Melanocytic Skin Lesions Research Articles

Cutaneous Oncology: From Research to Diagnosis and Management

Cutaneous Oncology: From Research to Diagnosis and Management

Eruptive Lentigines after Adalimumab Therapy

Adalimumab, a TNF-alpha antagonist, is the first fully humanized recombinant immunoglobulin G1 (IgG1) monoclonal antibody. It is presently widely used in the systemic treatment of rheumatoid arthritis, inflammatory bowel disease, moderate and severe psoriasis and hidradenitis suppurativa. However, its administration is associated with a two-fold risk of severe and possibly fatal infections and in some rare cases with congestive heart failure, lymphoma, lupus-like syndrome, cytopenias, hepatotoxicity and development of demyelinating neurological disorders. Furthermore, the occurrence of various types of melanocytic skin lesions has been reported during treatment with adalimumab. In the present paper we report the case of a female psoriatic patient who developed eruptive lentigines following treatment with this compound.

Development of diagnostic methods of malignant melanoma from 'noli me tangere' to dermoscopy

The first description of skin lesions suspicious for melanoma was made by Hippocrates, the father of medicine, in the 5th century BC. The famous Biblical quotation 'Noli me tangere' (Do not touch me) was a rule over the centuries, since it was thought that diseases could be spread or get worse by touching. The first nail blood vessels microscopy was done 1663 by J.C. Kohlhans. The term melanoma was introduced by Robert Carsswell in 1834. In 1858, Oliver Pemberton described 60 patients with melanoma and noted that the disease is also common among black race people. W.S. Hadley established the surgical treatment that was being implemented for almost a half of century and involved a wide tumour excision. Mc Govern, Clarck and Breslow described the stages of melanoma and Breslow, moreover, introduced the measurement of tumour thickness as a basic parameter of the disease. In 1916 C. Zaiss built a binocular microscope. The diagnosis of melanoma was notably improved in 80's of the last century by introduction of modern examination technologies, as well as using specific paths to analyze the tumour lesion, which all together made easier to come up with the diagnosis of melanoma. The use of standardized terminology for the description of skin structure started at the end of nineties, together with the use of algorithms for the differentiation of benign from malignant melanocytic skin lesions. Nowadays, there are four different algorithms for the diagnosis and determining of malignant melanoma-change: The ABCD rule (Stolz method), 7-point checklist (Argenziano), Menzies' scoring method, Structure analysis (Pehamberger et al, Kenneth et al, Argenziano et al.). The increasing influence of risk factors and the genetics have come to be the imperative for higher qualifications of medical professionals with the aim of early and proper diagnostics of melanoma.

In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography

One of the most challenging problems in clinical dermatology is the early detection of melanoma. Reflectance confocal microscopy (RCM) is an added tool to dermoscopy improving considerably diagnostic accuracy. However, diagnosis strongly depends on the experience of physicians. High-definition optical coherence tomography (HD-OCT) appears to offer additional structural and cellular information on melanocytic lesions complementary to that of RCM. However, the diagnostic potential of HD-OCT seems to be not high enough for ruling out the diagnosis of melanoma if based on morphology analysis. The aim of this paper is first to quantify in vivo optical properties such as light attenuation in melanocytic lesions by HD-OCT. The second objective is to determine the best critical value of these optical properties for melanoma diagnosis. The technique of semi-log plot whereby an exponential function becomes a straight line has been implemented on HD-OCT signals coming from four successive skin layers (epidermis, upper papillary dermis, deeper papillary dermis and superficial reticular dermis). This permitted the HD-OCT in vivo measurement of skin entrance signal (SES), relative attenuation factor normalized for the skin entrance signal (µraf1) and half value layer (z1/2). The diagnostic accuracy of HD-OCT for melanoma detection based on the optical properties, µraf1, SES and z1/2 was high (95.6, 82.2 and 88.9 %, respectively). High negative predictive values could be found for these optical properties (96.7, 89.3 and 96.3 %, respectively) compared to morphologic assessment alone (89.9 %), reducing the risk of mistreating a malignant lesion to a more acceptable level (3.3 % instead of 11.1 %). HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with in vivo analysis of optical properties of tissue scatterers in melanocytic lesions. In vivo HD-OCT analysis of optical properties permits melanoma diagnosis with higher accuracy than in vivo HD-OCT analysis of morphology alone.

