RESUMO
BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon (IFN)-α (subtypes 2a and 2b) has been used to treat MF/SS since 1984; however, its production was recently stopped. The recombinant pegylated (PEG) form of IFN-α-2a remains the only alternative IFN treatment, although it has not been approved for use in MF/SS. OBJECTIVES: To assess the effectiveness and safety of PEG-IFN-α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in a real-world setting. METHODS: We conducted an international, multicentre retrospective study of patients with MF and SS (of any stage) treated with PEG-IFN-α-2a from July 2012 to February 2022. Patients were included across 11 centres in 10 countries. The primary endpoints were to determine the TTNT of PEG-IFN-α-2a and adverse events (AEs) in MF/SS. RESULTS: In total, 105 patients were included [mean (SD) age 61 (13.1) years]; 42 (40.0%) had stage IA-IIA and 63 (60.0%) had stage IIB-IVB disease. PEG-IFN-α-2a was combined with other therapies in 67 (63.8%) patients, most commonly with extracorporeal photopheresis (36%) and bexarotene (22%). Patients with stage I-IIA disease achieved an overall response rate (ORR) of 57%; the ORR in those with stage IIB-IVB disease was 51%. Combination treatment resulted in a median TTNT of 10.4â months (range 0.6-50.7) vs. 7.0â months (range 0.7-52.4) for those who received monotherapy (P < 0.01). Overall, the mean (SD) TTNT was 9.2 (10.6) months and the ORR was 53.3% (n = 56). A complete response was seen in 13% of patients and a partial response in 40%. AEs were described in 68.6% (n = 72) of patients. Flu-like symptoms (n = 28; 26.7%), lymphopenia (n = 24; 22.9%) and elevated liver function (n = 10; 9.5%) were the most frequently reported. Grade 3-4 AEs were reported in 23 (21.9%) patients, mostly related to myelosuppression. CONCLUSIONS: PEG-IFN-α-2a for MF/SS resulted in an ORR of 53.3% and a mean (SD) TTNT of 9.2 (10.6) months. Combination regimens were superior to monotherapy and doses of 180â µg PEG-IFN-α-2a weekly were related to a higher ORR.
Mycosis fungoides (MF) and Sézary syndrome (SS) are rare types of cancers of the lymphatic system (lymphomas). They result in patches, plaques and/or tumours on the skin that usually need a combination of treatments to be controlled. A drug called interferon alpha (IFN-α) has been used to treat cutaneous lymphomas since 1984, but its production was recently stopped, so another form of it called 'recombinant pegylated IFN α-2a' (PEG-IFN-α-2a) is the only alternative IFN treatment, even though it has not been formally approved for MF/SS. The lack of studies on PEG-IFN-α-2a for MF/SS treatment has meant that its use can vary between institutions. This study aimed to investigate the effectiveness, the safety and how well PEG-IFN-α-2a is tolerated as single treatment or in combination with other MF/SS treatments. We carried out a study of patients with MF/SS treated with PEG-IFN-α-2a between July 2012 and February 2022. In total, 105 patients were included from 10 countries. We found that 53% of the patients responded to PEG-IFN-α-2a treatment. We also found that doses of 180â µg weekly, as well as combining PEG-IFN-α-2a with other treatments, resulted in higher response rates and a longer time until a new treatment needed to be added. However, at least one adverse event occurred in 69% of patients. The most common were flu-like symptoms, a reduction in the number of white blood cells and increased liver function. Severe adverse events occurred in 21% of the patients, mostly related to a reduction in the number of blood cells. Overall, our study findings suggest that PEG-IFN-α-2a is an effective and generally well-tolerated option among the treatments for MF/SS, with patients experiencing a better response when it was used as part of a combination therapy and on doses of 180â µg weekly.
