Benign Melanocytic Skin Lesions Research Articles

Problems and prospects in the treatment of various forms of pigmented nevi in children (a literature review)

Introduction. Pigmented nevi (PN) are formations in the skin layers which consist of accumulated melanocytes of various differentiation degrees and located in different layers of the skin. In modern society, this pathology causes serious medical and psychological problems; not infrequently , one can see unsatisfactory clinical and aesthetic outcomes. There is no any clear tactics which could take into account PN forms, location and child’s age. Purpose. To study modern problems and to outline prospects for treating various PN forms in children using the information obtained after literature search for the period 2005–2022. Material and methods. The authors made the literature search in domestic and foreign databases for the period 2005–2022. The following key words were used for the search: benign melanocytic skin lesions; pigmented nevus; laser radiation. 1627 literature sources were studied, 87 works were included in the review. Results. Despite of various techniques used for PN removal, unsatisfactory results are still noted in 41 % of patients with a complication rate of up to 50 %. After implementation laser scalpel for PN removal, complications in the form of hypertrophic and keloid scars were noted in 2–5 % of patients, postoperative hyperemia- in 21 % of cases, hyperpigmentation in 13 % and hypopigmentation in 34 %. The present review outlines advantages and disadvantages of various modalities used for removing PN. The authors also underline that the most promising ones are laser techniques in which laser light has a specific selectivity to pigmented tissues. The article has no information on parameters of laser irradiation which are required for treating definite forms of PN in children. Conclusion. Further research is needed to optimize existing and to develop new laser light techniques for treating various PN forms which should bring a significant improvement in outcomes.

Treatment of medium-sized facial nevus spilus with a dual-wavelength copper vapor laser

Nevus spilus (NS; synonym: speckled lentiginous nevus) − benign congenital or, more often, acquired melanocytic nevus − is characterized by numerous foci of hyperpigmentation located on a light brown background with possible transformation into malignant tumors. Its prevalence is ∼2% among the general population. NS sizes vary from 2 to 10 cm in diameter, but more extensive lesions have been described. Patients turn to a dermatologist when NS is located in aesthetically significant areas owing to cosmetic problems. Surgical methods for removing NS are associated with a risk of scarring. The use of various types of lasers for the treatment of NS has allowed successful results. However, it is accompanied by adverse effects such as scars, postinflammatory hyperpigmentation, and relapses. Our experience in treating benign melanocytic skin lesions using copper vapor laser (CVL) radiation, which allows selective heating of the pigment and blood vessels, gives us grounds for using CVL to treat NS. For the first time, we describe an innovative method of treating NS with dual-wavelength CVL radiation. A case of NS (medium size 50×40 mm) located in the cheek area was treated in a 39-year-old fair-skinned patient with type II skin, according to Fitzpatrick. NS treatment was carried out with the following parameters of the CVL (Yakhroma-Med model, P.N. Lebedev Physical Institute of the Russian Academy of Sciences): average power 0.6–0.8 W, with a power ratio of 3:2, at wavelengths of 511 and 578 nm. The pulse duration is 20 ns, the repetition rate is 16.6 kHz, the exposure time is 0.2–0.3 s, and the diameter of the light spot on the skin is 1 mm. After six treatments, the color of the hyperpigmented area, dark macules, and papules were eliminated. The follow-up period was 24 months. Medium-sized NS treatment with CVL provided complete elimination of the pathological focus and provided excellent cosmetic results. No relapse was observed within 24 months after treatment.

A multicentre pilot study investigating high-definition optical coherence tomography in the differentiation of cutaneous melanoma and melanocytic naevi.

