Real-life practice of reflectance confocal microscopy in France: A prospective multicenter study.

BACKGROUND: Studies demonstrating the potential utility of reflectance confocal microscopy (RCM) have been performed under experimental conditions. OBJECTIVE: To provide an overview of RCM practice in real-life. METHODS: A multicenter, prospective study carried out in 10 university dermatology departments in France. RESULTS: Overall, 410 patients were enrolled. One-half of the patients (48%) were referred by private practice dermatologists. They were referred for diagnosis (84.9%) or presurgical mapping (13%). For diagnosis, the lesions were located on the face (62%), arms and legs (14.9%), and trunk (13.6%), and presurgical mapping was almost exclusively on the face (90.9%). Among those referred for diagnosis, the main indication was suspicion of a skin tumor (92.8%). Of these, 50.6% were spared biopsies after RCM. When RCM indicated surgery, histology revealed malignant lesions in 72.7% of cases. The correlation between RCM and histopathology was high, with a correlation rate of 82.76% and a kappa coefficient of 0.73 (0.63; 0.82). LIMITATIONS: This study was performed in the settings of French tertiary referral hospitals. CONCLUSION: This study shows that in real-life RCM can be integrated into the workflow of a public private network, which enables a less invasive diagnostic procedure for patients.

Reliability and agreement testing of a new automated measurement method to determine facial vitiligo extent using standardized ultraviolet images and a dedicated algorithm.

BACKGROUND: Facial repigmentation is the primary outcome measure for most vitiligo trials. The Facial Vitiligo Area Scoring Index (F-VASI) score is often chosen as the primary outcome measure to assess the efficacy of treatments for facial vitiligo. Although useful, this scoring system remains subjective and has several limitations. OBJECTIVES: To assess the agreement and reliability of an algorithmic method to measure the percentage depigmentation of vitiligo on the face. METHODS: We developed a dedicated algorithm called Vitil-IA® to assess depigmentation on standardized facial ultraviolet (UV) pictures. We then conducted a cross-sectional study using the framework of the ERASE trial (NCT04843059) in 22 consecutive patients attending a tertiary care centre for vitiligo. Depigmentation was analysed before any treatment and, for 7 of them, after 3 and 6 months of narrowband UVB treatment combined with 16 mg methylprednisolone, both used twice weekly. Interoperator and interacquisition repeatability measures were assessed for the algorithm. The results of the algorithmic measurement were then compared with the F-VASI and the percentage of depigmented skin scores assessed by 13 raters, including 7 experts in the grading of vitiligo lesions. RESULTS: Thirty-one sets of pictures were analysed with the algorithmic method. Internal validation showed excellent reproducibility, with a variation of < 3%. The percentage of depigmentation assessed by the system showed high agreement with the percentage of depigmentation assessed by raters [mean error (ME) -11.94 and mean absolute error (MAE) 12.71 for the nonexpert group; ME 0.43 and MAE 5.57 for the expert group]. The intraclass correlation coefficient (ICC) for F-VASI was 0.45 [95% confidence interval (CI) 0.29-0.62] and 0.52 (95% CI 0.37-0.68) for nonexperts and experts, respectively. When the results were analysed separately for homogeneous and heterogeneous depigmentation, the ICC for homogeneous depigmentation was 0.47 (95% CI 0.31-0.77) and 0.85 (95% CI 0.72-0.94) for nonexperts and experts, respectively. When grading heterogeneous depigmentation, the ICC was 0.19 (95% CI 0.05-0.43) and 0.38 (95% CI 0.20-0.62) for nonexperts and experts, respectively. CONCLUSIONS: We demonstrated that the Vitil-IA algorithm provides a reliable assessment of facial involvement in vitiligo. The study underlines the limitations of the F-VASI score when performed by nonexperts for homogeneous vitiligo depigmentation, and in all raters when depigmentation is heterogeneous.

Role of ultra-high-frequency ultrasound in the diagnosis and management of basal cell carcinoma: pilot study based on 117 cases.

BACKGROUND: Ultrasound imaging has recently benefited from the introduction of a new 70 MHz transducer able to provide high-resolution images, i.e. ultra-high-frequency ultrasound (UHFUS). AIM: To study the morphological features of basal cell carcinomas (BCCs) and measure BCC thickness by means of UHFUS examination. METHODS: In this retrospective multicentric study, 171 consecutive patients underwent UHFUS examination between November 2018 and May 2019 for suspected BCC. Diagnosis was confirmed by histopathology. A series of morphological parameters including echogenicity, structure, borders, shape composition (presence of intralesional structures) were investigated along with objective measurements such as thickness (maximum distance between the surface of the epidermis and the deepest part of the tumour) and width. RESULTS: In total, 117 BCCs from 93 patients were examined, including superficial (n = 13; 11.1%), nodular (n = 64; 54.7%), infiltrative (n = 18; 15.4%), mixed subtypes (n = 20; 17.1%) and other subtypes (n = 2; 1.7%). The most frequently observed UHFUS parameters included: hypoechoic signal (n = 80; 68.4%, P < 0.001), homogeneous structure (n = 76, 65.0%, P = 0.01), well-defined borders (n = 77, 65.8%, P < 0.001) and elongated shape (n = 71, 60.7%, P < 0.001). An excellent correlation was found between the BCC thickness measured by UHFUS and the value estimated by histology (interclass correlation ≥ 0.80). CONCLUSION: UHFUS is a new rapid and easy noninvasive skin imaging technique able to provide data on the dimensions and morphology of BCCs in real time and at the bedside. These characteristics mean UHFUS has a number of possible applications, ranging from presurgical mapping to the detection of disease recurrence and treatment monitoring.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

Clinical and dermoscopic features of cutaneous BAP1-inactivated melanocytic tumors: Results of a multicenter case-control study by the International Dermoscopy Society.

