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Summary: Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death (PD)‐1 receptor. Common cutaneous adverse side‐effects of PD‐1 inhibitors include maculopapular rash, pruritus, vitiligo and lichenoid skin and mucosal reactions. Here we describe a man in his sixties with metastatic melanoma treated with pembrolizumab who subsequently developed fading or disappearance of pigmented skin lesions, lightening of the skin, and poliosis of the eyebrows, eyelashes and scalp and body hair. Compared with baseline high‐resolution three‐dimensional total‐body photography, we observed fading or disappearance of solar lentigines, seborrhoeic keratoses and melanocytic naevi, suggesting that PD‐1 inhibitors may affect the evolution of these benign skin lesions. With dermatoscopic follow‐up, altered lesions showed either blue‐grey peppering/granularity or fading in colour without other identifiable features. No halo lesions or lesions with surrounding inflammation were identified. One changed pigmented lesion that showed blue‐grey peppering/granularity on dermoscopy was biopsied and interpreted as a macular seborrhoeic keratosis with melanophages. Further studies are required to elucidate the effects of PD‐1 inhibition on benign skin lesions. [ABSTRACT FROM AUTHOR]

The article discusses variation in dermoscopic features of basal cell carcinoma as a function of anatomical location and pigmentation status. it mentions retrospective analysis of patient demographics and dermoscopic and clinical features of consecutive histopathologically proven BCCs. it mentions exploring the relationship between BCC subtype and anatomical location.

Background: Microvascular thrombosis is key to the pathogenesis of calciphylaxis. C5b-9-mediated microvascular injury reflective of complement pathway activation could be a key pathophysiologic event., Methods: We conducted a retrospective multicenter study of 24 patients who have had biopsy-supported calciphylaxis from the 2010-2022 data base from Emory where C5b-9 immunohistochemistry (IHC) had not been conducted and the 2019-2023 data base from Cornell where C5b-9 IHC was done as part of the routine calciphylaxis work up. IHC for C5b-9 on lesional biopsy specimens was assessed and correlated with routine light microscopic findings and clinical features., Results: Most of the patients in our study had uremic calciphylaxis associated with obesity, diabetes, dialysis, hypertension, hyperparathyroidism and elevated serum phosphorus. Most patients did not have defined procoagulant and/or hyperviscosity states. The vascular pathology was predominantly limited to the subcutaneous fat and ranged from a calcific intimal arteriopathy to microvascular thrombosis with endothelial injury with or without endothelial calcification. In most cases (ie, in excess of 80%), there was prominent deposition of C5b-9 within the vasculature including the microvasculature and arteries of the fat at least localized to injured vessels suggesting a causal association. In about 40% of cases, there was evidence of systemic complement pathway activation revealed by concurrent dermal microvascular C5b-9 deposition., Conclusions: Calciphylaxis is characterized by subcuticular vascular changes that reflect an interplay between complement triggered endothelial cell injury, resultant vascular thrombosis, and subsequent abluminal calcification. Complement inhibition therapy defines a potential intervention that should be explored., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: None disclosed.

Background: Pediatric melanoma presents with distinct clinical features compared to adult disease., Objective: Characterize risk factors and negative outcomes in pediatric melanoma., Methods: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers., Results: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls., Limitations: Retrospective nature, cohort size, control selection, and potential referral bias., Conclusion: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma., Competing Interests: Conflicts of interest SH reports honorarium from Elsevier and past consulting for Novan Pharmaceuticals., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Dermatologists with specialty training in pediatric dermatology are scarce, which can mean extended wait times and reduced access to care for patients. Lower compensation for pediatric dermatology visits compared with adult visits may affect physician career choice and contribute to workforce shortages., Objective: To evaluate differences in work relative value units (wRVUs) generated by pediatric and adult outpatient dermatology encounters., Design, Setting, and Participants: This cross-sectional study used data from outpatient dermatology encounters at a single-site academic center in Atlanta, Georgia, from September 1, 2016, to March 31, 2020. Encounters with patients younger than 18 years were classified as pediatric, and encounters with those 18 years or older were classified as adult. Encounters with missing data were excluded as were those generating 0 wRVUs, inpatient visits, nursing visits, postoperative encounters, cosmetic procedures, phototherapy visits, and Mohs surgery encounters., Main Outcomes and Measures: Work relative value units generated per encounter type were assessed through multivariable linear regression models adjusted for the potential confounder of sex., Results: The study included 12 989 pediatric dermatology encounters (mean [SD] age, 7.3 [5.2] years; 7586 [58.4%] girls) and 78 057 adult dermatology encounters (mean [SD] age, 54.9 [18.9] years; 45 724 [58.6%] women). Pediatric encounters were associated with 0.23 (95% CI, 0.21-0.25; P < .001) fewer wRVUs than adult encounters after adjusting for sex. In a mediation analysis, biopsies and destruction of premalignant lesions explained 74.1% (95% CI, 69.6%-77.9%; P < .001) of the wRVU difference between pediatric and adult encounters., Conclusions and Relevance: This cross-sectional study found significant differences in wRVUs generated between adult and pediatric dermatology encounters that were largely attributable to biopsies and destruction of premalignant lesions. Policies that increase the value of cognitive services to be on par with procedural care may mitigate wRVU differences and improve reimbursement for pediatric dermatologists.

Competing Interests: The authors made the following disclosures: L.A.V.O.: advisory boards—ChemoCentryx and Novartis; grant funding—Pfizer; paid investigator—ChemoCentryx. There are no other conflicts of interest to disclose.

Importance: Clinical productivity measures may be factors in financial incentives for providing care to specific patient populations and thus may perpetuate inequitable health care., Objective: To identify the association of patient race, age, and sex with work relative value units (wRVUs) generated by outpatient dermatology encounters., Design, Setting, and Participants: This cross-sectional study obtained demographic and billing data for outpatient dermatology encounters (ie, an encounter performed within a department of dermatology) from September 1, 2016, to March 31, 2020, at the Emory Clinic, an academic dermatologic practice in Atlanta, Georgia. Participants included adults aged 18 years or older with available age, race, and sex data in the electronic health record system., Main Outcomes and Measures: The primary outcome was wRVUs generated per encounter., Results: A total of 66 463 encounters among 30 036 unique patients were included. Patients had a mean (SD) age of 55.9 (18.5) years and were predominantly White (46 575 [70.1%]) and female (39 598 [59.6%]) individuals. In the general dermatologic practice, the mean (SD) wRVUs per encounter was 1.40 (0.71). In adjusted analysis, Black, Asian, and other races (eg, American Indian or Native American, Native Hawaiian or Other Pacific Islander, and multiple races); female sex; and younger age were associated with fewer wRVUs per outpatient dermatology encounter. Compared with general dermatologic visits with White patients, visits with Black patients generated 0.27 (95% CI, 0.25-0.28) fewer wRVUs per encounter, visits with Asian patients generated 0.22 (95% CI, 0.20-0.25) fewer wRVUs per encounter, and visits with patients of other race generated 0.19 (95% CI, 0.14-0.24) fewer wRVUs per encounter. Female sex was also associated with 0.11 (95% CI, 0.10-0.12) fewer wRVUs per encounter, and wRVUs per encounter increased by 0.006 (95% CI, 0.006-0.006) with each 1-year increase in age. In the general dermatologic practice excluding Mohs surgeons, destruction of premalignant lesions and biopsies were mediators for the observed differences in race (56.2% [95% CI, 53.1%-59.3%] for Black race, 53.2% [95% CI, 45.6%-63.8%] for Asian race, and 53.6% [95% CI, 40.4%-77.4%] for other races), age (65.6%; 95% CI, 60.5%-71.4%), and sex (82.3%; 95% CI, 72.7%-93.1%). In a data set including encounters with Mohs surgeons, the race, age, and sex differences in wRVUs per encounter were greater than in the general dermatologic data set. Mohs surgery for basal cell and squamous cell carcinomas was a mediator for the observed differences in race (46.0% [95% CI, 42.6%-49.4%] for Black race, 41.9% [95% CI, 35.5%-49.2%] for Asian race, and 34.6% [95% CI, 13.8%-51.5%] for other races), age (49.2%; 95% CI, 44.9%-53.7%), and sex (47.9%; 95% CI, 42.0%-54.6%)., Conclusions and Relevance: This cross-sectional study found that dermatology encounters with racial minority groups, women, and younger patients generated fewer wRVUs than encounters with older White male patients. This finding suggests that physician compensation based on wRVUs may encourage the provision of services that exacerbate disparities in access to dermatologic care.

