Single-center "Argentine" analysis of post-transplant lymphoproliferative disorders: incidence, histopathological characteristics and EBV status

ABSTRACT Introduction: Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations occurring after solid organ or bone marrow transplantation. The primary aims of our study were to characterize cumulative incidence of PTLDs, clinical and pathological features according to the Epstein-Barr virus (EBV) status and survival. Methods: This was a retrospective cohort study on adult and pediatric patients, from January 2001 to December 2017. The cumulative incidence of PTLD was calculated by analyzing all the patients transplanted at our hospital, based on the database of the Organ Donation and Ablation Authority of Argentina (INCUCAI). The Kaplan-Meier method was used to plot the survival. Results: Fifty-eight cases of biopsy-confirmed PTLD were identified and 12 cases of clinical data were incomplete and these patients were excluded. The median age at the time of the PTLD diagnosis was 17.5 years (interquartile range [IQR] 9 - 57). The median interval between transplant and PTLD diagnosis was 39 months (IQR 9 - 113). The most commonly transplanted organ was the liver (24 cases, 52.2%), followed by kidney (20 cases, 43.5%). The Epstein-Barr encoding region in situ hybridization (EBER ISH) was positive in 29 (69.8%) of the 43 evaluable biopsies. The PTLD cumulative incidence was 1.84% (95%CI 1.77 - 1.91) for solid organ and 0.84% (95%CI 0.48 - 1.2) for bone marrow transplant patients. The overall survival rate at 5 years was 0.77 (95%CI 0.61 - 0.87). Subgroups by the EBV EBER status, transplant type, PTLD subtype and age group (adult vs. pediatric) showed no statistically significant association with the overall survival. Conclusion: The PTLD incidence was similar to that of previous series and the EBER did not appear as a relevant factor in our patient survival.

Hydroa vacciniforme-like lymphoproliferative disorder in Ecuadorian children: A case series

We report the clinical and histopathological features of hydroa vacciniforme-like lymphoproliferative disorder in five indigenous and Mestizo children. All the children resided at higher altitudes, experiencing maximal solar exposure. All cases presented with prurigo along with Epstein-Barr virus infection. Histopathologic examination showed an atypical, CD30 + lymphocytic infiltrate with angiocentricity in all, while three cases demonstrated panniculitis-like infiltrate

Carcinoma tipo-linfoepitelioma pulmonar con expresión de virus de Epstein-Barr y PD-L1 / Pulmonary lymphoepithelioma-like carcinoma with ex pression of Epstein-Barr virus and PD-L1

Resumen El carcinoma tipo-linfoepitelioma pulmonar es una variante rara de carcinoma de células no pequeñas de pulmón, representa aproximadamente 0.7% de todos los casos. Está usualmente asociado con la infección por el virus de Epstein-Barr y es más prevalente en el Sureste de Asia; sin embargo, es extremadamente raro en Améri ca Latina. Informamos el caso de un hombre de 65 años de edad con un carcinoma tipo-linfoepitelioma pulmo nar, que se presentó con tos, disnea y pérdida de peso. La TAC de tórax mostró nódulo mal definido localizado en el pulmón derecho. Se realizó biopsia transtorácica de la lesión, y el estudio microscópico reveló células gran des poligonales dispuestas en mantos, infiltrados por abundantes linfocitos y células plasmáticas, alrededor del intersticio. Las células neoplásicas fueron positivas para citoqueratina 5/6 y p63, y negativas para Napsina A y el factor de transcripción tiroideo 1 (TTF-1). La expre sión de PD-L1 fue positivo (aproximadamente 100%) por inmunohistoquímica; así como el núcleo de las células neoplásicas mediante hibridación in situ para el RNA codificado por el virus de Epstein-Barr (EBER-ISH). El paciente recibió seis ciclos de un esquema combinado de quimioterapia basado en platino (gencitabina/cisplatino) más durvalumab. Presentó progresión de la enfermedad y finalmente murió 9 meses después del diagnóstico.

