High Risk Of Melanoma Research Articles

Three-Dimensional Total Body Photography, Digital Dermoscopy, and in vivo Reflectance Confocal Microscopy for Follow-Up Assessments of High-Risk Patients for Melanoma: A Prospective, Controlled Study.

The combination of total body photography (TBP) and digital dermoscopy (DD) for monitoring patients with a high risk for melanoma can allow early detection of melanoma. This study aimed to examine if the use of three-dimensional (3D)-TBP, DD, and reflectance confocal microscopy (RCM) for regular monitoring of patients at high risk for melanoma was beneficial in comparison to monitoring using dermoscopy alone. The intervention group (IG) underwent 3D-TBP examinations at every visit, along with DD and/or RCM for diagnosis and/or monitoring of pigmented lesions if necessary. The control group (CG) underwent dermoscopy examinations alone. A total of 600 patients (324 male and 276 female) were followed up over a median period of 23 months (mean, 2.85 visits) in the IG and 22 months (mean, 2.74 visits) in the CG (p = 0.009). DD and RCM monitoring were performed for 166 and 105 lesions, respectively. The number needed to treat (NNT) to diagnose melanoma with RCM was 2.83. The IG included more second primary melanomas (22 vs. 1, p = 0.022) and more excised nevi (186 vs. 10, p < 0.001), which consisted of more dysplastic nevi (137 vs. 2, p < 0.001). Among the melanomas diagnosed in the IG, three were diagnosed directly with RCM, nine with a combination of 3D-TBP and RCM, and 10 with dermoscopy alone. Follow-up assessments with a combination of 3D-TBP, DD, and RCM led to the detection of more melanomas in comparison to the CG. The use of RCM reduced the NNT for melanocytic lesions.

Goldfinger: A case of metal tattooing mimicking recurrent melanoma.

Metal tattooing can be a clinical mimic of melanoma of which dermatologists should be aware. Metal tattoos can vary in size and shape depending on the causative injury, usually they are blue, grey or black in colour. We report the case of a 73-year-old patient diagnosed with a nodular subungal melanoma on his middle left finger. Six months following his amputation he attended dermatology follow-up and was noted to have multiple blue-grey cutaneous macules measuring 1-2mm in size proximal to the amputation scar. While a careful occupational history, in this case, suggested the source of the dermal blue grey deposits around the scar, it remains important to confirm histologically especially in patients at high risk of recurrent melanoma.

Changes in the incidence of melanoma in Australia, 2006-2021, by age group and ancestry: a modelling study.

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. 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. Australia, 2006-2021. 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. 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. 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.

50709 Sun protective behaviors among patients at higher risk for melanoma

50709 Sun protective behaviors among patients at higher risk for melanoma

Multiple Onychopapillomas and BAP1 Tumor Predisposition Syndrome

BRCA1-associated protein (BAP1) tumor predisposition syndrome (TPDS) is a cancer genodermatosis associated with high risk of uveal and cutaneous melanoma, basal cell carcinoma, and multiple internal malignant neoplasms, including mesothelioma and renal cell carcinoma. Early detection of the syndrome is important for cancer surveillance and genetic counseling of family members who are at risk. To determine the prevalence of nail abnormalities in individuals with pathogenic germline variants in BAP1. In this prospective cohort study, individuals who were known carriers of pathogenic BAP1 germline variants were consecutively enrolled between October 10, 2023, and March 15, 2024. Dermatologic evaluation for nail abnormalities was performed, including a history of nail abnormalities and associated symptoms, physical examination, medical photography, and nail biopsy for histopathology. This was a single-center study conducted at the National Institutes of Health Clinical Center. Primary outcomes were the prevalence and spectrum of nail changes and histopathologic characterization. Among 47 participants (30 female [63.8%]; mean [SD] age, 46.4 [15.1] years) ranging in age from 13 to 72 years from 35 families, nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis. Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%]). This study found that BAP1 TPDS was associated with a high rate of nail abnormalities consistent with onychopapillomas in adult carriers of the disease. Findings suggest that this novel cutaneous sign may facilitate detection of the syndrome in family members who are at risk and patients with cancers associated with BAP1 given that multiple onychopapillomas are uncommon in the general population and may be a distinct clue to the presence of a pathogenic germline variant in the BAP1 gene.

