Epstein-Barr Virus-positive Diffuse Large B-cell Research Articles

Epstein-Barr Virus-Positive Diffuse Large B-cell Lymphoma Arising in Ulcerative Colitis: An Instructive Case Report and Literature Review

Epstein-Barr Virus-Positive Diffuse Large B-cell Lymphoma Arising in Ulcerative Colitis: An Instructive Case Report and Literature Review

Hemophagocytic lymphohistiocytosis in a patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy.

With the advent of chimeric antigen receptors T-cell therapy, understanding their role in the development of hemophagocytic lymphohistiocytosis has become increasingly complex. We describe a case of a young patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma, who was treated with axicabtagene ciloleucel. The patient developed progressive cytopenia and, on Day 73 post-infusion, met criteria for hemophagocytic lymphohistiocytosis. Bone marrow evaluation revealed hemophagocytosis without evidence of clonal B cells. The patient was treated with tocilizumab, dexamethasone, etoposide and anakinra, which eventually led to improvement. Unfortunately, the patient succumbed to an infection. Disease progression was confirmed posthumously.This case report explores the differential diagnosis of hyperinflammatory syndromes following chimeric antigen receptor T-cell therapy and highlights the reduced efficacy of this treatment in patients with a T-cell/histiocyte-rich background.

Kaempferol inhibits the proliferation and migration of Epstein-Barr virus-positive diffuse large B-cell lymphoma cells

Purpose: To assess the effect of kaempferol on the growth, apoptosis, and motility of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) cells, and to elucidate its mechanism of action. 
 Methods: Human DLBCL cells were used to generate EBV-positive (EBV +) cell line Pfeiffer. CCK-8, colony formation, flow cytometry (FCM), and immunoblot assays were employed to determine the effects of kaempferol on the growth and apoptosis of EBV + DLBCL cells. Cell motility was evaluated by Transwell and immunoblot assays. Immunoblot assay was further conducted to unravel the mechanism of action. 
 Results: Kaempferol inhibited the growth of EBV + DLBCL cells. It also enhanced the apoptosis of EBV + DLBCL cells, but inhibited the motility of the cells. Furthermore, kaempferol inhibited PI3K/AKT axis, thereby suppressing DLBCL. 
 Conclusion: Kaempferol inhibits the growth and motility of EBV + DLBCL cells via PI3K/AKT axis. It is therefore a potential drug for the treatment of DLBCL.

Polatuzumab Vedotin (Polivy)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses polatuzumab vedotin (Polivy), 30 mg or 140 mg single-use vial, lyophilized powder for solution for IV infusion.
 Indication: Polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, indicated for the treatment of adult patients with previously untreated large B-cell lymphoma, including diffuse large B-cell lymphoma not otherwise specified, high-grade B-cell lymphoma, Epstein-Barr virus-positive diffuse large B-cell lymphoma not otherwise specified, and T-cell/histiocyte-rich large B-cell lymphoma.

A Case of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma Occurring in Thyroid Gland

Epstein-Barr virus positive diffuse large B-cell lymphoma is very rare malignant tumor in thyroid gland. Compared to Epstein-Barr virus negative diffuse large B-cell lymphoma, it tends to have more extranodal involvement, does not respond to chemoimmunotherapy well, and has worse prognosis. We have encountered a patient with Epstein-Barr virus positive diffuse large B-cell lymphoma of thyroid gland in 75-year-old female presenting with aggravating dyspnea and neck pain.

EBV-Positive Diffuse Large B-Cell Lymphoma in Association with Polyurethane Textured Breast Implants: Case Report and Literature Overview.

Lymphomas associated with breast implants are mostly of the T-cell type which typically present as a late-onset seroma or palpable mass adjacent to the implant. Primary lymphomas of the breast, in the absence of breast implants, are mostly of the B-cell type. However, we present a case of an Epstein-Barr virus-positive diffuse large B-cell lymphoma in a patient with polyurethane textured implants. A 75-year-old woman presented with a sudden onset of swelling in her right breast. Her medical history revealed a unilateral mastectomy at the age of 48 for an invasive ductal adenocarcinoma in her left breast. Reconstruction was performed using bilateral McGhan style 150 implants. Nine years later, she was diagnosed with Baker IV capsular contracture and bilateral rupture, as seen on magnetic resonance imaging. A complete capsulectomy with implant change (Polytech, Replicon® SL HP) and mastopexy on the right was performed. Given her history and the sudden onset of swelling, the situation was concerning. Ultrasound showed a large mass in contact with the implant and an effusion around it. After mastectomy withexplantation and capsulectomy, she was diagnosed with an Epstein-Barr virus-associated diffuse large B-cell lymphoma (DLBCL) of the capsule in association with textured breast implants. We report the first case of polyurethane textured implant association with the rare entity of EBV+ DLBCL. Our aim is to renew awareness of the clinical significance of late periprosthetic seroma and highlight the need for documenting all cases to advance our understanding of breast implant-associated lymphoma. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Necrotic lymphadenopathy in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Necrotic lymphadenopathy in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Primary hepatic Epstein–Barr virus-positive diffuse large B-cell lymphoma associated with azathioprine immunosuppression: a case report

