Instrument-, age- and site-dependent variations of dermoscopic patterns of congenital melanocytic naevi: a multicentre study

BACKGROUND: Recently, we identified and described dermoscopic aspects, present with a higher frequency in congenital melanocytic lesions with respect to acquired naevi. We also classified small- and medium-sized congenital naevi (CN) into nine subtypes according to their macroscopic and dermoscopic aspects. OBJECTIVES: Because the recognition of dermoscopic features may be instrument dependent, in this study, we wanted to check whether dermoscopic patterns specific for CN can be identified in digital images acquired by means of different instruments. We also wanted to check the validity of our previously proposed classification and assess possible age- and site-dependent variations of dermoscopic patterns and naevus subtypes. PATIENTS/METHODS: Images corresponding to 384 small- or medium-sized CN were collected in eight different centres employing four different instruments. Lesion images were evaluated and checked for the presence of specific dermoscopic criteria, classified, and compared with a database of 350 acquired naevi. RESULTS: Specific and unspecific dermoscopic features were identifiable in images acquired by means of all four instrument types. The mean number of identified features per lesion did not vary according to the instrument employed for the acquisition of the images; however, it was lower for lesions recorded employing low magnifications. The previously proposed classification was easily applied to the whole image database. The variegated naevus type was identified as a highly specific clinical/dermoscopic pattern. Dermoscopic features varied according to age and location. The globular type prevailed in subjects under 11 years of age and on the trunk, whereas the majority of reticular lesions were located on the limbs. CONCLUSIONS: Because definite clinical and histological criteria for the diagnosis of the congenital nature of naevi are lacking, the use of dermoscopy can be of great help in identifying those lesions where the presence of specific dermoscopic features makes the diagnosis of CN more likely. Moreover, dermoscopy can be useful both for the classification of lesions already identified as congenital according to definite clinical and anamnestic data and for a possible correlation of naevus phenotype and dermoscopic patterns to the risk of developing a malignant melanoma in prospective studies.     

The role of pattern analysis and the ABCD rule of dermoscopy in the detection of histological atypia in melanocytic naevi

BACKGROUND: Clinical features of melanocytic naevi correlate poorly with the presence, histopathologically, of architectural disorder and cytological atypia, making the detection of histological atypia by means of macroscopic appearance unreliable. OBJECTIVES: The aim of this study was to investigate the diagnostic effectiveness of dermoscopy in the non-invasive detection of histological atypia in naevi. METHODS: Observers blinded for histological diagnosis classified a series of 168 melanocytic naevi as common or atypical on the basis of their clinical features and on their dermoscopic profile. The diagnostic performance of both methods compared with the true (histopathological) diagnosis was assessed. RESULTS: Dermoscopy using pattern analysis showed better results than clinical examination in the non-invasive detection of naevi with architectural disorder with or without cytological atypia (diagnostic accuracy 45% vs. 28%). A statistically significant difference in the frequency of dermoscopic parameters between atypical and common naevi was found for atypical pigment network (39% vs. 17%, P = 0.001) and dermoscopic regression structures (13% vs. 2%, P = 0.008). Dermoscopic features, which best predicted histological atypia in naevi, were regression structures (white scar-like areas or peppering), irregular vascular pattern and grey-blue areas (positive predictive values 83%, 83% and 73%, respectively). In contrast, no statistically significant difference in the mean values of the ABCD score between common and atypical naevi was found. The best diagnostic performance of dermoscopy by means of the ABCD rule (cut-off point of 4.0 of total dermoscopy score) was not dissimilar to that of clinical diagnosis (diagnostic accuracy 30%). CONCLUSIONS: Dermoscopy by means of pattern analysis enhances the diagnostic accuracy of dermatologists in the prediction of histological atypia in melanocytic naevi as compared with clinical examination alone.     

