Risk Factor For Melanoma Research Articles

Cutaneous Melanoma versus Vulvovaginal Melanoma-Risk Factors, Pathogenesis and Comparison of Immunotherapy Efficacy.

Simple SummaryMelanoma of the vulva and vagina is a relatively rare neoplasm, unlike melanoma of the skin. Its prognosis is poor, and its pathogenesis is not fully understood. Immunotherapy is one of the rapidly developing cancer treatment methods. In this article, we focus on the pathogenesis of lower genital tract melanomas and related risk factors and compare the effectiveness of two groups of drugs—anti-PD-L1 and anti-CTLA4 antibodies—in the treatment of this condition. This type of immunotherapy is a relatively common treatment method for cutaneous melanoma but not for the rare vulvovaginal melanoma. For vulvovaginal melanoma, the effects of these treatments appear to be limited; however, this requires further research. Cutaneous melanoma is a relatively common neoplasm, with fairly well understood pathogenesis, risk factors, prognosis and therapeutic protocols. The incidence of this disease is increasing every year. The situation is different for rare malignancies such as vulvar melanomas and for the even rarer vaginal melanomas. The risk factors for vulvovaginal tumors are not fully understood. The basis of treatment in both cases is surgical resection; however, other types of treatments such as immunotherapy are available. This paper focuses on comparing the pathogenesis and risk factors associated with these neoplasms as well as the efficacy of two groups of drugs—anti-PD-L1 and anti-CTLA4 inhibitors—against both cutaneous melanoma and melanoma of the lower genital tract (vulva and vagina). In the case of cutaneous melanoma, the situation looks more optimistic than for vulvovaginal melanoma, which has a much worse prognosis and, as it turns out, shows a poorer response to immune therapy.

Alcohol as a Non-UV Social-Environmental Risk Factor for Melanoma.

Simple SummaryMalignant melanoma is an aggressive cancer of the skin and the leading cause of death from skin cancer. One major risk factor linked to melanoma development is exposure to UV radiation. However, the sharp increase in melanoma cases cannot be explained only by more UV exposure. Identifying additional modifiable social-environmental risk factors for melanoma beyond UV exposure would greatly impact public health initiatives and the methods of patient outreach and education. Recent studies have shown the link between melanoma and alcohol consumption. This perspective review paper aims to understand the mechanisms underlying ethanol’s ability to induce human cancers, including melanoma.Although cancer mortality has declined among the general population, the incidence of melanoma continues to rise. While identifying high-risk cohorts with genetic risk factors improves public health initiatives and clinical care management, recognizing modifiable risk factors such as social-environmental risk factors would also affect the methods of patient outreach and education. One major modifiable social-environmental risk factor associated with melanoma is ultraviolet (UV) radiation. However, not all forms of melanoma are correlated with sun exposure or occur in sun-exposed areas. Additionally, UV exposure is rarely associated with tumor progression. Another social-environmental factor, pregnancy, does not explain the sharply increased incidence of melanoma. Recent studies have demonstrated that alcohol consumption is positively linked with an increased risk of cancers, including melanoma. This perspective review paper summarizes epidemiological data correlating melanoma incidence with alcohol consumption, describes the biochemical mechanisms of ethanol metabolism, and discusses how ethanol and ethanol metabolites contribute to human cancer, including melanoma.

Association of UV Radiation Exposure, Diagnostic Scrutiny, and Melanoma Incidence in US Counties

