On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.84 no.2 Rio de Janeiro Mar./Apr. 2009
CLINICAL, EPIDEMIOLOGICAL, LABORATORY AND THERAPEUTIC INVESTIGATION
Nurimar Conceição FernandesI; José Leonardo Rodrigues MachadoII
IAssociate Professor, Medical School,
Universidade Federal do Rio de Janeiro (UFRJ). Hospital Universitário
Clementino Fraga Filho Instituto de Puericultura e Pediatria Martagão
Gesteira Rio de Janeiro (RJ), Brazil
IIGraduate Studies in Medicine (Dermatology), Medical School, Universidade Federal do Rio de Janeiro (UFRJ) Rio de Janeiro (RJ), Brazil
BACKGROUND: The classification of the congenital melanocytic nevus (CMN)
and the magnitude of the risk of transformation into melanoma are still controversal.
OBJECTIVE: To analyse the profile of the CMN in the child and teenager at IPPMG-UFRJ according to sex, skin colour, age, clinical type, locations and evolution.
METHODS: Longitudinal study of retrospective and prospective cohort from 1994 to 2007. Aleatoric sample from spontaneous or referal demand.
RESULTS: 30 children and 30 teenagers showed 74 nevi: 60,8% (small), 27% (medium), 5,4% (large) and 6,7% (giant); from these, 45,9% were in the male sex and 54% in the female sex. There were 45,9% in white and 54% in non-white. Sex and skin colour didn't influence the clinical type. Among the small and medium nevi, 27,1% were located in the trunk, 23% in the head and neck; the large and giant ones in the head,neck, back and limbs; 28,3% were attended for more than 10 years, 47,3% between three and nine years and 24,4% for a time below three years; the small and medium CMN kept unchanged. The fading of the lesion was observed in one large and in two giant CMN. No cases of melanoma were observed.
CONCLUSION: An homogeneous distribution among white/non white and male/female; the sex and the ethnic group did not influence the clinical type; the small CMN was the most frequent clinical type mainly in the trunk.
BACKGROUND: The classification of the congenital melanocytic nevus (CMN)
and the magnitude of the risk of transformation into melanoma are still controversal.
Keywords: Adolescent; Child; Melanoma; Nevus, pigmented
Congenital melanocytic nevi (CMN) are morphologically rounded or oval with regular and irregular well-defined borders. They frequently have light brownish color with darker brown colored areas. The surface is papulous, rugous, verrucous or cerebriform; normally, they are single but large nevi have satellite lesions. They are asymptomatic and in some occasions have pruritus, hypersensitivity, xerosis and anhydrosis 1, 2.
As time goes by, they may grow hairs, become darker, in uniform hues of brown, dark brown or black or even get lighter, but they rarely regress. A common fact among large and giant CMN is the formation of nodules. In neonates they are normally lighter and have no hairs. Some develop an achromic halo with consequence effacement of the nevus (halo nevus) 1, 2.
CMN and acquired melanocytic nevi have similar histological characteristics. The following aspects may help us differentiate them: in CMN, melanocytic nevi are located between the reticular dermis fibers, in the two lower thirds of the dermis, and inside the hypodermis, also around and inside hair follicles, sweat glands, eccrine area, vessel walls and nerves 1. Diagnosis of CMN is primarily clinical and its presence at birth or immediately after it is conclusive 3.
There is great controversy in the classification of CMN. The one that seems to be the most appropriate classification and adopted by most authors is: small (< 1.5 cm); medium CMN (1.5 to 10 cm); large CMN (11 to 20 cm), and giant CMN (> 20 cm) (Figure 1 - 4 ).4
In general, the risk of malignant transformation of CMN ranges from 5-40% 1 and 4.5-10% 5. Literature review shows controversy regarding the risk of transformation of large/ giant (1% 42%) 6, 7 , medium (3-21%) 1, 8 and small CMN (8.1% 14.9%) 9. The development of melanomas in large and giant CMN occurs before puberty and in small and medium nevi it normally occurs after puberty 10, 11.