How concerns and experiences with medical malpractice affect dermatopathologists' perceptions of their diagnostic practices when interpreting cutaneous melanocytic lesions

We sought to identify characteristics associated with past malpractice lawsuits and how malpractice concerns may affect interpretive practices. We surveyed 207 of 301 (68.8%) eligible dermatopathologists who interpret melanocytic skin lesions in 10 states. The survey assessed dermatopathologists' demographic and clinical practice characteristics, perceptions of how medical malpractice concerns could influence their interpretive practices, and past malpractice lawsuits. Of dermatopathologists, 33% reported past malpractice experiences. Factors associated with being sued included older age (57 vs 48 years, P < .001), lack of board certification or fellowship training in dermatopathology (76.5% vs 53.2%, P = .001), and greater number of years interpreting melanocytic lesions (>20 years: 52.9% vs 20.1%, P < .001). Of participants, 64% reported being moderately or extremely confident in their melanocytic interpretations. Although most dermatopathologists believed that malpractice concerns increased their likelihood of ordering specialized pathology tests, obtaining recuts, and seeking a second opinion, none of these practices were associated with past malpractice. Most dermatopathologists reported concerns about potential harms to patients that may result from their assessments of melanocytic lesions. Limitations of this study include lack of validation of and details about the malpractice suits experienced by participating dermatopathologists. In addition, the study assessed perceptions of practice rather than actual practices that might be associated with malpractice incidents. Most dermatopathologists reported apprehension about how malpractice affects their clinical practice and are concerned about patient safety irrespective of whether they had actually experienced a medical malpractice suit.

Prior knowledge of the clinical picture does not introduce bias in the histopathologic diagnosis of melanocytic skin lesions.

A common debate among dermatopathologists is that prior knowledge of the clinical picture of melanocytic skin neoplasms may introduce a potential bias in the histopathologic examination. Histologic slides from 99 melanocytic skin neoplasms were circulated among 10 clinical dermatologists, all of them formally trained and board-certified dermatopathologists: 5 dermatopathologists had clinical images available after a 'blind' examination (Group 1); the other 5 had clinical images available before microscopic examination (Group 2). Data from the two groups were compared regarding 'consensus' (a diagnosis in agreement by ≥4 dermatopathologists/group), chance-corrected interobserver agreement (Fleiss' k) and level of diagnostic confidence (LDC: a 1-5 arbitrary scale indicating 'increasing reliability' of any given diagnosis). Compared with Group 1 dermatopathologists, Group 2 achieved a lower number of consensus (84 vs. 90) but a higher k value (0.74 vs. 0.69) and a greater mean LDC value (4.57 vs. 4.32). The same consensus was achieved by the two groups in 81/99 cases. Spitzoid neoplasms were most frequently controversial for both groups. The histopathologic interpretation of melanocytic neoplasms seems to be not biased by the knowledge of the clinical picture before histopathologic examination.

A histopathological study of melanocytic and pigmented skin lesions in patients with albinism.

Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by diminished pigmentation of the skin, hair and eyes. Individuals with OCA are at increased risk to develop sun-induced skin malignancies. The incidence of malignant melanoma in OCA individuals is, however, very low. The aim of this study was to document pigmented and melanocytic skin lesions occurring in patients with OCA. A prospective study was performed. Sixteen patients with OCA presenting at the Oncology and Dermatology Departments at Universitas Academic Hospital Annex in Bloemfontein, South Africa, were included. Selected clinically pigmented and/or melanocytic lesions were biopsied and studied by light microscopy. Twenty-four punch biopsies were taken. Ten dendritic freckles and 10 melanocytic nevi were confirmed histologically. The nevi, which occurred in eight patients, were found on sun-protected skin. All the freckles occurred on sun-exposed skin. Twelve patients had current or previous skin malignancies. No melanomas were present in the study population. Other skin lesions ranged from solar keratoses to squamous cell carcinomas. The majority of pigmented lesions were dendritic freckles that occurred on sun-exposed skin. None of the patients had a current or previous diagnosis of malignant melanoma.

