Criteria for melanocytic lesions in LC-OCT.

BACKGROUND: Line-field confocal optical coherence tomography (LC-OCT) is an emerging diagnostic tool with imaging depth reaching ~400 µm and a novel three-dimensional (3D) cube providing cellular resolution. As far as we are aware, there are only a limited number of papers that have reported diagnostic criteria for melanocytic lesions using this technique, and none of them have been multicentric. OBJECTIVES: Our aim was to establish the diagnostic criteria for melanocytic lesions using LC-OCT and identify the most significant architectural and cytologic features associated with malignancy. METHODS: A retrospective evaluation of 80 consecutive melanocytic lesions from a prospective multicentric data set spanning three European centres was conducted. We excluded facial, acral and mucosal lesions from the study. Dermoscopic and LC-OCT images were evaluated by a consensus of four observers. Multivariate logistic regression with backward elimination was employed. RESULTS: The main melanoma diagnostic criteria include detecting >10 pagetoid cells in 3D acquisition, irregular 3D epidermal architecture, disrupted dermoepidermal junction (DEJ) and clefting. Significant risk factors were irregular 3D epidermal architecture, >10 pagetoid cells, dendritic cells at DEJ without underlying inflammation. Novel malignancy criteria in vertical view were DEJ disruption and clefting around atypical melanocyte nests. Exclusive melanoma features were epidermal nests, epidermal consumption, dense dermal nests with atypia. Protective features in the absence of any malignancy indicators were DEJ ring pattern, cobblestone, elongated rete ridges (vertical), well-defined DEJ and wave pattern (vertical). CONCLUSIONS: A series of diagnostic criteria for the identification of melanocytic lesions with LC-OCT have been established. Validation of these criteria in clinical practice through future studies is essential to further establish their utility.

Understanding the anatomy of dermoscopy of melanocytic skin tumours: Correlation in vivo with line-field optical coherence tomography.

BACKGROUND: Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. OBJECTIVES: The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. METHODS: Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. RESULTS: 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. CONCLUSIONS: LC-OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.

Line-field confocal optical coherence tomography: a new tool for non-invasive differential diagnosis of pustular skin disorders.

BACKGROUND: The spectrum of pustular skin disorders (PSD) is large and particularly challenging, including inflammatory, infectious and amicrobial diseases. Moreover, although pustules represent the unifying clinical feature, they can be absent or not fully developed in the early stage of the disease. The line-field confocal optical coherence tomography (LC-OCT) is a recently developed imaging technique able to perform a non-invasive, in vivo, examination of the epidermis and upper dermis, reaching very high image resolution and virtual histology. OBJECTIVES: We aimed to investigate the potentialities of LC-OCT in the non-invasive differential diagnosis of a series of 11 PSD with different aetiology, microscopic features, body location and incidence rates. MATERIALS AND METHODS: Complete LC-OCT imaging (i.e. 2D/3D frames, videos) was performed on a total of 19 patients (10 females and 9 males) aged between 35 and 79 years. Images were blindly evaluated and compared with corresponding histopathologic findings. RESULTS: The LC-OCT imaging was able to detect with high accuracy the pustule structure including shape, margins, morphology and cellular content, along with peculiar epidermal and adnexal alterations in each condition, including: Acute Generalized Exanthematous Pustulosis, Generalized pustular psoriasis, Generalized pustular figurate erythema, Subcorneal Pustular Dermatosis, Intraepidermal IgA pustulosis, Palmoplantar pustulosis, Palmoplantar pustular psoriasis. Herpetic whitlow, Acrodermatitis continua of Hallopeau, Vesicopustular Sweet syndrome and Vesicopustular Eosinophilic cellulitis, with pustular appearance, were also compared. CONCLUSIONS: The new LC-OCT can represent a rapid, non-invasive and painless tool which can help differentiating among PSD of different aetiology and microscopic morphology in clinical mimickers in daily practice.

Line-field confocal optical coherence tomography of basosquamous carcinoma: a case series with histopathological correlation.

