Presence of herpesviruses, parvoviruses, and polyomaviruses in sinonasal lymphoma.

PURPOSE: Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been identified, their aetiology is unknown. Along with other predisposing factors, the viral association of lymphomas, such as Epstein-Barr virus (EBV) and Burkitt and Hodgkin lymphomas, is well-established. Modern molecular biology techniques have enabled the discovery of novel human viruses, exemplified by the protoparvovirus cutavirus (CuV), associated with cutaneous T-cell lymphoma. These findings, and the anatomical location of the sinonasal tract with its rich microbiome and infectious agents, justify in-depth studies among SL. METHODS: We analysed the presence of 20 viruses of Orthoherpesviridae, Parvoviridae, and Polyomaviridae by qPCR in 24 SL tumours. We performed RNAscope in situ hybridisation (RISH) to localize the viruses. Parvovirus-specific IgG was analysed by enzyme immunoassay and targeted next-generation sequencing (NGS) was applied to detect CuV in plasma. RESULTS: We detected viral DNA in 15/24 (63%) tumours; nine of EBV, six of human herpesvirus (HHV) -7, four each of HHV-6B and parvovirus B19, two of cytomegalovirus, and one each of CuV and Merkel-cell polyomavirus. We found tumours with up to four viruses per tumour, and localized CuV and EBV DNAs by RISH. Two of the ten plasma samples exhibited CuV IgG, and one plasma sample demonstrated CuV viremia by NGS. CONCLUSION: Viruses were frequent findings in SL. The EBV detection rate was high in diffuse large B-cell lymphoma, and co-detections with other viruses were prevalent.

Epstein - Barr Virus Salivary Shedding in Patients with Acute Infectious Diseases: A Pilot Study.

Background: Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Aim: Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. Since the occurrence of EBV in saliva during acute infectious diseases has not yet been systematically researched, we aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. Material and methods: This pilot cross-sectional study included consenting adults hospitalized for acute infectious conditions and their peers free of acute infectious diseases. A total of 40 patients with acute infectious diseases were enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. We fitted logit and general linear models to proportions and to ln (viral copy counts) to generate adjusted proportions and geometric mean values in the two groups of subjects. We used SAS for Windows 9.4. Results: The most common acute infectious disease was COVID-19 pneumonia, followed by hemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. Conclusions: The presented preliminary data do not indicate acute infectious conditions as a marked "contributor" in increasing salivary EBV shedding.

Epstein-Barr virus in gastric cancer and association with 30 bp del-latent membrane protein 1 polymorphism

SUMMARY OBJECTIVE: This study aimed to determine the frequencies of Epstein-Barr virus, types 1 and 2 infection, and 30 bp del-latent membrane protein 1 viral polymorphism in gastric adenocarcinomas, as well as to investigate the association between Epstein-Barr virus infection and tumor location, type, and the patient's sex. METHODS: Samples were collected from 38 patients treated at a university hospital in Rio de Janeiro, Brazil. Epstein-Barr virus detection and genotyping were performed by polymerase chain reaction, followed by polyacrylamide gel electrophoresis and staining by the silver nitrate method. RESULTS: Overall, 68.4% of patients had Epstein-Barr virus-positive tumors. Of these, 65.4% presented infection by Epstein-Barr virus type 1, 23.1% by Epstein-Barr virus type 2, and 11.5% had coinfection with types 1 and 2. The 30 bp del-latent membrane protein 1 polymorphism was found in 42.3% of Epstein-Barr virus-positive tumors, 23.1% had the wild-type virus, and 23.1% had the wild-type and the polymorphism concomitantly. In 11.5% of Epstein-Barr virus-positive tumors, it was impossible to determine whether there was polymorphism or not. Tumor location in the antrum (22 of 38) and diffuse type (27 of 38) were predominant. There was no significant difference in Epstein-Barr virus infection or the 30 bp del-latent membrane protein 1 polymorphism between men and women. CONCLUSION: Epstein-Barr virus infection was found in 68.4% of tumors investigated in this study. To the best of our knowledge, this is the first article showing the coinfection of Epstein-Barr virus types 1 and 2 in gastric carcinoma in Brazil.