Can we manage the melanocytic lesions with peripheral globules according to the grade of dysplasia?

Although excision of melanocytic nevi with high-grade dysplasia is recommended by the World Health Organization (WHO), clinical studies investigating the approach based on the grading dysplasia of melanocytic lesions with peripheral globules (PGs) are lacking. We investigated the grades of dysplasia and their distinguishable dermoscopic and clinical features to provide accurate data for managing these lesions. We retrospectively classified histologically confirmed melanocytic lesions with PGs according to the 2018 WHO Classification of Skin Tumours criteria in a university hospital in Turkey. Dermoscopic features, lesions, and patient characteristics were recorded. Sixty-six lesions of 56 patients were included. After classification, 9.1% (n: 6) of lesions were melanomas, 39.4% (n: 26) were high-grade dysplastic nevi, and 50% (n: 33) were low-grade dysplastic nevi (n: 33, 50%). There was one nevus with no dysplasia (n: 1, 1.5%). Univariate analysis revealed that ≥31 years of age, irregular shape of peripheral globules, black colour, total colour count, and maximum diameter of the lesion were associated with high-grade dysplasia and melanoma. In the multivariate analyses, ≥31 years of age (OR = 3.80, 95% CI, 1.17-12.37), irregular shape of peripheral globules (OR = 3.90, 95% CI, 1.15-13.2), and total colour count (OR = 3.21, 95% CI, 1.2-8.5) were significant predictive factors for the lesions with high-grade dysplasia and melanomas. To avoid the underdiagnosis of both melanomas and high-grade dysplastic nevi with PGs, the irregular shape of peripheral globules and multiple colours after the third decade may be useful in making an excision decision. The risk increases every 1-year increase in age. Excision is suggested for all melanocytic lesions with PGs for patients 60 years or older because of the high risk of melanoma and melanocytic nevus with high-grade dysplasia.

Melanoma-associated melanocortin 1 receptor variants confer redox signaling-dependent protection against oxidative DNA damage

Cutaneous melanoma, a lethal skin cancer, arises from malignant transformation of melanocytes. Solar ultraviolet radiation (UVR) is a major environmental risk factor for melanoma since its interaction with the skin generates DNA damage, either directly or indirectly via oxidative stress. Pheomelanin pigments exacerbate oxidative stress in melanocytes by UVR-dependent and independent mechanisms. Thus, oxidative stress is considered to contribute to melanomagenesis, particularly in people with pheomelanic pigmentation. The melanocortin 1 receptor gene (MC1R) is a major melanoma susceptibility gene. Frequent MC1R variants (varMC1R) associated with fair skin and red or yellow hair color display hypomorphic signaling to the cAMP pathway and are associated with higher melanoma risk. This association is thought to be due to production of photosensitizing pheomelanins as well as deficient induction of DNA damage repair downstream of varMC1R. However, the data on modulation of oxidative DNA damage repair by MC1R remain scarce. We recently demonstrated that varMC1R accelerates clearance of reactive oxygen species (ROS)-induced DNA strand breaks in an AKT-dependent manner. Here we show that varMC1R also protects against ROS-dependent formation of 8-oxodG, the most frequent oxidative DNA lesion. Since the base excision repair (BER) pathway mediates clearance of these DNA lesions, we analyzed induction of BER enzymes in human melanoma cells of varMC1R genotype. Agonist-mediated activation of both wildtype (wtMC1R) and varMC1R significantly induced OGG and APE-1/Ref1, the rate-limiting BER enzymes responsible for repair of 8-oxodG. Moreover, we found that NADPH oxidase (NOX)-dependent generation of ROS was responsible for AKT activation and oxidative DNA damage repair downstream of varMC1R. These observations provide a better understanding of the functional properties of melanoma-associated MC1R alleles and may be useful for the rational development of strategies to correct defective varMC1R responses for efficient photoprotection and melanoma prevention in fair-skinned individuals.

