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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.

Many dermatology residency programs adapted to the COVID-19 pandemic by transitioning to online teaching methods. This may impact the quality of education and the satisfaction of residents. Dermatology faculty and residents nationwide were surveyed regarding their experiences with the novel online curricula. A total of 65 individuals representing at least 20 ACGME-accredited dermatology programs responded. Many programs implemented a predominantly online curriculum (78%). Most participants reported that both clinical dermatology and dermatopathology were online during the pandemic's peak (90%). Among those who had experienced a live curriculum prior to the pandemic, 49% reported that a virtual curriculum had similar effectiveness, whereas 36% deemed it less effective. Open-ended questions suggested that disadvantages of a virtual curricula included too many distractions, lack of human features, and less spontaneous feedback. They also suggested advantages to an online curriculum included flexibility and more opportunities to hear from guest speakers. Dissatisfaction before the curriculum change was the same as after (7%), suggesting that the educational experience was not worsened. Failing to adjust the curriculum to residents' needs can contribute to lower satisfaction and inadequate education. The variation of responses signifies the importance of seeking sufficient feedback from residents to meet their educational needs.

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.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.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.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.

For patients with metastatic melanoma, immunotherapy agents represent a promising treatment option, and researchers are actively seeking to identify factors that may predict a favorable response in patients. Recent studies have elucidated possible associations between the gut microbiome and the effects of immunotherapy, where variations in the gut microbiome may influence treatment response and frequency of adverse effects. In this clinical review, we describe the current literature related to the gut microbiome in the setting of immunotherapy, and we provide an overview of interventions under investigation that may modulate the gut microbiome. These interventions include fecal microbiota transplantation, probiotics, and dietary modifications.

Background In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. Methods Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. Results Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). Conclusions CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.

Melanoma-screening examinations support early diagnosis, yet there is a national shortage of dermatologists and most at-risk patients lack access to dermatologic care. Primary care physicians (PCPs) in the United States often bridge these access gaps, and thus, play a critical role in the early detection of melanoma. However, most PCPs do not offer skin examinations. We conducted a systematic review and searched Ovid MEDLINE, EMBASE, and the Cochrane Library from 1946 to July 2019 to identify barriers for skin screening by providers, patients, and health systems following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Of 650 abstracts initially identified, 111 publications were included for full-text review and 48 studies met the inclusion criteria. Lack of dermatologic training (89.4%), time constraints (70%), and competing comorbidities (51%) are the most common barriers reported by PCPs. Low perceived risk (69%), long delays in appointment (46%), and lack of knowledge about melanoma (34.8%) are most frequently reported patient barriers. Qualitative reported barriers for health system are lack of public awareness, social prejudice leading to tanning booth usage, public surveillance programs requiring intensive resources, and widespread ABCD evaluation causing delays in seeking medical attention for melanomas. Numerous barriers remain that prevent the implementation of skin screening practices in clinical practice. A multi-faceted combination of efforts is essential for the execution of acceptable and effective skin cancer-screening practices, thus, increasing early diagnosis and lowering mortality rates and burden of disease for melanoma.

ImportanceTherapy 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.ObjectiveTo provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM.Evidence ReviewCase 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).FindingsThe 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 RelevanceFor 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.

The development of immune checkpoint inhibitor (ICI) therapy with anti-CTLA-4 and anti-PD-1/L1 monoclonal antibodies has led to a paradigm shift in cancer therapy. ICI neoadjuvant therapy followed by surgery has become the standard of care for several advanced-stage cancers. The pathology associated with ICI therapy is vast and includes neoadjuvant-associated tissue reactions and activation of tertiary lymphoid structures (TLSs) at the site of the tumor bed and off-target immune-related adverse events (irAEs). TLSs are thought to recapitulate lymph node function and may act as localized immune machinery to mount an antitumor response. B cell activation in TLSs during neoadjuvant ICI therapy has been correlated with antitumor response. We report a patient with a history of sarcomatoid squamous cell carcinoma treated with neoadjuvant ICI cemiplimab who developed clonal expansion of B cells in the TLSs of the tumor bed. The TLSs morphologically mimicked a low-grade B cell lymphoma with plasmacytic differentiation. Awareness of clonal expansion of B cells in TLSs during neoadjuvant ICI therapy is critical to recognize a response to ICI therapy and to avoiding an incorrect diagnosis of low-grade B cell lymphoma. This article is protected by copyright. All rights reserved.

