Invasive Cutaneous Melanoma Research Articles

Immunohistochemistry-Assisted Mohs Surgery for Invasive Eyelid and Periorbital Cutaneous Melanoma.

Prior studies describe wide local excision and "slow Mohs" outcomes for periocular melanoma. Mohs micrographic surgery (MMS) with immunohistochemistry maximizes tissue preservation and offers same-day comprehensive margin evaluation, which facilitates expedited repair, and coordination of oculoplastic reconstruction when necessary. To describe oncologic and reconstructive outcomes of invasive periocular cutaneous melanoma treated with immunohistochemistry-assisted MMS. Invasive melanoma cases affecting the eyelids or periorbital region treated with MMS between 2008 and 2018 were reviewed. Eyelid tumors and those in adjacent subunits were compared. Main outcome measures were recurrence, melanoma-specific death, and postreconstructive complications. Of 42 cases, 28 were classified as periorbital and 14 as eyelid involving. Most were T1 (37, 88.1%). There was 1 local recurrence in a patient with persistent positive conjunctival margin (2.4%). No local recurrences were observed in cases where negative Mohs margins were achieved, and no melanoma-related deaths occurred. Eyelid tumors were more likely to result in lid margin involving defects and require oculoplastic reconstruction. Eyelid complications developed in 10 cases (23.8%), and 5 (11.9%) required revision surgery. Mohs micrographic surgery for periocular melanoma results in low rates of local recurrence and melanoma-specific death. Initial tumor location can aid in reconstructive planning.

Socioeconomic disparity in the natural history of cutaneous melanoma: evidence from two large prospective cohorts

BackgroundPrevious 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.MethodsBased on...

Association of rurality and health professional shortages with the clinicopathologic characteristics of melanoma in North Carolina.

To assess rural-urban and health professional shortage area (HPSA)-related influences on the characteristics of melanoma in North Carolina. We conducted a single-center retrospective cohort study of patients living in North Carolina with an available pathology report for invasive cutaneous melanoma seen in the Duke University Health System from 01/01/2014 to 12/31/2020. Multivariable logistic regression models were employed to compare patient and tumor characteristics between rural versus urban county residence as well between melanoma thicknesses dichotomized into thin (≤1.0mm) and thicker (>1.0mm) tumors. The cohort included 807 patients, and rural patients accounted for 177 (21.9%) of invasive cutaneous melanomas. Rural patients had significantly higher odds of having thicker tumors than urban patients (odds ratio [OR] = 1.78, 95% confidence interval [CI]: 1.17-2.71; P =.008). Rural patients were significantly more likely to be female (OR = 1.59, 95% CI: 1.10-2.28; P =.013) and located in a population-based (OR = 2.66, 95% CI: 1.84-3.84; P<.001) or geographic-based (OR = 8.21, 95% CI: 3.33-20.22; P<.001) HPSA. Living in a medium- or high-shortage population-based HPSA was associated with higher odds of thicker tumors (OR = 2.65, 95% CI: 1.85-3.80; P<.001). Patients living in rural North Carolina counties were more likely than those in urban counties to be diagnosed with melanomas >1.0mm in thickness, a clinically significant difference with important prognostic implications. Interventions at the county- and state-level to address this disparity may include improving access to skin cancer screening and teledermatology programs, increasing partnerships with primary care providers, and targeting interventions to counties with health professional shortages.

Variation in initial biopsy technique for primary melanoma diagnosis: A population-based cohort study in New South Wales, Australia

BackgroundFactors associated with non-adherence to guideline-recommended complete excision of suspicious cutaneous lesions are unclear. ObjectiveTo analyse patient, melanoma and clinician factors associated with initial diagnostic biopsy type; and determine whether unwarranted variation from guidelines occurred. MethodsThis population-based, cohort study involved analysis of data from questionnaires completed by clinicians who managed patients with newly-diagnosed, histopathologically-confirmed primary invasive cutaneous melanomas reported to the NSW Cancer Registry between 2006-2007. ResultsOf 2267 biopsies, complete excision was attempted in 69.1% of cases, but histologically incomplete in 14.0%. Multivariable regression analyses showed complete excision was more likely than: incision biopsy in patients <70years (p=0.016); shave biopsy in patients <80years (p=0.034); shave biopsy in melanomas of Breslow thickness 0.8-1.0mm or 2.1-4.0mm (p=0.039); than either punch (p<0.001) or shave biopsy (p<0.003) in melanomas on trunk or limbs; and punch biopsy when treated by a surgeon (p<0.001). Complete excision was less likely than: punch biopsies in females (p<0.003); with LMM or unknown histopathology (p=0.004); shave biopsy in patients with LMM, or other melanoma subtype (p=0.003); punch, shave or incision biopsy when treated by a dermatologist (p<0.001). LimitationsGeneralisability of these findings may be limited to the time of data collection. ConclusionGuideline adherence for biopsy type undertaken for clinically suspected melanoma appeared to be sub-optimal.