BACKGROUND: Basosquamous carcinoma (BSC) is a rare and potentially aggressive cutaneous neoplasm combining histopathological features of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Line-field confocal optical coherence tomography (LC-OCT) is a new, non-invasive imaging technique featuring excellent resolution and penetration. To date, studies about the use of LC-OCT in the BCC and SCC fields are available, but similar investigations are lacking in the BSC field. OBJECTIVE: The goal of the present study was to identify/describe LC-OCT criteria of BSC. METHODS: Consecutively enrolled BSCs were imaged with dermoscopy and LC-OCT prior to surgical excision. Dermoscopic and LC-OCT images were evaluated, and histopathological slides were reviewed. RESULTS: Six BSCs from six patients [four (66.7%) males and two (33.3%) females; mean age 76.5 (62-96) years] were included. Identified LC-OCT criteria for BSC included BCC-associated (dermal lobules with millefeuille pattern, dilated vessels, bright cells within the epidermis, bright cells within lobules, stromal stretching, stromal brightness) and SCC-associated features (acanthosis, hyperkeratosis, disarranged epidermal architecture, broad strands, elastosis and glomerular vessels). Interruption of the dermal-epidermal junction and ulceration represented overlapping criteria. CONCLUSION: Line-field confocal-OCT is a new promising technique that may support the non-invasive recognition of BSC through the simultaneous detection of BCC-associated and SCC-associated features. We hypothesize that the use of LC-OCT might be helpful not only in the diagnostic setting but also in the follow-up surveillance for an early identification of recurrences. Further larger studies are needed to prove this hypothesis.

Super-high magnification dermoscopy can aid the differential diagnosis between melanoma and atypical naevi.

BACKGROUND: Dermoscopy is the most widely used noninvasive imaging technique for the clinical diagnosis of melanoma (MM). Super-high (× 400) magnification dermoscopy (D400) has recently been developed; compared with traditional dermoscopy, it can reveal additional features, down to the identification of single melanocytes in the skin. OBJECTIVES: To evaluate which structures are visible at D400 and to compare them in atypical naevi and MMs. METHODS: A prospective observational multicentre study was conducted. We enrolled patients who were identified as having atypical melanocytic skin lesions by clinical and/or × 20 magnification dermoscopy (D20) examination, and who were assigned to either excision or follow-up. Lesions were imaged by videodermoscopy at D20 and D400. The presence of pigmented cells and their features were assessed at D400. RESULTS: In total, there were 79 patients with 57 naevi and 31 MMs. Of the total 88 lesions, 63 (71.6%) were given a histological diagnosis, while the others were followed up for ≥ 12 months, during which they showed no change and were all diagnosed as naevi. Pigmented cells were identified in > 90% of the lesions at D400. Compared with naevi, MMs had a higher frequency of scattered, large, irregular (in shape and size), dendritic/roundish, violet/blue pigmented cells under D400 (P < 0.001). Moreover, dots (P < 0.01), out-of-focus blue structureless areas (P < 0.01) and vessels (P < 0.001) were also more frequent in MMs than in naevi at D400. CONCLUSIONS: This study showed that D400 can reveal many elements not otherwise visible in traditional D20 dermoscopy, such as pigmented cells and their morphology, which could be useful for the diagnosis of MM.

Line-field confocal optical coherence tomography for actinic keratosis and squamous cell carcinoma: a descriptive study.

BACKGROUND: Early and accurate diagnosis of cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) is fundamental to reduce their associated morbidity and to select the correct treatment. Line-field confocal optical coherence tomography (LC-OCT) is a new imaging device that can characterize healthy skin and basal cell carcinoma, but no large studies on keratinocyte cell tumours have yet been published. AIM: To identify and describe LC-OCT criteria associated with SCC and AK, and to compare LC-OCT findings in these tumours. METHODS: A retrospective observational multicentre study was conducted. Lesions were imaged with the LC-OCT device before surgery and examined histologically. LC-OCT criteria for AK/SCC were identified and their presence was evaluated in all study lesions. Univariate and multivariate analyses were performed to compare AK and SCCs, and to investigate differences between in situ and invasive tumours. RESULTS: In total, 158 patients with 50 AK and 108 SCCs (62 in situ and 46 invasive) were included. Cytological and architectural alterations were found in most lesions, and differences were found between AK and SCCs. Although the visualization of the dermoepidermal junction (DEJ) was often hampered by hyperkeratosis and acanthosis, an outlined DEJ without broad strands was observed in almost all AK and almost all in situ SCCs, but in only three invasive SCCs (P < 0.001) when the DEJ was detectable. CONCLUSION: Our results suggest that LC-OCT can help clinicians in the identification of AK and SCC and their differentiation, providing a real-time and noninvasive examination. Further studies are needed to confirm our data.

