Cutaneous T cell Lymphoma in Skin of Color: A Review.

People of color (POC) affected by skin cancer suffer disproportionately from worse morbidity and mortality. Although skin cancers occur most frequently in White individuals overall, cutaneous T-cell lymphoma (CTCL) is an exception. CTCL is a rare skin cancer comprising several subtypes of non-Hodgkin lymphoma; each contains a unique clinical profile that varies with race. Our aim is to review and compile the differences in epidemiology, clinical presentation, treatments, and outcomes of the CTCL subtypes in Black, Asian or Pacific-Islander (API), and Hispanic patients. The current literature supports that there are nuances in the course of CTCL that differ with race. Across multiple studies, racial differences in incidence patterns have been reported, with the highest rates among Black patients. Cutaneous manifestation of CTCL are highly variable in POC, and the predilection for clinical CTCL variants often differs with race, as well as severity of cutaneous involvement (BSA). Response to and type of treatment also differs among POC, and may be partially attributable to the varying CTCL subtypes experienced by certain races. Prognostic factors tend to vary with race, although Black patients consistently experience poor outcomes, while API patients may have a more favorable prognosis. Currently, there is no definitive conclusion to account for differences observed in CTCL skin of color patients, however biologic and socioeconomic factors have been proposed as potential drivers. As POC comprise an increasing portion of our population, adequate physician awareness and knowledge of racial nuances in CTCL are necessary to begin addressing these disparities.

Sequencing of Cutaneous Squamous Cell Carcinoma Primary Tumors and Patient-Matched Metastases Reveals ALK as a Potential Driver in Metastases and Low Mutational Concordance in Immunocompromised Patients.

Cutaneous squamous cell carcinoma is a common skin cancer that is responsible for 1,000,000 cases and up to 9,000 deaths annually in the United States. Metastases occur in 2-5% of patients and are responsible for significant morbidity and mortality. The objective of this study is to perform targeted next-generation sequencing on a cohort of squamous cell carcinoma primary tumors and patient-matched lymph node metastases. An oncology 76-gene panel was run from formalin-fixed paraffin-embedded samples of patient-matched primary squamous cell carcinomas (10) and resultant metastases (10). ALK was discovered to be a driver mutation in metastases using two different algorithms, oncoCLUSTand dNdScv. Mutational concordance between primary tumors and metastases was notably lower in immunosuppressed patients, especially among pathogenic mutations (41.7% vs. 83.3%, P = 0.01). Sequencing of matched squamous cell carcinoma primary tumors and lymph node metastases identified genes and pathways that may have clinical importance, most notably ALK as a potential driver mutation of metastasis. Sequencing of both primary tumors and metastases may improve the efficacy of targeted therapies.

What's Eating You? Culex Mosquitoes and West Nile Virus.

West Nile virus (WNV) commonly presents cutaneously as a maculopapular rash on the trunk and extremities that most often appears around the time of defervescence and may serve as a positive prognostic indicator. Several laboratory tests can aid in diagnosis of WNV, including an IgM enzyme-linked immunosorbent assay (ELISA), but an antibody response may not be detectable for up to 8 days after symptom onset. Taking a comprehensive history in any patient presenting with a generalized maculopapular rash, fever, nonspecific symptoms, or neurologic changes can aid the astute dermatologist in promptly recognizing the possibility of WNV.

Basal Cell Carcinoma Gene Mutations Differ Between Asian, Hispanic, and Caucasian Patients: A Pilot Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy worldwide. While most BCCs are treated surgically, advanced BCCs are often treated with gene-targeted therapies. While there has been a lot of research in BCC from Caucasian patients, research is lacking in patients with skin of color. OBJECTIVE: To identify potential variations in BCC gene mutations between Asian, Hispanic, and Caucasian patients. METHODS: A cohort study was performed from 2015 to 2017 with 23 patients treated for BCC at an urban academic hospital. Gene mutations were assessed using a targeted mutation panel for 76 cancer-associated genes from formalin-fixed paraffin-embedded (FFPE) samples. RESULTS: Groups studied comprised Asian (n=5), Hispanic (n=10), and Caucasian (n=8) patients. The Hispanic cohort had the highest number of mutations per patient on average (3.4 versus 2.8 for both Caucasian and Asian cohorts). GATA3 mutations were more prevalent in Hispanic patients (P=0.02, single factor ANOVA). ARID1A and PTEN mutations co-occurred in the Hispanic cohort (P<0.05). The most common mutation in the Asian cohort was TP53 (2/5). The Caucasian cohort had the highest percent of UVB mutations (68.4%). CONCLUSIONS: This study shows potential differences in the prevalence of somatic gene mutations for BCC patients of different races and ethnicities, which could inform the underlying pathogenesis, impact the efficacy of therapies in specific populations, and may also help identify novel therapeutic targets. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5884.