Melanoma Incidence and Mortality Trends in Sweden.

Over the past decades, many global regions have experienced a steady increase in the incidence of cutaneous melanoma. However, more recently, a downward trend has been observed in the younger age groups in Australia and the US. Yet, in Europe, none of the countries have reported any significant decline in melanoma incidence for any age group. To assess melanoma incidence and mortality trends in Sweden, with a focus on individuals younger than the average age of melanoma onset. This cohort study used data on the national population from the Swedish Melanoma Registry and the Swedish Cancer Registry, which cover more than 99% of all primary invasive cutaneous melanomas diagnosed in the country. All patients diagnosed from 1990 to 2022 were included. Incidence and mortality rates per 100 000 inhabitants were calculated for each year and shown as average annual rates for every 5-year period from 1990 to 2022. Joinpoint regression models were used to evaluate statistical significance of temporal trends and points of change. There were 34 800 primary invasive cutaneous melanomas (19 582 [56.3%] in females and 15 218 [43.7%] in males) reported in 33 324 individuals younger than 60 years (median [IQR] age, 48 [36-58] years) from 1990 to 2022. A consistent rise in melanoma incidence was observed among those 50 to 59 years old. The age groups from 20 to 29 years, 30 to 39 years, and 40 to 49 years showed an incidence peak in 2013 to 2015 followed by stable or significantly declining rates until 2022. In patients younger than 20 years, melanoma incidence remained low with no significant trends. There was also a significant decline in melanoma mortality among 30- to 59-year-old individuals, but not in those 60 years and older. The findings of this cohort study showed a significant recent downward trend in both melanoma incidence and melanoma mortality in the age group 30 to 49 years in Sweden. The reasons for these declines are unclear but may include UV protection, public health campaigns, changing population demographics, and the introduction of effective melanoma treatment. None of these possibilities were evaluated; further study is needed.

Pannexin 1 crosstalk with the Hippo pathway in malignant melanoma.

In this study, we explored the intricate relationship between Pannexin 1 (PANX1) and the Hippo signaling pathway effector, Yes-associated protein (YAP). Analysis of The Cancer Genome Atlas (TCGA) data revealed a significant positive correlation between PANX1 mRNA and core Hippo components, YAP, TAZ, and Hippo scaffold, IQGAP1, in invasive cutaneous melanoma and breast carcinoma. Furthermore, we demonstrated that PANX1 expression is upregulated in invasive melanoma cell lines and is associated with increased YAP protein levels. Notably, our investigations uncovered a previously unrecognized interaction between endogenous PANX1 and the Hippo scaffold protein IQGAP1 in melanoma cells. Moreover, our findings revealed that IQGAP1 exhibits differential expression in melanoma cells and plays a regulatory role in cellular morphology. Functional studies involving PANX1 knockdown provided compelling evidence that PANX1 modulates YAP protein levels and its co-transcriptional activity in both melanoma and breast carcinoma cells. Importantly, our study showcases the potential therapeutic relevance of targeting PANX1, as pharmacological inhibition of PANX1 using selective FDA-approved inhibitors or PANX1 knockdown reduced YAP abundance in melanoma cells. Furthermore, our Clariom™ S analysis unveiled key genes implicated in cell proliferation, such as neuroglin1 (NRG1), β-galactoside binding protein, galectin-3 (LGALS3), that are affected in PANX1-deficient cells. In summary, our investigation delves into the intricate interplay between PANX1 and YAP in the context of invasive melanoma, offering valuable insights into potential therapeutic strategies for effective treatment.

