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Unraveling the multidimensional complexities of melanoma has required concerted efforts by dedicated community of researchers and clinicians battling against this deadly form of skin cancer. Remarkable advances have been made in the realm of epidemiology, classification, diagnosis, and therapy of melanoma. The treatment of advanced melanomas has entered the golden era as targeted personalized therapies have emerged that have significantly altered the mortality rate. A paradigm shift in the approach to melanoma classification, diagnosis, prognosis, and staging is underway, fueled by discoveries of genetic alterations in melanocytic neoplasms. A morphologic clinicopathologic classification of melanoma is expected to be replaced by a more precise molecular based one. As validated, convenient, and cost-effective molecular-based tests emerge, molecular diagnostics will play a greater role in the clinical and histologic diagnosis of melanoma. Artificial intelligence augmented clinical and histologic diagnosis of melanoma is expected to make the process more streamlined and efficient. A more accurate model of prognosis and staging of melanoma is emerging based on molecular understanding melanoma. This contribution summarizes the recent advances in melanoma epidemiology, classification, diagnosis, and prognosis.

Introduction/Objective. Epidemiology of melanoma including the number of new cases and mortality have been established in most developed countries, but data on pathohistological features are mostly missing. The objective of the study was to investigate epidemiological, clinical, and pathohistological features of melanoma patients and compare the results with trends in other countries. Methods. Our sample comprised patients surgically treated for skin melanoma at the Hospital for Burns, Plastic and Reconstructive Surgery during the 2015–2017 period. Pathohistological, clinical, and demographic features of melanoma were studied. Results. The retrospective study comprised 201 patients (109 men and 92 women) aged 25–87 years. Melanoma was more common in men than in women (54.2% vs. 45.8%). Melanoma in male population most commonly presented on the trunk, while in females presentation on the trunk and lower extremities was almost equal. Superficial spreading melanoma was the most common type of melanoma (68.7%), without correlation to the sex. No correlation was observed in relation to the stage of the disease and the patient’s sex (p = 0.294). A statistical difference was observed in relation to the type of melanoma and the Breslow classification (p < 0.001). Breslow’s thickness correlated with neither age nor sex. In relation to tumor invasiveness, 12.4% of the lesions were classified as in situ lesions, while 87.6% of the lesions were invasive. The majority of patients were identified as stage pT1a. Conclusion. This study can help to identify patients at high risk for melanoma and contribute to optimize screening efforts in a defined target population.

Background: Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America., Methods: This 56-year (1967-2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long-term incidence of malignant cutaneous neoplasms in Mexican RTRs., Results: Over 56 years, 1642 RTRs (58% male) were studied. Median follow-up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5-7.9), with an incidence density rate of 6.5 (95% CI: 5.4-7.9) per 1000 person-years and a median latency of 9.8 years. Incidence increased with longer transplantation-related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6-9.1) for any skin cancer and 7.5 (95% CI: 3.8-14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer-related mortality rate of 2.7%. Limitations of the study include its single-center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure., Conclusions: Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non-White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs., (© 2024 the International Society of Dermatology.)

