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A unique collaboration of multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with 1- to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumour thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team (“Tumor Board”). Adjuvant therapies in stage III/IV patients are primarily anti–PD-1, independent of mutational status, or dabrafenib plus trametinib for BRAF-mutant patients. In distant metastasis, either resected or not, systemic treatment is indicated. For first-line treatment, particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In particular scenarios for patients with stage IV melanoma and a BRAF-V600 E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harbouring a BRAF-V600 E/K mutation, this therapy shall be offered in second-line. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future.

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New drugs have been recently approved as adjuvant therapies for melanoma. In this Bayesian network meta-analysis, we aimed to assess the best therapeutic option in terms of recurrence-free survival (RFS), overall survival (OS) and adverse events (AEs). PubMed, Embase, Cochrane library and the American Society of Clinical Oncology databases were searched from inception until 20 August 2018. We estimated adjusted hazard ratios (HRs) for RFS and OS and relative odds ratios (ORs) for AEs and surface under the cumulative ranking (SUCRA) probabilities were calculated. A number of 872 records were identified, and six were finally included in the meta-analysis. A total of 4244 patients in six studies were randomized. The following therapies were considered in the selected studies: combined dabrafenib and trametinib, vemurafenib, nivolumab, ipilimumab and pembrolizumab. Nivolumab demonstrated the highest probability (75.1%) of being the best in term of RFS, followed by dabrafenib+trametinib, pembrolizumab, ipilimumab and vemurafenib; however, OS was not estimable. Concerning AEs, pembrolizumab and nivolumab showed the highest probability to be less associated with any and 3–4 grade AEs (83.1% and 64.4%, respectively). In conclusion, all new drugs are highly effective in adjuvant setting, and the best choice is dependent of patient's context.

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed through dermatoscopy. If a melanoma is suspected, a histopathological examination is required. Sequential digital dermatoscopy and full-body photography can be used in risk persons to detect the development of melanomas at an earlier stage. Where available, confocal reflectance microscopy can improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the AJCC classification. Thin melanomas up to 0.8 mm tumor thickness does not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC whole-body examinations with CT or PET-CT in combination with brain MRI are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to support the frequency and extent of examinations. A stage-based follow-up scheme is proposed, which, according to the experience of the guideline group, covers the minimum requirements; further studies may be considered. This guideline is valid until the end of 2021.

Background: Moderate-to-severe atopic dermatitis (AD) generates a considerable consumption of healthcare resources and significant economic consequences for the patients and their families, healthcare systems (NHS) and society. Several studies on the burden of AD in paediatric patients are available in literature, while data in adults is scant. The purpose of this study was to estimate the direct and indirect costs of moderate to severe AD in adult patients in Italy. Methods: Patients with Eczema Area and Severity Index (EASI) Score >20 were included in a multicentre, observational study conducted in six outpatient dermatology clinics throughout the national territory. Data were retrospectively gathered through a case report form investigating healthcare resources consumption, out-of-pocket expenses and patients' and caregivers' productivity loss. Descriptive statistics was used to illustrate data. Univariate generalized linear model with gamma distribution and identity function link was used to describe association between costs and disease severity. Results: A total of 50 patients with a diagnosis of moderate-to-severe DA (EASI Score ≥20), equal to 89% of the total, were included in the analysis. The total annual burden of the disease, direct and indirect costs, amounted to € 4284 per patient; 19.3% accounted for direct medical costs, 19.9% for direct non-medical and 60.8% for indirect costs due to productivity loss. Conclusions: Moderate-to-severe AD in adults represents an important cost for the society imposing a high financial burden for the NHS, but even more for patients and caregivers. Results from this study may support identification of potential factors impacting on the choice of new therapeutic options to improve the clinical and economic management of this devastating disease.

Recently, 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) topical solution has been included in the National Italian portfolio for lesion-directed treatment of grade I/II actinic keratosis (AKs) located on the face or scalp. To describe the utility of dermoscopy and RCM in treatment response monitoring of a series of AKs treated with 5-FU/SA as lesion-directed therapy. Consecutive patients were prospectively treated for a maximum of 12 weeks with 5-FU/SA for AKs located on the face or scalp. Clinical, dermoscopic, and confocal images of one index AK were acquired at each visit and pre-specified criteria were evaluated. Clinical, dermoscopic, and confocal responses were evaluated at last follow-up visit. Fourteen patients were enrolled, of which five were treated for 12 weeks, seven for 8, and two for 4 weeks. At a median follow up of 30 weeks, 64.3% (9/14) index AKs achieved complete clinical, 50% (7/14) complete dermoscopic and 42.9% (6/14) complete confocal clearance. Local skin reaction was mild and significantly decreased during therapy administration. Although the small number of cases, our study underlines the utility of both dermoscopy and in-vivo RCM in 5-FU/SA treatment response monitoring for AKs located on the face or scalp.