Proposal of a new classification system for melanocytic naevi

The lack of consensus among clinicians and pathologists due to the mixture of clinical and histopathological features used to define the various melanocytic naevi underscores the need of a better classification system for these benign lesions. We describe a dermoscopic classification system for melanocytic naevi that is directed to clinicians dealing with the early diagnosis of melanoma, as well to pathologists, in order to promote better communication between these different specialists.     

New insights in naevogenesis: number, distribution and dermoscopic patterns of naevi in the elderly

Background/Objectives: It is well recognized that the number and patterns of acquired melanocytic naevi vary with age, but little is known about naevus patterns in the elderly. This is a cross‐sectional study assessing the prevalence, dermoscopic pattern and anatomical distribution of naevus subtypes in a stratified cohort aged between 60 and 89 years. Methods: Fifty‐nine patients who attended the Queensland Institute of Dermatology were recruited randomly and evenly distributed into three age groups: 60–69 years; 70–79 years; and 80–89 years. For each participant, total naevus count and morphological naevus types were recorded with respect to age, sex and anatomical location. Flat (Clark's) naevi were further subclassified according to the dermoscopic pattern as reticular, globular or structureless. Results: Using non‐parametric methods, naevus counts in the elderly decreased due to the disappearance of reticular naevi (P < 0.05). By contrast, structureless and intradermal (Unna's and Miescher's) naevi seemed to persist even into older age. Naevi on the trunk, limbs, head and neck represented 57.6%, 31.0% and 11.3%, respectively. Notably, no reticular naevi were found on the head and neck area. Conclusions: There is a progressive reduction in total naevus counts with advancing age with respect to a cohort aged greater than 60 years.     

Changes in the dermoscopic appearance of melanocytic naevi after photochemotherapy or narrow-band ultraviolet B phototherapy

BACKGROUND: Although phototherapeutic modalities are commonly used for the treatment of skin diseases, the effects of therapeutic ultraviolet (UV) irradiation on the dermoscopic appearance of melanocytic naevi are unknown. OBJECTIVES: We aimed to analyse the effects of photochemotherapy (psoralen plus ultraviolet A, PUVA) and narrow-band ultraviolet B phototherapy (NB-UVB) on the dermoscopic appearance of naevi. PATIENTS AND METHODS: We monitored 187 melanocytic naevi of 38 patients receiving NB-UVB or PUVA treatment for miscellaneous skin diseases. Dermoscopic images of naevi were taken before, shortly after, and after a median of 31 weeks after the UV therapy. A random selection of naevi was covered during UV treatment, the others remained uncovered. Baseline and follow-up images of naevi were viewed side by side on a computer screen to compare size, pigmentation, and dermoscopic structure of naevi. RESULTS: Twenty-one patients received NB-UVB treatment, and 17 patients received PUVA treatment. Of 187 naevi, 70 (37%) were covered and 117 (63%) were uncovered during UV treatment. When NB-UVB- and PUVA-treated patients were analysed together, an increase in size of uncovered lesions was seen in both treatment groups. Pigmentation appeared darker at the end of UV treatment in 67.5% (n=79) of uncovered naevi compared with 41.4% (n=29) of covered naevi (P<0.001). In patients receiving NB-UVB therapy, a significant increase in the number of dots or globules in 20.3% (n=14) of uncovered naevi compared with only 5.0% (n=2) of covered naevi (P=0.03) was found. This effect was not observed after PUVA therapy. With the exception of four naevi with continuous enlargement and seven naevi with a persisting increase in dots and globules, the observed changes were reversible. All naevi with persistent changes belonged to the NB-UVB group. CONCLUSION: In general, PUVA and NB-UVB therapy cause reversible dermoscopic changes in melanocytic naevi. Increase in dots and globules is more frequent with NB-UVB.     

