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Prevalence of common and atypical melanocytic nevi in Turkish children


European Journal of Dermatology. Volume 18, Number 4, 422-6, July-August 2008, Investigative report

DOI : 10.1684/ejd.2008.0459

Summary  

Author(s) : Melih Akyol, Abuzer Gaffar Atli, Sedat Özçelik, Ziynet Çinar, Filiz Altioğlu Çig, Hüdaverdi Bircan , Dermatology Department, School of Medicine of Cumhuriyet University, 58040-Sivas, Turkey, Biostatistics Department, School of Medicine of Cumhuriyet University, 58040-Sivas, Turkey, Business Department, School of Economics, Cumhuriyet University, 58140-Sivas, Turkey.

Summary : The incidence of malignant melanoma is increasing rapidly in the white population of the world. Therefore, it is necessary to know the etiological factors of malignant melanoma and to take preventive measures in high-risk groups in different populations. This study aimed to estimate the prevalence of common melanocytic nevi (CMN) and atypical melanocytic nevi (AMN) and to identify some phenotypic factors (eye and hair color, skin type), gender, and age associated with CMN and AMN presence in primary school children in a Turkish population. In this study, 1491 children aged from 7-15 were examined. Brown-black discrete lesions of two millimeters or larger, with the exceptions of solar lentigo and ephelides, were counted as CMN. The CMN prevalence was 73.85%, and the AMN prevalence was 3.45%. The numbers of CMN and AMN were found to be higher in boys than in girls. While more CMN were present in the head and neck areas than in other anatomic regions, the number of AMN was higher on the ventral and dorsal trunk. Our study provides evidence for a significant relationship between specific characteristics, including skin type, age, gender and the number of CMN in our population. However, CMN is more frequent in children having a lighter skin type, and its number increases with age. The results of our study and further studies which take sun-exposure characteristics and pigmentary factors into account, may facilitate the determination of the other factors affecting nevus production and the development of further strategies for following and preventing cutaneous melanoma in our geographical area.

Keywords : common melanocytic nevi, atypical melanocytic nevi, melanoma

ARTICLE

Auteur(s) : Melih Akyol1, Abuzer Gaffar Atli1, Sedat Özçelik1, Ziynet Çinar2, Filiz Altioğlu Çig1, Hüdaverdi Bircan3

1Dermatology Department, School of Medicine of Cumhuriyet University, 58040-Sivas, Turkey
2Biostatistics Department, School of Medicine of Cumhuriyet University, 58040-Sivas, Turkey
3Business Department, School of Economics, Cumhuriyet University, 58140-Sivas, Turkey

accepté le 15 Mars 2008

The incidence and mortality of cutaneous melanoma is increasing rapidly all around the world. Recently, Pinarbasi et al. [1] reported an increase of 11.7% within the last 5-year period, and 14.4% within the previous 5-year period (from 1994 to 2003) in melanoma cases in the population of Antalya in Turkey. Therefore, it is important to define the high-risk groups for the diagnosis and treatment of cutaneous melanoma [2].

Common melanocytic nevi (CMN) are benign tumors that are found in about 80-100% of the general population. The prevalence of atypical melanocytic nevi (AMN), diagnosed with a biopsy, is about 2-20% in the white race, and 1.5% in children [3]. CMN and AMN (especially) can be possible precursors of melanoma and they are accepted as independent risk factors [2, 4]. It is possible to designate the relationship between the number and distribution of CMN on the whole body and the cutaneous melanoma [2, 5, 6].

Defining the factors affecting nevus development, and having knowledge of the prevalence of CMN and AMN for each geographic region is imperative. The aim of the present study, the first to be performed in our country, was to estimate the prevalence of CMN and AMN and to identify some of the phenotypic factors, gender, and age associated with the presence of CMN and AMN in primary school children in a Turkish population.

Methods

This study took place in Sivas from January to June of 1999. Sivas is a city located in the middle Anatolia region of Turkey at 39.45 degrees latitude, 37.01 degrees longitude and 1285 m altitude. 1491 students were chosen from the 41139 primary school children, using a random sampling method (p = 0.90; α = 0.01; d = ± 0.02). In this sampling process, a list was created and there was a stratification by age, gender, schools, and student’s school numbers. This study protocol was approved by the Ethical Commitee of Cumhuriyet University Faculty of Medicine. The Ministry of Education, school directors, class teachers and families were informed and their written permissions were obtained.

Sociodemographic characteristics of the children were noted. The study was based on skin examination. The children gave oral assent at the time of the physical examination. Dermatologic examinations were done by two dermatologists in the school infirmaries or in rooms that were prepared for consultation. Children who were absent at the first examination, were examined at the second visit to the school.

Skin types were determined as I-VI according to Fitzpatrick. The hair colors were classified as black, brown, blonde, or red and the eye colors were classified as brown-black, hazel, green or blue. In this study, we did not examine the effects of sun exposure characteristics. With the exception of scalp and anogenital regions, the other anatomical regions were classified and evaluated as head-neck, ventral trunk, dorsal trunk, upper extremities, lower extremities, hands and feet. Brown-black discrete lesions of two millimeters or larger were counted as CMN. To minimize the error in differentiation of CMN from other pigmented lesions, two experienced clinicians counted the nevi separately. As there are no absolute criteria for diagnosis of CMN, any darkly pigmented lesion larger than two millimeters was counted as CMN if it was not considered to be a solar lentigo lesion (light brown pigmented lesions with irregular outlines located on sun-exposed areas) or freckles (poorly defined lesions light to medium brown, less than three millimeters) defined by relatively specific clinical criteria. Lentigo simplex was not excluded because there are no absolute clinical criteria to distinguish it from CMN. If a lesion had three or more of the following symptoms it was recorded as AMN: (a) ≥ 5 mm in diameter, (b) poorly defined borders that tend to fade into adjacent normal skin, (c) irregular borders, (d) highly variable color, (e) presentation of macular and papular areas in a single lesion.

In the statistical evaluation of the results, SPSS (version 10.0) and Epi Info (version 3.4.3) were used. For statistical analysis the number of CMN and AMN were used as dependent variables. The mean values of age according to gender were compared by independent-samples t test. The counts for CMN and AMN for different factor classes were reported by median nevus counts, including interquartile range. The number of children with at least one CMN, and AMN by anatomic sites, and by phenotypical characteristics, were noted as numeric and percentile values. The number of children having at least one CMN by anatomical sites, in both genders, was compared by chi-square test (with odds ratios).

For all predictor variables, including age and gender, logistic regression analysis was performed, and CMN were treated as a dichotomous variable according to whether the presence of one or more clinically CMN. Logistic regression-derived odds ratios, together with their 95% CI, were obtained. Some variables had small numbers. Therefore the numbers of blue and green eyes (light eye colour), blonde and red hair (light hair colour), and skin type I and II (light skin colour) were put together, and an analysis with this composed data was made.

First, we checked for multicollinearity. Because tolerance scores are not available through the logistic regression command in SPSS, we computed these values through the linear regression command, using CMN presence as the dependent variable, and gender, age groups, hair and eye colour, and skin type as independent variables. We checked correlations between the variables to see if there might be multicollinearity problems. The correlation matrix obtained indicated strong correlations between eye color and hair color, and between skin type and hair colour (p = 0.01). Additionally, tolerance values were calculated. That the tolerance value is low (1-R2) was accepted as a problem with multicollinearity. The tolerance value of hair colour was 0.89 < 1-R2 (0.95). Therefore hair colour was eliminated. Then, a logistic regression analysis was carried out for the remaining variables.

For each variable, a reference category was determined. In this case, four variables (gender, age, skin types and eye colour) were all simultaneously included in the model, and logistic regression analysis was completed.

Results

In this study, 760 of 1491 children were boys (51%) and 731 were girls (49%). The age of the children varied from 7-15, and the mean ages of the boys and girls were 9.96 ± 2.20, and 9.98 ± 2.09, respectively (p = 0.962). The prevalence of CMN was 73.85% (75.5% boys, 72.2% girls), and the prevalence of AMN was 3.45% (3.9% boys, 3% girls). The numbers of children with at least one CMN, and one AMN on any anatomical site by phenotypic characteristics, are shown in table 1.

The median count of total CMN and AMN counts in all cases were 2 (ranging from zero to 52), and 0 (ranging from zero to 8), respectively. The median counts of CMN in children with brown-black, hazel, blue, and green eyes were 2 (25-74 percentiles, 0-4), 2 (25-75 percentiles, 1-5), 2 (25-75 percentiles, 0.75-3.25), and 2 (25-75 percentiles, 1-4), respectively. The median counts of CMN in children with brown, black, blonde, and red hair were 2 (25-75 percentiles, 0-4), 2 (25-75 percentiles, 1-4), 2 (25-75 percentiles, 0-4), and 4.5 (2.5-5.75), respectively. The median counts of CMN in children with skin type I, II, III, and IV were 3 (25-75 percentiles, 2-5), 2 (25-75 percentiles, 1-5), 2 (25-75 percentiles, 0-4), and 1 (25-75 percentiles, 0-4), respectively. The median counts of CMN were 2 (25-75 percentiles, 0-4) in both genders.