Abstract Pulmonary lymphoepithelioma-like carcinoma is a rare type of non-small cell lung cancer, it accounts for approximately 0.7% of all cases. It is usually associated with Epstein-Barr virus infection and is more prevalent in Southeast Asia; however, it is extremely rare in Latin America. We present a 65-year-old man with a primary pulmonary lymphoepithelioma-like carcinoma, who presented with cough, dyspnoea and weight loss. Com puter tomographic scan of the thorax showed a nodule localized in the right lung. A transthoracic biopsy of the lung lesion was made and the microscopic obser vation revealed large polygonal cells that proliferated in a nest pattern with infiltration by lymphocytes and plasma cells around the interstitium. The tumour cells were positive for citokeratin 5/6 and p63, and negative for Napsin A and thyroid transcription factor 1 (TTF-1). PD-L1 expression was positive (approximately 100%) in the immunohistochemical study, and the nuclei of the tumour cells were positive for EBV-encoded small RNA in-situ hybridization (EBER-ISH). The patient underwent six cycles of platinum-based combination (gencitabine/ carboplatin) chemotherapy plus durvalumab. He pre sented progression of the disease and finally he died 9 months after diagnosis.

Linfoma de células T/NK primario de testículo. Caso clínico y revisión de la literatura

Natural killer/T cell lymphomas chiefly involving the midline facial structures including the nasal cavity or nasopharyns are a relatively rare type of non-Hodgkin's lymphoma. Apart from the upper respiratory tract, the disease occasionally presents in certain extranodal sites, such as the central nervous system, skin, gastrointestinal tract, or testes. We report a case of natural killer NK/T cell lymphoma as a testicular tumor in a 36-year-old man with a history of progressive swelling of his right testicle. Histologically, the testicular mass showed a diffuse infiltrate of medium-sized and atypical large lymphoid cells with angiocentric infiltration and areas of coagulative necrosis. Immunohistochemical studies demonstrated tumor cells staining positively with CD3, TIA-1, and Granzyme B. The Epstein-Barr virus genoma was detected by in situ hybridization. There were no abnormal findings in the nasal and nasopharyngeal regions. Classified as stage IEA, the patient received involved-field irradiation to contralateral testis (45 Gy), followed by systemic chemotherapy with a combination regimen ofL-asparaginase, methotrexate and dexamethasone. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

Disseminated Nasal subtype Extranodal NK/T-cell lymphoma and its diagnostic difficulties in antemortem biopsies

ABSTRACT Extranodal NK/T- cell lymphoma (ENKTCL) is an aggressive lymphoma driven by Epstein-Barr virus (EBV) infection in genetically susceptible individuals. It was historically called a lethal midline granuloma. Due to the angio-destructive nature of ENKTCL, lymphoma cells are often accompanied and masked by necrosis and dense inflammation in the biopsy. Further, the biopsy may show vasculitis, which can mimic granulomatosis with polyangiitis. Due to these masquerades, ENKTCL is often misdiagnosed in the biopsy. Several biopsies may be required to establish the diagnosis. We describe the clinical course and autopsy findings of a young female who presented with a hard-palate ulcer. Antemortem biopsies failed to establish the diagnosis. The autopsy revealed an advanced nasal subtype of Extranodal NK/T-cell lymphoma with dissemination to the kidneys, adrenals, liver, spleen, and small intestine.

Unique synapomorphies and high diversity in South American Raji-related Epstein-Barr virus genomes

