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Antiretroviral therapy (ART) may alter susceptibility to nonkeratinocyte skin cancers (NKSCs) by improving immunity in people living with HIV (PLWH). Using linked data from HIV and cancer registries in 12 US states/regions during the ART era (1996-2018), we calculated standardized incidence ratios (SIRs) for 27 NKSCs comparing incidence to the general population. Risk factors for NKSCs were evaluated using Poisson regression. There were 2,743 NKSCs diagnosed in 585,706 PLWH followed for 4,575,794 person-years. Kaposi sarcoma (KS) was the most common cancer (82%) followed by melanoma (12%) and cutaneous lymphoma (2.6%). Incidence was elevated for virus-related NKSCs: KS (SIR 147, 95%CI 141-153), diffuse large B-cell lymphoma (DLBCL, 5.19, 3.13-8.11), and Merkel cell carcinoma (MCC, 3.15, 1.93-4.87); elevated incidence for DLBCL and MCC was observed only among PLWH with a prior AIDS diagnosis. KS risk was highest among men who have sex with men. Incidence was not increased for melanoma, adnexal carcinomas, and sarcomas. Melanoma and MCC arose disproportionately on sun-exposed skin, supporting a role for ultraviolet radiation in their development. In conclusion, risk for most NKSCs was similar to the general population during the ART era, suggesting that PLWH without NKSC risk factors may not require intensive skin surveillance.

BACKGROUND: CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes. OBJECTIVE: We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1. METHODS: We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and non-carriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family. RESULTS: Histologic slides were evaluated for 290 melanomas (139 from 132 non-carriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in the majority of invasive melanomas from POT1 carriers (10 of 15 [67%], P

The characterization of the effects of solar UVR on a broad set of circulating markers in systemic immunity and inflammation may provide insight into the mechanisms responsible for the UVR associations observed for several benign and malignant diseases. We examined the associations between exposure to solar UVR and circulating levels of 78 markers among 1,819 individuals aged 55–74 years who participated in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial using multiplex assays. Solar UVR was derived by linking the geocoded locations of 10 screening centers across the continental United States and the date of blood draw to the National Solar Radiation Database from 1993 to 2005. We assessed associations between ambient solar UVR and dichotomized marker levels using adjusted weighted logistic regression models and applied a 5% false discovery rate criterion to P-values. UVR exposure was associated (P < 0.05) with 9 of the 78 markers. CCL27, CCL4, FGF2, GM-CSF, IFN-γ, soluble IL4R, IL-7, and IL-11 levels were lower with increasing UVR tertile, with adjusted ORs ranging from 0.66 to 0.80, and the significant association for CCL27 withstood multiple comparison correction. In contrast, CRP levels were elevated with increasing UVR. Solar UVR was associated with alterations in systemic immune and inflammation marker levels., Graphical abstract

IMPORTANCE: Nonkeratinocyte skin cancers are an important cause of morbidity and mortality for immunosuppressed solid organ transplant recipients (SOTRs), but the spectrum of disease and risk factor characteristics are unknown. OBJECTIVE: To characterize the spectrum of disease and risk factors for common and rare nonkeratinocyte skin cancers in SOTRs. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included 444 497 SOTRs who underwent a transplant in the US between January 1, 1987, and December 31, 2017, using linked data from the national transplant registry and 32 cancer registries. Data analysis was conducted from April 1, 2021, to September 30, 2021. MAIN OUTCOMES AND MEASURES: Standardized incidence ratios (SIRs) were used to assess risk relative to the general population, and Poisson regression was used to evaluate risk factors. RESULTS: A total of 2380 nonkeratinocyte skin cancers were identified among 444 497 SOTRs (median age at transplant, 50 years; range, 0-96 years; 274 276 [61.7%] male; 272 241 [61.2%] non-Hispanic White). Melanoma was the most common cancer (1471 [61.8%]), followed by Merkel cell carcinoma (334 [14.0%]), Kaposi sarcoma (186 [7.8%]), sebaceous carcinoma (170 [7.1%]), and cutaneous lymphomas (108 [4.5%]). Risks were most strongly elevated for cancers associated with viruses, including Kaposi sarcoma (SIR, 20.5; 95% CI, 17.7-23.7), Merkel cell carcinoma (SIR, 16.2; 95% CI, 14.5-18.1), and extranodal natural killer/T-cell lymphoma (SIR, 44.3; 95% CI, 5.37-160). Risks were also significantly elevated for sebaceous carcinoma (SIR, 15.2; 95% CI, 13.0-17.7), anaplastic large cell lymphoma (SIR, 6.82; 95% CI, 4.53-9.85), and diffuse large B-cell lymphoma (SIR, 5.17; 95% CI, 3.28-7.76). Several characteristics were independently associated with greater risk for multiple skin cancer types, including male sex, older age at transplant, factors associated with UV radiation exposure (non-Hispanic White race and ethnicity, living in an area with higher UV radiation exposure, and posttransplant diagnosis of keratinocyte carcinoma), and increasing time since transplantation. Treatment with mammalian target of rapamycin inhibitors was associated with reduced melanoma incidence (incidence rate ratio, 0.75; 95% CI, 0.57-0.98). A total of 847 skin cancers (39.4%) occurred on the head and neck. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that viruses, UV radiation exposure, and immunosuppression are associated with the development of skin cancer in SOTRs. Certain high-risk subgroups may benefit from increased skin surveillance, and treatment with mammalian target of rapamycin inhibitors could be effective for melanoma chemoprevention in the transplant population.

