Publications by authors named "Josep Malvehy"

240 Publications

Treatment-resistant actinic keratoses are characterized by distinct clinical and histological features.

Ital J Dermatol Venerol 2021 Apr;156(2):213-219

Faculty of Health, University Witten-Herdecke, Witten, Germany.

Background: Actinic keratoses (AK) are generally treated to reduce the risk of progression into invasive cutaneous squamous cell carcinoma (cSCC). However, this risk of transformation is low, and rather than focusing on these lesions, current treatment studies report on complete clearance of AKs in an entire field. This study aimed to investigate treatment-resistant AKs (trAK) after field therapy compared to randomly chosen AKs prior to treatment.

Methods: AKs were clinically assessed according to the grade of hyperkeratosis and pain on palpation, prior to treatment. TrAKs were biopsied and compared to AKs which were biopsied prior to any treatment. AKs were evaluated regarding histological severity (AKI-III), their basal growth grading (PROI-III), acantholysis, elastosis, follicular extension of atypical keratinocytes and accompanying infiltrate.

Results: Two hundred eleven AKs in 171 patients were identified. TrAKs (N.=79) were significantly more painful (64.6% vs. 22.0%; P<0.0001), showing acantholysis (57.0% vs. 33.3%; P=0.0007); and with distinct basal proliferation (PROIII) (64.4% vs. 46.2%; P=0.0099) compared to the control group (N.=132). In a multivariate analysis using logistic regression, pain and PRO III graded lesions were significant independent (P<0.0001 and P=0.0179) predictors for trAKs. Focusing on individual histological features in the trAK group, AKs with grade AKIII, PROIII or follicular extension reaching the sebaceous gland were the most common findings with 51.9%, 64.6%, and 59.5% AKs demonstrating this, respectively.

Conclusions: TrAKs are often painful, showing a distinct basal proliferation (PROIII) and acantholysis. As these features are also seen in invasive cSCCs, trAKs may represent a subgroup of AKs and, for this reason, it requires further evaluations.
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http://dx.doi.org/10.23736/S2784-8671.21.06892-9DOI Listing
April 2021

Visual Impact of Large and Giant Congenital Naevi: Comparison of Surgical Scars with Naevi Before Surgery.

Acta Derm Venereol 2021 May 6. Epub 2021 May 6.

Dermatology Department, Melanoma Group IDIBAPS, Hospital Clinic Barcelona - University of Barcelona, Villarroel 170, ES-08036 Barcelona, Spain.

Surgical attempts to remove large/giant congenital melanocytic naevi (LGCMN) are supported mainly by the theoretical improvement in patients' self-image; however such surgery can result in unaesthetic scarring. We hypothesize that difference in appearance itself has an impact, and hence surgery cannot negate this impact. The aim of this cross-sectional study was to explore how LGCMN and scarring are perceived by non-affected people. We surveyed the visual impact on 1,015 health and non-health professionals working in a university hospital. Participants were assigned to 1 of 3 surveys, which, based on photographs of children: (i) assessed the visual impact of LGCMN; (ii) the visual impact of scarring; (iii) compared the impact of LGCMN and scarring. Feelings and perceptions evoked by images of children, either with LGCMN or with scarring, were remarkably similar. However, when the images of the same child (with LGCMN or scarring) were shown together, respondents showed significantly increased preference for scarring.
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http://dx.doi.org/10.2340/00015555-3826DOI Listing
May 2021

The Usefulness of Dermoscopy for the Recognition of Malignant Collision Tumors.

Dermatology 2021 Mar 31:1-8. Epub 2021 Mar 31.

Epidemiology Department, Hospital Sant Pau i Santa Tecla, Tarragona, Spain.

Background: Preoperative diagnosis of malignant collision tumors (MCT) is extremely difficult. The value of dermoscopy to improve the correct detection of these tumors has not been previously studied. This study aims to evaluate the diagnostic accuracy of MCT with and without dermoscopy and to describe the dermoscopic features of a large series of MCT.

Methods: Dermoscopic images of 161 MCT were evaluated. Clinical and dermoscopic images of histopathologically proven MCT intermingled with other tumors were randomly presented to clinicians with different levels of experience, blinded to the diagnosis and objective of the study. The clinical and dermoscopic diagnostic accuracies were measured separately.