High-definition optical coherence tomography scanners have recently been developed. To assess the diagnostic performance of HD-OCT in the differentiation of benign melanocytic skin lesions (MSL) and cutaneous melanoma (CM). Patients with MSL were assessed by HD-OCT. All diagnoses were histopathologically confirmed. One blinded observer evaluated both slice and en-face HD-OCT images and diagnosed MLS on the basis of an algorithm adopted from reflectance confocal microscopy, recent HD-OCT reports, and conventional OCT. A total of 93 MSL were studied comprising 66 benign MSL and 27 CM. The sensitivity of HD-OCT was 74.1% [95% confidence interval (CI) 53.7-88.8%)], specificity was 92.4% (95% CI 83.2-97.5%). The positive predictive value was 80%, the negative predictive value 89.7%. The performance of HD-OCT depended on tumour thickness and the presence of borderline lesions indicated by high false negative rates in very thin melanomas and high false positive rates in dysplastic naevi. In the distinction of MSL, HD-OCT applied in an investigator blinded fashion has a moderate diagnostic performance. The diagnostic performance of HD-OCT of MSL should be reassessed in other clinical settings.

Computer-automated ABCD versus dermatologists with different degrees of experience in dermoscopy

Dermoscopy is a very useful and non-invasive technique for in vivo observation and preoperative diagnosis of pigmented skin lesions (PSLs) inasmuch as it enables analysis of surface and subsurface structures that are not discernible to the naked eye. The authors used the ABCD rule of dermoscopy to test the accuracy of melanoma diagnosis with respect to a panel of 165 PSLs and the intra- and inter-observer diagnostic agreement obtained between three dermatologists with different degrees of experience, one General Practitioner and a DDA for computer-assisted diagnosis (Nevuscreen(®), Arkè s.a.s., Avezzano, Italy). 165 Pigmented Skin Lesions from 165 patients were selected. Histopathological examination revealed 132 benign melanocytic skin lesions and 33 melanomas. The kappa statistic, sensitivity, specificity and predictive positive and negative values were calculated to measure agreement between all the human observers and in comparison with the automated DDA. Our results revealed poor reproducibility of the semi-quantitative algorithm devised by Stolz et al. independently of observers' experience in dermoscopy. Nevuscreen(®) (Arkè s.a.s., Avezzano, Italy) proved to be 'user friendly' to all observers, thus enabling a more critical evaluation of each lesion and representing a helpful tool for clinicians without significant experience in dermoscopy in improving and achieving more accurate diagnosis of PSLs.

Atypical melanocytic lesions of the thigh with spitzoid and dysplastic features: a clinicopathologic study of 29 cases

Melanocytic nevi in certain anatomic locations can display unusual histopathologic features potentially creating diagnostic uncertainty. Benign melanocytic nevi in sites such as acral, genital, and flexural areas may show unusual architecture and cytologic atypia, which can mimic dysplastic nevi and, sometimes, melanoma. Twenty-nine benign melanocytic skin lesions were identified in the thigh of 26 women and 3 men who showed atypical histologic features, including both dysplastic and spitzoid features. All lesions measured less than 1 cm in diameter. Eighteen cases showed features of compound nevi, and 11 were junctional. In all cases, the lesions displayed spitzoid features including large epithelioid and/or spindle cells, some melanocytes with ganglion-like cytomorphology, and focal suprabasilar upward migration. All cases showed dysplastic features. Clinical follow-up was available in 26 patients; no recurrences or metastases were observed. The demographic features and the anatomical sites of these melanocytic nevi appear to be reproducible, and in the assessment of histologically difficult cases, these data are helpful. It is our opinion that the malignant potential of these lesions with hybrid patterns (spitzoid/dysplastic) has yet to be determined, and although we favor these lesions to be benign, longer follow-up may yield a more complete understanding of their biologic potential.