Background: Pediatric melanoma is rare and diagnostically challenging., Objective: To characterize clinical and histopathologic features of fatal pediatric melanomas., Methods: Multicenter retrospective study of fatal melanoma cases in patients younger than 20 years diagnosed between 1994 and 2017., Results: Of 38 cases of fatal pediatric melanoma identified, 57% presented in white patients and 19% in Hispanic patients. The average age at diagnosis was 12.7 years (range, 0.0-19.9 y), and the average age at death was 15.6 years (range, 1.2-26.2 y). Among cases with known identifiable subtypes, 50% were nodular (8/16), 31% were superficial spreading (5/16), and 19% were spitzoid melanoma (3/16). One fourth (10/38) of melanomas arose in association with congenital melanocytic nevi., Limitations: Retrospective nature, cohort size, and potential referral bias., Conclusions: Pediatric melanoma can be fatal in diverse clinical presentations, including a striking prevalence of Hispanic patients compared to adult disease, and with a range of clinical subtypes, although no fatal cases of spitzoid melanoma were diagnosed during childhood., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children., Study Design: This was a multicenter, retrospective, case-control study of patients <20 years of age diagnosed with NMSC between 1995 and 2015 from 11 academic medical centers. The primary outcome measure was frequency of cases and controls with predisposing genetic conditions and/or iatrogenic exposures, including chemotherapy, radiation, systemic immunosuppression, and voriconazole., Results: Of the 124 children with NMSC (40 with basal cell carcinoma, 90 with squamous cell carcinoma), 70% had at least 1 identifiable risk factor. Forty-four percent of the cases had a predisposing genetic condition or skin lesion, and 29% had 1 or more iatrogenic exposures of prolonged immunosuppression, radiation therapy, chemotherapy, and/or voriconazole use. Prolonged immunosuppression and voriconazole use were associated with squamous cell carcinoma occurrence (cases vs controls; 30% vs 0%, P = .0002, and 15% vs 0%, P = .03, respectively), and radiation therapy and chemotherapy were associated with basal cell carcinoma occurrence (both 20% vs 1%, P < .0001). Forty-eight percent of initial skin cancers had been present for >12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001)., Conclusions: NMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Little evidence exists to guide the management of moderately dysplastic nevi excisionally biopsied without residual clinical pigmentation but with positive histologic margins (hereafter referred to as moderately dysplastic nevi with positive histologic margins)., Objective: To determine outcomes and risk for the development of subsequent cutaneous melanoma (CM) from moderately dysplastic nevi with positive histologic margins observed for 3 years or more., Design, Setting, and Participants: A multicenter (9 US academic dermatology sites) retrospective cohort study was conducted of patients 18 years or older with moderately dysplastic nevi with positive histologic margins and 3 years or more of follow-up data collected consecutively from January 1, 1990, to August 31, 2014. Records were reviewed for patient demographics, biopsy type, pathologic findings, and development of subsequent CM at the biopsy site or elsewhere on the body. The χ2 test, the Fisher exact test, and analysis of variance were used to assess univariate association for risk of subsequent CMs, in addition to multivariable logistic regression models. To confirm histologic grading, each site submitted 5 random representative slide cases for central dermatopathologic review. Statistical analysis was performed from October 1, 2017, to June 22, 2018., Main Outcomes and Measures: Development of CM at a biopsy site or elsewhere on the body where there were moderately dysplastic nevi with positive histologic margins., Results: A total of 467 moderately dysplastic nevi with positive histologic margins from 438 patients (193 women and 245 men; mean [SD] age, 46.7 [16.1] years) were evaluated. No cases developed into CM at biopsy sites, with a mean (SD) follow-up time of 6.9 (3.4) years. However, 100 patients (22.8%) developed a CM at a separate site. Results of multivariate analyses revealed that history of CM was significantly associated with the risk of development of subsequent CM at a separate site (odds ratio, 11.74; 95% CI, 5.71-24.15; P < .001), as were prior biopsied dysplastic nevi (odds ratio, 2.55; 95% CI, 1.23-5.28; P = .01). The results of a central dermatopathologic review revealed agreement in 35 of 40 cases (87.5%). Three of 40 cases (7.5%) were upgraded in degree of atypia; of these, 1 was interpreted as melanoma in situ. That patient remains without recurrence or evidence of CM after 5 years of follow-up., Conclusions and Relevance: This study suggests that close observation with routine skin surveillance is a reasonable management approach for moderately dysplastic nevi with positive histologic margins. However, having 2 or more biopsied dysplastic nevi (with 1 that is a moderately dysplastic nevus) appears to be associated with increased risk for subsequent CM at a separate site.