The mean age of children with melanoma caused from large/ giant CMN is seven years, confirming the maximum risk of malignant transformation in children and adolescent 12, 13.
Considering the scarcity of publications on CMN in Brazil, we aimed to analyze the clinical profile in children and adolescents at Instituto de Puericultura e Pediatria Martagão Gesteira.
MATERIAL AND METHODS
In the period 1994-2007, children (0-9 years) and adolescents (10-19 years) with CMN (detected at birth and up to two years of age by parents and/or guardians) participated in this longitudinal retrospective and prospective cohort study. The sample came from spontaneous and referred demand CMN as main complaint or detected during a visit for another dermatological complaint. The studied variables were age, gender, skin color (white/ non-white), clinical type, location and case progression.
1) Small CMN (< 1.5 cm) and medium CMN (1.5 to 10 cm)
every 6 months and photoprotection.
2) Large CMN (11 to 20 cm)
every three months in the first year of life and every six months after the first year until puberty.
3) Giant CMN (> 20 cm)
every three months in the first year of life and every six months after the first year until puberty; liver, spleen and lymph nodes palpation 14.
The statistical analysis was performed with chi-square test or Fisher test when chi-square test could not be used.
Concerning age at the time of inclusion in the study:
six children were aged one year;
15 were two years old;
10 were 3 years;
9 were 4 years;
9 were five years;
2 were six years;
four were 7 years;
one was 9 years;
2 adolescents were 10;
one was 11
and one was 12 years, amounting to 56 children and four adolescents (Table 1).
Considering the type of CMN and age at inclusion in the study, we detected homogeneous distribution, probably because of type of demand (spontaneous and/or referred) (Table 1).
In 2007, the sample comprised 30 children six white boys/ seven non-white boys; seven white girls / 10 non-white girls, and 30 adolescents five white and seven non-white boys and nine white and nine non-white girls. A total of 25 male children (11 white/ 14 non-white) and 35 female children (16 white / 19 non-white) were included (Table 2).
There were a total of 74 nevi: 45 small CMN (60. 8%), 20 medium CMN nevi (27%), four large CMN (5.4%), and 5 giant CMN (6.7%), divided as 34 (45.9%) lesions in male subjects and 40 (54%) in female subjects; six cases had two CMN, one case had five CMN, one had four small CMN, and one subject had two medium CMN (Table 3).
Concerning statistical analysis, first they were grouped as large and giant nevi and then a second analysis was made by grouping the number of medium, large and giant nevi, because separately the values were not statistically significant. The tests did not show correlation between the studied variables (p= 0.5; p= 0.24) (Table 3).
Thirty-four nevi (45.9%) were detected in white subjects and 40 nevi (54%) in non-white subjects. For statistical purposes, they were grouped as in the previous table, and we did not find any correlation between the variables (p= 0.23) (Table 4).
Among small and medium nevi, 18 (27.7%) were on the chest, 15 (23%) on the head and neck, 12 (18.4%) on the abdomen and groin, 11 (17%) on the lower limbs, eight (12.4%) were on the upper limbs, and one (1.5%) was on the genitals (Table 5). Table 5 shows all categories in a descriptive fashion, not including the statistical tests. We should observe that the trunk was the most frequent location.
Three large CMN were located on the thigh and one on the hand and upper limb. The five giant CMN were distributed as follows: 1) bathing trunk lesion; 2) thigh and lower limb; 3) back, chest and shoulder; 4) scalp; 5) scalp, neck and upper portion of the back.
Out of 74 studied nevi, 21 (28.3%) were followed up for more than 10 years, 35 (47.3%) were followed up between 3 and 9 years, and 18 (24.4%) for less than three years. There was no case of melanoma (Table 6).
