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OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. The mean age of this group when they started treatment upon registration on Biobadaderm was 16.1 years and the mean Psoriasis Area and Severity Index was 9.4. In 67% the first treatment recorded was with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. The mean age of this group when they started treatment upon registration on Biobadaderm was 16.1 years and the mean Psoriasis Area and Severity Index was 9.4. In 67% the first treatment recorded was with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs. (C) 2021 AEDV. Published by Elsevier Espana, S.L.U.

The association of multiple pilomatricomas with xeroderma pigmentosum has not been described. We report a case of a child with multiple pilomatricomas and photosensitivity who was found to have a pathogenic variant in exon 4 of XPA and a likely pathogenic variant in COL6A1.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. The mean age of this group when they started treatment upon registration on Biobadaderm was 16.1 years and the mean Psoriasis Area and Severity Index was 9.4. In 67% the first treatment recorded was with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs. (C) 2021 AEDV. Published by Elsevier Espana, S.L.U.

Three-dimensional (3D) wound measurement lacks a gold standard to test accuracy. It is useful to develop procedures to scan wounds and reconstruct their 3D model with low-cost techniques. We present a new procedure (Structure from Motion [SfM]-3DULC) that uses photographs for measuring nine wound variables. We also propose a new variant of ImageJ in which an orthophoto is used to measure the projected area (Ortho-ImageJ). In addition, we compare the wound measurements made by dermatologists and non-experts. A group of five experts in dermatology and five non-specialists measured 33 leg wounds five times per procedure. Intra-rater and inter-rater reliability scores of SfM-3DULC were evaluated with the intraclass correlation coefficient (ICC 2,1). The accuracy of the two new procedures (SfM-3DULC and Ortho-ImageJ) in the measurement of projected area was assessed by comparing their values with those obtained using ImageJ, with the Wilcoxon matched-pairs signed rank test (a = 0.05). This test was also used to analyse the differences between the measurements made by dermatologists and non-experts. All the variables measured by dermatologists using SfM-3DULC showed excellent scores of intra-rater reliability (ICC > 0.99) and inter-rater reliability (ICC > 0.98). No significant differences between the three procedures were found when comparing their projected area values. Significant differences between the measurements of dermatologists and non-experts were found in most of the variables: circularity coefficient, perimeter, projected area, surface area, and reference surface area. The wound measurement procedure SfM-3DULC has an excellent reliability, is accurate for the measurement of projected area, and can be used by dermatologists for wound monitoring in everyday clinical practice.

Several studies have focused on identifying microRNAs involved in the pathogenesis of melanoma. However, its association with clinicopathological features has been scarcely addressed. The aim of this study is to identify microRNAs expression profiles related to aggressive clinicopathological and molecular features, and to analyze the association with melanoma survival. A retrospective and observational study was performed in a series of 179 formalin-fixed paraffin embedded primary cutaneous melanomas. First, a screening analysis on a discovery set (n = 22) using miRNA gene chip array (Affymetrix, Santa Clara, California, USA) was performed. Differentially expressed microRNAs were detected employing the software Partek Genomic Suite. Validation of four microRNAs was subsequently performed in the entire series (n = 179) by quantitative real time PCR (qRT-PCR). MicroRNAs expression screening analysis identified 101 microRNAs differentially expressed according to Breslow thickness (=1 mm vs. >1 mm), 79 according to the presence or absence of ulceration, 78 according to mitosis/mm2 (