Misclassification of Aggressive Basal Cell Carcinoma Subtypes and Implications for Management.

BACKGROUND: Management of basal cell carcinoma (BCC) varies by histopathologic subtype; however, biopsies may inadequately characterize them as nonaggressive, risking potential suboptimal treatment. OBJECTIVE: To characterize the rate of undetected aggressive BCC subtypes by size, location, and histopathology type. MATERIALS AND METHODS: Retrospective cohort study of 928 BCCs treated with Mohs Micrographic Surgery (MMS) at a tertiary academic institution from 2015 to 2017, comparing patient and tumor characteristics and histopathologic subtype on biopsy versus Mohs. RESULTS: Among the 825 BCCs with known subtypes on biopsy, 68% (561/825) were classified as nonaggressive, 28% (159/561) of which were subsequently found to have aggressive subtypes on MMS. Aggressive features were more often underrepresented in biopsy samples taken from Area H compared with Area M/L (odd ratio [OR] 2.65, 95% confidence interval [CI] 1.73-4.08, p < .001) or those with nodular subtypes (OR 2.19, CI 1.08-4.45, p = .03). Of concern, these unsuspected aggressive BCCs required more Mohs stages for clearance (mean 2.37, SD 0.72, p < .001) compared with BCCs that remained nonaggressive on both biopsy and Mohs (mean 1.50, SD 0.75). CONCLUSION: Given the high percentage of BCCs with unsuspected aggressive subtypes, higher clinical suspicion for undiagnosed high-risk BCCs should be given to nodular BCCs and to BCCs on Area H.

The Effects of Lavender Essential Oil on Wound Healing: A Review of the Current Evidence.

Background: The commercialization of essential oils has expanded their presence in the United States, and emerging studies demonstrate that they may have a place in Western medicine. One oil with a significant body of evidence is lavender essential oil, which may have benefits in wound healing. Objectives: This review aims to present the scientific literature on therapeutic lavender essential oil with the goal of expanding the current repertoire of cost-effective wound healing options available to physicians and patients. Methods: A review was conducted according to PRISMA guidelines in PubMed, Cochrane Library, and Embase from June 2018 through March 2019 to identify articles related to lavender essential oil in the context of wound healing. Results: This search yielded 36 unique studies, 20 of which remained after screening. This review utilizes human clinical trials (n = 7), animal trials (n = 5), in vitro studies (n = 2), and previously conducted reviews (n = 6). Overall, these studies demonstrated a faster rate of wound healing, increased expression of collagen, and enhanced activity of proteins involved in the tissue remodeling process in wounds treated with lavender essential oil. Conclusions: The current body of literature suggests a potential therapeutic benefit of lavender essential oil in wound healing. However, standardization of the chemical composition and additional high-quality human clinical trials are needed to further evaluate the safety and efficacy of lavender essential oil in clinical practice.

Targeted next-generation sequencing of matched localized and metastatic primary high-risk SCCs identifies driver and co-occurring mutations and novel therapeutic targets.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is the second most common type of skin cancer and is responsible for over one million cases annually. While only 3-5 % of SCCs metastasize, those that do are associated with significant morbidity and mortality. Using gene mutations to help predict metastasis and select therapeutics is still being explored. OBJECTIVE: To present novel data from targeted sequencing of 20 case-matched localized and metastatic high-risk SCCs. METHODS: A cancer-associated gene panel of 76 genes was run from formalin-fixed paraffin-embedded samples of 20 case-matched localized (10) and metastatic (10) high-risk SCCs (Vela Diagnostics). RESULTS: Using spatial clustering analysis, primary driver mutations were identified asEGFR in localized SCC and CDH1 in metastatic SCC. ERBB4 and STK11 were found to be significant co-occurring mutations in localized SCC. Pathway analyses showed the RTK/RAS, TP53, TGF-b, NOTCH1, PI3K, and cell cycle pathways to be highly relevant in all high-risk SCCs with the Wnt pathway enhanced in metastatic SCC only. CONCLUSIONS: This study compared gene mutations between localized and metastatic SCC with the intent of identifying key differences and new potential targeted treatment options. To our knowledge, the co-occurrence ofERBB4 and STK11 mutations has not been previously reported. Targeted inhibition of CDH1 and the Wnt pathway should be further explored in metastatic SCC.