Regarding progression, we observed that medium CMN remained unaltered. One of the medium nevus on the abdomen presented an area of vitiligo on the medial margin. Among the four large CMN, the one located on the thigh experienced lightening and the three remaining nevi remained unaltered. Out of the 5 giant CMN, two (bathing trunk and the other one on the thigh and lower limb) showed lightening, especially of the margins, and remained unaltered.
The literature review shows that most studies about CMN approach only giant and large nevi. Few have used the methodology of this investigation, that is, including giant, large, medium and small CMN 11, 13, 15-18. Some have discussed about the risk of malignant transformation and CMN management based on the exclusive samples of large/giant CMN. Controversy in the classification of CMN based on time and information at the onset (especially of small CMN) is a setback to the current knowledge. A CMN, benign melanocytic nevus present at birth, may not be detected at the clinical examination of the newborn, owing to lack of visible pigment (late CMN). Late nevus develops pigment in a slow fashion and with time, it becomes visible in most cases during the first two years of life and it has clinical and histological characteristics that are indistinguishable from typical CMN. The inclusion criteria in the study were the information brought from parents and/or guardians about the time it occurred (up to two years).
Photographic documentation from the beginning is ideal but not always feasible, as we can see in the literature. In the present study, when there were questions about parents' information, the case was excluded. It has recently been proposed that nevus spillus join the spectrum of CMN regardless of being congenital or acquired. Finally, it was not included.
The distribution of cases in this study was homogenous between white and non-white subjects and male/female gender; gender and skin color did not influence the type of clinical nevi. In the literature, in a sample of 133 CMN of different sizes, the authors reported a 3:2 female/ male gender ratio, and most children were Caucasian and just one was black 15. To other authors 16, 18 no significant difference was observed concerning gender. By following up 46 CMN, the authors observed 29 female and 17 male subjects, 45 Caucasian and one non-Caucasian 17.
In our sample we observed small (60.8%) CMN, medium (27%), large (5.4%) and giant (6.7%) CMN. Other studies have reported 7% large CMN and 93% small ones 13; 28 (10%) giant nevi 16; 80.3% small/medium ones, and 19.7% large nevi 11. Our study confirmed the prevalence of small nevi, as referred by the literature.
Small CMN are located predominantly on the trunk, whereas medium CMN are more homogenously distributed. Percentages referred by the literature for different body areas are head (16%), neck (17%), chest (50%), upper limbs (7%), and lower limbs (4%), without any differences between boys and girls 16, 14.6% (chest) and 15.2% (abdomen) 11. In another study 18, nevi were preferably reported in the trunk and abdomen, with low concentration on the head and upper limbs. None were found in palmar and plantar regions and they were single in 90% of the cases.
The development of acquired MN may be related with some factors, including type of skin, ethnicity, genetic predisposition and exposure to ultraviolet light. Acquired nevi tend to be more numerous in areas chronically exposed to sunlight and in children of fair skin, blonde hair, and blue eyes. This fact has not been described for CMN 19.
Concerning the follow-up period, our study followed up patients on average for 5.7 years, whereas the literature reports mean follow-up period between 3.4 and 23.7 years 13,15,16,17.
In the present sample, among large CMN, one had partial lightening and among the five giant CMN, two had partial lightening. A study 15 showed lightening in 17% of large CMN. There is one published case of giant CMN 20 and two cases of medium nevi 21 with spontaneous regression. We observed that lightening is not an uncommon fact in large/ giant CMN. Bibliographic review showed that the course of CMN is varied: partial or total pigment regression; hypopigmentation halo (nevus halo) with spontaneous regression after formation of halo, and vitiligo area, in addition to halo onset. Pigment regression is a process in which dermal melanocytes loss their capability to produce pigment, and what is left is only the basal layer of melanocytes. Many theories have been proposed to explain these pigmentation abnormalities:
Natural precursors of melanin would be inhibitors of their production; as a consequence, melanocytes would lose the protective mechanisms that disable these precursors. The immune theory is the most accepted one for suppression of pigment production through humoral and cellular immunity action. Another hypothesis is that neurotoxic agents would be released close or inside the melanocytes, destroying melanin-producing cells or simply stopping their production. Transepidermal elimination of nevus cells as well as fatty degeneration are also mentioned 20, 21.