Although UV radiation exposure is the conventionally reported risk factor for cutaneous melanoma, an alternative exposure is diagnostic scrutiny: the more physicians look for and biopsy moles, the more melanoma they find. To assess the association of proxies for UV radiation exposure and diagnostic scrutiny with geographical patterns of melanoma incidence. This was a cross-sectional ecological analysis of the 727 continental US counties reporting to the Surveillance, Epidemiology, and End Results (SEER) Program (among a total of 3108 counties). Environmental data relevant to UV radiation exposure (from a variety of sources), Health Resources and Services Administration data relevant to diagnostic scrutiny, and SEER data on melanoma incidence among the non-Hispanic White population diagnosed with melanoma from 2012 through 2016 were combined. Data analysis was performed between January 2020 and July 2022. Three UV radiation proxies (UV daily dose, cloud variability, and temperature variability) and 3 diagnostic scrutiny proxies (median household income, dermatologists, and primary care physician supply). Melanoma incidence (in situ and invasive cancers). In total, 235 333 melanomas were diagnosed. Proxies for UV radiation exposure changed gradually across geography, while melanoma incidence and proxies for diagnostic scrutiny changed abruptly across contiguous counties. The UV daily dose, a variable the National Cancer Institute specifically developed for melanoma analyses, was uncorrelated with incidence (r = 0.03; P = .42). For context, smoking prevalence was highly correlated with lung cancer incidence in the same counties (r = 0.81; P < .001). Melanoma incidence was correlated with median household income (r = 0.43; P < .001). Counties with no dermatologists and shortages of primary care physicians had the lowest incidence, while counties amply supplied with both had the highest, despite having lower mean UV daily dose. There was little association between melanoma incidence and melanoma mortality (r = 0.09; P = .05), while the analogous association in lung cancer was strong (r = 0.96; P < .001). In this cross-sectional ecological study, the current geographical pattern of melanoma incidence across US counties was less associated with proxies for UV radiation exposure and more so with proxies for diagnostic scrutiny. Incidence-the fundamental epidemiologic measure of disease frequency-now had little association with the feared outcome of melanoma: death.

S2623 Metastatic Anorectal Melanoma as a Rare Cause of Hematochezia: A Case Report

Introduction: Anorectal melanoma is a rare and aggressive subtype of gastrointestinal cancer, accounting for 0.5% of all colorectal cancers. Misdiagnosis of anorectal melanoma is common, as cases oftentimes present with nonspecific symptoms including hematochezia. As such, timely and accurate diagnosis of anorectal melanoma is difficult due to its rarity and nonspecific presentation. Consequently, prognosis is poor due to frequent metastasis by the time of diagnosis. Case Description/Methods: A 65-year-old male with a history of basal cell carcinoma of the cheek and tobacco use presented with 10 days of hematochezia associated with dyschezia and change in caliber of stool. The patient was noted to have a 10-pound weight loss since a positive fecal immunochemical test 5 months prior. Notably, while he had not had a colonoscopy, his records revealed a prior sigmoidoscopy for similar complaints 4 years prior. Sigmoidoscopy was negative for polyps or tumors but diagnostic of segmental colitis associated with diverticulosis (SCAD); symptoms resolved after a course of oral mesalamine and antibiotics. Family history was positive for a brother with esophageal cancer. Labs were unremarkable for anemia or liver panel abnormalities. Computed tomography imaging of the abdomen showed sigmoid wall thickening, pelvic lymphadenopathy, and multiple liver lesions. Colonoscopy revealed a 0.8 × 0.5 × 0.1 cm anal mass with biopsies consistent with malignant melanoma; stains were positive for HMB45 and negative for p40 and p63. An ultrasound-guided liver biopsy showed metastatic melanoma positive for HMB45 (Figure 1). Discussion: Hematochezia can arise from anatomical, vascular, inflammatory, and neoplastic etiologies. Although neoplastic causes are the least common, anorectal melanoma represents an especially rare and dismal diagnosis from this category. Risk factors for anorectal melanoma are unknown, although HIV has been previously suggested. HIV screening in our patient was negative. An association between anorectal melanoma and SCAD is unclear. Management of anorectal melanoma is poorly described given the scarcity of the disease but typically consists of surgical resection, although the method and extent of resection is debated. Additionally, the benefit of adjuvant chemotherapy or radiation is unclear. Prognosis of anorectal melanoma is poor, with 5-year survival rates estimated to be no more than 20-30%.Figure 1.: (Left) A 0.8 × 0.5 × 0.1 cm anal mass was detected on colonoscopy. (Top, Right) Biopsy of .the anal mass was positive for immunostain HMB45. (Bottom, Right) Biopsy of the liver mass was positive for immunostain HMB45, suggestive of metastatic anorectal melanoma.