Recent evidence suggests the existence of a miRNA regulatory network involving human telomerase reverse transcriptase gene (hTERT), with miR-138-5p playing a central role in many types of cancers. However, little is known about the regulation of hTERT expression by microRNA (miRNAs) in melanocytic tumors. Here, we investigated the effects of miR-138-5p in hTERT regulation in melanoma cells lines. In vitro studies demonstrated higher miR-138-5p and lower hTERT messenger RNA (mRNA) expression in human epidermal melanocytes, compared with melanoma cell lines (A2058, A375, SK-MEL-28) by quantitative polymerase chain reaction (qPCR) observing a negative correlation between them. A2058 melanoma cells were selected to be transfected with miR-138-5p mimic or inhibitor. Using luciferase assay, hTERT was identified as a direct target of this miRNA. Overexpression of miR-138-5p detected by Western blot revealed a decrease in hTERT protein expression (p = 0.012), and qPCR showed a reduction in telomerase activity (p < 0.001). Moreover, suppressions in cell growth (p = 0.035) and migration abilities (p = 0.015) were observed in A2058-transfected cells using thiazolyl blue tetrazolium bromide and flow cytometry, respectively. This study identifies miR-138-5p as a crucial tumor suppressor miRNA involved in telomerase regulation. Targeting it as a combination therapy with immunotherapy or targeted therapies could be used in advanced melanoma treatment; however, more preclinical studies are necessary.

Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.

Primary cutaneous lymphomas are rare in pediatric patients. The clinical and histopathological manifestations may differ from those in adults. Due to their low frequency and the insidious clinical picture, the diagnosis is usually delayed. The Spanish Primary Cutaneous Lymphoma Registry was initiated in 2016 as a multicenter registry that would allow better insight into the epidemiological, clinical, histopathological, and treatment response characteristics of patients with primary cutaneous lymphomas.

Sonidegib is an antagonist of the transmembrane protein Smoothened in the Hedgehog signaling pathway. It is indicated for the treatment of locally advanced basal cell carcinoma (BCC) that is not amenable to curative surgery or radiotherapy. Sonidegib's efficacy and safety were demonstrated in the phase 2 BOLT trial, where 61% (95% CI, 48-72%) of patients with locally advanced BCC treated with sonidegib 200 mg achieved an objective response to treatment with a mean time to response of 4 months. The median duration of response was 26.1 months and the median progression-free survival was 22.1 months. The most common adverse events were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%); most events were grade 1 or 2. In this review, we summarize the main findings on the efficacy, safety, and tolerability of sonidegib and discuss the management of locally advanced BCC with this drug.

Specialist approaches to the diagnosis and treatment of melanoma have undergone many changes. This guideline aims to provide Spanish dermatologists with evidence-based information for resolving the most common doubts that arise in clinical practice. Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating melanoma were invited to participate in drafting the guideline. The group developed a new guideline on the basis of existing ones, using the ADAPTE collaboration process, first summarizing the care process and posing relevant clinical questions, then selecting guidelines with the best scores according to the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Finally, the group searched the selected guidelines for answers to the clinical questions, drafted recom-mendations, and sent them for external review. The guideline is structured around 21 clinicalquestions chosen for their relevance to issues that make clinical decisions about the manage-ment of melanoma difficult. Evidence from existing guidelines was used to answer the questions.A limitation of this guide derives from the scarce evidence available for answering some ques-tions. Moreover, some areas are changing rapidly, so recommendations must be updated often.The present guideline offers answers to clinical questions about the routine management ofmelanoma in clinical practice and provides dermatologists with a reference to guide decisions,taking into consideration the resources available and patient preferences. El diagnóstico y tratamiento del melanoma en atención especializada es un campo en el que se han producido numerosos cambios. El objetivo de esta guía es ofrecer a los dermatólogos espa˜noles una referencia para resolver las dudas clínicas más frecuentes basándose en la evidencia actual. Para la realización de esta guía se escogió a miembros del Grupo Espa˜nol de Dermato-Oncología y Cirugía con experiencia en el tratamiento de estos tumores y con interés en participar en la elaboración de la guía. Se hizo una adaptación de las guías de práctica clínica existentes mediante el método ADAPTE: inicialmente se resumió el proceso de atención y se elaboraron las preguntas clínicas relevantes. Se seleccionaron las guías mejor puntuadas mediante el instrumento AGREE II, realizando la búsqueda de las respuestas en dichas guías y elaborando las recomendaciones. Finalmente se sometió la guía a revisión externa. La guía se estructuró a partir de 21 preguntas clínicas que fueron seleccionadas por su relevancia, dadoque se centran en aspectos que pueden plantear decisiones difíciles en el manejo del melanoma,y se han respondido empleando la evidencia obtenida de las mejores guías existentes. Entre laslimitaciones de esta guía merece rese˜narse que la evidencia es escasa para responder a algunaspreguntas. En algunos aspectos el cambio es rápido y exige una actualización frecuente de laguía. Esta guía responde a preguntas habituales sobre el manejo del melanoma en la prácticaclínica diaria, sirviendo a los dermatólogos como referencia en la toma de decisiones, siempreteniendo presente los recursos y preferencias del paciente.

