Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.371
Filtrar
1.
Medicine (Baltimore) ; 99(1): e18503, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895784

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. In clinical practice, we have observed that some HLH patients who have features of systemic autoinflammatory diseases (SAIDs) exhibit unique clinical manifestations and outcomes different from other HLH patients.We analyzed data from 25 HLH patients who were considered to have SAIDs; data were collected from patients of our center between January 1, 2015 and September 1, 2018.The median age of the patients was 1.75 years. In the early phase, all patients had a fever and 92% of patients had a rash; 96% of patients had high white blood cell count (WBC), C-reaction protein, and erythrocyte sedimentation rate. With progression, the above laboratory results decreased gradually. During the HLH period, we compared SAIDs-related HLH and Epstein-Barr virus (EBV)-related HLH and found that rash was more common (92%, P < .001) and splenomegaly was less common (64%, P = .023) in SAIDs-related HLH. Further, WBC, ferritin, and Interleukin-6 levels in SAIDs-related HLH patients were higher than those in EBV-related HLH patients. In contrast, hemoglobin, triglyceride, sCD25, Interleukin-10, and interferon-γ levels in SAIDs-related HLH patients were lower compared with those in EBV-related HLH patients. SAIDs-related HLH patients received a modified HLH-2004 protocol at our center. Most patients had a good prognosis.We provide a summary of the unique clinical and laboratory features, treatment protocols, and outcomes of SAIDs patients with HLH at onset. The findings indicate that these patients had a better response to corticosteroids and cyclosporin compared with EBV-related HLH patients.


Assuntos
Doenças Autoimunes/patologia , Infecções por Vírus Epstein-Barr/patologia , Exantema/etiologia , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica/patologia , Corticosteroides/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/virologia , Sedimentação Sanguínea , Proteína C-Reativa , Ciclosporina/uso terapêutico , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Exantema/patologia , Exantema/virologia , Feminino , Humanos , Lactente , Contagem de Leucócitos , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Esplenomegalia/imunologia , Esplenomegalia/virologia , Resultado do Tratamento
2.
World Neurosurg ; 133: 10-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31550543

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) in an immunocompromised patient with organ transplantation demonstrated unusual brain magnetic resonance imaging (MRI) findings. Recognition of EBV-positive DLBCL by radiologists on MRI may prevent unnecessary neurosurgical resection, and it could be important to obtain viable cells for accurate diagnosis on stereotactic biopsy because of extensive necrosis. CASE DESCRIPTION: A 62-year-old woman presented to the emergency department with left hemiparesis grade III and dysarthria lasting for 3 weeks. She underwent kidney transplantation in 2007 and was taking immunosuppressants and had hypothyroidism. Brain MRI showed a 3.8-cm peripheral enhancing lesion with extensive central necrosis in association with marked perilesional edema. The irregular ringlike enhancing lesion showed diffusion restriction and mildly increased regional cerebral blood volume in the rim portion of the mass. 11C-Methionine positron emission tomography revealed slightly increased uptake in the peripheral lesion. The provisional diagnosis was a high-grade glioma. Stereotactic multiple biopsies were performed for the central necrotic area and peripheral enhancing lesion. The nonenhancing areas showed only necrotic material, without viable cells, and the enhancing portion showed viable cells for an accurate diagnosis in a frozen biopsy specimen. The pathologic diagnosis was EBV-positive DLBCL with extensive necrosis. Positron emission tomography of the chest, abdomen, pelvis, and neck soft tissues ruled out systemic diseases. She underwent whole-brain radiotherapy at a dose of 30.6 Gy. Eight months later, her neurologic symptoms had improved, with a stable brain lesion and improved perilesional edema. CONCLUSIONS: We report an immunocompromised patient with EBV-positive DLBCL, which showed atypical MRI findings, including extensive necrosis. Multiple biopsies were required for final diagnosis.