Melanoma-specific survival before and after inclusion in a familialmelanoma dermatologic surveillance program in CDKN2A mutation carriers and non-carriers.

Inherited mutations in the CDKN2A gene are among the strongest known risk factors for cutaneous melanoma. Further, previous studies have reported inferior melanoma-specific survival in CDKN2A mutation carriers. Here, the melanoma-specific survival was studied, depending on CDKN2A carrier status and if the melanomas had been diagnosed before or after families were included in a surveillance program. Melanoma-prone families participating in this study were identified through a nationwide preventive program starting in 1987. Information on melanoma tumours and deaths was obtained through the Swedish Cancer Registry and Cause of Death Registry. Kaplan-Meier and Cox proportional hazards regression models were used to assess melanoma-specific survival in four defined cohorts, CDKN2A mutation (MUT) carriers with first invasive melanoma before or after inclusion [MUT-pre (n=53) and MUT-post (n=43)] and likewise in CDKN2A wild type (WT) cases [WT-pre (n=255) and WT-post (n=122)]. The MUT-pre and MUT-post cases were diagnosed with their first invasive melanoma at a significantly younger ages (38 and 42 years, respectively) than the WT-pre and WT-post cases (48 and 57 years, respectively). The melanomas in the MUT-pre had significantly higher T stage compared with MUT-post (p=0.006), whereas no such difference was seen comparing WT-pre with WT-post (p=0.849). MUT-pre had compared with WT-pre, significantly worse melanoma-specific survival, unadjusted (HR 2.33, 95% CI 1.33-4.08, p=0.003) adjusted (HR 2.70, 95% CI 1.46-5.00, p=0.001). However, the MUT-post cases had compared with the WT-post cases, no significant survival differences. This study is the first to address the impact on survival from introducing a dermatologic surveillance program to familial melanoma cases with or without CDKN2A mutations. The CDKN2A-mut carriers appeared to have a clear benefit with less advanced melanomas diagnosed and better melanoma-specific survival after inclusion. Among the CDKN2A-wt cases, the effect of the inclusion on the studied outcomes was less evident.

The effect of screening on melanoma incidence and biopsy rates.

Cutaneous melanomas are common cancers in white-skinned populations, and early detection is promoted as a means of reducing morbidity and mortality. There is concern that increased skin screening is leading to overdiagnosis of indolent melanomas with low risk of lethality. The extent of melanoma overdiagnosis associated with screening is unknown. To estimate possible overdiagnosis by comparing subsequent melanoma incidence and biopsy rates among people subjected to skin screening those who were not. We recruited 43 762 residents of Queensland, Australia, aged 40-69 years, with no prior history of melanoma, selected at random from a population register in 2010. At baseline, participants completed a comprehensive melanoma risk factor survey and were asked if their skin had been examined by a doctor in the 3 years prior to baseline. We calculated incidence and relative risk of histologically confirmed melanoma (invasive and in situ) in years 2-7 of follow-up, obtained through linkage to the cancer registry. In secondary analyses, we measured biopsy rates in years 2-6 of follow-up. We used propensity score analysis to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). In total, 28 155 participants underwent skin screening prior to baseline. We observed 967 first-incident melanomas (381 invasive) during 197 191 person-years of follow-up. Those screened had higher rates of melanoma (aHR 1·29, 95% CI 1·02-1·63) and subsequent skin biopses (aHR 1·85, 95% CI 1·69-2·04) than unscreened participants. The higher risk associated with skin screening was evident for in situ melanoma (aHR 1·45, 95% CI 1·09-1·92) but not invasive melanoma (aHR 1·05, 95% CI 0·72-1·54). In secondary analyses, where screening was defined as having a skin biopsy in the first year after baseline, we observed significantly increased risks of melanoma (aHR 1·53, 95% CI 1·23-1·89) and subsequent biopsies (aHR 2·64, 95% CI 2·46-2·84) relative to those who did not have a biopsy. People who undergo skin screening subsequently experience higher rates of biopsies and melanoma (especially in situ melanoma), even after adjusting for all known risk factors, consistent with overdiagnosis. What is already known about this topic? Cutaneous melanomas are common cancers in white-skinned populations for which early detection is promoted as a means of reducing morbidity and mortality. There is concern that increased surveillance is leading to the overdiagnosis of indolent melanomas that are not destined to be lethal. The extent of melanoma overdiagnosis associated with surveillance is not known. What does this study add? People subjected to skin examinations by a doctor or who undergo skin biopsies subsequently have higher numbers of biopsies and higher rates of melanoma than people not subjected to either, even after adjusting for all known risk factors. These findings suggest that heightened surveillance leads to a proportion of melanomas being diagnosed that otherwise may not have come to clinical attention.

Body Site Distribution of Acquired Melanocytic Naevi and Associated Characteristics in the General Population of Caucasian Adults: A Scoping Review.

The number of melanocytic naevi is a major risk factor for melanoma. The divergent pathway hypothesis proposes that the propensity for naevus proliferation and malignant transformation may differ by body site and exposure to ultraviolet (UV) radiation. This scoping review aimed to summarise the evidence on the number and distribution of naevi (≥ 2 mm) on the body overall and by individual anatomical sites in Caucasian adults, and to assess whether studies used the International Agency for Research on Cancer (IARC) protocol to guide naevus counting processes. Systematic searches of Embase and PubMed identified 661 potentially relevant studies, and 12 remained eligible after full-text review. Studies varied widely in their counting protocols, reporting of naevus counts overall and by body sites, and used counting personnel with differing qualifications. Only one study used the IARC protocol. Studies reported that the highest number of naevi was on the trunk in males and on the arms in females. Body sites which receive intermittent exposure to UV radiation had higher density of naevi. Larger naevi (≥ 5 mm) were detected mostly on body sites intermittently exposed to UV radiation, and smaller naevi (< 5 mm) on chronically exposed sites. Studies reported that environmental and behavioural aspects related to UV radiation exposure, as well as genetic factors, all impact body site and size distribution of naevi. This review found that to overcome limitations of the current evidence, future studies should use consistent naevus counting protocols. Skin surface imaging could improve the reliability of findings. An updated IARC protocol is required that integrates these emerging standards and technologies to guide reliable and reproducible naevus counting in the future.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00806-x.

Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy.

Although immune checkpoint blockade (ICB) therapies have achieved great progress, the patient response varies among cancers. In this study, we analyzed the potential genomic indicators contributing to ICB therapy response. The results showed that high tumor mutation burden (TMB) failed to predict response in anti-PD1 treated melanoma. SERPINB3 was the most significant response-related gene in melanoma and mutations in either SERPINB3 or PEG3 can serve as an independent risk factor in melanoma. Some recurrent mutations in CSMD3 were only in responders or non-responders, indicating their diverse impacts on patient response. Enrichment scores (ES) of gene mutations in 12 biological pathways were significantly higher in responders or non-responders. Next, the P-TMB calculated from genes in these pathways was significantly related to patient response with prediction AUC 0.74–0.82 in all collected datasets. In conclusion, our work provides new insights into the application of TMB in predicting patient response, which will benefit to immunotherapy research.

Influence of Social and Psychosocial Factors on Summer Vacationers' Sun Protection Behaviors, the PRISME Study, France.

Objectives: Summer intermittent sun exposure is a major risk factor for melanoma. Socioeconomic position, cognitive and psychosocial factors play a role in sun protection behaviors but the underlying mechanisms are unknown. This study aimed to measure the influence of educational level on sun protection behaviors in French summer vacationers on the Mediterranean coastline, and to identify the mediating psychosocial factors in this pathway. Methods: In summer 2019, French vacationers aged 12–55 staying in coastline campsites were asked about their holiday sun protection behaviors, their knowledge, attitudes, perceived control, and social norm relative to sun protection. A structural equation model measured the direct and indirect effects of educational level on protection behaviors via cognitive and psychosocial factors. Results: Sun protection during vacation increased with educational level. Theoretical knowledge partially mediated this association, from 22% to 86%, particularly for intermediate educational levels. Conclusion: Our results highlight the importance of implementing suitable sun prevention interventions for vacationers, especially those with a lower socioeconomic position. Improving theoretical knowledge around sun protection may be an important part of broader efforts to encouraging improved preventive behaviors.

Assessing the effect of environmental and socio-economic factors on skin melanoma incidence: an island-wide spatial study in Gran Canaria (Spain), 2007–2018

IntroductionSkin melanoma incidence has risen in the last decades becoming a major public health problem in many regions of the world. Geographic variation of rates is not well understood.PurposeTo assess the spatial distribution of skin melanoma in Gran Canaria Island (Canary Islands, Spain) and to evaluate the role of environmental, socio-economic, and demographic factors in this distribution.MethodsWe performed a small-area study with disease mapping at the census-tract level (CT) in Gran Canaria between 2007 and 2018. After testing for spatial autocorrelation, we integrated individual-level health data with census-based demographic and socio-economic indicators, and satellite-based environmental data. Finally, we assessed the role of demographic, socio-economic and environmental factors on skin melanoma incidence using a Bayesian analytical framework, with options for non-spatial and spatial random effects.Results1058 patients were diagnosed with invasive skin melanoma in the study period and geolocated to a CT (number of CT in Gran Canaria = 565). We found evidence of global spatial autocorrelation in skin melanoma incidence (Moran’s I = 0.09, pseudo p-value = 0.001). A few hotspots were detected, fundamentally in urban northern tracts. A radial pattern of high values was also observed in selected ravines with historical isolation. Multivariable conditional autoregressive models identified urbanicity, percent of females, and a high socio-economic status as risk factors for disease. Solar radiation did not show a significant role.ConclusionUrbanicity and a high socio-economic status were identified as the main risk factors for skin melanoma. These associations might reflect differential melanoma susceptibilities or be explained by health inequalities in detection. This study also uncovered high-risk areas in particular ravines. Future targeted research in these regions might help better understand the role of genetic and toxic factors in melanoma pathogenesis.

Melanoma risk assessment and management: a qualitative study among Australian GPs

BackgroundPreventive guidelines for melanoma recommend that patients at high risk of melanoma receive targeted screening; however, this requires careful selection of those at high risk. To the authors’ knowledge, there has been no previous research into how all physicians approach the selection and management of high-risk individuals. Melanoma risk-prediction models are available to assist in the identification of high-risk patients but are not routinely used clinically.AimTo examine how GPs assessed and managed melanoma risk, and the opportunities for using melanoma risk-prediction models in primary care.Design and settingSemi-structured telephone interviews were conducted with 20 Australian GPs.MethodGPs who had completed a cross-sectional online questionnaire study on melanoma risk were purposively sampled and recruited. Semi-structured telephone interviews were conducted with Australian GPs between 9 July and 10 September 2019. Interviews were audiorecorded, professionally transcribed, and analysed using grounded theory.ResultsMelanoma risk assessment and its management can be understood as a linear workflow consisting of five clinical process domains with patient selection as the entry point. There was variation between GPs on the identification of melanoma risk factors, melanoma risk estimation, management, and patient education because of intuitive and analytical processes guiding risk assessment, and the influence of patient factors. GPs were largely receptive towards melanoma risk-prediction models, sharing facilitators for and barriers to their potential implementation.ConclusionFurther primary care interventions sensitive to existing workflow arrangements may be required to standardise melanoma risk-assessment and management processes.