The mean age for development of melanoma over CMN reported by the literature is seven years, placing the maximum risk at the childhood years (large/giant) and adolescence (medium); the risk of developing melanoma over small CMN is shown in adult age (about 60 years) 2, 9, 22, 23. The fact that small CMN is more frequent than giant ones and many times they are multiple leads us to the conclusion that its malignancy potential should be greater than for giant CMN. In 204 cases of melanoma it was observed that 44 (21.6%) resulted from a small CMN; no cases were seen before the age of 20 years and there was no preferred age range for transformation 23. The development of melanoma was not observed in 230 cases of CMN of medium size followed up until the age of 25 years 22.
Other authors have not reported transformation in 3,922 small/ medium CMN followed up for 10 years 13 and 164 small CMN during 25 years 16. For large CMN the estimated transformation potential is 3.8% 4.
We have not evidenced any case of malignant transformation. The studied literature refers that large/ giant CMN have higher risk of developing melanomas and that the risk of medium and small CMN is still controversial. The present sample of large and giant CMN is too small to assess the risk of malignant transformation and the follow-up time of small and medium nevi was not enough to assess malignant transformation, given that it happens only after adolescence.
Neurocutaneous melanocytosis (neurocutaneous melanosis) is a rare congenital disorder in which leptomeninges contains excessive layers of melanocytes and melanin. Large/ giant CMN on the neck, head and posterior midline is a risk factor for development of the disease. The presence of more than 20 satellite lesion is another risk factor 5,12,24,25. It may be symptomatic or asymptomatic; if symptomatic, neurological manifestations are observed before the age of 2 years. Out of 4 giant CMN, only one patient joined the study before the age of 2 years; out of 5 giant CMN, three joined the study up to the age of two years.
Magnetic Resonance Imaging (MRI) has higher sensitivity in detecting neurocutaneous melanocytosis within the first 4 to 6 weeks of life; given that the procedure requires general anesthesia, it is quite controversial. As the infant grows, small pigmented lesions become less evident. Some authors advocate for MRI or serial neurological examination for asymptomatic patients with risk of developing leptomeningeal melanocytosis. Others question the performance of MRI because there is no treatment for cases of asymptomatic melanocytosis. We agree with this questioning, because the positive response to the test does not change our management approach wait and see approach for large/ giant nevi 12, 26.
The differential diagnosis should be made with mongolian spots, coffee and milk spots, lentigo simplex, epidermal nevus and sebaceous nevus. Among them, epidermal nevus has brought a specific diagnostic difficulty. A non-white pre-school girl, aged 8 years, with medium-sized CMN on the dorsal region (case 26), developed papulous brownish lesion, of irregular borders on the right retroauricular region. The histopathology report of excision biopsy revealed verrucous epidermal nevus 27.
There is controversy in the classification of CMN, which hinders better comparative study 28, 29.
Based on observations of patients at IPPMG and literature data, the present investigation systematized the elements that may support dermatologists and pediatricians in the diagnosis and follow-up of patients with CMN.
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Mailing Address: How to cite this article: Fernandes NC, Machado JLR. Estudo clínico
dos nevos melanocíticos congênitos na criança e adolescente.
An Bras Dermatol. 2009;84(2):129-35.
Nurimar Conceição Fernandes
Rua Alexandre de Gusmão, no 28, Ap. 201
20520 120 Rio de Janeiro RJ
Tel./fax: 21 2568-4158
How to cite this article: Fernandes NC, Machado JLR. Estudo clínico dos nevos melanocíticos congênitos na criança e adolescente. An Bras Dermatol. 2009;84(2):129-35.