Sonidegib is an antagonist of the transmembrane protein Smoothened in the Hedgehog signaling pathway. It is indicated for the treatment of locally advanced basal cell carcinoma (BCC) that is not amenable to curative surgery or radiotherapy. Sonidegib's efficacy and safety were demonstrated in the phase 2 BOLT trial, where 61% (95% CI, 48-72%) of patients with locally advanced BCC treated with sonidegib 200 mg achieved an objective response to treatment with a mean time to response of 4 months. The median duration of response was 26.1 months and the median progression-free survival was 22.1 months. The most common adverse events were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%); most events were grade 1 or 2. In this review, we summarize the main findings on the efficacy, safety, and tolerability of sonidegib and discuss the management of locally advanced BCC with this drug.

Leishmaniasis, considered by the World Health Organization as one of the most important tropical diseases, is endemic in the Mediterranean Basin. The aim of this study was to evaluate epidemiological and clinical characteristics of cutaneous (CL) and mucocutaneous leishmaniasis (MCL) in La Fe University Hospital, Valencia, Spain. The particular focus was on diagnosis techniques and clinical differences according to the immunological status of the patients.

The SCORTEN score is a specific predictor of mortality for patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). There is little evidence in support of the common immunomodulating therapies for SJS/TEN.

We read with interest the article by Recalcati et al. about the report of cutaneous manifestations in COVID-19 patients. We would like to highlight that some potentially severe manifestations in these patients are not directly related to the coronavirus but to the medications administered.

Background: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. Objective: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. Methods: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. Results: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of = 5). Limitations: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. Conclusion: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Severe cutaneous adverse reactions (SCARs) [Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic syndrome (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed eruption (GBFE)] are severe drug reactions that often require hospitalization and could be fatal. BRAF and MEK inhibitors (BRAF/MEKi) are a standard of care in patients with BRAF-mutated metastatic melanomas. These agents are administered until disease progression or unacceptable toxicity occurs. This review has focus on BRAF/MEKi-induced SCARs. A systematic search of the following terms: 'vemurafenib', 'cobimetinib', 'dabrafenib', 'trametinib', 'encorafenib', 'binimetinib', 'Acute Generalized Exanthematous Pustulosis', 'Stevens Johnson syndrome', 'Toxic Epidermal Necrolysis', 'Generalized Bullous Fixed Eruption' 'Drug Hypersensitivity Syndrome', and 'DRESS' in simple combination (every drug with each disease) and all in combination, was performed on MEDLINE, EMBASE, Web of Knowledge and The Cochrane Library repositories, with no restriction on language, for original studies. One hundred sixty-eight original articles were found, 26 (retrospective series, case reports and conference abstracts) were selected, and 21 were included in the qualitative synthesis. A total of 31 SCAR cases (23 DRESS and 8 SJS/TEN - 1 SJS and 7 TEN -) were identified. Vemurafenib was the culprit drug in all but one case, which was dabrafenib-induced. Mean time to SCAR onset from drug intake was 15.5 and 11.4 days, for SJS/TEN and DRESS, respectively. For the DRESS cases, hepatic involvement occurred in 96% and renal alterations in 87% of patients. Overall, BRAF/MEKi-induced SCARs are rare. Among them, vemurafenib is the drug that requires more close monitoring for SCARs. Prior immunotherapy can favour SCARs. Vemurafenib DRESS is likely to occur within the first fifteen days of treatment accompanied by hepatic and renal involvement. Following vemurafenib-induced SCAR resolution, switching to dabrafenib seems to be a safe alternative for these patients' treatment.

Background The SCORTEN score is a specific predictor of the probability of death for patients diagnosed with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objectives To evaluate the overall accuracy of SCORTEN and the influence of several moderators such as age, sex, geographical region and age of the study. Methods A systematic search was performed on MEDLINE, The Cochrane Library, EMBASE, SCOPUS and Web of Knowledge, with no restriction on language (last update 5 February 2019 for all databases). Original studies on the use of SCORTEN were eligible. The standardized mortality ratio (SMR), defined as the quotient between the number of deaths observed and the number expected following SCORTEN, was taken as the measurement of analysis. Results Sixty-four papers were part of the main meta-analysis carried out in the study. A pooled log(SMR) of -0.0889 (95% CI: -0.2023 to 0.0245) was obtained, suggesting a reasonable behaviour of SCORTEN as a predictor of mortality. The possible influence of several factors in the accuracy of SCORTEN was studied by means of meta-regression models. Multivariate meta-regression allowed finding that the mean age of the patients and the ending year of the study are the only factors that significantly influence SCORTEN predictions. The mean age of the group of patients was associated with a significant increase in the observed/expected ratio, whereas a progressive reduction in the observed/expected ratio can be appreciated over the years. Finally, an underestimation of mortality was found for SCORTEN values of 3 or less and the opposite for those above 3 (SCORTEN range: 0-7). Conclusions The rarity of the disease and the heterogeneity of the studies included are major limitations. Despite the overall remarkable accuracy displayed by SCORTEN, the influence of several factors, as comorbidities (e.g. renal impairment), involved body surface area and patient's age, seem of enough relevance to consider a redefinition of the scale.

Epidermal necrolysis (EN) compromises a spectrum of life-threatening dermatoses (Stevens-Johnson Syndrome [SJS], overlap syndrome and toxic epidermal necrolysis [TEN]). Currently, no active therapeutic regimen with unequivocal benefit exists for SJS/TEN. SCORTEN is the widely-used prognostic scale specific for SJS/TEN. Nevertheless, a new prognostic scale, the ABCD-10, has been recently proposed. In this context, acute renal failure (ARF) seems to be an important comorbidity that could influence prognosis in SJS/TEN patients more than it is assumed by these two scales. Our objectives were to compare the accuracy of the SCORTEN and ABCD-10 scales in predicting the mortality in SJS/TEN, and to investigate the influence of renal failure on prognosis. The prognostic results of 18 patients with EN treated in two referral centers between 2013 and 2018 are presented. SCORTEN, ABCD-10 and renal function values were retrospectively collected for all patients. Out of the 18 patients who were analyzed, nine (50%) received only supportive therapy, four were treated with etanercept 50 mg in a single dose (22.2%) and five with corticosteroids (27.8%). Five patients developed ARF. Predicted mortality was 3.48 for SCORTEN and 2.33 for ABCD-10. Eventually, four patients died (22.2%), all had ARF and none of them received active treatment. Despite study limitations and in the absence of active treatment of choice, SCORTEN behaved as a reliable predictor of mortality in patients with EN, outperforming the newer ABCD-10. ARF was an early event associated with a poor prognosis, which could represent a prognostic marker to consider in the future.

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in humans and its incidence is both underestimated and on the rise. cSCC is referred to in the literature as high-risk cSCC, locally advanced cSCC, metastatic cSCC, advanced cSCC, and aggressive cSCC. These terms can give rise to confusion and are not always well defined. In this review, we aim to clarify the concepts underlying these terms with a view to standardizingthe description of this tumor, something we believe is necessary in light of the new drugs that have been approved or are in development for cSCC. (c) 2020 AEDV. Published by Elsevier Espana, S.L.U. This is an open access article under the CC-BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Pancreatic panniculitis (PP) is an infrequent manifestation of pancreatic pathology (2%). This condition has mainly been described in association with acute and chronic pancreatitis, in males aged 40-60 years with chronic alcoholism, as was the case of this patient. However, it might also be the outset manifestation of a pancreatic neoplasm.