Atopic dermatitis and melanocytic naevi

A study was performed to test the clinical impression that adults with severe atopic dermatitis (AD) have a low number of common naevi (CN). The number of CN > or = 2 mm was investigated in 51 Caucasian patients aged 20-63 years with severe AD since early childhood. The control group consisted of 379 randomly selected subjects, aged 30-50 years, investigated in an earlier study. Patients with AD had a significantly (P < 0.0001) lower total body count of CN (mean 9, median 5) compared with the control group (mean 67, median 53). It was also found that in the AD group there was a significant (P < 0.001) negative correlation between serum IgE and number of CN [r(s) = -0.50, 95% CI (-0.69; -0.24)]. The explanation for the low number of naevi that we have found in this highly selected subgroup of AD patients is not known. The atopic inflammation in the skin, genetics and treatment used for eczema are possible factors that may influence the formation of melanocytic naevi.     

The prevalence of melanocytic naevi among schoolchildren in South Hungary

Background Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, is an indispensable step in all primary prevention efforts. Objectives This paper aims to assess the prevalence of different pigmented lesions among schoolchildren and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors. Patients/methods A cross‐sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole‐body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables. Results One to 10 common melanocytic naevi were found in 27% of the participants, and the naevus numbers were in the range of 10–100 in 67%; 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Statistically significant associations were found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, a history of severe painful sunburns and a family history of a large number of melanocytic naevi. Conclusion Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of a large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.     

Single genetic mutations can account for melanocytic naevi

BACKGROUND: The nature of melanocytic naevi is unknown notwithstanding their considerable significance for clinician and pathologist and despite the wealth of existing knowledge about melanocyte biology. OBJECTIVES: To investigate how far a simple mutational model can explain the clinical and pathological features of melanocytic naevi, in particular their pattern of onset and frequency. METHODS: I have constructed a model of the development of the adult melanocyte population from a single stem cell. The total cutaneous melanocyte population in a human adult is already known, as well as the range of spontaneous mutation rates at a given gene site. For each cycle of mitosis during the post stem-cell expansion of the melanocyte population, I calculate the accumulated number of cells likely to be mutated at a particular (although unknown) gene site. The results are interpreted in the light of a hypothesis that each of these mutant melanocytes will go on to form a melanocytic naevus. Comparisons are made with neurofibromas, occurring in type 1 neurofibromatosis and as sporadic lesions. RESULTS: A single genetic mutation in melanocyte precursors is found to be sufficient to explain the clinical and pathological features of melanocytic naevi. CONCLUSIONS: I propose that melanocytic naevi are a consequence of single spontaneous genetic mutations which inevitably occur during the development of the adult population of cutaneous melanocytes.     

Pre-operative diagnosis of pigmented skin lesions: in vivo dermoscopy performs better than dermoscopy on photographic images

BACKGROUND: Epiluminescence microscopy (ELM) (dermoscopy, dermatoscopy) is a technique for non-invasive diagnosis of pigmented skin lesions that improves the diagnostic performance of dermatologists. Little is known about the possible influence of associated clinical features on the reliability of dermoscopic diagnosis during in vivo examination. OBJECTIVE: To compare diagnostic performance of in vivo dermoscopy (combined clinical and dermoscopic examination) with that of dermoscopy performed on photographic slides (pure dermoscopy). DESIGN: This case series comprised 256 pigmented skin lesions consecutively identified as suspicious or equivocal during examination in a general dermatological clinic. Clinical examination and in vivo dermoscopy were performed before excision by two trained dermatologists. The same observers carried out dermoscopy on photographic slides at a later time, and these three diagnostic classifications were reviewed together with the histological findings for the individual lesions. This was carried out in a university hospital. RESULTS: In vivo dermoscopy performed better than dermoscopy on photographic slides for classification of pigmented skin lesions compared with histological diagnosis, and both performed better than general clinical diagnosis. In vivo dermoscopic diagnosis of melanoma showed 98.1% sensitivity, 95.5% specificity and 96.1% diagnostic accuracy while dermoscopic diagnosis of melanoma on photographic slides was less reliable with 81.5% sensitivity, 86.7% specificity and 85.2% diagnostic accuracy. In particular, diagnosis of melanoma based on photographic slides led to nine false negative cases (three in situ, six invasive; thickness ranges 0.2-1.5 mm). CONCLUSIONS: In vivo dermoscopy, i.e. combined clinical and dermoscopic examination, is more reliable than dermoscopy on photographic slides. In clinical practice, therefore, in vivo dermoscopy cannot be considered independent from associated clinical characteristics of the lesions, which help the trained observer to reach a more precise classification. This may have implications on the reliability of ELM diagnosis made by an observer not fully trained in the clinical diagnosis of pigmented skin lesions or by a remote observer during digital ELM teleconsultation.     