BACKGROUND: Multiple BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) have been associated with a familial cancer syndrome involving germline mutations in BAP1. OBJECTIVES: We sought to describe the clinical and dermoscopic features of BIMTs. METHODS: This was a retrospective, multicenter, case-control study. Participating centers contributed clinical data, dermoscopic images, and histopathologic data of biopsy-proven BIMTs. We compared the dermoscopic features between BIMTs and control patients. RESULTS: The dataset consisted of 48 BIMTs from 31 patients (22 women; median age 37 years) and 80 control patients. Eleven patients had a BAP1 germline mutation. Clinically, most BIMTs presented as pink, dome-shaped papules (n = 24). Dermoscopically, we identified 5 patterns: structureless pink-to-tan with irregular eccentric dots/globules (n = 14, 29.8%); structureless pink-to-tan with peripheral vessels (n = 10, 21.3%); structureless pink-to-tan (n = 7, 14.9%); a network with raised, structureless, pink-to-tan areas (n = 7, 14.9%); and globular pattern (n = 4, 8.5%). The structureless with eccentric dots/globules pattern and network with raised structureless areas pattern were only identified in BIMT and were more common in patients with BAP1 germline mutations (P < .0001 and P = .001, respectively). LIMITATIONS: Limitations included our small sample size, retrospective design, the absence of germline genetic testing in all patients, and inclusion bias toward more atypical-looking BIMTs. CONCLUSIONS: Dome-shaped papules with pink-to-tan structureless areas and peripheral irregular dots/globules or network should raise the clinical suspicion for BIMT.

A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.

So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.

Fractionated bipolar radiofrequency and bipolar radiofrequency potentiated by infrared light for treating striae: A prospective randomized, comparative trial with objective evaluation.

BACKGROUND AND OBJECTIVE: Very few treatments for striae are based on prospective randomized trials. The objective of this study was to assess the efficacy of bipolar fractional radiofrequency and bipolar radiofrequency potentiated with infrared light, alone or combined, for treating abdominal stretch marks. STUDY DESIGN/MATERIALS AND METHODS: Bicentric prospective interventional randomized controlled trial in the department of Dermatology of University Hospital of Nice and Aesthetics Laser Center of Bordeaux, France. Men and women of age 18 years or above, who presented for the treatment of mature or immature abdominal striae were included. The patients' abdomens were divided into four equal quadrants. Bipolar radiofrequency potentiated with infrared light and fractional bipolar radiofrequency were applied, alone or combined, and compared to the remaining untreated quadrant. The main criterion of evaluation was the measurement of depth of striae, using 3D photography at 6 months follow-up. A global assessment was also rated by the physician performing the treatment and by the patients. Histological analysis and confocal laser microscopy were additionally performed. RESULTS: A total of 22 patients were enrolled, and 384 striae were measured. In per protocol analysis mean striae depth was decreased by 21.64%, observed at 6 months follow-up with the combined approach, compared to an increase of 1.73% in the control group (P < 0.0001). No significant difference in striae width was observed between the treated or control quadrants. Global assessment by the physician who performed the treatment and by the patient both showed greater improved with the combination treatment compared to control areas (P = 0.004 and P = 0.01, respectively). A more homogeneous interlacing pattern and thicker collagen fibers with a decreased proportion of elastic fibers was observed after treatment. CONCLUSION: Fractional bipolar radiofrequency, combined with bipolar radiofrequency potentiated by infrared light, is an effective treatment of both immature and mature striae of the abdomen.

[Reflectance confocal microscopy : what future for dermatology ?] / Microscopie confocale in vivo : quel avenir en dermatologie ?

Reflectance confocal microscopy is a non invasive imaging technique which provides in vivo and real time images of different skin tissues with a resolution close to histology, however with a depth limited to superficial dermis.The first lesions that were morphologically analyzed are melanocytic lesions. Reflectance confocal microscopy has been used for about ten years in dermatology. Its progressive improvement over the years has allowed it to be an efficient tool for diagnosing cutaneous tumors. It has been developed for inflammatory dermatosis, cutaneous infections, angiomas, cosmetology. Furthermore, it is also used to delimit the edges of lesions or the area to biopsy. This cutaneous imaging technique represents a major innovation and has its place in dermatological practice.