Preliminary analysis of the melanoma multimedia educational program for general practitioners on behalf of the Italian Melanoma Intergroup.

According to the National Oncological Plan 2023-2027 on the importance of multidisciplinary and interactive e-learning training, the Italian Melanoma Intergroup (IMI) has developed MelaMEd (Melanoma Multimedia Education), a national project for general practitioners (GPs) on the prevention and detection of cutaneous melanoma through an online platform and an online course. MelaMEd enables participants to i) recognize skin lesions that require specialist dermatological assessment, ii) select patients at high risk of melanoma and iii) be informed of the diagnosis and treatment pathway of patients with melanoma. A free online platform and online course were developed and launched in June 2022. Before starting the course, enrolled participants fill out a pre-training questionnaire concerning the basic knowledge of the disease and the recognition and management of suspicious lesions. After the course, participants will fill out the same questionnaire again. The online course will end in December 2023. Here we present a preliminary analysis of the pre-training results (January 2023-July 2023). The data have been analyzed descriptively. So far, five healthcare centers have participated in the project for a total of 1320 participants. Of these, 298 compiled the pre-training questionnaire. Forty-seven percent of them were aged <40 years. Respondents were almost divided between GPs (47%) and resident GPs (48%). Among the theoretical questions, the ABCDE rule and ugly duckling sign are well known (96% and 91% of correct answers, respectively), but a lower percentage (68%) of respondents knows the EFG rule for the recognition of nodular melanomas and the statement of Breslow thickness (29%). Regarding the series of clinical images of pigmented skin lesions and their management, the percentages rate of accuracy varied from 33% to 87%: melanoma (5 cases) ranges from 36% to 71%, melanocytic nevi (3 cases) from 33% to 84%, whereas the percentages rate of referral for dermatological evaluation varied from 44% to 99%. Melanoma cases referred to dermatologist ranges from 67% to 99%. This preliminary analysis on pre-train-ing questionnaire mainly showed a lack of knowledge of the two major points of melanoma diagnosis (EFG) and management (Breslow thickness), as well as a low rate of participants. We will compare the proportions of correct answers to the questionnaires before and after the course once available.

Comparison of the efficacy of skin examination using 3D total body photography to clinical and dermoscopic examination

BackgroundNon-melanoma skin cancer (NMSC) is the most common malignant tumor that poses a worldwide problem for health services. Three-dimensional total body photography (3D-TBP) is currently used as an adjunct to skin examination, particularly to monitor melanocytic lesions in patients at high risk of melanoma. ObjectivesThe authors investigate the efficacy and limitations of a skin examination for NMSC performed solely with 3D-TBP without patient contact. Methods130 patients with 167 skin lesions with suspected NMSC underwent skin examination with dermoscopy and subsequent surgery. In addition, a 3D-TBP was performed, which was subsequently assessed by an independent dermatologist and compared with the initial skin examination and histological findings. ResultsUsing 3D-TBP, a significantly lower sensitivity for the diagnosis of BCC (0.44 vs 0.77), a lower sensitivity for SCC (0.70 vs 0.78; p=0.754) and a significantly lower sensitivity for invasive skin tumors overall (0.66 vs 0.88; p<0.001) was achieved compared to clinical skin examination with dermoscopy. The location of the skin tumor did not influence the effectiveness of 3D-TBP. More advanced skin tumors with a greater tumor thickness (p<0001) or a higher infiltration level were detected more frequently with 3D-TBP (p=0.001). ConclusionThe results of this study show that 3D-TBP alone is inferior to traditional skin examination with dermoscopy. However, more advanced NMSCs were more likely being detected with 3D-TBP. Further studies need to investigate whether the effectiveness of 3D-TBP alone can be improved by using additional photographs of poorly visible areas of the body or digital dermoscopy.