Immune checkpoint inhibitors (ICIs) for cancer treatment have revolutionized the field of medicine. However, an unintended but frequent consequence of ICI therapy is the development of cutaneous immune-related adverse events (irAEs), such as lichenoid dermatitis irAEs (LD-irAEs). The hypertrophic variant of LD-irAE may be a diagnostic challenge since it can mimic superficially invasive squamous cell carcinoma (SCC). A 79-year-old woman with metastatic melanoma who began treatment with an ICI-pembrolizumab-plus exportin-1 (XPO1) inhibitor presented after 1 month of therapy with symmetrical violaceous papules coalescing into plaques and with two nodules of the bilateral dorsal hands. Biopsy of the nodules revealed an actinic keratosis and atypical epidermal proliferation concerning for SCC. However, in the ensuing 3 weeks, the patient developed multiple new erythematous, violaceous, and scaly macules and papules, some coalescing into plaques on the extremities. Biopsies of these lesions revealed exuberant irregular epidermal hyperplasia with hypermaturation and lichenoid infiltrate concentrated at the base of the elongated, broadened rete ridges, consistent with hypertrophic LD-irAE. Treatment included topical fluocinonide ointment, intralesional triamcinolone injections and oral acitretin. Distinguishing hypertrophic LD-irAE and SCC can be challenging since both entities share histopathologic features; thus, correlation with clinical presentation is essential for diagnosis and optimal patient management.

Transforming growth factor-beta1 (TGF-β1) is expressed in normal epidermis. TGF-β1 potently inhibits keratinocyte proliferation and immunomodulatory properties, mainly by suppressing immune responses to self-antigens. Lichen planus (LP) is a form of dermatitis caused by cell-mediated immune dysfunction, but the exact pathogenic pathways are unknown, which poses therapeutic challenges. We report on a 68-year-old man who developed multiple pruritic, discrete, and well-demarcated, flat-topped red-purple papules and macules on the back and upper arms following 4 cycles of treatment with TGF-β receptor I (TGFBR-I) inhibitor, ly3200882, for metastatic chondrosarcoma. The biopsy showed hyperkeratosis, wedge-shaped hypergranulosis, elongation of the rete ridges, and a dense band-like lymphohistiocytic infiltrate admixed with colloid bodies and pigment incontinence, consistent with LP. Temporal correlation suggested that the TGFBR-I inhibitor might be a trigger. Treatment with topical clobetasol and oral metronidazole led to partial resolution of the lesions with postinflammatory hyperpigmentation. We believe this is the first reported case of LP related to TGFBR-I inhibitor therapy. This report expands the list of cutaneous adverse events associated with this novel class of targeted therapy. More importantly, this report supports emerging evidence that failure of TGF-β1 activation/signal transduction is an important mechanism in the pathogenesis of LP and suggests the TGF-β1 pathway as a potential therapeutic target in this disease.

Another benefit of dietary fiber The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al . add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an observational study, the researchers found that melanoma patients reporting high fiber (prebiotic) consumption had a better response to checkpoint inhibitor immunotherapy compared with those patients reporting a low-fiber diet. The most marked benefit was observed for those patients reporting a combination of high fiber consumption and no use of over-the-counter probiotic supplements. These findings provide early insights as to how diet-related factors may influence the immune response. —PNK

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.

