EBV-Positive Plasmacytomas Involving a Nasopharyngeal Angiofibroma in an Adolescent

2021 ◽  
pp. 109352662199902
Author(s):  
Rachel Mariani ◽  
Rebecca L King ◽  
Huifei Liu

We report comprehensive characterization of an unusual collision tumor comprising extramedullary plasmacytomas and nasopharyngeal angiofibroma in a pediatric patient, which has yet to be reported. Histologically, the nasopharyngeal angiofibroma showed typical morphology with a diffuse, dense plasmacytic infiltrate in the stroma. The neoplastic plasma cells showed a spectrum of well-differentiated, plasmablastic, and anaplastic morphology, Epstein-Barr virus encoded RNA (EBER) positivity, and aberrant immunophenotype. Fluorescence in situ hybridization using a plasma cell myeloma targeted panel detected gains of 1q21.3 ( CKS1B, x3), 3q27 ( BCL6, x4), and 11q22.3 ( ATM, x3), but no rearrangement of ALK and MYC. A 50-gene next generation sequencing lymphoma panel failed to detect any pathogenic mutation. Plasmacytoma with EBER positivity and plasmablastic morphology must be distinguished from plasmablastic lymphoma due to different clinical management and prognosis. This case highlights the importance of a thorough pathological evaluation of a mass lesion with synchronous neoplastic processes.

2018 ◽  
Vol 97 (13) ◽  
pp. 1494-1500 ◽  
Author(s):  
H. Raybaud ◽  
C.V. Olivieri ◽  
L. Lupi-Pegurier ◽  
S. Pagnotta ◽  
R. Marsault ◽  
...  

Epstein-Barr virus (EBV), in addition to its transforming properties, contributes to the pathogenesis of several inflammatory diseases. Here, we investigated its involvement in oral lichen planus (OLP), a common autoimmune-like disease of unknown etiopathogenesis that can display a malignant potential. EBV-infected cells (EBV+ cells) were sought in a large series of clinically representative OLPs ( n = 99) through in situ hybridization to detect small noncoding EBV-encoded RNAs. Overall, our results demonstrated that EBV was commonly found in OLP (74%), with significantly higher frequency (83%) in the erosive form than in the reticular/keratinized type mild form (58%). Strikingly, many erosive OLPs were massively infiltrated by large numbers of EBV+ cells, which could represent a large part of the inflammatory infiltrate. Moreover, the number of EBV+ cells in each OLP section significantly correlated with local inflammatory parameters (OLP activity, infiltrate depth, infiltrate density), suggesting a direct relationship between EBV infection and inflammatory status. Finally, we characterized the nature of the infiltrated EBV+ cells by performing detailed immunohistochemistry profiles ( n = 21). Surprisingly, nearly all EBV+ cells detected in OLP lesions were CD138+ plasma cells (PCs) and more rarely CD20+ B cells. The presence of EBV+ PCs in erosive OLP was associated with profound changes in cytokine expression profile; notably, the expression of key inflammatory factors, such as IL1-β and IL8, were specifically increased in OLP heavily infiltrated with EBV+ PCs. Moreover, electron microscopy–based experiments showed that EBV+ PCs actively produced EBV viral particles, suggesting possible amplification of EBV infection within the lesion. Our study thus brings conclusive evidence showing that OLP is commonly infiltrated with EBV+ PCs, adding a further puzzling element to OLP pathogenesis, given that PCs are now considered to be major regulatory immune cells involved in several autoimmune diseases (ClinicalTrials.gov NCT02276573).


Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2671-2674 ◽  
Author(s):  
D Schlaifer ◽  
M March ◽  
S Krajewski ◽  
G Laurent ◽  
J Pris ◽  
...  

The expression of bcl-x protein, a bcl-2-related protein present in cortical thymocytes, activated lymphocytes, and plasma cells of reactive lymph nodes, was investigated in 44 cases of Hodgkin's disease (HD) in parallel with bcl-2 and Epstein-Barr virus (EBV) status. Eighty-six percent of the cases were positive for bcl-x, among them 27% with a strong signal in more than 75% of the Reed-Sternberg cells. Positivity for bcl-x was found in, respectively, 100% and 92% of the nodular sclerosis and mixed cellularity subtypes, although 4 cases of lymphocyte predominance subtype were negative. This finding was in contrast with the weaker positivity for bcl-2 staining in 44% of the cases. EBV small RNAs were detected in 43% of the cases by using in situ hybridization. Of interest, 100% of the EBV-positive samples were positive for bcl-x, whereas only 38% of these cases were bcl-2 positive. Our findings show that the bcl-x gene expression is high in HD, suggesting that bcl-x may have a role in the pathogenesis of at least some cases of HD via apoptosis regulation.


2008 ◽  
Vol 2 (3) ◽  
pp. 145-149 ◽  
Author(s):  
Román Carlos ◽  
Lester D. R. Thompson ◽  
Ana Carolina Netto ◽  
Luiz Gustavo Garcia Santos Pimenta ◽  
Jeane de Fátima Correia-Silva ◽  
...  

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 604-611 ◽  
Author(s):  
Yassine Al Tabaa ◽  
Edouard Tuaillon ◽  
Karine Bollore ◽  
Vincent Foulongne ◽  
Gael Petitjean ◽  
...  

AbstractThe Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes latency in resting memory B lymphocytes, and is involved in oncogenesis through poorly understood mechanisms. The EBV lytic cycle is initiated during plasma cell differentiation by mRNAs transcripts encoded by BZLF1, which induce the synthesis of EBV proteins such as the immediate-early antigen ZEBRA and the late membrane antigen gp350. Therefore, we assessed the capacity of circulating EBV-infected B lymphocytes from healthy EBV-seropositive subjects to enter and complete the EBV lytic cycle. Purified B lymphocytes were polyclonally stimulated and BZLF1- or gp350-secreting cells (BZLF1-SCs or gp350-SCs) were enumerated by ELISpot assays. The number of BZLF1-SCs ranged from 50 to 480/107 lymphocytes (median, 80; 25th-75th percentiles, 70-150) and gp350-SCs from 10 to 40/107 lymphocytes (median, 17; 25th-75th percentiles, 10-20). gp350-SCs represented only 7.7% to 28.6% of BZLF1-SCs (median, 15%; 25th-75th percentiles, 10.5%-20%). This EBV functional reservoir was preferentially restricted to plasma cells derived from CD27+ IgD− memory B lymphocytes. In 9 of 13 subjects, EBV DNA quantification in B-cell culture supernatants gave evidence of completion of EBV lytic cycle. These results demonstrate that EBV proteins can be secreted by EBV-infected B lymphocytes from healthy carriers, a majority generating an abortive EBV lytic cycle and a minority completing the cycle.


1981 ◽  
Vol 153 (2) ◽  
pp. 235-244 ◽  
Author(s):  
J E Robinson ◽  
D Smith ◽  
J Niederman

During the acute phase (1 wk of symptoms or less) of infectious mononucleosis (IM), 70--80% of circulating Epstein-Barr virus nuclear antigen (EBNA)-positive cells have differentiated toward plasma cells. Thus the characteristics of the infected cells in the majority of IM patients during early disease are indistinguishable from EBNA-positive tumor cells of a previously reported child who developed lymphoma during IM. IgA and IgG were the most frequent and IgM the least frequent immunoglobulin isotypes detected in EBNA-positive cells. In acute disease EBNA was present in 5.5--20% of T cell-depleted blood lymphocytes but in the 2nd or 3rd wk of illness the number of EBNA-positive cells sharply decreased to 0.4--1.4%. At the same time the fraction of antigen-positive cells containing cytoplasmic immunoglobulins also diminished, suggesting either that differentiation of infected cells was altered during the disease or that nondifferentiated antigen-positive cells had a survival advantage. Both the high proportion of plasmacytic EBNA-positive cells seen during acute disease and the apparent loss of differentiation by these cells later in disease may be regulated by host immunologic factors. Immunoglobulin-producing EBNA-positive cells may be the source of heterophile antibodies and other seemingly inappropriate antibodies usually found in serum during IM; however, increased numbers of noninfected plasma cells were present in some patients and may also be a potential source of these unusual antibodies.


Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2642-2649 ◽  
Author(s):  
A Osterborg ◽  
M Steinitz ◽  
N Lewin ◽  
S Bergenbrant ◽  
G Holm ◽  
...  

Abstract B-lymphocyte clones bearing an idiotypic Ig structure, which could also be found on the serum M-component, have been isolated from peripheral blood of a patient with monoclonal gammopathy (MG) using an immune- rosetting technique and limiting dilution. The majority of the cells had the surface phenotype id+/CD19+/CD20+/CD21+ or id+/CD19+/CD20+/CD21- . Some of the clones originated from spontaneous outgrowth of lymphocytes and some were derived from in vitro Epstein-Barr virus- infected lymphocytes. Three of the B-lymphocyte clones and the patient's bone marrow plasma cells appeared to have clonal identity as shown by the same Ig heavy chain gene rearrangements in Southern blot analysis using a JH probe. The study further supports the notion that the peripheral blood of patients with MG contains B lymphocytes that belong to the tumor clone.


2020 ◽  
Vol 143 ◽  
pp. 104128
Author(s):  
Charles V. Olivieri ◽  
Hélène Raybaud ◽  
Lilit Tonoyan ◽  
Sarah Abid ◽  
Robert Marsault ◽  
...  

2020 ◽  
Vol 117 (25) ◽  
pp. 14421-14432
Author(s):  
Thomas Sommermann ◽  
Tomoharu Yasuda ◽  
Jonathan Ronen ◽  
Tristan Wirtz ◽  
Timm Weber ◽  
...  

Epstein-Barr virus (EBV) is a B cell transforming virus that causes B cell malignancies under conditions of immune suppression. EBV orchestrates B cell transformation through its latent membrane proteins (LMPs) and Epstein-Barr nuclear antigens (EBNAs). We here identify secondary mutations in mouse B cell lymphomas induced by LMP1, to predict and identify key functions of other EBV genes during transformation. We find aberrant activation of early B cell factor 1 (EBF1) to promote transformation of LMP1-expressing B cells by inhibiting their differentiation to plasma cells. EBV EBNA3A phenocopies EBF1 activities in LMP1-expressing B cells, promoting transformation while inhibiting differentiation. In cells expressing LMP1 together with LMP2A, EBNA3A only promotes lymphomagenesis when the EBNA2 target Myc is also overexpressed. Collectively, our data support a model where proproliferative activities of LMP1, LMP2A, and EBNA2 in combination with EBNA3A-mediated inhibition of terminal plasma cell differentiation critically control EBV-mediated B cell lymphomagenesis.


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