Assuntos
Encéfalo/patologia , Infecções por Vírus Epstein-Barr/patologia , Linfoma Difuso de Grandes Células B/patologia , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Feminino , Humanos , Hospedeiro Imunocomprometido , Transplante de Rim , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Necrose/patologia , Necrose/virologia , Transplantados
3.
Virchows Arch ; 475(6): 757-762, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31673776

RESUMO

Epstein-Barr virus (EBV) has been associated with about 9% of all gastric carcinomas, but its role in gastric carcinogenesis remains unclear since there is lack of evidence of EBV presence in pre-neoplastic lesions of gastric mucosa. This study intends to determine the prevalence of EBV in gastric dysplasia and superficial neoplasia to clarify whether EBV infection is an early or late event in gastric cancer development. This retrospective study included a total of 242 gastric lesions from 199 consecutive patients who were referred for endoscopic resection. The histological classification of lesions includes 137 low- and high-grade dysplasia and 105 superficial carcinomas. EBV infection was investigated by EBER-ISH. Results showed that EBV was not detected in any epithelial cells of any case with dysplasia or superficial carcinomas, although we observed the presence of a small number of EBV-infected lymphocytes in 2.1% of all lesions. These results showed that EBV is not present in gastric dysplasia neither in superficial carcinomas suggesting that EBV carcinogenesis is a late event in well/moderately differentiated gastric carcinogenesis.


Assuntos
Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/patogenicidade , Neoplasias Gástricas/virologia , Estômago/virologia , Idoso , Carcinoma/patologia , Carcinoma/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Feminino , Mucosa Gástrica/patologia , Mucosa Gástrica/virologia , Humanos , Hibridização In Situ/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estômago/patologia , Neoplasias Gástricas/patologia
4.
PLoS Pathog ; 15(9): e1008030, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31518366

RESUMO

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with multiple human malignancies. EBV drives B-cell proliferation, which contributes to the pathogenesis of multiple lymphomas. Yet, knowledge of how EBV subverts host biosynthetic pathways to transform resting lymphocytes into activated lymphoblasts remains incomplete. Using a temporal proteomic dataset of EBV primary human B-cell infection, we identified that cholesterol and fatty acid biosynthetic pathways were amongst the most highly EBV induced. Epstein-Barr nuclear antigen 2 (EBNA2), sterol response element binding protein (SREBP) and MYC each had important roles in cholesterol and fatty acid pathway induction. Unexpectedly, HMG-CoA reductase inhibitor chemical epistasis experiments revealed that mevalonate pathway production of geranylgeranyl pyrophosphate (GGPP), rather than cholesterol, was necessary for EBV-driven B-cell outgrowth, perhaps because EBV upregulated the low-density lipoprotein receptor in newly infected cells for cholesterol uptake. Chemical and CRISPR genetic analyses highlighted downstream GGPP roles in EBV-infected cell small G protein Rab activation. Rab13 was highly EBV-induced in an EBNA3-dependent manner and served as a chaperone critical for latent membrane protein (LMP) 1 and 2A trafficking and target gene activation in newly infected and in lymphoblastoid B-cells. Collectively, these studies identify highlight multiple potential therapeutic targets for prevention of EBV-transformed B-cell growth and survival.


Assuntos
Linfócitos B/virologia , Ácidos Graxos/biossíntese , Herpesvirus Humano 4/patogenicidade , Ácido Mevalônico/metabolismo , Alquil e Aril Transferases/metabolismo , Linfócitos B/patologia , Proliferação de Células , Sobrevivência Celular , Colesterol/biossíntese , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Redes e Vias Metabólicas , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteínas Virais/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
6.
Surg Pathol Clin ; 12(3): 709-718, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352983

RESUMO

The diagnosis of B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, also called gray zone lymphoma (GZL), is frequently challenging. Incorrect diagnosis as either classic Hodgkin lymphoma or diffuse large B-cell lymphoma has significant implications for choice of upfront therapy based on recent large multi-institutional series from the United States and Europe. These studies have clarified some diagnostic challenges and provided guidance on the spectrum of morphologic features in this entity. This article clarifies some of the diagnostic conundrum surrounding GZL and provides an evidence-based approach to GZL diagnosis using morphology and immunohistochemistry.