Correlation between peak viral load and liver function damage in children with infectious mononucleosis induced by Epstein-Barr virus / 中国基层医药

Objective:To investigate the relationship between the peak load of Epstein-Barr virus (EPV) and live function damage in children with infectious mononucleosis caused by EPV.Methods:Eighty children with infectious mononucleosis caused by EPV who received treatment in Pingxiang People's Hospital from January 2018 to December 2021 were included in this study. Five mL of venous blood was taken from each child for detecting the peak load of EBV-DNA and liver function indicators. These children were divided into a low-load group ( n = 25, EBV-DNA load < 10 4 copies/mL), a medium-load group ( n = 34, EBV-DNA load of 10 4-10 5 copies/mL), and a high-load group ( n = 21, EBV-DNA load > 10 5 copies/mL) according to the peak EBV-DNA load. The relationships between different peak loads of EBV-DNA and live function, age, and sex were analyzed. Results:The rate of liver dysfunction in the high-load group [85.71% (18/21)] was significantly higher than [38.24% (13/34)] in the medium-load group and [20.00% (5/25)] in the low-load group ( χ2 = 11.90, 19.71, P = 0.001, P < 0.001). Alanine aminotransferase and aspartate aminotransferase levels in the high-load group were (156.24 ± 13.21) U/L and (171.69 ± 13.49) U/L, respectively, which were significantly higher than (125.89 ± 10.54) U/L and (143.26 ± 10.29) U/L in the medium-load group and (89.64 ± 6.75) U/L and (64.89 ± 5.74) U/L] in the low-load group (all P < 0.001). There was no significant difference in the peak load of EBV-DNA between children of different ages and between children of different sexes (both P > 0.05). Conclusion:Children with infectious mononucleosis caused by EPV have a high EBV-DNA peak load. A higher peak load of EVB-DNA indicates a higher risk of liver function damage. More attention should be paid in clinical practice. Effective diagnosis and treatment should be performed in time to control the patient's condition as early as possible.

Predictive indicators of a prolonged course of fever in children with infectious mononucleosis / 中国基层医药

Objective:To explore the relevant predictive indicators of fever course > 7 days in children with infectious mononucleosis.Methods:The clinical data of 163 children with infectious mononucleosis who received treatment in Xi'an Children's Hospital from January 2018 to October 2020 were retrospectively analyzed. According to the heat duration, the children were divided into the fever course > 7 days group ( n = 55) and the fever course ≤ 7 days group ( n = 108). The clinical manifestations and laboratory indexes on admission were compared between the two groups. A logistic regression model was used to analyze the influential factors of fever course in children. A receiver operating curve was used to evaluate the predictive value of heat course > 7 days for infectious mononucleosis. Results:The majority of children with infectious mononucleosis had a heat course of 7 days (21.5%). There were no significant differences in clinical manifestations between the fever course > 7 days group and the fever course ≤ 7 days group (all P > 0.05). Neutrophil count, the proportion of monocytes, aspartate aminotransferase, and the proportion of suppressor T (Ts) cells in the fever course > 7 days group were (15.97 ± 7.60) × 10 9/L, 7.75 (4.93, 10.75)%, 53.00 (22.00, 91.50) U/L, 70.00 (57.00, 75.00)%, respectively, which were significantly higher than (15.21 ± 5.29) × 10 9/L, 5.40 (3.40, 9.60)%, 40.00 (30.00, 63.75) U/L, 63.50 (55.00,70.75)% in the fever course ≤ 7 days group ( t = -5.10, Z = -2.31, Z = -2.26, Z = -2.12, all P < 0.05). The proportion of helper T (Th) cells and the ratio of Th/Ts cells in the fever course > 7 days group were 13.00 (9.00, 17.00)% and 0.19 (0.12, 0.30)%, respectively, which were significantly lower than 16.00 (12.25, 20.75)%, 0.26 (0.18, 0.37)% in the fever course ≤ 7 days group ( Z = 2.44, 2.48, both P < 0.05). Multivariate logistic regression analysis showed that the increased proportion of Ts cells ( OR = 0.96, 95% CI 0.922-0.978, P < 0.05) was an influential factor of the prolonged course of fever. The area under the receiver operating characteristic curve of the proportion of Ts cells was 0.637. The cut-off value, sensitivity, and specificity were 67.50%, 61.3%, and 64.3%, respectively. Conclusion:Children with infectious mononucleosis with a longer heat course have more severe immune responses. The proportion of Ts cells > 67.5% can be used as a risk factor for the fever course > 7 days in children with infectious mononucleosis.

Research progress of primary pulmonary lymphoepithelioma-like carcinoma / 国际肿瘤学杂志

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a distinct type of lung cancer with histological profiles similar to nasopharyngeal carcinoma. The development is associated with EBV and plasma EBV DNA has predictive value in the progression and prognosis of PPLELC. PPLELC is different from some other types of lung cancer in that it has a low mutation rate of the classical lung cancer driver genes and targeted therapy is ineffective for it. Chemotherapy combined with immunotherapy may be the best first-line treatment option for patients with advanced PPLELC.