Treatment of acquired junctional melanocytic naevi by Q-switched and normal mode ruby laser

BACKGROUND: Acquired junctional melanocytic naevi are harmless pigmented lesions of the epidermis, which can be of cosmetic concern. Various therapeutic approaches have been used in the treatment, but all these methods produce postoperative scarring or alterations in skin texture. Pigment laser treatment of benign pigmented lesions has shown a low potential for scarring by selectively targeting melanosomes in melanocytes and keratinocytes. OBJECTIVE: To find a fast, effective and safe treatment for the removal of acquired junctional melanocytic naevi. PATIENTS/METHODS: We first studied the effect of the Q-switched and normal mode ruby laser on 12 patients (eight women and four men) with acquired melanocytic naevi. The effect was monitored by histology and clinical photography. RESULTS: If the response to one treatment with the Q-switched laser mode was not completely effective, the lesions were subsequently treated with one or two sessions with the laser in normal mode. All flat lesions responded completely. After a follow-up period of 1 year they had not recurred. Slightly elevated lesions showed only a partial response, e.g. disappearance of the junctional part of the naevus but recurrence of the dermal part of the naevus. Red-brown junctional naevi as seen in skin types I and II did not respond well to ruby laser treatment. CONCLUSIONS: The Q-switched ruby laser was very successful in completely removing flat (non-palpable) acquired junctional melanocytic naevi, but not compound naevi, with one to three treatment sessions, without any scarring or pigmentary disturbance.     

Induction of eruptive benign melanocytic naevi by immune suppressive agents, including biologicals

BACKGROUND: Eruptive naevi have been described to potentially arise in immune compromised patients. OBJECTIVES: We describe three patients with eruptive benign melanocytic naevi during a phase of immunosuppressive therapy. METHODS/DIAGNOSIS: Two patients with Crohn disease were treated with either azathioprine monotherapy or a combination of azathioprine and infliximab, when eruptive naevi arose particularly at the palms and soles. Our third patient with plaque psoriasis developed eruptive naevi during two episodes of treatment: during a course with the biological agent alefacept and during etanercept therapy. CONCLUSIONS: We conclude that treatment with the recently available biological agents might be associated with the formation of eruptive naevi. Although positive evidence for the occurrence of malignant pigmented lesions is lacking, alertness to the development of eruptive melanocytic naevi during treatment with biological agents is indicated.     

Clinical selection of melanocytic lesions for dermoscopy decreases the identification of suspicious lesions in comparison with dermoscopy without clinical preselection