Results: A total of 161 histopathologically proven cases of MCT were collected. The most frequent MCT was basal cell carcinoma-seborrheic keratosis collision tumor (CT; 37.9%), followed by basal cell carcinoma-melanocytic nevus CT (19.9%), and melanoma-seborrheic keratosis CT (6.8%). Diagnostic accuracy among experts on dermoscopy was 71.4%. The study included 119 participants. The percentage of correct diagnoses was 8% by naked eye examination and 36.4% by dermoscopy (p < 0.001). The presence of the malignant component in the cases of MCT was not recognizable in 19.1% of cases by naked eye examination and in 11.8% of cases by dermoscopy (p < 0.001).

Conclusions: The diagnosis of MCT can be assisted and clarified by dermoscopy. However, many of these lesions manifest complex morphologies and continue to be challenging, even for experts on dermoscopy. Atypical, uncertain, or non-classifiable lesions still need a complete excision for the final diagnosis.
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http://dx.doi.org/10.1159/000514583DOI Listing
March 2021

Talimogene laherparepvec upregulates immune-cell populations in non-injected lesions: findings from a phase II, multicenter, open-label study in patients with stage IIIB-IVM1c melanoma.

J Immunother Cancer 2021 Mar;9(3)

First Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background: Talimogene laherparepvec (T-VEC), an oncolytic virus, was designed to selectively replicate in and lyse tumor cells, releasing tumor-derived antigen to stimulate a tumor-specific immune response.

Methods: In this phase II study in patients with unresectable stage IIIB-IV melanoma, we evaluated non-injected lesions to establish whether baseline or change in intratumoral CD8 T-cell density (determined using immunohistochemistry) correlated with T-VEC clinical response.

Results: Of 112 enrolled patients, 111 received ≥1 dose of T-VEC. After a median follow-up of 108.0 weeks, objective/complete response rates were 28%/14% in the overall population and 32%/18% in patients with stage IIIB-IVM1a disease. No unexpected toxicity occurred. Baseline and week 6 change from baseline CD8 T-cell density results were available for 91 and 65 patients, respectively. Neither baseline nor change in CD8 T-cell density correlated with objective response rate, changes in tumor burden, duration of response or durable response rate. However, a 2.4-fold median increase in CD8 T-cell density in non-injected lesions from baseline to week 6 was observed. In exploratory analyses, multiparameter immunofluorescence showed that after treatment there was an increase in the proportion of infiltrating CD8 T-cells expressing granzyme B and checkpoint markers (programmed death-1, programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen-4) in non-injected lesions, together with an increase in helper T-cells. Consistent with T-cell infiltrate, we observed an increase in the adaptive resistance marker PD-L1 in non-injected lesions.

Conclusions: This study indicates that T-VEC induces systemic immune activity and alters the tumor microenvironment in a way that will likely enhance the effects of other immunotherapy agents in combination therapy.

Trial Registration Number: NCT02366195.
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http://dx.doi.org/10.1136/jitc-2020-001621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011715PMC
March 2021

Clinicopathological, Genetic and Survival Advantages of Naevus-associated Melanomas: A Cohort Study.

Acta Derm Venereol 2021 Mar 31;101(3):adv00425. Epub 2021 Mar 31.

Department of Dermatology, Hospital Clinic of Barcelona, Barcelona, Spain.

Several studies have suggested that naevus-associated melanomas differ from de novo melanomas, being thinner and with less ulceration; however, the prognostic implication is unclear. The objective of this study was to describe clinicopathological, genetic and survival characteristics of de novo and naevus-associated melanomas in a cohort of primary invasive cutaneous melanomas over a 20-year period. Of the 2,227 patients included in the study, 509 (22.86%) had naevus-associated melanomas. Compared with patients with de novo melanoma, they were younger, with a fairer phototype and a higher naevus count, tumours were predominantly the superficial spreading subtype, American Joint Committee on Cancer stage I, located on the trunk, and there were fewer signs of invasiveness (thinner Breslow index, less ulceration, lower mitotic index and less satellitosis). Germline mutation-al status did not show any significant association. As determined through univariate analysis, overall surviv-al was significantly better in patients with naevus- associated melanoma (hazard ratio 0.64; 95% confidence interval 0.51-0.80, p < 0.001), but multivariate analysis did not support this prognostic indication (hazard ratio 0.94; 95% confidence interval 0.75-1.18, p < 0.606). Despite this, we conclude that naevus- associated and de novo melanomas should be considered as different subtypes of melanoma.
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http://dx.doi.org/10.2340/00015555-3780DOI Listing
March 2021

The Role of DICOM in Artificial Intelligence for Skin Disease.