Assuntos
Interferon-alfa , Micose Fungoide , Polietilenoglicóis , Proteínas Recombinantes , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Pessoa de Meia-Idade , Feminino , Masculino , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Idoso , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Resultado do Tratamento , Adulto , Fatores de Tempo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoAssuntos
Transtornos Linfoproliferativos , Pessoas Transgênero , Neoplasias do Colo do Útero , Feminino , Masculino , Humanos , Colo do Útero , PeleRESUMO
Introdução: Embora prevalente, a epidemiologia das queimaduras possui lacunas. Simultaneamente, a COVID-19 estabeleceu um cenário desafiador e com novos comportamentos humanos, que poderiam impactar nas características e na incidência de queimaduras. O objetivo geral do projeto foi descrever o perfil epidemiológico dos pacientes de uma Unidade de Tratamento de Queimados. Método: O estudo foi uma revisão prontuários de janeiro de 2018 até maio de 2022, incluindo uma amostra de 1164 admissões do Hospital Padre Albino (Catanduva-SP). A análise estatística foi realizada através do Google Sheets e JAMOVI, sendo aplicado o Teste U de Mann-Whitney para comparação de períodos de tempo antes e durante a pandemia. Antes da coleta de dados, o mesmo foi submetido e aprovado pelo Conselho de Ética em Pesquisa da instituição (parecer número 5.616.556, CAAE: 62621822.50000.5430). Resultados: As admissões apresentaram idade média de 31,38 anos e 17,88% de Superfície Corporal Queimada (SCQ), sendo 452 mulheres e 712 homens; a média de SCQ foi de 17 para mulheres e 18,6 para homens. O principal agente causador foi a escaldadura. No que tange à comparação por períodos, durante a pandemia a chama direta teve um aumento de 8% em relação ao período anterior (35%). A escaldadura ainda permaneceu com prevalência elevada, no entanto, apresentou queda de 2%, assim como as queimaduras por dermoabrasão, com queda de 10%. Conclusão: Os achados dos estudos possuem limites em termos de generalização e novos estudos precisam ser desenvolvidos. As mudanças observadas no período não foram significativas e sem relevância clínica.
Introduction: Although prevalent, the epidemiology of burns has gaps. At the same time, Covid-19 established a new scenario with new human behaviors, which could equally impact the characteristics and incidence of burns. The overall objective of the project was to describe the epidemiological profile of patients in a Burn Treatment Unit. Methods: The study was a chart review from January 2018 to May 2022, including a sample of 1164 admissions from Hospital Padre Albino (Catanduva, São Paulo, Brazil). Statistical analysis was performed using Google Sheets and JAMOVI, and Mann-Whitney U-test was applied for comparison of time periods before and during the pandemic. Before data collection, the study was submitted and approved by the Research Ethics Committee of the institution (document number 5.616.556, CAAE: 62621822.50000.5430). Results: The admissions presented a mean age of 31.38 years and 17.88% of body surface area burned, 452 women and 712 men, the mean age was 17 for women and 18.6 for men. The main agent was scalding. When it comes to period comparison, during the pandemic direct flaming had an 8% increase over the previous period (35%). The scalds still remained with high prevalence, however it presented a decrease of 2%, as well as the burns by dermabrasion, which had a decrease of 10%. Conclusion: The findings of the studies have limits in terms of generalization, and new studies need to be developed. The changes observed in the period were not significant and without clinical relevance.
