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Abstract
Context: Number of nevi is a risk factor for melanoma and basal cell carcinoma. Studies suggest that the dermoscopic pattern of nevi of melanoma patients may differ from healthy individuals. Similar data in patients with basal cell carcinoma is missing. Aims: The purpose of the study was to determine the number, anatomic distribution and dermoscopic pattern of nevi in melanoma and basal cell carcinoma patients. Settings and Design: An observational prospective study was conducted. Materials and Methods: Total body mole maps of 26 melanoma and 33 basal cell carcinoma patients were analysed. Statistical Analysis Used: Statistical analysis was done using the “IBM SPSS for Windows Version 22.0” package programme. Results: Number of nevi both on head and forearm were found significantly higher in the melanoma group (P = 0.015 and P = 0.031). Most frequent dermoscopic pattern was the complex pattern which was observed in 50.67% of melanoma and in 53.41% of basal cell carcinoma groups. Percentage of nevi with homogenous pattern located on the trunk and percentage of nevi with complex pattern located on the forearm was significantly higher in the melanoma group (P = 0.030 and P = 0.042). Conclusions: Higher number of nevi on the head and forearms; and more nevi showing homogenous pattern on the trunk and complex pattern on the forearms were the hallmarks of nevi in melanoma patients in comparison to basal cell carcinoma patients.
Keywords: Basal cell carcinoma, dermoscopy, melanocytic nevi, melanoma, risk factor
Introduction 
Increased number of melanocytic nevi has been associated with the development of melanoma. It is not clear whether the number of melanocytic nevi is a risk factors for basal cell carcinoma. Recently it has been reported that individuals with 15 or more melanocytic nevi located on the extremities had an increased risk both for melanoma and for basal cell carcinoma.[1]
Histopathological features of melanocytic nevi lead to typical dermoscopic patterns revealed by dermoscopic examination. Melanocytic nevi are defined in four different dermoscopic patterns namely, reticular, globular, homogeneous and complex. Recent studies suggested that the dermoscopic pattern observed in melanocytic nevi of melanoma patients may be different from that of healthy individuals. In a small study, the most common dermoscopic pattern of melanocytic nevi in melanoma patients was the complex dermoscopic pattern, whereas the patterns other than complex pattern were more common in healthy controls.[2] To the best of our knowledge, no study reveals the dermoscopic pattern of melanocytic nevi in basal cell carcinoma patients.
The aim of this study was to reveal and compare the number, the localization and the dermoscopic patterns of melanocytic nevi in melanoma and basal cell carcinoma patients.
Materials and Methods Patient selection
This study was carried out between 1 June 2019 and 30 June 2020 in a tertiary university hospital. Patients 18 years of age or older and patients who were under follow-up with a histopathologically confirmed diagnosis of melanoma or basal cell carcinoma were included in this study. Exclusion criteria for melanoma patients were the presence of xeroderma pigmentosum and/or similar cancer-related dermatological disease, basal cell carcinoma, squamous cell carcinoma, giant congenital melanocytic nevus, melanoma of unknown primary, uveal melanoma or acral lentiginous melanoma. Exclusion criteria for basal cell carcinoma patients were the presence of Gorlin syndrome and/or similar cancer-related dermatological disease, having a diagnosis of melanoma and/or squamous cell carcinoma.
Among 66 patients evaluated, 59 met the inclusion criteria and were assigned to melanoma (n = 26) and basal cell carcinoma (n = 33) groups. As shown in [Figure 1]. seven patients were excluded from the study because of the following characteristics: albinism (n = 1), melanoma of unknown primary (n = 1), acral lentiginous melanoma (n = 3), uveal melanoma (n = 1) and superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) (n = 1).
Figure 1: Flowchart of patients evaluated and excluded according to the exclusion criteriaEvaluation of skin cancer
Data concerning the details about tumour characteristics such as Breslow thickness, histologic subtypes, etc. were obtained from the software program used for medical information registry and/or by examining the pathology reports and medical reports brought by the patients who were diagnosed in external medical centres.
Data on melanocytic nevi count and dermoscopic pattern
Whole-body skin examinations of the patients were performed. After examining the melanocytic nevi of patients with a hand dermoscope (Dermlite DL4®) and marking them individually with a surgical marking pen, whole-body mole maps were obtained with a digital dermoscopy device (Fotofinder® Universe Version 2.0.39.3-x64). The total number of melanocytic nevi was calculated for each patient. To determine the number of melanocytic nevi according to the anatomical region, the number of melanocytic nevi in each anatomical region was recorded using human figures divided into six anatomical sub-regions: the head, trunk, arms, forearms, lower extremities and the genital area. Dermoscopic images of melanocytic nevi captured with digital dermoscopy device were analysed for dermoscopic pattern. Melanocytic nevi localized on the head, hand and/or foot regions were not included in the pattern analysis because of their special dermoscopic patterns. Analysis of the dermoscopic patterns of melanocytic nevi was made according to the 'New Brisbane Nevus Morphology Study Classification'.[3] In this classification, dermoscopic patterns of melanocytic nevi are categorized into four main subtypes: reticular, globular, homogeneous and complex. These patterns are represented in [Figure 2]. Additionally, dermoscopic patterns for each anatomic site was also recorded.