Assuntos
Linfoma de Células B/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/patologia , Feminino , Doença de Hodgkin/patologia , Humanos , Imunofenotipagem/métodos , Antígeno Ki-1/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias do Timo/patologia
7.
Cancer Biomark ; 25(3): 259-273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31282408

RESUMO

BACKGROUND: The expression of neuropilin-1 (NRP-1) in Epstein-Barr virus (EBV)-associated lymphomas and its relationships with clinicopathological parameters was investigated. METHODS: The researchers compared 111 cases of patients with lymphoma to 20 cases of reactive lymphoid hyperplasia. In situ hybridization was applied to observe the expression of EBV-encoded RNA (EBER) in lymphomas, and immunohistochemistry was used to detect the NRP-1 expression in lymphoma tissues and lymph node tissues with reactive hyperplasia. RESULTS: In these 111 cases, the EBER of 62 cases (55.9%) appeared positive. NRP-1 was relatively highly expressed in lymphomas (P= 0.019). Further, NRP-1 showed higher expression in lymphomas with positive EBER than in negative ones. A comprehensive analysis revealed that NRP-1 was differently expressed in NK/T-cell lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma (P= 0.027). Moreover, highly expressed NRP-1 was found to be a useful independent prognostic factor in assessing overall survival and progression-free survival rates in cases of non-Hodgkin's lymphoma (NHL). CONCLUSIONS: NRP-1 exhibited higher expression in lymphomas, and it was positively expressed in EBV-positive lymphomas. Moreover, highly expressed NRP-1 can be used as an undesirable independent prognostic factor in NHL.


Assuntos
Biomarcadores Tumorais/genética , Infecções por Vírus Epstein-Barr/genética , Linfoma/genética , Neuropilina-1/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidade , Humanos , Imuno-Histoquímica , Linfoma/classificação , Linfoma/patologia , Linfoma/virologia , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/virologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
8.
J Clin Exp Hematop ; 59(2): 64-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257347

RESUMO

Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCUs) were first described as a lymphoproliferative disorder in 2010. Clinically, EBVMCUs are shallow, sharply circumscribed, unifocal mucosal or cutaneous ulcers that occur in immunosuppressed patients, including those with advanced age-associated immunosenescence, iatrogenic immunosuppression, primary immune disorders, and HIV/AIDS-associated immune deficiencies. In general, patients exhibit indolent disease progression and spontaneous regression. Histologically, EBVMCUs are characterized by the proliferation of EBV-positive, variable-sized, atypical B-cells. According to conventional histopathologic criteria, EBVMCUs may diagnosed as lymphomas. However, EBVMCUs are recognized as pseudomalignant lesions because they spontaneously regress without anti-cancer treatment. Therefore, overtreatment must be carefully avoided and multilateral differentiation is important. In this article, we reviewed previously reported EBVMCUs focusing on their clinical and pathological aspects in comparison with other EBV-positive B-cell neoplasms.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/isolamento & purificação , Úlcera Cutânea/etiologia , Úlcera Cutânea/virologia , Animais , Linfócitos B/patologia , Linfócitos B/virologia , Gerenciamento Clínico , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/patologia , Humanos , Prognóstico , Pele/patologia , Pele/virologia , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/patologia
9.
Georgian Med News ; (290): 69-73, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31322518

RESUMO

Epstein-Barr virus (EBV) is referred to the viruses with lifelong persistence in the human body in active and latent phases. EBV initiates impairment of expression of cell microRNA, which participates in the regulation of immune system function and can be related to different pathological conditions, including allergopathy. Aim - to assess the levels of miR-146a and miR-155 expression in patients with allergopathy in combination with active and latent phases of EBV infection. Clinical, general laboratory, cytological, instrumental, specific allergological, molecular-genetic investigations were performed. Based on these investigations, patients were divided into two groups: 1st group (27 individuals) with allergopathy and active phase of chronic EBV-infection, 2nd group (19 individuals) with allergopathy and latent phase of EBV infection. Control group included 20 healthy individuals. Higher (р>0.05) levels of miR-146a expression were detected in patients of both groups compared with control group. Expression of miR-155 was higher (р>0.05) only in patients of the 1st group compared with control. No significant difference was noticed between investigated groups. In latent phase, EBV uses own mechanisms of latency to avoid immune surveillance, which are manifested by increase in miR-155 and miR-146а expression. In active phase, this vector of changes intensified and was associated with acute manifestations of allergopathy.