Abstract 1122: Selinexor synergizes with IL-12 to inhibit tumor growth in syngeneic mouse models of melanoma

Abstract Background: Melanoma is the most deadly skin cancer and represents 4.6% of all cancers diagnosed within the US (American Cancer Society). Risk factors for melanoma are almost entirely related to pale skin color and sunburns. Selinexor is a clinically approved oral inhibitor of nuclear exportation protein Exportin 1 (XPO1/CRM1). In preclinical studies, selinexor significantly inhibited growth of A375 and CHL-1 human melanoma cell lines in vivo at well tolerated doses (Yang et al. 2014). Interleukin 12 (IL-12) is a cytokine produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells in response to antigenic stimulation. IL-12 drives the differentiation of T-cells into T helper (Th1) cells, in addition to stimulating T-cell and NK cell activity, specifically through the activation of interferon-γ (IFN-γ). IL-12 exerts antitumor activity through IFN-γ-dependent and independent mechanisms, which include modulation of the immune system and anti-angiogenesis (Zhang et al. 2016). The objective of this study was to compare the impact and scheduling of recombinant mouse IL-12 alone and in combination with selinexor on the growth of murine B16F10 melanoma cells grown as subcutaneous tumors in C57B/6 mice. Methods: Sixty, 6-7 weeks old female C57B/6 mice were inoculated subcutaneously in the left flank with 1 x 105 B16F10 cells. Treatment was initiated when the tumors reached a mean volume of 100 mm3 (standard deviation ± 6.3 mm3). Mice were allocated to 6 groups of 10 such that mean tumor volume in each group was within the range of 11.8 to 13.4 mm3, then treated with: oral selinexor (10mg/kg, twice weekly on day 0 and 2) combined with a pre-dose of subcutaneous IL-12 (1µg/kg, once weekly on day -2); selinexor with post-dose IL-12 (1µg/kg, once weekly on day 3); selinexor alone; IL-12 alone (day -2); IL-12 alone (day 3); or vehicle. Animal weight was recorded daily, and tumors were measured 3 days a week to record percent of tumor growth inhibition (%TGI). Results: Both selinexor and IL-12 demonstrated single agent activity against B16F10 tumor in vivo. All treatment groups showed significant tumor growth inhibition as compared to vehicle. The group receiving selinexor with pre-dose IL-12 showed the largest tumor inhibition (%TGI=92%). Significant weight loss compared to vehicle occurred only in the single agent selinexor group (p=0.039). Conclusions: Synergistic anti-cancer activity of selinexor and IL-12 warrants further clinical investigation. Further mechanistic studies to understand the effects of IL-12 priming on increasing the effectiveness of selinexor will be undertaken. Citation Format: Shira Orr, Leah Henegar, Christopher J. Walker, Feng Wang, Trinayan Kashyap, Marie Maloof, Kathleen Martyn, Michael G. Kauffman, Sharon Shacham, Yosef Landesman. Selinexor synergizes with IL-12 to inhibit tumor growth in syngeneic mouse models of melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1122.

Cumulative Erythemal Ultraviolet Radiation and Risk of Cancer in 3 Large US Prospective Cohorts.

Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and noncutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined 3 US prospective cohorts, the Health Professionals Follow-up Study (HPFS) (1986) and Nurses' Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding nonmelanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 men; 212,449 women) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as referent, for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared with the lowest quintile, risk of any cancer was slightly increased across all other quintiles (highest quintile hazard ratio (HR)=1.04, 95% confidence interval (CI): 1.01, 1.07; P for heterogeneity= 0.41). All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR=1.17, 95% CI: 1.04, 1.31; P for heterogeneity= 0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and noncutaneous cancers.

Altitude Effect on Cutaneous Melanoma Epidemiology in the Veneto Region (Northern Italy): A Pilot Study

The incidence of cutaneous melanoma has been increasing in the last decades among the fair-skinned population. Despite its complex and multifactorial etiology, the exposure to ultraviolet radiation (UVR) is the most consistent modifiable risk factor for melanoma. Several factors influence the amount of UVR reaching the Earth’s surface. Our study aimed to explore the relationship between melanoma and altitude in an area with mixed geographic morphology, such as the Veneto region (Italy). We included 2752 melanoma patients who were referred to our centers between 1998 and 2014. Demographics, histological and clinical data, and survival information were extracted from a prospectively maintained local database. Head/neck and acral melanoma were more common in patients from the hills and the mountains, while limb and trunk melanoma were more common in patients living in plain and coastal areas. Breslow thickness, ulceration and mitotic rate impaired with increased altitude. However, the geographical area of origin was not associated with overall or disease-free survival. The geographical area of origin of melanoma patients and the “coast-plain-hill gradient” could help to estimate the influence of different sun exposure and to explain the importance of vitamin D levels in skin-cancer control.

