Skin Cancer – Research Article

Dermatology Received: April 30, 2020

Accepted: June 11, 2020
DOI: 10.1159/000510221 Published online: October 14, 2020

Cutaneous Melanoma Arising in

Congenital Melanocytic Nevus:
A Retrospective Observational Study
Stefano Caccavale a Giulia Calabrese a Emanuela Mattiello a Paolo Broganelli b
       

Alice Ramondetta b Gorizio Pieretti c Roberto Alfano d Giuseppe Argenziano a

       

a Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania
Luigi Vanvitelli, Naples, Italy; b Department of Medical Sciences, Section of Dermatology, University of Turin,
 

Turin, Italy; c Department of Plastic Surgery, University of Campania Luigi Vanvitelli, Naples, Italy; d Department of
   

Anesthesiology, Surgery and Emergency, University of Campania Luigi Vanvitelli, Naples, Italy

Keywords
Melanoma · Congenital melanocytic nevus · Oncological
dermatology · Dermoscopy · Dermatoscopy
Abstract
Background: Congenital melanocytic nevi (CMN) are benign
proliferations of melanocytes usually present at birth. The
magnitude of the melanoma risk for CMN is controversial,
generating an ongoing debate on the best approach to
manage these lesions. Objective: To perform a retrospec-
tive, observational study with the aim to evaluate the preva-
lence of CMN-associated melanomas in tertiary referral cen-
ters, as well as the eventual correlation between clinical,
dermoscopic, and histological features of CMN-associated
melanomas. Methods: A single-center retrospective obser-
vational study was performed on all clinical and dermoscop-
ic images of histologically confirmed melanomas arising on
CMN over a 14-year period (January 2005 to March 2019).
Results: Our database included 2,159 melanomas in the con-
sidered period. Of those, 27 (1.3%) were CMN-associated
melanomas. The mean age of patients with CMN-associated
melanoma was 33 years (range, 11–70 years). The mean di-
ameter of CMN-associated melanoma was 18 mm (range, 6
mm to 20 cm), and 56% were located on the back. Twenty-
one (77.8%) of CMN-associated melanomas arose on small
CMN (< 1.5 cm), 5 (18.5%) on medium-sized CMN (1.5–19.9
cm), and 1 (3.7%) on a large/giant type (≥20 cm). The major-
ity of CMN-associated melanomas (63%) exhibited a globu-
lar dermoscopic pattern in their benign part, while a blue-
white veil and irregular blotches were the most frequent der-
moscopic features in the malignant part. About three
quarters of melanomas occupied 10–50% of the nevus sur-
face. Breslow thickness was higher in melanomas involving
less than 10% of nevus surface (mean thickness, 1 mm) than
in those affecting 10–50 and >50% of the nevus surface (0.8
and 0.7 mm, respectively). Conclusions: In our series, small
CMN was the most frequent type of CMN-associated mela-
noma. Although the risk of melanoma is increasing by the
increasing size of CMN, our finding is definitely related to the
much higher prevalence of small CMN in the general popula-
tion as compared to the prevalence of intermediate-sized
and large CMN. Limitations: Small sample size, single-center
experience, retrospective design. © 2020 S. Karger AG, Basel
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karger@karger.com © 2020 S. Karger AG, Basel Stefano Caccavale

