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Skin lesions are caused due to multiple factors, like allergies, infections, exposition to the sun, etc. These skin diseases have become a challenge in medical diagnosis due to visual similarities, where image classification is an essential task to achieve an adequate diagnostic of different lesions. Melanoma is one of the best-known types of skin lesions due to the vast majority of skin cancer deaths. In this work, we propose an ensemble of improved convolutional neural networks combined with a test-time regularly spaced shifting technique for skin lesion classification. The shifting technique builds several versions of the test input image, which are shifted by displacement vectors that lie on a regular lattice in the plane of possible shifts. These shifted versions of the test image are subsequently passed on to each of the classifiers of an ensemble. Finally, all the outputs from the classifiers are combined to yield the final result. Experiment results show a significant improvement on the well-known HAM10000 dataset in terms of accuracy and F-score. In particular, it is demonstrated that our combination of ensembles with test-time regularly spaced shifting yields better performance than any of the two methods when applied alone. Yes

Malignant melanoma (MM) is the most aggressive and life-threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient-derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem-like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by highresolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum-derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC-derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic-based study aimed at characterizing exosomes derived from melanoma CSCs and patients’ serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC-derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia., MICIU FPU15/03682 FPU15/02350, Ministerio de Ciencia, Innovación y Universidades (MICIU) MAT2015-62644.C2.2.R RTI2018-101309-BC2, Instituto de Salud Carlos III PIE16-00045, Junta de Andalucía SOMM17/6109/UGR (UCE-PP2017-3), European Union (EU) SOMM17/6109/UGR (UCE-PP2017-3), Chair 'Doctors Galera-Requena in cancer stem cell research' CMC-CTS963, Fundación MEDINA

Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients., This study was supported by Grants from Fondo de Investigación Sanitaria (FIS) and Fondos FEDER PI16/00201 and PI19/01612 to F. García-Río, PI19/01363 to C. Cubillos-Zapata and PIE15/00065 to E. López-Collazo. M.A. Martínez-García is supported by the Spanish Ministry of Economy and Competitiveness—Instituto de Salud Carlos III (FIS 2016/ 01772) and co-financed by the European Development Regional Fund. A way to achieve Europe (ERDF). DG is supported in part by National Institutes of Health grants HL130984 and HL140548.

Background and objectives:Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. Material and methods: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. Results: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter > 4 cm or thickness > 6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (> 6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. Conclusions:In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays. Este estudio ha sido financiado parcialmente por una beca concedida por la Fundación Piel Sana de la Academia Española de Dermatología y Venereología. J.C. se encuentra parcialmente financiado por el proyecto PI18/00587 (Instituto de Salud Carlos III (ISCIII), cofinanciación FEDER. Yes Antecedentes y objetivos: La pandemia del coronavirus SARS-CoV-2 ha provocado un confinamiento indefinido. Una posible consecuencia de esta situación es un retraso en los procedimientos asistenciales de las enfermedades oncológicas. El objetivo de este estudio es estimar el hipotético impacto en la supervivencia que tendría el aumento del tamaño tanto para los carcinomas de células escamosas (CCE) como de los melanomas. Material y método: Estudio observacional retrospectivo de cohorte multicéntrico. Se desarrolló un modelo de crecimiento exponencial para cada tumor basado en el tiempo de evolución que refiere el paciente. Resultados:Se incluyeron un total de 200 pacientes con CCE localizados en la cabeza y el cuello y 1.000 pacientes con melanoma cutáneo. Se calculó una curva de crecimiento exponencial para cada tumor y se estimó el tamaño del tumor tras 1, 2 y 3 meses tras el diagnóstico. En la muestra, los CCE mayores de 4cm o >6mm de grosor (definidos como T3) pasaron de 83 (41,5%) en el grupo de estudio real a una estimación del 58,5, 70,5 y 72% tras 1, 2 y 3 meses de retraso quirúrgico estimado, respectivamente. Se estimó una disminución de la supervivencia específica de enfermedad (SEE) de un 6,2, 8,2 y 5,2% a los 2, 5 y 10 años, respectivamente, tras 3 meses de retraso. Para los melanomas ultragruesos (>6mm de Breslow) pasaron del 6,9% en el grupo de estudio al 21,9, 30,2 y 30,2% tras 1, 2 y 3 meses de demora. La SEE a los 5 y 10 años del grupo de estudio descendió un 14,4% en ambos tiempos. Conclusiones:En ausencia de un adecuado diagnóstico y tratamiento de los pacientes con CCE y melanoma en la actual situación de confinamiento en España, podemos llegar a asistir a un considerable aumento de los casos de CCE y melanomas gruesos y de gran tamaño. Se deben fomentar los esfuerzos para promocionar la autoexploración y facilitar el acceso a los dermatólogos para no aumentar la demora de estos pacientes.

Case Reports; Journal Article; Review; Superficial Acral Fibromyxoma is a rare tumor of soft tissues. It is a relatively new entity described in 2001 by Fetsch et al. It probably represents a fibrohistiocytic tumor with less than 170 described cases. We bring a new case of SAF on the 5th toe of the right foot, in a 43-year-old woman. After surgical excision with safety margins which included the nail apparatus, it has not recurred (22 months of follow up). We carried out a review of the location of all SAF published up to the present day. Yes

Proceso Asistencial Integrado, Hoja de ruta Yes El Proceso Asistencial Integrado Cáncer de Piel publicado en el año 2002 permitió el establecimiento de las bases para la coordinación entre profesionales de los dos ámbitos asistenciales, Atención Primaria y Hospitalaria, orientada a facilitar y proporcionar una atención precoz y basada en normas de calidad al paciente con sospecha de cáncer de piel. En la versión actual del Proceso Asistencial Integrado Cáncer de Piel debido a las particularidades del carcinoma cutáneo no melanoma y melanoma se ha decidido abordarlo por separado.

Journal Article; Melanomas represent 4% of all malignant tumors of the skin, yet account for 80% of deaths from skin cancer.While in the early stages patients can be successfully treated with surgical resection, metastatic melanoma prognosis is dismal. Several oncogenes have been identified in melanoma as BRAF, NRAS, c-Kit, and GNA11 GNAQ, each capable of activating MAPK pathway that increases cell proliferation and promotes angiogenesis, although NRAS and c-Kit also activate PI3 kinase pathway, including being more commonly BRAF activated oncogene. The treatment of choice for localised primary cutaneous melanoma is surgery plus lymphadenectomy if regional lymph nodes are involved. The justification for treatment in addition to surgery is based on the poor prognosis for high risk melanomas with a relapse index of 50-80%. Patients included in the high risk group should be assessed for adjuvant treatment with high doses of Interferon- α 2b, as it is the only treatment shown to significantly improve disease free and possibly global survival. In the future we will have to analyze all these therapeutic possibilities on specific targets, probably associated with chemotherapy and/or interferon in the adjuvant treatment, if we want to change the natural history of melanomas. Yes

Editora comercial para la Indian Association of Dermatologists, Venereologists and Leprologists.El pdf no esta de libre acceso solo la versión html cque se ha convertido a pdf. Proliferating trichilemmal cyst is a benign tumor that originates in the outer root sheath of hair follicle. Usually, it is located on the scalp in older women, but also have been reported in other sites such as back, chest, axilla, groin, gluteal region, thigh, vulva, and face. Malignant transformation of proliferating trichilemmal cyst is confirmed only on histological findings. This tumor has a variable biologic behavior with local recurrence and lymph node metastasis. Yes

Journal Article; A 54-year-old woman presented a peri-areolar nodule located in the skin of the right breast. Clinical examination showed a 6 x 5 cm exophytic, lobed, ulcerated, and bleeding nodule. The patient reported that the tumor had grown gradually over a period of 3 months. The patient had been diagnosed 8 years prior to presentation with infiltrating ductal carcinoma of the right breast (pT2NO). This tumor was treated with partial mastectomy (conservative surgery) and lymph node dissection, then subsequently received 30 tangent field radiotherapy sessions to the breast for a total dose of 45 Gy. The rest of her cutaneous exam was normal. There was no family history of any similar tumor. Yes

Background The inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-γ-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-γ treatment in human melanoma cell lines., Methods Basal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan® Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-γ-treated cells., Results Altered IFN-γ mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-α led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-γ treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-α treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-γ in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-γ signaling pathway., Conclusion We observed two distinct mechanisms of loss of IFN-γ inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-γ signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence of IFN-γ-mediated HLA class I expression in ESTDAB-159 cells is due to epigenetic blocking of IFN-regulatory factor 1 (IRF-1) transactivation., This work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS), Red Genomica del Cancer (C03/10), Plan Andaluz de Investigacion, Servicio Andaluz de Salud (SAS) in Spain, from the ESTDAB project (contract no. QLRI-CT-2001-01325), from the European Network for the identification and validation of Antigens and biomarkers in Cancer and their application in clinical Tumor immunology (ENACT, contract No. 503306), and from the European Cancer Immunotherapy project (OJ2004/C158, 518234).

Background The role of genes involved in the control of progression from the G1 to the S phase of the cell cycle in melanoma tumors in not fully known. The aim of our study was to analyse mutations in TP53, CDKN1A, CDKN2A, and CDKN2B genes in melanoma tumors and melanoma cell lines Methods We analysed 39 primary and metastatic melanomas and 9 melanoma cell lines by single-stranded conformational polymorphism (SSCP). Results The single-stranded technique showed heterozygous defects in the TP53 gene in 8 of 39 (20.5%) melanoma tumors: three new single point mutations in intronic sequences (introns 1 and 2) and exon 10, and three new single nucleotide polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2). One melanoma tumor exhibited two heterozygous alterations in the CDKN2A exon 1 one of which was novel (stop codon, and missense mutation). No defects were found in the remaining genes. Conclusion These results suggest that these genes are involved in melanoma tumorigenesis, although they may be not the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas should be studied.

Publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados) Yes El cáncer de piel es un proceso de alta prevalencia, con una incidencia en aumento progresivo que repercute de una forma muy importante en la salud de la población. La radiación ultravioleta (del sol) es el principal agente etiológico conocido y, por su ubicación geográfica, nuestra Comunidad Autónoma es una de las regiones de España con mayor número de horas de sol al año. Esto justifica, entre otras razones, el abordaje de este proceso. En este documento nos ocupamos de los tres tipos de cáncer de piel más frecuentes, no contemplando otros que, aun siendo importantes, tienen escasa incidencia. Tampoco nos referiremos a los tumores cutáneos benignos, ya que, si bien son muy frecuentes, no implican un gran problema sanitario.

© 2010 The Authors. doi: 10.2340/00015555-0810 Journal Compilation © 2010 Acta Dermato-Venereologica. ISSN 0001-5555 Sir, Congenital naevi of the melanocytic system include numerous types, which differ in their clinical appearance, pattern of distribution, and histopathological features (1). Examples are large congenital melanocytic naevus, macular naevus spilus, papular naevus spilus, cafe-aulait macules of neurofibromatosis 1, cafe-au-lait macules arranged in broad bands as noted in McCune-Albright syndrome, partial unilateral lentiginosis, naevus achromicus (naevus depigmentosus), phylloid hypermelanosis, and phylloid hypomelanosis (1–3). We describe here two patients with a systematized pigmentary naevus that differed from all naevi reported so far.