Front Med (Lausanne) 2020 10;7:619787. Epub 2021 Feb 10.

PixelMed Publishing, Bangor, PA, United States.

There is optimism that artificial intelligence (AI) will result in positive clinical outcomes, which is driving research and investment in the use of AI for skin disease. At present, AI for skin disease is embedded in research and development and not practiced widely in clinical dermatology. Clinical dermatology is also undergoing a technological transformation in terms of the development and adoption of standards that optimizes the quality use of imaging. Digital Imaging and Communications in Medicine (DICOM) is the international standard for medical imaging. DICOM is a continually evolving standard. There is considerable effort being invested in developing dermatology-specific extensions to the DICOM standard. The ability to encode relevant metadata and afford interoperability with the digital health ecosystem (e.g., image repositories, electronic medical records) has driven the initial impetus in the adoption of DICOM for dermatology. DICOM has a dedicated working group whose role is to develop a mechanism to support AI workflows and encode AI artifacts. DICOM can improve AI workflows by encoding derived objects (e.g., secondary images, visual explainability maps, AI algorithm output) and the efficient curation of multi-institutional datasets for machine learning training, testing, and validation. This can be achieved using DICOM mechanisms such as standardized image formats and metadata, metadata-based image retrieval, and de-identification protocols. DICOM can address several important technological and workflow challenges for the implementation of AI. However, many other technological, ethical, regulatory, medicolegal, and workforce barriers will need to be addressed before DICOM and AI can be used effectively in dermatology.
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http://dx.doi.org/10.3389/fmed.2020.619787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902872PMC
February 2021

Impact of the COVID-19 Pandemic on Dermatology Practice Worldwide: Results of a Survey Promoted by the International Dermoscopy Society (IDS).

Dermatol Pract Concept 2021 Jan 29;11(1):e2021153. Epub 2021 Jan 29.

Department of Dermatology and Venereology, Dermatology Clinic, Maggiore Hospital, University of Trieste, Italy.

Introduction: The International Dermoscopy Society (IDS) conducted an online survey to investigate the impact of coronavirus disease 2019 (COVID-19) outbreak on the daily practice of dermatologists working with skin cancer patients, to collect data regarding the frequency of skin manifestations noticed by the members, and to obtain information about the use of teledermatology during the pandemic.

Methods: All IDS members were asked to fill in a questionnaire, sent by email. A questionnaire available in English was sent to all IDS members (≈16.0000 members) by email. The questionnaire was anonymous, with a compiling time of less than 5 minutes. The survey was open for 30 days (from April 24, 2020 to May 24, 2020) and it could only be filled out once.

Results: Overall, 678 dermatologists responded to the questionnaire; 334 members stated that there has been a reduction of more than 75% in daily work activity during the pandemic, 265 dermatologists worked fewer days per week, and 118 experienced telemedicine for the first time. Acrodermatitis was the most frequently observed skin manifestation (n = 80) followed by urticarial rash (n = 69), morbilliform rash (n = 53) and purpuric manifestation (n = 40). In regard to the role of teledermatology, 565 dermatologists reported an increased number of teleconsultations, and the number of melanomas diagnosed during the pandemic was practically 0 for 385 (56.78%) of respondents.

Conclusion: This survey highlights that the outbreak had a negative impact on most dermatology services, with a significant reduction in consultation time spent for chronic patients, and an increased risk of missed melanoma and nonmelanoma skin cancer (NMSC) diagnosis. Moreover, our study confirms earlier findings of a wide range of skin manifestations associated with COVID-19.
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http://dx.doi.org/10.5826/dpc.1101a153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875667PMC
January 2021

A patient-centric dataset of images and metadata for identifying melanomas using clinical context.