Background: Melanocytic lesions with eccentric hyperpigmentation (EH), even though without other dermatoscopic features of melanoma, are often excised. Objective: Aiming to understand whether the EH in a pigmented lesion is an accurate criterion of malignancy, we evaluated the capability of two evaluators, with different expertise, to correctly diagnose a melanoma when analysing a given lesion in toto versus a partial analysis, with only the EH or the non-hyperpigmented portion (non-EH) visible. Methods: Dermatoscopic images of 240 lesions (107 melanomas and 133 nevi) typified by EH were selected. Facial, acral, mucosal lesions and lesions showing clear-cut features of melanoma (except for atypical network) were excluded. Clinical and dermoscopic features (main pattern and numbers of colours) were described for all cases. Each image was split in two through a software so that only the EH or the non-EH was visible. Two blinded evaluators examined three sets of images, two with customized images and one with the non-modified ones: they were asked to give a dichotomous diagnosis (melanoma or nevus) for each image. Results: Melanomas were significantly more frequently typified by colour variegation (3 colours in 44.8% and 4 colours in 41.1% of cases) and atypical network (88.1% in the EH). No significant differences in diagnostic accuracy emerged between the two evaluators. Sensitivity improved in the evaluation of the whole lesions (mean sensitivity 89.7%) in comparison with the evaluation of EH or non-EH alone (72.7–62.6%). Specificity increased when evaluating the EH (54.1%). Positive predictive value (PPV) and likelihood ratio (LR+) of EH resulted 52.3% and 1.4, meaning that in one case out of two with EH is a melanoma. Conclusions: Lesions with EH are challenging, regardless of dermoscopic experience. The EH is a robust criterion for malignancy, since the evaluation of the whole lesion, through an intralesional comparative approach, increases sensitivity.

The melanoma care landscape is changing fast in the last years. As a result of new insights in melanoma biology, prognosis and therapeutic options, both the American Joint Committee on Cancer (AJCC) and the World Health OrgaÂnization (WHO) Classification of Skin Tumors underwent substantial changes in 2018. Consequently, all the leading guidelines on melanoma management have been updated. Most of the recommendations derive from systematic reÂviews, while others are based on expert opinion, due to the lack of high-level evidence in some aspects of melanoma management. We provide a revision of all the available guidelines that have been updated to the 8th version of the AJCC classification system. Comparison is not provided for topics on which there is agreement on the standard of care.

Background: No large studies have defined the best treatment of actinic cheilitis. Methods: We conducted a systematic review to define the best therapies for actinic cheilitis in clinical response and recurrences. Results: We first identified 444 papers, and 49 were finally considered, including 789 patients and 843 treated areas. The following therapies were recorded in order of frequency: laser therapy, photodynamic therapy (PDT), 3% diclofenac in 2.5% hyaluronic acid, PDT + 5% imiquimod, aminolevulinic acid–laser or methyl-aminolevulinic acid–laser, 5% imiquimod, fluorouracil, partial surgery, 0.015% ingenol mebutate, 50% trichloroacetic acid, and laser + PDT. Concerning the primary outcome, complete clinical response was achieved in 76.5% of patients, and 10.2% had clinical recurrences. Partial surgery and laser therapy showed the highest complete response rates (14 of 14 [100%] and 244 of 260 [93.8%], respectively) with low recurrences. Only a limited number of patients were treated with other therapies, with the exception of PDT, with 68.9% complete responses and 12.6% of recurrences. Interestingly, when combined with 5% imiquimod, the efficacy of PDT was significantly enhanced. Limitations: Heterogeneity across studies. Conclusion: Laser therapy appears the best option among nonsurgical approaches for actinic cheilitis, and PDT showed higher efficacy when sequentially combined with 5% imiquimod. Larger studies are needed to confirm these data.

Two round tables involving experts were organized in order to reach a consensus on the management of patients with actinic keratosis (AK). In the first, seven clinical questions were selected and analyzed by a systematic literature review, using a Population, Intervention, Control, and Outcomes framework; in the second, the experts discussed relevant evidences and a consensus statement for each question was developed. Consensus was reached among experts on how to best treat AK patients with respect to different clinical scenarios and special populations. Lesion-directed treatments are preferred in patients with few AKs. Patients with multiple AKs are challenging, with more than one treatment usually needed to achieve complete lesion clearance or a high lesion response rate, therapy should be personalized, based on previous treatments, patient, and lesion characteristics. Methyl aminolevulinate-PDT, DL (day light) PDT, and imiquimod cream were demonstrated to have the lowest percentage of new AKs after post treatment follow-up. For IMQ 5% and 3.75%, a higher intensity of skin reactions is associated with higher efficacy. Photodynamic therapy (PDT) is the most studied treatment for AKs on the arms. Regular sunscreen use helps preventing new AKs. Oral nicotinamide 500 mg twice daily, systemic retinoids and regular sunscreen use were demonstrated to reduce the number of new squamous cell carcinomas in patients with AKs. Limited evidence is available for the treatment of AKs in organ transplant recipients. There is no evidence in favor or against the use of any of the available treatments in patients suffering from hematological cancer.

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