common histotype was superficial spreading melanoma (SSM). Favorable outcomes were associated with early detection and thinner lesions, whereas thicker or nodular melanomas and delayed diagnosis correlated with poorer prognosis. Molecular data were limited but suggested possible heterogeneity, with infrequent BRAF/NRAS mutations. The risk of melanoma arising in NS appears to be subtype-dependent rather than uniform. Routine prophylactic excision of NS lesions is not supported by current evidence. A structured clinical and dermoscopic follow-up - particularly for larger, congenital, and segmental lesions - may represent a balanced management strategy, facilitating earlier identification of malignant transformation and ultimately improving patient outcomes. Further molecular profiling studies are needed to clarify pathogenetic mechanisms and refine risk stratification.