Clinician’s Ability to Identify Non-Melanoma Skin Cancer on 3D-Total Body Photography Sectors that Were Initially Identified during In-Person Skin Examination with Dermoscopy

Introduction: Non-melanoma skin cancer (NMSC) is a cause of significant morbidity and mortality in high-risk individuals. Total body photography (TBP) is currently used to monitor melanocytic lesions in patients with high risk for melanoma. The authors examined if three-dimensional (3D)-TBP could be useful for diagnosis of NMSC. Methods: Patients (n = 129; 52 female, 77 male) with lesions suspicious for NMSC who had not yet had a biopsy underwent clinical examination followed by examination of each lesion with 3D-TBP Vectra^®WB360 (Canfield Scientific, Parsippany, NJ, USA) and dermoscopy. Results: The 129 patients had a total of 182 lesions. Histological examination was performed for 158 lesions; the diagnoses included basal cell carcinoma (BCC; n = 107), squamous cell carcinoma (SCC; n = 27), in-situ SCC (n = 15). Lesions were located in the head/neck region (n = 138), trunk (n = 21), and limbs (n = 23). Of the 182 lesions examined, 12 were not visible on 3D-TBP; reasons for not being visible included location under hair and on septal of nose. Two lesions appeared only as erythema in 3D-TBP but were clearly identifiable on conventional photographs. Sensitivity of 3D-TBP was lower than that of dermoscopy for BCC (73% vs. 79%, p = 0.327), higher for SCC (81% vs. 74%, p = 0.727), and lower for in-situ SCC (0% vs. 33%, p = 125). Specificity of 3D-TBP was lower than that of dermoscopy for BCC (77% vs. 82%, 0.581), lower for SCC (75% vs. 84%, p = 0.063), and higher for in-situ SCC (97% vs. 94%, p = 0.344). Diagnostic accuracy of 3D-TBP was lower than that of dermoscopy for BCC (75% vs. 80%), lower for SCC (76% vs. 82%), and lower for in-situ SCC (88% vs. 89%). Lesion location was not associated with diagnostic confidence in dermoscopy (p = 0.152) or 3D-TBP (p = 0.353). If only lesions with high confidence were included in the calculation, diagnostic accuracy increased for BCC (n = 27; sensitivity 85%, specificity 85%, diagnostic accuracy 85%), SCC (n = 10; sensitivity 90%, specificity 80%, diagnostic accuracy 83%), and for in-situ SCC (n = 2; sensitivity 0%, specificity 100%, diagnostic accuracy 95%). Conclusion: Diagnostic accuracy appears to be slightly lower for 3D-TBP in comparison to dermoscopy. However, there is no statistically significant difference in the sensitivity and specificity of 3D-TBP and dermoscopy for NMSC. Diagnostic accuracy increases, if only lesions with high confidence are included in the calculation. Further studies are necessary to determine if 3D-TBP can improve management of NMSC.

Facial naevus count in the identification of patients at higher risk of melanoma.

A high total body naevus count (TBNC) is a major risk factor for melanoma. The aim of our study was to investigate the correlation between the number of facial naevi and TBNC, and how the patient variables could influence this association. Our findings suggest that facial naevus count is a fast, easy and economical tool to identify individuals with a high TBNC and may be useful as screening method for physicians in all medical fields.