Sci Data 2021 01 28;8(1):34. Epub 2021 Jan 28.

The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, Brisbane, Australia.

Prior skin image datasets have not addressed patient-level information obtained from multiple skin lesions from the same patient. Though artificial intelligence classification algorithms have achieved expert-level performance in controlled studies examining single images, in practice dermatologists base their judgment holistically from multiple lesions on the same patient. The 2020 SIIM-ISIC Melanoma Classification challenge dataset described herein was constructed to address this discrepancy between prior challenges and clinical practice, providing for each image in the dataset an identifier allowing lesions from the same patient to be mapped to one another. This patient-level contextual information is frequently used by clinicians to diagnose melanoma and is especially useful in ruling out false positives in patients with many atypical nevi. The dataset represents 2,056 patients (20.8% with at least one melanoma, 79.2% with zero melanomas) from three continents with an average of 16 lesions per patient, consisting of 33,126 dermoscopic images and 584 (1.8%) histopathologically confirmed melanomas compared with benign melanoma mimickers.
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http://dx.doi.org/10.1038/s41597-021-00815-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843971PMC
January 2021

Six steps to reach optimal scanning in ex vivo confocal microscopy.

J Am Acad Dermatol 2021 Jan 19. Epub 2021 Jan 19.

Dermatology Department, Melanoma Unit, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunye, Universitat de Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1016/j.jaad.2021.01.044DOI Listing
January 2021

Differences in cutaneous melanoma survival between the 7th and 8th edition of the American Joint Committee on Cancer (AJCC). A multicentric population-based study.

Eur J Cancer 2021 Mar 5;145:29-37. Epub 2021 Jan 5.

Department of Dermatology, Hospital Clínic de Barcelona, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona University, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain. Electronic address:

Background: The 8th edition of the AJCC manual for melanoma includes many changes leading to major substage migrations, which could lead to important clinical reassessments.

Objectives: To evaluate the differences and prognostic value of the 8th AJCC classification in comparison with the 7th edition.

Methods: Clinical and histopathological data were retrieved from five melanoma referral centers including 7815 melanoma patients diagnosed between January 1998 and December 2018. All patients were reclassified and compared using the 7th and 8th classifications of the AJCC. Sankey plots were used to evaluate the migration of patients between the different versions. The primary outcome was overall survival (OS), and curves based on the Kaplan-Meier method were used to investigate survival differences between the 7th and 8th editions.

Results: The number of patients classified as stages IB, IIIA, and IIIB decreased while the patients classified as stages IA and IIIC increased notably. Migration analysis showed that many patients in group I were understaged whereas a significant percentage of patients in group III were upstaged. Indirect OS analysis showed a loss in the linearity in the AJCC 8th edition and the groups tended to overlap. Direct OS analysis between groups and versions of the AJCC showed a better prognosis within the new stage III patients, with no effect on those in stages I and II.

Conclusion: The 8th AJCC edition represents an important change in the classification of patients. We observe that the main migratory changes occur in stage I and III, that severity linearity is lost and groups overlap, and that a more advanced stage does not mean a worse prognosis.
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http://dx.doi.org/10.1016/j.ejca.2020.11.036DOI Listing
March 2021

Influence of germline genetic variants on dermoscopic features of melanoma.

Pigment Cell Melanoma Res 2021 May 31;34(3):618-628. Epub 2021 Jan 31.

Melanoma Unit, Dermatology Department, Hospital Clínic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.

Nevus count is highly determined by inherited variants and has been associated with the origin of melanoma. De novo melanomas (DNMMs) are more prevalent in patients with a low nevus count and have distinctive dermoscopic features than nevus-associated melanomas. We evaluated the impact of nine single nucleotide polymorphisms (SNPs) of MTAP (rs10811629, rs2218220, rs7023329 and rs751173), PLA2G6 (rs132985 and rs2284063), IRF4 (rs12203592), and PAX3 (rs10180903 and rs7600206) genes associated with nevus count and melanoma susceptibility, and the MC1R variants on dermoscopic features of 371 melanomas from 310 patients. All MTAP variants associated with a low nevus count were associated with regression structures (peppering and mixed regression), blue-whitish veil, shiny white structures, and pigment network. SNPs of PLA2G6 (rs132985), PAX3 (rs7600206), and IRF4 (rs12203592) genes were also associated with either shiny white structures or mixed regression (all corrected p-values ≤ .06). Melanomas from red hair color MC1R variants carriers showed lower total dermoscopy score (p-value = .015) and less blotches than melanomas from non-carriers (p-value = .048). Our results provide evidence that germline variants protective for melanoma risk and/or associated with a low nevus count are associated with certain dermoscopic features, more characteristic of de novo and worse prognosis melanomas.
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http://dx.doi.org/10.1111/pcmr.12954DOI Listing
May 2021