Treatment-related fluctuations in Guillain-Barré syndrome​: clinical features and predictors of recurrence / Fluctuaciones relacionadas al tratamiento en el Síndrome de Guillain-Barré: características clínicas y predictores de recurrencia

ABSTRACT Background: A treatment-related fluctuation (TRF) in a patient with Guillain-Barré syndrome (GBS) is defined as clinical deterioration within two months of symptom onset following previous stabilization or improvements with treatment. Objective: To investigate the clinical characteristics and factors that could increase the risk of relapse of GBS in patients with and without TRFs. Methods: Retrospective review of medical records of patients (>18 years) with GBS evaluated between January/2006 and July/2019. Demographic and clinical characteristics, ancillary studies, treatment received, and the clinical course of patients with and without TRFs were analyzed. Results: Overall, 124 cases of GBS were included; seven (5.6%) presented TRFs. GBS-TRF cases were triggered more frequently by infectious mononucleosis (28.57 vs. 8.55%; p=0.01). GBS-TRF were initially treated with plasmapheresis more frequently than those without TRF (14.29 vs. 1.70%; p=0.0349). Combined treatment (71.43 vs. 4.27%; p<0.001) and corticosteroids (42.86 vs. 1.71%; p<0.001) were more commonly used in the GBS-TRF group. GBS-TRF patients presented a higher median initial disability score (4 vs. 2; p=0.01). Conclusions: Patients with GBS triggered by infectious mononucleosis and a high degree of initial disability have higher chances of developing TRFs. Although patients with TRF were treated with plasmapheresis more often, the total number was too low to suggest a link between plasma exchange and TRF.

RESUMEN Antecedentes: Una fluctuación relacionada al tratamiento (FRT) en un paciente con síndrome de Guillain-Barré (SGB) se define como un deterioro clínico dentro de los dos meses posteriores al inicio de los síntomas después de una estabilización previa o mejoría con el tratamiento. Objetivo: Investigar las características clínicas y los factores que podrían incrementar el riesgo de recaída, comparando pacientes con SGB, con y sin FRT. Métodos: Revisión retrospectiva de historias clínicas de pacientes (>18 años) con SGB evaluados entre enero/2006 y julio/2019. Se analizaron las características demográficas y clínicas, los estudios complementarios, el tratamiento recibido y la evolución clínica de los pacientes con y sin FRT. Resultados: Se incluyeron 124 casos de SGB en el total; 7 (5,6%) presentaron FRT. Los casos de SGB con FRT se desencadenaron con mayor frecuencia por mononucleosis infecciosa (28,57 vs. 8,55%; p=0,01). Los casos de SGB con FRT se trataron inicialmente con plasmaféresis con más frecuencia que aquellos sin FRT (14,29 vs. 1,70%; p=0,0349). El tratamiento combinado (71,43 vs. 4,27%; p<0,001) y los corticosteroides (42,86 vs. 1,71%; p<0,001) se utilizaron con mayor frecuencia en el grupo de SGB con FRT. Los pacientes con FRT presentaron una escala de discapacidad inicial mediana más alta (4 vs. 2; p=0,01). Conclusiones: Aquellos SGB desencadenados por mononucleosis infecciosa y un alto grado de discapacidad inicial tienen una mayor probabilidad de desarrollar FRT. Aunque los pacientes con FRT fueron tratados con plasmaféresis con mayor frecuencia, el número total fue demasiado bajo para sugerir un vínculo entre la plasmaféresis y FRT.

Clinical characteristics and misdiagnosis analysis of infectious mononucleosis in children / 中国医师进修杂志

Objective:To summarize the clinical characteristics, causes of misdiagnosis and preventive measures of infectious mononucleosis (IM) in children, and to improve the ability of clinicians in early diagnosis of IM in children.Methods:The clinical data of 468 children with IM in Xi′an Children′s Hospital from January 2018 to December 2021 were retrospectively analyzed, including general situation, disease onset, diagnosis and misdiagnosis.Results:Among the 468 children, 33 cases were clinically diagnosed and 435 cases were a definitely diagnosed; 281 males (60.04%) and 187 females (39.96%); the incidence rate was highest in preschool children (43.80%, 205/468) and in autumn (33.12%, 155/468). The first symptoms were fever (52.99%, 248/468), eyelid edema (15.38%,72/468) and neck mass (14.96%, 70/468). The fever rate was 90.38% (423/468), and the median time of first fever appearance was on the first (first, second) day of disease course, and the median duration of fever was 6 (4, 8) d. The median time of first visit was on the third (first, fifth) day of disease course, and the time of diagnosis was on the seventh (fifth, ninth) day of disease course. Blood routine examination showed that the proportion of white blood cell count increased was 51.92% (243/468), the proportion of lymphocytes increased was 61.75% (289/468), and the proportion of abnormal lymphocytes increased (≥10%) in peripheral blood was 58.97% (276/468). The lymphocyte subsets of 364 children were detected, the rate of helper T lymphocytes (Th cells) decreased was 80.22% (292/364), the rate of suppressor T lymphocytes (Ts cells) increased was 99.45% (362/364), the value and decreased rate of Th cells/Ts cells were 0.24 (0.16, 0.40) and 100.00% (364/364), rate of B lymphocytes decreased was 93.96% (342/364), rates of natural killer cells decreased and increased were 35.16% (128/364) and 0.55% (2/364). The misdiagnosis rate was 55.13% (258/468), and the misdiagnosis time was on the fifth (fourth, seventh) day of disease course. Among the 258 misdiagnosed children, 105 cases (40.70%) were misdiagnosed as upper respiratory tract infection, 65 cases (25.19%) as acute suppurative tonsillitis, 27 cases (10.47%) as acute cervical lymphadenitis or neck mass.Conclusions:Due to the complex and diverse clinical manifestations of IM in children, it is easy to be misdiagnosed in the early stage of the disease. So, it is necessary for clinicians to master the clinical characteristics of IM in children, constantly improve the level of diagnosis and treatment, and reduce the misdiagnosis rate.

