scholarly journals Presence of Epstein-Barr virus in extranodal T-cell lymphomas: differences in relation to site

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1612-1618 ◽  
Author(s):  
PC de Bruin ◽  
M Jiwa ◽  
JJ Oudejans ◽  
P van der Valk ◽  
P van Heerde ◽  
...  

T-cell lymphomas with similar morphology but with different sites of origin have a different clinical behavior. The theoretical explanation for this finding originates from the hypothesis that non-Hodgkin's lymphomas (NHLs) are neoplastic equivalents of immunological reactions involving tissue-restricted lymphocytes. This hypothesis also implies that T-NHLs originating from different sites differ in their genesis, and thus may differ in oncogen expression, expression of adhesion molecules, or presence of certain DNA/RNA viral sequences. Therefore, we have investigated in T-cell lymphomas with similar morphology originating from different sites, ie, nose (n = 5; all pleomorphic small- or medium- and large-cell T-cell lymphomas [PTL]), skin (PTL, n = 6; anaplastic large-cell [ALCL], n = 11), gut (PTL, n = 8; ALCL, n = 4), and lung (PTL, n = 6), the presence of Epstein-Barr virus (EBV) at the DNA, RNA (EBER 1 and EBER 2), and protein level (LMP-1). A double- staining technique was used to detect EBER 1/2, LMP-1, and differentiation markers at the single-cell level. High numbers of EBER 1/2-positive tumor cells (> 100 per medium power field [mpf]) were found in five of five nasal T-cell lymphomas, none of 17 primary cutaneous T-cell lymphomas, one of 12 gastrointestinal T-cell lymphomas (ALCL), and two of six pulmonary T-cell lymphomas. These lymphomas are therefore called EBV-associated lymphomas. In contrast to our earlier findings in lymph nodes, no extranodal lymphomas were found, with only a few EBV-positive tumor cells. Five gastrointestinal cases positive for EBV by polymerase chain reaction (PCR) showed that EBER 1/2 was only found in sporadic nonneoplastic, ie, reactive lymphocytes. Angiocentricity was present in 18 PTL and one ALCL, but not associated with the presence of EBV. These results indicate that the presence of EBV in extranodal T-cell lymphomas is site-restricted and argues for a different pathogenesis of T-cell lymphomas with similar morphology but originating from different sites. The presence of EBV in most tumor cells in these EBV-associated lymphomas suggests that when present, EBV might be important in the pathogenesis of these lymphomas.

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1612-1618 ◽  
Author(s):  
PC de Bruin ◽  
M Jiwa ◽  
JJ Oudejans ◽  
P van der Valk ◽  
P van Heerde ◽  
...  

Abstract T-cell lymphomas with similar morphology but with different sites of origin have a different clinical behavior. The theoretical explanation for this finding originates from the hypothesis that non-Hodgkin's lymphomas (NHLs) are neoplastic equivalents of immunological reactions involving tissue-restricted lymphocytes. This hypothesis also implies that T-NHLs originating from different sites differ in their genesis, and thus may differ in oncogen expression, expression of adhesion molecules, or presence of certain DNA/RNA viral sequences. Therefore, we have investigated in T-cell lymphomas with similar morphology originating from different sites, ie, nose (n = 5; all pleomorphic small- or medium- and large-cell T-cell lymphomas [PTL]), skin (PTL, n = 6; anaplastic large-cell [ALCL], n = 11), gut (PTL, n = 8; ALCL, n = 4), and lung (PTL, n = 6), the presence of Epstein-Barr virus (EBV) at the DNA, RNA (EBER 1 and EBER 2), and protein level (LMP-1). A double- staining technique was used to detect EBER 1/2, LMP-1, and differentiation markers at the single-cell level. High numbers of EBER 1/2-positive tumor cells (> 100 per medium power field [mpf]) were found in five of five nasal T-cell lymphomas, none of 17 primary cutaneous T-cell lymphomas, one of 12 gastrointestinal T-cell lymphomas (ALCL), and two of six pulmonary T-cell lymphomas. These lymphomas are therefore called EBV-associated lymphomas. In contrast to our earlier findings in lymph nodes, no extranodal lymphomas were found, with only a few EBV-positive tumor cells. Five gastrointestinal cases positive for EBV by polymerase chain reaction (PCR) showed that EBER 1/2 was only found in sporadic nonneoplastic, ie, reactive lymphocytes. Angiocentricity was present in 18 PTL and one ALCL, but not associated with the presence of EBV. These results indicate that the presence of EBV in extranodal T-cell lymphomas is site-restricted and argues for a different pathogenesis of T-cell lymphomas with similar morphology but originating from different sites. The presence of EBV in most tumor cells in these EBV-associated lymphomas suggests that when present, EBV might be important in the pathogenesis of these lymphomas.


Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2688-2695 ◽  
Author(s):  
P Kanavaros ◽  
MC Lescs ◽  
J Briere ◽  
M Divine ◽  
F Galateau ◽  
...  

Recent evidence has shown that most nasal lymphomas (NL) are associated with a T-cell phenotype and are thus called nasal T-cell lymphomas (NTCL), but little information is available about the T-cell receptor (TCR) expression. The presence of Epstein-Barr virus (EBV) genome has been recently reported in NTCL in Oriental populations in which NL and EBV-associated tumors are more common and in occasional Occidental cases. This prompted us to investigate lymphoma biopsies from 7 non- Oriental patients with NTCL for the expression of natural killer (NK) and T-cell antigens, including TCR proteins, for the presence of EBV- encoded latent membrane protein (LMP) using immunohistochemistry and for the presence of EBV DNA and Epstein-Barr early region (EBER) RNA using in situ hybridization (ISH). Six cases displayed a CD3-, TCR alpha beta-, TCR gamma delta-, CD2+, CD7+, CD5-, CD4-, CD8-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas (PTCL) with extensive loss of T-cell antigens and expression of the NK-cell (CD56) antigen or, alternatively, NK-cell neoplasias. The remaining case was a gamma delta PTCL, as shown by the CD3+, TCR gamma delta+ phenotype and the biallelic gamma and delta TCR gene rearrangements. Using ISH, EBER RNA transcripts were detected in tumor cells in all cases and EBV DNA was shown in the 6 tested cases. In all cases, tumor cells expressed LMP. These findings support the concept that NTCL constitute a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibit an unusual TCR “silent” CD56+ or TCR gamma delta+ phenotype and harbor the EBV. In view of the LMP transforming potential, these data suggest that EBV may play a role in the pathogenesis of NTCL.


Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2688-2695 ◽  
Author(s):  
P Kanavaros ◽  
MC Lescs ◽  
J Briere ◽  
M Divine ◽  
F Galateau ◽  
...  

Abstract Recent evidence has shown that most nasal lymphomas (NL) are associated with a T-cell phenotype and are thus called nasal T-cell lymphomas (NTCL), but little information is available about the T-cell receptor (TCR) expression. The presence of Epstein-Barr virus (EBV) genome has been recently reported in NTCL in Oriental populations in which NL and EBV-associated tumors are more common and in occasional Occidental cases. This prompted us to investigate lymphoma biopsies from 7 non- Oriental patients with NTCL for the expression of natural killer (NK) and T-cell antigens, including TCR proteins, for the presence of EBV- encoded latent membrane protein (LMP) using immunohistochemistry and for the presence of EBV DNA and Epstein-Barr early region (EBER) RNA using in situ hybridization (ISH). Six cases displayed a CD3-, TCR alpha beta-, TCR gamma delta-, CD2+, CD7+, CD5-, CD4-, CD8-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas (PTCL) with extensive loss of T-cell antigens and expression of the NK-cell (CD56) antigen or, alternatively, NK-cell neoplasias. The remaining case was a gamma delta PTCL, as shown by the CD3+, TCR gamma delta+ phenotype and the biallelic gamma and delta TCR gene rearrangements. Using ISH, EBER RNA transcripts were detected in tumor cells in all cases and EBV DNA was shown in the 6 tested cases. In all cases, tumor cells expressed LMP. These findings support the concept that NTCL constitute a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibit an unusual TCR “silent” CD56+ or TCR gamma delta+ phenotype and harbor the EBV. In view of the LMP transforming potential, these data suggest that EBV may play a role in the pathogenesis of NTCL.


2015 ◽  
Vol 9 (1) ◽  
pp. 7-28 ◽  
Author(s):  
Abdelwahid Saeed Ali ◽  
Mubarak Al-Shraim ◽  
Ahmed Musa Al-Hakami ◽  
Ian M Jones

Epstein-Barr virus (EBV) is classified as a member in the orderherpesvirales, familyherpesviridae, subfamilygammaherpesvirinaeand the genuslymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL).In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies


Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4053-4060 ◽  
Author(s):  
K Sandvej ◽  
SC Peh ◽  
BS Andresen ◽  
G Pallesen

In this study, we have sequenced the C-terminal part of the Epstein- Barr virus (EBV)-BNLF-1 gene encoding for the latent membrane protein-1 from tissues of EBV-positive Danish Hodgkin's disease (HD) and of Danish and Malaysian peripheral T-cell lymphomas (PTLs) and from tonsils of Danish infectious mononucleosis (IM). Our study showed that some of the 7 single-base mutations and the 30-bp deletion previously detected between codons of amino acid 322 and 366 in the BNLF-1 gene of the nasopharyngeal carcinoma cell line CAO were present in all Malaysian PTLs and in 60% of the Danish PTLs. In HD and the IM cases, the mutations were present in about 30%. The 30-bp deletion and the single base mutations occurred independently, and mutations were detectable in the majority of EBV type B-positive cases. These findings suggest that the 30-bp deletion and the 7 single-base mutations in the C-terminal part of the CAO-BNLF-1 gene do not characterize a new EBV type A substrain. Rather, some of the positions of single base mutations and the 30-bp deletion are hot spots that may have mutated independently through the evolution of EBV strains.


2011 ◽  
Vol 59 (6) ◽  
pp. 1183-1193 ◽  
Author(s):  
Socorro M Rodríguez-Pinilla ◽  
Carlos Barrionuevo ◽  
Juan García ◽  
María de los Ángeles ◽  
Raquel Pajares ◽  
...  

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