Assuntos
Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/metabolismo , Hipersensibilidade/imunologia , MicroRNAs/genética , Adolescente , Adulto , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Latência Viral , Adulto Jovem
10.
Int J Med Sci ; 16(4): 556-566, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171907

RESUMO

Background: Clinical significance of germinal center B-cell (GCB) and non-GCB sub-categorization, expression of MYC, BCL2, BCL6, CD5 proteins and Epstein Barr virus encoded RNA (EBER) positivity in diffuse large B-cell lymphoma (DLBCL) remain controversial. Could these biomarkers accurately identify high risk DLBCL patients? Are MYC, BCL2 and BCL6 proteins expression feasible as baseline testing to predict c-Myc, BCL2 or BCL6 gene rearrangements? Aims: To investigate prognostic values of GCB/non-GCB sub-categorization, Double Protein Expression Lymphoma (DPL), Triple Protein Expression Lymphoma (TPL), positivity of CD5 protein and EBER in patients with DLBCL disease. To evaluate correlation between BCL2 , c-Myc and BCL6 gene rearrangements with BCL2, MYC and BCL6 proteins expression. Methods: Diagnostic tissue samples of 120 DLBCL patients between January 2012 to December 2013 from four major hospitals in Malaysia were selected. Samples were subjected to immunohistochemical staining, fluorescent in-situ hybridization (FISH) testing, and central pathological review. Pathological data were correlated with clinical characteristics and treatment outcome. Results: A total of 120 cases were analysed. Mean age of diagnosis was 54.1 years ± 14.6, 64 were males, 56 were females, mean follow up period was 25 months (ranged from 1 to 36 months). Of the 120 cases, 74.2% were non-GCB whereas 25.8% were GCB, 6.7% were EBER positive, 6.7% expressed CD5 protein, 13.3% were DPL and 40% were TPL. The prevalence of c-Myc, BCL2, BCL6 gene rearrangements were 5.8%, 5.8%, and 14.2%, respectively; and 1.6% were Double Hit Lymphoma (DHL). EBER positivity, DPL, TPL, c-Myc gene rearrangement, BCL2 gene rearrangement, extra copies of BCL2 gene and BCL6 gene rearrangement were associated with shorter median overall survival (P<0.05). IPI score was the significant determinants of median overall survival in DPL and TPL (P<0.05). CD5 protein expression and GCB/non-GCB sub-categorization did not affect treatment outcome (P>0.05). Overall, c-Myc, BCL2 and BCL6 gene rearrangements showed weak correlation with expression of MYC, BCL2 and BCL6 proteins (P>0.05). Fluorescent in situ hybridization is the preferred technique for prediction of treatment outcome in DLBCL patients. Conclusion: c-Myc, BCL2, and BCL6 gene rearrangements, EBER expression, DHL, TPL and IPI score are reliable risk stratification tools. MYC, BCL2 and BCL6 proteins expression are not applicable as baseline biomarkers to predict c-Myc, BCL2, and BCL6 gene rearrangements.


Assuntos
Infecções por Vírus Epstein-Barr/genética , Regulação Neoplásica da Expressão Gênica/genética , Linfoma Difuso de Grandes Células B/genética , Prognóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígenos CD5/genética , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Rearranjo Gênico/genética , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Malásia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Serpinas/genética , Resultado do Tratamento , Adulto Jovem
11.
Blood ; 133(26): 2753-2764, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31064750

