Keratosis Pilaris-Like Reaction Associated With Chromatin Remodeling Complex Inhibition in Uveal Melanoma.

This case series describes a constellation of novel adverse reactions in 3 of 9 patients with uveal melanoma receiving treatment targeting activity of the Brahma-associated factor chromatin remodeling complex.

The New Media Landscape and Its Effects on Skin Cancer Diagnostics, Prognostics, and Prevention: Scoping Review.

BACKGROUND: The wide availability of web-based sources, including social media (SM), has supported rapid, widespread dissemination of health information. This dissemination can be an asset during public health emergencies; however, it can also present challenges when the information is inaccurate or ill-informed. Of interest, many SM sources discuss cancer, specifically cutaneous melanoma and keratinocyte cancers (basal cell and squamous cell carcinoma). OBJECTIVE: Through a comprehensive and scoping review of the literature, this study aims to gain an actionable perspective of the state of SM information regarding skin cancer diagnostics, prognostics, and prevention. METHODS: We performed a scoping literature review to establish the relationship between SM and skin cancer. A literature search was conducted across MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus from January 2000 to June 2023. The included studies discussed SM and its relationship to and effect on skin cancer. RESULTS: Through the search, 1009 abstracts were initially identified, 188 received full-text review, and 112 met inclusion criteria. The included studies were divided into 7 groupings based on a publication's primary objective: misinformation (n=40, 36%), prevention campaign (n=19, 17%), engagement (n=16, 14%), research (n=12, 11%), education (n=11, 10%), demographics (n=10, 9%), and patient support (n=4, 3%), which were the most common identified themes. CONCLUSIONS: Through this review, we gained a better understanding of the SM environment addressing skin cancer information, and we gained insight into the best practices by which SM could be used to positively influence the health care information ecosystem.

Persistent poverty and incidence-based melanoma mortality in Texas.

PURPOSE: Previous studies have shown that individuals living in areas with persistent poverty (PP) experience worse cancer outcomes compared to those living in areas with transient or no persistent poverty (nPP). The association between PP and melanoma outcomes remains unexplored. We hypothesized that melanoma patients living in PP counties (defined as counties with ≥ 20% of residents living at or below the federal poverty level for the past two decennial censuses) would exhibit higher rates of incidence-based melanoma mortality (IMM). METHODS: We used Texas Cancer Registry data to identify the patients diagnosed with invasive melanoma or melanoma in situ (stages 0 through 4) between 2000 and 2018 (n = 82,458). Each patient's PP status was determined by their county of residence at the time of diagnosis. RESULTS: After adjusting for demographic variables, logistic regression analyses revealed that melanoma patients in PP counties had statistically significant higher IMM compared to those in nPP counties (17.4% versus 11.3%) with an adjusted odds ratio of 1.35 (95% CI 1.25-1.47). CONCLUSION: These findings highlight the relationship between persistent poverty and incidence-based melanoma mortality rates, revealing that melanoma patients residing in counties with persistent poverty have higher melanoma-specific mortality compared to those residing in counties with transient or no poverty. This study further emphasizes the importance of considering area-specific socioeconomic characteristics when implementing place-based interventions to facilitate early melanoma diagnosis and improve melanoma treatment outcomes.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

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.

A practical guide to clinical photography prior to skin biopsy: key tips and proposed workflow.

High-quality clinical photography has become an integral part of dermatology in the context of patient evaluation and monitoring, clinical teaching, and research. Technological advancements in smartphones have allowed dermatologists to incorporate photography in workflows; however, acquiring quality photos poses its own challenges. Outlining a best practice approach to image capture prior to biopsy will facilitate establishing a team-based approach for the implementation of clinical photography in workflow. We propose this guide with the intent of improving patient care though photography in the clinical setting and the goal of integrating high-quality photography into routine clinical practice.

Gut Microbiome in Patients With Early-Stage and Late-Stage Melanoma.

Importance: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression. Objective: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma. Design, Setting, and Participants: This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021. Main Outcomes and Measures: Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups. Results: A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy. Conclusions and Relevance: The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.

Educational interventions to promote sun-protection behaviors in adolescents in the United States: A systematic review.