BACKGROUND Epstein-Barr virus (EBV) is a human gammaherpesvirus etiologically linked to several benign and malignant diseases. EBV-associated malignancies exhibit an unusual global distribution that might be partly attributed to virus and host genetic backgrounds. OBJECTIVES To assemble a new genome of EBV (CEMO3) from a paediatric Burkitt's lymphoma from Rio de Janeiro State (Southeast Brazil). In addition, to perform global phylogenetic analysis using complete EBV genomes, including CEMO3, and investigate the genetic relationship of some South American (SA) genomes through EBV subgenomic targets. METHODS CEMO3 was sequenced through next generation sequencing and its coverage and gaps were corrected through the Sanger method. CEMO3 and 67 EBV genomes representing diverse geographic regions were evaluated through maximum likelihood phylogenetic analysis. Further, the polymorphism of subgenomic regions of some SA EBV genomes were assessed. FINDINGS The whole bulk tumour sequencing yielded 23,217 reads related to EBV, which 172,713 base pairs of the newly EBV genome CEMO3 was assembled. The CEMO3 and most SA EBV genomes clustered within the SA subclade closely related to the African Raji strain, forming the South American/Raji clade. Notably, these Raji-related genomes exhibit significant genetic diversity, characterised by distinctive synapomorphies at some gene levels absent in the original Raji strain. CONCLUSION The CEMO3 represents a new South American EBV genome assembled. Albeit the majority of EBV genomes from SA are Raji-related, it harbours a high diversity different from the original Raji strain.

Pathological Types,Expression of Mismatch Repair Protein,Human Epidermal Growth Factor Receptor 2,and Pan-TRK,and Eostein-Barr Virus Infection in Patients With Colorectal Cancer Resected in Tibet / 中国医学科学院学报

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

Analysis of LMP specific T cell immune response and clinical factors in stage III-IVa nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective:To explore the Epstein-Barr virus (EBV) latent infection membrane protein (LMP) 1 or LMP2 specific T cell immune response and clinical significance in stage III-IVa nasopharyngeal carcinoma (NPC), aiming to provide ideas and evidence for immunotherapy in NPC.Methods:Fifty-nine NPC patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from February 2018 to October 2020 for primary treatment were collected. Peripheral blood monocytes (PBMCs) were stimulated by LMP antigen. Intracellular cytokine staining and flow cytometry were applied to study the expression levels of IL-2, IL-13, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) from CD4 + T and CD8 + T cells, and then analyzed in conjunction with clinical factors. Results:The positive rates of total PBMCs to LMP1 and LMP2 in NPC patients were different. The positive rate of LMP1 specific CD4 + T cells was statistically higher in stage T 3-T 4 NPC than that in stage T 1-T 2 (51.0% vs. 10.0%, P=0.042). There were also differences in the expression of cytokines between LMP1 and LMP2, CD4 +T cells and CD8 +T cells. Survival analysis showed the 2-year and 3-year overall survival (OS) rates were 91.5% and 88.2%, and the 2-year and 3-year progression-free survival (PFS) rates were 83.3% and 75.3%. Univariate analysis suggested that smoking history, male and LMP1 stimulated IL-13 positive expression in CD4 + T cells affected the disease progression ( P=0.026, 0.045 and 0.006); multivariate analysis showed LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history were the independent prognostic factors affecting PFS ( P=0.017, 0.019). Conclusions:LMP1 and LMP2 generate specific T-cell immune response in PBMCs of NPC patients, with differential expression in two T-cell subsets. LMP1 and LMP2 specific T cell immune response is associated with primary tumor size and metastatic lymph node volume. LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history affects the disease progression.

Pharmaceutical practice of clinical pharmacist participation in a patient with Epstein-Barr virus encephalitis / 中国药房

OBJECTIVE To investigate the role of clinical pharmacists in the treatment of a patient with Epstein-Barr （EB） virus encephalitis. METHODS Clinical pharmacist participated in drug diagnosis and therapy for a patient with EB virus encephalitis. According to the physiological characteristics of the disease and the pharmacokinetic-pharmacodynamic characteristics of antibiotics， clinical pharmacists suggested that the dose should be adjusted as ceftriaxone 2 g， q12 h+meropenem 2 g， q8 h. Based on the uncontrolled infection of the patient， pharmacists suggested that ceftriaxone should be stopped and vancomycin 1 million U and q12 h should be used as alternative therapy. According to the results of etiology， pharmacists suggested that acyclovir should be discontinued and replaced with ganciclovir 5 mg/kg， q12 h. The electrolyte disturbance of the patient may be adverse drug reactions caused by Mannitol injection， it was recommended to stop the drug. RESULTS The clinician followed the advice of the clinical pharmacists. After treatment， the patient improved and was discharged. CONCLUSIONS Clinical pharmacists can carry out pharmaceutical care for patients with EB virus encephalitis， assist physicians in optimizing the treatment plan of patients， and ensure the effectiveness and safety of drug treatment.

