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Background: The clinical and pathological features of primary melanoma are not sufficiently sensitive to accurately predict which patients are at a greater risk of relapse. Recently, a 31‐gene expression profile (DecisionDx‐Melanoma) test has shown promising results. Objectives: To evaluate the early prognostic performance of a genetic signature in a multicentre prospectively evaluated cohort. Methods: Inclusion of patients with AJCC stages IB and II conducted between April 2015 and December 2016. All patients were followed up prospectively to assess their risk of relapse. Prognostic performance of this test was evaluated individually and later combined with the AJCC staging system. Prognostic accuracy of disease‐free survival was determined using Kaplan–Meier curves and Cox regression analysis. Results of the gene expression profile test were designated as Class 1 (low risk) and Class 2 (high risk). Results: Median follow‐up time was 26 months (IQR 22–30). The gene expression profile test was performed with 86 patients; seven had developed metastasis (8.1%) and all of them were in the Class 2 group, representing 21.2% of this group. Gene expression profile was an independent prognostic factor for relapse as indicated by multivariate Cox regression analysis, adjusted for AJCC stages and age. Conclusions: This prospective multicentre cohort study, performed in a Spanish Caucasian cohort, shows that this 31‐gene expression profile test could correctly identify patients at early AJCC stages who are at greater risk of relapse. We believe that gene expression profile in combination with the AJCC staging system could well improve the detection of patients who need intensive surveillance and optimize follow‐up strategies. [ABSTRACT FROM AUTHOR]

Isoflavones have been shown to have health-promoting activities in humans and are particularly abundant in soya bean. This study was conducted to determine how water deficit during seed fill affects the already known relationship between temperature and, alternately, solar radiation with soya bean seed isoflavone content. Isoflavone profile was analysed from seed samples of commercial cultivars grown in 76 environments in Argentina (29-38°S). Significant explanatory multiple linear regressions were detected for total isoflavones ( TI), aglycones ( AGL), glucosides ( GLC), malonyl glucosides ( MAL) and acetyl glucosides ( ACE) regarding the following: temperature during seed fill (TmR5R7) and precipitation minus potential evapotranspiration during the reproductive period (pp-PETR1R7), as well as for the combinations of these climatic variables. Cumulative solar radiation predicted isoflavone content but was less robust than TmR5R7 and pp- PETR1R7. To our knowledge, this is the first report of changes in the relationship between TI, as well as AGL, GLC, MAL, and ACE and TmR5R7 as a function of drought in the field. When pp- PETR1R7 was below 70 mm (indicating drought), TI, as well as AGL, GLC, MAL, and ACE decreased linearly with rising temperatures and with increasing water deficit (decreasing values of pp- PETR1R7), with both climatic variables exhibiting additive effects on isoflavones. Our results also suggest that water deficit (estimated by pp- PETR1R7) would be important for modelling the relationship between temperature and soya bean seed isoflavones in rainfed crops. [ABSTRACT FROM AUTHOR]

Background Digital follow-up is a useful method for the detection of melanoma in atypical mole syndrome patients. The combination of digital follow-up (DFU) and reflectance confocal microscopy ( RCM) could be useful to increase the accuracy in the classification of equivocal lesions in atypical mole syndrome patients. Objectives To assess the impact of RCM analysis on sensitivity and specificity of digital follow-up in a high-risk melanoma setting. Methods Retrospective study with dermoscopy and RCM of consecutive equivocal atypical melanocytic lesions exhibiting changes in digital dermoscopy in a referral centre. Results Sixty-four lesions from 51 patients were included. Thirteen changing lesions (20.3%) corresponded to eight melanomas in situ and five invasive melanomas with Breslow less than 1 mm. Fifty-one lesions corresponded to melanocytic naevus with variable atypia. Total dermoscopy scores were not different between naevus and melanoma neither in the baseline (mean 5.06 and 5.24; P = 0.37) nor in the follow-up dermoscopic control (mean 5.44 and 5.55; P = 0.37). The only significant dermoscopic feature associated with melanoma in multivariate analysis was the presence of streaks after follow-up ( P = 0.027; OR = 3.6; CI 1.50-8.70). The confocal microscopy evaluation (by means both the Modena and Barcelona methods) showed a sensitivity and specificity for the diagnosis of melanoma of 100% and 69% respectively. Based on our experience, the combination of RCM and DFU could have avoided 35 of 51 nevi excised. Conclusions Reflectance confocal microscopy evaluation of equivocal lesions detected by DFU improved the accuracy in the detection of melanoma. The combination of dermoscopy, DFU and confocal microscopy in equivocal lesions can be useful to dramatically reduce the number of excisions of benign lesions in atypical mole syndrome patients. [ABSTRACT FROM AUTHOR]

Background Histological features such as Breslow thickness, ulceration and mitosis are the main criteria to guide sentinel lymph node biopsy ( SLNB) in melanoma. Dermoscopy may add complementary information to these criteria. Objectives To evaluate the correlation between dermoscopy structures and SLNB positivity. Methods Retrospective analysis of 123 consecutive melanomas with Breslow thickness > 0·75 mm, SLNB performed during follow-up and dermoscopic images. Results Men were more likely to have a positive SLNB. The presence of ulceration and blotch and the absence of a pigmented network in dermoscopy correlated with positive SLNB. Histological ulceration also correlated with positive SLNB. A dermoscopy SCORE predicted SLN status with a sensitivity of 96·3% and a specificity of 30·2%. When sex and Breslow thickness were added ( SCOREBRESEX), the sensitivity remained at 96·3% but the specificity increased to 52·1%. This study is limited by the number of patients and was performed in only one institution. Conclusions Dermoscopy allowed a more precise prediction of SLN status. If a combined SCOREBRESEX was used to select patients for SLNB, 41·5% of procedures might be avoided. [ABSTRACT FROM AUTHOR]

The article discusses research done on imaging techniques for detecting melanoma. It references the study "Integration of Reflectance Confocal Microscopy in Sequential Dermoscopy Follow-up Improves Melanoma Detection Accuracy" by I. Stanganelli and colleagues published within the issue. Topics discussed include the major findings of the study, as well as its limitations.

