BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) secondary to acute lymphoblastic leukemia (ALL) is a rare disease with poor prognosis, usually attributed to delayed diagnosis. To date, only four cases of ALL developing DLBCL have been reported, while none of them exhibiting central nervous system (CNS) symptoms.
METHODS: Here, we report an unusual case of a 15-year-old boy diagnosed with ALL and treated based on the SCCLG-ALL 2016 protocol. While he was receiving maintenance treatment, the patient developed dizziness and vomiting. An Epstein-Barr virus (EBV)-positive DLBCL with CNS involvement was diagnosed from inguinal lymph nodes biopsy, EBV DNA tests and head magnetic resonance imaging (MRI). Meanwhile, a dramatic decrease of immune cells and immunoglobulin was detected in the occurrence of DLBCL. He received therapy based on SCCCG-NHL-2017 protocol immediately after the diagnosis.
CONCLUSIONS: We present the first retrospective report of four cases of non-Hodgkin lymphoma (NHL) secondary to ALL between 1990 and 2022. The pathogenesis of secondary DLBCL may be related to infection, immunodeficiency, genetic susceptibility, and treatment. Thus, the detection of EBV DNA during the full course of ALL therapy and genetic tests were needed in the occurrence of secondary DLBCL. Given to the rare rate and insufficient treatment experience, longer follow-up and enough sample size are needed.

BACKGROUND: EBV is a necessary but not sufficient factor in the pathophysiology of multiple sclerosis (MS). EBV antibodies to the nuclear antigen (EBNA1) and viral capsid antigen (VCA) rise rapidly prior to MS disease manifestations, and their absence has clinical utility with a high negative predictive value. It remains unclear whether EBV levels act as prognostic, monitoring, or pharmacodynamic/response biomarkers. Substantial literature on this topic exists but has not been systematically reviewed. We hypothesized that EBV levels against EBNA1 and VCA are potential prognostic and monitoring biomarkers in MS, and that patient population, MS clinical phenotype, and EBV assay method may play important roles in explaining variation among study outcomes.
METHODS: We systematically searched PubMed and EMBASE from inception to April 1, 2022. After removal of duplicates, records were screened by abstract. Remaining full-text articles were reviewed. Clinical and MRI data were extracted from full-text articles for comparison and synthesis.
RESULTS: Searches yielded 696 unique results; 285 were reviewed in full, and 36 met criteria for data extraction. Heterogeneity in sample population, clinical outcome measures, assay methods and statistical analyses precluded a meta-analysis. EBV levels were not consistently associated with clinical disease markers including conversion from CIS to RRMS, neurological disability, or disease phenotype. Studies using repeated-measures design suggest that EBNA1 levels may temporarily reflect inflammatory disease activity as assessed by gadolinium-enhancing Magnetic Resonance Imaging (MRI) lesions. Limited data also suggest a decrease in EBV levels following initiation of certain disease-modifying therapies.
CONCLUSIONS: Heterogeneous methodology limited generalization and meta-analysis. EBV antibody levels are unlikely to represent prognostic biomarkers in MS. The areas of highest ongoing promise relate to diagnostic exclusion and pharmacodynamic/disease response. Use of EBV antibodies as biomarkers in clinical practice remains additionally limited by lack of methodological precision, reliability, and validation.

Seroprevalence of anti-EBV antibodies was found to be almost 100% and 90% for multiple sclerosis patients and normal people, respectively. Furthermore, anti EBNA1 antibody which is an indicator of past EBV infection has a higher titer in the serum of Persons with MS (pwMS) compared to the EBV-infected subjects without MS. Though, this difference in anti-EBNA1 antibody titer between pwMS and non-MS controls is not a reliable marker to be used for discriminating pwMS and non-MS individuals. Some Studies have revealed specific epitopes on EBNA1 as the target for anti-EBNA1 antibodies in pwMS. Measuring antibody response against such specific epitopes can help better discriminate pwMS and non-MS individuals. This systematic review aims to obtain conclusive data from the studies which have sought to identify and map such epitopes on EBNA1. Five databases, including PubMed, Google Scholar, web of Science, Scopus, and Elsevier were searched for this purpose. Overall, 12 articles were finally included. Despite different articles describing not exactly the same epitopes, most of the epitopes described are within the amino acid sequence 385-420 of EBNA1. Among these epitopes, most of the epitopes have overlapping amino acid sequences with one another. The most highly overlapping sequence is RRPFF, which encompasses the amino acid 402 to 406 of EBNA1.