Background: Few studies have characterized reference values of normal human skin microanatomy parameters., Objective: To quantify histologic measurements of epidermal thickness, melanocyte density, hair follicle density, and eccrine gland density as a function of age and anatomic site., Method: We searched the PubMed, Embase, Web of Science, and Cochrane databases for articles published through May 25, 2017. Two reviewers independently screened 2016 articles; 327 relevant articles and 151 additional articles found via forward or reference citations underwent full-text review by 1 of 4 reviewers for relevance, data extraction, and critical appraisal. Weighted averages, meta-analysis, and meta-regression were used in statistical analysis., Results: A total of 56 articles were included; when all anatomic locations were used, the overall estimates for epidermal thickness, melanocyte density, hair follicle density, and eccrine gland density were 99.75 μm (95% confidence interval [CI], 83.25-116.25), 955.05 cells/mm 2 (95% CI. 880.89-1029.21), 1.40 hairs/mm 2 (95% CI. 0.91-1.89), and 1.28 glands/mm 2 (95% CI. 0.91-1.64), respectively., Limitations: There was significant data heterogeneity across studies, possibly because of differences in histological techniques and absence of standardized microanatomy definitions., Conclusions: We established summary estimates for normal human skin microanatomy parameters., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Nonhomologous end joining (NHEJ), a major pathway of DNA double-strand break (DSB) repair, is required during lymphocyte development to resolve the programmed DSBs generated during Variable, Diverse, and Joining [V(D)J] recombination. XRCC4-like factor (XLF) (also called Cernunnos or NHEJ1) is a unique component of the NHEJ pathway. Although germ-line mutations of other NHEJ factors abrogate lymphocyte development and lead to severe combined immunodeficiency (SCID), XLF mutations cause a progressive lymphocytopenia that is generally less severe than SCID. Accordingly, XLF-deficient murine lymphocytes show no measurable defects in V(D)J recombination. We reported earlier that ATM kinase and its substrate histone H2AX are both essential for V(D)J recombination in XLF-deficient lymphocytes, despite moderate role in V(D)J recombination in WT cells. p53-binding protein 1 (53BP1) is another substrate of ATM. 53BP1 deficiency led to small reduction of peripheral lymphocyte number by compromising both synapse and end-joining at modest level during V(D)J recombination. Here, we report that 53BP1/XLF double deficiency blocks lymphocyte development at early progenitor stages, owing to severe defects in end joining during chromosomal V(D)J recombination. The unrepaired DNA ends are rapidly degraded in 53BP1(-/-)XLF(-/-) cells, as reported for H2AX(-/-)XLF(-/-) cells, revealing an end protection role for 53BP1 reminiscent of H2AX. In contrast to the early embryonic lethality of H2AX(-/-)XLF(-/-) mice, 53BP1(-/-)XLF(-/-) mice are born alive and develop thymic lymphomas with translocations involving the T-cell receptor loci. Together, our findings identify a unique function for 53BP1 in end-joining and tumor suppression.