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Supplementary Methods, Tables 1-5, Figures 1-4. Contains additional Methods and Materials on the coding of variables in the risk model, recruitment of cases to the Leeds Case-Control study, imputation, comparing self reported and nurse derived mole counts and calculations for estimating absolute risk. Contains Tables 1-5 on missingness of pooled data, risk assessment for the Leeds dataset including imputed cases, comparisons of self classification and nurse classification of mole count/freckling in the Leeds controls. Contains Figures 1-4 showing the distribution of risk scores in the pooled and Leeds data, a bland-altman plot comparing nurse and self assessment of mole count on the back in Leeds controls and a cartoon used in the Leeds Case-Control study to determine mole count.

Background Although many hair disorders can be readily diagnosed based on their clinical appearance, their progression and response to treatment are often difficult to monitor, particularly in quantitative terms. We introduce an innovative technique utilizing a smartphone and computerized image analysis to expeditiously and automatically measure and compute hair density and diameter in patients in real time. Methods A smartphone equipped with a dermatoscope lens wirelessly transmits trichoscopy images to a computer for image processing. A black-and-white binary mask image representing hair and skin is produced, and the hairs are thinned into single-pixel-thick fiber skeletons. Further analysis based on these fibers allows morphometric characteristics such as hair shaft number and diameters to be computed rapidly. The hair-bearing scalps of fifty participants were imaged to assess the precision of our automated smartphone-based device in comparison with a specialized trichometry device for hair shaft density and diameter measurement. The precision and operation time of our technique relative to manual trichometry, which is commonly used by hair disorder specialists, is determined. Results An equivalence test, based on two 1-sided t tests, demonstrates statistical equivalence in hair density and diameter values between this automated technique and manual trichometry within a 20% margin. On average, this technique actively required 24 seconds of the clinician's time whereas manual trichometry necessitated 9.2 minutes. Conclusion Automated smartphone-based trichometry is a rapid, precise, and clinically feasible technique which can significantly facilitate the assessment and monitoring of hair loss. Its use could be easily integrated into clinical practice to improve standard trichoscopy.

It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild Type. BRAF mutant tumors had younger age at diagnosis, more associated nevi, more tumor infiltrating lymphocytes, and fewer thick tumors although at generally more advanced stage. NF1 mutant tumors were frequent on the head/neck in older patients with severe solar elastosis, thicker tumors but in earlier stages. Triple Wild Type tumors were predominantly male, frequently on the leg, with more perineural invasion. Mutations in TERT, TP53, CDKN2A and ARID2 were observed often, with TP53 mutations occurring particularly frequently in the NF1 sub-type. The InterMEL study will provide the most extensive multi-omic profiling of early-stage melanoma to date. Initial results demonstrate a nuanced understanding of the mutational and clinicopathological landscape of these early-stage tumors.

IntroductionWe are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. This ongoing study will target 1,000 melanomas within the international InterMEL consortium. We also evaluated tissue-derived predictors of extracted nucleic acids’ quality and success in downstream testing.MethodsFollowing a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACT™ assay, methylation-profiling (array), and miRNA expression (Nanostring nCounter).ResultsSufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (pConclusionOur experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma.

Background Despite the increasing trend of cutaneous malignant melanoma (CMM) incidence in Canada, especially among females, few risk factors other than ultraviolet radiation exposure, have been identified. Aim We conducted a case-control study of 406 CMM cases and 181 controls to evaluate the potential impact of body burdens of various persistent organic pollutants on CMM risk. Methods Detailed data on potential confounding factors, including lifetime repeated sun exposure and skin reaction to repeated sun exposure, were collected. Gas chromatography tandem mass spectrometry was used to assay plasma levels of 14 polychlorinated biphenyl (PCB) congeners and 11 organochlorine (OC) pesticides among cases and controls. Results Statistically significant trends of increased CMM risk were observed with increasing plasma concentrations of multiple PCB congeners, including PCBs 138, 153, 170, 180, 183 and 187. For example, compared to lowest plasma concentration quartile of PCB-138, the second, third and fourth quartiles were associated with 1.7 (95% CI: 0.9-2.9), 2.3 (95% CI: 1.3-4.1) and 2.4 (95% CI: 1.3-4.5) -fold increased risks of CMM, respectively. Similarly, increasing plasma concentrations of several OC pesticides (i.e., β-HCH, HCB, Mirex, oxychlordane and trans-Nonachlor) showed statistically significant trends with increased CMM risk. For example, compared to lowest plasma concentration quartile of β-HCH, the second, third and fourth quartiles were associated with 1.3 (95% CI: 0.7-2.3), 2.1 (95% CI: 1.2-3.7) and 2.3 (95% CI: 1.2-4.4) -fold increased risks of CMM, respectively. Conclusion Plasma levels of several persistent organic pollutants were highly correlated, suggesting that observed associations were not necessarily independent of each other. Given the highly correlated nature of exposure to PCB and OC analytes, sophisticated analyses that consider complex mixtures should be considered in future studies.

In recent years, vast developments in Computer-Aided Diagnosis (CAD) for skin diseases have generated much interest from clinicians and other eventual end-users of this technology. Introducing clinical domain knowledge to these machine learning strategies can help dispel the black box nature of these tools, strengthening clinician trust. Clinical domain knowledge also provides new information channels which can improve CAD diagnostic performance. In this paper, we propose a novel framework for malignant melanoma (MM) detection by fusing clinical images and dermoscopic images. The proposed method combines a multi-labeled deep feature extractor and clinically constrained classifier chain (CC). This allows the 7-point checklist, a clinician diagnostic algorithm, to be included in the decision level while maintaining the clinical importance of the major and minor criteria in the checklist. Our proposed framework achieved an average accuracy of 81.3% for detecting all criteria and melanoma when testing on a publicly available 7-point checklist dataset. This is the highest reported results, outperforming state-of-the-art methods in the literature by 6.4% or more. Analyses also show that the proposed system surpasses the single modality system of using either clinical images or dermoscopic images alone and the systems without adopting the approach of multi-label and clinically constrained classifier chain. Our carefully designed system demonstrates a substantial improvement over melanoma detection. By keeping the familiar major and minor criteria of the 7-point checklist and their corresponding weights, the proposed system may be more accepted by physicians as a human-interpretable CAD tool for automated melanoma detection.