Demodex folliculitis is a condition caused by inflammation of the pilosebaceous unit due to the Demodex folliculorum mite.1 The mite is a normal inhabitant of the human hair follicle and though they have been found in all areas of human skin, they predominate on the face. The face, with a high density of active sebaceous glands is a desirable home for demodex mites who feed on exfoliated epidermal cells and sebaceous gland secretions. The eruption of demodex folliculitis can mimic many common skin pathologies such as rosacea, acne vulgaris, and bacterial folliculitis.2 When demodex folliculitis occurs with immunocompromised patients, the clinical presentation can be atypical and severe.3 Herein, we report a case of severe demodex folliculitis and review of the literature.

To our knowledge, there is no available standardized educational curriculum designed to promote the incorporation of skin cancer examinations and procedures into general practice. To explore the contemporary training landscape, we conducted a systematic review of educational interventions designed to support skin cancer diagnostic examinations by primary care providers (PCPs). Our review uniquely encompasses all PCPs, including practicing physicians, residents, and advanced practice practitioners (APPs). The objective of this study is to review and synthesize worldwide data on educational interventions addressing PCP performance of skin cancer diagnostic examinations. A systematic review was performed in MEDLINE, Cochrane, EMBASE, and Scopus for English language articles worldwide published from 2000 onwards. Articles were screened for eligibility, and possibly overlapping datasets were resolved. Data extracted included curriculum content, delivery format, and educational outcomes. This review followed the PRISMA guidelines. A total of 63 studies were selected for data inclusion with one addressing training for resident physicians, 4 for APPs, and the remainder for practicing physicians. Educational interventions included in this review reflect the pre-SARS-CoV-2 pandemic educational environment: half provided live/synchronous instruction of about 5-h duration on average, and a quarter featured interactive components. Less than a quarter of interventions included practice change as a specific reported outcome. Without sustainable practice change, the anticipated long-term benefits of early cancer detection in patients remain limited. Previous and existing educational interventions designed to support skin cancer detection by PCPs demonstrate heterogeneous curriculum content, delivery methods, and educational outcomes. An ideal intervention would teach consensus-derived clinical competencies, provide meaningful learner feedback, and measure outcomes, such as knowledge/competency, confidence/attitudes, and practice change, using validated instruments. Supplementary Information The online version contains supplementary material available at 10.1007/s13187-021-02118-8.

Background Advances in molecular biology and genetics have contributed to breakthrough treatments directed at specific pathways associated with the development of cancer. Small-molecule inhibitors (Nibs) aimed at a variety of cellular pathways have been efficacious; however, they are associated with significant dermatologic toxicities. Methods We conducted a comprehensive review of dermatologic toxicities associated with Nibs categorized into the following five groups: (a) MAP kinase; (b) growth factor/multi-tyrosine kinase; (c) cell division/DNA repair; (d) signaling associated with myeloproliferative neoplasms; and (e) other signaling pathways. Prospective phase I, II, or III clinical trials, retrospective literature reviews, systematic reviews/meta-analyses, and case reviews/reports were included for analysis. Results Dermatologic toxicities reviewed were associated with every class of Nibs and ranged from mild to severe or life-threatening adverse skin reactions. Inflammatory reactions manifesting as maculopapular, papulopustular/acneiform, and eczematous lesions were frequent types of dermatologic toxicities seen with Nibs. Squamous cell carcinoma with keratoacanthoma-like features were associated with a subset of Nibs. Substantial overlap in dermatologic toxicities was found between Nibs. Conclusions Dermatologic toxicities from Nibs are diverse and may overlap between classes of Nibs. Recognition of the various types of toxicities from Nibs is critical for patient care in the era of "oncodermatology/dermatopathology". This article is protected by copyright. All rights reserved.