Application of fluorescencein situhybridization as a diagnostic tool in melanocytic lesions, using paraffin wax-embedded tissues and imprint-cytology specimens

Accurate histopathological diagnosis of certain melanocytic skin lesions as benign or malignant can be notoriously difficult. Recently, four-colour fluorescence in situ hybridization (FISH) has emerged as an important tool for classifying these lesions. To evaluate the sensitivity and specificity of a melanoma FISH probe kit for accurate diagnosis of melanocytic tumours, and to validate its use with imprint-cytology specimens from the cut surface of tumours. In total, 50 melanocytic skin lesions (31 malignant melanomas, 10 benign melanocytic naevi, and 9 histologically challenging benign melanocytic skin lesions) were evaluated. The samples comprise 47 tissue specimens embedded in paraffin wax, and three imprint-cytology specimens from the cut surface of melanomas. FISH was performed using four locus-specific identifier probes [Ras responsive element binding protein (RREB)1, myeloblastosis viral oncogene homologue (MYB), cyclin (CCN)D1 and centromere of chromosome (CEP)6], and results were compared with the clinical long-term follow-up and histopathological diagnosis data. The melanoma FISH probe distinguished between naevi and melanomas with a sensitivity of 100% and a specificity of 94.1%. The most sensitive criterion was a gain in 6p25 (RREB1), seen in 100% of cases, followed by CEP6-related MYB loss (48.1%), CCND1 gain (37%) and MYB gain (22.2%). More than three-quarters (77.8%) of melanomas were positive for two or more criteria. Positive FISH results were also obtained for the imprint-cytology specimens. FISH is a valuable diagnostic tool for differentiating between benign and malignant melanocytic lesions, providing a high degree of sensitivity and specificity. The probes displayed exceptional discriminative capacity in difficult or ambiguous lesions. To our knowledge, his is the first reported use of imprint-cytology specimens for FISH diagnosis.

The value of cyclooxygenase-2 expression in differentiating between early melanomas and histopathologically difficult types of benign human skin lesions

Early cutaneous melanomas may present a substantial diagnostic challenge. We have already reported that expression of cyclooxygenase-2 (COX-2) may be useful for differentiating between cutaneous melanomas and naevi. The purpose of this study was to examine the value of COX-2 in a challenging task of differential diagnosis of early melanomas and melanocytic naevi considered by histopathologists as morphologically difficult to unequivocally diagnose as benign lesions. The material for the study comprised formalin-fixed paraffin-embedded samples of 46 naevi (including 27 cases of dysplastic, Spitz and Reed naevi) and 30 early human cutaneous melanomas. The expression of COX-2 was detected immunohistochemically. Melanomas expressed COX-2 significantly more strongly compared with naevi. The test, on the basis of determination of the percentage fractions of COX-2-positive cells, allows for differentiation of early skin melanomas and naevi with high sensitivity and specificity. Receiver operating characteristic analysis of the test results yielded areas under receiver operating characteristics curves (AUC)=0.946±0.030 for central regions and AUC=0.941±0.031 for the peripheries of the lesions. The performance of the test in differentiating between melanomas and the naevi group comprising dysplastic, Spitz and Reed naevi was also good, with AUC=0.933±0.034 and 0.923±0.037 for the central and the border regions of the lesions, respectively. Using a more complex diagnostic algorithm also accounting for the staining intensity did not result in an improvement in the resolving power of the assay. A diagnostic algorithm using differences in the percentage fractions of cells expressing COX-2 may serve as a useful tool in aiding the differential diagnosis of 'histopathologically difficult' benign melanocytic skin lesions and early melanomas.

In vivo reflectance confocal microscopy: automated diagnostic image analysis of melanocytic skin tumours