RESUMO
Contexto: Amiloidose é um grupo de doenças caracterizadas pelo depósito de proteínas fibrilares, denominadas substância amiloide. Podem ser divididas em formas localizadas ou sistêmicas, sendo que dentre as localizadas, a forma nodular é a mais rara. Descrição do caso: Relatamos o caso de amiloidose primária localizada cutânea nodular que se apresentou com nódulos violáceos no dorso, e placas acastanhadas na região cervical há 8 anos sem evidências de envolvimento sistêmico. Discussão: Como cerca de 1% a 7% dos casos de amiloidose nodular localizada cutânea podem evoluir com envolvimento sistêmico, o seguimento dos pacientes faz-se necessário. O tratamento não é obrigatório, a retirada das lesões pode ser feita se o paciente o desejar, contudo as recidivas são frequentes. Conclusões: Mesmo possuindo baixa prevalência, a amiloidose nodular deve ser reconhecida pelo risco de progredir para acometimento sistêmico e associação com discrasias plasmocitárias, como mieloma múltiplo.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Plasmócitos , Plasmocitoma , Vermelho Congo , Amiloidose de Cadeia Leve de Imunoglobulina , AmiloidoseRESUMO
Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas. MF is the most common cutaneous lymphoma, and it is classified into classic Alibert-Bazin MF, folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin, each with characteristic clinical presentation, histopathological findings, and distinct clinical behaviors. SS is an aggressive leukemic variant of cutaneous lymphoma, and it is characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by malignant cells. There is a wide range of dermatological manifestations of MF/SS, and prompt recognition is essential for early diagnosis. Skin biopsy for histopathology and immunohistochemical analysis is imperative to confirm the diagnosis of MF/SS. Histopathology may also provide information that may influence prognosis and treatment. Staging follows the TNMB system. Besides advanced stage, other factors associated with poorer prognosis are advanced age, male gender, folliculotropism in histopathology of patients with infiltrated plaques and tumors in the head and neck region, large cell transformation, and elevated lactate dehydrogenase. Treatment is divided into skin-directed therapies (topical treatments, phototherapy, radiotherapy), and systemic therapies (biological response modifiers, targeted therapies, chemotherapy). Allogeneic bone marrow transplantation and extracorporeal photopheresis are other treatment modalities used in selected cases. This review discusses the main clinical characteristics, the histopathological/immunohistochemical findings, the staging system, and the therapeutic management of MF/SS.
RESUMO
Cutaneous metastases from solid tumors are uncommon events in clinical practice. Most of the time, the patient already has the diagnosis of a malignant neoplasm when the cutaneous metastasis is detected. However, in up to one-third of cases, cutaneous metastasis is identified before the primary tumor. Therefore, its identification may be essential for starting treatment, although it is usually indicative of poor prognosis. The diagnosis will depend on clinical, histopathological, and immunohistochemical analysis. Sometimes the identification of the primary site is difficult; however, a thorough analysis using imaging tests and constant surveillance is important.
Assuntos
Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologiaRESUMO
Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3, whereas the pathway analysis indicated a further downregulation of IL1B-associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.
Assuntos
Interleucina-18 , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Dermatite Esfoliativa/metabolismo , Inflamassomos/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Leucócitos Mononucleares/metabolismo , Síndrome de Sézary/metabolismo , Pele/metabolismo , Neoplasias Cutâneas/metabolismoRESUMO
Contexto: A mastocitose ocorre devido a uma proliferação neoplásica e clonal de mastócitos que se acumulam em um ou mais sistemas de órgãos. A doença é heterogênea, com manifestações que vão desde lesões cutâneas que podem regredir espontaneamente até neoplasias altamente agressivas associadas à falência de múltiplos órgãos e baixa sobrevida. Não há relatos na literatura de sua associação com líquen plano. Descrição do caso: Relatamos o caso de uma paciente com diagnóstico de mastocitose sistêmica agressiva que apresentou durante o acompanhamento quadro compatível com líquen plano. DiscussaÌo: O diagnóstico da mastocitose sistêmica é baseado em critérios que foram refinados recentemente. O tratamento classicamente envolve bloqueio de mediadores de mastócitos e terapia citorredutora para variantes avançadas da doença. Novas drogas como a midostaurina e o avapritinibe são promissoras. Conclusões: Mesmo não fazendo parte da rotina do dermatologista, a mastocitose sistêmica deve ser uma doença lembrada pelo acometimento da pele e potencial gravidade do quadro.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Mastocitose , Mastocitose Sistêmica , Mutação com Ganho de Função , Líquen Plano , MastócitosRESUMO
Detection of ALK rearrangement and/or expression of the ALK protein is an essential component in the evaluation of many neoplasms. Variability has been reported in the ability of different antibody clones to detect ALK expression. The ALK01 clone is commonly used to detect ALK expression in ALK-positive anaplastic large cell lymphoma (ALK + ALCL). However, this clone has been shown to lack sensitivity when used for solid tumors. The aim of this study was to determine if our high-sensitivity 5A4-based immunohistochemistry protocol is non-inferior to our ALK01-based protocol for the detection of ALK expression in ALK + ALCL. To compare the two protocols, we stained tissue microarrays of 126 hematolymphoid neoplasms and an additional 21 primary cutaneous ALK-negative anaplastic large cell lymphomas with both protocols. All 28 ALK + ALCL samples that were positive for the ALK01 antibody were also positive for the 5A4 clone. Three cases on the tissue microarray that were negative with the ALK01 antibody were clearly positive with the 5A4 antibody. We subsequently stained whole tissue sections of these three cases with the ALK01 antibody and found that these three cases were indeed positive with the ALK01 protocol, suggesting that the absence of staining on the tissue microarray samples was due to a combination of sampling error as well as a dimmer signal with the ALK01 protocol. Our study demonstrates that our 5A4-based protocol is non-inferior to the ALK01 antibody for the diagnosis of ALK-positive anaplastic large cell lymphoma, thus allowing our laboratory to discontinue the use of the ALK01-based protocol.