RESUMO

Patients with classic hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or natural killer (NK) cells in blood and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe but more common in Asia and South America. The disease can progress to a systemic form that may result in fatal lymphoma. We report our 11-year experience with 16 HVLPD patients from the United States and England and found that whites were less likely to develop systemic EBV disease (1/10) than nonwhites (5/6). All (10/10) of the white patients were generally in good health at last follow-up, while two-thirds (4/6) of the nonwhite patients required hematopoietic stem cell transplantation. Nonwhite patients had later age of onset of HVLPD than white patients (median age, 8 vs 5 years) and higher levels of EBV DNA (median, 1 515 000 vs 250 000 copies/ml) and more often had low numbers of NK cells (83% vs 50% of patients) and T-cell clones in the blood (83% vs 30% of patients). RNA-sequencing analysis of an HVLPD skin lesion in a white patient compared with his normal skin showed increased expression of interferon-γ and chemokines that attract T cells and NK cells. Thus, white patients with HVLPD were less likely to have systemic disease with EBV and had a much better prognosis than nonwhite patients. This trial was registered at www.clinicaltrials.gov as #NCT00369421 and #NCT00032513.


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Hidroa Vaciniforme/virologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/etnologia , Infecções por Vírus Epstein-Barr/imunologia , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Transtornos Linfoproliferativos/etnologia , Masculino
12.
PLoS One ; 14(5): e0216898, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31141539

RESUMO

NKL homeobox genes encode developmental transcription factors regulating basic processes in cell differentiation. According to their physiological expression pattern in early hematopoiesis and lymphopoiesis, particular members of this homeobox gene subclass constitute an NKL-code. B-cell specific NKL-code genes generate a regulatory network and their deregulation is implicated in B-cell lymphomagenesis. Epstein-Barr virus (EBV) infects B-cells and influences the activity of signalling pathways including JAK/STAT and several genes encoding developmental regulators. Therefore, EBV-infection impacts the pathogenesis and the outcome of B-cell malignancies including Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL). Here, we isolated EBV-positive and EBV-negative subclones from the DLBCL derived cell line DOHH-2. These subclones served as models to investigate the role of EBV in deregulation of the B-cell specific NKL-code members HHEX, HLX, MSX1 and NKX6-3. We showed that the EBV-encoded factors LMP1 and LMP2A activated the expression of HLX via STAT3. HLX in turn repressed NKX6-3, SPIB and IL4R which normally mediate plasma cell differentiation. In addition, HLX repressed the pro-apoptotic factor BCL2L11/BIM and hence supported cell survival. Thus, EBV aberrantly activated HLX in DLBCL, thereby disturbing both B-cell differentiation and apoptosis. The results of our study appreciate the pathogenic role of EBV in NKL homeobox gene deregulation and B-cell malignancies.


Assuntos
Infecções por Vírus Epstein-Barr/metabolismo , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 4/metabolismo , Proteínas de Homeodomínio/biossíntese , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas de Neoplasias/biossíntese , Fatores de Transcrição/biossíntese , Apoptose , Diferenciação Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Infecções por Vírus Epstein-Barr/patologia , Humanos , Linfoma Difuso de Grandes Células B/patologia , Proteínas da Matriz Viral/metabolismo
13.
Ann Hematol ; 98(8): 1877-1883, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144019

RESUMO

Secondary poor graft function (sPGF) is defined as secondary cytopenia after initial engraftment of allogeneic stem cell transplantation (allo-SCT). It has been shown to be associated with poor prognosis; however, there are very few reports on the incidence, risk factors, and outcomes of sPGF. Between January 2015 and December 2015, 564 patients, who received transplantation at Peking University People's Hospital, were retrospectively reviewed. Among the 490 patients who achieved initial engraftment of both neutrophils and platelets, 28 patients developed sPGF. The cumulative incidence of sPGF on day 100 was 5.7%. The median time of sPGF was 54.5 (34-91) days after transplantation. Low (< median) CD34+ cell dose (p = 0.019, HR 3.07 (95% CI, 1.207-7.813)), Epstein-Barr Virus (EBV) reactivation (p = 0.009, HR 3.648 (95%CI, 1.382-9.629)), and cytomegalovirus (CMV) reactivation (p = 0.003, HR 7.827 (95%CI, 2.002-30.602)) were identified as independent risk factors for sPGF. There was no significant difference in PGF incidence between the matched sibling donor (MSD) group and haploidentical donor (HID) group (p = 0.44). The overall survival of patients with sPGF at 1 year after transplantation was significantly poorer than that of patients with good graft function (GGF) (50.5% versus 87.2%, p < 0.001). In conclusion, sPGF developed in 5.7% patients after allo-SCT, especially in patients with CMV, EBV reactivation, or infusion with a low dose of CD34+ cells. The prognosis of sPGF is still poor owing to a lack of standard treatment.


Assuntos
Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/virologia , Doença Enxerto-Hospedeiro/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Ativação Viral/imunologia , Adolescente , Adulto , Idoso , Antígenos CD34/imunologia , Criança , Pré-Escolar , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/patologia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Feminino , Sobrevivência de Enxerto/fisiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/virologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Leucemia/mortalidade , Leucemia/patologia , Leucemia/virologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/virologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Haploidêntico
14.
Zhonghua Yan Ke Za Zhi ; 55(5): 374-380, 2019 May 11.
Artigo em Chinês | MEDLINE | ID: mdl-31137150

RESUMO

Objective: To evaluate the clinicopathological features of ocular natural killer(NK)/T cell lymphoma. Methods: Data of 21 patients (22 eyes) with ocular NK/T cell lymphoma treated at Eye & ENT Hospital of Fudan University from January 2006 to March 2018 were retrospectively analyzed for clinical data, morphology, immunophenotype and outcomes. Results: There were 10 males and 11 females with ages from 3 to 77 years (mean, 43 years). There were 20 unilateral cases (10 left eyes and 10 right eyes) and 1 bilateral case. Except for 1 case of corneal perforation resulting from the involvement of the conjunctiva and cornea, the other cases all involved the orbit (including eyelids and conjunctiva) as demonstrated by radiologic studies, with the lacrimal sac involved in 3 cases, and the nasal cavity or maxillary sinus involved in 2 cases. Three patients had been previously diagnosed sinonasal NK/T cell lymphoma with radiotherapy and chemotherapy. Two patients had a history of ovarian NK/T cell lymphoma with chemotherapy. One patient had multiple ulcers of skin and mucosa at presentation. There were 13 primary ocular NK/T cell lymphomas without evidence of nasal or systemic involvement. All patients presented with eyelid swelling and decreased visual acuity. There were proptosis in 18 cases, motility restriction in 13 cases, eyelid ulceration in 3 cases, and fever in 4 cases. They had all been previously diagnosed as orbital pseudotumor or cellulitis and there was no response to steroids and antibiotics. Pathological examination showed atypical lymphoid infiltration with an angioinvasive growth pattern causing coagulative necrosis. Cytologically, the medium-sized neoplastic cells showed irregular folded nuclei. The neoplastic cells were positive for cytoplasmic CD3ε, CD56, and cytotoxic molecules and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization. Seven patients were lost to follow-up. Ten patients died 2.0 to 17.0 months after diagnosis (mean, 6.3 months) despite treatment with chemotherapy and radiotherapy. Conclusions: Ocular NK/T cell lymphoma is a rare form of ocular lymphoma. There are primary NK/T cell lymphoma and secondary ocular NK/T cell lymphoma with nasal or systemic involvement. The rarity of this tumor and inflammatory signs make it challenging to identify these tumors early. The neoplastic cells are positive for cytoplasmic CD3ε, CD56, cytotoxic molecules and EBER in situ hybridization. Despite aggressive therapy, it demonstrates high lethality with poor prognosis. (Chin J Ophthalmol, 2019, 55: 374-380).


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Neoplasias Oculares/patologia , Células Matadoras Naturais/patologia , Linfoma de Células B , Linfoma de Células T/patologia , Neoplasias Orbitárias/patologia , Neoplasias Cutâneas/patologia , Linfócitos T/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/imunologia , Neoplasias Oculares/imunologia , Neoplasias Oculares/terapia , Neoplasias Oculares/virologia , Feminino , Humanos , Linfoma de Células T/imunologia , Linfoma de Células T/terapia , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/virologia , Resultado do Tratamento , Adulto Jovem
16.
Pediatr Blood Cancer ; 66(8): e27798, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31099136

RESUMO

BACKGROUND: Systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood (S-EBV-T-LPD) comprise three major forms: EBV-positive hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV-positive T-cell lymphoma (S-EBV-TCL), and systemic chronic active EBV infection (S-CAEBV). These disorders occur rarely in children in Western countries. Here, we described eight children of such entities. DESIGN: Eight cases (six clinical and two autopsy) with S-EBV-T-LPD of childhood were retrospectively identified from 1990 to 2015. Clinicopathologic parameters including histomorphology, immunophenotype, EBV studies, and T-cell receptor gene rearrangement studies were recorded. RESULTS: Patients include five females and three males of Hispanic, Asian, and Caucasian origins with an age range of 14 months to 9 years. Fever, hepatosplenomegaly, cytopenias, abnormal EBV serologies, and very high EBV viral loads were common findings. Histologic findings showed EBV+ T-cell infiltrates with variable degrees of architectural distortion and cytologic atypia ranging from no to mild cytologic atypia to overt lymphoma and tissue hemophagocytosis. All showed aberrant CD4+ or CD8+ T cells with dim to absent CD5, CD7, and CD3, and bright CD2 and CD45 by flow cytometry or loss of CD5 by immunohistochemistry. TCR gene rearrangement studies showed monoclonal rearrangements in all clinical cases (6/6). Outcomes were poor with treatment consisting of chemotherapy per the HLH-94 or HLH-2004 protocols with or without bone marrow transplant. CONCLUSION: In this large pediatric clinicopathologic study of S-EBV-T-LPD of childhood in the United States, EBV-HLH, S-EBV-TCL, and S-CAEBV show many overlapping features. Diagnosis is challenging, and overall outcome is poor using current HLH-directed therapies.


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/isolamento & purificação , Linfoma de Células T/patologia , Transtornos Linfoproliferativos/patologia , Linfócitos T/patologia , Atenção Terciária à Saúde/estatística & dados numéricos , Medula Óssea/patologia , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Humanos , Lactente , Fígado/patologia , Linfonodos/patologia , Linfoma de Células T/classificação , Linfoma de Células T/etiologia , Transtornos Linfoproliferativos/classificação , Transtornos Linfoproliferativos/etiologia , Masculino , Prognóstico , Estudos Retrospectivos
17.
Medicine (Baltimore) ; 98(14): e14839, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946311

RESUMO

Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELGC) is a rare primary stomach tumor, which has overlapping imaging features with mass forming gastric carcinoma (GC). The aim of our study was to present the computed tomography (CT) findings and clinical features of EBV-associated LELGC to increase awareness of this entity.The CT findings and clinical features of 4 patients with pathologically documented EBV-associated LELGC were retrospectively analyzed.Among the 4 patients, 3 were male, and 1 was female. The medium age was 51 years old. All cases were single lesions including 1 was in the gastric cardia, 1 was in the gastric body, and 2 were in the gastric antrum. A focal thickening of the gastric wall was conducted, with a large thickness-to-length ratio. The low-density stripe of the normal gastric wall abruptly terminated at the edge of the lesion. The CT images of 4 cases showed inhomogeneous density with the radiodensity values ranging from 25 to 48 HU. In addition, an ulcer was demonstrated with an irregular base and slightly raised borders in all cases. Enhancement after injection of contrast material was heterogeneous enhancement (n = 3) or homogeneous (n = 1). After enhancement, obvious enhancement was seen in 1 case, moderate enhancement was seen in 3 cases, with the peak value of the tumor in the portal phase. No evidence of lymph node involvement and distant invasion was observed.Although LELGC is quite rare, it should be considered in differential diagnosis of early GC, advanced GC, and lymphoma. The relatively typical CT appearance, combined the age and sex of patients, can suggest the diagnosis of LELGC.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Neoplasias Gástricas/diagnóstico por imagem , Estômago/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Conscientização , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Carcinoma/virologia , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/patologia , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Linfoma/patologia , Linfoma/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estômago/patologia , Estômago/virologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia
18.
PLoS Pathog ; 15(4): e1007541, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31017975