In vivo reflectance confocal microscopy (RCM) has been shown to be a valuable imaging tool in the diagnosis of melanocytic skin tumours. However, diagnostic image analysis performed by automated systems is to date quite rare. In this study, we investigated the applicability of an automated image analysis system using a machine learning algorithm on diagnostic discrimination of benign and malignant melanocytic skin tumours in RCM. Overall, 16,269 RCM tumour images were evaluated. Image analysis was based on features of the wavelet transform. A learning set of 6147 images was used to establish a classification tree algorithm and an independent test set of 10, 122 images was applied to validate the tree model (grouping method 1). Additionally, randomly generated 'new' learning and test sets, tumour images only and different skin layers were evaluated (grouping method 2, 3 and 4). The classification tree analysis correctly classified 93.60% of the melanoma and 90.40% of the nevi images of the learning set. When the classification tree was applied to the independent test set 46.71 ± 19.97% (range 7.81-83.87%) of the tumour images in benign melanocytic skin lesions were classified as 'malignant', in contrast to 55.68 ± 14.58% (range 30.65-83.59%; t-test: P < 0.036) in malignant melanocytic skin lesions (grouping method 1). Further investigations could not improve the results significantly (grouping method 2, 3 and 4). The automated RCM image analysis procedure holds promise for further investigations. However, to date our system cannot be applied to routine skin tumour screening.

Parkinson's Disease-Related Protein, α-Synuclein, in Malignant Melanoma

BackgroundMelanoma is the major cause of skin cancer death worldwide. Parkinson's disease is a neurodegenerative disorder that is caused by mutation of α-synuclein or other genes. Importantly, epidemiological studies have reported co-occurrence of melanoma and Parkinson's disease, suggesting that these two diseases could share common genetic components.Methodology/Principal FindingsRecently, we found that human melanoma cell lines highly express α-synuclein, whereas the protein is undetectable in the non-melanoma cancer cell lines tested. To investigate the expression of α-synuclein in human melanoma tissues, we immunostained sections of melanoma, nevus, non-melanocytic cutaneous carcinoma, and normal skin. α-Synuclein was positively detected in 86% of the primary and 85% of the metastatic melanoma sections, as well as in 89% of nevus sections. However, α-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.Conclusions/SignificanceThe Parkinson's disease-related protein, α-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi. Although α-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

Wavelet Analysis of Cutaneous Blood Flow in Melanocytic Skin Lesions

Laser Doppler flowmetry (LDF) is frequently used to study the microcirculation. Usually LDF time series are analyzed by conventional linear methods, mainly Fourier analysis. The aim of this study was to observe dynamic blood perfusion of the skin in malignant and benign melanocytic skin lesions. Wavelet transformation was performed on each LDF time series in order to calculate a vasomotion field. First, the differences in vasomotion between healthy and pigmented skin were evaluated visually on six different time scales of the vasomotion field. In order to quantify the findings, vasomotion scale variance (VSV) was calculated for each scale plane of the vasomotion field. These VSV were compared using contrast ΔVSV to determine the difference between healthy skin and a pigmented skin lesion in the same patient. After the measurements, the skin lesions were excised and examined histologically. We found that wavelet analysis of LDF time series is a specific, sensitive method for the in vivo identification of malignant melanoma. It is a non-invasive procedure and takes minimal time to be carried out.

Clinically equivocal melanocytic skin lesions with features of regression: a dermoscopic-pathological study

Benign melanocytic skin lesions may be difficult to differentiate from melanoma both clinically and dermoscopically. One of the most confounding dermoscopic features, commonly seen in melanoma but in our experience also in melanocytic naevi, is represented by the so-called blue-white structures (BWS). To evaluate diagnostic significance and histopathological correlates of BWS seen by dermoscopy in a series of clinically equivocal melanocytic skin lesions that were excised. Patients were recruited from six specialized pigmented lesion clinics in Austria, Italy and Spain over a period of 9 months. All consecutive patients showing one or more melanocytic lesions with BWS, but not classified as melanoma dermoscopically, were included. Each lesion was photographed clinically and dermoscopically. All images were reviewed by one of us and the degree, type and location of BWS evaluated for each lesion. A panel of four experienced dermatopathologists independently reviewed all specimens for diagnosis and one of them evaluated presence and degree of melanosis and/or fibrosis. The main outcome measures were the percentage and histopathological correlates of lesions with different degree, type and location of BWS. All included lesions with BWS (n = 158) showed partial or focal regression histopathologically. One hundred and thirty-five (85.4%) lesions were diagnosed as melanocytic naevi (complete histopathological interobserver agreement), whereas 23 (14.6%) were defined as equivocal because at least one of four pathologists diagnosed the given lesion as melanoma. Only one lesion was diagnosed as melanoma by all four pathologists. The majority of naevi exhibited blue areas (84.4%) with a central distribution (57%) and involving < 50% of the lesion surface (89.6%). By contrast, 78.3% of equivocal lesions revealed a combination of white and blue areas with an irregular distribution (60.9%) and involving > 50% of the lesion surface (47.8%). Using degree and type of BWS, an algorithm was constructed that can be applied for the management of lesions exhibiting dermoscopic features of regression.

