Morphologic characteristics of nevi associated with melanoma: a clinical, dermatoscopic and histopathologic analysis

Background The aim of this retrospective study was to determine the frequency of nevus-associated melanomas and to better characterize the preexisting nevus from a histopathologic, clinical and dermatoscopic point of view. Methods We reviewed the histopathologic slides of a consecutive series of 357 melanomas and corresponding clinical and dermatoscopic images, if available. Results We found that 31 (8.7%) melanomas were associated with a preexisting nevus, 284 (79.5%) melanomas developed de novo, and in 42 (11.8%) a preexisting nevus could not be excluded, although the alternative explanation that the entire lesion represented a melanoma was also possible. The preexisting nevus was a “superficial” or “superficial and deep” congenital nevus in 27 cases (87%) and a Clark nevus in 4 cases (13%). Clinical or dermatoscopic images were available in 149 (41.7%) cases. The preexisting nevus, if visible, looked inconspicuous clinically or dermatoscopically. The median invasion thickness of nevus-associated melanoma was not significantly different from “de novo” melanomas but the frequency of in situ melanomas was higher in the “de novo“ group (40.1% versus 16.1%). Patients with melanoma in association with a nevus were significantly younger (mean age=55 years, SD: 16 years) than patients with “de novo” melanomas (mean age=68 years SD: 15 years, p<0.001). When controlled for age and invasion thickness overall, survival did not differ significantly between patients with nevus-associated melanomas and patients with de novo melanomas. Conclusions From a histomorphologic point of view, the majority of melanomas arise de novo. If melanomas develop in a preexisting nevus, they usually occur in association with a “superficial” or “superficial and deep” congenital nevus.


Statistical Analysis
Continuous data are given as mean and standard deviations (SD) or as median and range, as appropriate. T-tests or Mann-Whitney U tests were used to compare groups and the chi-square test for the comparison of proportions. The Kaplan-Meier method and a Cox proportional hazards analysis were used to analyze differences in overall survival. All given P-values are two-tailed. A P-value <.05 was considered statistically significant.
The general characteristics of the melanomas are given in Table 1. After reviewing the histopathologic slides, we found that 284 melanomas (79.5%) developed de novo and 31 (8.7%) in association with a preexisting nevus. In 42 (11.8%) cases a preexisting nevus could not be excluded, although the alternative explanation that the entire lesion represented a melanoma was also possible.

Introduction
It is generally agreed that the majority of melanomas arise de novo [1][2][3][4][5]. Tsao et al stated that the risk of malignant transformation of any specific melanocytic nevus is low [5].
Some authors, however, believe that melanomas frequently develop in so called "dysplastic nevi" [6][7][8]. Kaddu [3]. The classification of the type of associated nevus is difficult because of the lack of a generally accepted classification of nevi. It has also been reported that patients with a melanoma in association with a preexisting nevus are significantly younger than patients with de novo melanomas [1,3]. The purpose of this study was to determine the frequency of melanoma in association with a preexisting nevus and to characterize the clinical, histopathologic and dermatoscopic appearance of nevi that are associated with melanoma.

General Characteristics
We analyzed a series of 357 consecutive cases of histologi-

Histopathologic Assessment and Review of Images
All cases were subjected to standard histopathologic processing. Histopathologic slides were reviewed by the study authors and classified into the following subgroups: (1) de novo melanomas, (2) melanomas arising in a preexisting nevus, and (3) non-decidable cases. Histopathologic review of the case was performed without knowledge of the respective clinical or dermatoscopic images. We used standard histopathologic criteria to differentiate between melanomas and nevi. For the classification of associated nevi, we used the nevus classification according to Ackerman and differentiated between Clark nevi, superficial congenital nevi (Ackerman nevi), and "superficial and deep" congenital nevi (Zitelli nevi) [9]. A schematic presentation of the histopathologic characteristics of these nevi is given in Figure 1. The two study authors reviewed all available clinical and derma-

Discussion
The results of our study support the view that most melanomas arise de novo. The proportion of nevus-associated melanomas in our study was smaller than 10% The concept of stepwise tumor progression from a common nevus over a "dysplastic nevus" to melanoma, as set forth by Clark and others, is not supported by our data [10]. We found that if melanomas develop in an associated nevus, it is most often a "superficial" or a "superficial and deep" congenital nevus.
A Clark nevus is less often associated with a melanoma. Our findings do not support the concept that "melanocytic dysplasia," if it exists, has any predictive value with regard to the chance that a melanoma may arise in a specific nevus.
Given the original description by Clark and coworkers, it has been proposed that the "dysplastic nevus" is a risk marker and a precursor of melanoma [11].
Recently the latter view has been ques-