Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis.

PURPOSE: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment. EXPERIMENTAL DESIGN: We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021. RESULTS: We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions. CONCLUSIONS: The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.

Cutaneous and Noncutaneous Adverse Effects in Patients with Advanced Melanoma Receiving Immunotherapy.

Relationships between cutaneous adverse effects (CAEs) and noncutaneous adverse effects (NCAEs) of melanoma immunotherapy may help identify patterns tied to distinct immunologic pathways. The objective of this study was to determine the associations between CAEs and NCAEs among patients with stages III-IV melanoma receiving immunotherapy and who were enrolled in a prospective cohort. Electronic medical record data were abstracted from the first immunotherapy infusion until 1 year later. CAEs were rash or itch. NCAEs were symptoms and/or laboratory abnormalities documented as immunotherapy related. NCAE onset and time to NCAE were compared between participants with and without CAEs using ORs and Wilcoxon rank sum tests. Of 34 participants, 11 (32.4%) developed no adverse effects, 7 (20.1%) developed CAEs only, 3 (8.8%) developed NCAEs only, and 13 (38.2%) developed both CAEs and NCAEs. After adjustment for age, sex, and immunotherapy regimen, CAE was associated with higher odds of NCAE development (OR = 9.72; 95% confidence interval = 1.2-76.8). Median NCAE onset was 63 days in those with CAEs and 168 days in those without CAEs (P = 0.41). Limitations included a small sample size, and larger prospective studies should be performed to confirm findings. CAE was associated with NCAE development. Early identification and treatment of NCAEs may reduce symptom burden and hospitalizations associated with NCAEs.

Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

BACKGROUND: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. METHODS: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6-12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. RESULTS: Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6-12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. CONCLUSIONS: Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Financial toxicity and skin cancer care in the US: population-based survey from 2011 to 2018.

This cross-sectional study aimed to examine financial toxicity among people with skin cancer using pooled National Health Interview Survey data from adults in 2011-2018. Material, behavioral, and psychological markers of financial toxicity were compared by lifetime skin cancer history (any melanoma, any skin cancer beside melanoma, and no skin cancer) using multivariable logistic regression models. Of 257,652 total participants, 1874 (0.73%) had known melanoma and 7073 (2.75%) had any skin cancer beside melanoma. History of skin cancers was not independently associated with increased markers of financial toxicity after adjustment for sociodemographic and medical co-morbidities.

Survival and tumor characteristics of patients presenting with single primary versus second primary melanoma lesions.

BACKGROUND: Patients with single primary melanomas have an increased risk of developing subsequent melanomas. Secondary tumors diagnosed within and after 3 months are termed "synchronous" and "asynchronous," respectively. OBJECTIVE: To compare tumor distributions and survival characteristics between patients with second primary melanomas and those with single primary melanomas. METHODS: Retrospective cohort study. Data were collected from an institutional database from 14,029 patients with a diagnosis of a primary melanoma seen between 1970 and 2004. RESULTS: The synchronous and asynchronous cohorts demonstrated significantly improved survival probabilities compared with the single primary cohort (P = .04 and .002, respectively). Single primary lesions (2.2 ± 2.3 mm) were significantly thicker than the first-identified synchronous (2.0 ± 1.7 mm) and asynchronous (1.7 ± 1.3 mm) lesions. Synchronous lesions were more likely to be anatomically concordant compared with asynchronous lesions (55.7% vs 38.2%, P < .001). LIMITATIONS: Single-center study design and incomplete records for second primary melanoma Breslow depth and histopathology. CONCLUSION: Patients with second primary melanomas demonstrated a significant survival advantage and thinner lesions compared with those with single primary melanomas. Our reported tumor distributions support the role of full body skin examinations, with attention to the region of initial diagnosis.

Patient satisfaction with the Veteran's Administration teledermatology service.

BACKGROUND: Teledermatology is comparable to face-to-face visits in providing accurate diagnoses and effective treatments. However, there are limited data regarding patient satisfaction with teledermatology models that more directly convey provider recommendations to patients. OBJECTIVE: To assess patient satisfaction with the teledermatology service at the Atlanta Veterans Affairs Medical Center (AVAMC). METHODS: A cross-sectional, phone-based questionnaire study of 175 AVAMC teledermatology patients was performed to investigate patient satisfaction. In phase 1 (n = 100), we compared the teleconsultative and telemedicine models. In phase 2 (n = 75), we compared patients who received 1 of 3 possible consult outcomes: reassurance, appointment for biopsy, or appointment for face-to-face evaluation. RESULTS: There were no statistically significant differences in satisfaction between patients who were seen with the telemedicine and teleconsultative models. Patients who received appointments for face-to-face evaluation or biopsy were more satisfied than patients who received reassurance only. Both phases were remarkable for high patient satisfaction among all cohorts. LIMITATIONS: This study was performed at a single Veterans Affairs medical center and is vulnerable to both nonresponse bias and recall bias. CONCLUSION: Overall, patients are satisfied with teledermatology services at the AVAMC. Strong partnership with referring primary care providers and clear delineation of responsibilities is vital to the teledermatology process.