Progress in DNA-sensing pathways in Epstein-Barr virus infection / 中华微生物学和免疫学杂志

Epstein-Barr virus (EBV) is generally susceptible in human beings and multi-organ systems can be involved in EBV infection, such as blood, respiratory, urinary, digestive and nervous systems. EBV infection also plays an important role in the pathogenesis of related tumors, autoimmune diseases and other diseases, posing a great threat to human health. As a DNA virus, EBV can be sensed by DNA recognition receptors to trigger a series of downstream immune responses. A DNA-sensing pathway consists of DNA sensors, adaptor molecules and downstream effector signals. Double-stranded DNA sensors mainly include absent in melanoma 2-like receptors (ALRs) and cyclic GMP-AMP synthase (cGAS). Adaptors were mainly stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Downstream immune responses mainly involve typeⅠIFN, inflammasomes and proinflammatory cytokines. As a double-stranded DNA virus of the Herpesviridae family, EBV triggers complex innate and adaptive immune responses in the host, especially the sensing pathways mediated by a variety of DNA recognition receptors, which play a key role in host immune defense and pathogen immune evasion. This review made the DNA sensor as the clue to comprehensively summarize the progress in the activation, regulatory mechanism and clinical relevance of DNA-sensing pathways in EBV infection in recent years, aiming to achieve a better understanding of the host innate immune responses during EBV infection and provide an immunological basis for the prevention and treatment of EBV infection-related diseases.

Central nervous system post-transplant lymphoproliferative disorder: a case report / 中华神经科杂志

Post-transplant lymphoproliferative disorder (PTLD) is a solid organ or hematopoietic stem cells transplant associated syndrome, and central nervous system PTLD(CNS-PTLD) is extremely rare. A case of CNS-PTLD occurring after 24 years of kidney transplant was reported, and pathological examination proved it to be diffuse large B cell lymphoma. Cerebrospinal fluid next generation sequencing and pathological examination supported that Epstein-Barr virus infection was associated with it.

The role of mammalian target of rapamycin inhibitor in virus infection of organ transplant recipients / 器官移植

At present, mammalian target of rapamycin (mTOR) inhibitors are commonly-used immunosuppressive drugs after organ transplantation, including sirolimus (rapamycin) and everolimus. mTOR inhibitors not only exert an immunosuppressive effect by inhibiting T cell proliferation, but also possess multiple potential functions, such as antiaging, anti-tumor and anti-virus infection, etc. Virus infection is one of the most common complications after organ transplantation. Current anti-viral treatments are limited and yield poor efficacy. In this article, the role of mTOR pathway in virus infection, the mechanism of common mTOR inhibitors and the role of mTOR inhibitors in different types of virus infections were reviewed, aiming to provide reference for clinical application and subsequent research of mTOR inhibitors in organ transplant recipients.

Advances in diagnosis and treatment of non-neoplastic Epstein-Barr virus infection-related diseases in children / 国际儿科学杂志

The infection rate of Epstein-Barr virus(EBV)in the population is as high as 95%.It is the first carcinogenic virus found by human beings.Children infected with EBV often cause non-neoplastic diseases, including infectious mononucleosis, chronic active EBV infection and hemophagocytic lymphohistiocytosis.Most of the diseases related to non-neoplastic EBV infection in children are self-limited diseases, and a few of them are complicated with serious complications or develop into neoplastic diseases.The pathogenesis of this kind of disease is complex, the condition is varied, and some children with gene defects have a poor prognosis.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an effective treatment for refractory children.At the same time, the condition of some critically ill children is progressing rapidly, so it is very important to create the opportunity of allo-HSCT for such children.