Deep learning-level melanoma detection by interpretable machine learning and imaging biomarker cues.

J Biomed Opt 2020 11;25(11)

The Rockefeller University, Laboratory of Investigative Dermatology, New York, New York, United States.

Significance: Melanoma is a deadly cancer that physicians struggle to diagnose early because they lack the knowledge to differentiate benign from malignant lesions. Deep machine learning approaches to image analysis offer promise but lack the transparency to be widely adopted as stand-alone diagnostics.

Aim: We aimed to create a transparent machine learning technology (i.e., not deep learning) to discriminate melanomas from nevi in dermoscopy images and an interface for sensory cue integration.

Approach: Imaging biomarker cues (IBCs) fed ensemble machine learning classifier (Eclass) training while raw images fed deep learning classifier training. We compared the areas under the diagnostic receiver operator curves.

Results: Our interpretable machine learning algorithm outperformed the leading deep-learning approach 75% of the time. The user interface displayed only the diagnostic imaging biomarkers as IBCs.

Conclusions: From a translational perspective, Eclass is better than convolutional machine learning diagnosis in that physicians can embrace it faster than black box outputs. Imaging biomarkers cues may be used during sensory cue integration in clinical screening. Our method may be applied to other image-based diagnostic analyses, including pathology and radiology.
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http://dx.doi.org/10.1117/1.JBO.25.11.112906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702097PMC
November 2020

Pseudonits or Hair Casts.

Dermatol Pract Concept 2020 Oct 26;10(4):e2020072. Epub 2020 Oct 26.

Department of Dermatology, University of Barcelona, Spain.

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http://dx.doi.org/10.5826/dpc.1004a72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588169PMC
October 2020

Incidence of Melanoma in Catalonia, Spain, Is Rapidly Increasing in the Elderly Population. A Multicentric Cohort Study.

J Clin Med 2020 Oct 23;9(11). Epub 2020 Oct 23.

Hospital Clinic de Barcelona, University of Barcelona, 08036 Barcelona, Spain.

The incidence of melanoma has been increasing worldwide during recent decades. The objective of the study was to analyse the trends in incidence for in situ and invasive melanoma in the Spanish region of Catalonia during the period of 2008-2017. We designed a cross-sectional study with an age-period-cohort analysis of melanoma patient data from the Network of Melanoma Centres in Catalonia. Our database covered a population of over seven million and included a total of 8626 patients with incident melanoma. The main outcome measures were crude and age-standardised incidence rates to the European 2013 standard population. Joinpoint regression models were used to evaluate the population trends. We observed an increase in the age-standardised incidence rate (per 100,000 population) of all melanoma subtypes from 11.56 in 2008 to 13.78 in 2017 with an average annual percent change (AAPC) of 3.5%. This incidence increase was seen exclusively in the older population. Moreover, the stratified analysis showed a statistically significant increase in the age-standardised incidence rate for invasive (AAPC 2.1%) and in situ melanoma (AAPC 6.5%). In conclusion, the incidence of melanoma has continued to increase in the elderly population over recent decades, with a rapidly increasing trend of in situ melanomas and the lentigo maligna subtype.
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http://dx.doi.org/10.3390/jcm9113396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690683PMC
October 2020

The Distinctive Genomic Landscape of Giant Congenital Melanocytic Nevi.

J Invest Dermatol 2021 Mar 13;141(3):692-695.e2. Epub 2020 Aug 13.

Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain; Molecular Biology CORE, Hospital Clínic de Barcelona. Melanoma Group, IDIBAPS, University of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1016/j.jid.2020.07.022DOI Listing
March 2021

Ultrasound findings of proliferative nodule arising in a congenital melanocytic nevus.

Melanoma Res 2020 10;30(5):528-529

Department of Dermatology, Melanoma Unit, Hospital Clinic, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.

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http://dx.doi.org/10.1097/CMR.0000000000000565DOI Listing
October 2020

Human-computer collaboration for skin cancer recognition.

Nat Med 2020 08 22;26(8):1229-1234. Epub 2020 Jun 22.

ViDIR Group, Department of Dermatology, Medical University of Vienna, Vienna, Austria.

The rapid increase in telemedicine coupled with recent advances in diagnostic artificial intelligence (AI) create the imperative to consider the opportunities and risks of inserting AI-based support into new paradigms of care. Here we build on recent achievements in the accuracy of image-based AI for skin cancer diagnosis to address the effects of varied representations of AI-based support across different levels of clinical expertise and multiple clinical workflows. We find that good quality AI-based support of clinical decision-making improves diagnostic accuracy over that of either AI or physicians alone, and that the least experienced clinicians gain the most from AI-based support. We further find that AI-based multiclass probabilities outperformed content-based image retrieval (CBIR) representations of AI in the mobile technology environment, and AI-based support had utility in simulations of second opinions and of telemedicine triage. In addition to demonstrating the potential benefits associated with good quality AI in the hands of non-expert clinicians, we find that faulty AI can mislead the entire spectrum of clinicians, including experts. Lastly, we show that insights derived from AI class-activation maps can inform improvements in human diagnosis. Together, our approach and findings offer a framework for future studies across the spectrum of image-based diagnostics to improve human-computer collaboration in clinical practice.
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http://dx.doi.org/10.1038/s41591-020-0942-0DOI Listing
August 2020

When Seborrheic Keratosis Is Wearing a Mask.

Dermatol Pract Concept 2020 20;10(2):e2020038. Epub 2020 Apr 20.

Dermatology Department, Hospital Clínic, Barcelona, Spain.

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http://dx.doi.org/10.5826/dpc.1002a38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190459PMC
April 2020

Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility.

Nat Genet 2020 05 27;52(5):494-504. Epub 2020 Apr 27.

Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain.

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
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http://dx.doi.org/10.1038/s41588-020-0611-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255059PMC
May 2020

Melanocortin-1 receptor (MC1R) genotypes do not correlate with size in two cohorts of medium-to-giant congenital melanocytic nevi.

Pigment Cell Melanoma Res 2020 09 20;33(5):685-694. Epub 2020 May 20.

Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.

Congenital melanocytic nevi (CMN) are cutaneous malformations whose prevalence is inversely correlated with projected adult size. CMN are caused by somatic mutations, but epidemiological studies suggest that germline genetic factors may influence CMN development. In CMN patients from the U.K., genetic variants in MC1R, such as p.V92M and loss-of-function variants, have been previously associated with larger CMN. We analyzed the association of MC1R variants with CMN characteristics in two distinct cohorts of medium-to-giant CMN patients from Spain (N = 113) and from France, Norway, Canada, and the United States (N = 53), similar at the clinical and phenotypical level except for the number of nevi per patient. We found that the p.V92M or loss-of-function MC1R variants either alone or in combination did not correlate with CMN size, in contrast to the U.K. CMN patients. An additional case-control analysis with 259 unaffected Spanish individuals showed a higher frequency of MC1R compound heterozygous or homozygous variant genotypes in Spanish CMN patients compared to the control population (15.9% vs. 9.3%; p = .075). Altogether, this study suggests that MC1R variants are not associated with CMN size in these non-UK cohorts. Additional studies are required to define the potential role of MC1R as a risk factor in CMN development.
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http://dx.doi.org/10.1111/pcmr.12883DOI Listing
September 2020

Sutton Naevi as Melanoma Simulators: Can Confocal Microscopy Help in the Diagnosis?

Acta Derm Venereol 2020 May 11;100(10):adv00134. Epub 2020 May 11.

Dermatology Department, Hospital Clínic and Melanoma Group IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), ES-08036 Barcelona, Spain.