Background: The prevalence of breast cancer has increased and has currently become one of the most common cancers. Although the majority of the world\'s population is infected with Epstein Barr Virus (EBV) during their lives, the severity of symptoms varies and not everyone infected with EBV is diagnosed with cancer. EBV might increase the risk for breast cancer either by activating the HER2/HER3 signaling cascades or by creating a state of prolonged immune stimulation. Materials and Methods: A systematic search of several electronic databases including PubMed, ScienceDirect, Cochrane, EBSCOhost, JSTOR, and Scopus, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. The primary outcome of this review was to assess the prevalence of people with breast cancer that had a prior EBV infection. Results: For this review, 24 case-control studies were accepted. Our analyses included 1.989 breast cancer cases versus 1.034 control cases. EBV was found to be present in 27.9% of breast cancer cases versus 8.02% found in the normal breast tissue of controls. All affected people were women with a mean age was 48.19 years. The most common type of breast cancer found in EBV-infected tissues was invasive breast cancer. Cases were reported sporadically in a wide geographical distribution, and the prevalence varied from 4.6% - 64.1%. Conclusions: A previous EBV infection might be associated with a higher risk for breast malignancy. The most common type is invasive cancer. It mainly affects women and geographical variances are observed. More studies are necessary to elucidate the role of EBV in the mechanisms of breast cancer. Also, it is crucial to improve the prevention and treatment strategies.

Epstein-Barr virus (EBV) infection may present with fulminant constitutional symptoms, cytopenia(s), and systemic lymphadenopathy, raising clinical suspicion for lymphoma and prompting lymph node and bone marrow biopsies. At the microscopic level, the histopathologic findings in cases of acute EBV lymphadenitis may mimic certain lymphoid neoplasms, creating a range of differential diagnoses and diagnostic pitfalls.We present a case of fulminant EBV infection in an adolescent whose clinical and radiographic findings led to lymph node and bone marrow biopsies to rule out lymphoma. One week after being diagnosed with acute EBV infection (infectious mononucleosis), a 17-year-old Caucasian male presented with worsening symptoms including persistent fever, progressive, painful lymphadenopathy, and splenomegaly. A peripheral blood smear showed lymphocytosis with many reactive lymphocytes, anemia, and thrombocytopenia. Laboratory studies showed elevated ferritin, triglycerides, and soluble IL-2/CD25. A cervical lymph node biopsy demonstrated an EBV-positive, reactive B-immunoblast proliferation with large atypical lymphoid cells mimicking Reed-Sternberg cells of Hodgkin lymphoma, in addition to patchy vasculitis, coagulative necrosis, and prominent hemophagocytic activity. Bilateral bone marrow biopsies showed a hypercellular marrow with patchy infiltrates of similar EBV-positive, large atypical lymphoid cells, as well as prominent hemophagocytic activity. The diagnosis of acute EBV associated lymphoproliferation with concurrent hemophagocytic lymphohistiocytosis (HLH) was rendered.Recognition of common and uncommon clinical presentations of acute EBV infection is essential, particularly when histopathologic findings raise suspicion for a possible hematolymphoid neoplasm. Both the lymph node architectural and viral cytopathic changes observed in EBV lymphadenitis exhibit significant morphologic overlap with classic Hodgkin lymphoma (cHL) and several other lymphomas, including anaplastic large cell lymphoma, diffuse large B cell lymphoma, and angioimmunoblastic T cell lymphoma. Recognition of immunohistochemical staining patterns in EBV lymphadenitis is critical to avoid misdiagnosis. Conversely, bona fide lymphoma, particularly cHL, can masquerade as EBV infection. We provide a concise discussion and tables of the histopathologic differential diagnosis of EBV lymphadenitis, including cHL and other lymphomas. Pathologists should include acute EBV infection within the differential diagnosis when confronted with clinical and pathologic findings concerning for lymphoma, particularly in adolescents and young adults.

BACKGROUND: Acute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. Epstein-Barr virus (EBV)-associated acute pancreatitis is a rare condition and it may occur in children and adults.
METHODS: A 3-year-old female was admitted to the \"G. Di Cristina\" Children\'s Hospital in Palermo for vomiting and abdominal pain. Laboratory investigations revealed elevated amylase and lipase, with normal liver function tests. Abdominal ultrasound demonstrated an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. Infectious disease serology was positive for the presence of EBV VCA IgM and IgG. A diagnosis of EBV-associated acute pancreatitis was made. The patient was treated conservatively and recovered.
CONCLUSIONS: Acute pancreatitis is rarely associated with EBV infection; a review of the English literature revealed only 10 pediatric and 6 adult cases. Patients with pancreatitis should always be evaluated for EBV serology, even in the absence of the typical clinical and hematological features of infectious mononucleosis. For these patients, good prognosis is generally expected.

UNASSIGNED: Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck that arises from the mucosal epithelium of the nasopharynx. Epstein-Barr virus (EBV) is a human herpes virus and the necessary cause for NPC. The 5-year survival rate for NPC patients is higher when diagnosed at an earlier stage of disease. Therefore, NPC screening should be prioritized for early detection. The objective of this narrative review is to synthesize the existing literature from the past decade describing evaluations of EBV-based serological markers for NPC screening.
UNASSIGNED: We performed a literature search in PubMed for studies published from 2010 to 2020. Studies were required to be English-language articles. Twelve articles fulfilled all inclusion criteria, including eight studies conducted among the general population in southeastern China, three studies in genetically high-risk Taiwanese families, and one study comparing EBV serology versus circulating EBV DNA for NPC prediction.
UNASSIGNED: Studies suggest that EBV-based serology has the potential to be an effective tool to aid in early detection of NPC. The synthesized research also collectively suggests that incorporation of antibody against multiple EBV targets, as well as efforts to optimize assay output, can improve the ability of EBV serological markers to detect NPC. Finally, recent data from the only randomized trial provide preliminary evidence that screening using anti-EBV immunoglobulin A (IgA) antibody may achieve the goal of reducing mortality from NPC.
UNASSIGNED: Late diagnosis is one of the reasons for poor survival after an NPC diagnosis. In high-risk areas, early diagnosis aided by EBV antibody could therefore improve survival.

Hodgkin lymphoma variant of Richter\'s transformation (HL-RT) is a rare event, occurring in < 1% chronic lymphocytic leukemia (CLL) cases, of which, in < 10% cases, HL is the first finding leading to a diagnosis of CLL that co-exists simultaneously. Here we report a 60 years old male patient who presented with an outside diagnosis of lymphocyte-rich classical HL. On evaluation, he had only B-symptoms in the form of low-grade fever and weight loss. Peripheral smear revealed mild leukocytosis with an absolute lymphocytosis and a few smudge cells. Bone marrow (BM) aspirate and biopsy exhibited diffuse infiltration by a small cell, low grade, Non-Hodgkin\'s lymphoma with no immunohistochemical evidence of HL. Flow cytometry performed on BM was consistent with classical immunoprofile of CLL. Meanwhile the lymph node received for review revealed diffuse effacement of nodal architecture by small mature lymphocytes with immunoprofile of CLL expressing CD20, CD5, and CD23. Interspersed between these cells, were a few eosinophils along with classical Reed Sternberg cells, expressing CD30, MUM-1, CD15, and dim PAX-5, with a surrounding rosette of T-Cells highlighted by CD3 and PD-1 and negative for CD45, CD20, and EBV immunohistochemistry. Fluorodeoxyglucose positron emission tomography (FDG-PET) scan revealed hepatosplenomegaly with multiple supra/infra diaphragmatic lymph nodes. So, a final diagnosis of HL-RT in CLL was considered. The patient is currently doing well after the first cycle of ABVD chemotherapy. HL-RT occurring in CLL is a rare event with heterogeneous clinical presentation, morphology, clonal origin, disease course, prognostic features, and survival.

BACKGROUND: This study aims to qualitatively and quantitatively review the association between Epstein-Barr virus (EBV) and oral squamous cell carcinoma (OSCC).
METHODS: PubMed, Scopus, and Web of Science databases were searched using the keywords \"EBV or Epstein Barr virus and Oral cancer or Oral squamous cell carcinoma\" for published case-control studies in the English language upto August 2019.
RESULTS: The search yielded 985 articles out of which 966 articles were excluded by screening their titles and abstracts as they were irrelevant or duplicates. Based on the full-text assessment of the remaining 19 articles, only 7 satisfied the inclusion criteria and were included in the qualitative analysis, out of which only 4 were compatible to be included in the meta-analysis. The diagnostic modalities used included immunohistochemistry, in situ hybridization and polymerase chain reaction. The diagnostic targets included latent membrane protein (LMP)-1, EBV determined nuclear antigen-1, EBV-encoded small non-polyadenylated RNA-2. The meta-analysis showed that there is an association between the EBV and OSCC.
CONCLUSIONS: Determining the association of EBV with OSCC is highly tedious due to the contrasting data obtained from individuals\' studies which in turn is due to the wide variations in the sensitivity and specificity of the diagnostic modalities used and diagnostic targets selected. Although the meta-analysis revealed an association between EBV and OSCC, the number and the quality of the studies included in the meta-analysis are limited, thus the association requires further validation for any conclusive inference.

Over the past few decades, several publications have investigated the role of Epstein-Barr virus (EBV) in head and neck squamous cell carcinomas, and an increasing number of them have shown its presence in laryngeal tumors. The purpose of this meta-analysis was to evaluate the association of EBV with laryngeal carcinoma. The search was carried out in two databases, Scopus and PubMed, using the following terms: \"Epstein-Barr virus\" and \"laryngeal carcinoma\". A total of 187 records were found, of which 31 were selected for meeting the inclusion and exclusion criteria. The meta-analysis yielded an overall pooled prevalence of 43.72% (95% confidence interval (CI): 34.35-53.08). Studies carried out in Europe and Eurasia had slightly higher pooled prevalence than other subgroups, while the prevalence of studies performed in developed countries was higher than in developing countries (46.37% vs. 34.02%). Furthermore, laryngeal carcinoma occurred almost three times as often among EBV-infected individuals compared to those without EBV infection (odds ratio = 2.86 (95% CI: 1.18-6.90); Begg\'s test, p = 0.843 and Egger\'s test, p = 0.866). Our findings support the idea that EBV is related to laryngeal carcinoma. However, further studies are needed before recognizing a definitive etiological role of EBV in the development and/or progression of laryngeal carcinomas.