RESUMO
The 2016 World Health Organization classification defines diffuse large B-cell lymphoma (DLBCL) subtypes based on Epstein-Barr virus (EBV) infection and oncogenic rearrangements of MYC/BCL2/BCL6 as drivers of lymphomagenesis. A subset of DLBCL, however, is characterized by activating mutations in MYD88/CD79B We investigated whether MYD88/CD79B mutations could improve the classification and prognostication of DLBCL. In 250 primary DLBCL, MYD88/CD79B mutations were identified by allele-specific polymerase chain reaction or next-generation-sequencing, MYC/BCL2/BCL6 rearrangements were analyzed by fluorescence in situ hybridization, and EBV was studied by EBV-encoded RNA in situ hybridization. Associations of molecular features with clinicopathologic characteristics, outcome, and prognosis according to the International Prognostic Index (IPI) were investigated. MYD88 and CD79B mutations were identified in 29.6% and 12.3%, MYC, BCL2, and BCL6 rearrangements in 10.6%, 13.6%, and 20.3%, and EBV in 11.7% of DLBCL, respectively. Prominent mutual exclusivity between EBV positivity, rearrangements, and MYD88/CD79B mutations established the value of molecular markers for the recognition of biologically distinct DLBCL subtypes. MYD88-mutated DLBCL had a significantly inferior 5-year overall survival than wild-type MYD88 DLBCL (log-rank; P=0.019). DLBCL without any of the studied aberrations had superior overall survival compared to cases carrying ≥1 aberrancy (log-rank; P=0.010). MYD88 mutations retained their adverse prognostic impact upon adjustment for other genetic and clinical variables by multivariable analysis and improved the prognostic performance of the IPI. This study demonstrates the clinical utility of defining MYD88-mutated DLBCL as a distinct molecular subtype with adverse prognosis. Our data call for sequence analysis of MYD88 in routine diagnostics of DLBCL to optimize classification and prognostication, and to guide the development of improved treatment strategies.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Fator 88 de Diferenciação Mieloide/genética , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4 , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Mutação , PrognósticoAssuntos
Antígeno B7-H1/imunologia , Neoplasias do Sistema Nervoso Central/imunologia , Linfoma de Células B/imunologia , Complexo Principal de Histocompatibilidade , Proteína 2 Ligante de Morte Celular Programada 1/imunologia , Neoplasias Testiculares/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Neoplasias do Sistema Nervoso Central/genética , Feminino , Deleção de Genes , Genes MHC Classe I , Genes MHC da Classe II , Humanos , Evasão da Resposta Imune , Linfoma de Células B/genética , Masculino , Pessoa de Meia-Idade , Mutação , Proteína 2 Ligante de Morte Celular Programada 1/genética , Neoplasias Testiculares/genéticaRESUMO
A patient in his late 30s presented with symptoms consistent with a nephrotic syndrome. Renal biopsy revealed membranous nephropathy. He also mentioned a spontaneous resolving 'rash' at his glans penis after unprotected intercourse. Therefore, he was tested for sexually transmitted diseases as a possible underlying cause of his nephrotic syndrome. Serology for syphilis was positive with high titres. After a single penicillin injection, there was fast and complete clinical recovery.
Assuntos
Glomerulonefrite Membranosa/etiologia , Síndrome Nefrótica/etiologia , Sífilis/complicações , Adulto , Glomerulonefrite Membranosa/patologia , Humanos , Rim/patologia , Rim/ultraestrutura , Masculino , Penicilinas/uso terapêutico , Sífilis/tratamento farmacológico , Sorodiagnóstico da SífilisAssuntos
Doenças Transmissíveis Emergentes/complicações , Dengue/complicações , Síndrome Hemolítico-Urêmica/virologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/virologia , Doenças Transmissíveis Emergentes/diagnóstico , Dengue/diagnóstico , Dengue/virologia , Vírus da Dengue/ultraestrutura , Olho/patologia , Membrana Basal Glomerular/ultraestrutura , Membrana Basal Glomerular/virologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Forkhead box (FOXP3) is considered to be a specific marker for regulatory T cells. The aim of this study was to correlate intragraft FOXP3 at mRNA and cellular levels during renal allograft rejection to response to therapy and late clinical outcome. METHODS: Immunostainings and quantitative reverse-transcriptase polymerase chain reaction for FOXP3, CD3, and transforming growth factor (TGF)-beta were performed and results were related to histopathologic and clinical outcome. RESULTS: A good correlation between immunohistochemical analysis and mRNA levels for both CD3 and FOXP3 was observed. Intragraft FOXP3 was significantly related to tubulitis and interstitial fibrosis. A strong correlation was found between FOXP3 and CD3 mRNA and between FOXP3 and TGF-beta mRNA. No correlation was found between FOXP3 and response to therapy. DISCUSSION: In conclusion, intragraft FOXP3 at both cellular and molecular levels parallels T-cell infiltration during acute rejection. FOXP3 does not predict response to antirejection therapy. FOXP3 correlates with renal fibrosis, TGF-beta, and poor late renal outcome.