Next-generation sequencing identifies novel single nucleotide polymorphisms in high-risk cutaneous squamous cell carcinoma: A pilot study.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) causes 1 million cases in the United States annually. There are germline single nucleotide polymorphisms (SNPs) that result in an increased risk of SCC and altered response to therapy. PREMISE: There may be biologically relevant SNPs not detected using traditional GWAS studies. HYPOTHESIS: There are clinically and biologically relevant SNPs in high-risk SCC that may only be appreciated with next-generation sequencing. HOW TO TEST HYPOTHESIS: We performed next-generation sequencing (NGS) on primary SCCs using a targeted mutation panel with 76 cancer-associated genes. We analysed the presence of SNPs in a cohort of 20 high-risk SCCs compared to the American population (AP) (dbSNP). RELEVANCE AND PERSPECTIVES: Missense rs3822214 was present in significantly more SCC cases versus the AP. While the remainder is synonymous SNPs, there is growing evidence suggesting clinical relevance of these variants. A larger cohort to validate these findings would be useful.

The proportion of male and female editors in women's health journals: A critical analysis and review of the sex gap.

BACKGROUND: Historically, women have been underrepresented in leadership positions in medicine. The reasons for this are multifactorial. In recent years, women's representation in medicine has improved. However, inequities in the proportion of men and women in medical leadership remain, especially with regard to editorial journal boards. OBJECTIVE: This study aimed to explore current trends of women in leadership positions on journal editorial boards. METHODS: A comprehensive search for women's health journals was performed in collaboration with university librarians in February 2019 using EMBASE, Scopus, SciFinder, and MEDLINE records for journals with relevance to women's health. Each journal was e-mailed to verify the accuracy of the journal editorial boards listed on their respective webpages. Five categories, as well as the totals for each journal, were analyzed for the proportion of women versus men: editor-in-chief, associate editor, deputy editor, and section editor, and other. RESULTS: Women comprised the minority of positions on women's health editorial boards. Of the total 1440 board members included, 602 members (42%) were women and 838 members (58%) were men. Women occupied 54 of 132 editor-in-chief positions (41%), 257 of 596 associate editor positions (43%), 13 of 42 deputy editor positions (30%), 46 of 120 section editor positions (38%), and 232 of 549 other editor positions (42%). CONCLUSION: Although the sex gap in leadership in medicine is improving, it is still present. Our findings suggest that women are underrepresented as editors at most levels in women's health journals centered on topics such as reproductive health, obstetrics and gynecology, perinatology, gynecological oncology, and breastfeeding. With sponsorship/mentorship for women, flexible scheduling, and considerate thought in leadership appointment, this sex gap will continue to improve.

Representation of women as editors in dermatology journals: A comprehensive review.

BACKGROUND: Despite a substantial increase in the number of women matriculating into medical school, a gender gap still exists with respect to academic leadership positions. This gap is apparent in the field of dermatology, particularly in the composition of dermatology journal editorial boards. To address this gap, we must first acknowledge its existence, examine potential reasons for its existence, and propose strategies to narrow the gap. OBJECTIVE: Our objective is to determine the representation of women as editors in dermatology journals. METHODS: A comprehensive search was performed for dermatology journals indexed in Medline, Journal Citation Reports, Scopus, and Embase in August, September, and October 2018. The editorial board of each journal was analyzed for the number and percentage of male and female editors in four different positions. We verified the accuracy of editorial boards listed on publisher websites by emailing administrative personnel. We also recorded the number of years from terminal degree for editorial board members of the 10 journals with the highest impact factors using SCImago Journal Rankings. RESULTS: Women occupied 18% of editor-in-chief positions, 36% of deputy editor roles, 22% of overall editorial board positions, and 22% of other board roles. The average number of years since terminal degree was not statistically different between women and men, with women averaging 30.2 years and men averaging 28.0 years since completion of terminal degree (p = .27). CONCLUSIONS: Our findings suggest that women are underrepresented as editors at all levels in dermatology journals. This supports prior findings reporting a minority of women in academic leadership roles. Thus, although women have made major advancements in the medical field over the past century, there remains room for progress with regard to equal representation in academic leadership roles, including editorial positions, professorships, and department chair roles.

Defining skin cancer local recurrence.