Association between sun-protective behaviors and family history of melanoma: Results from NHANES 2003 to 2004

To the Editor: Family history is an important nonmodifiable risk factor for melanoma present in approximately 8% to 12% of melanoma diagnoses.1 These patients have a 1.7 fold increased risk for developing melanoma compared with patients without affected first-degree relatives.1 In contrast, sun exposure is a significant yet modifiable risk factor for melanoma, which can be reduced by practicing appropriate sun-protective behaviors (SPB).2 Despite the increased melanoma risk associated with a positive family history, there have been limited population-based studies to assess how family history interplays with the propensity for SPB in at-risk individuals.

Attitudes, Barriers, Motivations to Sun Protection in Reunion Island's Schools: Qualitative Study.

The incidence of melanoma in Reunion Island is on the rise and is now one of the highest worldwide. Although the main risk factor of melanoma is sun exposure during childhood, sun protection measures remain insufficient in Reunionese schools. From November 2019 to November 2020, we conducted a qualitative study to explore the attitudes, barriers, and motivations to sun protection among the main actors of children’s protection in Reunion Island. Individual semi-directive interviews were performed with 14 children aged 6 to 10 years, 13 parents, and 13 teachers. The interviews were recorded and transcribed. Relevant data were coded, triangulated, analyzed, and then modeled following the methodology of grounded theory. Sufficiency of the data was sought. All 40 participants described their sun protection habits. Protection was lower during school activities than during leisure activities. Parents identified several practical and financial barriers to sun protection. Teachers pointed out the lack of adequate infrastructure and sun protection training. Responsibility for children’s protection was a point of disagreement between parents and teachers. Children limited their use of protection, mainly for reasons of comfort. Children’s sun protection in schools is the responsibility of educational staff, parents, and society at large. Improving communication between these various actors is necessary. Sun safety campaigns and reorganization of the school environment would allow for better protection of the child population.

Self-Assessment Questionnaire on Patient-Physician Concordance on Nevus Self-Count and Models Development to Predict High-Risk Phenotype >50 Nevi

Background: Cutaneous melanoma accounts for the majority of skin cancer-related deaths. Readily identifiable phenotypic characteristics and total body nevus count (TBNC) >50 are among the most important risk factors for cutaneous melanoma. Implementation of nevus self-count procedures and self-assessment of phenotypic traits as part of skin self-examination could be an excellent screening tool for identifying an at-risk target population. Objectives: Objectives of the study were to assess the skills of a central Italian and eastern Spanish population sample to recognize their skin lesions via the submission of a self-assessment questionnaire and to explore which self-assessment questionnaire item combination best predicts the high-risk condition of TBNC >50. Methods: Patients aged ≥18 years filled a self-assessment questionnaire, autonomously and prior to the dermatological visit. Subsequently, dermatologists performed total body skin examination and reported patients’ skin lesions on a separate questionnaire. Results: We reported fair to moderate patient-dermatologist agreement for skin lesion self-assessment. The item number of nevi on the back was the single questionnaire item most accurately predicting TBNC >50. The high-sensitivity and high-specificity classification and regression tree models for the prediction of TBNC >50 displayed different items combinations; the item nevus on the back was always the first and most important predictor in both our models. Conclusions: Patients were partially able to provide correct estimation of their whole-body nevus self-count. The item nevi on the back seems to be the first and most important predictor of TBNC >50 across our models. Delivery of high-sensitivity and high-specificity prediction models based on our questionnaire item combination may help defining a high-risk target population.