Assuntos
Linfoma Anaplásico de Células Grandes , Humanos , Anticorpos , Laboratórios , Linfoma Anaplásico de Células Grandes/diagnóstico , Receptores Proteína Tirosina Quinases/genética , Coloração e RotulagemRESUMO
Abstract Cutaneous metastases from solid tumors are uncommon events in clinical practice. Most of the time, the patient already has the diagnosis of a malignant neoplasm when the cutaneous metastasis is detected. However, in up to one-third of cases, cutaneous metastasis is identified before the primary tumor. Therefore, its identification may be essential for starting treatment, although it is usually indicative of poor prognosis. The diagnosis will depend on clinical, histopathological, and immunohistochemical analysis. Sometimes the identification of the primary site is difficult; however, a thorough analysis using imaging tests and constant surveillance is important.
RESUMO
Extranodal natural-killer/T-cell lymphoma (ENKTL) is a rare and aggressive Epstein-Barr virus related mature T-cell and natural-killer malignancy. Although highly prevalent in South America, few studies covering data from this geographic location have been published. Therefore, this study aims to report clinical characteristics, prognostic factors, and outcomes in a multicenter cohort of ENKTL patients from Brazil. This retrospective, observational and multicenter study included 98 ENKTL patients treated during two decades in Brazil. Data were extracted from the T-Cell Brazil Project database. In our cohort, 59/98 patients (60.2%) were male, with a median age of 50 years. Sixty-two patients (63.3%) had B-symptoms, 26/98 (26.5%) had Eastern Cooperative Oncology Group scale ≥ 2; 16/98 (16.3%) presented extranasal disease and 34.7% (34/98) were advanced-stage (Ann Arbor/Cotswolds III/IV). The median follow-up for the whole cohort was 49 months, with an estimated 2-year overall survival (OS) and progression-free survival (PFS) of 51.1% and 17.7%, respectively. In early-stage disease (IE/IIE), the median OS was 21.8 months for patients treated with concurrent radiotherapy plus chemotherapy (CCRT-VIPD [etoposide/vp-16, ifosfamide, cisplatin and dexamethasone), 16.2 months for sequential chemoradiotherapy (SCRT) followed by asparaginase-based regimens, and 56.7 months for SCRT followed by CHOP-like (cyclophosphamide, doxorrubicin, vincristine and prednisone) treatments, p = 0.211. CCRT was associated with higher rates of early-mortality, hematological toxicity, and mucositis. Median OS was 8.2 months for patients with advanced-stage disease receiving regimens containing asparaginase compared to 3.2 months for anthracycline-based therapy, p = 0.851. Chemo-radiotherapy (CRT) regimens demonstrated better OS (p = 0.001) and PFS (p = 0.007) than chemotherapy alone. Multivariate analysis revealed anemia, relapsed/refractory (R/R) disease and radiotherapy omission as poor outcome predictors for OS. Lymphopenia and radiotherapy omission adversely affected PFS. Concerning progression of disease within 24-months (POD-24), clinical stage III/IV was a poor outcome predictor. In this real-life Brazilian cohort, ENKTL presented dismal outcomes. Radiation therapy was an independent factor for increased OS and PFS, but CCRT regimens were associated with higher toxicities. Polychemotherapy based on anti-multi drug resistant agents was not associated with survival benefit in either early or advanced-stage disease in our patient cohort.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/radioterapia , Brasil/epidemiologia , Asparaginase , Estudos Retrospectivos , Herpesvirus Humano 4/genética , EtoposídeoRESUMO
ABSTRACT: Epstein-Barr virus-positive mucocutaneous ulcer is a recent and unusual type of lymphoproliferation, mostly associated with various forms of immunosuppression. In most cases, they regress spontaneously, but an increasing number of reports describe a spectral behavior of the lesion, which ranges from a simple ulcer with eosinophilia to aggressive ulcers. In these cases, Epstein-Barr virus-related lymphomas are the main differential diagnosis. We report a unique observation of this rare disease with mandibular involvement. Due to bone erosion, the patient was treated with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with complete healing of the ulcer on clinical examination and PET-scan control.