Table 2 shows the effects of all variables, including phenotypical characteristics, considered in the bivariate analysis. In the logistic regression model, while gender and age produced weak odds ratios, light skin type emerged as moderate risk factor. Eye colour was not a significant predictor. Boys had more CMN than girls. We found an increase of CMN with age.

Table 3 shows the number of children with at least one CMN, and AMN by anatomical sites. According to these results, while the number of CMN seems to be higher on the ventral and dorsal trunk regions in boys, the number of CMN is higher on the hands and feet in girls. While the number of CMN seems to be higher on the head-neck region, the number of AMN seems to be higher on the ventral and dorsal trunk.
Table 1 The number of children with at least one CMN, and one AMN on any anatomical site by phenotypical characteristics

CMN

AMN

Children

Characteristics

N

%

N

%

Eye colour

Brown-black (n = 1218)

890

73.1

42

3.5

Hazel (n = 149)

117

78.5

6

4

Blue (n = 22)

17

77.3

1

4.5

Green (n = 102)

78

76.5

3

2.9

Hair colour

Brown (n = 1333)

983

73.7

46

3.5

Black (n = 88)

69

78.4

2

2.2

Blonde (n = 66)

46

69.7

4

6

Red (n = 4)

4

100

0

0

Skin phototype

I (n = 17)

17

100

2

11.8

II (n = 60)

46

66.7

2

3.3

III (n = 1340)

989

73.8

46

3.5

IV (n = 74)

50

67.6

2

2.8

Gender

Boys (n = 760)

574

75.5

30

3.9

Girls (n = 731

528

72.2

22

3


Table 2 The results from a logistic regression model simultaneously adjusting for gender, age, skin type, and eye colour as predictors of having CMN

Logistic regression

Variables

Levels

  • Adjusted
  • Odds ratio


95% CI*

P-value

Gender

Female

1.0**

-

Male

1.3

1.0-1.5

0.010

Age (years)

7-10

1.0

-

11-14

1.4

1.2-1.4

0.001

Skin Type

III-IV

1.0

-

I-II

2.1

1.1-4.2

0.035

Eye Colour

Brown-black, hazel

1.0

-

Blue-green

1.3

0.8-1.9

0.060

*95% Confidence Interval.

**Denotes the reference category for each variable.


Table 3 The number of children with at least one CMN, and AMN by anatomic sites

CMN

AMN*

Boys (n = 760)

Girls (n = 731)

Boys (n = 760)

Girls (n = 731)

Anatomic sites

n

%

n

%

p

odds ratio

n

%

n

%

Head-Neck

304

40

269

36.8

0.223

1.1

5

0.7

0

0

Ventral trunk

274

36.1

213

29.1

0.005

1.3

13

1.7

5

0.7

Dorsal trunk

282

27.1

186

25.4

0.000

1.7

15

2

12

1.6

Upper extremities

199

26.2

181

24.8

0.567

1.0

6

0.8

2

0.3

Lower extremities

118

15.5

128

17.5

0.336

1.1

2

0.3

3

0.4

Hands

18

2.4

37

5.1

0.008

2.2

1

0.1

0

0

Feet

26

3.4

45

6.2

0.018

1.8

1

0.1

0

0

*Statistical analysis was not done because of inadequate count of cases.

Discussion

The prevalences of CMN and AMN are about 80-100% and 2-20% respectively in general population [3]. The prevalence of CMN (73.85%) and AMN (3.45%) that we found in our study are comparable to the literature. The yearly amount of sunny daytime in Sivas is approximately 2462 hours [7]. The equivalent period is 1685 hours for the Midlands of England, 1751 hours for Kaunas in Lithuania and 2928 hours for Queensland in Australia [8]. In tropical countries children are exposed to high doses of ambient ultraviolet light throughout the year. The effect of additional holidays with more intense sun exposure might be much more evident in children from higher latitudes and might be covered by the impact of the ubiquitous solar radiation in the tropics [9]. Traditional clothing may be effective for sun protection and against nevus development [10]. Although the daytime sun in our region is similar to that of Australia, the people living here are more covered by their clothes due to the cold climate. Therefore, only certain body parts are exposed to sunlight. In fact, the CMN count from the head-neck was higher than the counts from other anatomic regions in our study. It seems likely that clothing style and sun protection may reduce the number of CMN, but also other factors (genetic and environmental) should be kept in mind.

In previous studies it has been shown that, in patients with dysplastic nevus syndrome, there was a higher concentration of CMN in sun-exposed vs sun-protected areas [8, 11]. In addition, the number of nevi may increase or decrease with the amount of sun exposure [12-14]. In our study, the head-neck region had the highest number of CMN (40.5%) and it was the anatomical region that, for the subjects of our study, was more exposed to sunlight. As we did not define the risk factors for development of CMN, such as history of sunburns, and freckles, our research, just like the previous studies, could not clearly figure out the effect of sunlight on CMN development [8, 11-14]. This may be considered as a limitation of our study.

Gender variations in nevus density with higher nevus counts in boys compared to girls have been documented before [15-18]. Gallagher et al. [15] found that the densities of nevus in the ventral trunk and head-neck regions are higher in adult males compared to females. However, the nevus density in the upper and lower extremities is higher for females. It is not clear why girls have higher CMN count on their hands and feet. That the truncal region is exposed to sunlight in boys more than girls may explain why boys have a higher CMN count on their ventral and dorsal trunk. However the results of this study do not include the effects of sun exposure on the development of CMN.

Again, research performed on students in Holland, Switzerland and Australia has shown that CMN is higher in males and increases with age [16-18]. The results of our study show that CMN is more frequent in boys and its number increases with age. Also, as opposed to other research [8, 19, 20], the number of AMN does not increase with age.

Pigmentary factors indicate the children who are at a high risk for CMN development. The children with skin type II and fair hair colour are the most prone to develop many CMN. Skin type I has lower nevus counts, which might be due to better protection of these sun-sensitive children by their parents [9]. That skin types I and II were most prone to develop many CMN is shown to be important in our study, because people in our region do have not comprehensive information about sun-protection, the children with skin types I and II may not be sufficiently protected from the sun. However we did not use a questionnaire form, including questions about sun protection methods. This was another limitation of our study.

Dulon et al. [21] found that the median number of total nevus counts was 11, and no nevus was identified on 222 children (1.9%). In a study from Western Australia, English et al. [22] reported that the mean nevus count at age 10 was 7. Additionally, Autier et al. [23] found a median of 6 nevi ≥ 2 mm per child. Although the prevalence of CMN in our study is similar to those of other populations, we found that the median number of CMN counts in children in Anatolia was lower than those of the previous studies from other geographical regions. Sivas has a cold climate, and the people must be covered by clothes for more than six months of the year. This indispensable sun-protection may explain these lower CMN counts.

The estimated prevalence of clinically atypical nevi ranges from 7 to 18% in different populations. These variations, at least in part, may arise from the use of different diagnostic criteria in different studies. Additionally, differences in sun exposure among populations of different studies may also contribute to these variations. The predilection of atypical nevi for intermittently sun-exposed areas (especially the trunk), their positive association with a history of painful sunburn (in which the pain lasts more than two days) or blistering sunburn, and the finding that people with clinically atypical nevi often have sun-sensitive skin types, suggest that the development of dysplastic nevi could be related to acute, intense, sun exposure [24]. Because the highest number of CMN was on the head-neck region, and the highest number of AMN was on the ventral and dorsal trunk, no relationship between CMN and AMN according to anatomical region can be defined.

Different results were found in studies that analyzed the effects of hair color, skin type, and eye colour on nevus prevalence [17, 25-27]. Gallagher et al. [28] did not find a relationship between light skin colour or eye colour and nevus prevalence. In other studies, it was proposed that individuals having light skin, eye and hair colour may have a high nevus prevalence [17, 25-27]. Also, in our study, there was a significant relationship between light skin colour and the presence of CMN, in our population, but we did not find a relationship between light eye colour and CMN prevalence.

The results of our study and further studies which take sun-exposure characteristics and pigmentary factors into account may facilitate the determination of additional factors affecting nevus development and may help to design preventive strategies for cutaneous melanoma in our geographical area.

Acknowledgements

Financial support: Cumhuriyet University Research Fund, Sivas, Turkey. Conflict of interest: none.

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