Definitions of skin cancer recurrence are variable and nonstandardized, which can lead to inconsistent and potentially inappropriate management of tumors of uncertain recurrence status. Defining recurrence is important given the potential association with metastasis in both melanoma and nonmelanoma skin cancer. A review of the literature across multiple disciplines involved in the care of skin cancer patients reveals that although criteria for recurrence are provided in the majority of cases, most are vague and inconsistent. Given the presumably increased morbidity and mortality associated with recurrent tumors, accurate identification and appropriate management is paramount. In addition, value-based health care necessitates validated and relevant outcome measures that are standardized and, thus, enable tracking of comparable and corresponding outcomes. A universal definition of localized skin cancer recurrence would ultimately allow for improved surveillance and informed therapeutic strategies to decrease morbidity and mortality of patients afflicted with skin cancer, the most common cancer nationwide.

Virtual Reality to Improve the Experience of the Mohs Patient-A Prospective Interventional Study.

BACKGROUND: Nonmelanoma skin cancer is the most common cancer in the United States with significant quality of life impact. OBJECTIVE: To assess the utility of a highly immersive virtual reality (VR) experience in the context of outpatient skin cancer surgery as a means to minimize patient-reported feelings of anxiety or pain. The authors also sought to assess the effects on patient-reported overall satisfaction. MATERIALS AND METHODS: Patients completed a pre-VR experience survey after completion of their first Mohs surgery layer, followed by a 10-minute VR experience, and a post-VR experience survey. Differences in the pre-VR survey and post-VR survey were compared using the chi-square test. The anxiety scores were compared using a t-test. RESULTS: In all but 2 questions, there was a trend toward improvement of the anxiety-related sensations after completion of the VR experience. There were statistically significant differences for 4 questions: "Are you currently feeling unable to relax" (p = .0013), "are you currently feeling fear of the worst happening" (p < .0001), "are you currently feeling terrified or afraid" (p = .0046), and "are you currently feeling nervous" (p < .0001). CONCLUSION: Virtual reality experiences during the Mohs surgical day significantly improved measures of anxiety and patient satisfaction.

A Retrospective Cohort Study of Cutaneous Squamous Cell Carcinoma With Lymph Node Metastasis: Risk Factors and Clinical Course.

BACKGROUND: The single most important prognostic indicator for mortality in patients with cutaneous squamous cell carcinoma (SCC) is the development of nodal metastasis (NM). OBJECTIVE: To characterize the risk factors for and clinical course of cutaneous SCC with NM. METHODS: Ten-year retrospective cohort study (2006-2017) at an academic tertiary care center reviewing 53 cutaneous SCC tumors with NM. RESULTS: Most patients were men (84.6%, 44/52), and almost all primary tumors were on the head and neck (96.2%, 51/53). Most primary tumors were characterized by known "high-risk features" including perineural invasion (56.6%, 30/53), diameter ≥2 cm (54.7%, 29/53), invasion beyond subcutaneous fat (43.4%, 23/53), and poor differentiation (32.1%, 17/53). In addition, many tumors were recurrent (52.8%, 28/53), and many patients were immunosuppressed (30.8%, 16/52). Disease-free survival after treatment of nodal disease was 7.5% (4/53) at 5 years. CONCLUSION: To the best of the authors' knowledge, this study is the largest retrospective cohort of cutaneous SCC with NM to date. The results verify the significance of "high-risk features" used by current staging systems while highlighting additional features that may have prognostic value. This study may be used to refine current staging systems, improve early detection, and optimize management for these aggressive tumors.

Cetuximab as a Component of Multimodality Treatment of High-Risk Cutaneous Squamous Cell Carcinoma: A Retrospective Analysis From a Single Tertiary Academic Medical Center.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and has potential for regional or distant metastasis. Despite the standardization of features associated with high-risk cSCC, an advanced subset of cSCC, there is no established consensus regarding proper management of this tumor. OBJECTIVE: To evaluate the efficacy of cetuximab, add to existing management options, and aid in the development of standardized treatment for this tumor. MATERIALS AND METHODS: Medical records were searched using Current Procedural Terminology codes for cetuximab and cSCC. Demographic data and tumor characteristics, along with treatment regimens and follow-up times, were collected. A total of 20 cases were examined. RESULTS: Of the 20 cases, 3 experienced a complete response and 7 experienced a partial response, yielding an overall response of 50% and a combined median disease-free survival of 6.35 months (range 1-46.8 months). CONCLUSION: As most of the patients who experienced a response received cetuximab as part of a multimodality treatment approach, cetuximab may be most efficacious when administered with concurrent therapies such as surgery or radiation. Further larger prospective studies to determine the optimal dosing and frequency of cetuximab and the utility of concurrent therapies are warranted.