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Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

On the basis of the clinical impression and current knowledge, acquired melanocytic nevi and melanomas may not occur in random localizations. The goal of this study was to identify whether their distribution on the back is random and whether the location of melanoma correlates with its adjacent lesions. Therefore, patient-level and lesion-level spatial analyses were performed using the Clark‒Evans test for complete spatial randomness. A total of 311 patients with three-dimensional total body photography (average age of 40.08 [30‒49] years; male/female ratio: 128/183) with 5,108 eligible lesions in total were included in the study (mean sum of eligible lesions per patient of 16.42 [3‒199]). The patient-level analysis revealed that the distributions of acquired melanocytic neoplasms were more likely to deviate toward clustering than dispersion (average z-score of ‒0.55 [95% confidence interval = ‒0.69 to ‒0.41; P < 0.001]). The lesion-level analysis indicated a higher portion of melanomas (n = 57 of 72, 79.2% [95% confidence interval = 69.4‒88.9%]) appearing in proximity to neighboring melanocytic neoplasms than to nevi (n = 2,281 of 5,036, 45.3% [95% confidence interval = 43.9‒46.7%]). In conclusion, the nevi and melanomas' distribution on the back tends toward clustering as opposed to dispersion. Furthermore, melanomas are more likely to appear proximally to their neighboring neoplasms than to nevi. These findings may justify various oncogenic theories and improve diagnostic methodology., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The primary cause of the increase in melanoma incidence in the United States has been suggested to be overdiagnosis. We used Surveillance, Epidemiology, and End Result Program data from 1975 to 2017 to examine epidemiologic trends of melanoma incidence and mortality and better characterize overdiagnosis in white Americans. Over the 43-year period, incidence and mortality showed discordant temporal changes across population subgroups; trends most suggestive of overdiagnosis alone were present in females aged 55-74. Other groups showed mixed changes suggestive of overdiagnosis plus changes in underlying disease risk (decreasing risk in younger individuals and increasing risk in older males). Cohort effects were identified for male and female mortality and male incidence but were not as apparent for female incidence, suggesting that period effects have had a greater influence on changes in incidence over time in females. Encouraging trends included long-term declines in mortality in younger individuals and recent stabilization of invasive incidence in individuals aged 15-44 years and males aged 45-54 years. Melanoma in situ incidence, however, has continued to increase throughout the population. Overdiagnosis appears to be relatively greater in American females and for melanoma in situ., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Basal cell carcinoma (BCC) is the most common skin cancer, with over 2 million cases diagnosed annually in the United States. Conventionally, BCC is diagnosed by naked eye examination and dermoscopy. Suspicious lesions are either removed or biopsied for histopathological confirmation, thus lowering the specificity of noninvasive BCC diagnosis. Recently, reflectance confocal microscopy, a noninvasive diagnostic technique that can image skin lesions at cellular level resolution, has shown to improve specificity in BCC diagnosis and reduced the number needed to biopsy by 2-3 times. In this study, we developed and evaluated a deep learning-based artificial intelligence model to automatically detect BCC in reflectance confocal microscopy images. The proposed model achieved an area under the curve for the receiver operator characteristic curve of 89.7% (stack level) and 88.3% (lesion level), a performance on par with that of reflectance confocal microscopy experts. Furthermore, the model achieved an area under the curve of 86.1% on a held-out test set from international collaborators, demonstrating the reproducibility and generalizability of the proposed automated diagnostic approach. These results provide a clear indication that the clinical deployment of decision support systems for the detection of BCC in reflectance confocal microscopy images has the potential for optimizing the evaluation and diagnosis of patients with skin cancer., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The incidence of melanoma has been increasing dramatically among teenage and young adult women over the past several decades. Despite a causal link between ultraviolet light exposure and melanoma, a significant proportion of young women intentionally tan. Furthermore, we know very little about the family's role in melanoma-related risk practices., Methods: This study examined 22 interviews of adolescent girls and their mothers discussing topics related to sun protection and tanning behavior., Results: Qualitative analysis elicited four primary themes: (1) high rates of prior discussion about indoor tanning; (2) discussion of other risky behaviors that are considered more important than tanning; (3) a desire for increased knowledge of risky tanning behavior; and (4) change in tanning behavior with relevant life experience., Conclusions: Results emphasize the value of educational interventions designed to raise melanoma-related risk awareness and suggest the potential benefit of improving knowledge maintenance and family engagement through information sharing., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the joint effect of sun exposure and sunburn on nevus counts (on the natural logarithm scale; log nevi) and the role of sun sensitivity., Methods: We describe an analysis of cross-sectional data from 443 children enrolled in the prospective Study of Nevi in Children. To evaluate the joint effect, we partitioned the sum of squares because of interaction between sunburn and sun exposure into orthogonal components representing (1) monotonic increase in log nevi with increasing sun exposure (rate of increase of log nevi depends on sunburn), and (2) nonmonotonic pattern., Results: In unadjusted analyses, there was a marginally significant monotonic pattern of interaction (P = .08). In adjusted analyses, sun exposure was associated with higher log nevi among those without sunburn (P < .001), but not among those with sunburn (P = .14). Sunburn was independently associated with log nevi (P = .02), even though sun sensitivity explained 29% (95% confidence interval: 2%-56%, P = .04) of its effect. Children with high sun sensitivity and sunburn had more nevi, regardless of sun exposure., Conclusions: A program of increasing sun protection in early childhood as a strategy for reducing nevi, when applied to the general population, may not equally benefit everyone., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In the United States, the Surveillance, Epidemiology, and End Results (SEER) Program is the authoritative source for population-based data on melanoma incidence and mortality. However, missing data on tumor thickness may lead to biased analyses in this frequently used database. We sought to characterize invasive melanomas with unknown thickness with emphasis on their association with melanoma survival, and to employ techniques to overcome the limitations of missing data on tumor thickness., Methods: We conducted a retrospective cohort analysis of non-occult invasive melanomas in the SEER database from 1989 to 2008., Results: Of 182184 cases, 24329 (13%) had unknown thickness. From 1989-1993 to 2004-2008, the proportion of unknown thickness cases decreased from 22% to 9% (P(trend) < 0.001). Unknown thickness cases had a significantly increased risk of death due to melanoma (hazard ratio [HR] 3.09, 95% confidence interval [CI]: 2.99, 3.19) than known thickness cases with an increasing trend over time (P(trend) < 0.001). In multivariate analysis, unknown thickness was found to be independently associated with poorer prognostic factors and lack of cancer-directed surgical treatment. Melanoma survival of cases with unknown thickness appeared most similar to 2.01-4.00 mm thickness cases. Multiple imputation demonstrated that imputed tumor thickness was significantly associated with melanoma survival (HR 1.31, 95% CI: 1.30, 1.32) and Clark level (odds ratio [OR] 1.85, 95% CI: 1.82, 1.89) though the strength of associations were not as strong as the associations of original SEER-coded known tumor thickness with melanoma survival (HR 1.46, 95% CI: 1.45, 1.47) and Clark level (OR 2.92, 95% CI 2.89, 2.95), respectively., Conclusions: Exclusion of missing data on melanoma thickness from SEER introduces a selection bias that leads to an underestimation in the prevalence of fatal and likely thicker melanomas. Multiple imputation appears to be an effective tool to predict missing tumor thickness data., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Melanoma accounts for the majority of deaths from skin cancer. Women tend to be diagnosed at a younger age and have better survival than men. A tumor-host interaction might be responsible for these gender-specific differences. Recently, a functional single-nucleotide polymorphism in the promoter of the human homolog of mouse double minute 2 (MDM2) gene was characterized: single-nucleotide polymorphism (SNP)309 increases the MDM2 transcription. In melanoma, the effects for SNP309 and the related tumor protein p53 (TP53) Arg72Pro are inconsistent among published reports. This study investigated the association between SNP309 (RefSNP accession ID (rs)2279744) and TP53 codon 72 (rs1042522) polymorphisms, with outcome in a hospital-based cohort of 990 patients with melanoma. We assessed whether these polymorphisms were associated with clinicopathological and phenotypic characteristics and whether these SNPs affect the age of onset of the disease, recurrence, and survival. No significant associations were found between the SNPs and survival. However, women carrying the SNP309 GG genotype were less likely to be diagnosed at a younger age: odds ratio(adjusted<50) 0.52 (0.29-0.92). Our results suggest that women carrying the SNP309 GG genotype might be at lower risk of developing melanoma at a younger age compared with those carrying TG or TT. Further studies are needed to determine whether a nearby functional polymorphism is responsible for this effect in premenopausal women.

Nevi are important risk markers of melanoma. The study aim was to describe changes in nevi of children using longitudinal data from a population-based cohort. Overview back photography and dermoscopic imaging of up to 4 index back nevi was performed at age 11 years (baseline) and repeated at age 14 years (follow-up). Of 443 children (39% females) imaged at baseline, 366 children (39% females) had repeated imaging 3 years later. At age 14, median back nevus counts increased by two; 75% of students (n=274) had at least one new back nevus and 28% (n=103) had at least one nevus that disappeared. Of 936 index nevi imaged dermoscopically at baseline and follow-up, 69% (645 nevi) had retained the same dermoscopic classification from baseline evaluation. Only 4% (n=13) of nevi assessed as globular at baseline were classified as reticular at follow-up, and just 3% (n=3) of baseline reticular nevi were classified as globular at follow-up. Of 9 (1%) index nevi that disappeared at follow-up, none showed halo or regression at baseline. In conclusion, the relative stability of dermoscopic pattern of individual nevi in the face of the overall volatility of nevi during adolescence suggests that specific dermoscopic patterns may represent distinct biological nevus subsets.

Relative to other specialties, dermatologists have been slow to adopt advanced technologic diagnostic aids. Most skin disease can be diagnosed by simple visual inspection, and the skin is readily accessible for a diagnostic biopsy. Diagnostic aids, such as total body photography and dermoscopy, improve the clinician's ability to diagnose melanoma beyond unaided visual inspection, however, and are now considered mainstream methods for early detection. Emerging technologies such as in vivo reflectance confocal microscopy are currently being investigated to determine their utility for noninvasive diagnosis of melanoma. This review summarizes the currently available cutaneous imaging devices and new frontiers in noninvasive diagnosis of skin disease. We anticipate that multimodal systems that combine different imaging technologies will further improve our ability to detect, at the bedside, melanoma at an earlier stage.

A system was designed and developed for simultaneous fluorescence and reflectance contrast in vivo confocal imaging of murine skin using 488 nm (fluorescence mode) and 830 nm (reflectance mode) laser light sources. B16 melanoma cells and B16-enhanced green fluorescent protein (EGFP) cells were inoculated intradermally into transgenic C57BL/6-TgN (ACTbEGFP) 10sb and non-transgenic C57BL/6 mice, respectively. The inoculation sites were imaged sequentially over a 20 d period. The in vivo confocal images were correlated with ex vivo conventional microscopy. The combined modality system provided single-cell resolution and adequate image registration. In fluorescence mode, B16 melanoma cells appeared as dark objects in the bright background of the GFP expressing murine cells of the C57BL/6 transgenic mouse, and the B16-EGFP melanoma cells had a bright signal within a dark background in C57BL/6 mice. In the C57BL/6 transgenic mouse, a population of fluorescent dendritic cells was observed in the vicinity of the tumor cells. The reflectance images provide a useful reference for those areas in the dermal tissues lacking a fluorescent signal. Combined reflectance/fluorescence in vivo confocal laser scanning microscopy holds significant promise for studies of tumor progression in murine skin.

We conducted a descriptive study to assess the relationship between increasing age and the reporting of melanoma signs/symptoms in 634 hospital-based and 624 population-based incident cases of melanoma. Multivariate logistic regression was used to evaluate the relationship between older age (> or = 50 years) and the reporting of melanoma signs/symptoms. Older patients were less likely to report itching and change in elevation of their lesions (P < 0.05). Change in color was also less likely to be reported by older patients, although not statistically significant. Ulceration of the lesion was reported significantly more by older patients (P < 0.05). Older individuals may be less likely to report itching and change in elevation/color of their lesions, but more likely to report ulceration, a symptom associated with advanced disease and poor prognosis. Further research is necessary to provide a better understanding of the development of melanoma in older populations so that new strategies can be explored to improve early detection in this age group.