The risk factors for hemophagocytic syndrome in childhood Epstein-Barr virus-associated infectious mononucleosis / 中国医师进修杂志

Objective:To explore the risk factors for hemophagocytic syndrome (HPS) in childhood Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM).Methods:From January 2013 to December 2017, the medical charts of all children who were diagnosed with EBV-associated IM and HPS in Children′s Hospital of Soochow University were analyzed retrospectively. Statistical analyses were performed using SPSS version 22.0.Results:A total of 316 IM and 59 HPS were enrolled. The age was (4.26 ± 2.95) years old with a male-to-female ratio of 1.2∶1. In addition to the diagnostic criteria of HPS, there were significantly lower rates of fever >10 d, hepatomegaly, jaundice, alanine aminotransferase >500 U/L, aspartate aminotransferase >500 U/L, LDH >1 000 U/L, C-reactive protein >50 mg/L and hypoalbuminemia in children with EBV-associated IM compared to those with HPS, and the differences were statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that fever >10 d, eyelid edema, lymphadenopathy and purulent tonsils were independent predictors of HPS in children with EBV-associated IM ( P<0.05). Hepatomegaly and fever >10 d were risk factors ( OR = 16.079 and 12.138, 95% CI 2.788 to 92.744 and 2.878 to 51.180). Eyelid edema, lymphadenopathy and purulent tonsils were protective factors ( OR = 0.087, 0.006 and 0.031; 95% CI 0.010 to 0.723, 0.001 to 0.058 and 0.007 to 0.146). Conclusions:Hepatomegaly and fever >10 d are the risk factors for hemophagocytic syndrome in childhood EBV-associated infectious mononucleosis.

Extranodal nk/t-cell lymphoma, nasal type: case report

ABSTRACT Introduction: Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a highly aggressive non-Hodgkin's lymphoma of unknown etiology. Clinical manifestations are usually nasal obstruction, epistaxis, and inflammatory signs. Diagnosis can be difficult to achieve and requires histo-pathology and immunohistochemistry studies. Radiotherapy and chemotherapy have been proposed as treatment, depending on the stage of the disease. Case presentation: A 44-year-old male patient, previously healthy, attended the outpatient service due to clinical nasal obstruction, secretion, edema, and facial erythema for 2 months. Facial cellulitis was initially diagnosed, but since there was no improvement with antibiotic treatment, the patient was referred to the emergency department of a higher complexity center, where complementary imaging showed a mass in the right nasal cavity. A histopathological analysis established that it was an ENKL, so radiotherapy was indicated; however, as a result of the advanced stage of this neoplasm, the patient died. Conclusion: Timely diagnosis of ENKL is crucial to improve life expectancy. Nevertheless, it may represent a clinical challenge due to its nonspecific presentation.

RESUMEN Introducción. El linfoma extranodal nasal de células T/natural killer (ENKL) es un linfoma no Hodgkin altamente agresivo y de etiología desconocida. Sus manifestaciones clínicas suelen ser obstrucción nasal, epistaxis y signos inflamatorios; sin embargo, el diagnóstico puede llegar a ser difícil, requiriendo histopatología e inmunohistoquímica para su detección. Como tratamiento se han propuesto radioterapia y quimioterapia, según el estadio de la enfermedad. Presentación del caso. Paciente masculino de 44 años de edad, previamente sano, quien asistió al servicio de consulta externa por cuadro clínico de 2 meses de evolución consistente en síntomas de obstrucción y secreción nasal, edema y eritema facial. Se realizó diagnóstico inicial de celulitis facial, pero dado que no hubo mejoría con el tratamiento antibiótico, el sujeto fue remitido al servicio de urgencias de una institución de mayor complejidad, donde se le practicaron imágenes complementarias que mostraron una masa en la cavidad nasal derecha; mediante análisis histopatológico se estableció que se trataba de un ENKL, por lo que se indicó radioterapia; sin embargo, a consecuencia del estadio avanzado de dicha patología, el paciente falleció. Conclusión. El diagnóstico oportuno de ENKL es crucial para mejorar la expectativa de vida de quienes lo padecen; sin embargo, puede representar un reto clínico debido a su presentación inespecífica.