BackgroundHepatic masses are relatively common findings, and the diagnostic approach often begins by identifying patient and mass characteristics that are risk factors for malignancy. Chronic immunosuppression is a known risk factor for various malignancies, and azathioprine in particular has been reported in association with solid and hematologic malignancies, including diffuse large B-cell lymphoma.Case presentationA 46-year-old white woman presented to clinic with several weeks of gastrointestinal symptoms and was found to have a hepatic mass on imaging. Her history was notable for neuromyelitis optica spectrum disorder on chronic immunosuppression with azathioprine. It was initially thought to be an inflammatory adenoma. On 6-month follow-up imaging, the mass had grown rapidly in size and was surgically resected. Further workup determined the mass to be an iatrogenic immunodeficiency-associated Epstein–Barr virus-positive diffuse large B-cell lymphoma confined to the liver. Azathioprine was discontinued and the patient underwent treatment with rituximab with no evidence of recurrence 2 years after the initiation of treatment.ConclusionsThis case report describes the first time hepatic Epstein–Barr virus-positive diffuse large B-cell lymphoma has been reported with azathioprine, which highlights the unique sequelae of chronic immunosuppression, including atypical hematologic malignancies, and the importance of considering chronic immunosuppression in the diagnostic evaluation of a hepatic mass.

TET2 and LILRB1 mutations are frequent in Epstein-Barr virus-positive diffuse large B-cell lymphoma especially in elderly patients.

Diffuse large B-cell lymphoma (DLBCL) harboring Epstein-Barr virus (EBV) primarily occurs in patients who have underlying immunodeficiency or in elderly patients but is also reported in young, immunocompetent patients. The authors investigated the pathologic differences in EBV-positive DLBCL in these three groups of patients. In total, 57 patients with EBV-positive DLBCL were included in the study; of these, 16 patients had associated immunodeficiency, 10 were young (younger than 50years), and 31 were elderly (aged 50years or older). Immunostaining for CD8, CD68, PD-L1, and EBV nuclear antigen 2, and panel-based next-generation sequencing was performed on formalin-fixed, paraffin-embedded blocks. Immunohistochemistry revealed EBV nuclear antigen 2 positivity in 21 of the 49 patients. The degree of CD8-positive and CD68-positive immune cell infiltration and PD-L1 expression did not differ significantly in each group. Extranodal site involvement was more common in young patients (p=.021). In mutational analysis, the genes with the highest mutation frequency were PCLO (n=14), TET2 (n=10), and LILRB1 (n=10). For the TET2 gene, all 10 mutations were found in elderly patients (p=.007). Compared with a validation cohort, both TET2 and LILRB1 showed a higher mutation frequency in EBV-positive patients than in EBV-negative patients. EBV-positive DLBCL occurring in three different age and immune status groups showed similar pathologic characteristics. Notably, a high frequency of TET2 and LILRB1 mutations was characteristic of this disease in elderly patients. Further studies are needed to determine the role of TET2 and LILRB1 mutations in the development of EBV-positive DLBCL along with immune senescence. Epstein-Barr virus-positive diffuse large B-cell lymphoma occurring in three different groups (immunodeficiency-associated, young, and elderly) showed similar pathologic characteristics. The frequency of TET2 and LILRB1 mutations was high in elderly patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.

The Incidence of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis.

Simple SummaryThe worldwide prevalence of Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL) is undetermined. There is no clearly defined cut-off for EBV-encoded RNA (EBER) positivity in tumor cells by in situ hybridization. A lack of common criteria for positive expression of EBER has been raised as a limitation for interpreting and understanding the geographic and ethnic disparity of prevalence of EBV+ DLBCL. We conducted a systematic literature review and meta-analysis to establish the proportions of EBV+ DLBCL patients. Results showed that the pooled proportion of EBER positivity was 7.9% in patients with de novo DLBCL. The prevalence of EBV+ DLBCL was significantly higher in Asia and South America compared with Western countries. A tendency for lower pooled proportions was observed in studies using a higher cut-off for EBER positivity. The patients’ age did not significantly affect the prevalence. These findings may improve our current knowledge of the EBV+ DLBCL.The worldwide prevalence of Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL) is undetermined. There is no clearly defined cut-off for EBV-encoded RNA (EBER) positivity in tumor cells by in-situ hybridization. The purpose of this study was to establish the proportions of EBV+ DLBCL patients and influence of the different cut-offs for EBER positivity, geographical location, and age on the prevalence of EBV+ DLBCL. PubMed and EMBASE were searched for studies published up to May 28, 2020 that reported proportions of EBER positivity in immunocompetent and de novo DLBCL patients. The pooled proportions were computed by an inverse variance method for calculating the weights and the DerSimonian–Laird method. Multiple subgroup analyses were conducted to explore any heterogeneity. Thirty-one studies (8249 patients) were included. The pooled proportion of EBV+ DLBCL was 7.9% (95% CI, 6.2–10.0%) with significant heterogeneity among studies (p < 0.001). The prevalence of EBV+ DLBCL was significantly higher in Asia and South America compared with Western countries (p < 0.01). The cut-offs for EBER positivity (10%, 20%, 50%) and patients’ age (≥50 years vs. <50 years) did not significantly affect the prevalence (p ≥ 0.10). EBV+ DLBCL is rare with a pooled proportion of 7.9% in patients with DLBCL and the geographic heterogeneity was confirmed.

Cutaneous Epstein-Barr virus–positive diffuse large B-cell lymphoma, not otherwise specified: A systematic review and comparative analysis with Epstein-Barr virus–negative, leg type

To the Editor: Epstein-Barr virus (EBV)–positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an EBV-associated B-cell lymphoma often presenting in elderly patients without any known immunodeficiencies.1,2 For a systematic review to characterize cutaneous EBV-positive DLBCL-NOS, we searched 5 databases (Supplemental Fig 1; available via Mendeley at https://doi.org/10.17632/dby7kdtzk8.1).3 We also searched the Asan Medical Center database for cases of cutaneous EBV-positive DLBCL-NOS and primary cutaneous EBV-negative DLBCL–leg type for comparative analysis.

Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified: A diagnostic challenge

Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the 2016 World Health Organization classification of lymphoid neoplasms. EBV+DLBCL, NOS, is an aggressive B-cell lymphoma associated with chronic EBV infection and poor prognosis with standard chemotherapeutic approaches. We present the case of a 71-year-old male hospitalized for generalized lymphadenopathy, unexplained weight loss, and intermittent fever with pancytopenia and a very high EBV viral load. An inguinal lymph node was biopsied and reported at two different centers as Classic Hodgkin lymphoma and EBV associated lymphoproliferative, respectively. The patient was subsequently rebiopsied and a cervical lymph node was subjected to detail histopathologic and immunohistochemical evaluation by clonality studies resulting in a final diagnosis of EBV positive DLBCL, NOS. This case highlights the potential diagnostic pitfalls due to the morphologic heterogeneity of this entity and immunohistochemical overlap with Hodgkin lymphoma, T-cell rich large B-cell Lymphoma, and diffuse large B-cell lymphoma (DLBCL, NOS).

Composite Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma and Epstein-Barr virus-negative diffuse large B-cell lymphoma in the parotid salivary gland of a patient with Sj\xf6gren\u2019s syndrome and rheumatoid arthritis: a case report

BackgroundEpstein-Barr virus is associated with many human hematopoietic neoplasms; however, Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma is extremely rare. In routine clinical practice, detection of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma in a tissue sample presumes a clonal relation between these neoplasms and that diffuse large B-cell lymphoma developed by transformation of the mucosa-associated lymphoid tissue lymphoma. However, evidence to support this presumption is sparse and controversial. Assessment of the clonal relationship of the lymphoid components of a composite lymphoma is important for understanding its pathogenesis and correct diagnosis.Case presentationWe present an unusual case of composite lymphoma (Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma/Epstein-Barr virus-negative diffuse large B-cell lymphoma) in the parotid salivary gland of a 62-year-old Caucasian woman with Sjögren’s syndrome and rheumatoid arthritis. Simultaneous occurrence of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma in the parotid salivary gland led us to initially assume a clonal relationship between diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. Epstein-Barr virus was detected by in situ hybridization and polymerase chain reaction in the mucosa-associated lymphoid tissue lymphoma, but not in diffuse large B-cell lymphoma, suggesting that these lymphomas were not clonally related. Fragment analysis of frame region 3 polymerase chain reaction products from microdissected mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma components revealed different clonal pattern rearrangements of the immunoglobulin heavy chain gene.ConclusionsOur patient’s case highlights the importance of assessing the clonal relationships of the lymphoid components of a composite lymphoma and Epstein-Barr virus screening in mucosa-associated lymphoid tissue lymphoma in patients with autoimmune disease.

Epstein–Barr virus-positive diffuse large B-cell lymphoma features disrupted antigen capture/presentation and hijacked T-cell suppression

ABSTRACT Background: B cells can function as antigen-presenting cells by presenting antigens captured by the B-cell receptor (BCR) on Class II Major Histocompatibility Complex (MHC II) to T cells. In addition, B-cells can also maintain immune homeostasis by expressing PD-L1 and suppressing T-cell activity. Epstein-Barr virus (EBV) infection can disrupt B-cell function and lead to B cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Here we show that EBV-positive DLBCL (EBV+ DLBCL) has decreased expression of BCR and MHC II, but over-expressed PD-L1, which may lead to immune evasion. Methods: An EBV+ DLBCL cohort (n = 30) and an EBV- DLBCL control cohort (n = 83) were established. Immunostaining of PD-L1, MHC II, MHC II Transactivator (CIITA) and pBTK was performed on automated stainer. H-score was used to denote the results of staining of PD-L1 and pBTK. Break apart and deletion of CIITA locus was studied by fluorescent in situ hybridization. Surface immunoglobulin mean fluorescent insensitivity (MFI) was detected by flow cytometry to demonstrate the level BCR. Results: EBV+ DLBCL showed significantly lower expression of CIITA and MHC II compared to EBV- DLBCL. Genetic aberrations involving CIITA were also more common in EBV+ DLBCL, with 23% break apart events and 6% deletion events, comparted to 2% break apart and 0% deletion in EBV- DLBCL. In addition to the loss of antigen presentation molecule, the antigen capture receptor, BCR, was also down-regulated in EBV+ DLBCL. Accordingly, BCR signaling was also significantly decreased in EBV+ DLBCL as denoted by the respective pBTK levels. Conclusions: EBV+ DLBCL shows over expression of the T-cell inhibitory ligand, PD-L1. Antigen capture and presentation system were disrupted, and T-cell inhibitory molecule was hijacked in EBV+ DLBCL, which may contribute to immune escape in this high risk disease. Therapies targeting these aberrations may improve the outcome of patients with EBV+ DLBCL.

The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma

ObjectiveEpstein‐Barr virus‐positive diffuse large B‐cell lymphoma (EBV‐pos DLBCL) is a recently identified entity. Data regarding outcome to frontline immuno‐chemotherapy are conflicting. Although the prognostic impact of the tumour microenvironment (TME) in EBV‐neg DLBCL is well‐established, it remains untested whether the TME influences survival in EBV‐pos DLBCL. There are no data with new digital gene expression technologies that simultaneously interrogate the virus, B cells and the tumour microenvironment (TME).MethodsWe used the NanoString™ platform in a population‐based cohort of 433 patients to establish if the technology could detect EBV in the tumour biopsies and to investigate the influence that EBV has on the complex tumour microenvironment of DLBCL.ResultsIncidence of EBV‐pos DLBCL was 6.9% with 5‐year survival of 65% vs 82% in EBV‐neg DLBCL (P = 0.018). EBV‐pos tissues had similar expression of T‐cell genes compared to EBV‐neg DLBCL but higher levels of the antigen‐presenting molecule B2M. This was countered by elevated PD‐L1, PD‐L2, LAG3 and TIM3 immune checkpoints and a higher CD163/CD68 “M2” macrophage score.ConclusionIn EBV‐pos DLBCL, the TME is immuno‐tolerogenic and may explain the poor outcomes seen in this subtype of DLBCL.

Primary cutaneous Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL) in a patient taking fingolimod

A 55-year-old man with relapsing-remitting multiple sclerosis on fingolimod presented to the dermatology clinic with skin lesions on the left temple and cheek. Histopathology showed a diffuse infiltrate of enlarged, atypical lymphocytes throughout the dermis with an overlying grenz zone and a subpopulation of scattered smaller lymphocytes and plasma cells. Epstein-Barr virus-encoded RNA in situ hybridization stain was positive. Based on the morphologic and immunophenotypic findings, a diagnosis of EBV-positive diffuse large B-cell lymphoma was made. This case aims to raise awareness for the dermatologist that patients on fingolimod may be at increased risk of lymphoproliferative disorders.

Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma in Human Immunodeficiency Virus–Infected Patient: Presentation of a Case and Review of the Literature

Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma in Human Immunodeficiency Virus–Infected Patient: Presentation of a Case and Review of the Literature

Genetic heterogeneity and mutational signature in Chinese Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is typically an aggressive tumor in elderly patients. However, in a subset of young patients, EBV+ DLBCL follows a relatively indolent clinical course and exhibits a good response to chemotherapy. This lymphoma comprises polymorphous lymphoma and large cell lymphomas subtypes, with the latter subtype showing a significantly poorer prognosis. It is unknown whether the genetic background differs between age groups and histopathological subtypes. To investigate the genetic basis, heterogeneity, and recurrently mutated genes in EBV+ DLBCL, we performed whole-exome sequencing of DNA from 11 tissue samples of this lymphoma. Sequencing revealed that the most common substitution was the transition C>T/G>A. Genetic features—including the numbers of mutated genes in exonic region, single-nucleotide variants (SNV), and indels—did not significantly differ between age groups or histological subtypes. Matching with the COSMIC database revealed that the main mutational signature was signature 3, which is associated with failure of DNA double-strand break-repair by homologous recombination. Mutant-Allele Tumor Heterogeneity (MATH) scores showed that EBV+ DLBCL exhibited broad intratumor heterogeneity, and were positively correlated with Ann Arbor Stage and ≥2 extranodal lesion sites. We identified 57 selected recurrently mutated genes. The most commonly mutated five genes—LNP1 (11/11), PRSS3 (10/11), MUC3A (9/11), FADS6 (9/11), and TRAK1 (8/11)—were validated by Sanger sequencing. These mutated genes have not previously been identified. Overall, our present results demonstrate the tremendous genetic heterogeneity underlying EBV+ DLBCLs, and highlight the need for personalized therapeutic approaches to treating these patients.

Outcomes among North American patients with diffuse large B-cell lymphoma are independent of tumor Epstein-Barr virus positivity or immunosuppression.

The prevalence, presenting clinical and pathological characteristics, and outcomes for patients with diffuse large B-cell lymphoma that is Epstein-Barr virus positive remain uncertain as does the impact of congenital or iatrogenic immunosuppression. Patients with newly diagnosed diffuse large B-cell lymphoma with available tissue arrays were identified from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource. Patients infected with human immunodeficiency virus or who had undergone a prior organ transplant were excluded. Epstein-Barr virus-associated ribonucleic acid testing was performed on all tissue arrays. A history of significant congenital or iatrogenic immunosuppression was determined for all patients. At enrollment, 16 of the 362 (4.4%) biopsies were positive for Epstein-Barr virus. Thirty-nine (10.8%) patients had a significant history of immunosuppression. Patients with Epstein-Barr-positive diffuse large B-cell lymphoma had no unique clinical characteristics but on pathology exhibited a higher frequency of CD30 positivity (25.0% versus 8.1%, respectively; P<0.01), and non-germinal-center subtype (62.5% versus 34.1%, respectively; P<0.01). No baseline clinical characteristics were associated with a history of immunosuppression. With a median follow up of 59 months, and after adjustment for International Prognostic Index, there was no association of Epstein-Barr virus positivity or immunosuppression with event-free survival at 24 months (odds ratio=0.49; 95% confidence interval: 0.13–1.84 and odds ratio=0.81; 95% confidence interval: 0.37–1.77) or overall survival (hazard ratio=0.86; 95% confidence interval: 0.38–1.97 and hazard ratio=1.00; 95% confidence interval: 0.57–1.74). In contrast to non-Western populations, our North American population had a low prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma that did not convey an adverse prognosis. A history of immunosuppression, while known to be a risk factor for the development of diffuse large B-cell lymphoma, did not affect subsequent prognosis.

Spontaneous regression of Epstein-Barr virus-associated lymphoproliferative disorder in a juvenile idiopathic arthritis patient after the discontinuation of methotrexate and etanercept.

A case of a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) since the age of 4 years is reported here. This patient also suffered from multiple congenital anomalies. On long-term treatment with oral methotrexate (MTX) and etanercept, multiple subcutaneous nodules were detected, which were accompanied by increased lactate dehydrogenase and uric acid levels. A biopsy of the largest nodule revealed Epstein-Barr (EB) virus-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified as clinical stage IIIA due to a mediastinal lesion. Immunosuppressive treatment was discontinued immediately, which led to regression of the remaining nodules and normalization of the lactate dehydrogenase levels. The patient was considered to have an iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the World health organization (WHO). To our knowledge, this is the first case report of a JIA patient with EBV-positive DLBCL following the administration of etanercept and methotrexate and spontaneous regression of lymphoproliferation after the discontinuation of antirheumatic treatment.