Figure 2: Analysis of the dermoscopic patterns of melanocytic nevus was made according to the “New Brisbane Nevus Morphology Study”. Images are examples of (a) reticular pattern, (b) globular pattern, (c) homogeneous pattern and (d-i) complex patternStatistical method
Statistical analysis was done using the 'IBM SPSS for Windows Version 22.0' package programme. Descriptive statistics such as number and percentage for qualitative variables, mean, standard deviation and median for quantitative variables were given as descriptive statistics. The difference between the two independent groups in terms of numerical variables was examined using the Mann–Whitney U test, which is one of the non-parametric methods, since the numerical variables did not show the normal distribution and were discrete numeric data types. In cases where this test was performed, the median, 25th percentile and 75th percentile were given as descriptive statistics. The relationship between two quantitative variables was analysed using the Spearman correlation coefficient, one of the non-parametric methods. The relationship between two independent qualitative variables was examined by Chi-square analysis. In the cross tables prepared, Fisher's exact test was taken into consideration in cases where the frequency value below 5 was high in the cells, and Pearson's Chi-square Test was taken into consideration when there was not much. The relationship between two dependent categorical variables with two categories was examined with the McNemar Test, and the relationship between two dependent categorical variables with more than two categories was examined with the Marginal Homogeneity Test. The relationship between two categories and more than two dependent variables was examined using the Cochran Q test.
Ethics committee approval
Approval for the study was obtained from the Non-Interventional Clinical Research Ethics Committee. All participants provided written informed consent before enrolment. The informed consent form was signed by the patients and the researchers.
Results Melanocytic nevi count
The total number of melanocytic nevi in the melanoma group (n = 26) and the basal cell carcinoma group (n = 33) were 1532 and 1637, respectively. The median number of total body melanocytic nevi was 51.50 (range 24-85) in the melanoma group and 26.00 (range 13-52) in the basal cell carcinoma group. When the patient groups were compared in terms of the number of total body melanocytic nevi, no statistically significant difference was found (P = 0.116).
[Table 1]. shows the distribution of melanocytic nevi according to the anatomical sites. The number of melanocytic nevi on the head and the forearms were significantly higher in the melanoma group than in the basal cell carcinoma group (P = 0.015 for head and P = 0.007 for the forearms).
Table 1: Distribution of the number of melanocytic nevi according to the anatomical region in the melanoma and basal cell carcinoma groupsPattern analysis
Excluding the head (n = 273), hands (n = 43) and feet (n = 31) the number of melanocytic nevi analysed in terms of dermoscopic pattern was 1328 (86.68%) in the melanoma group and 1494 (91.26%) in the basal cell carcinoma group. The most common dermoscopic pattern observed in the melanoma group was complex pattern (n = 673, 50.67%) followed by reticular (n = 458, 34.48%), homogeneous (n = 159, 11.97%) and globular pattern (n = 38, 2.86%). Likewise, in the basal cell carcinoma group the most common dermoscopic pattern was again the complex pattern (n = 798, 53.41%) followed by reticular (n = 474, 31.72%), homogeneous (n = 192, 12.85%) and globular pattern (n = 30, 2.00%). There was no significant difference in the distribution of the dermoscopic patterns between the melanoma and basal cell carcinoma groups.
Distribution of dermoscopic patterns according to the anatomical regions is shown in [Table 2]. When the two groups were compared in terms of dermoscopic patterns in certain anatomic sites, the homogeneous dermoscopic pattern on the trunk was statistically significantly higher in the melanoma group (P = 0.030) as well as the complex pattern in the forearms was statistically significantly higher in the melanoma group (P = 0.009).
Table 2: Distribution of the dermoscopic patterns of the melanocytic nevi according to the anatomical regions in the melanoma and basal cell carcinoma groups Discussion The number of melanocytic nevi is an important risk factor for melanoma. A study conducted by Randi et al.[4] determined the average number of melanocytic nevi in 542 melanoma patients and found 25.8 ± 2.2 melanocytic nevi in men and 20.4 ± 1.5 melanocytic nevi in women. It has been suggested that the number of melanocytic nevi creates even a higher risk than sun exposure for melanoma development.[5] Gandini et al.[6] compared individuals with 15 and less than 15 melanocytic nevi. They reported that the risk of developing melanoma was seven times higher in the first group. It was concluded that each additional melanocytic nevus increased the development of melanoma by 2-4%. The relationship between the number of melanocytic nevi and basal cell carcinoma has rarely been a subject of research. In a study conducted in Denmark, Lock-Andersen et al.[7] reported the median number of melanocytic nevi as 54 and the 25th and 75th percentile range as 25-106 in the basal cell carcinoma group. In our study, the median number of melanocytic nevi was found as 51.50 in the melanoma group and 26 in the basal cell carcinoma group; while the mean number of melanocytic nevus was 58.92 ± 46.16 in the melanoma and 49.60 ± 57.03 in the basal cell carcinoma group. Although the mean and median number of melanocytic nevi appeared to be different, no statistically significant difference was found. The fact that there was no difference in the number of melanocytic nevi between the melanoma and basal cell carcinoma groups in our study suggested that the number of melanocytic nevi may play a similar role as a risk factor for melanoma and basal cell carcinoma.