Since the introduction of the National Health Service Breast Screening Programme (NHSBSP), the number of ductal carcinoma in situ (DCIS) cases has increased considerably. Despite its increased incidence, some NHS leaflets and reports do not mention it, and the general public seems largely unaware of its existence. There are numerous biological studies dealing with this condition, but its psychosocial aspects seem to have been neglected. We have only been able to locate two British studies (Farmer, A. 1996. Unpublished PhD thesis, University of Southampton; Webb, C. and Koch, T. 1997. J. Adv. Nurs., 25, 154-525) that address some of the psychosocial issues associated with DCIS. This paper starts by defining DCIS and explaining its usual presentation, natural history and epidemiology. The treatment options for DCIS are described, together with the great deal of confusion and lack of agreement that accompanies them. The psychological issues that women with screen-detected DCIS have to deal with are different from those affecting women diagnosed with symptomatic breast cancer, and a summary of these issues is given. Finally, some suggestions for future psychosocial research are provided. Because the UK as a whole was not covered by the NHSBSP until 1990 (Baum, M. 1995. Lancet, 346, 436; Gage and Fouquet, 1997), the main focus will be on papers published from that year onwards, although some key papers published before then will also be included. The papers reviewed here were found in MEDLINE, EMBASE and BIDS (ISI). [ABSTRACT FROM AUTHOR]

Background Desmoplastic malignant melanoma ( DMM) is a rare and usually misdiagnosed type of melanoma. Delayed detection at complicated anatomical locations can lead to the necessity of alternative therapies. Objective Characterization of DMM on the nose, which is the second more frequent type of MM. Methods Review of case series of eight pathologically proven DMM on the nose from two referral centres with a mean follow-up of 69 ± 40.5 months. Results According to a single centre experience, there is a more than 70-fold increased risk of having a DMM on the nose compared with a non- DMM ( P < 0.0005, CI99% 16.3-317.3). Clinical and pathological misdiagnoses were frequent, only three of the eight cases were properly diagnosed and treated and indeed they did not experience relapses. Due to non-clinical suspicion and superficial biopsies, three cases were initially pathologically misdiagnosed as basal cell carcinomas and a nevus respectively. Atypical vessels and remnants of pigment on dermoscopy are indicative findings even in non-pigmented cases. Although not significant, the mean disease-free survival differed between cases with a correct initial management (four cases, 66.7 ± 57.3 months) in contrast to improper (four cases, 16.25 ± 18.9 months). Electrochemotherapy achieved a complete local control of disease in two cases unsuitable for surgery. Conclusions Use of dermoscopy and correctly selected biopsy of lesions on the face is mandatory to improve early diagnosis of DMM. Improper management of challenging cases implies a more complicated therapy and loco-regional invasion risk. Electrochemotherapy could be a promising therapy in local advanced tumours. [ABSTRACT FROM AUTHOR]

Background The number needed to treat ( NNT) ratio is an effective method for measuring accuracy in melanoma detection. Dermoscopy reduces the number of false positives and subsequently unnecessary excisions. In vivo reflectance confocal microscopy ( RCM) is a noninvasive technique that allows examination of the skin with cellular resolution. Objectives To assess the impact of RCM analysis on the number of equivocal lesions, assumed to be melanocytic, excised for every melanoma. Methods Consecutive patients ( n = 343) presenting with doubtful lesions were considered for enrolment. The lesions were analysed by dermoscopy and RCM, with histopathological assessment considered the reference standard. The main outcome was the NNT, calculated as the proportion of equivocal lesions excised for every melanoma. Results Dermoscopy alone obtained a hypothetical NNT of 3·73; the combination of dermoscopy and RCM identified 264 equivocal lesions that qualified for excision, 92 of which were confirmed to be a melanoma, resulting in an NNT of 2·87, whereas the analysis of RCM images classified 103 lesions as melanoma, with a consequent NNT of 1·12. The difference in the reduction of this ratio was statistically significant between the three groups ( P < 0·0001). There was no significant improvement in sensitivity when comparing the combination of dermoscopy and RCM with RCM alone (94·6% vs. 97·8%; P = 0·043). However, the differences between specificities were statistically significant ( P < 1 × 10−6), favouring RCM alone. Conclusion The addition of RCM analysis to dermoscopy reduces unnecessary excisions with a high diagnostic accuracy and could be a means for reducing the economic impact associated with the management of skin cancer. [ABSTRACT FROM AUTHOR]

Background Cutaneous melanoma tumour is classified into clinicohistopathological subtypes that may be associated with different genetic and host factors. Variation in the MC1R gene is one of the main factors of risk variation in sporadic melanoma. The relationship between MC1R variants and the risk of developing a specific subtype of melanoma has not been previously explored. Objectives To analyse whether certain MC1R variants are associated with particular melanoma subtypes with specific clinicohistopathological features. Methods An association study was performed between MC1R gene variants and clinicopathological subtypes of primary melanoma derived from 1679 patients. Results We detected 53 MC1 R variants (11 synonymous and 42 nonsynonymous). Recurrent nonsynonymous variants were p. V60L (30·0%), p. V92 M (11·7%), p. D294 H (9·4%), p. R151 C (8·8%), p. R160 W (6·2%), p. R163 Q (4·2%) p. R142 H (3·3%), p.I155 T (3·8%), p. V122 M (1·5%) and p. D84 E (1·0%). Melanoma subtypes showed differences in the total number of MC1 R variants ( P = 0·028) and the number of red hair colour variants ( P = 0·035). Furthermore, an association between p. R163 Q and lentigo maligna melanoma was detected under a dominant model of heritance (odds ratio 2·16, 95% confidence interval 1·07-4·37; P = 0·044). No association was found between p. R163 Q and Fitzpatrick skin phototype, eye colour or skin colour, indicating that the association was independent of the role of MC1 R in pigmentation. No association was observed between MC1 R polymorphisms and other melanoma subtypes. Conclusions Our findings suggest that certain MC1 R variants could increase melanoma risk due to their impact on pathways other than pigmentation, and may therefore be linked to specific melanoma subtypes. [ABSTRACT FROM AUTHOR]

Background UV radiation and the presence of melanocytic nevi are the main risk factors of sporadic melanoma (MM). Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the possible role of an oral Polypodium leucotomos (PL) extract to improve systemic photoprotection in patients at risk of skin cancer analyzing the ability to decrease UV-induced erythema. We also studied the interaction among MC1R polymorphisms and CDKN2A status with the minimal erythematous dose (MED) and their influence in the response after oral PL. Methods A total of 61 patients (25 with familial and/or multiple MM, 20 with sporadic MM and 16 with atypical mole syndrome without history of MM) were exposed to varying doses of artificial UVB radiation without and after oral administration of a total dose of 1080mg of PL. Results Oral PL treatment significantly increased the MED mean in all group patients (0.123 to 0.161 J/cm2, p<0.05). Although not significant, we noticed a stronger effect of PL on the MED of patients with familial MM compared to those with MM ( U=273, p=0.06). Among the patients with familial MM, those exhibiting a mutated CDKN2A and/or polymorphisms in MC1R had the bigger differences in response to treatment with PL. Limitations Reduced number of patients. No control population. Conclusions Administration of PL leads to a significant reduction of sensitivity to UVR (p<0.05) in all patients. Dark-eye patients and patients with higher UVR sensibility (lower basal MED) would be the most benefited from oral PL treatment. [ABSTRACT FROM AUTHOR]

The aim of this research was to determine whether the new geographic information technologies, included as teaching objectives in the new European Space for Higher Education Engineering degrees, develop spatial abilities. Bearing this in mind, a first year seminar using the INSPIRE Geoportal (Infrastructure for Spatial Information in Europe) was designed, involving 46 engineering students from the University of La Laguna. The spatial orientation ability development was analysed through statistical inference methods, using the Perspective Taking/Spatial Orientation Test. [ABSTRACT FROM PUBLISHER]