Primary care physicians (PCPs) are often the first line of defense against skin cancers. Despite this, many PCPs do not receive a comprehensive training in skin conditions. Educational interventions aimed at skin cancer screening instruction for PCPs offer an opportunity to detect skin cancer at earlier stages and subsequent improved morbidity and mortality. A scoping review was conducted to collect data about previously reported skin cancer screening interventions for PCPs. A structured literature search found 51 studies describing 37 unique educational interventions. Curriculum elements utilized by the interventions were divided into categories that would facilitate comparison including curriculum components, delivery format, delivery timing, and outcome measures. The interventions varied widely in design, including literature-based interventions, live teaching sessions, and online courses with durations ranging from 5 min to 24 months. While several interventions demonstrated improvements in skin cancer knowledge and competency by written exams, only a few revealed positive clinical practice changes by biopsy review or referral analysis. Examining successful interventions could aid in developing a skin cancer detection curriculum for PCPs that can produce positive clinical practice and population-based changes in the management of skin cancer.

Neither patient experienced myelosuppression. Acitretin was briefly withheld when the latter patient had hypercholesterolemia until pravastatin was started and cholesterol normalized. Both patients tapered down to acitretin, 10 mg/d after 4 months. After 3 additional months, they tapered to 10 mg every other day for prevention for up to 10 months. At 1-year follow-up, both patients remained without clinical recurrence (Figs 1, D and ​and2,2, D)

Background Multiple BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) have been associated with a familial cancer syndrome involving germline mutations in BAP1. Objectives We sought to describe the clinical and dermoscopic features of BIMTs. Methods This was a retrospective, multicenter, case-control study. Participating centers contributed clinical data, dermoscopic images, and histopathologic data of biopsy-proven BIMTs. We compared the dermoscopic features between BIMTs and control patients. Results The dataset consisted of 48 BIMTs from 31 patients (22 women; median age 37 years) and 80 control patients. Eleven patients had a BAP1 germline mutation. Clinically, most BIMTs presented as pink, dome-shaped papules (n = 24). Dermoscopically, we identified 5 patterns: structureless pink-to-tan with irregular eccentric dots/globules (n = 14, 29.8%); structureless pink-to-tan with peripheral vessels (n = 10, 21.3%); structureless pink-to-tan (n = 7, 14.9%); a network with raised, structureless, pink-to-tan areas (n = 7, 14.9%); and globular pattern (n = 4, 8.5%). The structureless with eccentric dots/globules pattern and network with raised structureless areas pattern were only identified in BIMT and were more common in patients with BAP1 germline mutations (P Limitations Limitations included our small sample size, retrospective design, the absence of germline genetic testing in all patients, and inclusion bias toward more atypical-looking BIMTs. Conclusions Dome-shaped papules with pink-to-tan structureless areas and peripheral irregular dots/globules or network should raise the clinical suspicion for BIMT.

INTRODUCTION: Primary care providers have greater access to patients despite often lacking the appropriate training or time to implement effective skin cancer screenings in their busy practices.(1) Through collaborative efforts with Oregon’s War on Melanoma public health campaign and other primary care trainings, we created “Melanoma Toolkit for Early Detection” (MTED): a training curriculum and resource repository for primary care providers. METHODS AND RESULTS: MTED consisted of three self-paced modules. Each participant completed a pre- and post-test consisting of demographic, confidence, and image identification questions. A subsequent optional 6-month follow-up image identification test was also provided. Of the 96 participants, 40 completed all the modules, the pre, and post-test. On average, scores increased by 6.0 (95% CI: 3.5 to 8.6) percentage points (P

Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence, and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike, prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for patients with melanoma and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome, and offer recommendations for the best path forward.