Extranodal NK/T cell lymphoma, nasal type: An updated overview.

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is an aggressive malignancy associated with Epstein-Barr virus infection, with a geographic and racial predilection for some Asian and Latin American countries. ENKTCL-NT manifests as a necrotic process affecting nasal or upper aerodigestive structures and, rarely, extranasal sites such as skin, and the gastrointestinal tract. ENKTCL-NT was characterized by its poor prognosis irrespective of clinical stage and therapy. However, during the last two decades, advances in its clinicopathologic, genetic and molecular characterization have been achieved, as have changes in the chemotherapy regimens that, in combination with radiotherapy, are significantly improving the survival of these patients, especially in initial stages. For these reasons, we present an overview of the historical background of ENKTCL-NT along with an updated review of its potential etiological factors, clinicopathologic and molecular features, as well as its prognostic models, current treatment protocols, and future directions on potential promising therapeutic approaches.

Treatment of EB virus positive diffuse large B cell lymphoma / 国际肿瘤学杂志

Epstein-Barr virus (EBV) positive diffuse large B cell lymphoma (DLBCL) is a rare type of B cell lymphoma associated with chronic EBV infection. The main subtype is activated B cell-like and it′s invasive. The response to combined chemotherapy is worse than that of EBV negative patients, and the prognosis is poor. As the researches on pathogenesis and biological characteristics of EBV positive DLBCL deepen, new therapeutic strategies are emerging, such as antiviral therapy, monoclonal antibody, inhibitors of signaling pathway and immunotherapy including cellular immunotherapy and immune checkpoint inhibitor. These new therapeutic strategies can improve the efficacy and reduce the occurrence of adverse reactions.

Clinical features and therapeutic efficacy analysis of Epstein-Barr virus-positive T-cell lymphoma patients with hemophagocytic syndrome / 白血病·淋巴瘤

Objective:To investigate the effects of hemophagocytic syndrome also known as hemophagocytic lymphohistiocytosis (HLH) on the clinical features and therapeutic efficacy of patients with Epstein-Barr virus-positive T-cell lymphoma (EBV-TCL).Methods:The clinical data of patients with EBV-TCL diagnosed by pathological examination in the First Affiliated Hospital of Guangzhou Medical University from November 2015 to August 2020 were retrospectively analyzed. According to whether they were accompanied with HLH at the time of onset, patients were divided into HLH group (10 cases) and non-HLH group (13 cases), and the clinical features and prognosis of the two groups were compared. The curative effects of different treatment methods and patients with different plasma EBV-DNA titers were compared.Results:Among 23 patients, 3 cases (13.0%) were in Ann Arbor stage Ⅰ-Ⅱ, 20 cases (87.0%) were in stage Ⅲ-Ⅳ; the International Prognostic Index (IPI) score was 1 point in 3 cases (13.0%), 2 points in 4 cases (17.4%), 3 points in 8 cases (34.8%), 4 points in 8 cases (34.8%). In the HLH group, there were 2 cases of aggressive NK-cell leukemia and 3 cases of childhood systemic EBV-TCL. There were no cases of above two pathological types in the non-HLH group. In the HLH group, the proportions of patients with fever, bone marrow invasion, IPI score > 2 points, and EBV-DNA > 10 4 copies/ml were higher than those in the non-HLH group (all P < 0.05). The objective response rate (complete remission plus partial remission) of all patients after chemotherapy was 47.8% (11/23); there were 3 cases undergoing hematopoietic stem cell transplantation in both the HLH group and the non-HLH group, and all achieved objective remission. The objective remission of 7 patients and 10 patients who did not undergo hematopoietic stem cell transplantation in the HLH group and non-HLH group after lymphoma chemotherapy had 0 case and 5 cases, respectively, and the difference was statistically significant ( P = 0.044). In the chemotherapy alone group, 5 of 17 patients had objective remission, 6 patients in the chemotherapy plus transplantation group had objective remission, and the difference was statistically significant ( P = 0.039). Among 16 patients whose plasma EBV-DNA titers turned negative, 11 patients had objective remission, and 7 patients whose plasma EBV-DNA titers were continuously positive had no objective remission, and the difference was statistically significant ( P = 0.001). The 1-year overall survival rate of all patients was 69.3%, and the 2-year overall survival rate was 52.0%. In the HLH group, the 1-year and 2-year overall survival rates of 7 patients receiving chemotherapy alone and 3 patients receiving chemotherapy plus transplantation were 42.9% and 66.7%, respectively. In the non-HLH group, the 1-year overall survival rates of 10 patients receiving chemotherapy alone and 3 patients receiving chemotherapy plus transplantation were 80.0% and 100.0%, respectively; the 2-year overall survival rates were 26.7% and 100.0%,respectively. The overall survival of patients receiving chemotherapy plus transplantation was better than that of those receiving chemotherapy alone in both the HLH group and the non-HLH group, and differences were statistically significant (all P < 0.05). Conclusions:The general clinical stage of patients with EBV-TCL is later, and the prognosis of EBV-TCL patients with HLH is worse. The therapeutic efficacy may be related to plasma EBV-DNA titers. Hematopoietic stem cell transplantation can improve the remission rate.