Dendritic cells in reflectance confocal microscopy are a clue for early melanoma diagnosis in extrafacial flat pigmented melanocytic lesions.

Differential diagnosis of extrafacial flat pigmented lesions with dermoscopic reticular and/or homogeneous pattern is challenging. Dendritic cells upon reflectance confocal microscopy (RCM) still represent a pitfall. This study aims to determine the role of dendritic cells upon RCM in the epidermis and dermo‐epidermal junction (DEJ), together with common RCM features for melanoma and nevi, in dermoscopically equivocal extrafacial flat pigmented lesions. A retrospective evaluation of RCM images of melanocytic extrafacial flat pigmented lesions with reticular and/or homogeneous dermoscopic pattern and with histopathological diagnosis, was performed. A multivariate model of RCM features was used to obtain a score of independent risk factors. A total of 698 lesions were included. Increasing patient age, epidermal dendritic cells, many dendritic cells in the DEJ (>30%) and many (>5/mm2) round atypical cells were independent risk factors for melanoma. Edged papillae and melanophages were indicative of nevus. A score based on these features was developed to assist in melanoma differential diagnosis. The RCM observation of abundant (>30%) dendritic cells in the DEJ is highly suggestive of malignity. This independent risk factor should also be considered for improved differential diagnosis of extrafacial melanoma.

Use of the multi-theory model (MTM) in explaining initiation and sustenance of indoor tanning cessation among college students.

Skin cancer, including melanoma, is the most common cancer worldwide and a significant public health concern. A significant risk factor for melanoma is through increased exposure to ultraviolet (UV) radiation through the use of indoor tanning beds. Although rates of indoor tanning bed use have decreased in recent years, young adults, particularly White, college-age women, comprise the majority of indoor tanning bed users in the United States. The purpose of this cross-sectional study was to explore and explain the initiation and sustenance of indoor tanning cessation among college students using the multi-theory model (MTM) of health behavior change. Data were collected from 254 college students who reported current indoor tanning use using a validated 46-item survey to assess demographics and the MTM constructs. Data were analyzed using multiple linear regression to determine the ability of the MTM constructs to predict the initiation and sustenance of indoor tanning cessation. For initiation of indoor tanning cessation, participatory dialogue: advantages (B = 0.038, p = 0.001), behavioral confidence (B = 0.129, p < 0.001) and changes in the physical environment (B = 0.088, p < 0.001) were significantly associated with indoor tanning cessation following covariate adjustment. For sustenance, only emotional transformation (B = 0.140, p < 0.001) demonstrated a significant relationship with indoor tanning cessation, following adjustment. Findings from this study demonstrate the utility of the MTM in explaining indoor tanning cessation and designing intervention strategies and clinical recommendations to encourage indoor tanning cessation among college students.

Ambient UVR and Environmental Arsenic Exposure in Relation to Cutaneous Melanoma in Iowa.

Intermittent sun exposure is the major environmental risk factor for cutaneous melanoma (CM). Cumulative sun exposure and other environmental agents, such as environmental arsenic exposure, have not shown consistent associations. Ambient ultraviolet radiation (UVR) was used to measure individual total sun exposure as this is thought to be less prone to misclassification and recall bias. Data were analyzed from 1096 CM cases and 1033 controls in the Iowa Study of Skin Cancer and Its Causes, a population-based, case-control study. Self-reported residential histories were linked to satellite-derived ambient UVR, spatially derived environmental soil arsenic concentration, and drinking water arsenic concentrations. In men and women, ambient UVR during childhood and adolescence was not associated with CM but was positively associated during adulthood. Lifetime ambient UVR was positively associated with CM in men (OR for highest vs. lowest quartile: 6.09, 95% confidence interval (CI) 2.21–16.8), but this association was not as strong among women (OR for highest vs. lowest quartile: 2.15, 95% CI 0.84–5.54). No association was detected for environmental soil or drinking water arsenic concentrations and CM. Our findings suggest that lifetime and adulthood sun exposures may be important risk factors for CM.