We investigated the relationship between patient knowledge, awareness, and delay in seeking medical attention for melanoma. The study population was comprised of 255 cases with cutaneous melanoma newly diagnosed during January 15, 1987 to May 15, 1989, who were part of a population-based case control study. Personal interviews were conducted to obtain information on patient's knowledge of melanoma signs and symptoms, skin awareness, delay in seeking medical attention, and related covariates. The adjusted odds ratio for the association between skin awareness and delay was 0.30 (95% confidence interval 0.12-0.71). Odds ratios ranged from 0.43 to 0.81 for knowledge and delay. Awareness of skin changes was associated with a reduced Breslow depth for stage I melanomas. Individuals who are aware of skin changes and abnormalities appear to be less likely to delay seeking medical attention for melanoma. Knowledge of melanoma signs and symptoms may also contribute to a decreased delay in melanoma diagnosis.

Melanocytic neoplasia is characterized by the aberrant overproduction of multiple cytokines in vitro. However, it is largely unknown how cytokine expression relates to melanoma progression in vivo. Transforming growth factor beta (TGF-beta) is a multifunctional cytokine commonly produced by cultured melanoma cells. The in situ expression of all three TGF-beta isoforms (TGF-beta1, -2, and -3) was determined immunohistochemically in melanocytes and in 51 melanocytic lesions using isoform-specific antibodies. Significant linear trends of expression were observed from melanocytes through nevi and primary and metastatic melanomas for all three isoforms. TGF-beta1 was expressed by some melanocytes and almost uniformly by nevi and melanomas. TGF-beta2 and -3 were not expressed in normal melanocytes but were expressed in nevi and early and advanced primary (radial and vertical growth phase) and metastatic melanomas in a tumor-progression-related manner. TGF-beta2 was heterogeneously expressed in advanced primary and metastatic melanomas, whereas TGF-beta3 was uniformly and highly expressed in these lesions. Thus, expression of TGF-beta isoforms in melanocytes and melanocytic lesions is heterogeneous and related to tumor progression, and expression of TGF-beta2 and TGF-beta3 commences at critical junctures during progression of nevi to primary melanomas.

Cells isolated from congenital melanocytic nevi and cultured in vitro have growth characteristics that resemble their premalignant stage in situ. A serum-free, chemically defined medium has been developed that allows continuous growth of established nevus cultures for up to several months. Like primary melanoma cells, nevus cells in high-calcium-containing W489 medium require insulin for growth. In contrast to melanoma cells, nevus cells in serum-free medium require the presence of alpha-melanocyte-stimulating hormone, which enhanced intracellular levels of cyclic adenosine monophosphate. In contrast to the requirements of normal human melanocytes from newborn foreskin, congenital nevus cells grow with less dependency on basic fibroblast growth factor (bFGF). Nevus cultures contain bFGF-like activity, and they express bFGF mRNA. Nevic cells of compound nevi also express bFGF mRNA in situ but only in the junctional areas. These results indicate that bFGF plays an important growth regulatory role for nevus cells in vitro and in vivo.

A historical cohort of 153 patients with dysplastic nevi was studied for the development of melanoma. Each subject had a minimum follow-up of 5 years, with an average study follow-up of 94 months. Eleven new melanomas developed in 11 patients between 11 and 143 months (average 61 months) into the study period. Age-adjusted melanoma incidence in the cohort was 692/100,000 person years. Development of melanoma was strongly correlated with prior personal and/or family history of melanoma. Even among the 89 patients with no personal or family history of melanoma, the age-adjusted incidence of melanoma was an alarming 154/100,000 person years. Within this small, non-randomly ascertained cohort no association could be discerned between melanoma incidence and total number of banal or dysplastic nevi. These findings support the public health significance of the recognition of dysplastic nevi and confirm the importance of family history in evaluating melanoma risk associated with dysplastic nevi.