BG02 A case of Werner syndrome: undiagnosed progeroid syndrome presenting as female pattern hair loss

Abstract A 27-year-old woman of Pakistani heritage with a background of type 2 diabetes, hypertension, hypothyroidism, infertility and Achilles tendinopathy was referred to the dermatology department for diffuse hair loss. She had greying of the scalp hair from the age of 20 years and, on examination, there were signs of hair fragility and thinning. Biopsies showed female pattern hair loss. Topical minoxidil 5% twice daily was advised. At the consultation, it was noted that her facial features included a thin nose with micrognathia. She had dental implants and had undergone cataract surgery at 19 years of age. Scleroderma-like changes were noted on the face and over the distal joints, alongside axillary freckling and excessive lentigines for her age and skin type. She was of short stature and low weight, with a body mass index (BMI) of 15.4 kg m–2. There was thenar and hypothenar wasting and loss of gluteal fat. Her parents were consanguineous (first cousins). One of her brothers, who had similar facial features, died aged 30 years from osteosarcoma. The patient and her partner had undergone two unsuccessful cycles of in vitro fertilization following 5 years of failure to conceive naturally. Medication consisted of atorvastatin, Calcichew, levothyroxine, lisinopril, metformin, pioglitazone and repaglinide. Routine bloods and hormone profile were normal. Despite her age, BMI and statin treatment, blood lipids were raised and a liver ultrasound showed fatty changes. The dermatology department queried Werner syndrome and referral to a tertiary lipodystrophy clinic was made. The lipodystrophy genetic panel was completed. Homozygous null mutation at the WRN locus was found confirming a diagnosis of Werner syndrome. Werner syndrome is an extremely rare autosomal recessive form of progeroid syndrome first described by Otto Werner in 1904. The hallmark sign is the striking disproportion between the patient’s age and appearance. WRN encodes the eponymous WRN protein, a member of the RecQ-like DNA helicase family. The prognosis is unfavourable, with a mean survival of 54 years. Primary causes of mortality are cardiovascular disease and malignancy, with melanoma, thyroid cancer, osteosarcoma and soft tissue sarcoma being the most common forms. There is currently no specific treatment. Management is close multidisciplinary monitoring and treatment of associated conditions. A 2010 study of the Werner syndrome mouse model found vitamin C supplementation to be beneficial (Massip L, Garand C, Paquet ER et al. Vitamin C restores healthy aging in a mouse model for Werner syndrome. FASEB J 2010; 24:158–72). As the condition results in excess damage on ultraviolet exposure and a high risk of melanoma, as well as nonmelanoma skin cancers, an annual dermatology skin check is required.

A higher risk for melanoma in patients with Parkinson’s disease: Based on the results from National Health and Nutrition Examination Survey 2001 – 2004

The relationship between Parkinson&amp;rsquo;s disease (PD) and melanoma has been controversial. The present study used data from the 2001 &amp;ndash; 2004 National Health and Nutrition Examination Survey database. This study included individuals aged &amp;ge;20 years with complete data on PD and melanoma, in which 48 participants were comorbid with the melanoma group, and 5774 were not. Both univariate and multivariate logistic regression analyses were conducted to investigate the connection. There was a higher proportion of PD in the melanoma group than in the non-melanoma group (2.45% vs. 0.30%). Univariate logistic regression analysis revealed that individuals with PD had an 8.32-fold higher risk of developing melanoma than those without PD. In addition, PD was significantly correlated with melanoma (OR, 8.747; 95% CI, 1.264 &amp;ndash; 60.506; p = 0.030) after controlling for covariates in multivariate analysis. In conclusion, our research indicates a significant correlation between PD and melanoma in American adults.

Acceptability of a Hypothetical Reduction in Routinely Scheduled Clinic Visits Among Patients With History of a Localized Melanoma (MEL-SELF): Pilot Randomized Clinical Trial.