La microscopie confocale (MC) par réflectance est une technique d'imagerie non invasive qui permet d'obtenir in vivo et en temps réel des images de différents tissus de la peau avec une résolution proche de l'histologie, avec toutefois une profondeur limitée au derme superficiel.Les premières lésions qui ont été analysées morphologiquement sont les lésions mélanocytaires. Utilisée depuis une dizaine d'années en dermatologie, la MC est arrivée à maturité pour le diagnostic des tumeurs cutanées. Elle se développe pour les dermatoses inflammatoires, les infections cutanées, les angiomes, la cosmétologie mais aussi lors d'excision pour préciser les limites d'une lésion ou la zone d'intérêt à biopsier. Cette technique d'imagerie cutanée représente une innovation majeure et a une place logique en pratique dermatologique.

Immunohistochemistry as a potential tool for routine detection of the NRAS Q61R mutation in patients with metastatic melanoma.

BACKGROUND: It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS-activating mutations confer resistance to RAF inhibitors, and NRAS-mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors. OBJECTIVE: We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma. METHODS: We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing. RESULTS: Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity. LIMITATIONS: Limitations include retrospective design and lack of multicenter interobserver reproducibility. CONCLUSION: The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.

Treatment of keloids with laser-assisted topical steroid delivery: a retrospective study of 23 cases.

Topical or intralesional corticosteroids are referred to as gold standard treatments for keloids. Recent studies showed that ablative fractional laser (AFL) treatment facilitates delivery of topical drug deeply into the skin by creating vertical channels. The objective of the present study was to assess the ablative erbium laser in fractionated mode, combined with topical high potent corticosteroid cream for treating resistant keloid scars. We conducted a retrospective study in the laser center of the Department of Dermatology (University Hospital of Nice, France), from January 2010 to June 2012, on patients with keloids who were resistant to a first-line of treatment. A 2940-nm ablative fractional erbium laser was used. Topical betamethasone cream was applied twice a day under occlusion with transparent film dressings. A total of 23 patients with 70 keloids were treated from January 2010 to June 2012. The median percentage of improvement was 50% (range -43 to 84). The mean follow-up was 8 months (range 3-18), and a recurrence was observed for eight lesions (22%). Although this observation warrants a prospective comparative evaluation, it supports the interest of the laser-assisted delivery of steroids for treating keloids scars.

Diagnosis and treatment monitoring of toenail onychomycosis by reflectance confocal microscopy: prospective cohort study in 58 patients.

BACKGROUND: The clinical presentation of onychomycosis is often nonspecific and can lead to inappropriate antifungal therapy. Available mycologic tests share many drawbacks. OBJECTIVE: We sought to evaluate the accuracy of reflectance confocal microscopy (RCM) for the diagnosis of onychomycosis compared with standard mycologic tests. METHODS: In all, 58 patients with suspected onychomycosis were enrolled prospectively. RCM, potassium hydroxide preparation, and fungal culture were performed at baseline and after treatment in patients with confirmed onychomycosis. RCM diagnosis of onychomycosis was based on the presence of filamentous and/or roundish structures in the nail plate, corresponding respectively to septate hyphae and/or arthroconidia. RESULTS: Of patients, 46 of 58 were correctly classified by RCM, with a diagnosis yield of 79.3%, sensitivity of 52.9%, specificity of 90.2%, positive predictive value of 69.2%, and negative predictive value of 82.2%. The use of a handheld RCM imager permitted a faster examination with the same accuracy. RCM performed after treatment in 9 patients showed a normal nail plate, and healing was confirmed by mycologic tests or by follow-up. LIMITATIONS: Existing RCM scanner heads are not intended for nail examination. CONCLUSION: RCM has excellent specificity and can be used as a rapid, office-based test to strengthen the prescription of antifungal therapy and for follow-up. Technical improvement could aid sensitivity.

Aurora B is regulated by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway and is a valuable potential target in melanoma cells.

Metastatic melanoma is a deadly skin cancer and is resistant to almost all existing treatment. Vemurafenib, which targets the BRAFV600E mutation, is one of the drugs that improves patient outcome, but the patients next develop secondary resistance and a return to cancer. Thus, new therapeutic strategies are needed to treat melanomas and to increase the duration of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor response. The ERK pathway controls cell proliferation, and Aurora B plays a pivotal role in cell division. Here, we confirm that Aurora B is highly expressed in metastatic melanoma cells and that Aurora B inhibition triggers both senescence-like phenotypes and cell death in melanoma cells. Furthermore, we show that the BRAF/ERK axis controls Aurora B expression at the transcriptional level, likely through the transcription factor FOXM1. Our results provide insight into the mechanism of Aurora B regulation and the first molecular basis of Aurora B regulation in melanoma cells. The inhibition of Aurora B expression that we observed in vemurafenib-sensitive melanoma cells was rescued in cells resistant to this drug. Consistently, these latter cells remain sensitive to the effect of the Aurora B inhibitor. Noteworthy, wild-type BRAF melanoma cells are also sensitive to Aurora B inhibition. Collectively, our findings, showing that Aurora B is a potential target in melanoma cells, particularly in those vemurafenib-resistant, may open new avenues to improve the treatment of metastatic melanoma.