Line-field confocal optical coherence tomography of basal cell carcinoma: a descriptive study.

BACKGROUND: Early diagnosis and subtype classification of basal cell carcinoma (BCC) are crucial to reduce morbidity and optimize treatment. Good accuracy in differentiating BCC from clinical imitators has been achieved with existing diagnostic strategies but lower performance in discriminating BCC subtypes. Line-field confocal optical coherence tomography (LC-OCT) is a new technology able to combine the technical advantages of reflectance confocal microscopy and OCT. OBJECTIVES: To identify and describe LC-OCT criteria associated with BCC and explore their association with BCC subtypes. METHODS: Basal cell carcinoma were imaged with a handheld LC-OCT device before surgical excision. LC-OCT images were retrospectively evaluated by three observers for presence/absence of criteria for BCC. Multivariate logistic regression models were used to find independent predictors of BCC subtypes. RESULTS: Eighty-nine histopathologically proven BCCs were included, of which 66 (74.2%) were pure subtypes [superficial BCC (sBCC): 19/66 (28.8%); nodular BCC (nBCC): 31/66 (47.0%); infiltrative BCC (iBCC): 16/66 (24.2%)]. Lobules, blood vessels and small bright cells within epidermis/lobules were the most frequent criteria for BCC. LC-OCT criteria independently associated with sBCC were presence of hemispheric lobules, absence of lobule separation from the epidermis, absence of stretching of the stroma; with nBCC were presence of macrolobules, absence of lobule connection to the epidermis; and with iBCC were presence of branched lobules. CONCLUSIONS: This was the first study describing the characteristics of BCC under LC-OCT examination. We proposed morphologic criteria, which could be potentially useful for diagnosis and subtype classification of BCC, as well as for its therapeutic management. Future studies are needed to assess these hypotheses.

Secukinumab treatment leads to normalization of quality of life and disease symptoms in psoriasis patients with or without prior systemic psoriasis therapy: the PROSE study results.

INTRODUCTION: Psoriatic disease is associated with considerable impairment of quality of life (QoL). The PROSE study (NCT02752776) investigated the impact of secukinumab treatment on patient-reported outcomes (PRO) in patients with moderate to severe psoriasis stratified by their treatment history. METHODS: PROSE was a prospective, non-randomised, multicentre study. Patients were categorized at baseline according to treatment history as naïve [naïve to any systemic therapy (N = 663)], conventional systemic [previously exposed to ≥1 conventional systemic (CS) therapy (N = 673)] and biologics [previously exposed to ≥1 biologic therapy (N = 324)]. QoL PROs, efficacy and safety of secukinumab 300 mg were assessed for a period of 52 weeks. RESULTS: The primary objective was met with 70.8% patients achieving a Dermatology Life Quality Index (DLQI) 0/1 response at Week 16 (naϊve, 74.7%; CS, 71.3%; biologic, 61.7%), with effects sustained up to Week 52. Mean Family DLQI (FDLQI) score decreased from 11.5 at baseline (naϊve, 11.3; CS, 11.4; biologic, 12.1) to 2.5 at Week 16 (naϊve, 2.5; CS, 2.3; biologic: 3.5). Substantial improvements in EuroQoL 5-Dimension Health Questionnaire, Numeric Rating Scale for pain, itching and scaling, Health Assessment Questionnaire-Disability Index, Treatment Satisfaction Questionnaire for Medication, and Patient Benefit Index were also observed at Week 16. The QoL gains were associated with substantial improvements in Psoriasis Area and Severity Index and Investigator Global Assessment mod 2011 0/1 response. No meaningful difference was observed in the efficacy or QoL improvements across patient subpopulations. All QoL and efficacy parameter improvements were sustained up to Week 52. Secukinumab treatment was well-tolerated, and no new safety signals were observed. CONCLUSION: Secukinumab treatment resulted in complete normalization of QoL in a substantial proportion of psoriasis patients, and their families, regardless of their prior treatment history.

The impact of anatomical location and sun exposure on the dermoscopic recognition of atypical nevi and early melanomas: usefulness of an integrated clinical-dermoscopic method (iDScore).