[Clinicopathological features of primary EB virus positive nodal T/NK cell lymphoma].

Objective: To investigate the clinicopathological features of primary Epstein-Barrvirus (EBV) positive nodal T/NK-cell lymphomas (EBV+nodal TNKL). Methods: The clinicopathological features of 7 cases of EBV+nodal TNKL diagnosed between November 2015 and May 2019 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry, PCR gene rearrangement and in situ hybridization.Follow-up data were also collected. Results: There were 5 males and 2 females with a median age of 54 years (ranged from 41 to 75 years). All patients presented with multiple lymphadenopathies and common B symptoms (5/7) and at an advanced Ann Arbor stage Ⅲ/Ⅳ(6/7). Bone marrow involvementwas detected in 1 patient.Six cases of T-cell origin had monomorphic patterns, and the tumor cells showed CD56 negativity and TCRαß+/TCRγδ－ with T-cell clonality. One case of NK-cell origin had polymorphic pattern, and the tumor cells showed CD56 positivity and TCRαß-/TCRγδ-without T-cell clonality. All cases were positive for the cytotoxic markers, but showed various CD4/CD8 expression. All 7 cases were diffusely positive for EBV (>100 cell/high power field). Six of the patients received chemotherapy, and 1 patient declined the treatments. During the follow-up period ranging from 3 to 48 months, 5 of the 7 patients died of the disease. Conclusions: EBV+nodal TNKL is a rare entity and is characterized by cytotoxic molecule expression, T/NK-cell derivation, and a predominance of nodal involvement at an advanced stage. It should be differentiated from other EBV+T/NK cell lymphoproliferative disorders, especially extranodal NK/T cell lymphoma.

[Clinicopathological features of fibrin-associated diffuse large B cell lymphoma arising within concurrent atrial myxoma: report of six cases].

Objective: To investigate the clinicopathological features, treatment and prognosis of fibrin-associated diffuse large B cell lymphoma (DLBCL) arising within concurrent atrial myxoma. Methods: Six cases of fibrin-associated DLBCL arising within concurrent atrial myxoma diagnosed at the Department of Pathology, Guangdong General Hospital, from 2006 to 2019 were included. The histology, immunophenotype, treatment and prognoses were analyzed. Results: The patients' age ranged from 46 to 78 years (mean 59 years). There were 3 males and 3 females. The tumors were all discovered incidentally on histological examination of surgical pathology specimens excised for atrial myxoma. All patients appeared to have morphological features of DLBCL, B lineage immunophenotype, high proliferative index and latency type III of Epstein-Barr viral infection. They had complete tumor resections without adjuvant chemotherapy and were healthy at 5- to 120-month follow-ups. Conclusions: Fibrin-associated DLBCL arising within concurrent atrial myxoma is an unusual form of DLBCL associated with chronic inflammation, and its clinical outcome is indolent. The findings suggest that this type of lymphoma does not warrant excessive or unnecessary treatments after complete resection.