BACKGROUND: In most cases dermoscopy is performed only on lesions selected by clinical inspection which present worrying clinical features or appear to deviate from the patient's average type of naevus. Thus, possible early malignant melanomas (MMs) or MM precursors, lacking typical clinical characteristics, may elude the dermoscopic examination. OBJECTIVES: To perform a comparison between two different approaches to the patient's examination, one based on a clinical preselection of lesions to be examined by dermoscopy, and the other consisting of the dermoscopic scrutiny of all melanocytic lesions with a diameter>or=2 mm (total dermoscopy). METHODS: Sixty-three consecutive patients with MM, undergoing periodic dermoscopic examinations of their naevi, were enrolled in the study. The patients first underwent an assessment of the entire skin with the unaided eye for the identification of lesions for dermoscopy. Subsequently, the patients underwent dermoscopic examination of all melanocytic lesions. Images of naevi identified by clinical examination or by total dermoscopy as having dermoscopic aspects characteristic of a suspicious lesion, i.e. necessitating either surgical excision or follow-up examinations, were separately recorded, classified and described employing the ABCD rule of dermoscopy and the seven-point checklist. RESULTS: Five hundred and fifty-one lesions were chosen by clinical inspection for subsequent dermoscopic examination; among these, 117 were considered for excision or follow-up. Ninety-two further lesions were identified for excision or follow-up by employing only total dermoscopy. Dermoscopy scores of lesions selected by clinical inspection plus dermoscopy were similar to those identified by dermoscopy alone. In the former group, 13 lesions showed either an ABCD or a seven-point score corresponding to a suspicious lesion, whereas eight such lesions were identified only by total dermoscopy. Thus, by clinical selection plus dermoscopy we were able to identify only 62% of dermoscopically suspicious lesions. CONCLUSIONS: Clinical selection of melanocytic lesions for dermoscopic examination is associated with the 'loss' of a conspicuous number of lesions which deserve surgical excision or follow-up examinations. Total dermoscopy, enabling the detection of suspicious lesions, together with storage, retrieval and sequential comparison of their images, could enhance MM diagnosis by follow-up, in comparison with clinical preselection for dermoscopy.     

Macrophages in melanocytic naevi

Summary Whereas the inflammatory infiltrates of malignant melanoma have been widely investigated, little is known about the infiltrates accompanying benign melanocytic naevi. Using monoclonal antibodies directed against HLA-DR antigens, the CD1 antigen, the transferrin receptor and functionally divergent macrophage subpopulations, frozen fresh material of 87 melanocytic naevi (MN), ten primary cutaneous melanomas (PCM) and ten samples of normal skin were studied. Compared with normal skin, abundant HLA-DR⁺ cells were found in the stroma of MN equivalent to the quantity present in PCM. In MN we found higher numbers of dermal CD1⁺ dendritic cells compared with PCM and normal skin. There were more macrophages that expressed the transferrin receptor or the antigens 27E10, RM3/1 and 25F9 in MN than in normal skin but fewer than in PCM. No significant differences were found between congenital MN (n=40), common acquired MN (n=27) and dysplastic MN (n=20) macrophage subpopulations. Also, no correlations were evident between macrophage infiltrates and naevus location or patients' age. Our data show that potential melanoma precursors among melanocytic naevi cannot be identified by the pattern of macrophage infiltrates.     

In vivo confocal scanning laser microscopy of common naevi with globular, homogeneous and reticular pattern in dermoscopy

BACKGROUND: A systematic examination and comparison of confocal scanning laser microscopy (CSLM) features of benign naevi showing different dermoscopic patterns has never been performed. OBJECTIVES: Systematically to assess CSLM features of dermoscopically benign reticular, globular and homogeneous naevi and to correlate CSLM findings with dermoscopy and histopathology. METHODS: CSLM was performed on 30 naevi in 29 patients including 10 reticular, 10 globular and 10 homogeneous naevi showing a uniform pigmentation pattern with dermoscopy. Cytomorphological and architectural features of each naevus were assessed and distinct characteristics for each group of naevi were defined. CSLM features were correlated with the histopathological findings and their applicability for the diagnosis of naevi with different dermoscopic patterns was assessed by two blinded observers. RESULTS: A correct diagnosis was made in 26 and 28 of 30 cases, respectively, by two blinded observers using previously defined CSLM features. Well-defined melanocytic caps, well-defined edged papillae and black papillae concurrently with the absence of white papillae were found in all reticular naevi (10 of 10). Numerous, large junctional/dermal melanocytic nests (10 of 10), ill-defined edged papillae (eight of 10) and white papillae (nine of 10) were found in globular naevi. Homogeneous naevi showed an intermediate pattern between reticular and globular naevi: ill-defined edged papillae (10 of 10), black and white papillae within the same naevus (eight of 10) and junctional/dermal melanocytic nests (three of 10) were seen. CONCLUSIONS: Different dermoscopic patterns of benign naevi are reflected in different architectural features in CSLM. As benign naevi show a regular architecture of monomorphous melanocytes in contrast to melanomas, similar dermoscopic features of naevi and early melanomas may be differentiated by CSLM.     