Importance Risk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights. Objective To assess SC incidence and patient survival after solid organ transplantation. Design, Setting, and Participants This cohort study, conducted from January 1, 1987, to December 31, 2017, used data from the Transplant Cancer Match Study, which links transplant and cancer registry data for 17 states and 1 metropolitan area in the United States. Altogether, these registries account for approximately 46% of all US transplants. Data on demographic and transplant characteristics as well as induction and initial maintenance immunosuppressive therapies were obtained from the transplant registry. Standardized incidence ratios (SIRs) comparing SC incidence among SOTRs to the general population were calculated. Incidence rate ratios (IRRs) comparing SC risk between SOTR subgroups were calculated using multivariate Poisson regression. Cox regression was used to compare overall survival between SC cases in SOTRs and other individuals. Main Outcomes and Measures Sebaceous carcinoma incidence and overall patient survival after transplantation compared with the general population. Results A total of 326 282 transplant procedures were performed for 301 075 patients (No. [%] age at transplant, 126 550 [38.8%] aged 0-44 years; 82 394 [25.3%] aged 45-54 years; 82 082 [25.5%] aged 55-64 years; 35 256 [10.8%] aged ≥65 years; 201 354 male patients [61.7%]; 202 557 White patients [62.1%]). A total of 102 SCs were diagnosed in 301 075 SOTRs, corresponding to a 25-fold increased incidence (SIR, 24.8; 95% CI, 20.2-30.1). Incidence was especially elevated among lung recipients (SIR, 47.7; 95% CI, 20.6-94.0) and after a posttransplant diagnosis of cutaneous squamous cell carcinoma (SIR, 104.0; 95% CI, 62.8-163.0). Among SOTRs, factors independently associated with SC risk included male sex (IRR, 2.46; 95% CI, 1.48-4.07; P

Sebaceous carcinoma (SC) is an aggressive skin tumor. Although ultraviolet radiation (UVR) is an important risk factor for some skin cancer types, no population-level study has evaluated for an association between UVR and SC risk. Herein, we examined satellite-based ambient UVR in relation to SC incidence using Surveillance, Epidemiology, and End Results 18 cancer registry data (2000–2016). There were 3503 microscopically confirmed cases of SC diagnosed during the study period. For non-Hispanic whites, there was an association between increasing ambient UVR and SC risk (incidence rate ratio [per UVR quartile] = 1.15, 95% confidence interval = 1.11 to 1.19; two-sided P