After treatment for a localized melanoma, patients attend routinely scheduled clinics to monitor for new primary or recurrent melanoma. Patient-led surveillance (skin self-examination with patient-performed teledermoscopy) is an alternative model of follow-up that could replace some routinely scheduled visits. This study aims to assess the acceptability of a hypothetical reduction in routinely scheduled visits among participants of the Melanoma Self Surveillance (MEL-SELF) pilot randomized clinical trial of patient-led surveillance (intervention) versus usual care (control). Patients previously treated for localized melanoma in New South Wales who were participating in the MEL-SELF pilot randomized clinical trial were asked to respond to a web-based questionnaire at baseline and after 6 months on trial. We used mixed methods to analyze the data. The main outcome of interest was the acceptability of a hypothetical reduction in routinely scheduled visits for melanoma surveillance. Of 100 randomized participants, 87 answered the questionnaire at baseline, 66 answered the questionnaire at 6 months, and 79 provided a free-text explanation at either time point. At 6 months, 33% (17/51) of the control group and 35% (17/49) of the intervention group indicated that a hypothetical reduction in routinely scheduled visits with all melanoma doctors was at least slightly acceptable (difference in proportions -1%, 95% CI -20% to 17%; P=.89). Participants suggested that prerequisites for a reduction in routinely scheduled visits would include that sufficient time had elapsed since the previous diagnosis without a new primary melanoma or recurrence, an unscheduled appointment could be made at short notice if the patient noticed something concerning, their melanoma doctor had suggested reducing their clinic visit frequency, and patients had confidence that patient-led surveillance was a safe and effective alternative. Participants suggested that a reduction in routinely scheduled visits would not be acceptable where they perceived a very high risk of new or recurrent melanoma, low self-efficacy in skin self-examination and in the use of technologies for the patient-led surveillance intervention, and where they had a preference for clinician-led surveillance. Some patients said that a partial reduction to once a year may be acceptable. Some patients may be receptive to a reduction in routinely scheduled visits if they are assured that patient-led surveillance is safe and effective. Australian New Zealand Clinical Trials Registry ACTRN12616001716459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371865&isReview=true; ClinicalTrials.gov NCT03581188; https://clinicaltrials.gov/ct2/show/NCT03581188. RR2-10.1001/jamadermatol.2021.4704.

Sun exposure and associated risks: Insight from an international survey with a focus on the population with past medical history of skin cancers.

e21575 Background: This survey investigates knowledge and behaviors regarding sun exposure among population who have been treated for skin cancer (melanoma/non melanoma) or pre-cancerous lesions in 17 countries. Methods: The survey (N = 17,001) was conducted online in 17 countries (5 continents) from 28 September-18 October 2021. Automated selection from the Ipsos online Panel ensured samples of 1,000 individuals in each country fit the quotas method based on gender, age, employment status, and country regions. Data covered demographics, phototype, exposure habits and practices, knowledge and understanding of risks. The current focus in this abstract was defined as individuals with a history of melanoma/non melanoma skin cancer, pre-cancerous lesions. Results: This sub population represents 8% of the general population (n = 1372), it comprised 54% men, average age was 49.9 years (SD:17.6) and 58% were of phototype 1-2. 90% were aware of sun-related skin-health issues (vs 88% in the general population). 79% did know that sun protection is useful when the weather is overcast, a better knowledge compared to the general population (61%). However, 34% indicated it was safe to expose themselves without protection when already tanned, a larger misconception compared to the general population (23%). 54% did not understand the difference between UVA and UVB vs 70% in the general population. Only 28% systematically/often use all protections measures during exposure; still a higher practice compared to the general population (12%). However, 42% said they protected from the sun all year round, a better habit compared to the general population (23%). During sun exposure, among the 91% who declared using sunscreen, 74% applied sunscreen only once or twice a day, a similar practice among general population (74%). And when already tanned 38% decreased frequency of application and/or used lower protection (44% among general population). 82% regretted not having previously used better protection, a much stronger regret compared to the general population (57%). Conclusions: Although individuals who have been treated for skin cancer or pre-cancerous lesions had better knowledge and behavioral attitudes compared to the general population, this survey shows that even a population at high risk of melanoma and having a regular medical follow-up does not sufficiently perceive the importance of photoprotection in a prevention objective. This leads to discuss the implementation of new information tools with more impact.