52451 Intraoperative immunohistochemistry during Mohs micrographic surgery and staged excision decreases local recurrence rates for invasive cutaneous melanoma: A systematic review and meta-analysis

52451 Intraoperative immunohistochemistry during Mohs micrographic surgery and staged excision decreases local recurrence rates for invasive cutaneous melanoma: A systematic review and meta-analysis

Exploring the Germline Genetics of In Situ and Invasive Cutaneous Melanoma

It is unknown whether germline genetic factors influence in situ melanoma risk differently than invasive melanoma risk. To determine whether differences in risk of in situ melanoma and invasive melanoma are heritable. Three genome-wide association study meta-analyses were conducted of in situ melanoma vs controls, invasive melanoma vs controls, and in situ vs invasive melanoma (case-case) using 4 population-based genetic cohorts: the UK Biobank, the FinnGen cohort, the QSkin Sun and Health Study, and the Queensland Study of Melanoma: Environmental and Genetic Associations (Q-MEGA). Melanoma status was determined using International Statistical Classification of Diseases and Related Health Problems codes from cancer registry data. Data were collected from 1987 to 2022, and data were analyzed from September 2022 to June 2023. In situ and invasive cutaneous melanoma. To test whether in situ and invasive melanoma have independent heritable components, genetic effect estimates were calculated for single-nucleotide variants (SNV; formerly single-nucleotide polymorphisms) throughout the genome for each melanoma. Then, SNV-based heritability was estimated, the genetic correlation between melanoma subtypes was assessed, and polygenic risk scores (PRS) were generated for in situ vs invasive status in Q-MEGA participants. A total of 6 genome-wide significant loci associated with in situ melanoma and 18 loci with invasive melanoma were identified. A strong genetic correlation (genetic r = 0.96; 95% CI, 0.76-1.15) was observed between the 2 classifications. Notably, loci near IRF4, KLF4, and HULC had significantly larger effects for in situ melanoma compared with invasive melanoma, while MC1R had a significantly larger effect on invasive melanoma compared with in situ melanoma. Heritability estimates were consistent for both, with in situ melanoma heritability of 6.7% (95% CI, 4.1-9.3) and invasive melanoma heritability of 4.9% (95% CI, 2.8-7.2). Finally, a PRS, derived from comparing invasive melanoma with in situ melanoma genetic risk, was on average significantly higher in participants with invasive melanoma (odds ratio per 1-SD increase in PRS, 1.43; 95% CI, 1.16-1.77). There is much shared genetic architecture between in situ melanoma and invasive melanoma. Despite indistinguishable heritability estimates between the melanoma classifications, PRS suggest germline genetics may influence whether a person gets in situ melanoma or invasive melanoma. PRS could potentially help stratify populations based on invasive melanoma risk, informing future screening programs without exacerbating the current burden of melanoma overdiagnosis.

Clinical and Imaging Follow-Up for High-Risk Cutaneous Melanoma: Current Evidence and Guidelines.

The most recent (eighth) edition of the American Joint Committee on Cancer (AJCC) staging system divides invasive cutaneous melanoma into two broad groups: "low-risk" (stage IA-IIA) and "high-risk" (stage IIB-IV). While surveillance imaging for high-risk melanoma patients makes intuitive sense, supporting data are limited in that they are mostly respective and used varying methods, schedules, and endpoints. As a result, there is a lack of uniformity across different dermatologic and oncologic organizations regarding recommendations for follow-up, especially regarding imaging. That said, the bulk of retrospective and prospective data support imaging follow-up for high-risk patients. Currently, it seems that either positron emission tomography (PET) or whole-body computerized tomography (CT) are reasonable options for follow-up, with brain magnetic resonance imaging (MRI) preferred for the detection of brain metastases in patients who can undergo it. The current era of effective systemic therapies (ESTs), which can improve disease-free survival (DFS) and overall survival (OS) beyond lead-time bias, has emphasized the role of imaging in detecting various patterns of EST response and treatment relapse, as well as the importance of radiologic tumor burden.

Incidental Cutaneous Melanoma

A young man admitted to the hospital with sepsis and cellulitis was incidentally found to have invasive cutaneous melanoma. Recognition of melanoma is important to ensure timely diagnosis and treatment.

North-south differences in incidence and surveillance of cutaneous malignant melanoma in Italy.