Complications of congenital melanocytic naevi in children: analysis of 16 years' experience and clinical practice

Background Congenital melanocytic naevi (CMNs) can be associated with abnormalities of the cental nervous system (CNS) and/or with melanoma. Quoted incidences for these complications vary in the literature, as do recommendations for investigations and follow‐up. Objectives To determine the incidence of complications, and to identify phenotypic features associated with a higher risk of complications. Methods We reviewed records of 224 patients with CMNs seen in Dermatology clinic between 1991 and 2007. Patients were excluded if they had a complication at the time of referral. Magnetic resonance imaging (MRI) of the CNS was offered on the basis of CMN phenotype. Follow up was in clinic and/or by postal questionnaires. Results One hundred and twenty patients (54 boys and 66 girls) who had MRI of the CNS were included in the analysis. Mean age at MRI was 2·46 years (median 1·20). Mean follow up was 8·35 years (median 7·86). Sixty‐five per cent had naevi > 20 cm projected adult size or multiple CMNs (40% > 40 cm), and 83% had satellite lesions at birth. Outcome measures were MRI abnormality, clinical neurological abnormality, any tumour, malignant melanoma, and death. No complications were seen in the 16 patients with no satellite lesions at birth. MRI and/or clinical neurological abnormalities were found in 22 patients (18%) and were significantly associated with projected adult size of the CMN (particularly > 40 cm), and independently with male gender. Tumours occurred in five patients, two of which were malignant melanoma (1·7%). Due to small numbers there was no significant association between phenotype and occurrence of tumours. Three patients (2·5%) died (one from neuromelanosis and two from melanoma in patients with normal MRI scans). Death was significantly associated with CMN size > 40 cm. Importantly, there was no significant association between CMN distribution (including posterior axial location) and adverse outcomes. Conclusions This is the largest study of CNS imaging in patients with CMNs. We report a newly recognized association between male gender and neurological complications, dispute the previously reported association between CMN site and neurological complications, and quantify the associations between CMN size, satellite lesions and neurological complications. We make recommendations for the management of these patients.     

Surveillance of patients at high risk for cutaneous malignant melanoma using digital dermoscopy

BACKGROUND: Dermoscopy has improved the sensitivity and specificity of clinical diagnosis of melanoma from 60% to over 90%. However, in order not to miss melanoma a certain percentage of suspicious but benign lesions has to be excised. OBJECTIVES: To evaluate the dermoscopic changes and the rates of excision in benign melanocytic naevi and cutaneous malignant melanoma in long-term follow-up of high-risk patients using digital dermoscopy. METHODS: Digital dermoscopic images of 2015 atypical melanocytic naevi in 196 high-risk patients were analysed retrospectively. Among others, the following data were collected for each naevus: changes in surface area, overall architecture, dermoscopic patterns and distribution of pigmentation. All tumours suspicious for melanoma or showing asymmetrical changes were excised. RESULTS: During a median follow-up time of 25 months 128 (6.4%) of all naevi showed changes in size or architecture. Eighty-six per cent of all changes in patients who attended more than one visit were observed at the first follow-up visit. Thirty-three lesions showing changes were excised and two melanomas in situ and 31 melanocytic naevi were diagnosed. CONCLUSIONS: Follow-up examinations using digital dermoscopy revealed unchanged morphology in the large majority of melanocytic naevi. Excisions were only performed in cases of asymmetrical growth, asymmetrical changes of pigmentation, or development of dermoscopic features indicative of melanoma. The ratio of 33 lesions excised in order to identify two melanomas in situ seems reasonable and may be further reduced in future.