www.karger.com/drm Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine
University of Campania Luigi Vanvitelli
Via Sergio Pansini, 5, IT–80131 Naples (Italy)
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 Background
Congenital melanocytic nevi (CMN) are neural crest-
derived, benign proliferations of melanocytes usually
present at birth [1]. However, many authors refer the term
“congenital” to any melanocytic nevus that appears with-
in the first 2 years of life (“tardive” CMN). These authors
interpret the late onset of CMN as a consequence of initial
insufficient melanin synthesis and/or their small size,
which could make them clinically invisible during the first
months of life, or the effect of postnatal migration of me-
lanocytic precursor cells from perineural areas to the der-
mis [2]. Stinco et al. [3] found no difference in terms of
dermoscopic appearance between conventional and tar-
dive CMN; thus, the authors proposed to consider both as
a unique group of “congenital-type” melanocytic nevi [2].
It is important to avoid confusion between “tardive” CMN
and “congenital nevus-like nevi”: the latter are clinically
similar to CMN but are not present since early life [2].
The overall prevalence of CMN varies from 0.5 to
31.7% [4]. Although many clinical criteria for categoriz-
ing CMN have been described in the literature to predict
adverse outcomes, size is considered the principal one. In
adults, the most used classification system divides CMN
into three categories based on the largest diameter: small
(<1.5 cm), medium (1.5–19.9 cm), and large/giant (≥20
cm). Small CMN have an estimated incidence of 1 in 100
live births, while that of large CMN is 1 in 20,000 [5]. They
occur with an equal rate in males and females and in all
ethnic groups and races [6].
Numerous cancers have been associated with CMN, in
particular melanoma. In one word, the larger the diame-
ter, the higher the risk of melanoma development in con-
junction with a preexisting CMN. However, the magni-
tude of melanoma risk for CMN is controversial, generat-
ing an ongoing debate on the best approach to manage
these lesions.
Dermoscopy is an important diagnostic tool for distin-
guishing dermoscopic features of CMN and differentiate
other pigmented lesions, such as acquired melanocytic
nevi and Becker nevi. The identification of dermoscopic
features common to CMN provides additional informa-
tion, being extremely useful when clinical and histologi-
cal features are not present. Dermoscopy is effective also
in detecting early malignant changes [7].
Several studies assessed the risk of melanoma in small,
medium, or large CMN, but not many analyzed the prev-
alence of CMN-associated melanomas in a real clinical

Clinical and dermoscopic images of all

histologically confirmed melanomas acquired over
a 14-year period (2005–2019)

All clinical and dermoscopic images of melanoma

retrospectively collected from the database (n = 2,195) Patients of the database affected by
melanoma with absent or incomplete
clinical information excluded (n = 36)
Clinical and dermoscopic images of melanoma arising in
CMN collected (n = 27) among 2,159 melanomas (1.3%)

Size and topography of 27 CMN evaluated

on clinical images

CMN distinguished in small (n = 21),

medium-sized (n = 5), and large/giant type (n = 1)

Global dermoscopic pattern of CMN and local features of melanomas,

Breslow thickness, and percentage of melanoma in the context of CMN
surface analyzed by three different researchers

Fig. 1. Flowchart of the Materials and Methods

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2 Dermatology Caccavale et al.

DOI: 10.1159/000510221
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setting. To contribute to the expansion of the knowledge
in this area, we have performed a retrospective, observa-
tional study with the aim to evaluate the prevalence of
CMN-associated melanomas in tertiary referral centers,
as well as the eventual correlation between clinical, der-
moscopic, and histological features of CMN-associated
melanomas.
Materials and Methods
For further details, see the online supplementary material (see
www.karger.com/doi/10.1159/000510221 for all online suppl. ma-
terial) (Fig. 1, 2).
Results
Our database included 2,159 diagnosed melanomas in
the period from January 2005 to March 2019 (about 150
melanomas/year). We found 27 CMN-associated mela-
nomas in the considered time interval (about 2 cases/
year). All cases were clinically and histologically docu-
mented. The percentage of CMN-associated melanomas
compared to the total number of melanomas diagnosed
in the same period was about 1.3%. The average age of our
patients affected by melanoma arising in CMN was 33
years (range, 11–70 years) (Fig. 3). A slight predominance
for the female gender was found (about 52%).

Color version available online

Fig. 2. a Clinical picture of a nodular mela- b
noma developed within a large CMN in a
70-year-old patient. b Dermoscopic image
of an invasive melanoma (Breslow thick-
ness, 0.7 mm), arising in a CMN of an
11-year-old boy. c Dermoscopic image of
an invasive melanoma (Breslow thickness,
0.7 mm) developed within a CMN in a
a c
15-year-old girl.