Assuntos
Infecções por Vírus Epstein-Barr , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Úlcera/tratamento farmacológico , VincristinaRESUMO
Contexto: A pandemia da doença do coronavírus (COVID-19) revelou uma miríade de manifestações sistêmicas e cutâneas possivelmente relacionadas à infecção por síndrome respiratória aguda grave ocasionada pelo coronavírus (SARS-CoV-2). O comprometimento pulmonar é a causa mais frequente de hospitalização e a progressão para síndrome respiratória aguda grave geralmente requer tratamento com ventilação mecânica na posição pronada. Períodos prolongados e repetidos de pronação aumentam o risco de complicações, incluindo úlcera de pressão, cegueira e neuropatia periférica. Descrição do caso: Relatamos três casos de complicações cutâneas relacionadas à ventilação em pronação avaliadas durante interconsultas no maior hospital terciário universitário da América Latina, e salientamos potenciais causas e medidas de prevenção. Discussão: Complicações da ventilação em pronação para tratamento da COVID-19 são provavelmente resultantes da interação entre múltiplos fatores, dentre os quais as condições clínicas do paciente, períodos prolongados na posição pronada e limitações para mudanças de decúbito. Conclusões: Medidas de prevenção para complicações da pronação e diagnóstico precoce são fundamentais para evitar aumento da morbidade e sequelas graves e irreversíveis associadas à COVID-19.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Dermatopatias , Pronação , Ventilação Pulmonar , SARS-CoV-2 , COVID-19Assuntos
Linfoma Cutâneo de Células T , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Biópsia com Agulha de Grande Calibre , Humanos , Linfonodos/patologia , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/patologia , Micose Fungoide/cirurgia , Síndrome de Sézary/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
Abstract Background: Mucocutaneous adverse events are common during anticancer treatment, with variable consequences for the patient and their therapeutic regimen. Objective: To evaluate the most common adverse events, as well as the drugs associated with their appearance and the consequences for cancer treatment. Methods: A retrospective study was carried out through the analysis of patients treated at the Clinical Dermatology Unit of a public oncologic hospital. Results: A total of 138 patients with 200 adverse events were evaluated. The most commonly identified adverse events were nail and periungual changes (20%), papulopustular eruptions (13%), acneiform eruptions (12%), hand-foot syndrome (6.5%), hand-foot skin reaction (6%), and xerosis (6%). The most frequently associated antineoplastic treatment groups were classical chemotherapy (46.2%), target therapy (32.3%), and other non-antineoplastic drugs used in neoplasia protocols (16.5%). Of the total number of patients, 17.4% had their treatment suspended or changed due to a dermatological adverse event. Study limitations: Retrospective study and analysis of patients who were referred for specialized dermatological examination only, not allowing the assessment of the actual incidence of adverse events. Conclusion: A wide variety of dermatological manifestations are secondary to antineoplastic treatment with several different drugs resulting, not rarely, in the interruption or modification of therapeutic regimens.
Assuntos
Humanos , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Pele , Estudos Retrospectivos , HospitaisRESUMO
Sézary syndrome is an aggressive leukemic variant of cutaneous T-cell lymphomas, characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by CD4+ malignant T-cells. The pathogenesis of Sézary syndrome is not fully understood. However, the course of the disease is strongly influenced by the tumor microenvironment, which is altered by a combination of cytokines, chemokines, and growth factors. The crosstalk between malignant and reactive cells affects the immunologic response against tumor cells causing immune dysregulation. This review focuses on the interaction of malignant Sézary cells and the tumor microenvironment.