The feasibility of using manual segmentation in a multifeature computer-aided diagnosis system for classification of skin lesions: a retrospective comparative study

ObjectivesTo investigate the feasibility of manual segmentation by users of different backgrounds in a previously developed multifeature computer-aided diagnosis (CADx) system to classify melanocytic and non-melanocytic skin lesions based on...

Moderne Diagnoseverfahren in der Dermatoonkologie

New technologies, such as confocal laser scanning microscopy (CLSM), optical coherence tomography (OCT), electrical impedance spectroscopy (EIS) and multispectral analysis have greatly enriched the possibilities of diagnostics in dermatological oncology. They can be supplementary tools to dermatoscopy and histopathology to make a more precise diagnosis of skin lesions. Increasing relevance of new systems for diagnosis and monitoring of dermatological therapy. Presentation of the technology and the diagnostic range of application for various skin lesions. Presentation of scientifically relevant studies and statistical data, discussion of basic research and expert recommendations. The diagnostic spectrum of dermatological oncology has been significantly enriched in recent years. New technologies, such as CLSM, OCT, EIS and multispectral analysis are non-invasive and therefore painless for the patient. In only a few minutes these techniques deliver valid data and findings and provide dermatologists with more accurate diagnostic information about benign or malignant melanocytic skin lesions or the various forms of white skin cancer. In recent years, non-invasive diagnostic and analytical imaging procedures have been progressively established in dermatological oncology and supplement classical dermatoscopy and histopathology. With respect to the follow-up of different therapeutic modalities unnecessary tissue biopsies and scars can be reduced for patients.

Dermoscopic Characteristic Structures of Melanocytic Lesions

Dermoscopy has recorded continuous development in the past decades. Both global and individual features of dermoscopic morphology that play an role in identifying melanomas have enjoyed particular attention by researchers. Dermoscopy has gained an undoubted place in the detection of early melanomas. This paper is a review of data existent in literature that approach of dermoscopic morphology features of melanocytic pigmented skin lesions. This work highlights such situations where these features may be found in non-melanocytic pigmented skin lesions thus inducing confused diagnosis.

Computer-Aided Decision Support for Melanoma Detection Applied on Melanocytic and Nonmelanocytic Skin Lesions: A Comparison of Two Systems Based on Automatic Analysis of Dermoscopic Images.

Commercially available clinical decision support systems (CDSSs) for skin cancer have been designed for the detection of melanoma only. Correct use of the systems requires expert knowledge, hampering their utility for nonexperts. Furthermore, there are no systems to detect other common skin cancer types, that is, nonmelanoma skin cancer (NMSC). As early diagnosis of skin cancer is essential, there is a need for a CDSS that is applicable to all types of skin lesions and is suitable for nonexperts. Nevus Doctor (ND) is a CDSS being developed by the authors. We here investigate ND's ability to detect both melanoma and NMSC and the opportunities for improvement. An independent test set of dermoscopic images of 870 skin lesions, including 44 melanomas and 101 NMSCs, were analysed by ND. Its sensitivity to melanoma and NMSC was compared to that of Mole Expert (ME), a commercially available CDSS, using the same set of lesions. ND and ME had similar sensitivity to melanoma. For ND at 95% melanoma sensitivity, the NMSC sensitivity was 100%, and the specificity was 12%. The melanomas misclassified by ND at 95% sensitivity were correctly classified by ME, and vice versa. ND is able to detect NMSC without sacrificing melanoma sensitivity.

High-definition optical coherence tomography of melanocytic skin lesions.

High-definition optical coherence tomography (HD-OCT) scanners have recently been developed. We assessed micromorphological HD-OCT correlates of benign naevi (BN) and malignant melanoma (MM). 28 BN and 20 MM were studied using HD-OCT and histology. Epidermal honeycomb/cobblestone pattern, regular junctional cell nests, and edged papillae are more often observed in BN, whereas fusion of rete ridges, pagetoid cells and junctional and/or dermal nests with atypical cells are more frequently seen in MM. A high overlap of HD-OCT features in BN and MM was observed and in 20% of MM we did not find evidence for malignancy in OCT images at all. Using HD-OCT it is possible to visualize architectural and cellular alterations of melanocytic skin lesions. The overlap of HD-OCT features seen in BN and MM and the absence of suspicious HD-OCT features in some MM represents an important limitation of HD-OCT affecting the sensitivity of HD-OCT in diagnosing MM. High-definition optical coherence tomography and the corresponding vertically sectioned histology of a compound naevus.

Four-class classification of skin lesions with task decomposition strategy.

This paper proposes a new computer-aided method for the skin lesion classification applicable to both melanocytic skin lesions (MSLs) and nonmelanocytic skin lesions (NoMSLs). The computer-aided skin lesion classification has drawn attention as an aid for detection of skin cancers. Several researchers have developed methods to distinguish between melanoma and nevus, which are both categorized as MSL. However, most of these studies did not focus on NoMSLs such as basal cell carcinoma (BCC), the most common skin cancer and seborrheic keratosis (SK) despite their high incidence rates. It is preferable to deal with these NoMSLs as well as MSLs especially for the potential users who are not enough capable of diagnosing pigmented skin lesions on their own such as dermatologists in training and physicians with different expertise. We developed a new method to distinguish among melanomas, nevi, BCCs, and SKs. Our method calculates 828 candidate features grouped into three categories: color, subregion, and texture. We introduced two types of classification models: a layered model that uses a task decomposition strategy and flat models to serve as performance baselines. We tested our methods on 964 dermoscopy images: 105 melanomas, 692 nevi, 69 BCCs, and 98 SKs. The layered model outperformed the flat models, achieving detection rates of 90.48%, 82.51%, 82.61%, and 80.61% for melanomas, nevi, BCCs, and SKs, respectively. We also identified specific features effective for the classification task including irregularity of color distribution. The results show promise for enhancing the capability of the computer-aided skin lesion classification.

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.

Retrospective analysis of melanocytic lesions in children at the National Cancer Institute-RJ.

Skin cancer is the most common neoplasm in Brazil. Melanoma accounts for 4% of these neoplasms. Although childhood melanoma is rare, there is evidence that its incidence is increasing, placing it among the most important public health problems for the future. This work sought to conduct a retrospective review of cases of suspected melanocytic skin lesions in children, their diagnosis and management, and evaluate the sentinel lymph node biopsy method in some cases of cutaneous melanoma.

Modern non-invasive diagnostic techniques in the detection of early cutaneous melanoma.

Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Melanoma is a malignant tumor with a high tendency to metastasize. Therefore, an extremely important part of the therapeutic process is to identify the disease at an early stage: in situ or stage I. Many tools for early diagnosis of melanoma are available today, including dermoscopy, videodermoscopy and in vivo reflectance confocal microscopy. Other methods such as high frequency ultrasound, optical coherence tomography and electrical impedance spectroscopy may serve as additional diagnostic aids. Modern imaging techniques also allow the monitoring of melanocytic skin lesions over months or years to detect the moment of malignant transformation. This review summarizes the current knowledge about modern diagnostic techniques, which may aid early diagnosis of melanoma.

Extension of automated melanoma screening for non-melanocytic skin lesions

In this paper, we present an automated melanoma screening system that supports not only melanocytic skin lesions (MSLs) but also non-melanocytic skin lesions (NoMSLs). Melanoma is known as the most fatal skin cancer. Therefore, early detection is highly desired. However, melanoma diagnosis is not easy even for expert dermatologists. Several researchers have developed automated methods for melanoma detection but they mostly focused only on MSLs while NoMSLs have been almost neglected. To expand the scope to NoMSLs, we developed two melanoma classification models, namely the single-shot model and the double-shot model. The single-shot model differentiates melanomas from all the other skin lesions including NoMSLs. The double-shot model divides the task into two subtasks. Firstly, it differentiates MSLs from NoMSLs and then differentiates melanomas from the other MSLs. The single-shot achieved a sensitivity (SE) of 92.9% and a specificity (SP) of 83.9%, while the double-shot achieved an SE of 97.6% and an SP of 87.7% with ten image features. Through a detailed data analysis, we confirmed that the double-shot can exploit effective image features more than the single-shot as a result of its task decomposition method.

Nevomelanocytic atypia detection by in vivo reflectance confocal microscopy

Background and objectiveIn vivo reflectance confocal microscopy (RCM) is a promising novel technology for non-invasive early diagnostics of cutaneous melanoma. However, the possibility to detect melanocytic atypia in nevi by means of in vivo RCM remains unknown. The aim of the study was to evaluate the significance of in vivo RCM features of melanocytic atypia for the diagnosis of melanocytic nevi, dysplastic nevi and cutaneous melanoma. Materials and methodsA total of 138 melanocytic skin lesions comprising 25 melanocytic nevi, 69 dysplastic nevi and 44 melanomas were analyzed by means of dermoscopy, in vivo RCM and routine histopathology. In vivo RCM images were analyzed for the arrangement of keratinocytes in epidermis, pagetoid cells and junctional melanocytic nests and correlated refractivity aspects of nests with histopathology. ResultsSeparately and all together taken the in vivo RCM features of melanocytic atypia were significant in differential diagnosis of benign and malignant melanocytic skin lesions, though none of the features was significant in discriminating nevi without cytologic atypia of dysplastic nevi. In vivo RCM feature of dense cell clusters corresponded with melanin containing nevomelanocytes on histopathology though exact correspondence of non-homogeneous and atypical sparse cell clusters remained questionable. ConclusionsNevus with histopathologically confirmed nevomelanocytic atypia (dysplastic nevus) could not be distinguished from nevus without atypia using analyzed in vivo RCM features of melanocytic atypia. More accurate diagnostics by means of in vivo RCM needs further investigation on reflectance of single and nested cutaneous melanocytes in benign and malignant skin lesions.

Computer-Aided Diagnosis of Skin Lesions Using Conventional Digital Photography: A Reliability and Feasibility Study

BackgroundComputer-aided diagnosis (CADx) software that provides a second opinion has been widely used to assist physicians with various tasks. In dermatology, however, CADx has been mostly limited to melanoma or melanocytic skin cancer diagnosis. The frequency of non-melanocytic skin cancers and the accessibility of regular digital macrographs have raised interest in developing CADx for broader applications.ObjectivesTo investigate the feasibility of using CADx to diagnose both melanocytic and non-melanocytic skin lesions based on conventional digital photographic images.MethodsThis study was approved by an institutional review board, and the requirement to obtain informed consent was waived. In total, 769 conventional photographs of melanocytic and non-melanocytic skin lesions were retrospectively reviewed and used to develop a CADx system. Conventional and new color-related image features were developed to classify the lesions as benign or malignant using support vector machines (SVMs). The performance of CADx was compared with that of dermatologists.ResultsThe clinicians' overall sensitivity, specificity, and accuracy were 83.33%, 85.88%, and 85.31%, respectively. New color correlation and principal component analysis (PCA) features improved the classification ability of the baseline CADx (p = 0.001). The estimated area under the receiver operating characteristic (ROC) curve (Az) of the proposed CADx system was 0.949, with a sensitivity and specificity of 85.63% and 87.65%, respectively, and a maximum accuracy of 90.64%.ConclusionsWe have developed an effective CADx system to classify both melanocytic and non-melanocytic skin lesions using conventional digital macrographs. The system's performance was similar to that of dermatologists at our institute. Through improved feature extraction and SVM analysis, we found that conventional digital macrographs were feasible for providing useful information for CADx applications. The new color-related features significantly improved CADx applications for skin cancer.