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Leiomiossarcoma , Neoplasias Cutâneas , Humanos , Feminino , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Leiomiossarcoma/diagnóstico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Masculino , Pessoa de Meia-Idade , Idoso , Fatores Sexuais , Adulto , Disparidades nos Níveis de Saúde , Idoso de 80 Anos ou maisRESUMO
IMPORTANCE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction occurring 2 to 8 weeks after medication initiation. Diagnosis is clinical; RegiSCAR scoring includes biopsy "suggestive of DRESS," undefined in the literature. OBJECTIVE: This study correlates DRESS dermatopathology, culprit drugs, disease course, and outcome severity compared with maculopapular drug reactions (MDR). METHODS: Between 2014 and 2023, a retrospective cohort study at a tertiary care institute reviewed 55 patients with DRESS, assessing demographics, culprit drug, illness course, and histopathology. Biopsies of 15 patients with DRESS and 15 MDR patients were graded by a predefined histopathological scoring system. Statistical analysis (significant P -value<0.05) included the Fisher exact probability, ANOVA, and correlation tests. RESULTS: Among 55 patients with DRESS (mean age 50.13, 28 female/27 male), 15 (mean age 50.4, 7 female/8 male) had diagnostic biopsies. Compared with MDR patients, patients with DRESS exhibited significantly more interface dermatitis ( P = 0.04), lichenoid dermatitis ( P = 0.0007), pigment incontinence ( P = 0.04), and periadnexal interface dermatitis ( P = 0.002). MDR biopsies displayed perivascular inflammation and higher eosinophils than DRESS, trending toward significance. CONCLUSIONS: Key histopathologic features are interface dermatitis, periadnexal interface dermatitis, lichenoid dermatitis, pigment incontinence, and neutrophils dominance over eosinophils indicate DRESS clinically.
Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Humanos , Feminino , Masculino , Síndrome de Hipersensibilidade a Medicamentos/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , BiópsiaAssuntos
Leiomiossarcoma , Neoplasias Cutâneas , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/patologia , Leiomiossarcoma/etnologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Etnicidade/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Idoso de 80 Anos ou maisAssuntos
Asiático , Melanoma , Havaiano Nativo ou Outro Ilhéu do Pacífico , Neoplasias Cutâneas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Asiático/estatística & dados numéricos , Melanoma/epidemiologia , Melanoma/mortalidade , Melanoma Maligno Cutâneo , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Fatores Sexuais , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/mortalidadeAssuntos
Melanoma , Humanos , Estados Unidos , Estudos Retrospectivos , Melanoma/cirurgia , Etnicidade , Grupos RaciaisRESUMO
Importance: De novo bullous pemphigoid (BP) is a rare immune-mediated adverse event from immune checkpoint inhibitors (ICIs) that can necessitate permanent discontinuation of the anticancer therapy, but the risk factors for developing this toxic effect are unknown. Objective: To compare potential risk factors for BP in patients treated with ICIs who did and did not develop BP. Design, Setting, and Participants: This cohort and nested propensity score-matched case-control study was conducted at the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Massachusetts General Hospital. All patients at these facilities with de novo BP after ICI treatment were compared with all patients on the cancer registry who were treated with ICIs between October 1, 2014, and December 31, 2020. Patients with incomplete or blinded data regarding the ICI agent or total cycles were excluded. Exposures: In the cohort, assessed potential risk factors included age at ICI introduction, sex, ICI molecular target, and cancer type, which were then used as matching variables. In the propensity score-matched case-control analysis, risk factors assessed included sex, race and ethnicity, cancer stage, metastasis sites, idiopathic BP comorbidities, pre-ICI vaccination, radiation history, body mass index, and derived neutrophil-to-lymphocyte ratio. Main Outcomes and Measures: Diagnosis of BP at any point after ICI treatment, confirmed by direct immunofluorescence, indirect immunofluorescence, autoantibody serologies, or diagnostic consensus among study board-certified dermatologists. Odds ratios (ORs) and 95% CIs were calculated for all risk factors. In the secondary analysis, best overall responses to ICIs between cases and controls were compared by Fisher exact test. Results: Among 5636 patients treated with ICIs at Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Massachusetts General Hospital during the study period, 35 (0.6%; median [IQR] age, 72.8 [13.4] years; 71.4% [25] male patients) developed BP. In a multivariate logistic regression model that assessed 2955 patients with complete data in the cancer registry, age 70 years or older (OR, 2.32; 95% CI, 1.19-4.59; P = .01), having melanoma (OR, 3.21; 95% CI, 1.51-6.58; P < .003), and having nonmelanoma skin cancer (OR, 8.32; 95% CI, 2.81-21.13; P < .001) were significantly associated with developing BP. In the nested 1:2 case-control comparison of all 35 cases to 70 propensity score-matched controls, a complete or partial response on initial restaging imaging was a risk factor for BP development (OR, 3.37; 95% CI, 1.35-9.30; P = .01). Bullous pemphigoid cases also more frequently exhibited overall tumor response to ICIs than matched controls (29 of 35 [82.9%] vs 43 of 70 [61.4%]; P = .03). Conclusions and Relevance: In this cohort study, age 70 years or older and skin cancer were associated with increased risk of developing ICI-associated BP. Given the association of BP with improved initial and best overall tumor responses, early identification and toxic effect-directed treatment should be prioritized, especially in individuals at risk for developing de novo BP.