Background and objectives Telomerase is an enzyme involved in maintaining the length of telomeres and cell senescence. Numerous studies have shown that in more than 90% of malignant tumors telomerase activity is detected. Material and methods Retrospective observational study in a series of 85 cases of primary melanomas, 12 metastatic melanomas, and 22 melanocytic nevi. We used the monoclonal antibody hTERT (human telomerase reverse transcriptase, Rockland) to assess telomerase activity. The SPSS software package was used to analyze data. Results Telomerase expression was present in all the melanocytic neoplasms analyzed. Expression was heterogenous and moderate or high in the melanomas. In contrast, expression was homogeneous and lower in the nevi. Heterogeneous expression was associated with rapid melanoma growth (P = .028), a Breslow thickness of more than 4 mm (P = .004), mitosis (P = .032), and mutations in the TERT gene (P = .002). Activity was less intense in intradermal nevi, and more intense in compound and dysplastic nevi (P = .054). Conclusions Telomerase expression is found in all melanocytic neoplasms but is higher in melanomas than in nevi. A heterogeneous pattern of expression in melanomas is associated with more aggressive tumors.

Recent publication of the results of clinical trials in which lymph node dissection was not associated with any survival benefit in patients with sentinel node metastasis makes it necessary to reconsider the treatment of patients with melanoma. This article provides an update on the available evidence on the diverse factors (routes of metastatic spread, predictors, adjuvant therapy, etc.) that must be considered when treating patients with sentinel node-positive melanoma. The authors propose a decision-making algorithm for use in this clinical setting. The current evidence no longer supports lymph node dissection in patients with Low-risk sentinel node metastasis (sentinel node tumor load

Introduction: In numerous clinical practice guidelines, emphasis is placed on the need for coordinated care of psoriatic arthritis (PsA) between rheumatologists and the objective was to develop experience-based points to consider facilitating the implementation of multidisciplinary units (Dermatology/Rheumatology) for the management of patients with PsA. Methods: A scientific committee of rheumatology and dermatology experts in the management of PsA, and with experience in joint care, discussed the critical aspects of multidisciplinary PsA Units. The discussion became the basis for a Delphi survey in two rounds submitted to a panel of 24 specialists in rheumatology and dermatology not involved in PsA units. The statements and practices that reached a consensus were summarized and further elaborated. Results: After two Delphi rounds, agreement was reached for 49 of the 50 proposed statements. These included a justification of the units, objectives, and utilities, as well as operational aspects of the units, such as the minimal and ideal premises, referral criteria, and necessary resources. The statements were compiled in 11 points to consider. Conclusions: This consensus offers some points to consider, including premises and recommendations, for the development of specialized Units in the management of PsA based on expert opinion. We trust these guidelines may facilitate their implementation in the future.

Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples. A custom panel was designed to cover the coding regions of 35 melanoma-related genes. Panel average coverage was 2,575.5 reads per amplicon, with 92,8% of targeted bases covered >= 500x. Deep coverage enabled sensitive discovery of mutations in as low as 0.5% mutant allele frequency. Eighty-five percent (85/100) of the melanomas had at least one somatic mutation. The most prevalent mutated genes were BRAF (50%; 50/199), NRAS (15%; 15/100), PREX2 (14%; 14/100), GRIN2A (13%; 13/100), and ERBB4 (12%; 12/100). Turn-around-time and costs for NGS-based analysis was reduced in comparison to conventional molecular approaches. The results of this study demonstrate the cost-effectiveness and feasibility of a custom-designed targeted NGS panel, and suggest the implementation of targeted NGS into daily routine practice.

