Diagnostic impact of reflectance confocal microscopy as a second-level examination for facial skin lesions.

BACKGROUND AND OBJECTIVE: Benign and malignant facial skin lesions may be difficult to differentiate clinically and with dermoscopy. The present study aimed to evaluate the potential utility of in vivo reflectance confocal microscopy (RCM) as a second-level examination for facial skin neoplasms. PATIENTS AND METHODS: Retrospective and blinded evaluation of 160 consecutive facial lesions was carried out in two separate steps. Clinical and dermoscopic images were assessed first, followed by combined evaluation of clinical/dermoscopic and RCM images. Our study included 60 % malignant lesions, comprising 43 % melanomas, 9 % basal cell carcinomas, 5 % in situ squamous cell carcinomas and 3 % lymphomas. RESULTS: Ancillary RCM significantly improved diagnostic specificity for the detection of malignancy compared to clinical/dermoscopic evaluation alone (58 % vs 28 %). However, sensitivity was slightly lower for RCM-based image evaluation (93 % vs 95 %) due to misclassification of one in situ SCC and one lymphoma. In terms of melanoma diagnosis, RCM-based image evaluation was generally superior; sensitivity was only slightly increased (88 % vs 87 %), but melanoma specificity was significantly higher (84 % vs 58 %). CONCLUSION: RCM is a valuable diagnostic adjunct for facial skin lesions; unnecessary biopsies in this cosmetically sensitive area could be reduced by one third without missing a melanoma.

Noninvasive RCM for Differentiation of Melanotic Macules From Melanocytic Lesions-Blinded Evaluation of a Series of 42 Pigmented Macules.

BACKGROUND: Differentiation of melanotic macules from melanocytic lesions, most importantly of melanoma, is a common problem on clinical-dermoscopic examination. OBJECTIVE: To assess the value of noninvasive reflectance confocal microscopy (RCM) in the differential diagnosis of melanotic macules and melanocytic lesions. PATIENTS AND METHODS: Reflectance confocal microscopy images of 42 pigmented macules on mucocutaneous junctions of genitalia and lips, including 31 melanotic macules, 6 nevi, and 5 melanomas, were retrospectively and independently assessed in a blinded manner by one expert observer and 2 less experienced observers together. RESULTS: The authors differentiated 3 subtypes of melanotic macules; 2 subtypes ("solar lentigo type" and regular subtype of "dendritic type" melanotic macules) could be classified with confidence as benign by all RCM investigators, comprising 64% of melanotic macules. The third subtype (irregular subtype of "dendritic type" melanotic macules; 36%) displaying RCM features overlapping with melanoma was difficult to differentiate and should be biopsied not to miss a melanoma. The RCM differentiation between melanotic macules and nevi was easily performed. CONCLUSION: RCM has the potential to increase the diagnostic accuracy in the noninvasive differentiation of pigmented macules on mucocutaneous junctions.

Multiplex Assays in Allergy Diagnosis: Allergy Explorer 2 versus ImmunoCAP ISAC E112i.

ImmunoCAP ISAC E112i (ISAC) and Allergy Explorer 2 (ALEX2) detect specific immunoglobulin E (IgE) reactivity. Both multiplex assays contain molecular allergens and ALEX2 additionally includes allergen extracts and inhibitors that block the binding of IgE to cross-reacting carbohydrate determinants (CCDs). This study aimed to compare the performance of ISAC and ALEX2 by determining the IgE reactivity against allergen extracts and/or allergen components and by using qualitative, semiquantitative, and quantitative analyses of all comparable allergen components in sera from 216 participants recruited in South Tyrol/Italy. For extract sensitization in ALEX2, the analysis revealed negative corresponding allergen components in 18.4% and at least one positive corresponding allergen component in 81.6% of all cases. For ISAC, the corresponding results were 23.5% and 76.5% of cases, respectively. The ALEX2 CCD inhibitor eliminated CCD-positive signals detected by ISAC in 88.5% of cases. Based on sensitization values of 0.3-14.9 ISU or kUA/L, there was good agreement between ALEX2 and ISAC, although ALEX2 showed higher values than ISAC. The addition of allergen-extract tests in ALEX2 resulted in the detection of more sensitizations than with corresponding allergen components alone. In the range of <15 ISU or kUA/L, ALEX2 may be more effective in detecting sensitizations.

Seborrheic keratosis: reflectance confocal microscopy features and correlation with dermoscopy.

BACKGROUND: Differentiation between seborrheic keratosis (SK) and skin cancers may be difficult. Reflectance confocal microscopy (RCM) enables noninvasive assessment of skin neoplasms at cellular-level resolution. OBJECTIVE: We sought to describe RCM features of SK and to correlate these RCM findings with dermoscopic structures. METHODS: Clinical, dermoscopic, and RCM images of 45 consecutive SK were obtained at a private and university dermatology clinic. Fourteen SK were biopsied because of equivocal clinical or dermoscopic features. RESULTS: With RCM, all SK displayed a regular honeycomb pattern of the epidermis and densely packed, round to polymorphous, well-circumscribed dermal papillae at the dermoepidermal junction, features suggestive of a benign neoplasm. RCM features indicating the diagnosis of SK were also observed, including epidermal projections (43/45 SK; 96%) and keratin-filled invaginations (36/45 SK; 80%) at the lesion surface; corneal pseudocysts at epidermal layers (19/45 SK; 42%); and melanophages (21/45 SK; 47%) and dilated round and linear blood vessels (21/45 SK; 47%) in the papillary dermis. Of biopsied SK, 93% (13/14) displayed at least 3 characteristic RCM findings in the absence of RCM features suggestive of malignancy. LIMITATIONS: This was a limited study sample and retrospective study design. CONCLUSIONS: SK display a distinct set of RCM criteria despite their variable clinical and dermoscopic appearances.

Influence of time on dermoscopic diagnosis and management.

BACKGROUND/OBJECTIVES: Dermoscopy aids in clinical decision-making. However, time pressure is a common reason precluding its use. We evaluated the effect of time on lesion recognition and management decisions utilising clinical and dermoscopic images. METHOD: In all, 100 dermoscopic images were presented to 15 dermatologists with experience in dermoscopy and seven non-experts (dermatology residents). Each lesion was displayed thrice in succession. The dermoscopic image was initially presented for 1 s (t1). The same dermoscopic image was shown again without time constraints (t2) and then a final time with additional images of the clinical context (t3). Participants provided a diagnosis, their level of confidence and biopsy predilection after evaluating each image. RESULTS: For benign lesions, both groups rarely changed their diagnosis. However, an improvement in the number of correct benign diagnoses was observed when the lesion was shown in a clinical context. For malignant lesions, both groups improved when more time and clinical context was given; nevertheless, non-experts were more likely to change the diagnosis towards the correct one as more time was given and tended to perform more biopsies, in particular of benign lesions. Limitations were a small number of participants and an artificial study setting. CONCLUSION: Dermoscopy uses analytical and non-analytical reasoning approaches. We suggest that non-analytical reasoning is employed when rapid clinical decisions need to be made, especially during the evaluation of benign lesions. We conclude that dermoscopy is relatively rapid and non-time-consuming technique that adds relevant information and guides clinicians towards appropriate management decisions.

New diagnostics for melanoma detection: from artificial intelligence to RNA microarrays.

Early detection of melanoma remains crucial to ensuring a favorable prognosis. Dermoscopy and total body photography are well-established noninvasive aids that increase the diagnostic accuracy of dermatologists in their daily routine, beyond that of a naked-eye examination. New noninvasive diagnostic techniques, such as reflectance confocal microscopy, multispectral digital imaging and RNA microarrays, are currently being investigated to determine their utility for melanoma detection. This review presents emerging technologies for noninvasive melanoma diagnosis, and discusses their advantages and limitations.

Pilot study on the acceptance of mobile teledermatology for the home monitoring of high-need patients with psoriasis.

BACKGROUND/OBJECTIVES: The willingness to be educated is one of the highest desires among patients with psoriasis. Therefore, a collaborative model of management would appear to be essential in enhancing patient satisfaction in this challenging condition. The present study aimed at examining the applicability of a mobile teledermatology service in this regard and assessing the association between patient acceptance and perceived health-related quality of life. METHODS: High-need patients with psoriasis performed visits over 12 weeks transmitting clinical images together with some relevant clinical information via mobile phones to teledermatologists, who provided treatment instructions. Ten patients and two teledermatologists completed 20-item patient (weeks 6 and 12) and 10-item physician (at week 12) acceptance questionnaires. In addition, patients answered the dermatology life quality index (DLQI) at weeks 0, 6 and 12. RESULTS: Both patients and teledermatologists were pleased with the service with high acceptance rates (patients: 81.0% at week 6 and 82.9% at week 12; teledermatologists: 74.0%). In addition, 80% of the patients considered the service an alternative to in-person consultation and 90% felt they were in good hands but had achieved a more flexible and empowered lifestyle. No significant correlations were found between patient acceptance and DLQI. Both teledermatologists found the service a convenient and reliable tool for patient monitoring. Neither patients nor teledermatologists thought further in-person consultations necessary. CONCLUSION: Mobile teledermatology is a valuable tool for the home monitoring of patients with psoriasis that makes a meaningful difference in their lives. It is well accepted by both patients and the physicians involved.