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Melanoma , Penfigoide Bolhoso , Neoplasias Cutâneas , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/epidemiologiaRESUMO
The neutrophil NADPH oxidase produces both intracellular and extracellular reactive oxygen species (ROS). Although oxidase activity is essential for microbial killing, and ROS can act as signaling molecules in the inflammatory process, excessive extracellular ROS directly contributes to inflammatory tissue damage, as well as to cancer progression and immune dysregulation in the tumor microenvironment. How specific signaling pathways contribute to ROS localization is unclear. Here we used a systems pharmacology approach to identify the specific Class I PI3-K isoform p110ß, and PLD1, but not PLD2, as critical regulators of extracellular, but not intracellular ROS production in primary neutrophils. Combined crystallographic and molecular dynamics analysis of the PX domain of the oxidase component p47phox, which binds the lipid products of PI 3-K and PLD, was used to clarify the membrane-binding mechanism and guide the design of mutant mice whose p47phox is unable to bind 3-phosphorylated inositol phospholipids. Neutrophils from these K43A mutant animals were specifically deficient in extracellular, but not intracellular, ROS production, and showed increased dependency on signaling through the remaining PLD1 arm. These findings identify the PX domain of p47phox as a critical integrator of PLD1 and p110ß signaling for extracellular ROS production, and as a potential therapeutic target for modulating tissue damage and extracellular signaling during inflammation.
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Classe I de Fosfatidilinositol 3-Quinases , NADPH Oxidases , Neutrófilos , Espécies Reativas de Oxigênio , Animais , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Ativação Enzimática , Inflamação , Camundongos , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Neutrófilos/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisAssuntos
Antibacterianos/efeitos adversos , Diuréticos/efeitos adversos , Toxidermias/imunologia , Tolerância Imunológica/efeitos dos fármacos , Penfigoide Bolhoso/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Tardio , Toxidermias/diagnóstico , Toxidermias/patologia , Feminino , Humanos , Masculino , Diagnóstico Ausente , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/patologia , Polimedicação , Estudos Retrospectivos , Pele/imunologia , Pele/patologia , Fatores de TempoRESUMO
BACKGROUND: Previous studies have found familial aggregation of melanoma and keratinocyte cancers (KCs). OBJECTIVE: We sought to determine the risk of melanoma and KCs in those with a positive family history of melanoma while controlling for pigmentary and environmental risk factors. METHODS: We prospectively followed 216,115 participants from the Nurses' Health Study, Nurse's Health Study 2, and Health Professionals Follow-up Study for more than 20 years. Cox proportional hazards regression controlling for known risk factors for skin cancer was used to estimate association between family history of melanoma and melanoma and KCs. RESULTS: Compared with those without a family history of melanoma, individuals with a family history of melanoma had a 74% increased risk of melanoma (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.45-2.09), a 22% increased risk of squamous cell carcinoma (HR, 1.22; 95% CI, 1.06-1.40), and a 27% increased risk of basal cell carcinoma (HR, 1.27; 95% CI, 1.12-1.44). Family history of melanoma increased the risk of development of truncal melanoma in both sexes, extremity melanoma in women, and extremity squamous cell carcinoma in women. LIMITATIONS: Limitations of this study include self-reported family history and detection bias. CONCLUSION: Individuals with a family history of melanoma are at an increased risk of melanoma and KCs.
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Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Extremidades , Saúde da Família , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Linhagem , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Neoplasias Cutâneas/genética , Tronco , Estados Unidos/epidemiologiaAssuntos
Dermatologia , Utilização de Instalações e Serviços/estatística & dados numéricos , Melanoma/patologia , Visita a Consultório Médico , Neoplasias Cutâneas/patologia , Idoso , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Fatores de Tempo , Carga TumoralRESUMO
BACKGROUND: The presence of nevi portends an increased risk for melanoma. OBJECTIVE: We sought to examine the association between extremity nevus count and the risk of melanoma and keratinocyte cancers. METHODS: We evaluated prospective cohorts of 176,317 women (the Nurses' Health Study, 1986-2012 and the Nurses' Health Study 2, 1989-2013) and 32,383 men (Health Professionals Follow-up Study, 1986-2012). Information on nevus count (none, 1-5, 6-14, ≥15) on the extremity was collected at baseline. RESULTS: There were 1704 incident cases of melanoma, 2296 incident cases of squamous cell carcinoma, and 30,457 incident cases of basal cell carcinoma, with a total of 4,655,043 person-years for melanoma and 4,267,708 person-years for keratinocyte cancers. The presence of an extremity nevus was associated with an increased risk of melanoma in all anatomic areas and increased risk of basal cell carcinoma (BCC). Individuals with ≥15 nevi had the highest risk of melanoma and BCC compared to those without any extremity nevi (melanoma hazard ratio 2.79 [95% confidence interval 2.04-3.83]; BCC HR 1.40 [95% confidence interval 1.32-1.49]). No significant association was observed for squamous cell carcinoma. LIMITATIONS: Limitations of our study included self-reported nevus count and detection bias. CONCLUSIONS: Extremity nevus count is a helpful clinical marker in risk-stratifying individuals for BCC and melanoma on all body sites.
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Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Melanoma/epidemiologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Carga Tumoral , Feminino , Antebraço , Humanos , Incidência , Perna (Membro) , Masculino , Estudos Prospectivos , Fatores de Risco , Estados UnidosRESUMO
Nevus sebaceus of Jadassohn, a congenital cutaneous hamartoma, has the potential to develop into various epidermal adnexal-origin neoplasms. While the most common neoplasms are trichoblastoma or syringocystadenoma, proliferating trichilemmal cysts are exceptionally rare. We report a case of a 63-year-old Cuban male with a giant proliferating trichilemmal cyst arising from a nevus sebaceus on the right shoulder which had been growing for 30 years. Proliferating trichilemmal cysts arising from nevus sebaceus cases are difficult to diagnose clinically and histologically as they are very rare and have not been defined by exact diagnostic criteria. Our case creates awareness of this particular tumor in nevus sebaceus and shares clinical and histological diagnostic information that can be used to make a proper diagnosis.