Sutton naevi can sometimes present a challenging appearance with atypical presentation, also by dermoscopy. Reflectance confocal microscopy could help in making a diagnosis. This study prospectively collected two groups of Sutton nevi: the first one was composed by typical white halo naevi monitored for one year (13, 23%) and the second one was made up of atypical lesions excised in order to rule out melanoma, which were histologically diagnosed as Sutton naevi (21, 37%). These two groups of Sutton naevi were compared to a retrospectively collected cohort of thin melanomas with histologic regression features (23, 40%). On dermoscopy, atypical Sutton naevi and melanomas were indistinguishable. Reflectance confocal microscopy demonstrated significant differences at the dermo-epidermal junction: marked dermo-epidermal junction thickening and non-edged papilla were associated with melanoma, while the presence of nests was associated with Sutton naevi. However, reflectance confocal microscopy also detected marked intraepidermal pagetoid cells in Sutton naevi that were a combination of MelanA+ and CD1a+ cells. Sutton naevi can simulate melanoma, under both dermoscopy and reflectance confocal microscopy. Nevertheless, relevant confocal dermo-epidermal junction features and the clinical scenario can be helpful to make a final diagnosis, especially in those situations where melanoma must be ruled out.
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http://dx.doi.org/10.2340/00015555-3488DOI Listing
May 2020

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment.

Eur J Cancer 2020 03 26;128:83-102. Epub 2020 Feb 26.

Aix Marseille University, APHM Hospital, Marseille France.

In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for non-surgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics.
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http://dx.doi.org/10.1016/j.ejca.2020.01.008DOI Listing
March 2020

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention.

Eur J Cancer 2020 03 26;128:60-82. Epub 2020 Feb 26.

Aix Marseille University, APHM Hospital, Marseille France.

Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (<4%). Further risk stratification into low-risk or high-risk common primary cSCC is recommended based on proposed high-risk factors. Advanced cSCC is classified as locally advanced (lacSCC), and metastatic (mcSCC) including locoregional metastatic or distant metastatic cSCC. Current systems used for staging include the American Joint Committee on Cancer (AJCC) 8th edition, the Union for International Cancer Control (UICC) 8th edition, and Brigham and Women's Hospital (BWH) system. Physical examination for all cSCCs should include total body skin examination and clinical palpation of lymph nodes, especially of the draining basins. Radiologic imaging such as ultrasound of the regional lymph nodes, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography-computed tomography (PET-CT) scans are recommended for staging of high-risk cSCC. Sentinel lymph node biopsy is currently not recommended. Nicotinamide, oral retinoids, and topical 5-FU have been used for the chemoprevention of subsequent cSCCs in high-risk patients but are not routinely recommended. Education about sun protection measures including reducing sun exposure, use of protective clothing, regular use of sunscreens and avoidance of artificial tanning, is recommended.
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http://dx.doi.org/10.1016/j.ejca.2020.01.007DOI Listing
March 2020

Microblotches on Dermoscopy of Melanocytic Lesions are Associated with Melanoma: A Cross-sectional Study.

Acta Derm Venereol 2020 Apr 6;100(8):adv00106. Epub 2020 Apr 6.

Department of Dermatology, Melanoma Unit, Hospital Clínic of Barcelona, Barcelona, Spain.

Numerous dermoscopic structures for the early detection of melanoma have been described. The aim of this study was to illustrate the characteristics of dermoscopic structures that are similar to blotches, but smaller (termed microblotches), and to evaluate their association with other well-known dermoscopic structures. A cross-sectional study design, including 165 dermoscopic images of melanoma was used to define microblotches, and 241 consecutive images of naevi from the HAM10000 database, were studied to evaluate the prevalence of this criterion in both groups. Microblotches were defined as sharply demarcated structures ≤1 mm, with geographical borders visible only with dermoscopy. Microblotches were present in 38.7% of the melanomas and 6.7% of the naevi. Moreover, microblotches were associated with an odds ratio (OR) of malignancy of 5.79, and were more frequent in invasive melanoma than in the in-situ subtype (OR 2.92). Histologically, they correspond to hyperpigmented parakeratosis or epidermal consumption. In conclusion, microblotches are related to melanomas. This finding could help dermatologists to differentiate between naevi and melanomas.
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http://dx.doi.org/10.2340/00015555-3436DOI Listing
April 2020