Equivocal Longitudinal Melanonychia in a 3-Year-Old Caucasian Girl: Rapid Evolution and Fading during Digital Dermoscopy Follow-Up.

Introduction: Nail matrix nevi (NMN) in pediatric patients manifest as longitudinal melanonychia (LM) and can share clinical, dermoscopic, and histopathological characteristics with subungual melanoma. Equivocal findings in childhood LM may reflect dynamic processes during the natural life cycle of NMN in children. Case Presentation: We present a case of a heavily pigmented LM with equivocal clinical and dermoscopic findings in a 3-year-old Caucasian girl, which exhibited signs of evolution, maturation, and almost complete involution within a short time period during digital follow-up, attributed to the natural course of NMN. Discussion/Conclusion: Considering the rarity of subungual melanoma in childhood, our case underlines the significance of clinical and digital dermoscopy follow-up in the evaluation of childhood LM in order to avoid unnecessary biopsies and potential permanent nail dystrophy.

In vivo analysis of solar lentigines by reflectance confocal microscopy before and after Q-switched ruby laser treatment.

Solar lentigines are benign lesions usually found on sun-damaged skin. We investigated twelve cases of solar lentigines through dermoscopy and reflectance confocal microscopy, performed before, and 30 min and 10 days after, a single treatment with a Q-switched ruby laser. At baseline, all lesions showed characteristic features of solar lentigines in reflectance confocal microscopy analysis: regular honeycomb patterns, edged dermal papillae and cord-like rete ridges at the dermoepidermal junction. Thirty minutes post-laser treatment, blurred epidermal intercellular connections, dark structureless areas of different sizes and shapes in the lower epidermal layers, and hyporeflective dermal papillae, reflecting epidermal and dermal oedema, were observed. Ten days post-treatment highly reflective round-to polygonal areas and aggregated granules, representing extracellular melanin, were detected in all epidermal layers featuring regular honeycomb patterns. Reflectance confocal microscopy can be used to visualise dynamic skin processes, allowing non-invasive in vivo follow-up of skin lesions after treatment.

Dermoscopy and in vivo reflectance confocal microscopy of a congenital nevus of the nipple.

We report a 26-year-old male with a 4 mm diameter, asymmetric, irregularly pigmented and bordered, brown maculopapular lesion on the right nipple present since childhood with enlargement of the lesion within the last 3 months. Dermoscopy revealed a global globular pattern with the presence of focally light brown globules and irregular black globules in its centre. In vivo reflectance confocal microscopy (RCM) revealed dense junctional and dermal melanocytic nests of different sizes and shapes that appeared as sharply demarcated round to oval reflective structures; cellular outlines of single melanocytes were not always detected. In the centre of the lesion within the upper dermis, irregularly shaped, homogeneously reflecting structures were observed. As a clear differentiation between clusters of melanophages and melanocytic nests could not be made with certainty, an excisional biopsy was performed to establish the diagnosis of compound nevus with features of congenital nevus. Therefore, to prove that dermoscopic globules correlated with melanophages, the correlation between dermoscopic RCM and histopathology was necessary.

In vivo reflectance confocal microscopy of erythematosquamous skin diseases.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) represents a promising imaging tool that allows a non-invasive examination of skin morphology in real time at nearly histological resolution, showing microanatomical structures and individual cells. OBJECTIVES: The aim of our study was to evaluate the diagnostic accuracy of confocal examination of erythematosquamous skin diseases, to define typical RCM-features and assess them for their presence or absence, diagnostic performance and reliability. METHODS: Three independent observers received standardized instructions about diagnostic RCM-features of erythematosquamous skin diseases. A total of 1700 RCM images obtained from 75 patients with psoriasis, contact dermatitis, mycosis fungoides, chronic discoid lupus erythematosus (CDLE) or subacute cutaneous lupus erythematosus (SCLE) and from 10 'healthy adults' without any skin disease were evaluated by each observer. RESULTS: Overall, sensitivity and specificity values as observed by three observers were, respectively, 89.13% and 95.41% for psoriasis; 83.33% and 92.31% for contact dermatitis; 62.96% and 94.53% for SCLE/CDLE; and 63.33% and 92.89% for mycosis fungoides. CONCLUSIONS: Reflectance confocal microscopy examination appears to be a promising method for non-invasive assessment of erythematosquamous skin diseases. This study provides a set of well-described morphological criteria with obvious diagnostic impact, which should be used in further investigations.

Monitoring efficacy of cryotherapy for superficial basal cell carcinomas with in vivo reflectance confocal microscopy: a preliminary study.

BACKGROUND: Superficial BCCs (sBCCs) usually appear as multiple lesions in chronic sun-damaged skin of elderly people and may show a destructive growth if left untreated. Non-invasive treatment modalities, such as cryotherapy have been employed for sBCCs, all failing to provide tissue for confirming diagnosis and assessing adequacy of tumour removal. Reflectance confocal microscopy (RCM), a new non-invasive imaging technique has proven to be a useful tool for detection of basal cell carcinoma in vivo. OBJECTIVE: To non-invasively assess efficacy of cryotherapy for sBCCs by cytomorphologic analysis using RCM. METHODS: We examined 10 histologically proven sBCCs located on the trunk of 5 consecutive patients with a mean age of 84.6 years. SBCCs were frozen twice using a spray nitrogen cryoprobe. RCM imaging was performed in each sBCC before cryotherapy and after 5 and 24h to monitor resulting tissue injury. Distinct cytomorphologic characteristics were determined by three observers allowing non-invasive evaluation of therapeutic efficacy of treatment immediately after cryotherapy. Tumour clearance was assessed by RCM imaging 3 months after therapy followed by histopathologic examination. RESULTS: Characteristic RCM-features of BCC were present in all lesions before cryotherapy. Five hours after cryotherapy, all 10 sBCCs showed small bright round to polygonal structures at basal layer and black round to oval areas of varying size with such bright structures floating therein, correlating to cell necrosis and incipient blistering. Eight sBCCs showed also cell necrosis in upper dermis. After 24h all sBCCs showed necrotic cells beneath collagen bundles. Tumour clearance on later histopathologic examination was only proven in those lesions showing damage to the upper dermis after 5h with RCM. CONCLUSION: Early cell necrosis within upper dermal structures seems to correlate with ablation of overlying tumour tissue. When it is not produced by cryotherapy, a second treatment should be considered.

Correlation of image analysis features and visual morphology in melanocytic skin tumours using in vivo confocal laser scanning microscopy.

BACKGROUND/PURPOSE: In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the non-invasive examination of skin cancer morphology at a quasi histological resolution without biopsy. Previous studies dealt with the search for diagnostic, but subjective visual criteria. In this study we examined the correlation between objectively reproducible image-analysis features und visual morphology in melanocytic skin tumours using CLSM. METHODS: Eight hundred and fifty-seven CLSM tumour images including 408 benign nevi and 449 melanoma images were evaluated. Image analysis was based on features of the wavelet transform and classification tree analysis (CART) was used for classification purposes. In a second step, morphologic details of CLSM images, which have turned out to be of diagnostic significance by the classification algorithm were evaluated. RESULTS: CART analysis of the whole set of CLSM images correctly classified 97.55% of all melanoma images and 96.32% of all nevi images. Seven classification tree nodes seemed to indicate benign nevi, whereas six nodes were suggestive for melanoma morphology. The visual examination of selected nodes demonstrated that monomorphic melanocytic cells and melanocytic cell nests are characteristic for benign nevi whereas polymorphic melanocytic cells, disarray of melanocytic architecture and poorly defined or absent keratinocyte cell borders are characteristic for melanoma. CONCLUSION: Well-known, but subjective CLSM criteria could be objectively reproduced by image analysis features and classification tree analysis. Moreover, features not accessible to the human eye seem to contribute to classification success.

Diagnostic image analysis of malignant melanoma in in vivo confocal laser-scanning microscopy: a preliminary study.

BACKGROUND/PURPOSE: In this study we assessed the applicability of image analysis and a machine learning algorithm on diagnostic discrimination of benign and malignant melanocytic skin tumours in in vivo confocal laser-scanning microscopy (CLSM). METHODS: A total of 857 CLSM tumour images including 408 benign nevi and 449 melanoma images was evaluated. Image analysis was based on features of the wavelet transform. For classification purposes we used a classification tree software (CART). Moreover, automated image analysis results were compared with the prediction success of an independent human observer. RESULTS: CART analysis of the whole set of CLSM tumour images correctly classified 97.55% and 96.32% of melanoma and nevi images. In contrast, sensitivity and specificity of 85.52% and 80.15% could be reached by the human observer. When the image set was randomly divided into a learning (67% of the images) and a test set (33% of the images), overall 97.31% and 81.03% of the tumour images in the learning and test set could be classified correctly by the CART procedure. CONCLUSION: Provided automated decisions can be used as a second opinion. This can be valuable in assisting diagnostic decisions in this new and exciting imaging technique.