Comparative Analysis of Primary and Reactivated EB Virus Infection Associated Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To compare the clinical characteristics of children with hemophagocytic lymphocytosis (HLH) associated with primary Epstein-Barr virus (EBV) infection and EBV reactivation, and explore the effects of different EBV infection status on the clinical indexes and prognosis of HLH.@*METHODS@#The clinical data of 51 children with EBV associated HLH treated in Henan Children's Hospital from June 2016 to June 2021 were collected. According to the detection results of plasma EBV antibody spectrum, they were divided into EBV primary infection-associated HLH group (18 cases) and EBV reactivation-associated HLH group (33 cases). The clinical features, laboratory indexes and prognosis of the two groups were analyzed and compared.@*RESULTS@#There were no significant differences in age, gender, hepatomegaly, splenomegaly, lymphadenopathy, neutrophil count in peripheral blood, hemoglobin content, platelet count, plasma EBV-DNA load, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, albumin, fibrinogen, triglyceride, ferritin, hemophagocytosis in bone marrow, NK cell activity and sCD25 between the two groups(P>0.05). The central nervous system involvement and CD4/CD8 in EBV reactivation-associated HLH group were significantly higher than those in primary infection-associated HLH group, but the total bilirubin was significantly lower than that in primary infection-associated HLH group (P<0.05). After treatment according to HLH-2004 protocol, the remission rate, 5-year OS rate and 5-year EFS rate of patients in EBV reactivation-associated HLH group were significantly lower than those in EBV primary infection-associated HLH group (P<0.05).@*CONCLUSION@#EBV reactivation-associated HLH is more likely to cause central nervous system involvement and the prognosis is worser than EBV primary infection-associated HLH, which requires intensive treatment.

Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Amplifications of AURKA and AURKB in a Burkitt lymphoma immunodeficiency-associated type: a case report

ABSTRACT In equatorial Brazil, the association of Burkitt lymphoma and Epstein-Barr virus manifests at high rates. Here, we report, for the first time, amplifications of aurora kinase genes (AURKA/B) in a patient with a history of periodontal abscess and the presence of a remaining nodule, diagnosed with Burkitt lymphoma and Epstein-Barr virus, and /HIV positive. The patient was a 38-year-old man who presented with a 2-week-old severe jaw pain and a 3-day-old severe bilateral headache. He had a history of human papilloma virus. Interphase FISH analysis showed AURKA and AURKB amplification. The patient's condition worsened, progressing to death a month after the initial care. Changes in the MYCC and AURKA pathways are directly associated with genomic instability. Thus, MYCC rearrangements and higher expression of AURKA/B may be associated with therapy resistance, highlighting the importance of AURKA/B evaluation in Burkitt lymphoma.

Pronostico desfavorable de linfoma t/nk: reporte de casos

El linfoma de células T/NK tiene una frecuencia de presentación inusual, caracterizado por una progresión rápida y de mal pronóstico. Ocurrencia aludida a regiones de Asia y Latinoamérica por la fuerte incidencia de infección por el virus de Epstein- Barr. Su presentación puede ser nasal o en otra localización. Los esquemas de tratamiento suelen conllevar respuestas insuficientes, empero protocolos con base en L-Asparaginasa reflejarían mejores resultados. El presente reporte corresponde a 4 casos de este tipo de linfoma, 2 de tipo nasal y 2 de diversa presentación. Todos evolucionaron desfavorablemente, en parte por el mal pronóstico atribuido y también por el diagnóstico suscitado en etapas avanzadas de enfermedad concatenadas a dificultades económicas para sostener el tratamiento, factores intervinientes en nuestro medio.

NK/T cell lymphoma is an unusual neoplasm, characterized by fast progression and poor prognosis. It is present in regions of Asia and Latin America associated to a high incidence of Epstein-Barr virus infection. Its presentation can be nasal or in another location. Treatment schemes usually lead to insufficient responses, however protocols based on L-Asparaginase would reflect better results. This report concerns 4 cases of this lymphoma, 2 nasal type and 2 of a different presentation. Patients responses were unfavorable, partly due to the poor prognosis att r ibuted and also due to the diagnosis raised in advanced stages of the disease as well as to economic difficulties to sustain treatment, intervening factors in our country.

Relato de caso: linfoma de células t/nk extranodal tipo nasal / Case Report: Extranodal Nk/T-Cell Lymphoma, N a s a l Ty p e / Reporte de caso: linfoma extranodal de células t/nk de tipo nasal

Introdução: O linfoma não-Hodgkin é dividido em linfomas de células B e linfomas de células T, e o linfoma extranodal de células T / NK do tipo nasal está dentro do último grupo.Relato de caso: Paciente do sexo masculino de 30 anos, relata que há 6 meses, de forma progressiva e de início insidioso, apresenta tumor cervical à direita de crescimento progressivo, pelo qual foi encaminhado ao ambulatório de cabeça e pescoço onde apresentou seus principais sinais e sintomas adenopatia cervical direita, sintoma B e tumoração ao nível da nasofaringe, envolvendo o teto, parede posterior e face lateral; se movimenta com auxílio, com extenso conglomerado linfonodal supraclavicular direito, eritematoso, com calor local, além de áreas de ulceração e secreção serosa.Conclusão: O diagnóstico e tratamento precoces desta doença são as únicas ferramentas para melhorar o mau prognóstico e o grave impacto na qualidade de vida dos pacientes que a padecem

Introduction: Non-Hodgkin's lymphomas are divided into B-cell lymphomas and T-cell lymphomas, and extranodal NK/T-cell lymphoma, nasal type, is in the latter group.Case report: A 30-year-old male patient, for six months, progressively and with an insidious onset, has had a right-sided cervical tumor with progressive growth. He came to a head and neck outpatient clinic where the main signs and symptoms detected were right cervical lymphadenopathy, B-symptoms, and a tumor in the nasopharynx affecting the roof, posterior wall, and lateral wall. The patient moves with assistance and has an enlarged, erythematous warm right supraclavicular lymph node conglomerate. In addition, he has some ulcerated areas with serous drainage.Conclusion: Early diagnosis and treatment of this disease are the only tools to improve these patients' poor prognosis and severely deteriorated quality of life.

Introducción:El linfoma no Hodgkin se divide en linfomas de células B y linfomas de células T; y en este último grupo se encuentra el linfoma extraganglionar de células T / NK de tipo nasal.Caso clínico: Un paciente masculino de 30 años refiere que durante 6 meses de forma progresiva, y con un início insidioso, presenta una tumoración cervical en el lado derecho de crecimiento progresivo, por lo que acude a la consulta externa de cabeza y cuello, donde los signos y síntomas principales fueron adenopatía cervical derecha, síntoma B, y una tumoración a nivel de nasofaringe, que afecta el techo, la pared posterior y la cara lateral. Se moviliza con ayuda, con un extenso conglomerado ganglionar supraclavicular derecho, eritematoso, con calor local. Además, también muestra algunas áreas de ulceración y secreción serosa. Conclusión: El diagnóstico y tratamiento precoz de esta enfermedad son las únicas herramientas para mejorar el mal pronóstico y el deterioro severo en la calidad de vida de los pacientes que la padecen

Infectious mononucleosis with follicular tonsillitis and urinary tract infection

Despite the prevalence of Epstein-Barr virus (EBV) infection, new reports of weird and atypical manifestations of the infection continue to emerge, raising the question of how well we know this pathogen. The clinical appearance of patients who become infected throughout their youth or early adulthood is changing as the infection age rises in developed countries. Other physical symptoms are less noticeable and liver involvement is more noticeable throughout these stages. To inform health-care professionals of this change, an update on infectious mononucleosis variable manifestation is necessary. This case presented a 28-year-old female presented with a history of fever, nausea, and vomiting with odynophagia and cervical lymphadenopathy. Complete blood count and peripheral blood film examination revealed lymphocytic leukocytosis with many reactive lymphocytes. Her monospot test for EBV was positive along with a urine culture positive for Staphylococcus aureus.