Follow-up of melanocytic skin lesions with digital epiluminescence microscopy: Patterns of modifications observed in early melanoma, atypical nevi, and common nevi

Background: Digital epiluminescence microscopy (DELM) has been reported to be a useful technique for the follow-up of melanocytic nevi. One of the promises of this technique is to identify modifications over time that indicate impending or incipient malignancy and to facilitate surveillance of melanocytic skin lesions, particularly in patients with multiple clinically atypical nevi. Objective: Our purpose was to report on patterns of modifications over time observed in benign melanocytic skin lesions and melanoma. Methods: A total of 1862 sequentially recorded DELM images of melanocytic lesions from 202 patients (mean age, 36.1 years; 54.0% female patients) with multiple clinically atypical nevi were included in the analysis. The median follow-up interval was 12.6 months. Melanocytic lesions with substantial modifications over time (enlargement, changes in shape, regression, color changes or appearance of ELM structures known to be associated with melanoma) were excised and referred to histopathologic examination. Results: A total of 75 melanocytic skin lesions (4.0%) from 52 patients (mean age, 33.3 years; 63.5% female patients) showed substantial modifications over time and were excised and referred to histopathologic examination. Eight changing lesions were histologically diagnosed as early melanomas. These lesions frequently showed focal enlargement associated with a change in shape as well as appearance of ELM structures that are known to be associated with melanoma. In contrast, the majority of benign changing lesions (common and atypical nevi) showed symmetric enlargement without substantial structural ELM changes. Six of the 8 patients in whom melanoma developed were unaware of the fact that the lesion had changed over time. Conclusion: We demonstrate that follow-up of melanocytic lesions with DELM helps to identify patterns of morphologic modifications typical for early melanoma. DELM may therefore serve as a useful tool to improve the surveillance of patients with multiple atypical nevi. (J Am Acad Dermatol 2000;43:467–76.).

Two types of pattern modification detected on the follow-up of benign melanocytic skin lesions by digitized epiluminescence microscopy.

Digital epiluminescence microscopy (DELM) is currently being developed for the diagnosis of pigmented skin lesions (PSL) and the early diagnosis of malignant melanoma. So far there are only few studies documenting if modifications in PSL may be detected by DELM over time. Our purpose was to determine if DELM is an adequate tool for the follow-up of PSL and if any detectable modifications occur within PSL over time. We followed 150 PSL over 2 years in 67 patients using a DELM system. At the end of the follow-up period, the retrieved DELM images were analysed by two observers and evaluated for the presence and type of modifications. Modifications were observed in 69% of the PSL. These modifications were of two types. Type 1 corresponded to an increase in the pigment content of the lesion without modification of either its size or architecture, and was probably related to sun-related seasonal variation. Type 2 included an increase in the size and various variations in the architecture, corresponding to a progression of the lesion. Correlation of the type of modification with the type of PSL, as defined by its epiluminescence microscopy (ELM) patterns, indicated that type 2 modifications were associated with lesions initially showing ELM signs of 'dysplasia', whereas lesions showing only type 1 modifications did not show such patterns. We have documented the feasibility of following up PSL with DELM. The pattern of modification of a PSL over time could be correlated with its nature.