Skin Cancer Behavioral Risk Factors and Screening Among U.S. Adults in Same-Sex Relationships: A Population-Based Study from 2000 to 2015.

Purpose: Skin cancer is prevalent in sexual minority men but little is known about risk factors and screening specifically among couples in same-sex relationships (SSR). We aimed to compare sunburns, sun-protective behaviors, indoor tanning, and total body skin examinations (TBSEs) between people in SSR with those in opposite-sex relationships (OSR). Methods: We conducted a pooled cross-sectional analysis of 2000-2015 data from the National Health Interview Survey, a nationally representative survey of the United States civilian population. Results: Of 102,365 adults with a spouse or married partner, 448 (0.4%) were men in SSR, 48,312 (48.1%) men in OSR, 497 (0.5%) women in SSR, and 53,108 women in OSR (51.9%). Men in SSR were more likely than men in OSR to seek shade (adjusted odds ratio [aOR] = 1.41; 95% confidence interval [CI] = 1.07-1.85), tan indoors (aOR = 3.71; 95% CI = 2.38-5.78), and receive any TBSE (aOR = 2.45; 95% CI = 1.69-3.54) after adjusting for sociodemographic factors, health insurance status, and health behaviors. Men in SSR were less likely than men in OSR to wear long pants (aOR = 0.63; 95% CI = 0.46-0.85) and caps or visors (aOR = 0.50; 95% CI = 0.36-0.69). No differences in sunburns, sun-protective behaviors, indoor tanning, and TBSE between women in SSR and OSR were observed after multivariable adjustment. Conclusion: Patterns of sun-protective behaviors and indoor tanning among men in SSR, compared with men in OSR, demonstrate modifiable behaviors that may mitigate skin cancer risk. Dyadic counseling and public health interventions geared toward men in SSR may promote sun-protective behaviors and reduce indoor tanning.

Dermoscopic Photographs Impact Confidence and Management of Remotely Triaged Skin Lesions.

Introduction: Improving remote triage is crucial given expansions in tele-dermatology and with limited in-person care during COVID-19. In addition to clinical pictures, dermoscopic images may provide utility for triage. Objectives: To determine if dermoscopic images enhance confidence, triage accuracy, and triage prioritization for tele-dermatology. Methods: In this preliminary parallel convergent mixed-methods study, a cohort of dermatologists and residents assessed skin lesions using clinical and dermoscopic images. For each case, participants viewed a clinical image and determined diagnostic category, management, urgency, and decision-making confidence. They subsequently viewed the associated dermoscopy and answered the same questions. A moderated focus group discussion followed to explore perceptions on the role of dermoscopy in tele-dermatology. Results: Dermoscopy improved recognition of malignancies by 23% and significantly reduced triage urgency measures for non-malignant lesions. Participants endorsed specific utilities of tele-dermoscopy, such as for evaluating pigmented lesions, with limitations including poor image quality. Conclusions: Dermoscopic images may be useful when remotely triaging skin lesions. Standardized imaging protocols are needed.

Validation of actinic keratosis diagnosis and treatment codes among veterans living with HIV.

PURPOSE: Actinic keratoses (AK) diagnosis, billing, and pharmacy codes have not been validated among people living with human immunodeficiency virus (HIV), preventing use in epidemiologic and clinical research. We aimed to calculate the positive predictive value (PPV) of AK diagnosis codes, procedural codes for destruction of pre-malignant lesions, and pharmacy codes for topical 5-fluorouracil. METHODS: Patients diagnosed with HIV within the Infectious Disease clinic at the Atlanta Veterans Affairs Medical Center from 1/1/2002 to 8/5/2017 were eligible. Patients were included if they had any of the following: encounters with a diagnosis for AK (International Classification of Diseases [ICD]-9: 702.0; ICD-10: L57.0), procedural codes for destruction of premalignant lesions (Current Procedural Terminology [CPT]: 17000, 17003, and 17004), and prescriptions for topical 5-fluorouracil. PPV and binomial 95% confidence intervals were calculated. RESULTS: PPV was 91.9% (89.1-94.7) for 369 encounters with an AK diagnosis. For procedural codes, PPV was 52.6% (48.1-57.2) for 454 encounters with destruction of 1 pre-malignant lesion, 63.7% (58.4-68.9) for 322 encounters with destruction of 2-14 lesions, and 57.7% (38.7-76.7) for 26 encounters with destruction of 15+ lesions. PPV was 72.9% (63.5-82.4) for 85 encounters with a prescription of topical 5-fluorouracil. CONCLUSION: AK diagnosis codes are appropriate to use in epidemiologic and health policy research among people living with HIV and may be more reliable than destruction of pre-malignant lesion CPT codes.

Skin Cancer Risk Factors and Screening Among Asian American Individuals.

IMPORTANCE: Asian American individuals are the fastest growing racial group in the US but remain underrepresented in health disparities research, including research on skin cancer risk factors and screening. Improved understanding of preventable skin cancer risk factors and screening may demonstrate unmet needs among Asian American individuals. OBJECTIVE: To examine sunburns, sun-protective behaviors, indoor tanning, and total body skin examinations (TBSEs) for skin cancer screening among Asian American subgroups compared with non-Hispanic White individuals. DESIGN, SETTING, AND PARTICIPANTS: The National Health Interview Survey is a nationally representative cross-sectional survey in the US that assesses health behaviors. Self-identified Asian Indian, Chinese, Filipino, non-Hispanic White, and other Asian respondents from survey years 2000, 2005, 2010, and 2015 were included. Data were analyzed from July to November 2021. MAIN OUTCOMES AND MEASURES: Any sunburn within the last year; sun-protective behaviors included applying sunscreen, staying under shade, wearing long-sleeved shirts, wearing long clothing to the ankles, wearing hats, and wearing caps most of the time or always when out in the sun; any indoor tanning within the last year; any TBSE ever. RESULTS: Of 84 030 participants, 5694 were Asian American (6.8%) and 78 336 (93.2%) were Non-Hispanic White; of these individuals, 1073 (weighted prevalence, 21.0%) were Asian Indian, 1165 (19.4%) Chinese, 1312 (23.5%) Filipino, and 2144 (36.1%) Other Asian. All Asian American subgroups were more likely to seek shade, wear long clothing to the ankles, and wear long-sleeved shirts but less likely to sunburn, apply sunscreen, tan indoors, and receive TBSE than Non-Hispanic White individuals. Asian Indian individuals were less likely than Chinese participants to apply sunscreen (adjusted odds ratio [aOR], 0.55; 95% CI, 0.41-0.74) or wear a hat (aOR, 0.53; 95% CI, 0.37-0.76) and more likely to wear long-sleeved shirts (aOR, 1.89; 95% CI, 1.52-2.33) or long clothing to the ankles (aOR, 1.56; 95% CI, 1.28-1.90). CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study found that disaggregated comparisons among Asian American individuals demonstrated differences in skin cancer risk factors that may be used to identify high-risk subgroups and inform culturally aware counseling when indicated. Future studies should further sample Asian American individuals to evaluate for potential masked health disparities through disaggregated analysis.

High-frequency ultrasound in clinical dermatology: a review.

BACKGROUND: Ultrasound was first introduced in clinical dermatology in 1979. Since that time, ultrasound technology has continued to develop along with its popularity and utility. Today, high-frequency ultrasound (HFUS), or ultrasound using a frequency of at least 10 megahertz (MHz), allows for high-resolution imaging of the skin from the stratum corneum to the deep fascia. This non-invasive and easy-to-interpret tool allows physicians to assess skin findings in real-time, enabling enhanced diagnostic, management, and surgical capabilities. In this review, we discuss how HFUS fits into the landscape of skin imaging. We provide a brief history of its introduction to dermatology, explain key principles of ultrasonography, and review its use in characterizing normal skin, common neoplasms of the skin, dermatologic diseases and cosmetic dermatology. CONCLUSION: As frequency advancements in ultrasonography continue, the broad applications of this imaging modality will continue to grow. HFUS is a fast, safe and readily available tool that can aid in diagnosing, monitoring and treating dermatologic conditions by providing more objective assessment measures.

Validation of the Three-Item Skindex-Mini Among Hidradenitis Suppurativa Patients With Diverse Racial Backgrounds.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that severely impairs patients' quality of life (QoL). Instruments such as the 10-item Dermatology Life Quality Index and 16-item Skindex-16 have been used to assess QoL in HS; however, it is unknown whether the shorter 3-item Skindex-mini can also provide an accurate assessment of skin-related QoL in patients with HS. OBJECTIVES: The aim was to assess how well the Skindex-16 correlates with its shorter adaptation, the Skindex-mini, in capturing QoL among patients with HS. METHODS: This retrospective cross-sectional study included all HS patients seen in the HS Clinic at The Emory Clinic between January 1, 2019, and August 16, 2019. We compared the correlation between the symptom, emotion, and function domains of the Skindex-16 and Skindex-mini using Pearson correlation coefficients (CC). Secondary outcome measures included individual survey item analysis, ItchyQuant scores, and numeric rating scale of pain. RESULTS: We identified 108 encounters among 75 unique hidradenitis suppurativa patients (43 black/African American, 18 white, 5 Asian/Pacific Islander, 3 Latino, 4 Other, 2 unknown). Pearson CC between the Skindex-16 and Skindex-mini domain scores for all encounters were 0.770 (P < .001), 0.787 (P < .001), and 0.801 (P < .001) for the symptom, emotion, and function domains, respectively. The mean pain and ItchyQuant scores were 4.14 (SD 3.31) and 3.55 (SD 3.34), respectively. CONCLUSIONS: The Skindex-mini correlated highly with the Skindex-16 in a racially diverse group of patients with HS. The Skindex-mini is a streamlined QoL instrument that could be practically implemented into routine clinical care among diverse patients presenting to dermatology.