Melanoma-screening examinations support early diagnosis, yet there is a national shortage of dermatologists and most at-risk patients lack access to dermatologic care. Primary care physicians (PCPs) in the United States often bridge these access gaps, and thus, play a critical role in the early detection of melanoma. However, most PCPs do not offer skin examinations. We conducted a systematic review and searched Ovid MEDLINE, EMBASE, and the Cochrane Library from 1946 to July 2019 to identify barriers for skin screening by providers, patients, and health systems following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Of 650 abstracts initially identified, 111 publications were included for full-text review and 48 studies met the inclusion criteria. Lack of dermatologic training (89.4%), time constraints (70%), and competing comorbidities (51%) are the most common barriers reported by PCPs. Low perceived risk (69%), long delays in appointment (46%), and lack of knowledge about melanoma (34.8%) are most frequently reported patient barriers. Qualitative reported barriers for health system are lack of public awareness, social prejudice leading to tanning booth usage, public surveillance programs requiring intensive resources, and widespread ABCD evaluation causing delays in seeking medical attention for melanomas. Numerous barriers remain that prevent the implementation of skin screening practices in clinical practice. A multi-faceted combination of efforts is essential for the execution of acceptable and effective skin cancer-screening practices, thus, increasing early diagnosis and lowering mortality rates and burden of disease for melanoma.

Background: Accurate medical image interpretation is an essential proficiency for multiple medical specialties, including dermatologists and primary care providers. A dermatoscope, a ×10-×20 magnifying lens paired with a light source, enables enhanced visualization of skin cancer structures beyond standard visual inspection. Skilled interpretation of dermoscopic images improves diagnostic accuracy for skin cancer. Objectives: Design and validation of Cutaneous Neoplasm Diagnostic Self-Efficacy Instrument (CNDSEI)—a new tool to assess dermatology residents’ confidence in dermoscopic diagnosis of skin tumors. Methods: In the 2018-2019 academic year, the authors administered the CNDSEI and the Long Dermoscopy Assessment (LDA), to measure dermoscopic image interpretation accuracy, to residents in 9 dermatology residency programs prior to dermoscopy educational intervention exposure. The authors conducted CNDSEI item analysis with inspection of response distribution histograms, assessed internal reliability using Cronbach’s coefficient alpha (α) and construct validity by comparing baseline CNDSEI and LDA results for corresponding lesions with one-way analysis of variance (ANOVA). Results: At baseline, residents respectively demonstrated significantly higher and lower CNDSEI scores for correctly and incorrectly diagnosed lesions on the LDA (P = 0.001). The internal consistency reliability of CNDSEI responses for the majority (13/15) of the lesion types was excellent (α ≥ 0.9) or good (0.8≥ α

IMPORTANCE: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care. OBJECTIVE: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. EVIDENCE REVIEW: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed. FINDINGS: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility. CONCLUSIONS AND RELEVANCE: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

Small-molecule inhibitors (nibs) have revolutionized cancer therapy with the emergence of clinically efficacious treatment for advanced-stage malignancies. Fibroblast growth factor receptor (FGFR) inhibitors have shown therapeutic efficacy in malignancies with molecular-genetic alterations in the FGFR/fibroblast growth factor pathway. In a phase 1 clinical trial, erdafitinib, a pan FGFR inhibitor, was well tolerated with a manageable toxicity profile. Hyperphosphatemia was a frequent adverse event in patients treated with erdafitinib; however, no serious complications were observed with this therapy. Here, we report the development of calcinosis cutis dermatologic toxicity in a patient with hyperphosphatemia while treated with a novel selective FGFR inhibitor, INCB 54828-101. Awareness of this form of dermatologic toxicity from an FGFR inhibitor will be important for close monitoring of serum levels of phosphate, FGF23, vitamin D, and calcitriol, the management of adverse serum chemistry with chelators, and treatment decisions to either reduce dose or withhold FGFR inhibitor.