Síndrome Hemofagocítico en Niños Reporte de Caso / Hemophagocytic Syndromein children: a case report

Introducción:El síndrome hemofagocítico (SHF) es reconocido como un conjunto de signos clínicos y hallazgos laboratoriales que tienen un grave compromiso en la salud y vitalidad de los niños con una incidencia de 1.2 casos/millón/año. Puede pasar subdiagnosticado y confundido con sepsis de foco inespecífico Caso clínico:Niño de 4 años de edad, sin antecedentes de importancia. Ingresado desde el servicio de emergencia por presentar 20 días de fiebre y dolor abdominal. Requirió intubación por franca falla respiratoria y el ingreso a la Unidad de Cuidados Intensivos Pediátricos. Con hipotensión e insuficiencia hepática, pancitopeniay esplenomegalia. Evolución: Se descartaron infecciones bacterianas con policultivos, SARS-Cov 2negativo,se descartaron inmunodeficiencias congénitas y adquiridas.TORCHnegativo, VDRL no reactivo.La prueba de Epstein Barr fue positivo para IgM.Se determinó endocarditis con derrame pericárdico global. Estudio de biopsia medular normocromía, normocitosis, pancitopenia y blastos <5%, sin infiltración tumoral. Se estableció el Diagnóstico de SHFse inicióciclosporina y corticoterapia.Requirió ventilación mecánica por 20 días con período de pronación de 36 horas. Fue dado de alta a pediatríay posteriormente a domicilio, para control por consulta externa. Conclusión: El diagnóstico del SHF es inusual y subestimado al momento de la evaluación clínica. En el presente reporte se asocia a la presencia del Virus Epstein Barr

Introduction: Hemophagocytic syndrome (HPS) is recognized as a set of clinical signs and laboratory findings that have a serious compromise on the health and vitality of children with an incidence of 1.2 cases / million / year. It can be underdiagnosed and confused with sepsis with a non-specific focus. Clinical case: 4-year-old boy, with no significant history. Admitted from the emergency service due to 20 days of fever and abdominal pain. She required intubation due to frank respiratory failureand admission to the Pediatric Intensive Care Unit. With hypotension and liver failure, pancytopenia and splenomegaly. Evolution: Bacterial infections were ruled out with polycultures, SARS-Cov 2 negative, congenital and acquired immunodeficiencies were ruled out. Negative TORCH, non-reactive VDRL. The Epstein Barr test was positive for IgM. Endocarditis with global pericardial effusion was determined. Medullary biopsy study normochromia, normocytosis, pancytopenia, and blasts <5%, without tumor infiltration. The diagnosis of SHF was established, cyclosporine and corticosteroid therapy were started. He required mechanical ventilation for 20 days with a 36-hour pronation period. He was discharged to pediatrics and later at home, for outpatient control. Conclusion: The diagnosis of HHS is unusual and underestimated at the time of clinical evaluation. In this report it is associated with the presence of the Epstein Barr Virus

Síndrome hemafagocítico, enfrentamiento diagnóstico y terapéutico actual. Revisión a partir de un caso relacionado a virus Epstein-Barr / Hemophagocytic syndrome, current diagnostic and therapeutic approach

Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HLH) is a highly lethal hyper-inflammatory disorder that leads to a storm of cytokines, hemophagocytosis and multiple organ failure. It can be primary, which is inherited, or secondary. In the latter, virus infections are a frequent trigger, predominantly the family of herpes viruses, such as Epstein-Barr virus. An early treatment is recommended. Until recently there was no consensus about the management of secondary cases. The protocols for the treatment of primary HLH were used, which include cytotoxic agents and corticosteroids. We herein review the current diagnostic and therapeutic approach of HLH, based on a case associated with a reactivation of the Epstein-Barr virus in an immunocompetent adolescent. We highlight the importance of suspecting this disease in patients with a persistent inflammatory response state or with a fever of unknown origin, in order to carry out a timely treatment, with the least toxicity, and appropriate to the characteristics of each individual, which is the current therapeutic trend.

Caracterización clínica y epidemiológica del carcinoma nasofaríngeo y su relación con el virus Epstein-Barr / Nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, clinical and epidemiological description

RESUMEN Fundamento: El carcinoma nasofaríngeo es el tumor maligno más frecuente del cavum. Estos tumores se diferencian de otros carcinomas epidermoide de la cabeza y cuello por su histología característica y su relación con el virus de Epstein-Barr. Objetivo: Caracterizar clínica y epidemiológicamente el carcinoma de nasofaringe y su relación con el virus Epstein-Barr, en el Instituto Nacional de Oncología y Radiobiología, Ciudad de la Habana, en el período de enero a diciembre de 2012. Metodología: Se realizó un estudio retrospectivo; se trabajó con un total de 16 historias clínicas. Se observaron variables como edad, sexo, tipo histológico, estadiamiento clínico, presencia del virus Epstein-Barr en el tumor, tratamiento aplicado, respuesta al tratamiento, recaída y estado del paciente. Resultados: El 50 % tenían entre 45-55 años de edad, 75 % eran hombres, el 50 % diagnosticados con tipo 3, 100 % negativo a la inmunohistoquímica para virus Epstein-Barr, predominó la etapa III con 43.75 %, el 56.25 % de los casos se trataron con radio-quimioterapia más quimioterapia, el 50 % tuvo respuesta completa, la recaída fue de 37.50 % y el 68.75 % de los pacientes estaba vivo a los 60 meses. Conclusiones: En esta pequeña población con carcinoma nasofaríngeo, la totalidad de la población fue negativa a la presencia de virus Epstein-Barr por técnicas de inmunohistoquímica, por lo que su negatividad se hizo representativa en los tipo 3 y etapas avanzadas y no tuvo impacto en la respuesta al tratamiento y la supervivencia global.

ABSTRACT Background: Nasopharyngeal carcinoma is the most common malignant tumor of the cavum. These tumors differ from some other epidermoid carcinomas of the head and neck by their histology features and their Epstein-Barr virus relationship. Objective: To describe clinically and epidemiologically the nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, at the National Institute of Oncology and Radiobiology, Havana City, from January to December 2012. Methodology: A retrospective study was conducted; with a total of 16 medical records. Variables such as age, sex, histological type, clinical staging, and presence of Epstein - Barr virus in the tumor, applied treatment, response to treatment, relapse and patient status were observed. Results: 50 % were between 45-55 years old, 75 % were men, 50 % diagnosed with type 3, 100 % negative to Epstein-Barr virus immunohistochemistry, stage III predominated with 43.75 %, 56.25 % of the cases were treated with radio-chemotherapy plus chemotherapy, 50 % had a complete response, relapse was 37.50 % and at 60 months 68.75 % of the patients were still alive. Conclusions: In this small population with nasopharyngeal carcinoma, the entire population was negative to the presence of Epstein-Barr virus applying immunohistochemical techniques, so its negativity became representative in type 3 and advanced stages and had no impact on the treatment response and overall survival.

Caracterización clínica y epidemiológica del carcinoma nasofaríngeo y su relación con el virus Epstein-Barr / Nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, clinical and epidemiological description

RESUMEN Fundamento: El carcinoma nasofaríngeo es el tumor maligno más frecuente del cavum. Estos tumores se diferencian de otros carcinomas epidermoide de la cabeza y cuello por su histología característica y su relación con el virus de Epstein-Barr. Objetivo: Caracterizar clínica y epidemiológicamente el carcinoma de nasofaringe y su relación con el virus Epstein-Barr, en el Instituto Nacional de Oncología y Radiobiología, Ciudad de la Habana, en el período de enero a diciembre de 2012. Metodología: Se realizó un estudio retrospectivo; se trabajó con un total de 16 historias clínicas. Se observaron variables como edad, sexo, tipo histológico, estadiamiento clínico, presencia del virus Epstein-Barr en el tumor, tratamiento aplicado, respuesta al tratamiento, recaída y estado del paciente. Resultados: El 50 % tenían entre 45-55 años de edad, 75 % eran hombres, el 50 % diagnosticados con tipo 3, 100 % negativo a la inmunohistoquímica para virus Epstein-Barr, predominó la etapa III con 43.75 %, el 56.25 % de los casos se trataron con radio-quimioterapia más quimioterapia, el 50 % tuvo respuesta completa, la recaída fue de 37.50 % y el 68.75 % de los pacientes estaba vivo a los 60 meses. Conclusiones: En esta pequeña población con carcinoma nasofaríngeo, la totalidad de la población fue negativa a la presencia de virus Epstein-Barr por técnicas de inmunohistoquímica, por lo que su negatividad se hizo representativa en los tipo 3 y etapas avanzadas y no tuvo impacto en la respuesta al tratamiento y la supervivencia global.

ABSTRACT Background: Nasopharyngeal carcinoma is the most common malignant tumor of the cavum. These tumors differ from some other epidermoid carcinomas of the head and neck by their histology features and their Epstein-Barr virus relationship. Objective: To describe clinically and epidemiologically the nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, at the National Institute of Oncology and Radiobiology, Havana City, from January to December 2012. Methodology: A retrospective study was conducted; with a total of 16 medical records. Variables such as age, sex, histological type, clinical staging, and presence of Epstein - Barr virus in the tumor, applied treatment, response to treatment, relapse and patient status were observed. Results: 50 % were between 45-55 years old, 75 % were men, 50 % diagnosed with type 3, 100 % negative to Epstein-Barr virus immunohistochemistry, stage III predominated with 43.75 %, 56.25 % of the cases were treated with radio-chemotherapy plus chemotherapy, 50 % had a complete response, relapse was 37.50 % and at 60 months 68.75 % of the patients were still alive. Conclusions: In this small population with nasopharyngeal carcinoma, the entire population was negative to the presence of Epstein-Barr virus applying immunohistochemical techniques, so its negativity became representative in type 3 and advanced stages and had no impact on the treatment response and overall survival.