CDKN2A and CDK4 are well-established melanoma susceptibility genes, but their effect on tumor location and distribution is unknown. We used a case-case study design to assess for differences in tumor location between mutation carriers (CDKN2A = 141 patients, 348 melanomas; CDK4 = 15 patients, 54 melanomas) and noncarriers (104 patients, 157 melanomas) in US melanoma-prone families. Associations between groups were assessed with chi-square tests. Odds ratios (ORs) for tumor location were adjusted for diagnosis age, gender, and superficial spreading subtype. Models included random effects to account for within individual and family correlations. Compared with having a truncal melanoma, CDK4 (vs. noncarriers: lower extremities OR = 14.5, 95% confidence interval [CI] = 5.02-42.0, P0.001; upper extremities OR = 6.88, 95% CI = 2.37-19.9, P0.001; head and neck OR = 18.6, 95% CI = 4.04-85.2, P0.001) and CDKN2A (vs. noncarriers: lower extremities OR = 3.01, 95% CI = 1.56-5.82, P0.05; upper extremities OR = 1.91, 95% CI = 1.03-3.52, P 0.05; head and neck OR = 5.40, 95% CI = 2.10-13.9, P0.001) carriers had higher odds of developing melanoma at all other sites. Similar findings were observed for analyses stratified by gender, age, and first versus subsequent melanoma diagnoses. Further studies are needed to understand the biology underlying these genotype-associated patterns of tumor development, which could provide new insights into melanoma treatment and prevention.

Background Teledermatology may improve dermatologic care access in underserved areas and expand the clinical experience of dermatologists-in-training. The potential for teledermatology to supplement global health curricula in dermatology residency education has not been explored. Methods An international virtual grand rounds (VGR) curriculum was created based on teledermatology cases from Kabul, Afghanistan. The learning objectives included understanding the diagnosis and management of skin diseases in unfamiliar resource-limited settings and highlighting socioeconomic, cross-cultural, and ethical issues. A 17-item, Likert scale questionnaire was used to assess the effectiveness of the curriculum, including specific Accreditation Council for Graduate Medical Education (ACGME) competencies, as well as interest in global health and teledermatology. Results The survey was completed by 85 of 118 VGR attendees (72% response rate). Most respondents considered the curriculum valuable to their education (mean 4.5 on a 5-point Likert scale; standard deviation, 0.5), learned more about diagnosis and treatment of skin diseases in international settings (4.5; 0.6) and in the US (4.1; 0.8), and learned more about socioeconomic, cultural, and ethical issues in skin health (4.6; 0.5). The majority also reported being more interested in global dermatology (4.1; 0.8) and would recommend VGR to a colleague (4.5; 0.6). Conclusion This pilot curriculum provided an innovative platform to enhance undergraduate and graduate medical education in international dermatology. International teledermatology education may be used to address multiple ACGME core competencies and increase resident awareness of sociocultural determinants of skin health.

Trends in the training, supply, availability, career decisions, and retirement of US dermatology physicians are not well delineated. The current study evaluates whether growth in the dermatology workforce will keep pace with population expansion in the United States. A dermatologist supply model was projected to 2030 drawing on data from the American Academy of Dermatology, American Medical Association, Bureau of Labor Statistics, American Association of Medical Colleges, and other associations. The clinically active dermatologist workforce in 2015 was 36 per capita (1,000,000); entry following postgraduate training was age 30 with career separation at age 65 on average. Added to the provider model are physician assistants and nurse practitioners in dermatology practices. A linear regression micro simulation model based on age cohorts produced a per capita supply of dermatology providers of 61 (±3) per 1,000,000 by 2030, up from 47 in 2016. The dermatology workforce is growing faster than population expansion. Workforce estimates could be affected by changing trends in retirement and training of dermatology providers. Investments in training of nurse practitioners and physician assistants, in addition to training more doctors, may be an effective strategy for increasing access to care in populations with low dermatologist density.

Trends in the training, supply, availability, career decisions, and retirement of US dermatology physicians are not well delineated. The current study evaluates whether growth in the dermatology workforce will keep pace with population expansion in the United States. A dermatologist supply model was projected to 2030 drawing on data from the American Academy of Dermatology, American Medical Association, Bureau of Labor Statistics, American Association of Medical Colleges, and other associations. The clinically active dermatologist workforce in 2015 was 36 per capita (1,000,000); entry following postgraduate training was age 30 with career separation at age 65 on average. Added to the provider model are physician assistants and nurse practitioners in dermatology practices. A linear regression micro simulation model based on age cohorts produced a per capita supply of dermatology providers of 61 (±3) per 1,000,000 by 2030, up from 47 in 2016. The dermatology workforce is growing faster than population expansion. Workforce estimates could be affected by changing trends in retirement and training of dermatology providers. Investments in training of nurse practitioners and physician assistants, in addition to training more doctors, may be an effective strategy for increasing access to care in populations with low dermatologist density.