In Italy, the incidence of cutaneous malignant melanoma is two-fold higher in the north than in the south. This gradient might be associated with differences in incidence trends and disease surveillance. We compared the time trends in incidence rates, mortality rates, dermatologic office visit rates and skin biopsy rates between the Emilia-Romagna Region (northern Italy) and the Sicily Region (southern Italy). The cancer registries of Parma, Modena, Ferrara and Romagna (current population, 2,606,465) and Catania-Messina-Enna, Siracusa and Ragusa (2,775,019) provided incidence and mortality records for the years 2008-2017. The records of outpatient services delivered in public health facilities were obtained from the two Regional Administrations. Trends in rates were assessed with the estimated average annual percent change. North-south differences were expressed as age-standardised rate ratios. In the context of a generalised increasing incidence trend, which was more moderate in the female population of the Sicily Region, the standardised rate ratios were: 5.31 (males) and 5.20 (females) for in situ cutaneous malignant melanoma; 2.10 and 2.07 for invasive cutaneous malignant melanoma, with an excess incidence concentrated in lesions ⩽1.00 mm thick (3.58 and 3.05); 3.00 and 2.44 for dermatologic office visits; and 5.25 and 5.02 for skin biopsies. Mortality was stable in both Regions. In the Emilia-Romagna Region, as compared with the Sicily Region, a higher incidence of cutaneous malignant melanoma -especially of in situ and early invasive cutaneous malignant melanoma- coexisted with a higher level of clinical surveillance. The question of the direction of the cause-effect relationship between increased incidence and increased diagnostic scrutiny remains open.

[Translated article] Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation

IntroductionThe incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. MethodsREGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. ResultsA total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. ConclusionsThe distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Could the mitotic count improve personalized prognosis in melanoma patients?

A number of studies have indicated that the mitotic rate may be a predictive factor for poor prognosis in melanoma patients. The aim of this study was to investigate whether the mitotic rate is associated with other prognostic clinical and anatomopathological characteristics. After adjusting for other anatomopathological characteristics, we then verified the prognostic value of the number of mitoses, determining in which population subgroup this variable may have greater prognostic significance on 3-year mortality. The Veneto Cancer Registry (Registro Tumori del Veneto-RTV), a high-resolution population-based dataset covering the regional population of approximately 4.9 million residents, served as the clinical data source for the analysis. Inclusion criteria included all incident cases of invasive cutaneous malignant melanoma recorded in the RTV in 2015 (1,050 cases) and 2017 (1,205 cases) for which the number of mitoses was available. Mitotic classes were represented by Kaplan-Meier curves for short-term overall survival. Cox regression calculated hazard ratios in multivariable models to evaluate the independent prognostic role of different mitotic rate cut-offs. The results indicate that the mitotic rate is associated with other survival prognostic factors: the variables comprising the TNM stage (e.g., tumor thickness, ulceration, lymph node status and presence of metastasis) and the characteristics that are not included in the TNM stage (e.g., age, site of tumor, type of morphology, growth pattern and TIL). Moreover, this study demonstrated that, even after adjusting for these prognostic factors, mitoses per mm2 are associated with higher mortality, particularly in T2 patients. In conclusion, these findings revealed the need to include the mitotic rate in the histological diagnosis because it correlates with the prognosis as an independent factor. The mitotic rate can be used to develop a personalized medicine approach in the treatment and follow-up monitoring of melanoma patients.

Intraoperative Immunohistochemistry During Mohs Micrographic Surgery and Staged Excision Decreases Local Recurrence Rates for Invasive Cutaneous Melanoma: A Systematic Review and Meta-Analysis.

Mohs micrographic surgery (MMS) is increasingly used to treat cutaneous melanoma. However, it is unclear whether intraoperative immunohistochemistry (IHC) improves surgical outcomes. To determine whether intraoperative IHC during MMS and staged excision is associated with a decreased risk of poor surgical outcomes. Search of 6 databases identified comparative and noncomparative studies that reported local recurrence after MMS or staged excision with or without IHC for melanoma. Random-effects meta-analysis was used to estimate pooled local recurrence rates, nodal recurrence, distant recurrence, and disease-specific mortality. Overall, 57 studies representing 12,043 patients with cutaneous melanoma and 12,590 tumors met inclusion criteria. Combined MMS and staged excision with IHC was associated with decreased local recurrence in patients with invasive melanoma (0.3%, 95% CI: 0-0.6) versus hematoxylin and eosin alone (1.8%, 95% CI: 0.8%-2.8%) [ p < .001]. Secondary outcomes including nodal recurrence, distant recurrence, and disease-specific mortality were not significantly different between these 2 groups. Study heterogeneity was moderately-high. Local recurrence of invasive melanoma is significantly lower after MMS and staged excision with IHC as opposed to without IHC. These findings suggest that the use of intraoperative IHC during MMS or staged excision should strongly be considered, particularly for invasive melanoma.Trial Registration PROSPERO Identifier: CRD42023435630.

Abstract 6173: The development and evaluation of a convolutional neural network for melanoma detection in whole slide images

Abstract The current melanoma staging system is predictive of 74% of the variance in survival, with prognostic biomarkers subject to high levels of inter-observer variation. The application of convolutional neural networks (CNNs) to whole slide images (WSIs), may reveal new insights into tumor morphology and therefore patient prognosis. Melanoma morphology appears to be of greater significance than in other solid tumors, with Breslow thickness remaining the strongest prognostic indicator. Other biomarkers based on tumor morphology have been generated and although some have been found to be prognostically superior to Breslow thickness, none have been integrated into clinical workflows. This may in part be explained by their demands on pathologist time. Therefore, this work outlines the development and evaluation of a CNN for invasive cutaneous melanoma detection in WSIs, which may be used for prognostic biomarker generation. 1,157 WSIs containing cutaneous melanoma from five datasets (three from the University of Leeds, one from the Melanoma Institute Australia, as well as The Cancer Genome Atlas) have been used in the initial development and evaluation of the CNN. A custom-designed 2-class tumor segmentation network with a fully convolutional architecture was trained using annotations. The CNN was evaluated using various methodologies, including comparison at per-pixel and per-tumor levels as compared to manual annotation, as well as variation across 3 scanning platforms (Leica Aperio AT2 (Milton Keynes, UK), Roche Ventana DP600 (Arizona, US) and Hamamatsu NanoZoomer S360 (Hamamatsu City, Japan). The CNN detected and located invasive melanoma tissue of no specific type with an average per-pixel sensitivity and specificity of 97.6% and 99.9% respectively across the 5 test sets. There were no statistical differences between tumor dimensions generated by the CNN as compared to manual annotation. Similarly, there were no statistically significant differences between CNN generated tumor dimensions across three scanning platforms. We have developed and performed initial evaluation of a CNN which appears to accurately detect invasive cutaneous melanoma of no specific type in WSIs for objective evaluation of tumor morphology. Future work should interrogate these data further for its propensity to predict survival outcomes. Citation Format: Emily L. Clarke, Derek Magee, Julia Newton-Bishop, William Merchant, Marlous Hall, Robert Insall, Nigel Maher, Richard Scolyer, Grace Farnworth, Anisah Ali, Sally O'Shea, Darren Treanor. The development and evaluation of a convolutional neural network for melanoma detection in whole slide images [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6173.

Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento

IntroductionThe incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. MethodsREGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. ResultsA total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. ConclusionsThe distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Lymphatic expression of the proliferation marker Ki67 is linked to sentinel node positivity, recurrence and mortality in primary cutaneous melanoma.

Lymphangiogenesis is a precursor to lymphovascular invasion, and may therefore signal a higher risk of metastasis and mortality in primary cutaneous melanoma. This retrospective longitudinal study aimed to evaluate whether emergent lymphangiogenesis, as measured through co-expression of endothelial proteins with the proliferation marker Ki67, was associated with poorer prognosis in a cohort of patients with single primary cutaneous melanoma. We screened all patients with a single locally invasive primary cutaneous melanoma who received sentinel lymph node biopsy at a tertiary dermatology centre in Brisbane, Australia between 1994 and 2007. Primary melanoma sections were stained via Opal multiplex immunofluorescence, and categorized according to the presence of Ki67 within either CD31+ or D2-40+ endothelial cells. Multivariate Cox regression modelling was used to evaluate associations between endothelial Ki67 positivity and clinical outcomes, with adjustment for age, sex, Breslow depth, ulceration, and anatomical location. Overall, 264 patients were available for analysis, with a median follow-up duration of 7.1 years. The presence of D2-40+ /Ki67+ co-expression was associated with greater melanoma-specific mortality (adjusted hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.33-3.10; p = 0.001) and recurrence (adjusted HR: 1.70; 95% CI: 1.33-3.10; p = 0.001) relative to absence. CD31+ /Ki67+ co-expression was not prognostic in this cohort. Lymphatic proliferation, as measured through D2-40+ /Ki67+ co-expression, predicted greater melanoma-specific mortality and recurrence in this cohort of primary cutaneous melanoma.