Checkpoint inhibitors (CPIs) restore the function of effector immunocytes to target and destroy cancer cells. Immune-related adverse events (irAEs) are a consequence of immune reactivation, with unpredictable inflammatory response, loss of self-tolerance, and development of autoimmunity. Adverse events from CPIs that present as dermatologic toxicities have diverse clinical and histopathologic features. CPI-associated dermatologic toxicities may exhibit histopathologic features of lichenoid dermatitis, bullous pemphigoid, and granulomatous/sarcoid-like reactions. Suprabasal acantholytic dermatologic toxicities associated with CPIs are particularly rare but represent an emerging histopathologic pattern and include lichenoid dermatitis with suprabasal acantholysis/vesicle formation to Grover disease (transient acantholytic dermatosis). Here, we report two patients who developed suprabasal acantholytic dermatologic toxicities during CPI therapy. One patient exhibited a CPI-associated autoimmune blistering disease with paraneoplastic pemphigus (PNP)-like features restricted to histopathology and immunofluorescence, while the other patient had Grover-like lesions. A review of the literature revealed a spectrum of suprabasal acantholytic dermatologic toxicities associated CPIs that may present as lichenoid dermatitis with acantholysis/vesicle formation, Grover-like eruptions, and lesions with PNP-like features restricted to histopathology and immunofluorescence. It is important for clinicians and pathologists to recognize the types of dermatologic toxicities associated with CPIs to direct appropriate therapeutic strategies.

LL-37 is a naturally occurring 37-amino-acid peptide that is part of the innate immune system in human skin. Preclinical studies have showed that intra-tumoral injections of LL-37 stimulate the innate immune system by activation of plasmacytoid dendritic cells, which mediate tumor destruction. LL-37 intra-tumoral injections have been utilized in a phase 1 clinical trial for melanoma patients with cutaneous metastases. We report dermatologic toxicity in a 63-year-old woman with stage IIIC melanoma of the right calf and inguinal lymph nodes. She was previously treated with nivolumab and combination chemotherapy (cisplatin, vinblastine and dacarbazine) and subsequently treated with LL-37 injections upon progression of both prior regimens. She received a total of 8 weekly LL-37 injections, with interval clinical shrinkage of injected lesions. However, approximately 45 days after initiation of this therapy, she presented with multiple verrucous papules and a vesiculo-bullous lesion on the trunk and extremities. Clinically, most of these lesions were thought to be either squamous cell carcinoma or inflamed seborrheic keratosis. Histologically, 11 of the total 12 skin biopsies showed similar histopathologic features, with a prominent lichenoid inflammatory infiltrate admixed with eosinophils and an overlying atypical squamous epithelial proliferation with verrucous and keratoacanthoma-like features and varying degrees of keratinocytic atypia. Interestingly, a majority of the lesions did not show spongiosis (11/12). All lesions resolved within 2 months of cessation of LL-37 injection therapy. This case highlights adverse dermatological manifestations of LL-37 therapy, similar to the consequences of other novel therapies.

Immunotherapies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have showed significant therapeutic benefit in patients with clinically advanced solid malignancies, including melanoma. However, immune-related adverse events (irAE) are common, and novel dermatologic toxicities continue to emerge as more patients are treated with immunotherapy. Here we describe a patient treated with combination immunotherapy of ipilimumab and pembrolizumab, who developed asymptomatic erythematous patches on both legs. Histopathologic examination revealed a cutaneous interstitial granulomatous dermatitis. Notably, our patient did not require cessation of immunotherapy for these lesions, which subsequently remained stable, while the patient's melanoma remained controlled. This case expands the dermatologic toxicity profile of immune checkpoint blockade, as recognition of such toxicities is critical to optimal patient management.