BACKGROUND: The anatomical location of atypical melanocytic skin lesion (aMSL) was never combined into an algorithm for discriminating early melanomas (EM) from atypical nevi (AN). AIMS: To investigate the impact of body location on the intuitive diagnosis performed in teledermoscopy by dermatologists of different skill levels. A further aim was to evaluate how the integration of the body location could improve an algorithm-aided diagnosis. METHODS: We retrospectively collected 980 standardized dermoscopic images of aMSL cases (663 AN, 317 EM): data on the anatomical location were collected according to 15 body sites classified into 4 macro-areas of chronically/frequently/seldom/rarely exposure. Through a teledermatology web platform, 111 variously skilled dermoscopists performed either the intuitive diagnosis and 3 algorithm-assisted diagnostic tests (i.e. iDScore, 7-point checklist, ABCD rule) on each case, for a total of 3330 examinations. RESULTS: In the rarely photoexposed area (side, bottom, abdomen), AN were the most tricky (i.e. highest quote of false positives), due to a frequent recognition of dermoscopic features usually considered as suggestive for melanoma in these lesions; the EM at these sites received the highest quote of false negatives, being generally interpreted as 'featureless' according to these traditional parameters, that were more frequently displayed on the chronically photoexposed area. In rarely and seldom photoexposed area, intuitive diagnosis fails to achieve adequate accuracy for all aMSLs, as the ABCD rule and the 7-point checklist; by applying the iDScore algorithm the diagnostic performance was increased by 15% in young and 17% in experts. CONCLUSIONS: The body location of an aMSL can affect the quality of intuitive dermoscopic diagnosis, especially in sun-protected areas. Accuracy can be improved by using the iDScore algorithm that assigns a different partial score of each body site.

In vivo characterization of healthy human skin with a novel, non-invasive imaging technique: line-field confocal optical coherence tomography.

BACKGROUND: Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive optical technique recently developed for skin examination in vivo. It provides real-time, high-resolution vertical images with an isotropic resolution of ~1 µm and a penetration depth of ~500 µm. OBJECTIVES: Study goals were to qualitatively/quantitatively characterize healthy skin at different body sites using LC-OCT. METHODS: The skin of young healthy volunteers was imaged with a handheld LC-OCT imaging device. Seven body sites (back of the hand, forehead, cheek, nose, chest, forearm and back) were investigated. An independent qualitative [cutaneous structures' description; visibility of keratinocytes' nuclei and dermal-epidermal junction (DEJ)] and quantitative [stratum corneum (SC)/epidermal thicknesses; height of dermal papillae] assessment of the LC-OCT images was performed. RESULTS: A total of 88 LC-OCT images were collected from 29 participants (20 females; nine males; mean age 25.9 years). Keratinocytes' nuclei and DEJ were visible in the totality of images. The different layers of the epidermis and the remaining cutaneous structures/findings were visualized. Body sites-related variability was detected for SC/epidermal thicknesses and height of dermal papillae. Inter-observer agreement was excellent (SC thickness), good-to-excellent (epidermal thickness) and moderate-to-good (papillae). CONCLUSIONS: Line-field confocal-OCT provides non-invasive, real-time imaging of the skin in vivo with deep penetration and high resolution, enabling the visualization of single cells. The histology-like vertical view provides an easy way to recognize/measure different cutaneous structures/findings. LC-OCT appears as a promising technique for the examination of physiological/pathological skin.

Structural skin changes in elderly people investigated by reflectance confocal microscopy.

BACKGROUND: Reflectance confocal microscopy (RCM) is particularly suitable for the study of skin ageing because it provides nearly histological information in vivo and non-invasively. However, there are no studies that evaluated RCM skin features of a large population older than 70 years. OBJECTIVES: The aim of our investigation was to study age-related skin changes in an elderly population by RCM and to evaluate their topographical and gender differences. METHODS: We obtained RCM images of photoprotected (volar arm) and chronic (face) and intermittently photoexposed (dorsal forearm) body sites of 209 volunteers (105 women and 104 men, mean age: 77.5, range 74-81 years). 15 previously reported and new RCM parameters related to skin ageing were assessed. RESULTS: Photoexposed sites had thicker suprapapillary epidermis, more linear, distant and thin furrows, higher presence of mottled pigmentation, polycyclic papillae and coarse and huddled collagen and lower presence of dermal papillae than the photoprotected site. Irregular honeycomb pattern was not higher in photoexposed sites, indicating that it is probably more dependent on intrinsic ageing. Two ageing scores defined for facial skin ageing (epidermal disarray score and epidermal hyperplasia score) were found useful for the identification of photoageing. Gender differences only concerned some RCM parameters (i.e. thickness of different layers of the epidermis, furrows and collagen score) and some body sites, in line with the fact that women and men of our cohort had no major differences in clinically visible skin ageing. CONCLUSIONS: Our study confirmed that RCM is a powerful non-invasive technique to microscopically quantify ageing signs and our observations contribute to highlight the differences between intrinsic and extrinsic ageing.