Color version available online

80

70
70
65
62
60
55

50 49 49
44 45
42
Age, years

40 40
40
34
31 31 31
30 29
27
25
21 21
19
20 17 18 18 18
15
11
10

0
Patients
Fig. 3. The age of patients at the time of di-
agnosis.
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Melanoma in Congenital Melanocytic Dermatology 3

Nevus DOI: 10.1159/000510221
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 Color version available online

Color version available online

■ Back: 56%
7% ■ Chest: 15%
■ Limb: 11%
■ Abdomen: 11%
11% ■ Head/neck: 7%

11% 56%

Fig. 6. Clinical and dermoscopic pictures of a small CMN during

15% follow-up in a child.

reticular, 7.4% a homogenous, and 7.4% a mixed pattern.

The most frequent dermoscopic features of melanomas
arising in CMN were a blue-white veil and irregular
Fig. 4. Body areas affected by CMN-associated melanoma.
blotches (60 and 30%, respectively).
Only 4 melanomas (14.8%) extended over more than
Color version available online
50% of a CMN’s total area, while three quarters of them
1.25
(74.1%) occupied 10–50% of the nevus surface. Finally, a
1.0 small group (11.1%) of melanomas took up < 10% of a
1.00
Breslow thickness, mm

0.8 CMN’s total area.

0.75 0.7 Breslow thickness was higher in the group of patients
aged 0–20 and 51–70 years (1 and 0.9 mm, respectively)
0.50
rather than the group aged 21–50 years (0.7 mm). More-
0.25 over, Breslow thickness was higher in melanomas involv-
ing less than 10% of nevus surface (mean thickness, 1
0 mm) than in those affecting 10–50 and > 50% of nevus
<10% 10–50% >50%
Area of CMN involved by melanoma
surface (mean thickness, 0.8 and 0.7 mm, respectively)
(Fig. 5).

Fig. 5. Correlation between Breslow thickness and the area of a

CMN covered by melanoma. Discussion

According to our data, the development of melanoma

The mean diameter of CMN-associated melanoma in CMN represents a rare, but possible, event in a real
was 18 mm (range, 6–20 cm). clinical setting. In our series, CMN-associated melano-
Of the 27 CMN-associated melanomas, 21 (77.8%) mas represent 1.3% of the total number of diagnosed mel-
arose on small CMN (<1.5 cm), 5 (18.5%) on medium- anomas over a 14-year period of time, with small CMN
sized CMN (1.5–19.9 cm), and just 1 (3.7%) on the large/ being the most frequent type of CMN-associated mela-
giant type (≥20 cm) (Fig. 2a). noma. This finding is definitely related to the higher prev-
CMN associated-melanomas were found in the fol- alence of small CMN in the general population. In other
lowing areas: back (56% of the lesions), chest (15%), limbs words, it is true that giant CMN carry the higher risk to
(11%), abdomen (11%), head-neck (7%) (Fig. 4). develop melanoma but, due to their low prevalence in the
Twenty-two melanomas arising in the context of CMN general population, it is very uncommon to find a mela-
were invasive, and 5 melanomas were in situ. The average noma associated to a large CMN in a routine setting. In
Breslow thickness was 1 mm (range, 0.2–5 mm for inva- contrast, although the risk is very low for a small CMN,
sive melanomas). they are relatively frequent in the general population;
The majority of CMN (63%) exhibited a globular der- thus, it is more probable to find a melanoma associated
moscopic pattern in their benign part; 22.2% showed a to a small CMN in a real clinical setting.
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Fig. 7. A medium size CMN of the forehead excised in two surgical stages.
As a matter of fact, most of the studies correlating ne-
vus size and melanoma risk were performed for large and
medium size CMN. The risk has been calculated to be less
than 1% for medium size CMN [4], while it has been es-
timated at 10–15% for giant CMN >40 cm [8]. For me-
dium size and large CMN, the risk of melanoma develop-
ment is not limited to adulthood; in fact, CMN is consid-
ered the greatest risk factor for pediatric melanoma [9,
10].
For small CMN, the risk of malignant transformation
is considered very low but the few studies addressing this
risk reported contradictory results [9, 11–15].
To our knowledge, unlike giant CMN, no melanoma
arising in small CMN during childhood has been de-
scribed in the literature. The youngest patient included in
our study was an 11-year-old boy with a 0.7-mm thick-
ness melanoma arising in a 12-mm diameter CMN
(Fig. 2b and 3). This was the only case of melanoma dur-
ing childhood in the considered period. We observed 6
cases of melanoma on CMN during adolescence (12–19
years) (Fig. 3). However, according to our data, the risk
seems to be higher for adult patients.
In our series, most CMN-associated melanomas
(56%) occurred on the back (site of irregular sun expo-
sure) (Fig. 4). Among Caucasian populations, melano-
ma develops more frequently on the back and shoulders
for men and on the lower limbs for women. Since the
number of female and male patients was almost the
same in our study, consequently the back seems to be a
preferential site of CMN-associated melanomas, regard-
less of gender. In the literature, data on preferential lo-
calization and on gender predilection for CMN-associ-
ated melanomas are not available, as well as there are no
studies concerning the dermoscopic features of these le-
sions. In our cohort, the most frequent ones were blue-
white veil and irregular blotches (60 and 30% of cases,
respectively) for melanomas, and globular pattern for
CMN (63%).
Melanoma in Congenital Melanocytic
Nevus
Color version available online
Breslow thickness is the most important prognostic
parameter in evaluating the primary melanoma. Accord-
ing to previous studies, melanoma arising in CMN is usu-
ally located superficially within small or medium size
CMN and more deeply within large CMN. Therefore,
melanoma arising in large CMN should be associated
with a higher Breslow thickness at presentation [8]. In our
study, the average Breslow thickness was 1 mm, and the
melanoma associated to the largest CMN in our series (20
cm of diameter) was 1.2 mm in Breslow thickness.
Obviously, this study has some limitations. First, it is
a single, tertiary referral center experience; second, it is a
retrospective study conducted on a small sample size, de-
spite the long period in which it was carried out (more
than 14 years). Third, and most importantly, the criteria
for histopathological diagnosis of congenital nevus are
debatable, especially for small CMN. All these limitations
could partially restrict the practical conclusions that can
be drawn from this study. However, the topic is not sim-
ple, and these observations could be the starting point for
larger studies.
In conclusion, the treatment of CMN needs to be in-
dividualized and address not only melanoma risk, but
also psychosocial and aesthetic aspects [16–20]. In large/
giant CMN, early excision is usually associated with high-
er complexity and greater cosmetic impairment. Accord-
ingly, annual clinical and dermoscopic monitoring is a
valid alternative for the management of large CMN.
Currently, no consensus regarding the management of
small CMN exists. Given the low risk of melanoma devel-
opment within small CMN and their frequency in clinical
practice, our recommendation is observation with clini-
cal and dermoscopic follow-up [17, 20] (Fig. 6).
The most difficult and controversial area of clinical
management concerns medium-sized CMN. According
to our personal opinion and experience, we recommend
annual monitoring during childhood and excision after
puberty to patients with medium size CMN (Fig. 7).
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 Key Message Disclosure Statement

Small congenital melanocytic nevus is most frequently associ- The authors have no conflicts of interest to declare. There was
ated with melanoma for its higher prevalence in the general popu- no funding received for this study.
lation.

Statement of Ethics
The study was conducted in accordance with the principles
outlined in the Declaration of Helsinki and the International Con-
ference on Harmonisation Good Clinical Practice guidelines.
Author Contributions
S.C., E.M., and G.A.: conceptualization, data acquisition, and
investigation. S.C., G.C., and G.A.: writing original draft and edit-
ing. S.C., G.C., G.A., P.B., A.R., G.P., and R.A.: methodology. S.C.
and G.A.: project administration.

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