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BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.
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Melanoma , Nomogramas , Humanos , Melanoma/genética , Melanoma/patologia , Prognóstico , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Although sentinel lymph node biopsy (SLNB) status is a strong prognostic indicator for cutaneous melanoma, unnecessary SLNBs have substantial cost and morbidity burden. OBJECTIVE: This study was designed to develop, validate, and present a personalized, clinical, decision-making tool using nationally representative data with clinically actionable probability thresholds (Expected Lymphatic Metastasis Outcome [ELMO]). METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) Registry from 2000 to 2017 and the National Cancer Database (NCDB) from 2004 to 2015 were used to develop and internally validate a logistic ridge regression predictive model for SLNB positivity. External validation was done with 1568 patients at a large tertiary referral center. RESULTS: The development cohort included 134,809 patients, and the internal validation cohort included 38,518 patients. ELMO (AUC 0.85) resulted in a 29.54% SLNB reduction rate and greater sensitivity in predicting SLNB status for T1b, T2a, and T2b tumors than previous models. In external validation, ELMO had an accuracy of 0.7586 and AUC of 0.7218. Limitations of this study are potential miscoding, unaccounted confounders, and effect modification. CONCLUSIONS: ELMO ( https://melanoma-sentinel.herokuapp.com/ ) has been developed and validated (internally and externally) by using the largest publicly available dataset of melanoma patients and was found to have high accuracy compared with other published models and gene expression tests. Individualized risk estimates for SLNB positivity are critical in facilitating thorough decision-making for healthcare providers and patients with melanoma.
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Linfadenopatia , Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Metástase Linfática , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Modelos Logísticos , Estudos Retrospectivos , Melanoma Maligno CutâneoRESUMO
Surgical Technique for Treating Thin MelanomaProspective data comparing the safety and efficacy of complete margin assessment and conventional wide excision in the treatment of melanoma are lacking. This article reviews the evidence and proposes a trial to determine which surgical method is better for treating thin invasive melanoma and melanoma in situ in high-risk anatomical locations.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Recidiva Local de NeoplasiaRESUMO
Immune related adverse events (irAEs) are one of the leading causes of discontinuation of cancer immunotherapy treatment. Despite extensive research into the frequency and types of irAEs, little is known about the cell types and pathways through which these drugs cause the observed side effects. To identify cell types and pathways of interest, we have analyzed single cell sequencing data of PBMCs from patients who developed skin irAEs as a result of their immunotherapy treatment. Using Azimuth's cell type identification software for PBMCs and GSEA pathway analysis, we found macrophage cell populations and reactive oxygen species related pathways to be upregulated. These results provide important groundwork to build a complete picture of the mechanisms which cause irAEs and finding ways to more effectively treat them.
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Melanoma remains a leading cause of cancer morbidity and mortality. Recent literature suggests that statin use may improve outcomes in patients with cancer. In order to determine whether statins may improve survival in melanoma patients, we analyzed data from the Veterans Health Administration Corporate Data Warehouse that contains individually identifiable clinical and demographic information from the 1990s to the present for over 19 million individual veterans. We found that melanoma patients who were taking a statin had better 5-year OS when compared with veterans not taking statins. This relationship remained significant in a multivariate model (hazard ratio, 0.38; 95% confidence interval, 0.34-0.43 for statin user vs. nonuser). Importantly, this effect was much larger than the effect of statins in the general population and was remained after controlling for the use of other medications (beta-blocker), implying that statins may have a direct effect on survival in melanoma patients.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Melanoma , Neoplasias Cutâneas , Antagonistas Adrenérgicos beta , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Melanoma/tratamento farmacológico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Squamous cell carcinoma in situ (SCCIS) of the glans penis with urethral involvement is a rare entity that is well-suited for Mohs micrographic surgery (MMS) given its high risk of local recurrence. However, MMS in this area is technically challenging, and surgery at this site often relies on the use of meatotomy for improved tumor visualization. We describe a less invasive approach to harvesting Mohs layers of the glans penis and distal urethra that obviates the need for meatotomy. For SCCIS tumors limited to the distal urethra, this is a straightforward technique that minimizes morbidity while still benefitting from the complete margin assessment and high cure rates associated with MMS.
