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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.

IMPORTANCE The influence of regression on the status of the sentinel node (SN) is controversial. In many centers, the presence of regression in thin melanomas supports the performance of an SN biopsy. OBJECTIVE To identify whether regression in primary melanoma has any influence on SN involvement. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of melanomas with a Breslow thickness greater than 0.75 mm and undergoing SN biopsy from January 1, 2003, through December 31, 2010, at Instituto Valenciano de Oncologia, which receives melanoma patients from regional hospitals and dermatology practices. Only cases with paraffin blocks or histologic slides representative of the primary tumor and available for review were included in the study. Melanomas from 201 patients met these criteria and constitute the core of this study. EXPOSURES Sentinel node biopsy in melanoma. MAIN OUTCOMES AND MEASURES Presence or absence of regression in the primary melanoma, type (early vs late), and extension were correlated with the presence or absence of metastasis in the SNs. In addition, the main clinical and histologic characteristics of the primary melanoma were correlated with the status of SN and the regression features. RESULTS Regression was found in 52 melanomas (25.9%). Regression did not show a statistically significant association with SN status. When melanomas were subdivided by Breslow thickness into 4 groups, those with regression had a lower frequency of positive SNs in 3 of the 4 groups (4.00 mm), although differences did not reach statistical significance in any group. We found no influence by type of regression or its extension on the SN status. Regression was found more frequently in thin melanomas (

Although surgery is usually the first-line treatment for nonmelanoma skin cancers, radiotherapy (RT) may be indicated in selected cases. Radiation therapy as primary therapy can result in excellent control rates, cosmetics, and quality of life. Brachytherapy is a radiation treatment modality that offers the most conformal option to patients. A new modality for skin brachytherapy is electronic brachytherapy. This involves the placement of a high dose rate X-ray source directly in a skin applicator close to the skin surface, and therefore combines the benefits of brachytherapy with those of low energy X-ray radiotherapy. The Esteya electronic brachytherapy system is specifically designed for skin surface brachytherapy procedures. The purpose of this manuscript is to describe the clinical implementation of the new Esteya electronic brachytherapy system, which may provide guidance for users of this system. The information covered includes patient selection, treatment planning (depth evaluation and margin determination), patient marking, and setup. The justification for the hypofractionated regimen is described and compared with others protocols in the literature. Quality assurance (QA) aspects including daily testing are also included. We emphasize that these are guidelines, and clinical judgment and experience must always prevail in the care of patients, as with any medical treatment. We conclude that clinical implementation of the Esteya brachytherapy system is simple for patients and providers, and should allow for precise and safe treatment of nonmelanoma skin cancers.

Purpose: The purpose of this study is to compare high frequency ultrasonography (HFUS) and histpathologic assessment done by punch biopsy in order to determine depth of basal cell carcinoma (BCC), in both superficial and nodular BCCs prior to brachytherapy treatment. Material and methods: This study includes 20 patients with 10 superficial and 10 nodular BCCs. First, punch biopsy was done to confirm the diagnosis and to measure tumour depth (Breslow rate). Subsequently, HFUS was done to measure tumour depth to search for correlation of these two techniques. Results: Neither clear tendency nor significance of the punch biopsy vs. HFUS depth determination is observed. Depth value differences with both modalities resulted patient dependent and then consequence of its uncertainty. Conceptually, HFUS should determine the macroscopic lesion (gross tumour volume - GTV), while punch biopsy is able to detect the microscopic extension (clinical target volume - CTV). Uncertainties of HFUS are difficult to address, while punch biopsy is done just on a small lesion section, not necessarily the deepest one. Conclusions: According to the results, HFUS is less accurate at very shallow depths. Nodular cases present higher depth determination differences than superficial ones. In our clinical practice, we decided to prescribe at 3 mm depth when HFUS measurements give depth lesion values smaller than this value.

Spitz nevus is a benign melanocytic proliferation that shows relatively characteristic clinicopathologic features. Despite this, Spitz nevus is clinically confused with many other lesions, and histopathologically it is sometimes difficult to distinguish it from melanoma. However, Spitz nevus rarely causes differential diagnostic problems with granulomatous dermatitis. This article describes an 8-year-old girl who presented with a nodule on her right arm, a clinical appearance of a pyogenic granuloma. Histopathologically, there was a dermal lesion composed of aggregates of large epithelioid cells surrounded by a heavy inflammatory infiltrate, mimicking a sarcoid-like granulomatous dermatitis. Immunohistochemistry showed epithelioid cells with strong nuclear and cytoplasmic staining with S-100 protein, thus establishing the diagnosis of a melanocytic tumor. The heavy T-cell lymphocytic infiltrate that accompanies the large epithelioid cells caused its granulomatous appearance. Molecular assessment showed H27H mutation in the HRAS gene. We suggest the term 'pseudogranulomatous' for this variant of Spitz nevus because it indicates that the lesion is not authentically granulomatous and simply mimics a granulomatous dermatitis.

Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious.

INTRODUCTION: It is important to identify subgroups within the general population that have an elevated risk of developing cutaneous melanoma because preventive and early-detection measures are useful in this setting. The findings of most studies that have evaluated risk factors for cutaneous melanoma are of limited application in Spain because the populations studied have different pigmentary traits and are subject to different environmental factors. OBJECTIVE: To identify the phenotypic characteristics and amount of exposure to sunlight that constitute risk factors for cutaneous melanoma in the population of the Autonomous Community of Valencia, Spain. METHODS: We performed a multicenter observational case-control study. In total, the study included 242 patients with melanoma undergoing treatment in 5 hospitals and 173 controls enrolled from among the companions of the patients between January 2007 and June 2008. The information was collected by means of a standardized, validated questionnaire. The odds ratio (OR) was calculated for each variable and adjusted using a multiple logistic regression model. RESULTS: The risk factors found to be statistically significant were skin phototypes I and II, blond or red hair, light eye color, abundant melanocytic nevi, and a personal history of actinic keratosis or nonmelanoma skin cancer. After the multivariate analysis, only blond or red hair (OR=1.9), multiple melanocytic nevi (OR=3.1), skin phototypes i and ii (OR=2.1), and a personal history of actinic keratosis (OR=3.5) or nonmelanoma skin cancer (OR=8.1) maintained significance in the model as independent predictive variables for melanoma. CONCLUSIONS: Our study supports the importance of certain factors that indicate genetic predisposition (hair color and skin phototype) and environmental factors associated with exposure to sunlight. Patients with multiple acquired melanocytic nevi and patients with markers of chronic skin sun damage (actinic keratosis and nonmelanoma cancer) presented a significant increase in risk.

Chrysalis, also named shiny white streaks, are white, linear structures only visible with polarized dermoscopy. They have been reported in several tumors included melanomas and Spitz nevi, and their histological substrate is believed to be dermal fibrosis. We have performed a correlation study between the dermoscopic and the histopathological features of 9 Spitz nevi. Chrysalis were present in 4 Spitz nevi (44%) and in all of them there was a high degree of fibroplasia. In one case, chrysalis, evident at the center of the lesion, progressively merged with negative pigment network at the periphery. We suggest that chrysalis and negative pigment network are manifestations of the same histopathological finding: increased collagen occurring at different levels of the dermis.

Different melanocytic nevi have been reported as being associated with dermal cysts. Signet ring cell melanocytic nevus is a rare variant of melanocytic nevus characterized by cells with signet ring morphology within a common melanocytic nevus. This article describes an exceptional case of melanocytic nevus composed exclusively of signet ring cells over a trichilemmal cyst. Histologically, above the cyst, there was a small, symmetrical and sharply demarcated lesion showing a compound proliferation of small, round, monomorphous cells with signet ring morphology. Immunohistochemically, signet ring cells were negative for cytokeratin AE1/3, leukocyte common antigen, HMB-45, and CD34. Occasionally, isolated signet ring cells were positive for S-100 and melan A. Melanocytic nevus composed of signet ring cells should raise the differential diagnosis with other cutaneous tumors exhibiting signet ring cells. Previous cases of this entity reported in the literature are also reviewed.