Is There More Than One Road to Nevus-Associated Melanoma?

The association of melanoma with a preexisting nevus is still a debated subject. Histopathological data support an associated nevus in approximately 30% of all excised melanomas. The annual risk of an individual melanocytic nevus becoming malignant is extremely low and has been estimated to be approximately 0.0005% (or less than 1 in 200,000) before the age of 40 years, to 0.003% (1 in 33,000) in patients older than 60 years. Current understanding, based on the noticeable, small, truly congenital nevi and nevi acquired early in life, is that the first develops before puberty, presents with a dermoscopic globular pattern, and persists for the lifetime, becoming later a dermal nevus in the adult. In contrast, acquired melanocytic nevi develop mostly at puberty and usually undergo spontaneous involution after the fifth decade of life. The purpose of this review is to analyze the data of the literature and to propose, on the basis of epidemiological and clinical-dermoscopic characteristics, a new model of melanogenesis of nevus-associated melanoma.


00) before th
age of 40 years, to 0.003% (1 in 33,000) in patients older than 60 years [2,3].However, since many studies propose a direct correlation between the number of moles and melanoma development (roughly 2-to 14-fold), efforts to curb the rise in melanoma have centered on the detection of early changes in melanocytic nevi [2].

The association of melanoma with a preexisting nevus is still a debated subject.Histopathological data support an associated nevus in approximately 30% of all excised melanomas.The annual risk of an individual melanocytic nevus becoming malignant is extremely low and has been estimated to be approxim tely 0.0005% (or less than 1 in 200,000) before the age of 40 years, to 0.003% (1 in 33,000) in patients older than 60 years.Current understanding, based on the noticeable, small, truly congenital nevi and nevi acquired early in life, is that t e first develops before puberty, presents with a dermoscopic globular pattern, and persists for the lifetime, becoming later a dermal nevus in the adult.In contrast, acquired melanocytic nevi develop mostly at puberty and usually undergo spontaneous involution after the fifth decade of life.The purpose of this review is to analyze the data of the literature and to propose, on the basis of epidemiological and clinical-dermoscopic characteristics, a new model of melanogenesis of nevus-associated melanoma.


ABSTRACT

in some cases, it is extremely difficult to determine the original association with a preexisting nevus [1,3].


Clinical and Dermoscopic Aspects

Currently, there is widespread agreement about certain clinical features of NAM and its age-and sex-related incidence, whereas some discordance regarding the histological subtype and anatomic site is reported among different studies.

In most studies, NAM appears to be a superficial spreading type of melanoma generally occurring on the trunk.On the other hand, DNM is associated with a nodul

subtype,
as well as with an anatomic location on the extremities, which has better outcomes than on the trunk in several

urvival models [2,3].

In the met
-analysis of Pampena et al, no relevant differences were observed between NAM and DNM groups regarding the melanoma subtype and body site.Superficial spreading melanoma was the most common frequent subtype, whereas the trunk and the e tremities were the most common locations [1].

To our knowledge, it is difficult to distinguish NAM and DNM based on dermoscopy, and moreover there are only a limited number of studies about this topic.

Stante et al found that an atypical pigment network and regression structures were associated with mel noma arising in a nevus [4].

To detect dermoscopic parameters, a further study by Shitara et al was conducted [5].

A case-control test set of NAM vs DNM, paired by Breslow thickness and histopathological subtype, was analyzed by 2 blinded experienced dermoscopists, according to criteria suc as presence of nevus, pattern analysis, and ABCD dermoscopy score.The results showed that the presence of irregular globules, streaks, and a negative pigme t network were significantly related to NAM.In contrast, the presence of a blue-white veil was not associated with NAM.No significan differences were found between the other dermoscopic criteria or in any global patter in pattern analysis [5].


Histopathological Features

NAM is defined by the coexistence of nevus components and melanoma features in histopathological examination.A higher prevalence of invasive melanoma is reported for both NAM and DNM groups; however, in situ melanomas are slightly more prevalent in NAMs [1].

Cymerman et al reported that DNM was associated with mean Breslow thickness greater than 1.0 mm, ulceration, and stage greater than I [3]; even Pampena et al found a significantly lower mean Breslow thickness in NAMs than Observations imply that nevi undergo dynamic proliferations that appear and disappear throughout the lifetime.

Currently, nevi are merged into 2 categories

congenital and acquired.

C
rrent understanding, based on the striking, small, truly congenital nev and nevi acquired early in life, is that the first develops before puberty, presents with a dermoscopic globular pattern, and persists for the lifetime, becoming later a dermal nevus in the adult [3,4].In contrast, acquired melanocytic nevi develop mostly at puberty and usually undergo spontaneous involution

fter the fift
decade of life.

However, in the realm of acquired nevi, we can distinguish 2 types of nevi: compound nevi with a super icial or with a deep dermal component.While the former is dermoscopically characterized by a reticular pattern, the latter is typified by a central elevated part showing a structureless pattern (deep dermal component) and a flat peripheral, reticular component (lateral junctional shoulders) [4,5].Although the majority of both nevus types undergo spontaneous involution, some of the dermal components of deep compound nevi may also p rsist until advanced age.There is global agreement that in certain cases melanoma develops in conjunction with a preexisting melanocytic nevus.

Nevus-associated melanoma (NAM) is diagn

ed on the
asis of the presence of histopathological evidence of nevus components and melanoma features.Conversely, de novo melanoma (DNM) is defined as melanoma without histopathological evidence of a preexisting nevus

data on
elanomas that arise from preexisting melanocytic nevi and those that arise de novo is limited, and the effect of the origin of melanoma on disease characteristics and prognosis remains unclear.

Currently available data from the literature about clinical, histological, dermoscopic, and molecular features and prognosis of NAM are summarized in Table 1.


Epidemiology

The prevalence of NAM varies across studies.Only one-thir of melanomas arise in association with a preexisting nevus.

The literature describes a wide range of NAM prevalence, from 4% to 72%.Lin et al reviewed 25 studies and found that 36% of melanomas were associated with a preexisting nevus [2].Recently, Pampena et al conducted a systematic r