The smart approach: feasibility of lentigo maligna superficial margin assessment with hand-held reflectance confocal microscopy technology.

BACKGROUND: Lentigo maligna may be challenging to clear surgically. OBJECTIVE: To evaluate feasibility of using superficial skin cuts as RCM imaging anchors for attaining negative surgical margins in lentigo maligna. METHODS: Included patients presented with lentigo maligna near cosmetically sensitive facial structures. We evaluated, with hand-held-RCM, microscopic clearance of melanoma beyond its dermoscopically detected edges. Evaluated margins were annotated using shallow skin cuts. If a margin was positive at 'first-step' RCM evaluation, we sequentially advanced the margin radially outward at that segment by 2-mm intervals until an RCM-negative margin was identified. Prior to final surgical excision, we placed sutures at the outmost skin cuts to allow comparison of RCM and histopathological margin assessments. Primary outcome measure was histopathological verification that RCM-negative margins were clear of melanoma. RESULTS: The study included 126 first-step margin evaluations in 23 patients, median age 70 years (range: 43-91). Seventeen patients (74%) had primary in-situ melanoma and six (26%) invasive melanoma, mean thickness 0.3 mm (range 0.2-0.4 mm). Six cases (26%) showed complete negative RCM margins on 'first-step', 11 (48%) were negative at 'second-step', and four (17%) at 'third-step'. In two additional cases (9%), margins clearance could not be determined via RCM due to widespread dendritic cells proliferation. The RCM-negative margins in all 21 cases proved clear of melanoma on histopathology. Of the 15 cases that returned at 1-year follow-up, none showed any residual melanoma on dermoscopic and RCM examinations. Interobserver reproducibility showed fair agreement between bedside RCM reader and blinded remote-site reader, with Spearman's rho of 0.48 and Cohen's kappa of 0.43; using bedside reader as reference, the remote reader's sensitivity was 92% and specificity 57% in positive margin detection. CONCLUSIONS: Margin mapping of lentigo maligna with hand-held-RCM, using superficial skin cuts, appears feasible. This approach needs validation by larger studies.

Improving diagnostic sensitivity of combined dermoscopy and reflectance confocal microscopy imaging through double reader concordance evaluation in telemedicine settings: A retrospective study of 1000 equivocal cases.

BACKGROUND: Reflectance confocal microscopy (RCM) is an imaging device that permits non-invasive visualization of cellular morphology and has been shown to improve diagnostic accuracy of dermoscopically equivocal cutaneous lesions. The application of double reader concordance evaluation of dermoscopy-RCM image sets in retrospective settings and its potential application to telemedicine evaluation has not been tested in a large study population. OBJECTIVE: To improve diagnostic sensitivity of RCM image diagnosis using a double reader concordance evaluation approach; to reduce mismanagement of equivocal cutaneous lesions in retrospective consultation and telemedicine settings. METHODS: 1000 combined dermoscopy-RCM image sets were evaluated in blind by 10 readers with advanced training and internship in dermoscopy and RCM evaluation. We compared sensitivity and specificity of single reader evaluation versus double reader concordance evaluation as well as the effect of diagnostic confidence on lesion management in a retrospective setting. RESULTS: Single reader evaluation resulted in an overall sensitivity of 95.2% and specificity of 76.3%, with misdiagnosis of 8 melanomas, 4 basal cell carcinomas and 2 squamous cell carcinomas. Combined double reader evaluation resulted in an overall sensitivity of 98.3% and specificity of 65.5%, with misdiagnosis of 1 in-situ melanoma and 2 basal cell carcinomas. CONCLUSION: Evaluation of dermoscopy-RCM image sets of cutaneous lesions by single reader evaluation in retrospective settings is limited by sensitivity levels that may result in potential mismanagement of malignant lesions. Double reader blind concordance evaluation may improve the sensitivity of diagnosis and management safety. The use of a second check can be implemented in telemedicine settings where expert consultation and second opinions may be required.

Improving Diagnostic Accuracy of Dermoscopically Equivocal Pink Cutaneous Lesions with Reflectance Confocal Microscopy in Telemedicine Settings: Double Reader Concordance Evaluation of 316 Cases.

BACKGROUND: Solitary pink lesions in differential diagnosis with hypopigmented/amelanotic melanoma present a diagnostic challenge in daily practice and are regularly referred for second expert opinion. Reflectance confocal microscopy (RCM) has been shown to improve diagnostic accuracy of dermoscopically equivocal pink lesions. No studies have been performed to evaluate the effect of adding a second expert reader and automatic removal of lesions with discordant management recommendations and its potential effect on diagnostic sensitivity and final management of these lesions in retrospective or telemedicine settings. OBJECTIVE: To improve diagnostic accuracy and reduce potential mismanagement of dermoscopically equivocal pink cutaneous lesions by implementing double reader concordance evaluation of RCM images. METHODS: 316 dermoscopically equivocal pink lesions with dermoscopy-RCM image sets were evaluated retrospectively. Accuracy of three readers was evaluated by single reader evaluation of dermoscopy only and dermoscopy-RCM image sets and finally by double reader evaluation of dermoscopy-RCM image sets. Lesions with discordant diagnosis between two readers were automatically recommended for excision. RESULTS: Dermoscopy only evaluation resulted in an overall sensitivity of 95.9% and specificity of 33.6%, with 1 of 12 amelanotic melanomas mismanaged. Dermoscopy-RCM image set single reader evaluation resulted in an overall sensitivity of 93.9% and overall specificity of 54.2%, with 1 of 12 melanomas mismanaged. Dermoscopy-RCM image set double reader concordance evaluation resulted in an overall sensitivity of 98.3% and specificity of 42.7%, with no amelanotic melanoma mismanagement. CONCLUSION: Evaluation of dermoscopy-RCM image sets of equivocal pink lesions by a single reader in telemedicine settings is limited by the potential for misdiagnosis of dangerous malignant lesions. Double reader concordance evaluation with automatic referral of lesions for removal in the case of discordant diagnosis improves the diagnostic sensitivity in this subset of lesions and reduce potential misdiagnosis in settings where a second expert opinion may be employed.

Melanoma and naevi with a globular pattern: confocal microscopy as an aid for diagnostic differentiation.

BACKGROUND: Dermoscopically, one of the most common findings in melanocytic lesions is a globular pattern. A regular globular pattern is a common finding in naevi. Melanoma can also show a globular pattern, with globules typically irregular in size, colour and distribution. OBJECTIVES: To investigate the likelihood of diagnosing melanoma according to distinct dermoscopic and confocal aspects. METHODS: Dermoscopic and confocal aspects of 83 excised melanocytic lesions dermoscopically showing globules were analysed. RESULTS: Our study population included 39 acquired melanocytic naevi, 16 Spitz naevi and 28 melanomas. Univariate analysis showed that regular distribution of globules on dermoscopy is associated with a ninefold lower risk for melanoma, whereas an irregular distribution is associated with an almost 10-fold increased risk for melanoma. Concerning confocal features, dense nests are associated with a fivefold lower risk for melanoma, whereas loosely arranged nests are associated with an almost sixfold risk for melanoma; moreover, the presence of round cells is associated with a 17-fold lower risk for melanoma, whereas pleomorphic cells are associated with an almost 16-fold risk for melanoma. CONCLUSIONS: So that melanoma is not missed, clinicians should carefully analyse globular lesions in adults, focusing, in particular, on the distribution of globules and on the presence of confocal cytological atypia.

Update on non-invasive imaging techniques in early diagnosis of non-melanoma skin cancer.

UNLABELLED: Non-melanoma skin cancer (NMSC) is the most common malignancy in fair skinned populations. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are non-invasive imaging techniques that play an important role in diagnosis of skin tumors. The aim of this study was to provide new insights into the role of non-invasive tecniques in the diagnosis of non-melanoma skin cancers, concentrating especially on dermoscopy, RCM and OCT. The analysis of the studies obtained from the most recent literature, taking into account previous essential reported information in this field. A search concerning the role of dermoscopy, RCM and OCT in the diagnosis of NMSC was performed on PubMed. EXCLUSION CRITERIA: duplicated studies, single case report, and papers with language other than English New and old literature about early diagnosis of NMSC through non-invasive imaging techniques were analyzed. The role and the diagnostic accuracy of dermoscopy, RCM and OCT for the diagnosis of NMSC were reported according to the data given by literature. The development of non-invasive diagnostic devices (especially dermoscopy, RCM and OCT) allows tissue imaging in-vivo contributing to a more accurate diagnosis of skin cancer, sparing time for the patient and costs for the public health system.

Dermoscopic yellow structures in basal cell carcinoma.

BACKGROUND: Yellowish structures in dermoscopy comprise milia-like cysts (MLCs) and yellow lobular-like structures. OBJECTIVE: This study aimed at establishing the frequency of these features in BCC and at describing their dermoscopic details. METHODS: A retrospective analysis of digital dermoscopic images referring to 400 BCCs was performed. Images were evaluated for the presence of starry and cloudy MLCs and yellow lobular-like structures. RESULTS: Among the 400 BCCs constituting our database, 40 presented yellowish structures (10%). "Yellow" BCCs were located more frequently on the head and were mainly of the nodular type. MLCs were observed in 7.75% of the cases (with a mean number of 4.9 MLCs per lesion), whereas yellow globules were noticed in 4.2% /ucodep of the lesions. CONCLUSION: In the presence of BCC specific dermoscopic criteria, the observation of MLCs and yellow lobular-like structures should not prompt the dermatologist to exclude the diagnosis of BCC.

Dermoscopy of small melanomas: just miniaturized dermoscopy?

BACKGROUND: Small malignant melanomas (MMs) are usually MMs in an initial growth phase, deserving attention by the clinician aiming at an early diagnosis. OBJECTIVES: To identify clues for early diagnosis of small MMs, by comparing the dermoscopic features of MMs < 4 mm (micromelanomas) with those of larger MMs. METHODS: Our database consists of dermoscopic images of 482 MMs, which have been retrieved and measured digitally. The ABCD (asymmetry, border, colour, dimension) and 7-point criteria were evaluated for the whole database by three expert dermoscopists, whereas the main dermoscopic pattern was assessed only for micromelanomas. The dermoscopic aspects were correlated to clinical and histological features. RESULTS: Most 7-point and ABCD scores, and criteria referring to micromelanomas, differed from those of the MM database as a whole. Lesion asymmetry, number of colours, blue-whitish veil, atypical vessels, irregular globules/dots and regression increased according to MM diameter. An inverse trend was observed for atypical network and irregular pigmentation, which were more frequently observed in micromelanomas than in larger ones. Among the 22 micromelanomas, 12 lesions were in situ, whereas the other 10 were 0·2-2 mm thick. The clinical and dermoscopic characteristics of the two groups were similar. CONCLUSIONS: Micromelanomas are not a rarity. However, the clinician should be aware of the fact that the majority of them lack most of the dermoscopic features presented by larger lesions.

Methods for the assessment of the efficacy of products and slimming treatments for cellulite according to the Italian Interdisciplinary Group for the standardization of efficacy tests on cosmetic products.

Cellulite is a very common skin alteration with a complex pathogenesis; different degrees of severity of cellulite can be observed in most part of people after puberty, and numerous cosmetic or more invasive treatments have been proposed, with variable efficacy. Since reproducible methods of evaluation of the effectiveness of cellulite treatments are lacking, the purpose of our group was to define and set general testing principles for evaluating the efficacy of slimming products and treatments/remodeling methods for cellulite, to achieve a delineation of reliable and reproducible research steps following a well-designed and scientifically valid methodology. After a careful review of literature and textbooks and according to personal experience, we defined assessment protocols based on clinical and instrumental tools. In order to make studies reliable, reproducible and safe, a protocol standardization is needed. The sponsor is responsible for assuring quality and information concerning the product under investigation; moreover, investigators should be experienced on cellulite evaluation and treatment, and, finally, the duration and modalities of application of the product should be specified. A treated VS non treated area comparison can be performed, to evaluate the severity of cellulite and the clinical outcomes of the treatment. Besides clinical evaluation, instrumental methods should always be implemented to provide objective data for treatment outcome.

Reflectance confocal microscopy for diagnosis of mammary and extramammary Paget's disease.

BACKGROUND: Paget's disease is an intraepidermal adenocarcinoma that is difficult to diagnose clinically as it mimics inflammatory or infectious diseases. As a consequence, it may be clinically misdiagnosed resulting in a delay in appropriate management. Reflectance confocal microscopy allows the visualization of the upper layers of the skin and mucosa at cellular resolution. Paget's disease is characterized histologically by the presence of neoplastic cells scattered throughout all layers of the epidermis in a pattern similar to that also observed in melanoma (and termed Pagetoid spread). OBJECTIVE: In vivo confocal microscopy is an excellent diagnostic tool for detecting Pagetoid spread and for diagnosing melanoma. We therefore hypothesized that it may also assist in the diagnosis of Paget's disease. METHODS: In this study, we describe the confocal features of nine cases of extramammary Paget's disease and one case of mammary one. RESULTS: Large atypical Pagetoid cells were present singly and in clusters in all 10 cases and were readily visualized on ex vivo and in vivo confocal microscopy. The presence of Pagetoid spread and other confocal features, in the appropriate clinical context, is suggestive Paget's disease and should allow distinction from other inflammatory diseases that may appear similar clinically. CONCLUSION: The use of confocal microscopy is likely to facilitate earlier diagnosis of Paget's disease and the instigation of appropriate management with concomitant improvement in clinical outcomes.