Study protocol for a randomised controlled trial to evaluate the use of melanoma surveillance photography to the Improve early detection of MelanomA in ultra-hiGh and high-risk patiEnts (the IMAGE trial)

IntroductionMelanoma surveillance photography (MSP) is a comprehensive surveillance method that comprises two- or three-dimensional total body photography with tagged digital dermoscopy, performed at prescribed intervals. It has the potential to reduce unnecessary biopsies and enhance early detection of melanoma, but it is not yet standard care for all high-risk patients in Australia. This protocol describes a randomised controlled trial (RCT) designed to evaluate the clinical impact and cost-effectiveness of using MSP for the surveillance of individuals at ultra-high or high risk of melanoma from a health system perspective.Methods and designThis is a registry-based, unblinded, multi-site, parallel-arm RCT that will be conducted over 3 years. We aim to recruit 580 participants from three Australian states: Victoria, New South Wales and Queensland, via state cancer registries or direct referral from clinicians. Eligible participants within 24 months of a primary cutaneous melanoma diagnosis will be randomised 1:1 to receive either MSP in addition to their routine clinical surveillance (intervention group) or routine clinical surveillance without MSP (control group). Most participants will continue surveillance with their usual care provider, and the frequency of follow-up visits in both groups will depend on the stage of their primary melanoma and risk factors. The primary outcome measure of the study is the number of unnecessary biopsies (i.e. false positives, being cases where a lesion is biopsied due to suspected melanoma on clinical examination, either with or without MSP, but the resulting histopathology finding is negative for melanoma). Secondary outcomes include the evaluation of health economic outcomes, quality of life and patient acceptability. Two sub-studies will explore the benefit of MSP in high-risk patients prior to a melanoma diagnosis and the diagnostic performance of MSP in the teledermatology setting compared to the en face clinical setting.DiscussionThis trial will determine the clinical efficacy, cost-effectiveness and affordability of MSP to facilitate policy decision-making at the national and local levels, across primary and specialist care.Trial registrationClinicalTrials.gov NCT04385732. Registered on May 13, 2020.

Tranexamic acid use is not associated with the risk of melanoma in Danish women: A nested case-control study using Danish health registries

BackgroundRepurposing already approved drugs in a cancer setting has gained increasing interest in recent years. Tranexamic acid is an anti-fibrinolytic drug that has recently been suggested as an anti-cancer drug due to its anti-inflammatory and anti-carcinogenic effects in animal studies. In this study, we aimed to investigate the possible melanoma-preventive role of tranexamic acid in Danish women. MethodIn this nested case-control study, we identified female cases 18–60 years with first-time melanoma during 2000–2015 and age-matched them with 10 female controls. The odds ratio (OR) of melanoma with tranexamic acid ever- or high use (≥ 100,000 mg) was estimated using conditional logistic regression. ResultsA total of 7986 women with incident melanoma were eligible for study inclusion and were matched to 79,860 controls. Most exposed cases and controls were exposed to low cumulative doses of tranexamic acid corresponding to around 5 days of continuous treatment (1000 mg 3 times daily) for the presumed main indication, i.e., menorrhagia.The crude OR associating tranexamic ever use with melanoma was 1.04 (95% CI 0.98–1.11, p = 0.20), and the adjusted OR was 1.03 (0.97–1.10, p = 0.32). We found no dose-response pattern or effect measure modification by age, histologic type, localization, or clinical stage. However, prolonged use with cumulative doses of tranexamic acid (≥ 100,000 mg) was associated with an increased risk of melanoma (adjusted OR 1.23,95 %, CI 0.96–1.56), compared with non-use. ConclusionWe found no association between tranexamic acid use and the risk of melanoma in Danish women. This could be explained by underlying dose- or biological factors, and sporadic use patterns. A higher risk of melanoma was seen among prolonged users which could be due to surveillance bias.