RESUMO

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that considerable levels of p62-mediated selective autophagy are spontaneously induced, and correlate with ROS-Keap1-NRF2 pathway activity, in virus-transformed cells. Inhibition of autophagy results in p62 accumulation in the nucleus, and promotes ROS-induced DNA damage and cell death, as well as downregulates the DNA repair proteins CHK1 and RAD51. In contrast, MG132-mediated proteasome inhibition, which induces rigorous autophagy, promotes p62 degradation but accumulation of the DNA repair proteins CHK1 and RAD51. However, pretreatment with an autophagy inhibitor offsets the effects of MG132 on CHK1 and RAD51 levels. These findings imply that p62 accumulation in the nucleus in response to autophagy inhibition promotes proteasome-mediated CHK1 and RAD51 protein instability. This claim is further supported by the findings that transient expression of a p62 mutant, which is constitutively localized in the nucleus, in B cell lines with low endogenous p62 levels recaptures the effects of autophagy inhibition on CHK1 and RAD51 protein stability. These results indicate that proteasomal degradation of RAD51 and CHK1 is dependent on p62 accumulation in the nucleus. However, small hairpin RNA (shRNA)-mediated p62 depletion in EBV-transformed lymphoblastic cell lines (LCLs) had no apparent effects on the protein levels of CHK1 and RAD51, likely due to the constitutive localization of p62 in the cytoplasm and incomplete knockdown is insufficient to manifest its nuclear effects on these proteins. Rather, shRNA-mediated p62 depletion in EBV-transformed LCLs results in significant increases of endogenous RNF168-γH2AX damage foci and chromatin ubiquitination, indicative of activation of RNF168-mediated DNA repair mechanisms. Our results have unveiled a pivotal role for p62-mediated selective autophagy that governs DDR in the setting of oncogenic virus latent infection, and provide a novel insight into virus-mediated oncogenesis.


Assuntos
Autofagia , Transformação Celular Viral , Dano ao DNA , Infecções por Vírus Epstein-Barr/patologia , Estresse Oxidativo , Proteínas de Ligação a RNA/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Cromatina , Reparo do DNA , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/fisiologia , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Complexo de Endopeptidases do Proteassoma , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Ubiquitina/metabolismo , Latência Viral
19.
J Cutan Pathol ; 46(9): 637-644, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30980412

RESUMO

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL) is a systemic peripheral T-cell lymphoma with a follicular helper T-cell (TFH ) immunophenotype that frequently involves the skin. However, the histopathology of cutaneous involvement by AITL has not been fully established. METHODS: We reviewed the clinicopathological features of 19 patients seen at our institution with AITL involving the skin. Pan-T-cell and TFH marker expression was evaluated by immunohistochemistry. Epstein-Barr virus (EBV) was detected using in situ hybridization (ISH) for Epstein-Barr virus-encoded small RNA (EBER). T-cell receptor (TCR) gene rearrangement was evaluated by PCR. RESULTS: AITL affected both trunk and extremities in 15/19 cases (79%). Perivascular infiltration by small and/or medium-sized lymphocytes was seen in 18/19 (95%). Granulomatous inflammation was identified in 4/19 (21%). Aberrant loss of CD2, CD5, or CD7 was identified in 1/18 (6%), 2/18 (11%), or 7/19 (37%) cases, respectively. Seventeen of eighteen evaluable cases (95%) expressed 2 to 3 TFH markers: PD-1 in 19/19 (100%), BCL6 in 94% (17/18), and CD10 in 37% (7/19). EBV-positive cells were detected in 3/18 (17%) with varying density. Clonal TCR gene rearrangement was identified in 9/11 (82%). CONCLUSIONS: Cutaneous involvement by AITL shows relatively non-specific histopathological features. However, an immunohistochemical panel including TFH markers and EBER ISH is useful in differential diagnosis.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4/imunologia , Linfoma Cutâneo de Células T , Linfoma de Células T Periférico , Neoplasias Cutâneas , Linfócitos T Auxiliares-Indutores , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Imunofenotipagem , Linfoma Cutâneo de Células T/imunologia , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/virologia , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Auxiliares-Indutores/virologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA