Assuntos
Miosite , Esclerodermia Difusa , Humanos , Miosite/imunologia , Miosite/diagnóstico , Miosite/patologia , Miosite/complicações , Esclerodermia Difusa/imunologia , Esclerodermia Difusa/complicações , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/patologia , Feminino , Autoanticorpos/sangue , Autoanticorpos/imunologia , Pessoa de Meia-Idade , Neurônios Motores/patologia , Neurônios Motores/imunologia , Síndrome , MasculinoRESUMO
Japanese patients with very high-risk cutaneous squamous cell carcinomas (cSCCs), based on the National Comprehensive Cancer Network guidelines, have been reported to display a higher cumulative incidence of relapse and disease-specific death (DSD) than those with high-risk cSCC. Therefore, prognosis prediction is crucial for Japanese patients with very high-risk cSCCs. Herein, we aimed to evaluate the prognostic prediction ability of our novel Japanese Risk Factor Scoring Systems (JARF scoring) in a Japanese cohort of cSSC patients. Data of 424 Japanese patients with resectable very high-risk cSCCs were analysed. We compared the prognostic ability of the following three staging systems: Brigham and Women's Hospital (BWH) tumour staging, number of NCCN very high-risk factors, and JARF scoring, including recurrent tumour, high-risk histological features, deep tumour invasion and lymphatic or vascular involvement as risk factors. The prognostic ability of these staging systems was evaluated according to the cumulative incidence of local recurrence (LR), regional lymph node metastasis (RLNM), DSD, and overall survival (OS). When BWH staging was used, high T stage led to significantly poor outcomes only in the cumulative incidence of RLNM (p = 0.01). The presence of very high-risk NCCN factors led to significantly poor outcomes in terms of RLNM (p = 0.03) and OS (p = 0.02). Meanwhile, a high number of risk factors in the JARF scoring system clearly led to poor outcomes in terms of LR (p = 0.01), RLNM (p < 0.01), DSD (p = 0.03), and OS (p < 0.01). The JARF scoring system may accurately predict the risk of recurrence and death in very high-risk cSCC patients in Japan.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos Transversais , População do Leste Asiático , Japão , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaAssuntos
Dermatite , Dermatopatias Vesiculobolhosas , Humanos , Imunoglobulina A , Masculino , Feminino , Pessoa de Meia-IdadeAssuntos
Carcinoma de Células Escamosas , Epidermodisplasia Verruciforme , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Epidermodisplasia Verruciforme/diagnóstico , Epidermodisplasia Verruciforme/genética , Epidermodisplasia Verruciforme/patologia , Proteínas de Membrana/genética , Mutação , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Efficacy of anti-PD-1 antibody monotherapy (PD1) or anti-PD-1 plus anti-CTLA-4 combination therapy (PD1 +CTLA4) for melanoma is affected by its clinical subtype. The amount of tumor mutation burden (TMB) caused by cumulative sun damage (CSD) is occasionally used to explain this; however, their relationship in Japanese nonacral cutaneous melanoma (NACM) is still unclear. OBJECTIVE: To analyze the ICI efficacy and its relationship with CSD of the primary lesion in Japanese patients with NACM. METHODS: Japanese patients with advanced BRAF wild-type NACM who received first-line ICIs were recruited. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), and the degree of solar elastosis (SE) were evaluated. RESULTS: A total of 146 patients (PD1 group 113 and PD1 +CTLA4 group 33) were included. No significant differences in ORR were observed between the PD1 and PD1 +CTLA4 groups (35 % vs. 36 %; P = 0.67) or PFS and OS (median PFS 6.1 months vs. 8.5 months; P = 0.46, median OS 28.1 months vs. not reached; P = 0.59). Multivariate survival analysis revealed that PD1 +CTLA4 did not prolong the PFS and OS. The SE score had no effect on either PFS or OS. CONCLUSIONS: ICI efficacy was not as high as those reported in Western countries, and PD1 +CTLA4 did not present better clinical efficacy compared to PD1. Indicators of CSD did not serve as a predictor for clinical advantage. These findings may partially support the theory that ICI efficacy is affected by CSD; however, other unrecognized factors may also exist.
Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Antígeno CTLA-4/genética , População do Leste Asiático , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Melanoma Maligno CutâneoAssuntos
Micose Fungoide , Leucemia-Linfoma Linfoblástico de Células Precursoras , Neoplasias Cutâneas , Humanos , Dasatinibe/uso terapêutico , Micose Fungoide/tratamento farmacológico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
BACKGROUND/AIM: Radiotherapy for angiosarcoma of the scalp has not been standardised yet. Hence, we aimed to retrospectively analyse the outcomes of patients treated with electron beam therapy or intensity-modulated radiation therapy (IMRT) for unresectable angiosarcoma of the scalp. PATIENTS AND METHODS: Data from patients treated with chemoradiotherapy or radiotherapy alone for unresectable angiosarcoma of the scalp between March 2009 and March 2021 were evaluated. Survival and local control rates were analysed using the Kaplan-Meier method, and the log-rank test was used to compare groups. Adverse events were analysed using the Common Terminology Criteria for Adverse Events ver. 5.0. RESULTS: Sixteen patients were eligible for the study. Eight patients were treated with electron beam therapy and eight patients with IMRT. The median follow-up period was 18.0 months. The median radiation dose was 57 Gy in 19 fractions in the electron beam therapy group and 70 Gy in 35 fractions in the IMRT group. In the IMRT group, acute non-haematologic toxicity was observed in two patients with grade 3 dermatitis. The one-year overall survival rate, progression-free survival rate, and local control rate in the electron beam therapy group were 80.8%, 56.3%, and 77.4%, respectively, and the corresponding values in the IMRT group were 100%, 75%, and 100%, respectively. One-year local control was significantly better in the IMRT group compared to that in the electron beam therapy group (p=0.016). CONCLUSION: IMRT for angiosarcoma of the scalp may improve local control rates compared to electron beam therapy, but long-term follow-up studies are required to validate this finding.
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Hemangiossarcoma , Radioterapia de Intensidade Modulada , Humanos , Hemangiossarcoma/radioterapia , Couro Cabeludo , Radioterapia de Intensidade Modulada/efeitos adversos , Elétrons , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: In cutaneous squamous cell carcinoma (cSCC), adherence to guideline-recommended fixed surgical margins is often difficult, and narrower margins are preferable. This study aimed to evaluate relapse and disease-specific death with narrower margins for high or very high-risk cSCC. PATIENTS/METHODS: We retrospectively investigated high or very high-risk cSCC patients who underwent tumor excision. Patients were divided into guideline-recommended standard margin group (SMG) and narrower-margin group (NMG). Co-primary outcomes were local relapse, SCC relapse, and SCC death. Cumulative incidence function (CIF) was used to describe SCC death probability and competing risk mortality. Gray's test was used to compare differences in CIF between the groups. RESULTS: In total, 1,000 patients with cSCC (high-risk, 570; very high-risk, 430) were included. In the high-risk cohort, there were no significant differences in incomplete excision rate (IER) between SMG and NMG (2.6 % vs. 3.0 %, P > 0.99). However, in the very high-risk cohort, IER in SMG was significantly lower than in NMG (8.9 % vs. 16.2 %, P = 0.03). No significant differences were observed between SMG and NMG for local relapse (high-risk, P = 0.56; very high-risk, P = 0.70), SCC relapse (high-risk, P = 0.30; very high-risk, P = 0.47), and SCC death (high-risk, P = 0.23; very high-risk, P = 0.83). CONCLUSIONS: Surgical margin size has limited impact on margin control, relapse, and disease-specific death in high-risk cSCC.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
HINTERGRUND UND ZIELE: Bei kutanen Plattenepithelkarzinomen (PEK) ist die Einhaltung der in Leitlinien empfohlenen festen Resektionsränder oft schwierig und knappere Ränder sind wünschenswert. Ziel dieser Studie war die Bewertung des Auftretens von Rezidiven und krankheitsspezifischen Todesfällen bei knapperen Resektionsrändern für PEK mit hohem oder sehr hohem Risiko. PATIENTEN/METHODEN: PEK-Patienten mit hohem oder sehr hohem Risiko, bei denen eine Tumorexzision durchgeführt wurde, wurden retrospektiv untersucht. Die Patienten wurden in eine Gruppe mit Standardrand gemäß Leitlinienempfehlung (standard margin group, SMG) und eine Gruppe mit knapperen Rändern (narrower-margin group, NMG) eingeteilt. Gemeinsame primäre Endpunkte waren lokales Rezidiv, PEK-Rezidiv und PEK-bedingter Tod. Die Wahrscheinlichkeit eines PEK-bedingten Tods und konkurrierender Mortalitätsrisiken wurde mittels kumulativer Inzidenzfunktion (CIF) beschrieben. Unterschiede bei der CIF zwischen den Gruppen wurden mit dem Test nach Gray verglichen. ERGEBNISSE: Insgesamt wurden 1.000 Patienten mit PEK (hohes Risiko, 570; sehr hohes Risiko, 430) eingeschlossen. In der Kohorte mit hohem Risiko gab es keine signifikanten Unterschiede bei der unvollständigen Exzisionsrate (IER) zwischen SMG und NMG (2,6 % vs. 3,0 %, P > 0,99). In der Kohorte mit sehr hohem Risiko war die IER in der SMG jedoch signifikant geringer als in der NMG (8.9 % vs. 16.2 %, P = 0,03). Keine signifikanten Unterschiede zwischen SMG und NMG wurden für Lokalrezidiv (hohes Risiko, P = 0.56; sehr hohes Risiko, P = 0,70), PEK-Rezidiv (hohes Risiko, P = 0,30; sehr hohes Risiko, P = 0,47) und PEK-bedingtem Tod (hohes Risiko, P = 0,23; sehr hohes Risiko, P = 0,83) beobachtet. SCHLUSSFOLGERUNGEN: Die Größe des Resektionsrands hat einen begrenzten Einfluss auf Randkontrolle, Rezidive und krankheitsspezifischen Tod bei PEK mit hohem Risiko.
RESUMO
The protein long interspersed nuclear elements-1 (LINE-1) serves as a useful surrogate marker of global methylation but little is known for Merkel cell carcinoma. LINE-1 expression was found only in Merkel cell polyomavirus (MCPyV)-positive Merkel cell carcinomas but not in MCPyV-negative Merkel cell carcinomas, suggesting that epigenetic dysregulation may be associated with MCPyV expression.
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Carcinoma de Célula de Merkel , Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Neoplasias Cutâneas , Infecções Tumorais por Vírus , Biomarcadores , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/patologia , Humanos , Poliomavírus das Células de Merkel/genética , Neoplasias Cutâneas/patologiaRESUMO
INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening, neutrophilic, autoinflammatory skin disease characterised by recurrent flares of generalised sterile pustules and associated systemic features. Inconsistent diagnostic criteria and a lack of approved therapies pose serious challenges to GPP management. Our objectives were to discuss the challenges encountered in the care of patients with GPP and identify healthcare provider (HCP) educational needs and clinical practice gaps in GPP management. METHODS: On 24 July 2020, 13 dermatologists from 10 countries (Brazil, Canada, China, Egypt, France, Germany, Japan, Malaysia, the UK and the USA) attended a workshop to share experiences in managing patients with GPP. Educational needs and clinical practice gaps grouped according to healthcare system level were discussed and ranked using interactive polling. RESULTS: Lack of experience of GPP among HCPs was identified as an important individual HCP-level clinical practice gap. Limited understanding of the presentation and pathogenesis of GPP among non-specialists means misdiagnosis is common, delaying referral and treatment. In countries where patients may present to general practitioners or emergency department HCPs, GPP is often mistaken for an infection. Among dermatologists who can accurately diagnose GPP, limited knowledge of treatments may necessitate referral to a colleague with more experience in GPP. At the organisational level, important needs identified were educating emergency department HCPs to recognise GPP as an autoinflammatory disease and improving communication, cooperation and definitions of roles within multidisciplinary teams supporting patients with GPP. At the regulatory level, robust clinical trial data, clear and consistent treatment guidelines and approved therapies were identified as high priorities. CONCLUSIONS: The educational imperative most consistently identified across the participating countries is for HCPs to understand that GPP can be life-threatening if appropriate treatment initiation is delayed, and to recognise when to refer patients to a colleague with more experience of GPP management.
RESUMO
A 37-year-old Japanese man with a 3-year history of diffuse cutaneous systemic sclerosis was admitted to our hospital with high fever, arthralgia, myalgia, and muscle weakness. A physical examination revealed facial erythema, Gottron's sign, and mechanic's hands in addition to skin sclerosis. Laboratory data revealed significantly elevated levels of creatine kinase and decreased complement. Anti-RNP, anti-Smith, anti-DNA, anti-ß2 -glycoprotein 1, anti-polymyositis (PM)/Scl75, and anti-PM/Scl100 antibodies were detected. He also had urinary protein, interstitial lung disease, pericarditis, multifocal cerebral infarctions, and leukoencephalopathy. Thus, a diagnosis of overlap syndrome of diffuse cutaneous systemic sclerosis, dermatomyositis, and systemic lupus erythematosus with antiphospholipid syndrome was made. Because of the intractable course, he was treated with multiple immunosuppressive and immunomodulatory drugs, including three rounds of 1000 mg methylprednisolone pulse therapy. This is the first case report of anti-PM/Scl antibody-positive overlap syndrome of three major connective tissue diseases.
Assuntos
Síndrome Antifosfolipídica , Dermatomiosite , Lúpus Eritematoso Sistêmico , Polimiosite , Esclerodermia Difusa , Escleroderma Sistêmico , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Autoanticorpos , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Humanos , Masculino , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológicoRESUMO
FGFR3 encodes a transmembrane receptor tyrosine kinase that has six autophosphorylation sites of tyrosine. Among them, Y770 is a negative regulatory site for the downstream signaling of FGFR3. Constitutive active mutations in FGFR3 are involved in human developmental disorders including familial acanthosis nigricans, an autosomal dominant disorder characterized by general hyperpigmentation with mild acanthosis of the epidermis. Here, we report two unrelated cases of familial acanthosis nigricans with a heterozygous c.2302G>T (p.E768*) mutation in FGFR3 (NM_000142.5). FGFR3 mRNA purified from the skin lesion neither showed aberrant splicing nor nonsense-mediated mRNA decay, indicating that the FGFR3 mutant simply lacked the C-terminal 768-806 amino acids including Y770. While all of the known pathogenic mutations were missense mutations in FGFR3 showing autosomal dominant trait, the c.2302G>T mutation of FGFR3 is a unique autosomal dominant nonsense mutation that causes familial acanthosis nigricans probably via loss of negative regulatory autophosphorylation site of FGFR3.