Solute Carrier Family 45 Member 2 Germline Variants in the Colombian Population with Melanoma

Background: The solute carrier family 45-member 2 (SLC45A2) gene, located on chromosome 5p13.2, is involved in melanin biosynthesis. Single-nucleotide variants (SNVs) in this gene are associated with skin, eye, and hair color variations in the population. SNVs p.L374F (C/T) and p.E272K (C/G) are additionally associated with protection against melanoma. Objectives: This study aimed to evaluate the association of SNVs p.L374F and p.E272K with the development of melanoma in a sample of individuals from Bogotá, Colombia. Methods: In this case-control study, DNA samples were obtained from individuals after signing an informed consent form. Genotyping was performed by real-time polymerase chain reaction high-resolution melting (PCR-HRM). Results: Phototype II was found in 19% of the subjects, phototype III in 70%, and phototype IV in 11%. Eighty percent of the subjects had brown eyes and dark brown hair color. Both SNVs were in Hardy-Weinberg equilibrium. The p.Glu272Lys variant was found to be a protective factor for melanoma, while the p.Phe374Leu variant was found to be a risk factor. The study also found that a CG haplotype was a risk factor for melanoma [odds ratio (OR), 2.75; 95% CI, 1.22 - 6.22; P = 0.021]. The study also found a strong correlation between variants and phototypes, as well as the sex of the patients. The study also analyzed the impact of these variants on the protein structure and found that the p.Phe374Leu variant has a probable pathogenic effect on the function of the protein. Conclusions: The frequencies found for the SLC45A2 gene variants are consistent with other studies conducted in the Latin American population, where the predominant phototypes are II and III. The CG haplotype is associated with a higher risk of melanoma.

Melanoma on tattoos: a case study and review of the literature

Decorative tattooing is a very widespread and constantly increasing practice, especially among young people. Here, we report a case study of melanoma occurring on a tattoo on the left arm and provide an overview of all cases reported so far. A systematic literature search of publications was conducted from inception to September 2021 via Medline (PubMed), Scopus and Google Scholar, in order to identify all cases of primitive melanomas arising on tattoos. In total, 35 cases (32 males, three females) of melanoma arising on tattoos on skin were identified. Interestingly, most melanomas occurred on dark blue (10/35), black (12/35) or blue tattoos (3/35). Due to the low number of melanoma cases arising on tattoos, it is not possible to confirm whether tattoos play a cancerogenic role. However, tattooing may make it more difficult to detect and monitor pigmented lesions, potentially delaying the diagnosis of cutaneous malignancies. Patients at high risk of melanoma should be warned about the risks associated with such procedures.

Cutaneous Melanoma: Sheep in Wolves Clothing?

Cutaneous melanoma incidence in European-origin populations has risen steeply, however, mortality has not, as 73 years of Danish cancer data strikingly show. It has been suggested that such divergent trends in the US are due to overdiagnosis from increasing diagnostic scrutiny and lowering diagnostic threshold. Alternatively, the increase in melanoma incidence may be largely due to increased sun exposure, which would imply that most of these new, sun-caused, melanomas are non-lethal. Consistent with this hypothesis, Icelandic data show an increase in melanoma incidence, predominantly in young women (<50 years), which paralleled increasing sunbed use that remitted after a campaign against sunbeds. Meanwhile, melanoma mortality in young people remained virtually zero. The increase in mortality was mainly in the elderly (>50 years) and dictated by year of birth. This transient excess of melanoma in young people is most likely attributable to skin burns from sunbeds which, like sunburns, carry a high risk of melanoma. High exposure of naevi to UV radiation can induce transient clinical and pathological features of melanoma, which might explain some of the apparent rise in incidence. Ways of distinguishing non-lethal from potentially lethal thin melanomas are sorely needed.