Most recent studies on the coronavirus disease 2019 (COVID-19) pandemic and cutaneous melanoma (CM) focused more on delayed diagnosis or advanced presentation. We aimed to ascertain mortality trends of CM between 2012 and 2022, focusing on the effects of the COVID-19 pandemic. In this serial population-based study, the National Vital Statistics System dataset was queried for mortality data. Excess CM-related mortality rates were estimated by calculating the difference between observed and projected mortality rates during the pandemic. Totally there were 108,853 CM-associated deaths in 2012-2022. CM-associated mortality saw a declining trend from 2012 to 2019 overall. However, it increased sharply in 2020 (ASMR 3.73 per 100,000 persons, 5.95% excess mortality), and remained high in 2021 and 2022, with the ASMRs of 3.82 and 3.81, corresponding to 11.17% and 13.20% excess mortality, respectively. The nonmetro areas had the most pronounced rise in mortality with 12.20% excess death in 2020, 15.33% in 2021 and 20.52% in 2022, corresponding to a 4-6 times excess mortality risk compared to large metro areas during the pandemic. The elderly had the most pronounced rise in mortality, but the mortality in the younger population was reduced., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy., Design: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration., Results: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < .001 and 95% CI 2.81-11.47, P < .001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = .001 and 95% CI 1.76-141.00, P = .014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = .046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis., Conclusions: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Copper is an essential trace element obtained from food. There is a paucity of observational or prospective studies that have investigated the relationship between copper and melanoma risk. Copper serves as a cofactor for pivotal enzymes involved in mitochondrial respiration, antioxidant defense, and neurotransmitter synthesis. Undoubtedly, copper plays an indispensable role in the initiation and progression of tumors, particularly melanoma; however, further investigations are warranted to elucidate the underlying mechanisms linking copper and melanoma risk. Given the availability of dietary copper and serum copper data in the NHANES database, we conducted an investigation into the association between dietary copper intake and serum copper levels with melanoma risk. We enrolled 26,401 individuals with dietary copper data in the 2007-2018 NHANES database. To mitigate confounding variables, a propensity score matching (PSM) was performed. To assess the association between dietary copper intake and melanoma risk, we employed a multivariate logistic regression analysis before and after PSM. The restricted cubic spline analysis was utilized to determine whether there is a non-linear relationship between dietary copper intake and melanoma risk, with subgroup analysis conducted to determine beneficiaries. Then, those with blood copper data from the enrolled population with dietary copper intake were screened out, and subsequently, multivariate logistic regression models were subsequently constructed to investigate the association between serum copper levels and melanoma risk after PSM. Mendelian analysis was further utilized to validate the results of the NHANES database using serum copper as the exposure factor and melanoma as the outcome variable. The study found that melanoma risk was associated with dietary copper intake before and after PSM, demonstrated by multiple logistic regression. The relationship between dietary copper intake and melanoma risk was non-linear, with a reduced risk observed above approximately 2.5 mg/day, as shown by the RCS. The evidence suggests that an increased intake of copper is linked to a decreased risk of melanoma. To clarify the mechanism behind the increased risk of melanoma due to higher dietary copper intake, we analyzed the population data from the NHANES database on serum copper and dietary copper intake. Our results indicated that there is no causal relationship between serum copper and melanoma risk. Mendelian randomization analysis of multi-database data sources confirmed the conclusion of the NHANES database analysis. Dietary copper is a protective factor against melanoma, and serum copper or blood copper is not associated with melanoma risk. This suggests that serum or blood copper is not responsible for the protective effect of dietary copper intake on melanoma risk, and the mechanisms need to be further investigated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Observational studies have indicated that inflammatory bowel disease (IBD) patients have higher incidence of skin carcinoma (SC), including melanoma skin carcinoma (MSC) and nonmelanoma skin carcinoma (NMSC) than healthy people. However, whether there is a causal relationship between the 2 is unclear. The purpose of this study was to evaluate the causality of IBD on SC using the Mendelian randomization (MR) analysis. We performed a two-sample MR analysis using publicly available genome-wide association study data. Eligible instrumental variables were selected based on the 3 core assumptions of MR analysis. The inverse-variance weighted (IVW) approach served as the primary analytical method. Supplementary analyses were conducted using MR-Egger regression, the weighted median, the weighted mode, and MR pleiotropy residual sum and outlier methods. Genetically predicted IBD (IVW odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.02-1.13, P = .011) and ulcerative colitis (UC; IVW OR = 1.09, 95% CI: 1.03-1.16, P = .003) were associated with an increased risk of MSC. Results of complementary methods were consistent with those of the IVW method with the exception of the weighted mode. In addition, Crohn disease (CD; IVW OR = 1.04, 95% CI: 0.99-1.08, P = .128) did not have a causal effect on MSC. Moreover, IBD (IVW OR = 1.03, 95% CI: 1.00-1.07, P = .034) and CD (IVW OR = 1.03, 95% CI: 1.00-1.06, P = .045) were associated with an increased risk of NMSC. However, UC (IVW OR = 1.00, 95% CI: 0.97-1.04, P = .803) was not significantly associated with an increased risk of NMSC. Our study revealed genetically predicted associations between IBD and the risks of MSC and NMSC in European populations. Furthermore, UC was associated with an increased risk of MSC, while CD was associated with a higher risk of NMSC. However, the potential influence of immunosuppressive agents or biologics cannot be excluded., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Previous studies on the associations between socioeconomic status (SES) and cutaneous malignant melanoma (CMM) failed to distinguish the effects of different SES factors under an individual-data-based prospective study design., Methods: Based on UK Biobank (UKB) and China Kadoorie Biobank (CKB), we estimated the effects of four SES factors on transitions from baseline to CMM in situ, subsequently to invasive CMM and further CMM mortality by applying multistate models. We further explored to which extent the associations between SES and CMM incidence could be explained by potential mediators including sun exposure, lifestyle and ageing in UKB., Results: In multistate analyses, good household income was independently associated with an increased risk of CMM in situ (HR=1.38, 95% CI: 1.21 to 1.58) and invasive CMM (HR=1.34, 95% CI: 1.22 to 1.48) in UKB. These findings were partly validated in CKB. Especially in UKB, we observed an increased risk of CMM in situ and invasive CMM among participants with good type of house; only good education was independently associated with lower risk of evolving to invasive CMM among patients with CMM in situ (HR=0.69, 95% CI: 0.52 to 0.92); only good household income was independently associated with lower risk of CMM mortality among patients with CMM (HR=0.65, 95% CI: 0.45 to 0.95). In mediation analysis, the proportions attributable to the mediating effect were <6% for all selected variables, including self-reported sun exposure-related factors., Conclusion: SES factors have different effects on the incidence and progression of CMM. The association between SES and incident CMM is neither causal nor well explained by selected mediators., Competing Interests: Competing interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. This research has been conducted using the China Kadoorie Biobank (CKB) resource (www.ckbiobank.org, Request No. DAR-2023-00149). Publication of results does not require or imply approval by the membership of the CKB Collaborative Group., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Aluminium industry workers are at risk of long-term health consequences., Aims: To investigate mortality and cancer incidence in bauxite mine and alumina refinery workers., Methods: A pre-existing cohort of workers was re-linked with the Australian National Death Index, and the Australian Cancer Database to provide additional death (7 years) and cancer (9 years) data. Standardized mortality ratios (SMRs) and standardized incidence rates (SIRs) were estimated by job category, duration of employment and time since first employment., Results: Linkage was performed for 6935 (6207 male) workers. Compared with the general population, there was a reduced or similar risk of death for mine/refinery workers for all causes except mesothelioma which was increased amongst male production workers [SMR 2.42, 95% CI 1.11-4.60]. Mesothelioma incidence was also increased amongst males [SIR 2.50, 95% CI 1.60-3.71]. Male office workers had a greater incidence of prostate cancer [SIR 1.30, 95% CI 1.06-1.57] and thyroid cancer [SIR 3.47, 95% CI 1.66-6.38]. Melanoma incidence was increased in female office workers [SIR 2.27, 95% CI 1.36-3.54]. Lip cancer incidence was increased in male maintenance/production workers [SIR 2.04, 95% CI 1.02-3.65]. Overall cancer incidence was otherwise similar to the general Australian population., Conclusions: Overall risk of death and incidence of cancer for bauxite mine and alumina refinery workers was similar to the general population. Incidence and risk of death from mesothelioma were higher, likely due to historic asbestos exposure in this and other industries. The increased risk of melanoma, lip, prostate and thyroid cancers requires further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Occupational Medicine.)

Melanoma is the most commonly fatal type of skin cancer, and it is an important and growing public health problem in the United States and worldwide. Fortunately, incidence rates are decreasing in young people, stabilizing in middle-aged people, and increasing in older individuals. Herein, the authors further describe trends in melanoma incidence and mortality, review the literature on risk factors, and provide an up-to-date assessment of population-wide screening and new technology being utilized in melanoma screening., Competing Interests: Disclosure The authors have nothing to disclosure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced., Methods: All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR)., Results: A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only - 0.01%. The 5-year overall survival (OS) and relative survival (RS) were 24.5 and 32.4%, respectively. Relative survival did not increase over time. The addition of adjuvant radiotherapy to surgery was not associated with a higher OS and RS compared to surgery alone., Conclusion: Sinonasal mucosal melanoma is a rare disease with stable incidence rates in the Netherlands between 2001 and 2021. There has been no improvement in survival over the course of the inclusion period. The study reaffirms that adjuvant radiotherapy does not seem to improve patient outcomes. Given the generally poor outcomes for SNMM patients, novel therapeutic options ought to be considered in order to improve care., (© 2024. The Author(s).)

Background: Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high-income countries and it features peculiar clinicopathological traits. Very few studies have addressed the quality of care and the costs for adolescents and young adults (AYA) population., Objective: To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost-of-illness and the diagnostic-therapeutic performance indicators by patient age category., Methods: This population-based cohort study included 2435 incident CMM (age range 15-65 years; age 15-39 = 394; age 40-65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's-V tested the strength of association between pairs of variables. The Kaplan-Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper-Pearson exact method., Results: In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low-stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004)., Conclusions: In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients., (© 2024 European Academy of Dermatology and Venereology.)

Background: The French healthcare system has been affected by the COVID-19 pandemic in 2020, including cancer care., Methods: In order to evaluate the impact of this pandemic on cancer incidence, the Isere Departmental Cancer Registry compared the actual 2020 incidence of melanoma, breast, colorectal, prostate and lung cancers with the expected 2020 incidence based on data collected by the Registry between 2015 and 2019, taking into account periods of lockdown and reopening. When available, cancer stages and/or prognostic scores were recorded., Results: During the period of initial confinement, a 54%, 50% and 36,8% drop in incidence was observed for breast, prostate and colorectal cancer respectively. Although their annual incidence remained stable, a worsening trend emerged as a decline in the number of low stages/scores at diagnosis in favour of higher stages/scores towards the end of 2020. In contrast, a significant 17,8% drop was observed in annual incidence of melanoma, particularly for Breslow scores < 1 (-27,4%). However, this trend was noticeable before the lockdown, as well as the 14% reduction in the incidence of lung cancer in women, but not in men., Conclusion: The incidence of certain cancers was caught up over the year but the COVID-19 pandemic seems to be associated with a change in their severity at diagnosis throughout 2020. The downward trends in female lung cancer and melanoma incidence point to complex underlying phenomena. Further analysis is still needed to assess the global impact of the COVID-19 pandemic on cancer incidence., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: The location of cutaneous melanoma is associated with photoexposure., Objectives: To retrospectively analyze changes in the location of cutaneous melanoma over the past 30 years., Patients and Methods: All patients treated at our hospital for cutaneous melanoma from 1988 through 2017 were prospectively collected. Data obtained in cases diagnosed from 1988 through June 2006 were compared to those diagnosed from July 2006 through 2017., Results: A total of 1,937 patients (876 men and 1061 women; median age, 57 years; interquartile range 27) were diagnosed with primary cutaneous melanoma. The location of melanoma was head and neck (470 cases), trunk (745 cases), upper limbs (239 cases), and lower limbs (483 cases). From July 2006 through 2017 we detected an increase in the incidence of head and neck melanomas (19.9% vs 28.6%, p <0.001). A drop in the incidence of melanomas located in the lower extremities was also seen in women (39.8% vs 30.4%, p <0.001), and in the trunk men (57.5% vs 47.3%, p=0.003). In the multivariate analyses, only the decrease in melanomas located in lower extremities in women remained significant., Conclusion: The increased incidence of head and neck melanomas in both sexes and the decrease in trunk melanomas in men can be attributed to the aging of our population. The reduction in the incidence of melanomas in the lower extremities in women could be associated with changes in photoexposure patterns. Analyzing the factors possibly associated with these changes would contribute to better understanding the pathogenesis of cutaneous melanoma for prevention purposes., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Conflicts of interest Dr Hawryluk discloses unrelated conflicts of Apogee (advisory board), UpToDate (author/reviewer-honorarium), Skin Analytics (consultant, ended 2023). Authors Ugwu and Weiss have no conflicts of interest or financial disclosures.

Purpose: This study performed a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationships of C-reactive protein and 41 inflammatory regulators with melanoma, including data from UK Biobank, Cardiovascular Risk in Young Finns Study, and Cohorts for Inflammation Work Group., Methods: We selected the inverse variance weighting (IVW) to merge the estimated causal effects of multiple SNPs into a weighted average. To evaluate the heterogeneities of IVW, the Cochran Q statistic, and I 2 index were used. What's more, several sensitivity analyses were employed, including IVW, MR-Egger, weighted median, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO)., Results: With SNPs reaching P < 5 × 10 -8 , the analyses findings revealed that IL-16 had a significant positively association with genetically risk of melanoma (OR IVW : 1.05; 95% CI: 1.03-1.07; P < 0.001), and high levels of MCP1 (OR IVW : 1.13; 95% CI: 1.03-1.23; P = 0.01) were suggestively associated with melanoma susceptibility. What's more, TNF-β (OR IVW : 1.07; 95% CI: 1.01-1.13; P = 0.02) and IL-8 (OR IVW : 1.08, 95% CI: 1.01-1.16; P = 0.03) were demonstrated a positive association with the risk of melanoma under a less stringent cut-off (P < 5 × 10 -6 ). Conversely, we found a facilitative effect of melanoma susceptibility on IP-10 and inhibitory effects on IL-6, IL-1b, and GRO-α., Conclusion: The genetic evidence that we have uncovered indicates a potential association between the levels of specific inflammatory markers (IL-16, IL-8, MCP-1, and TNF-β) and the risk of melanoma. Further research is imperative to translate these findings into clinical applications., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The location of cutaneous melanoma is associated with photoexposure., Objectives: To retrospectively analyze changes in the location of cutaneous melanoma over the past 30 years., Patients and Methods: All patients treated at our hospital for cutaneous melanoma from 1988 through 2017 were prospectively collected. Data obtained in cases diagnosed from 1988 through June 2006 were compared to those diagnosed from July 2006 through 2017., Results: A total of 1,937 patients (876 men and 1061 women; median age, 57 years; interquartile range 27) were diagnosed with primary cutaneous melanoma. The location of melanoma was head and neck (470 cases), trunk (745 cases), upper limbs (239 cases), and lower limbs (483 cases). From July 2006 through 2017 we detected an increase in the incidence of head and neck melanomas (19.9% vs 28.6%, p <0.001). A drop in the incidence of melanomas located in the lower extremities was also seen in women (39.8% vs 30.4%, p <0.001), and in the trunk men (57.5% vs 47.3%, p=0.003). In the multivariate analyses, only the decrease in melanomas located in lower extremities in women remained significant., Conclusion: The increased incidence of head and neck melanomas in both sexes and the decrease in trunk melanomas in men can be attributed to the aging of our population. The reduction in the incidence of melanomas in the lower extremities in women could be associated with changes in photoexposure patterns. Analyzing the factors possibly associated with these changes would contribute to better understanding the pathogenesis of cutaneous melanoma for prevention purposes., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Background: There is a growing trend to include non-randomised studies of interventions (NRSIs) in rare events meta-analyses of randomised controlled trials (RCTs) to complement the evidence from the latter. An important consideration when combining RCTs and NRSIs is how to address potential bias and down-weighting of NRSIs in the pooled estimates. The aim of this study is to explore the use of a power prior approach in a Bayesian framework for integrating RCTs and NRSIs to assess the effect of rare events., Methods: We proposed a method of specifying the down-weighting factor based on judgments of the relative magnitude (no information, and low, moderate, serious and critical risk of bias) of the overall risk of bias for each NRSI using the ROBINS-I tool. The methods were illustrated using two meta-analyses, with particular interest in the risk of diabetic ketoacidosis (DKA) in patients using sodium/glucose cotransporter-2 (SGLT-2) inhibitors compared with active comparators, and the association between low-dose methotrexate exposure and melanoma., Results: No significant results were observed for these two analyses when the data from RCTs only were pooled (risk of DKA: OR = 0.82, 95% confidence interval (CI): 0.25-2.69; risk of melanoma: OR = 1.94, 95%CI: 0.72-5.27). When RCTs and NRSIs were directly combined without distinction in the same meta-analysis, both meta-analyses showed significant results (risk of DKA: OR = 1.50, 95%CI: 1.11-2.03; risk of melanoma: OR = 1.16, 95%CI: 1.08-1.24). Using Bayesian analysis to account for NRSI bias, there was a 90% probability of an increased risk of DKA in users receiving SGLT-2 inhibitors and an 91% probability of an increased risk of melanoma in patients using low-dose methotrexate., Conclusions: Our study showed that including NRSIs in a meta-analysis of RCTs for rare events could increase the certainty and comprehensiveness of the evidence. The estimates obtained from NRSIs are generally considered to be biased, and the possible influence of NRSIs on the certainty of the combined evidence needs to be carefully investigated., (© 2024. The Author(s).)

Cataract is a leading cause of blindness worldwide, necessitating a deeper understanding of its risk factors. We analyzed two cohorts: 1000 individuals from the general Swedish population and 933 patients who received plaque brachytherapy for uveal melanoma. Using Kaplan-Meier and cumulative incidence analyses, as well as Cox and competing risk regressions, we assessed whether there is a relationship between sex and cataract surgery. In the general population, female sex was a significant risk factor for cataract surgery, with a 10-year incidence of 16% compared to 10% for males (subdistribution hazard ratio adjusted for age, 1.35, P < 0.001). In the brachytherapy cohort, female sex was not associated with an increased incidence of cataract surgery, with a 10-year incidence of 25% versus 23% for males (HR 1.08, P = 0.61). Visual acuity at the time of cataract surgery did not significantly differ between sexes in either cohort, suggesting that differences in surgery rates are not due to health-seeking behavior or surgery assessment thresholds. These findings indicate that female sex is associated with a higher risk of cataract surgery in the general population, but not among those treated with plaque brachytherapy for uveal melanoma., (© 2024. The Author(s).)

Background and Objectives : The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods : We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results : In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p < 0.001) compared to HCV-negative patients. TriNetX data analysis revealed that HCV-positive patients had a 53% lower risk of developing melanoma (RR = 0.470, 95% CI: 0.443-0.498, p < 0.001). However, HCV-positive melanoma patients had higher all-cause mortality (HR = 1.360, 95% CI: 1.189-1.556, p < 0.001). An in silico analysis identified key molecular players, including IL-6 and CTLA4, in the HCV-melanoma network. Conclusions : While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.

The prognosis of patients with mycosis fungoides is variable. As the current literature is scarce and shows mixed results this study investigates the incidence of other primary malignancies in mycosis fungoides patients. A retrospective, nationwide, population- based cohort study was performed with patients with mycosis fungoides between 2000 and 2020 in The Netherlands. All histopathology reports were requested from the Nationwide Network and Registry of Histo- and Cytopathology and screened for other primary malignancies. Lifelong incidence rates were used to compare the incidence of malignancies in mycosis fungoides patients and the general population. In total 1,024 patients were included with a mean follow-up of 10 years (SD 6). A total of 294 cases of other primary malignancies were found with 29% of the mycosis fungoides patients developing at least 1 other primary malignancy. Only cutaneous (odds ratio [OR] 2.54; CI 2.0-3.2) and haematological malignancies (OR 2.62; CI 2.00-3.42) had a statistically significant higher incidence than the Dutch population overall. Mycosis fungoides patients have a significantly increased risk of developing melanomas (OR 2.76; CI 2.11-3.59) and cutaneous squamous cell carcinomas mycosis fungoides (OR 2.34; CI 1.58-3.45). This study shows no association between mycosis fungoides and other solid organ tumours; however, such patients are significantly at risk of developing other haematological and cutaneous malignancies. Clinicians should be aware of this increased risk.

Melanoma is a malignant tumor with the highest growth rate in the incidence and is the leading cause of death due to skin cancers. In Poland, approximately 1500 cases of melanoma are detected annually in advanced or metastatic stages. Intensive preventive measures can contribute to its early-stage diagnosis, consequently reducing the number of fatalities. The aim of the study was to assess the occurrence of melanoma risk factors among the residents of Silesia region and their knowledge about the diagnosis and prevention of this cancer. An original questionnaire was used in the study, and its completion was anonymous. The study was conducted among the residents of the Silesian Voivodeship. A total of 400 (100%) individuals were examined. Among them were 243 women and 157 men. The participants' ages ranged from 16 to 84 years (mean age = 34.38 ± 18.39). The participants were burdened with melanoma development risk factors such as fair skin complexion (235; 58.75%), having more than 50 pigmented lesions (158; 39.50%) and sunburns (105; 26.25%). Over 40% (166; 41.50%) of the participants had never examined their pigmented lesions. A staggering 78% (311; 77.75%) of the respondents had never undergone dermatoscopic examination, and over 50% (215; 53.75%) did not know what this examination entailed. Just under 16% (63; 15.75%) of the participants stated that their family doctor had examined their pigmented lesions, and almost % (154; 97.47%) of those with numerous pigmented lesions had never been referred to a dermatologist for dermatoscopy. The surveyed residents of the Silesian Voivodeship were burdened with numerous risk factors for melanoma development, with the most common being fair skin complexion, having more than 50 pigmented lesions, and sunburns. The knowledge of the participants regarding the diagnosis and prevention of melanoma development was insufficient, thus highlighting the necessity for conducting systematic educational initiatives in the mentioned field. These initiatives should ultimately lead to the preservation of health and life, as well as the maintenance of its high quality., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Monitoring melanoma incidence time trends by tumour thickness is essential to understanding the evolution of melanoma occurrence and guiding prevention strategies. To assess long-term incidence trends, tumour thickness was extracted from pathology reports in the Cancer Registry of Norway (1983-2007) and the Norwegian Melanoma Registry (2008-2019), n = 45,635 patients. Across all anatomic sites, T1 (≤ 1 mm) incidence increased most (men annual percentage change [AAPC] = 4.6, 95% confidence interval [95% CI] 4.2-5.0; women AAPC = 3.2, 95% CI 2.8-3.6); the increase was steep until 1989/90, followed by a plateau, and a further steep increase from 2004/05. Increased incidence was also observed for T2 (>1.0-2.0) melanoma (men AAPC = 2.8, 95% CI 2.4-3.2; women AAPC = 1.5, 95% CI 1.1-1.9), and T3 (>2.0-4.0) in men (AAPC = 1.4, 95% CI 0.9-1.9). T4 (>4.0) melanoma followed a similar overall pattern (men AAPC = 1.3, 95% CI 0.9-1.7, head/neck, upper limbs, and trunk; women AAPC = 0.9, 95% CI 0.4-1.4, upper limbs and trunk). Men had the highest T3 and T4 incidence and the sex difference increased with age. Regarding birth cohorts, age-specific incidence increased in all T categories in the oldest age groups, while stabilizing in younger patients born after 1950. Overall, the steep increase in T1 melanoma was not accompanied by a decrease in thick melanoma.

Objectives: To estimate the incidence of melanoma in Australia among people with ancestries associated with low, moderate, or high risk of melanoma, by sex and 5-year age group; to establish whether age-specific incidence rates by ancestry risk group have changed over time., Study Design: Modelling study; United States (SEER database) melanoma incidence rates for representative ancestral populations and Australian census data (2006, 2011, 2016, 2021) used to estimate Australian melanoma incidence rates by ancestry-based risk., Setting, Participants: Australia, 2006-2021., Main Outcome Measures: Age-specific invasive melanoma incidence rates, and average annual percentage change (AAPC) in age-specific melanoma rates, by ancestry-based risk group, sex, and 5-year age group., Results: The proportion of people in Australia who reported high risk (European) ancestry declined from 85.3% in 2006 to 71.1% in 2021. The estimated age-standardised melanoma incidence rate was higher for people with high risk ancestry (2021: males, 82.2 [95% confidence interval {CI}, 80.5-83.8] cases per 100 000 population; females, 58.5 [95% CI, 57.0-59.9] cases per 100 000 population) than for all Australians (males, 67.8 [95% CI, 66.5-69.2] cases per 100 000 population; females, 45.4 [95% CI, 44.3-46.5] cases per 100 000 population). AAPCs were consistently positive for Australians aged 50 years or older, both overall and for people with high risk ancestry, but were statistically significant only for some age groups beyond 65 years. AAPCs were negative for people aged 34 years or younger, but were generally not statistically significant., Conclusions: Melanoma incidence has declined in some younger age groups in Australia, including among people with high risk ancestry. Social and behavioural changes over the same period that lead to lower levels of ultraviolet radiation exposure probably contributed to these changes., (© 2024 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Purpose: To evaluate the clinical features and prognosis of conjunctival melanoma in Japanese patients., Study Design: Retrospective observational case series., Methods: Twenty patients (8 men and 12 women) diagnosed with conjunctival melanoma at a singlehospital between 2003 and 2017 were analyzed. Data on clinical presentation, sex, age, the affected eye, tumor location, tumor origin, tumor stage according to the American Joint Committee on Cancer staging system (eighth edition), treatment, outcomes, local recurrence, metastasis, and survival were extracted from the patients' medical records and reviewed., Results: The mean age at diagnosis was 64.2 ± 14.8 years. Tumor locations at the first examination included the bulbar conjunctiva (n = 19), plica (n = 13), and fornix (n = 12). The tumor stage was T1 in 5 cases (25%), T2 in 12 cases (60%), T3 in 3 cases (15%), and T4 in none. The mean follow-up duration was 91.7 ± 46.0 months. The local recurrence rates at 1, 5, and 10 years were 5.0%, 18.8%, and 31.5%, respectively, whilst the metastasis rates were 5.0%, 25.6%, and 32.4%, respectively. Four of the 6 patients who experienced metastasis died; duration from metastasis to death was 17.5 months (range, 7-25). The 5-year survival rate for conjunctival melanoma was 78.8%. Tumor thickness was significantly associated with survival duration on univariate Cox regression analyses., Conclusion: The mortality rate for conjunctival melanoma in the Japanese population was lower and higher than that reported in the Chinese and United States populations, respectively. Tumor thickness was a prognostic factor for survival in patients with conjunctival melanoma., (© 2024. Japanese Ophthalmological Society.)

The study of the increasing incidence of melanoma over the past few decades is essential regarding prevention and optimization of health resources. We collected cases of melanoma from Hospital son Llàtzer from the Migjorn health sector of Mallorca, Spain from 2003 through 2021, and calculated the incidence of melanoma adjusted to the standard European population. In addition, other demographic and clinicopathological data were descriptively analyzed too. A total of 690 new cases of melanoma were detected with a progressive increase in the age-standardized incidence from 7.47 cases per 100,000 inhabitants/year in 2003 up to 23.84 in 2021 mainly due to early stages of the disease. The incidence of melanoma has increased significantly in Mallorca probably due to the increasing population coming from northern Europe (low phototypes), sun exposure habits (tourism, fishing, agriculture), and improved early diagnosis., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The mortality-to-incidence ratio (MIR) can be used to approximate healthcare inequities and is helpful to understand/compare cancer survival between geographic regions/jurisdictions. We investigated cutaneous melanoma (CM) outcomes through MIR analysis in Canadian jurisdictions and census divisions (CDs) between 1992 and 2016., Methods: Data were obtained from the national databases from 1992 to 2016 for all Canadian jurisdictions, except Quebec. Age-standardized overall and median MIRs were calculated per province per year, while crude MIRs were calculated for CDs. Generalized linear regression models were conducted to study the effect of province and year on MIR, while a mixed effect regression model was used to determine how healthcare and socioeconomic factors affect MIR, while accounting for possible clustering effects (eg, year and province)., Results: We identified 106,015 CM cases and 20,570 CM deaths between 1992 and 2016. National MIR from 1992 to 2016 demonstrated a significant linear decrease ( P value < .0001). The national median MIR was 15.4 (ie, 0.154 × 100), whereby Manitoba (19.9), Ontario (19.5), Saskatchewan (18.5), British Columbia (16.1), and Newfoundland and Labrador (15.9) demonstrated higher MIRs than the Canadian average. CDs with the highest MIRs were commonly identified in the southern regions of provinces. No healthcare or socioeconomic factors were found to be significantly associated with higher MIR at the provincial level., Conclusion: MIRs have decreased at the national and provincial levels in recent decades, which is reassuring. Higher MIRs were noted in select rural CDs and in the Canadian territories, reinforcing the importance of proper dermatological care in all parts of the country., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The worldwide incidence of melanoma has increased in the last 40 years. Our aim was to describe the clinic-pathological characteristics and outcomes of three cohorts of patients diagnosed with melanoma in a Latin-American cancer institute during the last 20 years., Methods: We evaluated three retrospective patient cohorts diagnosed with melanoma at Instituto Nacional de Enfermedades Neoplasicas (INEN), a public hospital in Lima, Peru, for the years 2005-2006, 2010-2011, and 2017-2018. Survival rate differences were assessed using the Log-rank test., Results: Overall, 584 patients were included (only trunk and extremities); 51% were male, the mean age was 61 (3-97) years, and 48% of patients resided in rural areas. The mean time to diagnosis was 22.6 months, and the mean Breslow thickness was 7.4 mm (T4). Lower extremity was the most common location (72%). A majority of the patients (55%) had metastases at the time of presentation, with 36% in stage III and 19% in stage IV. Cohorts were distributed as 2005-2006 (n = 171), 2010-2011 (n = 223), and 2017-2018 (n = 190). No immunotherapy was used. Cohort C exhibited the most significant increase in stage IV diagnoses (12.3%, 15.7%, 28.4%, respectively; p < 0.01). The median overall survival rates at the three-year follow-up demonstrated a decline over the years for stages II (97%, 98%, 57%, respectively; p < 0.05) and III (66%, 77%, 37%; p < 0.01)., Conclusions: There has been a worsening in the incidence of late-stage metastatic melanoma in Peru throughout the years, coupled with a significant decline in overall survival rates. This is underscored by the fact that half of the population lives in regions devoid of oncological access., (© 2024. Society of Surgical Oncology.)

Aim: Oral malignant melanoma (OMM) is a rare and aggressive malignant tumour arising from the proliferation of melanocytes and accounts for only 0.5 % of all oral malignancies. It is invasive and tends to metastasise. The aim of this study is to determine the patient profile of OMM and to provide information about the clinical features and treatment plans of the disease., Materials and Methods: The Pubmed database was searched for OMM cases published as case reports in the last 10 years. The search was limited to English and open-access case reports. A total of 49 OMMs in 45 patients from 43 case reports were analyzed. In addition to the age, gender, smoking and alcohol consumption habits of the patients, data on the signs and symptoms of OMM, location of the lesion, imaging modalities used in diagnosis and treatment, lymph node involvement, presence of metastasis, survival time, and treatment modalities were recorded., Results: In OMM cases, 18 (40 %) of the patients were female, 27 (60 %) were male, and the mean age was 53.13 ± 16.09 years. The most common symptom was "swelling" (n = 23, 33.8 %) and the most common finding was "hyperpigmentation" (n = 40, 24.4 %). The most common site of OMM was the maxilla (n = 21, 46.7 %). According to the rate of use of imaging modalities in the cases, it was determined that "advanced imaging modalities" were mostly used (n = 24, 53.3 %). It was determined that 22.2 % (n = 10) of the patients died within the first 5 years. Combined treatment (n = 21, 46.5 %) were mostly applied to the patients., Conclusion: OMM is more common in the maxilla, in males and in the fifth decade of life, and advanced imaging modalities are most commonly used to detect the disease. Because of its poor prognosis, knowing the patient profile and common clinical features of OMM will increase the clinical awareness of physicians., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: We aimed to develop tools that could predict the occurrence of distant metastases in melanoma and its prognosis based on clinical and pathological characteristics., Materials and Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database of melanoma patients diagnosed between 2010 and 2019. Logistic analyses were performed to identify independent risk factors associated with distant metastasis. Additionally, multivariate Cox analyses were conducted to determine independent prognostic factors for patients with distant metastasis. Two nomograms were established and evaluated with the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Furthermore, we performed a retrospective analysis of melanoma with distant metastasis from our institute between March 2018 and June 2022., Results: Of the total 19 396 melanoma patients, 352 (1.8%) had distant metastases at the time of diagnosis. The following clinical and pathological characteristics were identified as independent risk factors for distant metastasis in melanoma: N stage, tumor size, ulceration, mitosis, primary tumor site, and pathological subtype. Furthermore, tumor size, pathological subtype, and radiotherapy were identified as independent prognostic factors. The results of the training and validation cohorts' ROC curves, calibration, DCA, and Kaplan-Meier survival curves demonstrate the effectiveness of the two nomograms. The retrospective study results from our center supported the results from the SEER database., Conclusion: The clinical and pathological characteristics of melanoma can predict a patient's risk of metastasis and prognosis, and the two nomograms are expected to be effective tools to guide therapy decisions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To update and extend the examination of cancer incidence in a cohort of Danish firefighters, now adding 7 years of follow-up and 2766 additional firefighters. The primary focus was directed toward cancer sites that recently contributed to the hazard evaluation conducted by the International Agency for Research on Cancer (IARC)., Methods: The updated cohort consisted of 11,827 male Danish firefighters who were followed up for cancer from 1968 to 2021. Cohort cancer morbidity was compared with a working population reference group, and standardized incidence ratios (SIR) were used for estimation of relative risks, along with 95% confidence intervals (95% CI)., Results: Among full-time firefighters, SIR of skin melanoma was 1.30 (95% CI: 1.02-1.66), and SIR = 1.37 (95% CI: 1.02-1.85) for over 5 years of employment. Slightly positive associations were also observed for cancer of the urinary bladder (SIR = 1.16; 95% CI: 0.93-1.45), prostate (SIR = 1.11; 95% CI: 0.97-1.28), and testis (SIR = 1.11; 95% CI: 0.75-1.63)., Conclusions: This updated study provides evidence indicating an elevated risk of skin melanoma in firefighters. Consistent with IARC's evaluation, we also identified positive associations for urinary bladder, prostate, and testis cancer. In contrast, our findings did not suggest an increased risk of colon cancer, non-Hodgkin lymphoma, and mesothelioma. The latter may be due to small numbers in our still relatively young cohort. Continuous follow-up for cancer in firefighters is warranted, including assessment of influence from surveillance bias., (© 2024 Wiley Periodicals LLC.)

Background: Melanoma is a highly malignant tumor. Moreover, its prevalence is increasing at a rapid rate year after year. Currently, UV light is the leading cause of melanoma, although numerous other risk factors exist, including arsenic. The link between arsenic and the likelihood of developing melanoma has long been debated. As a result, we conducted a meta-analysis of the available data to investigate the association between arsenic exposure and melanoma., Methods: We identified seven non-randomized controlled studies with 41,949 participants by searching the Chinese CNKI, Embase, PubMed, and Cochrane Library databases. We then used random-effects or fixed-effects models to evaluate the pooled odds ratios (OR) and their 95% confidence intervals (CI). Subgroup analyses were also carried out with different included regions., Results: Participants in the study who were exposed to arsenic had a somewhat higher chance of developing melanoma than those who were not (OR = 1.47, 95% CI 1.01-2.13). A subgroup analysis was also carried out for the US region, and the findings were not statistically significant (OR = 1.40, 95% CI 0.94-2.07)., Conclusion: This meta-analysis shows that arsenic exposure relates to an increased risk of melanoma., (© 2024 the International Society of Dermatology.)

Background: The overall incidence of melanoma has increased steadily for several years. The relative change in incidence at different ages has not been fully described.  Objective: To describe how incidence at different ages has changed over time and to consider what aspects of tumour biology may explain the observed pattern of change in incidence.  Methods: The slope of incidence vs age measures the acceleration of cancer incidence with age. We described the pattern of change over time in the overall incidence of melanoma, as well as in acceleration. We used data for males and females from 3 different countries in the 17 sequential 5-year birth-cohort categories from 1895-99 to 1975-79, from which we derived the incidence patterns.  Results: Over time, there has been a tendency for the overall incidence of melanoma to increase and for the acceleration (slope) of the age-incidence curves to decline. The changing patterns of melanoma incidence and acceleration differ between males and females and between the countries analysed.  Conclusions: The observed pattern in melanoma of rising incidence and declining acceleration occurs in other cancers in response to genetic knockouts of mechanisms that protect against cancer. Perhaps some protective mechanism with respect to melanoma may be less effective now than in the past, possibly because of more intense environmental challenges.

The aim of this study was to explore the epidemiology of cutaneous malignant melanoma (CMM) and the associated risk factors influencing its occurrence and survival among Koreans aged <20 years. In this retrospective cohort investigation, we identified cases of incident melanoma diagnosed in Korean patients aged 0-19 years between 2004 and 2019, utilizing the National Health Insurance database. We assessed annual fluctuations in age-adjusted incidence rates and examined 5-year survival rates based on various factors, including sex, age, income level, sun-exposed sites, and the Charlson Comorbidity Index. Of 1160 patients, 51.4% were male and 48.6% were female. The mean age of the patients was 11 years, mostly belonging to the top 25% high-income group. The head and neck regions were the most frequently affected sites. The overall age-adjusted incidence rate of melanoma was 0.22 per 100,000 persons. This rate witnessed a decline of 4.5% annually from 2004 to 2012, followed by a subsequent increase of 12.6% annually from 2012 to 2019. Notably, patients with CMM in low-sun-exposed sites exhibited poorer survival rates compared with those in high-sun-exposed areas ( P  < 0.05). The incidence of melanomas in children and adolescents in Korea has shown a rising trend since 2012. Further research is needed to investigate the etiology and risk factors in pediatric patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The Greying with age phenotype in horses involves loss of hair pigmentation whereas skin pigmentation is not reduced, and a predisposition to melanoma. The causal mutation was initially reported as a duplication of a 4.6 kb intronic sequence in Syntaxin 17. The speed of greying varies considerably among Grey horses. Here we demonstrate the presence of two different Grey alleles, G2 carrying two tandem copies of the duplicated sequence and G3 carrying three. The latter is by far the most common allele, probably due to strong selection for the striking white phenotype. Our results reveal a remarkable dosage effect where the G3 allele is associated with fast greying and high incidence of melanoma whereas G2 is associated with slow greying and low incidence of melanoma. The copy number expansion transforms a weak enhancer to a strong melanocyte-specific enhancer that underlies hair greying (G2 and G3) and a drastically elevated risk of melanoma (G3 only). Our direct pedigree-based observation of the origin of a G2 allele from a G3 allele by copy number contraction demonstrates the dynamic evolution of this locus and provides the ultimate evidence for causality of the copy number variation of the 4.6 kb intronic sequence., (© 2024. The Author(s).)

Lower extremity nodular melanoma (NM) is a common malignant tumor with a poor prognosis. We aims to identify the prognostic factors and develop a nomogram model to predict overall survival (OS) in patients with lower extremity NM. A total of 746 patients with lower extremity NM were selected and randomly divided into a training set (522 cases) and a validation set (224 cases) from the Surveillance, Epidemiology, and End Results(SEER) database. The training set underwent univariate and multivariate Cox regression analyses to identify independent prognostic factors associated with patient outcomes, and to develop a nomogram model. The effectiveness of the nomogram was subsequently validated using the validation set. Multivariable Cox regression analysis of the training set indicated that age, ulceration, radiotherapy, chemotherapy, primary site of first malignant tumor, and Breslow thickness were independent variables associated with OS. In the training set, the area under the curve (AUC) of the nomogram for predicting 3-year and 5-year OS was 0.796 and 0.811, respectively. In the validation set, the AUC for predicting 3-year and 5-year OS was 0.694 and 0.702, respectively. The Harrell's C-index for the training set and validation set were 0.754 (95% CI: 0.721-0.787) and 0.670 (95% CI: 0.607-0.733), respectively. Calibration curves for both training and validation sets showed good agreement. In this study, we develop and validate a nomogram to predict OS in patients with lower extremity NM. The nomogram demonstrated reasonable reliability and clinical applicability. Nomograms are important tools assessing prognosis and aiding clinical decision-making., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Increasing melanoma incidence with less increasing mortality is observed in several countries. This discrepancy is not well understood., Objectives: In this study, our aim was to discuss factors [ultraviolet radiation (UVR) exposure, melanoma treatment, diagnostic activity, overdiagnosis, pathologists' diagnostic threshold and clinicians' propensity to remove suspect skin lesions] that might influence melanoma incidence and mortality in Denmark., Methods: This was a register study with the number of melanocyte-related lesions and melanoma mortality based on comprehensive national pathology and mortality databases for the period 1999-2019. We investigated melanocyte-related diagnoses and mortality in a population of 5.5 million with a national healthcare system. Age-adjusted melanoma mortality and age-adjusted incidence of benign naevi, atypical lesion, or melanoma in situ and of invasive melanoma were computed for data analysis., Results: In total, 1 434 798 biopsies were taken from 704 682 individuals (65% female). The mean age at biopsy was 39.8 years in males and 37.6 in females. In males and females, the incidence of invasive melanoma increased by 87% during the period 1999-2011. During the subsequent period it increased by 9% in males but remained unchanged in females. The incidence of melanoma in situ increased by 476% in males and 357% in females during the study period, while the increases for atypical melanocytic lesions were 1928% and 1686%, respectively. Biopsy rates increased by 153% in males and 118% in females from 1999 through 2011 but fell by 20% in males and 22% in females during the subsequent period. Mortality varied slightly from year to year without any significant time trend for males or females. We identified no evidence of increased UVR exposure over the latest 30 years in Denmark. Immunotherapy of advanced melanoma was introduced in Denmark in 2010 and came into general use in 2014., Conclusions: Comprehensive national data demonstrate increasing melanoma incidence correlated with increasing biopsy rates, but with no change in mortality. Previously suggested explanations for such a trend are a lowered threshold of melanoma diagnosis among pathologists, increased diagnostic activity in the presence of overdiagnosis and improved melanoma treatment. Because the study is observational and we have more explanatory factors than outcomes, the findings do not warrant conclusions about causal relationships., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Acral melanoma is a clinical subtype of melanoma with high mortality, on which research is limited in scope. This study aimed to assess incidence trends and melanoma-specific survival rates for acral melanoma in the Swedish population from 1990 to 2020.This cross-sectional study included patients with an acral melanoma diagnosis from 1990 to 2020 from the nationwide, population-based Swedish Melanoma Registry. Analyses on acral melanoma melanoma-specific survival rates were adjusted for age, sex, histopathological subtype, and tumour thickness. Clinicopathological features and melanoma-specific survival rates were compared between diagnostic periods: 1990-1999, 2000-2009, and 2010-2020, respectively. Changes in standardized incidence rates in 1996-2020 were evaluated separately for males and females. In total, 1,000 acral melanomas in 999 patients were included in the study. No significant yearly change in standardized incidence rates for either males or females was observed, even though the absolute number of cases increased. Factors such as male sex, age ≥ 70 years, and Breslow thickness > 1.0 were independently linked to lower melanoma-specific survival. The 5-year melanoma-specific survival across the studied period ranged from 75.8% to 77.9% for females, and from 62.4% to 71.7% for males.