Purpose: Surface electronic brachytherapy (EBT) is an alternative radiotherapy solution to external beam electron radiotherapy and high-dose-rate radionuclide-based brachytherapy. In fact, it is also an alternative solution to surgery for a subgroup of patients. The objective of this work is to confirm the clinical efficacy, toxicity and cosmesis of a new EBT system, namely Esteya (R) in the treatment of nodular and superficial basal cell carcinoma (BCC). Material and methods: This is a prospective single-center, non-randomized pilot study to assess the efficacy and safety of EBT in nodular and superficial BCC using the Esteya (R) system. The study was conducted from June 2014 to February 2015. The follow up time was 6 months for all cases. Results: Twenty patients with 23 lesions were included. A complete response was documented in all lesions (100%). A low level of toxicity was observed after the 4th fraction in all cases. Erythema was the most frequent adverse event. Cosmesis was excellent, with more than 60% of cases without skin alteration and with subtle changes in the rest. Conclusions: Electronic brachytherapy with Esteya (R) appears to be an effective, simple, safe, and comfortable treatment for nodular and superficial BCC associated with excellent cosmesis. It could be a good choice for elderly patients, patients with contraindications for surgery (due to comorbidities or anticoagulant drugs) or patients where surgery would result in a more disfiguring outcome. A longer follow-up and more studies are needed to confirm these preliminary results.

INTRODUCTION AND OBJECTIVES: Cutaneous chronic graft-vs-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Phototherapy is a therapeutic option for patients with skin involvement and for those who require high doses of corticosteroids. We analyze the cases treated in our department and review the literature. MATERIAL AND METHODS: All patients with GVHD treated with phototherapy in the dermatology department of Hospital Universitario y Politecnico la Fe in Valencia, Spain between March 2011 and October 2014 were identified. Data were gathered retrospectively. RESULTS: There were 16 patients: 10 treated with psoralen-UV-A and 6 with narrowband-UV-B. Complete response was achieved in 9 patients and partial response in 7; 2 patients with partial responses relapsed after treatment. Ten patients were able to decrease their dose of corticosteroids during treatment, and a further 3 decreased the number of other immunosuppressant drugs. No serious adverse effects occurred. CONCLUSIONS: Phototherapy is a good therapeutic option for patients with chronic GVHD with extensive cutaneous involvement, as well as for those who fail to respond to topical treatment or who have become steroid-dependent. The main benefits are that, as the treatment targets the skin, it reduces corticosteroid requirements and has a good safety profile. Treatment must be individualized and, in our experience, both the initial dose and the maximum dose per session can be lower than for other diseases.

The pathogenesis and prognostic implications of regression in melanoma are not well understood. It has traditionally been considered an immunologically mediated phenomenon. Improvement in the knowledge of the mechanisms that lead to regression may prove to be of great value in an era in which treatments oriented to the augmentation of the host's immunity against melanoma have demonstrated excellent clinical results. This study was designed to improve the understanding of the mechanisms underlying melanoma regression and the differences between similar situations in benign melanocytic nevus. The study sample consisted of 77 lesions: 62 melanomas and 15 halo nevi. The following markers were included in the study: CD4, CD8, FoxP3, PD1, CD123, granzyme, and TIA-1. Staining was evaluated in 5 categories, according to the percentage of labeled cells. Granzyme, PD1, and TIA-1 stained significantly more cells in halo nevi than in melanomas with regression (P < 0.01). The ratio CD123/TIA-1 was higher in melanomas than in halo nevi (1 vs. 0.67, P < 0.05). Regression in the 62 melanomas was categorized as early in 14 cases and late in 48 cases. Early regression was associated with a higher percentage of CD123, CD4, and TIA-1 staining than late regression. The inflammatory infiltrate found in halo nevi is characterized by a higher number of active cytotoxic T cells and regulatory PD1-positive T cells than the infiltrate found in melanoma with regression. CD123 staining was higher in early regression than in late regression, suggesting the presence of a tolerogenic mechanism in this phenomenon's initiation phase.