Health Economic Consequences Associated With COVID-19–Related Delay in Melanoma Diagnosis in Europe

The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet. To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe. This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous melanomas stages I to IV according to the American Joint Committee on Cancer (AJCC) seventh and eighth editions, including melanomas of unknown primary (T0). Data were collected from January 2017 to December 2021 in Switzerland and from January 2019 to December 2021 in Hungary. Data were used to develop an estimation of melanoma upstaging rates in AJCC stages, which was verified with peripandemic data. Years of life lost (YLL) were calculated and were, together with cost data, used for financial estimations. The total financial burden was assessed through direct and indirect treatment costs. Models were building using data from 50 072 patients aged 18 years and older with invasive primary cutaneous melanomas stages I to IV according to the AJCC seventh and eighth edition, including melanomas of unknown primary (T0) from 2 European tertiary centers. Data from European cancer registries included patient-based direct and indirect cost data, country-level economic indicators, melanoma incidence, and population rates per country. Data were analyzed from July 2021 to September 2022. COVID-19 lockdown-related delay of melanoma detection and consecutive public health and economic burden. As lockdown restrictions varied by country, lockdown scenario was defined as elimination of routine medical examinations and severely restricted access to follow-up examinations for at least 4 weeks. Primary outcomes were the total burden of a delay in melanoma diagnosis during COVID-19 lockdown periods, measured using the direct (in US$) and indirect (calculated as YLL plus years lost due to disability [YLD] and disability-adjusted life-years [DALYs]) costs for Europe. Secondary outcomes included estimation of upstaging rate, estimated YLD, YLL, and DALY for each European country, absolute direct and indirect treatment costs per European country, proportion of the relative direct and indirect treatment costs for the countries, and European health expenditure. There were an estimated 111 464 (range, 52 454-295 051) YLL due to pandemic-associated delay in melanoma diagnosis in Europe, and estimated total additional costs were $7.65 (range, $3.60 to $20.25) billion. Indirect treatment costs were the main cost driver, accounting for 94.5% of total costs. Estimates for YLD in Europe resulted in 15 360 years for the 17% upstaging model, ranging from 7228 years (8% upstaging model) to 40 660 years (45% upstaging model). Together, YLL and YLD constitute the overall disease burden, ranging from 59 682 DALYs (8% upstaging model) to 335 711 DALYs (45% upstaging model), with 126 824 DALYs for the real-world 17% scenario. This economic analysis emphasizes the importance of continuing secondary skin cancer prevention measures during pandemics. Beyond the personal outcomes of a delayed melanoma diagnosis, the additional economic and public health consequences are underscored, emphasizing the need to include indirect economic costs in future decision-making processes. These estimates on DALYs and the associated financial losses complement previous studies highlighting the cost-effectiveness of screening for melanoma.

BioMEL: a translational research biobank of melanocytic lesions and melanoma

IntroductionDiagnosing invasive cutaneous melanoma (CM) can be challenging due to subjectivity in distinguishing equivocal nevi, melanoma in situ and thin CMs. The underlying molecular mechanisms of progression from nevus to...

The Burden of Thin Melanomas in Tuscany, Italy, 1985–2017: Age- and Sex-Specific Temporal Trends in Incidence and Mortality

A steady increase in the incidence and mortality burden correlated to thin melanomas (≤1 mm) has been reported in recent years in some international studies, but there is currently a paucity of data from the Mediterranean area. We aimed to describe the epidemiological characteristics of thin melanoma in Tuscany, Central Italy. A total of 6002 first cutaneous invasive melanomas occurring from 1985 to 2017 were selected for analysis; data were retrieved from the local population-based cancer registry. The standardized incidence rate was 15.0 per 100,000 in the population, higher among men than women (16.5 vs. 14.1). Incidence rates tended to increase over time across all age group-specific population strata, with annual percent changes moderately higher among men (+8.0%) than women (+6.9%), especially among the elderly. Among both sexes and in each age group, the trend toward increasing incidence rates was particularly strong for thin melanomas. Survival was better among women than men across all categories of thickness. Approximately 15% of deaths occurred among patients with thin lesions, with no major temporal changes in recent years. This study contributes to an improved understanding of melanoma epidemiology in Tuscany and underscores the need for primary prevention strategies tackling the growing burden of thin melanomas.