Background Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo. Granulomatous/sarcoid-like lesions are now being recognized with the current class of checkpoint inhibitors (CPIs) that involve the dermis, the subcutaneous tissue (panniculitis), and lymph nodes. Case presentation We report 3 patients who developed granulomatous/sarcoid-like lesions while being treated with immune checkpoint therapy for advanced-stage melanoma, and we provide a comprehensive review of the literature in which similar cases are described. To date, 26 patients (including the 3 from this report) have been described with a median age of 57 years who developed granulomatous/sarcoid-like lesions associated with CPIs (median onset 6 months), of which 77% of patients had melanoma as primary tumor. To manage this adverse side effect, therapy was withheld in 38% of patients and 44% of the patients were treated with systemic steroids and 8% patients with localized therapy (one patient with intralesional triamcinolone). 96% of patients demonstrated either resolution or improvement of granulomatous/sarcoid-like lesions associated with CPIs irrespective of medical intervention. Therapeutic response, stable disease, or remission of primary malignancy was observed in 71% of reported patients who developed granulomatous/sarcoid-like lesions associated with CPIs over a median follow-up of 11.5 months since initiation of treatment. Conclusions The development of granulomatous/sarcoid-like lesions associated with CPIs is a recognized manifestation with the current class of immune checkpoint therapy that may clinically and radiographically mimic disease recurrence. Awareness of this type of toxicity is important for appropriate management and possible measurement of therapeutic response in a subset of patients who manifest this type of immune-mediated reaction.

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.

Author(s): Jeter, Joanne M; Bowles, Tawnya L; Curiel-Lewandrowski, Clara; Swetter, Susan M; Filipp, Fabian V; Abdel-Malek, Zalfa A; Geskin, Larisa J; Brewer, Jerry D; Arbiser, Jack L; Gershenwald, Jeffrey E; Chu, Emily Y; Kirkwood, John M; Box, Neil F; Funchain, Pauline; Fisher, David E; Kendra, Kari L; Marghoob, Ashfaq A; Chen, Suephy C; Ming, Michael E; Albertini, Mark R; Vetto, John T; Margolin, Kim A; Pagoto, Sherry L; Hay, Jennifer L; Grossman, Douglas; Ellis, Darrel L; Kashani-Sabet, Mohammed; Mangold, Aaron R; Markovic, Svetomir N; Jr, Meyskens Frank L; Nelson, Kelly C; Powers, Jennifer G; Robinson, June K; Sahni, Debjani; Sekulic, Aleksandar; Sondak, Vernon K; Wei, Maria L; Zager, Jonathan S; Dellavalle, Robert P; Thompson, John A; Weinstock, Martin A; Leachman, Sancy A; Cassidy, Pamela B

Lentigo maligna melanoma (LMM) is a variant of melanoma that typically occurs on chronically sun-exposed skin of elderly individuals. Clinically, it presents as an irregular brown macule or patch on sun-damaged skin, most commonly on the head and neck region. Histologically, it is characterized by growth of predominantly solitary units of melanocytes with variable density initially along the dermoepidermal junction. This chapter discusses the clinical and histopathologic findings, ancillary tests, differential diagnosis, and management of LMM.

Importance Dermoscopy education in US dermatology residency programs varies widely, and there is currently no existing expert consensus identifying what is most important for resident physicians to know. Objectives To identify consensus-based learning constructs representing an appropriate foundational proficiency in dermoscopic image interpretation for dermatology resident physicians, including dermoscopic diagnoses, associated features, and representative teaching images. Defining these foundational proficiency learning constructs will facilitate further skill development in dermoscopic image interpretation to help residents achieve clinical proficiency. Design, Setting, and Participants A 2-phase modified Delphi surveying technique was used to identify resident learning constructs in 3 sequential sets of surveys—diagnoses, features, and images. Expert panelists were recruited through an email distributed to the 32 members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group. Twenty-six (81%) opted to participate. Surveys were distributed using RedCAP software. Main Outcomes and Measures Consensus on diagnoses, associated dermoscopic features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for US dermatology resident physicians. Results Twenty-six pigmented lesion and dermoscopy specialists completed 8 rounds of surveys, with 100% (26/26) response rate in all rounds. A final list of 32 diagnoses and 116 associated dermoscopic features was generated. Three hundred seventy-eight representative teaching images reached consensus with panelists. Conclusions and Relevance Consensus achieved in this modified Delphi process identified common dermoscopic diagnoses, associated features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for dermatology residency training. This list of validated objectives provides a consensus-based foundation of key learning points in dermoscopy to help resident physicians achieve clinical proficiency in dermoscopic image interpretation.