The most prevalent modifiable risk factor for skin cancer is cumulative lifetime exposure to ultraviolet (UV) radiation, supporting the development of interventions promoting the early adoption of sun-protection behaviors. This systematic review summarizes behavioral interventions designed to promote sun-protection behaviors and reduce harmful UV exposure among U.S. adolescents. Ten studies describing 15 intervention arms were ultimately included in this review and comprised seven cross-sectional studies, a cohort study, a quasi-experimental study, and a randomized controlled trial. Most interventions included in this review were effective in increasing awareness of skin cancer and knowledge of the risk factors for skin cancer, but knowledge did not correlate with self-reported frequency of sun-protection behaviors in this population.

Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune-related adverse event reveal upregulation of toll-like receptor 4/complement-induced innate immune response and increased density of TH 1 T-cells.

BACKGROUND: Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP-irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. METHODS: BP-irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T-cells (CD3 and CD8), T helper 1 (TH 1) cells (Tbet), TH 2 cells (Gata3), TH 17 cells (RORγT), and regulatory T-cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. RESULTS: Compared with de novo BP controls, BP-irAE samples exhibited upregulation of 30 mRNA transcripts (p < 0.025), including toll-like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p < 0.025), including genes associated with TH 2, TH 17, and B-cell immune response. BP-irAE demonstrated a greater density of Tbet+ (TH 1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. CONCLUSIONS: BP-irAE exhibited activation of the TLR4/complement-driven classical innate immune response pathway, with dermal TH 1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP-irAE.

Thematic analyses of participant survey responses following dermatology ECHO programs with dermoscopy: Practical tips and lessons learned.

Introduction: Skin cancer is a major public health concern in the United States, reflecting approximately one in every three cancer diagnoses. Despite the high incidence of skin cancer, access to dermatologists is limited, especially in rural areas. Primary care physicians play a pivotal role in the evaluation of skin conditions, but dermatology training gaps exist in primary care training programs. Objectives: This study examines the use of the Project ECHO (Extension for Community Healthcare Outcomes) knowledge-sharing framework to provide dermoscopy and skin cancer detection training to primary care providers (PCPs). Methods: Responses to surveys administered to participants in two separate dermoscopy-focused Project ECHO courses were analyzed. Survey responses were collected over a 4-year period for the two courses, which were delivered in Maine and Texas. Thematic analysis of the qualitative data was performed, revealing codes and subcodes that indicated several overall trends. Results: Overall, most respondents indicated the ECHO sessions to be helpful, reporting an increase in confidence and knowledge in dermoscopy. Other codes reflected a positive reception of the learning materials and teaching styles. Furthermore, participant survey analyses highlighted areas of improvement for future ECHO course sessions. Conclusions: This thematic analysis of Project ECHO courses in dermatology with dermoscopy demonstrates the feasibility of using virtual educational platforms to effectively teach PCPs about dermoscopy and skin cancer, with high levels of participant satisfaction. The need to keeping the educational sessions brief, avoid scheduling sessions on high-volume patient care days, and provide a means for participants to obtain hands-on training in the operation of a dermatoscope were among the top lessons learned.

The social vulnerability index as a risk stratification tool for health disparity research in cancer patients: a scoping review.

PURPOSE: The social vulnerability index (SVI), developed by the Centers for Disease Control and Prevention, is a novel composite measure encompassing multiple variables that correspond to key social determinants of health. The objective of this review was to investigate innovative applications of the SVI to oncology research and to employ the framework of the cancer care continuum to elucidate further research opportunities. METHODS: A systematic search for relevant articles was performed in five databases from inception to 13 May 2022. Included studies applied the SVI to analyze outcomes in cancer patients. Study characteristics, patent populations, data sources, and outcomes were extracted from each article. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: In total, 31 studies were included. Along the cancer care continuum, five applied the SVI to examine geographic disparities in potentially cancer-causing exposures; seven in cancer diagnosis; fourteen in cancer treatment; nine in treatment recovery; one in survivorship care; and two in end-of-life care. Fifteen examined disparities in mortality. CONCLUSION: In highlighting place-based disparities in patient outcomes, the SVI represents a promising tool for future oncology research. As a reliable geocoded dataset, the SVI may inform the development and implementation of targeted interventions to prevent cancer morbidity and mortality at the neighborhood level.

Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing.

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Expert Consensus Statement on Proficiency Standards for Dermoscopy Education in Primary Care.

BACKGROUND: Primary care providers (PCPs) frequently address dermatologic concerns and perform skin examinations during clinical encounters. For PCPs who evaluate concerning skin lesions, dermoscopy (a noninvasive skin visualization technique) has been shown to increase the sensitivity for skin cancer diagnosis compared with unassisted clinical examinations. Because no formal consensus existed on the fundamental knowledge and skills that PCPs should have with respect to dermoscopy for skin cancer detection, the objective of this study was to develop an expert consensus statement on proficiency standards for PCPs learning or using dermoscopy. METHODS: A 2-phase modified Delphi method was used to develop 2 proficiency standards. In the study's first phase, a focus group of PCPs and dermatologists generated a list of dermoscopic diagnoses and associated features. In the second phase, a larger panel evaluated the proposed list and determined whether each diagnosis was reflective of a foundational or intermediate proficiency or neither. RESULTS: Of the 35 initial panelists, 5 PCPs were lost to follow-up or withdrew; 30 completed the fifth and last round. The final consensus-based list contained 39 dermoscopic diagnoses and associated features. CONCLUSIONS: This consensus statement will inform the development of PCP-targeted dermoscopy training initiatives designed to support early cancer detection.

A Pilot Educational Intervention to Support Primary Care Provider Performance of Skin Cancer Examinations.

Educational interventions to support Primary Care Provider (PCP) performance of skin cancer examinations typically train PCPs to "triage and refer," an approach that may result in diagnostic delays in regions without appropriate access to dermatology care. To address the needs of PCPs and patients in regions without appropriate access to dermatology care, we developed a multi-faceted pilot intervention, including a curriculum and telementoring, designed to support PCP performance of skin cancer detection examinations. Our intervention offers two levels of proficiency: "triage and refer" and "diagnose and manage." The pilot intervention was conducted in collaboration with the Texas Tech University of Health Sciences Center El Paso, TX Family and Community Medicine Department (TTUHSC-El Paso). Participation in the intervention was voluntary, and 18-22 family medicine resident physicians completed the intervention tests. The participating family medicine resident physicians demonstrated statistically significant gains in knowledge and self-efficacy at the immediate post-intervention time points. Further adaption of the pilot intervention is needed to meet the needs of practicing PCPs. The pilot tests require further adaption and validation. Translating education delivery from live/synchronous to interactive virtual/asynchronous modules will support greater educational dissemination, and telementoring support is essential to address challenging cases encountered during patient care.

The diverse landscape of dermatologic toxicities of non-immune checkpoint inhibitor monoclonal antibody-based cancer therapy.

BACKGROUND: Since their first approval 25 years ago, monoclonal antibodies (mAbs) have become important targeted cancer therapeutics. However, dermatologic toxicities associated with non-immune checkpoint inhibitor (non-ICI) mAbs may complicate the course of cancer treatment. Data on the incidence and types of these reactions are limited. METHODS: A comprehensive review was conducted on dermatologic toxicities associated with different classes of non-ICI mAbs approved for treatment of solid tumors and hematologic malignancies. The review included prospective Phase 1, 2, and 3 clinical trials; retrospective literature reviews; systematic reviews/meta-analyses; and case series/reports. RESULTS: Dermatologic toxicities were associated with several types of non-ICI mAbs. Inflammatory reactions were the most common dermatologic toxicities, manifesting as maculopapular, urticarial, papulopustular/acneiform, and lichenoid/interface cutaneous adverse events (cAEs) with non-ICI mAbs. Immunobullous reactions were rare and a subset of non-ICI mAbs were associated with the development of vitiligo cAEs. CONCLUSION: Dermatologic toxicities of non-ICI mAbs are diverse and mostly limited to inflammatory reactions. Awareness of the spectrum of the histopathologic patterns of cAE from non-ICI mAbs therapy is critical in the era of oncodermatology and oncodermatopathology.