Different classifications have been used in dermoscopic pattern analysis in the literature. The seven-category system defined by Hoffman-Wellenhof, the old Brisbane Nevus Morphology Study classification and the New Brisbane Nevus Morphology Study classification are the most commonly used ones.[3] Differences between pattern classifications prevent the use of a common language and make it difficult to compare the studies and reach a conclusion. The large number of pattern classifications is the best proof of the absence of an ideal dermoscopic pattern classification. A worldwide accepted melanocytic nevi dermoscopic pattern classification may help in better-identifying populations at risk for melanoma development. It is obvious that an ideal pattern classification needs future studies. Nevertheless, in this study, we used the New Brisbane Nevus Morphology Study Classification.
There are only a few studies investigating the dermoscopic patterns of melanoma patients. Lipoff et al.[2] compared 20 melanoma and 20 control patients and analysed the dermoscopic patterns of 187 nevi on the back of melanoma patients and 150 nevi on the back of the control group. The researchers reported that the complex dermoscopic pattern in the melanoma group was 2.9 times more common than in the control group. The small sample size, dermoscopic analysis of nevi located only on the back and the retrospective design are the limitations of their study. As far as we know, there is no study investigating the dermoscopic pattern of melanocytic nevi in basal cell carcinoma. The most common dermoscopic pattern in both groups was the complex pattern in our study, and we found no statistically significant difference in the pattern distribution between the two groups. Furthermore, in another study we found that the most common dermoscopic pattern of melanocytic nevi in healthy adults was also complex (unpublished data). Thus, we concluded that independent from the diagnosis, the most common dermoscopic pattern observed in adults is the complex pattern.
There are many studies showing that the number of melanocytic nevi in different anatomical regions affect the risk of melanoma at different rates. The number of studies examining the same relationship for basal cell carcinoma is very limited. Wei et al.[1] found that individuals with 6-14 melanocytic nevus on the lower extremities and on the forearms increase the risk of melanoma 2.54-fold and 2.61-fold, respectively. They also found that the increase in the risk of basal cell carcinoma development in individuals with 6-14 melanocytic nevi on the lower extremities and on the forearms was 1.56-fold and 1.08-fold, respectively. In our study, although the median number of total nevi was similar in the melanoma and basal cell carcinoma patients, taking anatomic localization of the nevi into consideration, we found that melanoma patients have a higher number of melanocytic nevi on their forearms and on their heads. As the forearm and the head are easy to reach and observe body parts for physicians and also for individuals themselves and their families, we suggest multiple nevi at these sites should be alarming for melanoma.
Our knowledge about the dermoscopic patterns of nevi is expanding after the wide use of dermoscopy in our daily practices. Zalaudek et al.[8],[9] evaluated the change of melanocytic nevi with age in healthy individuals and found that the globular pattern was more frequent in the upper half of the body in children and adolescents, while this pattern decreased after the age of 20. They observed that the reticular pattern was the most common nevus pattern after 20 years of age on the upper and middle back. There are only very few studies dealing with the distribution of dermoscopic nevus patterns according to the anatomical region in patients with melanoma or basal cell carcinoma. In our study, the most common dermoscopic pattern in all anatomical regions was the complex nevus pattern in both groups. However, the percentages of homogeneous nevus patterns on the trunk and the percentage of complex patterns on the forearm were statistically significantly high in the melanoma group in comparison to the basal cell carcinoma group. We are not sure about the meaning of this finding. We might have made better suggestions if we knew more about the histopathologic correlates of homogeneous and complex nevus patterns. We do not even know whether the homogenous or complex nevus pattern is a phase of an ageing nevus or not? Or might these patterns be a physiologic response of a nevus to chronic or intermittent intense sun exposure? We think that the forearm is one of the best anatomical regions that exhibit the effects of chronic sun exposure. The higher number of melanocytic nevi and the high rate of complex nevus patterns on the forearms of the melanoma patients found in our study may suggest a relation between chronic sun exposure and complex nevus pattern. Besides, the trunk may be considered the anatomical region that best exhibits the effects of intermittent intense sun exposure. Thus, we may suggest that melanoma patients had a greater tendency to form homogeneous nevus patterns following intermittent intense sun exposure.
As a result, melanoma and basal cell carcinoma groups have a similar number of melanocytic nevi, but the number of nevi differs according to the anatomical regions. The small sample size is the limitation of our study. Our findings need to be consolidated with larger sample-sized studies. There is a need for a more valid dermoscopic pattern classification that will be universally accepted, and we need to know the dermatopathologic correlates of each dermoscopic nevus pattern. Our study gave us the impression that nevus patterns may be telling us more than we expect and deserve deeper investigations.
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Conflicts of interest
There are no conflicts of interest.
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