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Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias Penianas , Neoplasias Cutâneas , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Masculino , Cirurgia de Mohs/métodos , Recidiva Local de Neoplasia , Neoplasias Penianas/patologia , Neoplasias Penianas/cirurgia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Uretra/patologia , Uretra/cirurgiaRESUMO
Despite advances in melanoma treatment, more than 70% of patients with distant metastasis die within 5 years. Proactive treatment of early melanoma to prevent metastasis could save lives and reduce overall healthcare costs. Currently, there are no treatments specifically designed to prevent early melanoma from progressing to metastasis. We used the Connectivity Map to conduct an in silico drug screen and identified 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) as a drug class that might prevent melanoma metastasis. To confirm the in vitro effect of statins, RNA sequencing was completed on A375 cells after treatment with fluvastatin to describe changes in the melanoma transcriptome. Statins induced differential expression in genes associated with metastasis and are used in commercially available prognostic tests for melanoma metastasis. Finally, we completed a chart review of 475 patients with melanoma. Patients taking statins were less likely to have metastasis at the time of melanoma diagnosis in both univariate and multivariate analyses (24.7% taking statins vs. 37.6% not taking statins, absolute risk reduction = 12.9%, P = 0.038). These findings suggest that statins might be useful as a treatment to prevent melanoma metastasis. Prospective trials are required to verify our findings and to determine the mechanism of metastasis prevention.
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Reposicionamento de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Transcriptoma/efeitos dos fármacos , Idoso , Simulação por Computador , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Melanoma/genética , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de SobrevidaRESUMO
BACKGROUND: Keratinocyte carcinomas (KC) impact patient quality of life (QoL). There is a need for validated QoL instruments specific to KC. The Basal and Squamous Cell Carcinoma QoL (BaSQoL) questionnaire was developed to comprehensively measure issues of importance to patients with KC. OBJECTIVE: To validate and characterize the BaSQoL questionnaire for QoL measurement after diagnosis and treatment of KC. METHODS: This was a prospective, observational study. Patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) were asked to fill out BaSQoL, Skin Cancer Index (SCI), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Descriptive statistics and classical test theory were used to assess validity. RESULTS: One hundred eighty-seven subjects enrolled in this study: 122 with BCC and 65 with SCC. One hundred seventy-one subjects (91.4%) completed questionnaires at all 3 time points; 16 patients (8.6%) were lost to follow-up. Overall performance using classical test theory was good, with good internal consistency (Cronbach's α 0.63-0.80). BaSQoL subscales were strongly correlated with subscales of the SCI, demonstrating convergent validity, and weakly correlated with HADS, showing divergent validity. CONCLUSION: The English language version of BaSQoL has good face, content, and construct validity. This study validates BaSQoL for use in English-speaking patients with BCC and SCC.
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Carcinoma Basocelular/psicologia , Carcinoma de Células Escamosas/psicologia , Qualidade de Vida , Neoplasias Cutâneas/psicologia , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , PsicometriaRESUMO
BACKGROUND: The scalp presents unique surgical challenges, and specialized techniques are sometimes required to achieve optimal results. Tumors arising on the scalp may also be at increased risk of complications such as in-transit metastasis and perineural invasion. OBJECTIVE: To review challenges to Mohs micrographic surgery on the scalp and techniques for successful tumor extirpation and reconstruction. METHODS AND MATERIALS: This article reviews our experience with tumors of the scalp including techniques that we have found helpful both for tumor removal and for reconstruction. CONCLUSION: Familiarity with the anatomy of the scalp as well as common challenges encountered during Mohs surgery may help improve outcomes and impart increase confidence to the practicing surgeon.
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Neoplasias de Cabeça e Pescoço/cirurgia , Cirurgia de Mohs/métodos , Couro Cabeludo/cirurgia , Neoplasias Cutâneas/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Cirurgia de Mohs/efeitos adversos , Invasividade Neoplásica , Metástase Neoplásica , Complicações Pós-Operatórias , Procedimentos de Cirurgia Plástica , Couro Cabeludo/patologia , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Cutaneous warts have high prevalence and cause significant morbidity. Understanding the mechanisms by which warts evade the immune system could lead to targeted and improved treatments. OBJECTIVE: To determine whether cutaneous warts express programmed cell death ligand 1 (PD-L1) and to characterize the expression of programmed cell death 1 (PD-1) within the immune infiltrate of inflamed lesions. METHODS: In total, 44 biopsies of cutaneous warts were retrieved from the Department of Dermatopathology archives of the University of California, San Francisco. Biopsies were stained with hematoxylin and eosin and PD-L1 monoclonal antibody, and biopsies of inflamed lesions were stained with PD-1 monoclonal antibody. RESULTS: PD-L1 was expressed on keratinocytes in cases of verrucae vulgares (12/30, 40%) and myrmecia (7/14, 50%) and was associated with an interface inflammatory reaction. PD-1 was expressed by the inflammatory infiltrate in verrucae vulgares (21/24, 88%) and myrmecia (5/8, 63%). LIMITATIONS: This was a retrospective observational study conducted at a single institution. CONCLUSION: Many cutaneous warts express PD-L1, suggesting that human papillomavirus might use this pathway to promote immune dysfunction. This discovery helps explain the recalcitrance of warts to current therapies and provides a rationale for investigating anti-PD-1 immunotherapy as a potential treatment for warts.