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Nevus-Associated and De Novo Melanoma: A Cross-Sectional Study on Prognostic Differences
by
, , , ,
Emi Dika
1,2
,
Federico Venturi
1,2
,
Biagio Scotti
1,2
,
Alberto Gualandi
1,2,
Carlotta Baraldi
1,2,
Sabina Vaccari
1,2,
Sebastiano Posenato
1,2,
Corrado Zengarini
1,
Aurora Alessandrini
1,2,
Leonardo Veneziano
1,2,
Marco Ardigò
3,4 and
Elisabetta Magnaterra
1,2,* 1
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
2
Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy
3
Dermatology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
4
Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Milano, Italy
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(23), 3859; https://doi.org/10.3390/cancers17233859 (registering DOI)
Submission received: 26 October 2025
/
Revised: 20 November 2025
/
Accepted: 29 November 2025
/
Published: 30 November 2025
(This article belongs to the Special Issue Oncologic Pathology: Diagnostic Challenges, Molecular Advances, and Clinical Correlations)
Simple Summary
Melanoma is a serious subtype of tumor of the skin that can develop either from healthy skin or from a pre-existing mole. Understanding whether a melanoma arises on its own or from a mole is important, as this may influence how the tumor behaves and how it should be managed. In this study, we analyzed nearly 400 patients with melanoma to compare nevus associated melanoma and de novo melanoma. We found that melanomas associated with nevi were usually thinner, showed fewer signs of aggressive growth, and were more common in younger patients and on the trunk. However, long-term survival was similar between the two groups. These findings highlight the importance of regular skin checks, especially for people with many moles, and suggest that further research into the biological differences between these melanoma subtypes may help improve prevention and treatment strategies.
Abstract
Background/Objectives: Melanomas may develop de novo or in association with a pre-existing nevus (nevus-associated melanoma, NAM). Whether these subtypes differ in their clinical and biological behavior remains uncertain. We aimed to compare the clinicopathologic features and outcomes of NAM and de novo melanoma (DNM) in a large single-center cohort. Methods: We retrospectively analyzed 378 patients with invasive melanoma diagnosed between 2007 and 2021 at a tertiary referral center. Tumors were classified as NAM when histopathologic continuity with a nevus was present, and as DNM otherwise. Clinical, histologic, and prognostic variables were compared using univariate and multivariate analyses. Results: Of 378 melanomas, 90 (24%) were NAM and 288 (76%) were DNM. Patients with NAM were slightly younger (mean 52 vs. 54 years) and more often presented with tumors on the trunk (65.6% vs. 51.7%). NAMs exhibited lower Breslow thickness (0.55 vs. 0.84 mm), reduced mitotic activity (0.17 vs. 1.21/mm2), and less frequent ulceration (2.2% vs. 9.4%). Distant metastases occurred only in DNM (6.6%). Sentinel lymph node positivity (1.1% vs. 6.3%) and melanoma-specific mortality (0% vs. 0.69%) did not differ significantly. Multivariate analysis identified Breslow thickness and mitotic rate as independent predictors of subtype. Conclusions: NAMs present with more favorable histopathologic features than DNMs, yet long-term outcomes appear similar. These findings support divergent pathways of melanoma development and underscore the need for molecular and imaging studies to refine risk stratification and guide management.