Reflectance confocal microscopy criteria of lichen planus-like keratosis.

BACKGROUND: Lichen planus-like keratosis (LPLK) may be difficult to differentiate from melanoma and other skin cancers on sun-damaged skin based on clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) allows evaluation of skin lesions at high resolution. OBJECTIVES: The aim of this study was to identify criteria for specific diagnosis of LPLK using in vivo RCM. METHODS: Lesions included in the study were derived from patients presenting for skin examination at a private dermatology practice specializing in skin cancer. We retrospectively analysed RCM features of 28 biopsy-proven LPLK and compared them to RCM findings in skin cancers on sun-damaged skin, including five in situ squamous cell carcinomas, six actinic keratoses, seven superficial basal cell carcinomas and eight melanomas. RESULTS: The main RCM features of LPLK and their relative frequencies were: (i) typical honeycomb pattern of the spinous layer (78.6%); (ii) elongated cords and/or bulbous projections at the dermal-epidermal junction (75%); and (iii) numerous plump-bright cells and/or bright stellate spots in the superficial dermis (92.9%). These RCM features correlated with the following histopathological findings respectively: (i) spinous-granular layers without significant atypia of keratinocytes; (ii) elongated, bulbous rete ridges; and (iii) dense infiltration of melanophages and lymphocytes in superficial dermis. We propose diagnostic criteria that classify correctly 71.4% of LPLK, while avoiding misclassification of any of the skin cancers in the present series as LPLK. CONCLUSIONS: We identified RCM criteria for diagnosis of LPLK that correlate well with histopathological findings and that allow differentiation of LPLK from skin cancer.

Grey-blue regression in melanoma in situ-evaluation on 111 cases.

As fibrosis and melanosis are often seen in malignant melanoma, the presence of dermoscopic signs of regression may represent a clue for the diagnosis of malignancy. Our aim was to assess the frequency and extent of 11 dermoscopic features of regression evaluating dermoscopic images of 111 melanomas in situ (MIS). Regression structures (grey-blue areas, white areas, peppering, and/or blue-whitish veil) were present in 80.1% of the lesions. Approximately 80% of the lesions showed regression of dermoscopic structures and light brown areas. Most lesions showed the presence of grey-blue areas (74.7%), whereas peppering was observable in 30.6% of MIS. Areas of fibrosis were mainly observable as structureless areas with a pinkish hue (50.4%). Based on our data, the reticular pattern of blue regression and light brown areas can be considered a significant discriminator and a reliable predictor of MIS.

Reticular grey-blue areas of regression as a dermoscopic marker of melanoma in situ.

BACKGROUND: By dermoscopy, regression structures are substantially defined by the presence of white and blue areas in the lesion image. As fibrosis and melanosis are often seen in malignant melanoma (MM), the presence of dermoscopic signs of regression may represent a clue for the diagnosis of malignancy. OBJECTIVES: To assess the frequency and extent of dermoscopic signs of regression in melanoma in situ (MIS) and to describe its dermoscopic features. METHODS: Dermoscopic images of 85 MIS, 85 invasive MMs and 85 dermoscopically equivocal lesions with a histological diagnosis of naevus were evaluated by three dermatologists, who assessed the presence of 11 parameters of regression. RESULTS: The number of regression parameters per lesion increased according to melanoma thickness. White areas, the grey-blue veil and widespread blue areas were more frequent in invasive MMs than in the other two lesion groups, whereas light brown areas and regression of dermoscopic structures were more frequent in MIS. Peppering was observable in the same percentage of MIS and invasive MMs. Blue areas were more frequently structureless in equivocal lesions and invasive MMs, whereas the reticular pattern prevailed in MIS. CONCLUSIONS: Frequency, morphology, extent and distribution of regression vary according to melanoma thickness and diameter. Lesions with reticular blue regression and light brown areas should undergo surgical excision for the suspicion of MIS. Moreover, the identification of the reticular pattern of blue regression can be considered a significant discriminator and a reliable predictor of MIS.