The Role of Dermoscopy in Provider-to-Provider Store-and-Forward Dermatology eConsults: A Scoping Review of the Recent Literature.

Purpose of Review: This scoping review maps recent literature on dermatology provider-to-provider asynchronous store-and-forward (SAF) electronic consult (eConsult) platforms with dermoscopy. It offers a descriptive overview, highlighting benefits and challenges. Recent Findings: Incorporating dermoscopy into SAF eConsults improves diagnostic accuracy for benign and malignant skin neoplasms. Diagnostic and treatment concordance with traditional face-to-face (FTF) visits is high. SAF eConsults with dermoscopy enhance access to dermatological care by improving triage and reducing wait times for FTF visits. Pediatric patients benefit with improved evaluation of melanocytic and vascular growths. eConsult platforms with dermoscopy serve as a telementoring opportunity for clinicians interested in improving their dermoscopy skills. Summary: Adding dermoscopy to SAF eConsults is valuable and results in improved diagnostic accuracy and reduced need for FTF visits. Implementation barriers can be overcome through collaboration between primary care and dermatology. Dermoscopy in SAF eConsults has significant potential for managing skin conditions and reducing the burden caused by unnecessary FTF visit and biopsies.

Theory-Based Approaches to Support Dermoscopic Image Interpretation Education: A Review of the Literature.

Introduction: Efficient interpretation of dermoscopic images relies on pattern recognition, and the development of expert-level proficiency typically requires extensive training and years of practice. While traditional methods of transferring knowledge have proven effective, technological advances may significantly improve upon these strategies and better equip dermoscopy learners with the pattern recognition skills required for real-world practice. Objectives: A narrative review of the literature was performed to explore emerging directions in medical image interpretation education that may enhance dermoscopy education. This article represents the first of a two-part review series on this topic. Methods: To promote innovation in dermoscopy education, the International Skin Imaging Collaborative (ISIC) assembled a 12-member Education Working Group that comprises international dermoscopy experts and educational scientists. Based on a preliminary literature review and their experiences as educators, the group developed and refined a list of innovative approaches through multiple rounds of discussion and feedback. For each approach, literature searches were performed for relevant articles. Results: Through a consensus-based approach, the group identified a number of emerging directions in image interpretation education. The following theory-based approaches will be discussed in this first part: whole-task learning, microlearning, perceptual learning, and adaptive learning. Conclusions: Compared to traditional methods, these theory-based approaches may enhance dermoscopy education by making learning more engaging and interactive and reducing the amount of time required to develop expert-level pattern recognition skills. Further exploration is needed to determine how these approaches can be seamlessly and successfully integrated to optimize dermoscopy education.

Instructional Strategies to Enhance Dermoscopic Image Interpretation Education: a Review of the Literature.

Introduction: In image interpretation education, many educators have shifted away from traditional methods that involve passive instruction and fragmented learning to interactive ones that promote active engagement and integrated knowledge. By training pattern recognition skills in an effective manner, these interactive approaches provide a promising direction for dermoscopy education. Objectives: A narrative review of the literature was performed to probe emerging directions in medical image interpretation education that may support dermoscopy education. This article represents the second of a two-part review series. Methods: To promote innovation in dermoscopy education, the International Skin Imaging Collaborative (ISIC) assembled an Education Working Group that comprises international dermoscopy experts and educational scientists. Based on a preliminary literature review and their experiences as educators, the group developed and refined a list of innovative approaches through multiple rounds of discussion and feedback. For each approach, literature searches were performed for relevant articles. Results: Through a consensus-based approach, the group identified a number of theory-based approaches, as discussed in the first part of this series. The group also acknowledged the role of motivation, metacognition, and early failures in optimizing the learning process. Other promising teaching tools included gamification, social media, and perceptual and adaptive learning modules (PALMs). Conclusions: Over the years, many dermoscopy educators may have intuitively adopted these instructional strategies in response to learner feedback, personal observations, and changes in the learning environment. For dermoscopy training, PALMs may be especially valuable in that they provide immediate feedback and adapt the training schedule to the individual's performance.