Random-pattern cutaneous flaps are very useful in Reconstructive Surgery; an adequate vascular contribution is an important factor for the survival of the flaps. We designed an experimental study elevating a total of 36 dorsal flaps, divided in 4 groups: a) 9 were controls, to which 0.9% physiological solution was applied, b) 9 with a transoperatory application of type A botulinum toxin throughout the length of the flap, c) 9 with an application of type A botulinum toxin 7 days before surgery and d), 9 with type A botulinum toxin with epinephrine applied transsurgery in all the flap. The skin flaps were analyzed 7 days after surgery with Image J program and the T Student test. We take a medium of the necrotic area: a) for the controls of 72.17±3.9%, b) botulinum toxin transsurgery 5.09±1.2% p=0.032, c) botulinum toxin applied 7 days before 24.97±2.7% p=0.041 and d) botulinum toxin with epinephrine 23.90±3.9% p=0.045. We conclude that botulinum toxin acts as a protector against the suffering process - ischemia of the tissues, thanks to its vasodilator action and that it should be applied in the beginning of the surgical procedure. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In recent years numerous reports have been published regarding satisfactory thalidomide therapy for refractory chronic cutaneous lesions of lupus erythematosus (CCLE); to date, in the literature, there is just one report describing two patients affected by hyperkeratotic CCLE successfully treated with thalidomide. METHODS: Six patients affected by a hypertrophic/verrucous variant of CCLE were treated with thalidomide during the period October 1999 to December 2002 and their medical records were retrospectively reviewed. The initial dose of thalidomide was 100 mg/die by mouth for all the cases, while the duration of therapy was variable among the patients. RESULTS: All six patients responded to treatment: two had partial resolution of the lesions and four achieved almost complete clearing of cutaneous disease. Response to treatment was seen in the first month of therapy in all the patients. Follow-up nerve conduction studies were negative but a patient had to discontinue the drug because of neurological problems. DISCUSSION/CONCLUSION: Our case series confirms the efficacy of a 'low-dose' thalidomide regimen in verrucous/hyperkeratotic CCLE, which is normally unresponsive to conventional treatment; in this setting, thalidomide should be kept in mind as an extremely valid therapeutic option despite the lack of prospective, randomized, double-blind, placebo-controlled studies. [ABSTRACT FROM AUTHOR]

Background: Around 0.5% of cutaneous melanoma (CM) patients will present with synchronous melanomas when first seen. Moreover, 26–40% of patients with multiple primary melanomas present with synchronous lesions. Objectives: To assess the prevalence, clinical and histopathological characteristics, germline mutations and outcome in patients with synchronous melanoma. Methods: Clinical and histopathological data from 4703 melanoma patients were included. Clinical, histological and genetic mutational status information was analysed. Kaplan–Meier curves were used to investigate survival outcomes. Results: A total of 144 patients (3.06%) presented simultaneously with two or more primary melanomas. During follow‐up, 25.7% of patients with synchronous melanoma developed a new primary melanoma compared to 8.6% of patients diagnosed with single melanoma (P < 0.001). Germinal CDKN2A mutations were identified in 10.7% of patients with synchronous melanomas and genetic variants in MC1R in 72%. No significant differences in all survival outcomes between patients with synchronous melanomas and single melanomas were found. Conclusion: Synchronous melanomas are more frequent than previously reported and are more frequent in older patients compared to single melanomas. Moreover, these patients have a higher risk of developing a new primary melanoma during follow‐up and have higher rates of germline susceptibility variants. Nevertheless, these findings were not associated with worse outcomes. [ABSTRACT FROM AUTHOR]

The article discusses a 5-year retrospective study on the long-term effectiveness and tolerability of apremilast in patients with moderate-to-severe plaque psoriasis in Italy. A total of 335 patients were treated with apremilast, with demographic characteristics and treatment outcomes recorded. Results showed significant reductions in Psoriasis Area and Severity Index (PASI) scores over the study period, with a majority of patients achieving PASI 75, PASI 90, and PASI 100. The study concluded that apremilast demonstrated effectiveness and tolerability as a treatment option for patients with contraindications to biological treatments. [Extracted from the article]

Background Objective Methods Results Conclusion There is a need for unified guidance in the management of acneiform rash induced by epidermal growth factor receptor inhibitors (EGFRi) among dermatologists.To establish unified international guidelines for the management of acneiform rash caused by EGFR inhibitors, based on an experts' Delphi consensus.The initiative was led by five members of the European Academy of Dermatology and Venereology Task Force ‘Dermatology for Cancer Patients’ who developed a questionnaire that was circulated to a group of 32 supportive oncodermatology experts in Europe, Canada, Argentina, the US States and Asia. The questionnaire consisted of 84 statements in total, regarding diagnosis and treatment of EGFRi‐induced acneiform rash. Experts responded to an anonymous 5‐point Likert scale survey. The coordinators collected the first‐round responses that were checked for consensus (≥75% agreement in positive [agree or strongly agree] or in negative [disagree or strongly disagree] vote). The statements that did not reach strong consensus in the first round were revised, according to experts' feedback, for a second‐round survey.Strong consensus was reached in 75/84 (89.3%) of the statements, whilst moderate consensus was achieved in 6/84 elements. Key points include consideration of low‐dose isotretinoin for refractory grade II/III acneiform rash, use of topical steroid‐sparing agents like topical pimecrolimus in the maintenance phase and use of doxycycline in either 100 or 200 mg per day as prophylactic treatment. Interestingly, experts did not recommend topical antibiotics, neither for prevention, nor for treatment. Consensus failure in 3/84 objects is mostly related to the lack of robust data on these topics.This consensus offers crucial insights often overlooked by radiotherapists, general practitioners, dermatologists and oncologists, and it is expected to improve the management of oncologic patients treated with EGFRi in different settings and continents. [ABSTRACT FROM AUTHOR]

ParaHydrogen Induced Polarization-Side Arm Hydrogenation (PHIP-SAH) is an inexpensive tool to obtain hyperpolarized pyruvate (and other metabolites) that can be applied to in vivo diagnostics, for the investigation of metabolic processes. This method is based on hydrogenation, using hydrogen enriched in the para-isomer, of unsaturated substrates, catalyzed, usually, by a homogeneous rhodium(I) complex. In this work, the effect of the solvent on the hydrogenation efficiency and the hyperpolarization level were investigated. Coordinating solvents, such as acetone and methanol, can increase significantly either the efficiency or the hyperpolarization level, but they are not compatible with the intended metabolic applications. The phase extraction of the hyperpolarized product (sodium pyruvate) in an aqueous solution was obtained carrying out the hydrogenation reaction in chloroform and toluene. The traces of the organic solvents in the water phase were removed, by means of filtration through a lipophilic resin, thus improving the biocompatibility of the aqueous solution of the hyperpolarized product. [Display omitted] • Hydrogenation in acetone or methanol can be quite efficient or give high polarization. • Chloroform and toluene were used to extract pyruvate in an aqueous solvent. • Traces of solvents are removed from the aqueous solution using a lipophilic resin. [ABSTRACT FROM AUTHOR]

A letter to the editor on the presentation of erythema multiforme as cholestatic acute hepatitis caused by epstein-barr virus

We sought to describe the clinico-epidemiological and histological characteristics and long-term follow-up of a series of patients with SJS/TEN-like CLE. Palm and sole involvement was seen in 50% of patients in a recently reported case series.4 As we found similar results, this finding could help to differentiate this CLE subtype from drug-induced SJS/TEN. Three patients were diagnosed with TEN-like CLE, three with SJS/TEN-like overlap and three with SJS-like CLE. [Extracted from the article]

Background: In vivo reflectance confocal microscopy (RCM) enables the study of architectural and cytological aspects in horizontal sections, which closely correlate with histologic features. However, traditional histopathological vertical sections cannot totally reproduce the image of the in vivo RCM horizontal section. Objective: To evaluate the concordance between in vivo RCM and histopathologic transverse sections for melanocytic lesions, basal cell carcinoma and seborrheic keratoses. Methods: Prospectively collected benign melanocytic and non‐melanocytic tumours diagnosed by dermoscopy were evaluated for common RCM features and compared to histopathology in horizontal sections with haematoxylin and eosin staining. Results: A total of 44 skin tumours including 19 melanocytic lesions (nine compound, five junctional and five intradermal nevi), 12 basal cell carcinomas and 13 seborrheic keratoses were collected in the Department of Dermatology of Hospital Clinic of Barcelona. The RCM features that had statistically significant agreement with the histopathological horizontal sections were the preserved and visible honeycomb pattern, well defined DEJ, small bright particles, dermal nests, tumour islands and dark silhouettes, clefting, collagen bundles, thickened collagen bundles and cytologic atypia. Conclusions: Histopathology evaluation of horizontal sections of skin tumours can be correlated with main RCM findings. The results of this study have improved the understanding and interpretation of RCM features in relation to skin tumours, thus reinforcing the utility of RCM as a diagnostic tool. [ABSTRACT FROM AUTHOR]

This article examines the effectiveness of risankizumab, a medication used to treat moderate-to-severe plaque psoriasis. The study found that risankizumab was effective in improving psoriasis symptoms, with a high percentage of patients experiencing significant improvement and complete skin clearance. The study also found that patients who had not previously been treated with biologic drugs and those with a shorter disease history had better responses to the treatment. However, the study has some limitations, and further research is needed to fully understand the long-term effects of risankizumab on psoriasis. [Extracted from the article]

Background: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark‐skinned individuals, are underrepresented. Objectives: We report a comprehensive pooled analysis of established high‐ and intermediate‐penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium. Methods: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country. Results: We included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1; 95% CI 3.3–19.7), >3 affected members (OR 2.6; 95% CI 1.3–5.2) and occurrence of pancreatic cancer (OR 4.8; 95% CI 2.4–9.4) in the family (AUC 0.76, 95% CI 0.71–0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4; 95% CI 1.0–2.0 and OR 4.3; 95% CI 1.2–14.6, respectively). Conclusions: Variants in known high‐penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk assessment. [ABSTRACT FROM AUTHOR]

Objective: This international needs assessment was mandated by the European Society of Cardiology (ESC) to obtain an in-depth understanding of the current gaps and challenges of European cardiology professionals, with the aim to provide evidence for the development of needs-driven educational and professional development activities. Methods: This ethics-approved needs assessment was conducted among cardiologists from all sub-specialties across 56 countries of Europe and the Mediterranean basin. A mixed-methods research approach was used, combining qualitative in-depth interviews and focus groups with a quantitative survey. Results: Seventy-four (74) cardiologists participated in the qualitative phase and 866 completed the survey. Respondents represented 52 of the 56 targeted countries. Three themes were identified: 1) Challenges in the clinical decision-making process, 2) Challenges in establishing the patient-physician relationship, and 3) Sub-optimal team communication and collaboration. Specific gaps and causalities related to each challenge were found. Although most of the gaps were common across countries and sub-specialties, some significant differences were noted. Conclusion: The findings of this needs assessment indicate gaps and challenges in clinical practice across countries and across sub-specialities. Taking cardiology as an example, this study identifies clear areas of focus, especially around issues of collaboration and communication, for targeted competency-based education in Europe. [ABSTRACT FROM PUBLISHER]

Summary: Background: Many follow‐up guidelines for patients with high‐risk melanoma include expensive imaging studies, serum biomarkers and regular visits to the dermatologist, with little attention to cost‐effectiveness. Objectives: To establish the cost‐effectiveness of chest–abdomen–pelvis computed tomography (CT) and brain magnetic resonance imaging (MRI) in a follow‐up protocol for patients at high risk of relapse. Methods: This was a prospective single‐centre cohort study of 290 patients with clinicopathological American Joint Committee on Cancer (AJCC) stage IIB, IIC and III melanoma. Patients had a body CT scan and brain MRI every 6 months and were withdrawn from the study after completing a 5‐year follow‐up or when metastases were detected. A cost‐effectiveness analysis for each follow‐up radiological procedure was performed. Results: Patients underwent 1805 body CT scans and 1683 brain MRIs. Seventy‐six metastases (26·2%) were identified by CT or MRI. CT scan was cost‐effective in the first 4 years (cost‐effectiveness ratio €4710·70–€14 437·10/patient with metastasis); brain MRI was cost‐effective during the first year (cost‐effectiveness ratio €14 090·60/patient with metastasis). Limitations included lack of survival analysis and comparisons with willingness‐to‐pay thresholds. Conclusions: Six‐monthly CT scan of the chest, abdomen and pelvis is a cost‐effective technique for the early detection of metastases in the first 4 years of follow‐up in patients with AJCC stage IIC and III melanoma, and in the first 3 years in patients with AJCC stage IIB melanoma. In addition, brain MRI has been shown to be cost‐effective only in the first year of follow‐up in patients with AJCC stage IIC and III melanoma. What's already known about this topic? Follow‐up guidelines for patients with melanoma vary widely between countries and few studies have quantified the cost‐effectiveness of these protocols. What does this study add? We discovered that computed tomography is cost‐effective in the first 3 years in stage IIB melanoma and in the first 4 years of follow‐up in stage IIC–III melanoma.Brain magnetic resonance imaging is cost‐effective in the first year in stage IIC–III melanoma. Respond to this article [ABSTRACT FROM AUTHOR]

A letter to the editor about compound blue nevus as a potential simulator of melanoma is presented.

Examines a case of bullous herpes zoster. Manifestations of the skin disease; Classifications of herpes zoster; Morphological variation of the disease.

Patients with genodermatosis such as Gorlin syndrome (GS) and Xeroderma pigmentosum (XP) require a close follow-up for early diagnosis and treatment of skin cancer. We aimed to evaluate the efficacy of methyl-aminolevulinate (MAL) photodynamic therapy (PDT) in basal cell carcinomas (BCCs) from patients with GS and XP, and to determine the utility of reflectance confocal microscopy (RCM) in the diagnosis and the evaluation of therapeutic response. We included four patients with GS and two siblings with XP. Single or multiple lesions in localized areas were treated with 1-3 cycles of MAL PDT. RCM was performed before and 3 months after the treatment in target lesions in all the patients. Patients were followed up for 3 years. In XP patients, we treated 13 pigmented BCCs on the face. All the lesions responded to the treatment and six lesions showed a complete clinical clearing. In GS patients, facial or trunk areas with multiple BCCs were treated (up to 200). Complete clinical remission was obtained in 25-67% of the lesions. Some nodular and pigmented lesions failed to achieve a complete remission. RCM could identify already described confocal features for BCC. Tumour remissions could be assessed by this technique. Methyl-aminolevulinate PDT may be useful for the treatment of superficial BCC in GS and XP. In some nodular lesions, PDT may complement surgery reducing tumour size. RCM may be regarded in the future as a complementary technique in BCC for the diagnosis and post-treatment assessment to non-invasive therapeutic modalities. [ABSTRACT FROM AUTHOR]

Summary: Background: Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma. Efforts are under way to identify preventable and treatable factors associated with greater melanoma aggressiveness, but no studies to date have examined the relationship between T2DM and the aggressiveness of cutaneous melanoma at diagnosis. Objectives: To explore potential associations between T2DM, glycaemic control and metformin treatment and the aggressiveness of cutaneous melanoma. Methods: We conducted a cross‐sectional multicentric study in 443 patients diagnosed with cutaneous melanoma. At diagnosis, all patients completed a standardized protocol, and a fasting blood sample was extracted to analyse their glucose levels, glycated haemoglobin concentration and markers of systemic inflammation. Melanoma characteristics and aggressiveness factors [Breslow thickness, ulceration, tumour mitotic rate (TMR), sentinel lymph node (SLN) involvement and tumour stage] were also recorded. Results: The mean (SD) age of the patients was 55·98 (15·3) years and 50·6% were male. The median Breslow thickness was 0·85 mm. In total, 48 (10·8%) patients were diagnosed with T2DM and this finding was associated with a Breslow thickness > 2 mm [odds ratio (OR) 2·6, 95% confidence interval (CI) 1·4–4·9; P = 0·004)] and > 4 mm (OR 3·6, 95% CI 1·7–7·9; P = 0·001), TMR > 5 per mm2 (OR 4·5, 95% CI 1·4–13·7; P = 0·009), SLN involvement (OR 2·3, 95% CI 1–5·7; P = 0·038) and tumour stages III–IV (vs. I–II) (OR 3·4, 95% CI 1·6–7·4; P = 0·002), after adjusting for age, sex, obesity, alcohol intake and smoking habits. No significant associations emerged between glycated haemoglobin levels, metformin treatment and melanoma aggressiveness. Conclusions: T2DM, rather than glycaemic control and metformin treatment, is associated with increased cutaneous melanoma aggressiveness at diagnosis. What is already known about this topic?Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma, at least in men, in addition to protective antitumoral activity as a result of metformin treatment. What does this study add?This multicentric study of a large series of prospectively recruited and well‐characterized patients with cutaneous melanoma shows, for the first time, that the presence of underlying T2DM, rather than metformin treatment, is associated with markers of increased tumour aggressiveness independently of confounders.Patients with melanoma and T2DM constitute a more aggressive phenotype of this tumour, unrelated to treatment with metformin.Melanoma prevention should be strengthened in patients with T2DM to minimize the negative impact of this metabolic disorder on melanoma aggressiveness. Linked Comment: A.E. Cust. Br J Dermatol 2021; 185:692–693. Plain language summary available online [ABSTRACT FROM AUTHOR]

Hyperpolarization‐enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13C, 15N, or 129Xe due to their long spin‐polarization lifetimes and the absence of a proton‐background signal from water and fat in the images. Here we present a novel type of 1H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long‐lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para‐enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization‐enhanced 1H‐imaging modality presented here can allow for hyperpolarized imaging without the need for low‐abundance, low‐sensitivity heteronuclei. [ABSTRACT FROM AUTHOR]

Hyperpolarisationsverstärkte Magnetresonanztomographie kann zur Untersuchung biomolekularer Prozesse im Körper verwendet werden, erfordert aber die Verwendung von Hetero‐Kernen wie 13C, 15N oder 129Xe. Hier stellen wir eine neue Art der Hyperpolarisierten Protonen Bildgebung vor, bei der die hyperpolarisierte Spinordnung in einem nicht magnetischen und langlebigen korrelierten (Singulett‐) Zustand eingeschlossen ist und nur durch eine spezifische biochemische Reaktion für die Bildgebung freigesetzt wird. In dieser Arbeit erzeugen wir hyperpolarisiertes Fumarat durch chemische Reaktion eines Eduktes mit para‐angereichertem Wasserstoffgas. Der Singulettzustand der Fumarat Protonen wird als Antiphasen‐NMR‐Signale durch enzymatische Umwandlung zu Malat in D2O freigesetzt. Anhand dieses Modellsystems zeigen wir zwei Pulssequenzen, um die NMR‐Signale für die Bildgebung zu rephasieren und die Hintergrundsignale von Wasser zu unterdrücken. Die hier vorgestellte hyperpolarisationsverstärkte Protonen Bildgebungstechnik ermöglicht eine hyperpolarisierte Bildgebung, ohne dass hierfür Hetero‐Kerne mit ihrer niedrigen natürlichen Häufigkeit und geringen Empfindlichkeit benötigt werden. [ABSTRACT FROM AUTHOR]

Background: The anatomical location of atypical melanocytic skin lesion (aMSL) was never combined into an algorithm for discriminating early melanomas (EM) from atypical nevi (AN). Aims: To investigate the impact of body location on the intuitive diagnosis performed in teledermoscopy by dermatologists of different skill levels. A further aim was to evaluate how the integration of the body location could improve an algorithm‐aided diagnosis. Methods: We retrospectively collected 980 standardized dermoscopic images of aMSL cases (663 AN, 317 EM): data on the anatomical location were collected according to 15 body sites classified into 4 macro‐areas of chronically/frequently/seldom/rarely exposure. Through a teledermatology web platform, 111 variously skilled dermoscopists performed either the intuitive diagnosis and 3 algorithm‐assisted diagnostic tests (i.e. iDScore, 7‐point checklist, ABCD rule) on each case, for a total of 3330 examinations. Results: In the rarely photoexposed area (side, bottom, abdomen), AN were the most tricky (i.e. highest quote of false positives), due to a frequent recognition of dermoscopic features usually considered as suggestive for melanoma in these lesions; the EM at these sites received the highest quote of false negatives, being generally interpreted as 'featureless' according to these traditional parameters, that were more frequently displayed on the chronically photoexposed area. In rarely and seldom photoexposed area, intuitive diagnosis fails to achieve adequate accuracy for all aMSLs, as the ABCD rule and the 7‐point checklist; by applying the iDScore algorithm the diagnostic performance was increased by 15% in young and 17% in experts. Conclusions: The body location of an aMSL can affect the quality of intuitive dermoscopic diagnosis, especially in sun‐protected areas. Accuracy can be improved by using the iDScore algorithm that assigns a different partial score of each body site. Linked Commentary: T. Deinlein. J Eur Acad Dermatol Venereol 2021; 35: 566. https://doi.org/10.1111/jdv.17141. [ABSTRACT FROM AUTHOR]

Background: MC1R polymorphisms interact with CDKN2A mutations modulating melanoma risk and contribute to a less suspicious clinical and dermoscopic appearance of melanomas. Different strategies, including dermoscopic comparative approach and digital monitoring, are used for the melanoma diagnosis in this context. Objective: To analyse the diagnostic accuracy of the morphologic approach and comparative approach in dermoscopy, and to detect melanoma in familial melanoma (FamMM) patients according to different genetic backgrounds. Methods: Two independent readers evaluated 415 lesions belonging to 25 FamMM: 26 melanomas (62% in situ, 36% early invasive) and 389 naevi, blinded for dermoscopic and histopathologic diagnosis, following two different steps. First step‐Randomized: all lesions were randomly located in one single folder. Second step‐Comparative approach: the lesions were clustered by patient. Sensitivity, specificity and number needed to excise (NNE) for melanoma diagnosis were calculated for both diagnostic strategies. Sensitivity and specificity were also assessed regarding the genetic background. Results: The comparative approach showed lower sensitivity compared to the morphologic approach (69.2 and 73.1 vs. 76.9 both readers) but better specificity (95.9 and 95.1 vs. 84.3 and 90.2, respectively). NNE was better in the comparative approach. The readers had more difficulties diagnosing lesions from CDKN2A mutation carriers with red hair colour (RHC) MC1R variants. Conclusion: The comparative approach can be useful in high‐risk patients to decrease the NNE. Early melanomas in CDKN2A carriers with RHC polymorphisms are more difficult to diagnose even with the comparative approach and benefit from the detection of changes during digital dermoscopy monitoring for early diagnosis. Linked Commentary: A. Lallas. J Eur Acad Dermatol Venereol 2021; 35: 274‐275. https://doi.org/10.1111/jdv.17104. [ABSTRACT FROM AUTHOR]

Two patients (a 35-year-old woman and a 33-year-old man, just returned from trips to Jamaica and Barbados, respectively) presented with cutaneous larva migrans with folliculitis, a rare and atypical clinical presentation of this infestation. Histopathological examination revealed a follicular and perifollicular infiltrate prevalently consisting of lymphocytes and neutrophils, with numerous eosinophils. Both patients were successfully treated with oral albendazole. [ABSTRACT FROM AUTHOR]

Background: Most of the models to predict prognosis after an ischemic stroke include complex mathematical equations or too many variables, making them difficult to use in the daily clinic. We want to predict disability 3 months after an ischemic stroke in an independent patient not receiving recanalization treatment within the first 24 h, using a minimum set of variables and an easy tool to facilitate its implementation. As a secondary aim, we calculated the capacity of the score to predict an excellent/devastating outcome and mortality. Methods: Eight hundred and forty-four patients were evaluated. A multivariable ordinal logistic regression was used to obtain the score. The Modified Rankin Scale (mRS) was used to estimate disability at the third month. The results were replicated in another independent cohort (378 patients). The "polr" function of R was used to perform the regression, stratifying the sample into seven groups with different cutoffs (from mRS 0 to 6). Results: The Parsifal score was generated with: age, previous mRS, initial NIHSS, glycemia on admission, and dyslipidemia. This score predicts disability with an accuracy of 80–76% (discovery–replication cohorts). It has an AUC of 0.86 in the discovery and replication cohort. The specificity was 90–80% (discovery–replication cohorts); while, the sensitivity was 64–74% (discovery–replication cohorts). The prediction of an excellent or devastating outcome, as well as mortality, obtained good discrimination with AUC > 0.80. Conclusions: The Parsifal Score is a model that predicts disability at the third month, with only five variables, with good discrimination and calibration, and being replicated in an independent cohort. [ABSTRACT FROM AUTHOR]

Background: The role of S100B protein in detecting early melanoma relapses is controversial, since most metastasis occur within normal values of S100B. Objective: The aim of this study was to assess the performance of S100B in detecting early disease progression in high‐risk melanoma patients. Methods: Retrospective cohort study including patients with an initial diagnosis of stage IIB, IIC and III melanoma between January 2003 and July 2013. All patients were followed up in accordance with an intensive protocol based on imaging studies and serum S100B levels every 3–6 months. We compared two methods to evaluate changes in S100B. The classic method referring to a single determination of S100B above the cut‐off level at the time of metastasis, which was evaluated in all patients. And a new method based on monthly changes of S100, which was used in the setting of patients with S100B levels within the normal range. Results: Overall, 289 of patients were followed up for 44 months (IQR 17–73) and 45% developed metastases. During the study period, 129 patients relapsed of which 46 (35.7%) present elevated values of S100B at the time of relapse. The classic method had a sensitivity and specificity of S100B protein of 35.7% and 92.5%, respectively. Furthermore, for the patients that relapsed with normal values of S100B, the new method was applied and showed a sensitivity and specificity of 41.1% and 92.4%, respectively, allowing to detect additional relapses that were missing by the classic method. Conclusion: During follow‐up of high‐risk melanoma patients, rising serum S100B values within the normal range can be an important clue to disease progression. Linked Commentary: C. Posch. J Eur Acad Dermatol Venereol 2020; 34: 1386–1386. https://doi.org/10.1111/jdv.16731. [ABSTRACT FROM AUTHOR]

Background: Although live and teledermoscopic examination has been successfully used to achieve non‐invasive diagnosis of melanocytic skin lesions (MSLs), early melanoma (EM) and atypical nevi (AN) continue to be a challenge, and none of the various algorithms proposed have been sufficiently accurate. We designed a scoring classifier diagnostic method, the iDScore that combines clinical data of the patient with dermoscopic features of the MSL. Objective: To test the accuracy of the iDScore in differentiating EM from AN in a teledermoscopy setting and to compare it with intuitive diagnosis, the ABCD rule and the seven‐point checklist. Materials and methods: A dedicated teledermoscopy web platform was designed. This involved the following: (i) collecting a large integrated clinical–historical–dermoscopic data set of difficult MSLs from eight European dermatology centres; (ii) online testing, education and training in using the iDScore. A total of 904 images were combined with age, sex, lesion diameter and body site data and evaluated on the platform by 111 participants with four levels of skill in dermoscopy. Each testing session consisted of 30 blind cases to examine consecutively by the above four methods. 'Management decisions' and personal participant data were also recorded. Results: iDScore‐aided diagnosis achieved satisfactory diagnostic accuracy for all lesions, irrespective of centre of affiliation, showing an average AUC of 0.776 in all participant testing sessions. All skill groups improved their accuracy by 10–16% with respect to intuitive diagnosis and the other methods, showing high concordance and avoiding wrong management decisions. Conclusion: We demonstrated the validity of the iDScore method for managing suspicious MSLs in a large multicentric data set and a teledermoscopic setting. The platform designed for the iDScore project provides ready support for physicians of any dermoscopy skill level and is useful for education and training. [ABSTRACT FROM AUTHOR]

Summary: Background: The p.V600E mutation in the BRAF protein is the most frequent mutation in cutaneous melanoma and is a recurrent alteration found in common benign naevi. Analysis of the cell‐free BRAF c.1799T>A, p.V600E mutation (cfBRAFV600E) in plasma has emerged as a biomarker for monitoring prognosis and treatment response in patients with melanoma. Objectives: To quantify cfBRAFV600E levels in plasma from patients with melanoma and from patients without melanoma undergoing regular follow‐up of their melanocytic lesions, in order to assess the clinical significance of the test. Methods: We quantified cfBRAFV600E by droplet digital polymerase chain reaction in plasma from 146 patients without melanoma undergoing continuous dermatological screening, from 26 stage III and seven stage IV patients with BRAF‐mutant melanoma, and from 32 patients with melanoma who were free of disease for 3 or more years. Results: Among disease‐free patients and individuals without melanoma, 52% presented a high naevus count (> 50) and 49% had clinically atypical naevi. cfBRAFV600E was detected in 71% of patients with stage IV melanoma and 15% with stage III, and in 1·4% of individuals without melanoma. No cfBRAFV600E mutation was detected in disease‐free patients with melanoma. Individuals without melanoma had lower cfBRAFV600E levels than patients with melanoma. We established a variant allelic frequency of 0·26% or 5 copies mL−1 of cfBRAFV600E as the optimal cutoff value for identifying patients with melanoma with > 99% specificity. Conclusions: This study suggests that naevus‐related factors do not influence the detection of cfBRAFV600E in individuals without melanoma, and supports the clinical diagnostic value of plasma cfBRAFV600E quantification in patients with melanoma. What's already known about this topic? The analysis of the BRAF c.1799T>A (p.V600E) mutation in cell‐free (cf)DNA has emerged as a potential biomarker for monitoring prognosis and treatment response in patients with metastatic BRAFV600E melanoma.The BRAFV600E alteration is a common genetic alteration found in benign proliferations such as melanocytic naevi.No information exists about the impact of the number of common acquired naevi or the presence of clinically atypical naevi in cfBRAFV600E detection in an individual. What does this study add? The cfBRAFV600E mutation is detected in plasma from a reduced number of individuals without melanoma undergoing continuous dermatological follow‐up.A high number of naevi or the presence of clinically atypical naevi are factors that do not influence cfBRAFV600E detection in an individual.Both total cfBRAF concentration and cfBRAFV600E frequency are effective biomarkers in patients with advanced melanoma but not in patients at early stages or with micrometastases. What is the translational message? Detection of cfBRAFV600E in an individual is not influenced by naevus‐related factors.cfBRAFV600E is a robust and reliable biomarker that can be used in dermatological surveillance programmes. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Women have a better melanoma prognosis, and fairer skin/hair colour. The presence of inherited MC1R variants has been associated with a better melanoma prognosis, but its interaction with sex is unknown. Objectives: To evaluate the relationship between germline MC1R status and survival, and determine any association with sex. Methods: This was a cohort study including 1341 patients with melanoma from the Melanoma Unit of the Hospital Clinic of Barcelona, between January 1996 and April 2018. We examined known sex‐related prognosis factors as they relate to features of melanoma and evaluated the sex‐specific role of MC1R in overall and melanoma‐specific survival. Hazard ratios (HRs) were calculated using univariate and multivariate Cox logistic regression. Results: Men showed lower overall survival than women (P < 0·001) and the presence of inherited MC1R variants was not associated with better survival in our cohort. However, in women the presence of MC1R variants was associated with better overall survival in the multivariate analysis [HR 0·57, 95% confidence interval (CI) 0·38–0·85; P = 0·006] but not in men [HR 1·26, 95% CI 0·89–1·79; P = 0·185 (P‐value for interaction 0·004)]. Analysis performed for melanoma‐specific survival showed the same level of significance. Conclusions: Inherited MC1R variants are associated with improved overall survival in women with melanoma but not in men. Intrinsic sex‐dependent features can modify the role of specific genes in melanoma prognosis. We believe that survival studies of patients with melanoma should include analysis by sex and MC1R genotype. What's already known about this topic? Inherited MC1R variants have been associated with a better melanoma prognosis, but their interaction with sex is unknown. What does this study add? MC1R variants are related to better overall survival and melanoma‐specific survival in women but not in men. What is the translational message? These differences between the sexes could imply future changes in melanoma follow‐up and treatment strategies.This provides a basis for understanding the interaction between sex‐related genes and germline variants in cancer. Respond to this article Linked Editorial:Craig and Virós. Br J Dermatol 2020; 182:5–6. [ABSTRACT FROM AUTHOR]

In order to study this, we retrospectively reviewed confocal findings of 20 cases of inflamed tumours: 5 thin melanomas with regression features on histopathology, 5 banal naevi and 10 histologically proven Sutton's naevi. In conclusion, marked inflamed naevi such as Sutton's naevi can simulate melanoma when assessed by RCM and vice versa: they could be a pitfall in RCM evaluation even in the hands of confocal experts. [Extracted from the article]

Summary: Background: Germline mutations in telomere‐related genes such as POT1 and TERT predispose individuals to familial melanoma. Objectives: To evaluate the prevalence of germline mutations in POT1 and TERT in a large cohort of Spanish melanoma‐prone families (at least two affected first‐ or second‐degree relatives). Methods: Overall, 228 CDKN2A wild‐type melanoma‐prone families were included in the study. Screening of POT1 was performed in one affected person from each family and TERT was sequenced in one affected patient from 202 families (26 families were excluded owing to DNA exhaustion/degradation). TERT promoter sequencing was extended to an additional 30 families with CDKN2A mutation and 70 patients with sporadic multiple primary melanoma (MPM) with a family history of other cancers. Results: We identified four families with potentially pathogenic POT1 germline mutations: a missense variant c.233T>C (p.Ile78Thr); a nonsense variant c.1030G>T (p.Glu344*); and two other variants, c.255G>A (r.125_255del) and c.1792G>A (r.1791_1792insAGTA, p.Asp598Serfs*22), which we confirmed disrupted POT1 mRNA splicing. A TERT promoter variant of unknown significance (c.‐125C>A) was detected in a patient with MPM, but no germline mutations were detected in TERT promoter in cases of familial melanoma. Conclusions: Overall, 1·7% of our CDKN2A/CDK4‐wild type Spanish melanoma‐prone families carry probably damaging mutations in POT1. The frequency of TERT promoter germline mutations in families with melanoma in our population is extremely rare. What's already known about this topic? Germline mutations in telomere‐related genes predispose to familial melanoma.The prevalence of germline mutations in telomere‐related genes has not been widely studied in melanoma families of Iberian descent. What does this study add? This study evaluates for the first time the prevalence of POT1 and TERT promoter mutations in a hospital‐based series of 228 CDKN2A‐negative families with melanoma from Barcelona, Spain.We identified POT1, but no TERT promoter, mutations in 1·7% of families.The results will facilitate genetic counselling and screening of families with melanoma. What is the translational message? Analysis of telomere‐related genes showed rare POT1 variants in a subset of Spanish melanoma‐prone families, while mutations in the TERT promoter were extremely rare.If extended to additional families and cancer types, these findings may have important implications for genetic counselling. Linked Comment: Toland. Br J Dermatol 2019; 181:14–15. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Histiocytoid Sweet syndrome (HSS) is an uncommon histopathological variant of SS, characterized by an inflammatory infiltrate with a predominance of immature myeloid cells, which may be misinterpreted as histiocytes.1 HSS has been associated with malignancies, drugs, infections and autoimmune diseases.1 Few cases of drug-induced HSS have been reported, and in many of them a protein kinase inhibitor was considered the culprit drug.1,2 A 71-year-old woman with a I HER2 i -negative and oestrogen receptor-positive invasive lobular breast carcinoma presented with a 2-day history of fever (38.5°C) and painful skin lesions on her trunk and limbs. Histological examination of skin biopsies revealed marked oedema in the superficial dermis and a periadnexal and perivascular inflammatory infiltrate extending to the mid and deep dermis (Fig. Severe skin reactions (grade >= 3) occur in < 1% of patients and have rarely been reported in the literature.4,5 To our knowledge, this is the first report of HSS induced by a CDK4/6 inhibitor. [Extracted from the article]

Dermal fillers may induce late-onset adverse skin reactions in patients under BRAF inhibitors Histiocytoses are disorders characterized by inflammation and the accumulation of cells derived from the monocyte and macrophage lineages, which results in tissue damage. Although the development of sarcoidosis-like lesions seems to be a paradoxical adverse event of BRAF/MEK inhibitors, recent data confirm their immunomodulatory effect.5 Three reported cases of sarcoidosis occurring during BRAF-inhibitor treatment for ECD have demonstrated an original intracellular mechanism of granuloma formation linked to paradoxical ERK expression.2 Contrary to Amoura I et al i .,2 median duration of BRAF inhibition treatment before occurrence of sarcoidosis-like lesions was 8 months. [Extracted from the article]

The patient progressively developed tolerable fatigue, mild muscle spasms and a decrease in global hair growth, while he noticed moustache hair thickening and hardening. Physical examination revealed mild diffuse alopecia on the scalp and normal hair on the moustache area with only one persisting enlarged hair shaft (Fig. c-d). GLO:3NZ/01jan20:jdv15842-fig-0001.jpg PHOTO (COLOR): Acquired moustache trichomegaly during treatment with vismodegib and resolution after treatment withdrawal (a) Trichomegaly of the moustache and goatee seen 5 months after the start of vismodegib treatment (b) Trichoscopy of moustache area showing hair shaft thickness heterogeneity, with a single enlarged hair per follicle opening. [Extracted from the article]

Background Poromas are benign cutaneous sweat gland tumours that are challenging to identify. The dermoscopic features of poromas are not well characterized. Objective To determine the clinical-dermoscopic features of poromas. Methods Cross-sectional, observational study of 113 poromas and 106 matched control lesions from 16 contributors and eight countries. Blinded reviewers evaluated the clinical and dermoscopic features present in each clinical and dermoscopic image. Results Poromas were most commonly non-pigmented (85.8%), papules (35.4%) and located on non-acral sites (65.5%). In multivariate analysis, dermoscopic features associated with poroma included white interlacing areas around vessels (OR: 7.9, 95% CI: 1.9-32.5, P = 0.004), yellow structureless areas (OR: 2.5, 95% CI: 1.1-6.0, P = 0.04), milkyred globules (OR: 3.9, 95% CI: 1.4-11.1, P = 0.01) and poorly visualized vessels (OR: 33.3, 95% CI: 1.9-586.5, P = 0.02). The presence of branched vessels with rounded endings was positively associated with poromas but did not reach statistical significance (OR: 2.4, 95% CI: 0.8-6.5, P = 0.10). The presence of any of these five features was associated with a sensitivity and specificity of 62.8% and 82.0%, respectively. Conclusion We identified dermoscopic features that are specific to the diagnosis of poroma. Overall, however, the prevalence of these features was low. Significant clinical and dermoscopic variability is a hallmark of these uncommon tumours, which are most prevalent on non-acral sites. [ABSTRACT FROM AUTHOR]

Background Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques. Objective We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images. Methods A total of 223 facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical, dermoscopic and RCM examination was compared. Interinvestigator variability and confidence level in the diagnosis were also evaluated. Results Overall diagnostic accuracy of the two imaging techniques was good (area under the curve of the sROC function: 0.89). RCM was more sensitive (80%, vs. 61%) and less specific (81% vs. 92%) than dermoscopy for LM/LMM. In particular, RCM showed a higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher interinvestigator agreement and a higher confidence level in the diagnosis than dermoscopy. Conclusion Reflectance confocal microscopy and dermoscopy are both useful techniques for the diagnosis of facial lesions and in particular LM/LMM. RCM is particularly suitable for the identification of hypomelanotic and recurrent LM/LMM. [ABSTRACT FROM AUTHOR]

Introduction Different protocols have been used to follow up melanoma patients in stage I–II. However, there is no consensus on the complementary tests that should be requested or the appropriate intervals between visits. Our aim is to compare an ultrasound-based follow-up with a clinical follow-up. Patients and methods Analysis of two prospectively collected cohorts of melanoma patients in stage IB–IIA from two tertiary referral centres in Barcelona (clinical-based follow-up [C-FU]) and Turin (ultrasound-based follow-up [US-FU]). Kaplan–Meier curves were used to evaluate distant metastases-free survival (DMFS), disease-free interval (DFI), nodal metastases-free survival (NMFS) and melanoma-specific survival (MSS). Results A total of 1149 patients in the American Joint Committee on Cancer stage IB and IIA were included in this study, of which 554 subjects (48%) were enrolled for a C-FU, and 595 patients (52%) received a protocolised US-FU. The median age was 53.8 years (interquartile range [IQR] 41.5–65.2) with a median follow-up time of 4.14 years (IQR 1.2–7.6). During follow-up, 69 patients (12.5%) in C-FU and 72 patients (12.1%) in US-FU developed disease progression. Median time to relapse for the first metastatic site was 2.11 years (IQR 1.14–4.04) for skin metastases, 1.32 (IQR 0.57–3.29) for lymph node metastases and 2.84 (IQR 1.32–4.60) for distant metastases. The pattern of progression and the total proportion of metastases were not significantly different ( P = .44) in the two centres. No difference in DFI, DMFS, NMFS and MSS was found between the two cohorts. Conclusion Ultrasound-based follow-up does not increase the survival of melanoma patients in stage IB–IIA. [ABSTRACT FROM AUTHOR]

Background Longitudinal melanonychia might be difficult to differentiate and the use of dermoscopy can be useful for the preoperative evaluation and management decision. Objectives The aim of our study was to investigate clinical and dermoscopic criteria of acquired longitudinal melanonychia in adults to identify the best predictors of melanoma using a multivariate analysis and to explore eventual new dermoscopic criteria for nail melanoma diagnosis. Methods In this retrospective observational study, 82 histopathologically diagnosed, acquired nail pigmented bands were collected and examined. All variables were included in the analysis and examined as possible predictors of nail melanoma. Both univariate and multivariable analyses have been performed. Results Among 82 cases, 25 were diagnosed as nail melanoma and 57 as benign lesions (including 32 melanocytic nevi and 25 benign melanocytic hyperplasia). Melanoma cases were significantly associated with a width of the pigmented band higher than 2/3 of the nail plate, grey and black colours, irregularly pigmented lines, Hutchinson and micro-Hutchinson signs, and nail dystrophy. Granular pigmentation, a newly defined dermoscopic criterion, was found in 40% of melanomas and only in 3.51% of benign lesions. Conclusions Dermoscopic examination of longitudinal melanonychia provides useful information that could help clinicians to improve melanoma recognition. [ABSTRACT FROM AUTHOR]