Anecdotal reports of children experiencing eczema flares during winter and summer months along with global variation in eczema prevalence has fueled speculation that climate may modulate disease activity. The aim of this study was to determine whether long-term weather patterns affect the severity and persistence of eczema symptoms in children. We performed a prospective cohort study of US children (N=5,595) enrolled in PEER (Pediatric Eczema Elective Registry) between 2004 and 2012 to evaluate the effect of climate (daily temperature, daily sun exposure, daily humidity) on the severity of eczema symptoms. Odds ratios (ORs) were calculated for the patient-evaluated outcome of disease control. Multivariate logistic regression modeling adjusting for gender, race, income, and topical medication use demonstrated that higher temperature (OR=0.90, 95% confidence interval (CI): 0.87–0.93, P

Connexins (Cx) are structural proteins that form gap junctions, which are vital to cell-cell communication and help to regulate cell division. The purpose of this study was to evaluate if there are diagnostically important differences in immunostaining for connexins 43 (Cx43) and 26 (Cx26) in melanoma compared with nevi. Formalin-fixed paraffin-embedded sections of 34 histologically well-characterized melanocytic lesions, 17 primary malignant melanomas (MM), and 17 nevi were stained with a polyclonal antibody to Cx43 and a polyclonal antibody to Cx26. Immunoreactivity in tumor cells was evaluated semiquantitatively based on extent (1%-100%) and intensity (0-3) of reactivity. A score of 0-300 was generated by the product of the extent and intensity readings in each case. Significantly higher Cx43 immunoreactivity was detected in MM (mean intensity score = 253.5; 95% confidence interval, 227.9-279.2; P = 0.002) compared with nevi (mean intensity score = 152.4; 95% confidence interval, 104.9-199.8). In contrast, Cx26 immunoreactivity was less than 5% or entirely absent in all melanocytic tumors (n = 34). The significantly higher Cx43 staining in MM when compared with nevi suggests an oncogenic role for this protein in melanocytic tumor progression. Consequently, the evaluation of immunohistochemical staining for Cx43 in conjunction with other ancillary stains and tumor histology may be helpful in distinguishing MM from nevi, although positive Cx26 reactivity suggests that a cutaneous neoplasm is of nonmelanocytic origin.

Author(s): Shi, Lucy L; Sargen, Michael R; Chen, Suephy C; Arbiser, Jack L; Pollack, Brian P | Abstract: Background: Botulinum toxin type A (BTX-A) injections are an effective treatment for controlling hyperhidrosis at sites of amputation. Hyperesthesia associated with amputated limbs is a major barrier to performing this procedure under local anesthesia.Objective: To present a novel method for improving local anesthesia with BTX-A injections.Methods a Results: A 29-year-old military veteran with a below-the-knee amputation of his right leg was suffering from amputation site hyperhidrosis, which was impeding his ability to comfortably wear a prosthesis. Prior to presenting to our clinic, the patient received one treatment of BTX-A injections to his amputation stump while under general anesthesia for surgical repair of trauma-related injuries. In our dermatology clinic, we repeated the procedure using topical lidocaine-prilocaine (30 gm total) for local anesthesia. This provided effective relief of hyperhidrosis for 6 months, but the procedure was very painful (9/10 intensity). We repeated the same procedure 6 months later, using ice in addition to topical lidocaine-prilocaine (30 gm) for local anesthesia; this resulted in reduced pain (3/10 intensity) for the patient.Conclusions: We suggest using ice in combination with a topical anesthetic as an effective method for pain control that avoids general anesthesia in treating amputation-associated hyperhidrosis.

Background Inherited susceptibility genes have been associated with histopathologic characteristics of tumors. Objective We sought to identify associations between histology of melanomas and CDKN2A genotype. Methods This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations. Results Compared with CDKN2A − cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation ( P trend = .02) and increased pagetoid scatter ( P trend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A − (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation. Limitations Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype. Conclusion Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase.