Clinicopathological, Genetic and Survival Advantages of Naevus-associated Melanomas: A Cohort Study

Abstract

Several studies have suggested that naevus-associated melanomas differ from de novo melanomas, being thinner and with less ulceration; however, the prognostic implication is unclear. The objective of this study was to describe clinicopathological, genetic and survival characteristics of de novo and naevus-associated melanomas in a cohort of primary invasive cutaneous melanomas over a 20-year period. Of the 2,227 patients included in the study, 509 (22.86%) had naevus-associated melanomas. Compared with patients with de novo melanoma, they were younger, with a fairer phototype and a higher naevus count, tumours were predominantly the superficial spreading subtype, American Joint Committee on Cancer stage I, located on the trunk, and there were fewer signs of invasiveness (thinner Breslow index, less ulceration, lower mitotic index and less satellitosis). Germline mutational status did not show any significant association. As determined through univariate analysis, overall survival was significantly better in patients with naevus-associated melanoma (hazard ratio 0.64; 95% confidence interval 0.51–0.80, p < 0.001), but multivariate analysis did not support this prognostic indication (hazard ratio 0.94; 95% confidence interval 0.75–1.18, p < 0.606). Despite this, we conclude that naevus-associated and de novo melanomas should be considered as different subtypes of melanoma.

A review of nevus‐associated melanoma: What is the evidence?

“…Different characteristics of NAM compared to de novo melanoma have been reported in several studies, supporting the divergent models of melanoma development. De novo melanoma has been described in older patients compared to NAM 12,13,19,22,28,29 . Also, de novo melanoma was more likely than NAM to be associated with female gender, ulceration and location on the head/neck or extremities compared to trunk, while it was less likely to have regression present 13 .…”

“…There are conflicting findings in the survival of de novo vs. NAM, although most studies showed no effect of the nevus association after multivariate adjustment for factors known to affect survival such as Breslow thickness and ulceration 12,13,18,38 (Table 2). In one study, Cymerman et al.…”

“…De novo melanoma has been described in older patients compared to NAM. 12,13,19,22,28,29 Also, de novo melanoma was more likely than NAM to be associated with female gender, ulceration and location on the head/neck or extremities compared to trunk, while it was less likely to have regression present. 13 NAM compared to de novo melanoma has been associated with thinner tumours, possibly due to an obliteration of the nevus component by the growing tumour in thicker lesions.…”

“…Regarding LMM, no case of nevus remnants was reported in LMM in some studies, 26,29,32 while others have reported the presence of nevus remnants in a small number of LMMs. 12,18,19,22,23,25,28,33 Even though some misclassification in the histologic diagnosis of the subtype cannot be ruled out, most of these evaluations have been performed by expert histopathologists.…”

“…Higher nevus counts have been associated with NAM compared to de novo melanoma, supporting that NAM development may be mediated by a divergent pathway. 12,19,24,28 There are conflicting findings in the survival of de novo vs. NAM, although most studies showed no effect of the nevus association after multivariate adjustment for factors known to affect survival such as Breslow thickness and ulceration 12,13,18,38 (Table 2). In one study, Cymerman et al found that de novo melanoma was an independent factor predicting worse overall survival in one of the two patient cohorts studied.…”