Abstract
Among the 300 peripheral T-cell lymphomas (PTCL) searched for EBV positive non-resting B-cells by EBER in situ hybridization 12 have been identified with various forms of EBV-driven B-cell proliferation. This could be categorized into three major forms. i. In the first form scattered immature, mononuclear B-cells of immuno-, centroblastic type with CD20+. CD30+ CD45+, LMP1+ phenotype, reactive appearance and polyclonal immunoglobulin heavy chains gene rearrangement (IgH-R) were admixed to the PTCL cells. ii. The second form mimicked diffuse large B-cell lymphoma as homogenous sheets, largely demarcated from the PTCL, of mononuclear, immature B-cell of CD20+, CD30+, CD45+, LMP1+, EBNA-2+ phenotype but with lack of monoclonal IgH-R were present. iii. In the third form scattered Hodgkin-Reed-Sternberg (HRS) type of cells were noticed which exhibited the CD15+/−, CD20−/+, CD30+, CD45−, LMP1+, EBNA-2- phenotype and in 50% showed clonal IgH gene rearrangement in whole tissue DNA extract. The IgH associated transcription factors’ (OCT2, BOB.1/OBF.1, PU.1) expression patterns in these cells corresponded to those of HRS cells in cHL. Based on analysis of 65 PTCLs, we have identified in the positive cases a highly significant increase of EBV+ small, reactive, resting B-cell compartment (75.9 / 100 HPF in PTCL vs. 1.5 / 100 HPF in control lymph nodes) likely to be due to the decreased immune surveillance. This progressive accumulation of EBV+ by-stander B-cell population in PTCLs might be the source of various B-cell proliferations, which in any form represent major diagnostic pitfalls and require a careful differential diagnostic procedure.
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Abbreviations
- CDR:
-
complementary determining region
- CHL:
-
classical Hodgkin lymphoma
- DLBCL:
-
diffuse large B-cell lymphoma
- EBER:
-
Epstein Barr early response gene
- EBNA:
-
Epstein Barr nuclear antigen
- EBV:
-
Epstein Barr virus
- FR:
-
framework region
- HPF:
-
high power field
- HRS:
-
Hodgkin Reed Sternberg
- IgH-R:
-
immunoglobulin heavy chain gene rearrangement
- LBC:
-
large B-cell
- LBCR-TCL:
-
large B-cell rich T-cell lymphoma
- LMP-1:
-
latent membrane protein-1
- NOS:
-
not otherwise specified
- PCR:
-
polymerase chain reaction
- PTCL:
-
peripheral T-cell lymphoma
- PTCL-LB:
-
PTCL with proliferation of large B-cells
- TCR-BCL:
-
T-cell rich B-cell lymphoma
- TCR-γ-R:
-
T-cell receptor gamma gene rearrangement
- TF:
-
transcription factor
- TL:
-
T-cell lymphoma
References
Barry ST, Jaffe SE, Sorbara L et al (2003) Peripheral T-cell lymphomas expressing CD30 and CD15. Am J Surg Pathol 27:1513–1521
Quintanilla-Martinez L, Fend F, Rodriguez Moguel L et al (1999) Peripheral T-cell lymphoma with Reed-Sternberg-like cell of B-cell phenotype and genotype associated with Epstein-Barr virus infection. Am J Surg Pathol 23:1233–1240
Pajor L, Kajtár B, Jáksó P et al (2006) Epstein-Barr virus-induced B-cell proliferation of Hodgkin’s and Reed-Sternberg cell pheno- and genotype may develop in peripheral T-cell lymphomas. Histopathology 49:553–557
Ho WYJ, Ho CSF, Chan CLA et al (1998) Frequent detection of Epstein-Barr virus-infected B cells in peripheral T-cell lymphomas. J Pathol 185:79–85
Niedobitek G, Baumann I, Brabletz T et al (2000) Hodgkin’s disease and peripheral T-cell lymphoma: composite lymphoma with evidence of Epstein-Barr virus infection. J Pathol 191:394–399
Zettl A, Lee S-S, Rüdiger T et al (2002) Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Am J Clin Pathol 117:368–379
Tornoczky T, Kelényi G, Pajor L et al (1998) EBER oligonucleotide RNA in situ hybridization in EBV associated neoplasms. Patol Oncol Res 4:201–205
Trainor KJ, Brisco MJ, Wan JH et al (1991) Gene rearrangement in B- and T-lymphoproliferative disease detected by the polymerase chain reaction. Blood 78:192–196
Pajor L, Matolcsy A, Vass JA et al (1998) Phenotypic and genotypic analyses of blastic cell population suggest that pure B-lymphoblastic leukaemia may arise from myelodysplastic syndrome. Leuk Res 22:13–17
Higgins PTJ, Rijn M, Jones DC et al (2000) Peripheral T-cell lymphoma complicated by a proliferation of large B cells. Am J Clin Pathol 114:236–247
Reichard KK, Schwartz JE, Higgins PJ et al (2006) CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells. Modern Pathol 19:337–343
Thorley-Lawson AD, Gross A (2004) Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med 350:1328–1337
Klein E (2004) Non-proliferative interactions of Epstein-Barr virus and human B lymphocytes. Fiola Biol-Prague 50:131–135
Amon W, Farrell JP (2005) Reactivation of Epstein-Barr virus from latency. Rev Med Virol 15:149–156
Atayar C, Poppema S, Blokzijl T et al (2005) Expression of the T-cell transciption factors, GATA-3 and T-bet, in the neoplastic cells of Hodgkin lymphomas. Am J Pathol 166:127–134
McCune CR, Syrbu IS, Vasef AM (2006) Expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB.1, and PU.1 in Hodgkin’s and non-Hodgkin’s lymphomas: a comparative study using high throughput tissue microarrays. Modern Pathol 19:1010–1018
Korbjuhn P, Anagnostopoulos I, Hummel M et al (1993) Frequent latent Epstein-Barr virus infection of neoplastic T cells and Bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas. Blood 82:217–223
Suwiwat S, Pradutkanchana J, Ishida T et al (2007) Quantitative analysis of cell-free Epstein-Barr virus DNA in the plasma of patients with peripheral T-cell and NK-cell lymphomas and peripheral T-cell proliferative diseases. J Clin Virol 40:277–283
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This work was supported by the grant 268/2006 sponsored by the Hungarian Scientific Council of Health (ETT).
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Smuk, G., Illés, Á., Keresztes, K. et al. Pheno- and Genotypic Features of Epstein-Barr Virus Associated B-Cell Lymphoproliferations in Peripheral T-Cell Lymphomas. Pathol. Oncol. Res. 16, 377–383 (2010). https://doi.org/10.1007/s12253-009-9233-2
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DOI: https://doi.org/10.1007/s12253-009-9233-2