Validation of an integrated dermoscopic scoring method in an European teledermoscopy web platform: the iDScore project for early detection of melanoma.

BACKGROUND: Although live and teledermoscopic examination has been successfully used to achieve non-invasive diagnosis of melanocytic skin lesions (MSLs), early melanoma (EM) and atypical nevi (AN) continue to be a challenge, and none of the various algorithms proposed have been sufficiently accurate. We designed a scoring classifier diagnostic method, the iDScore that combines clinical data of the patient with dermoscopic features of the MSL. OBJECTIVE: To test the accuracy of the iDScore in differentiating EM from AN in a teledermoscopy setting and to compare it with intuitive diagnosis, the ABCD rule and the seven-point checklist. MATERIALS AND METHODS: A dedicated teledermoscopy web platform was designed. This involved the following: (i) collecting a large integrated clinical-historical-dermoscopic data set of difficult MSLs from eight European dermatology centres; (ii) online testing, education and training in using the iDScore. A total of 904 images were combined with age, sex, lesion diameter and body site data and evaluated on the platform by 111 participants with four levels of skill in dermoscopy. Each testing session consisted of 30 blind cases to examine consecutively by the above four methods. 'Management decisions' and personal participant data were also recorded. RESULTS: iDScore-aided diagnosis achieved satisfactory diagnostic accuracy for all lesions, irrespective of centre of affiliation, showing an average AUC of 0.776 in all participant testing sessions. All skill groups improved their accuracy by 10-16% with respect to intuitive diagnosis and the other methods, showing high concordance and avoiding wrong management decisions. CONCLUSION: We demonstrated the validity of the iDScore method for managing suspicious MSLs in a large multicentric data set and a teledermoscopic setting. The platform designed for the iDScore project provides ready support for physicians of any dermoscopy skill level and is useful for education and training.

Tattoo complications in treated and non-treated psoriatic patients.

BACKGROUND: Tattooing is a widespread phenomenon, with an estimated prevalence of 10-30% in Western populations. For psoriasis patients, current recommendations are to avoid having a tattoo if the disease is active and they are receiving immunosuppressive treatments. Although scientific data supporting these recommendations are lacking, dermatologists are often reluctant to advocate tattooing in psoriasis patients. OBJECTIVE: We aimed to evaluate the frequency of tattoo complications in patients with psoriasis and determine whether the occurrence of complications was associated with psoriasis status and treatments received at the time of tattooing. METHODS: We performed a multicentre cross-sectional study. Adults with psoriasis were consecutively included and classified as tattooed or non-tattooed. Prevalence of complications associated with tattoos was then evaluated according to psoriasis onset and treatments. The study was divided into three parts, in which data were collected through a series of questionnaires filled in by the dermatologist. Complications included pruritus, oedema, allergic reaction/eczema, infection/superinfection, granuloma, lichenification, photosensitivity, Koebner phenomenon and psoriasis flare after tattooing. Diagnosis of complications was made retrospectively. RESULTS: We included 2053 psoriatic patients, 20.2% had 894 tattoos. Amongst non-tattooed patients, 15.4% had wished to be tattooed, with psoriasis being stated as a reason for not having a tattoo by 44.0% and 5.7% indicating that they planned to have a tattoo in the future. Local complications, such as oedema, pruritus, allergy and Koebner phenomenon, were reported in tattoos in 6.6%, most frequently in patients with psoriasis requiring treatment at the time of tattooing (P < 0.0001). No severe complications were reported. CONCLUSIONS: The rate of tattoo complications in psoriasis patients was low. Although the risk of complications was highest amongst patients with psoriasis requiring treatment at the time of tattooing, all the complications observed were benign. These results can be helpful for practitioners to give objective information to patients.

Nipple and areola lesions: review of dermoscopy and reflectance confocal microscopy features.

The differential diagnosis of nipple and areola complex (NAC) lesions encompasses a large spectrum of conditions from benign tumours to inflammatory diseases that could be challenging to recognize on clinical ground. While melanoma (MM) of the NAC is exceedingly rare, benign lesions are more frequent but could be difficult to distinguish from MM. Besides MM, other malignant tumours can affect this area and in particular Paget's disease (PD). For clinically doubtful lesions, biopsy is required, with possible functional and aesthetic consequences in this sensitive area. Dermoscopy and reflectance confocal microscopy (RCM) are widely used techniques for the diagnosis of many skin lesions, but their use for NAC lesions is not well established. The objective of this study was to evaluate current literature on these imaging techniques for NAC lesions. We searched in Medline, PubMed and Cochrane database all studies up to November 2018 dealing with dermoscopy, RCM and this special site. We found that the most described malignant tumour was PD and that only two primary MMs of the NAC have been reported with these imaging techniques. Although there are few data on diagnostic accuracy of non-invasive imaging techniques for NAC lesions, it seems that dermoscopy and RCM can add relevant information to be integrated with clinical examination for the diagnosis of NAC lesions and in particular for the differential diagnosis of PD and eczema.

Evaluation of large clinically atypical vulvar pigmentation with RCM: atypical melanosis or early melanoma?

BACKGROUND: Vulvar melanosis can occasionally be clinically challenging by mimicking an early melanoma. OBJECTIVE: To report our experience of initial evaluation and follow-up in this peculiar subset of vulvar melanosis using reflectance confocal microscopy (RCM). METHODS: We retrospectively evaluated 18 consecutive cases referred for atypical vulvar pigmentation or for which melanoma was considered and that underwent both RCM examination and histopathological assessment. In 13 cases with available dermoscopic pictures, RCM classification was compared to dermoscopic diagnosis, and in all cases, the density of melanocytes was evaluated on biopsies using MelanA immunostaining. RESULTS: Among the 18 atypical pigmented lesions, 17 vulvar melanosis and one melanoma were histologically determined. RCM concluded a benign vulvar melanosis in 10 of 17 cases, whereas dermoscopy did so in three of 12 cases. RCM identified the only early malignant lentiginous melanoma. In several cases of vulvar melanosis, RCM could identify foci of melanocytic hyperplasia in an otherwise benign pattern. CONCLUSIONS: In this clinically and dermoscopically challenging subset of vulvar pigmentations, RCM appears relevant for initial extensive evaluation, especially to target initial biopsy sampling, and to perform non-invasive monitoring of foci of melanocytic hyperplasia.

Morphological classification of melanoma metastasis with reflectance confocal microscopy.

BACKGROUND: Cutaneous malignant melanoma metastases differential diagnosis is challenging, as clinical and dermoscopic features can simulate primary melanoma or other benign or malignant skin neoplasms, and in-vivo reflectance confocal microscopy could assist. Our aim was to identify specific reflectance confocal microscopy features for cutaneous malignant melanoma metastases, and epidermal and dermal involvement. METHODS: A retrospective, multicentre observational study of lesions with proven cutaneous malignant melanoma metastases diagnosis between January 2005 and December 2016. Lesions were retrospectively assessed according to morphological features observed at reflectance confocal microscopy. Potential homogeneous subgroups of epidermal or dermal involvement were investigated with cluster analysis. RESULTS: Cutaneous malignant melanoma metastases (51 lesions in 29 patients) exhibited different frequencies of features according to metastasis dermoscopy patterns. Lesions classified at dermoscopy with nevus-like globular and non-globular patterns were more likely to be epidermotropic, showing characteristics of epidermal and dermal involvement at reflectance confocal microscopy. Other dermoscopy pattern classifications were more likely to be dermotropic, showing characteristics od dermal involvement at reflectance confocal microscopy. Distinguishing features at reflectance confocal microscopy included irregular (78%) and altered (63%) epidermis, pagetoid infiltration (51%), disarranged junctional architecture (63%), non-edged papillae (76%), dense and sparse, and cerebriform nests in the upper dermis (74%), and vascularity (51%). Cluster analysis identified three groups, which were retrospectively correlated with histopathological diagnoses of dermotropic and epidermotropic diagnoses (P < 0.001). The third cluster represents lesions with deep dermis morphological changes, which were too deep for evaluation with reflectance confocal microscopy. CONCLUSIONS: Specific reflectance confocal microscopy features of cutaneous malignant melanoma metastases for correct diagnosis, and subtype diagnosis, seem achievable in most cases where morphological alterations are located above the deep dermis.

Aspect en microscopie confocale par réflectance in vivo des kératoses actiniques: Reflectance confocal microscopy features of actinic keratoses.

Though the diagnosis of actinic keratoses is most often clinical, it is sometimes necessary to use non-invasive imaging methods to confirm this diagnosis. Reflectance confocal microscopic examination of actinic keratosis may reveal hyperkeratosis (i.e., detached, isolated or scaly corneocytes), parakeratosis (i.e., nucleated cells in the stratum corneum), dilated vessels and signs of solar elastosis, including clusters of moderately reflecting material and/or undulating shiny elastic fibres that are clearly visible in the superficial dermis. Hopefully, new in vivo microscopic imaging techniques such as line-field confocal optical coherence tomography will make it possible to obtain a three-dimensional examination of the skin and, thus, to further improve diagnostic accuracy of these lesions. © 2019 Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Kératoses actiniques : comprendre et traiter réalisé avec le soutien institutionnel de Galderma International.

Methotrexate efficacy and tolerance in plaque psoriasis. A prospective real-life multicentre study in France.

BACKGROUND: Methotrexate (MTX) is a major systemic treatment for moderate to severe plaque psoriasis. A randomized trial has recently been published evaluating a single weekly dosage (17.5mg), but few prospective real-life data are available. The main objective of this study was to prospectively evaluate the efficacy of MTX in real-life. The secondary objectives were to evaluate predictive parameters for treatment efficacy and the frequency of adverse events. PATIENTS AND METHODS: A prospective cohort involving consecutive at in 25 centres belonging to GEM RESOPSO included all adults with plaque psoriasis in whom MTX treatment was initiated. The efficacy criterion was achievement of PASI 75 at week (W) 12/16. The impact of demographic data, psoriasis characteristics (duration, topography, rheumatism), dosage (W12/16 dosage, cumulative dose after 4 weeks), and mode of administration (subcutaneous vs. oral, concomitant use of folic acid) on efficacy was evaluated. Intention-to-treat (ITT),per protocol (PP), and multivariate analyses were performed. RESULTS: Two hundred and fifty-six patients (F/M: 105/151; mean age: 45.0 years; rheumatism: 12.6%) with plaque psoriasis were included. 99 patients were not analysed at W12/16 (16 because of inefficacy, 16 because of intolerance, 56 were lost to follow-up or had data missing). PASI 75 was achieved in 98 patients, with efficacy of 38.3% in the ITT analysis and 58.3% in the PP analysis. In the ITT analysis, absence of previous use of cyclosporine (P=0.01) and a cumulative dose of MTX>60mg after 4 weeks (P<0.0001) were associated with higher PASI 75 rates. In the PP analysis, only absence of previous use of cyclosporine (P=0.0009) was associated with a better PASI 75 results. There was no association between PASI 75 and patient characteristics (including body mass index), clinical aspects of psoriasis, route of administration, combination with folic acid, or W12/16 dose. Adverse events were reported by 34.8% of patients. These consisted mainly of digestive disorders (nausea, abdominal pain), asthenia and moderate hepatic cytolysis. The frequency of adverse events was correlated with methotrexate dosage. DISCUSSION: The efficacy of MTX in plaque psoriasis in this real-life study of 256 patients is consistent with the data in the literature, including the recently published randomized trial (41% PASI 75). This rate was unaffected by patient weight, route of administration and combined use of folic acid. Absence of previous use of cyclosporine appears to be associated with better efficacy although there is no clear explanation for this. The initial dosage (high dose in the first month) appears to be associated with superior efficacy for W12/W16.

Evaluation of the Active Targeting of Melanin Granules after Intravenous Injection of Dendronized Nanoparticles.

The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [177Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell, which reduces the diffusion across the cells' membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [177Lu]Lu-NPs10@D1_ICF_DOTAGA at 2 h post-intravenous injection (pi), and the highest tumor uptake of the control probe [177Lu]Lu-NPs10@D1_DOTAGA at 30 min pi, probably due to the enhanced permeability and retention effect. In addition, ex vivo confocal microscopy studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA.