Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Angio-immunoblastic T cell lymphoma (AILD-TL) rich in large B cells and associated with Epstein–Barr virus infection. A different subtype of AILD-TL?

Leukemia volume 16, pages 2134–2141 (2002)Cite this article

Abstract

We studied eight patients with characteristic features of angio-immunoblastic T cell lymphoma (AILD-TL) associated with more than 25% of large B cells. Polymerase chain reaction (PCR) analysis showed a clonal rearrangement of the T cell receptor (TCR)-gamma chain gene in all cases. One additional case showed a clonal rearrangement of the TCR-beta chain gene by Southern blot hybridization. PCR analysis showed a clonal immunoglobulin rearrangement in three cases presenting with more than 50% of large B cells whereas the other cases had a germline configuration. In 6/8 cases, double-labeling immunohistochemistry and in situ hybridization demonstrated that Epstein–Barr virus (EBV) was mostly present in the large B cells but also detected in some T cells. We further evaluated the frequency of AILD-TL with more than 25% of large B cells in the 106 cases collected by the French GELA group and found an incidence of 18%. The outcome of these patients did not differ significantly from those with less than 25% of B cells. With this approach we confirm the heterogeneity of AILD-TL features and the possible association with a substantial numbers of CD20+, EBV+ large B cells. We propose to denominate these cases as ‘AILD-TL rich in large B cells’ and to consider them as a different entity which can be misdiagnosed as a reactive process or as T cell rich B cell lymphoma.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Frizzera G, Moran E, Rappaport H . Angio-immunoblastic lymphadenopathy with dysproteinemia Lancet 1974 1: 1070–1073

    Article  CAS  PubMed  Google Scholar 

  2. Harris N, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peters C, Falini B, Gatter KC . A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group Blood 1994 84: 1361–1392

    CAS  PubMed  Google Scholar 

  3. Jaffe ES, Harris NL, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J . Classification of lymphoid neoplasms. Lymphomas classification-from controversy to consensus: the REAL and the WHO Ann Oncol 2000 11 (Suppl. 1): 3–10

    Google Scholar 

  4. The Non Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group Classification of Non Hodgkin's Lymphoma Blood 1997 89: 3909–3918

  5. Feller AC, Griesser H, Schiling CV, Wacker HH, Dallenbach F, Bartels H, Kuse R, Mak TW, Lennert K . Clonal gene rearrangement patterns correlate with immunophenotype and clinical parameters in patients with angioimmunoblastic lymphadenopathy Am J Pathol 1988 133: 549–556

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Lipford EH, Smith HR, Pittaluga S, Jaffe ES, Steinberg AD, Cossman J . Clonality of angioimmunoblastic lymphadenopathy and implications for its evolution to malignant lymphoma J Clin Invest 1987 79: 637–642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Weiss L, Strickler JG, Dorfman R, Horning SJ, Warnke R, Sklar J . Clonal T-cell populations in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma Am J Pathol 1986 122: 392–397

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Abruzzo LV, Schmidt K, Weiss LM, Jaffe ES, Medeiros LJ, Sander CA, Raffeld M . B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein–Barr virus Blood 1993 82: 241–246

    CAS  PubMed  Google Scholar 

  9. Matsue K, Itoh M, Tsukuda K, Kokubo T, Hirose Y . Development of Epstein–Barr virus-associated B cell lymphoma after intensive treatment of patients with angioimmunoblastic lymphadenopathy with dysproteinemia Int J Hematol 1998 67: 319–329

    Article  CAS  PubMed  Google Scholar 

  10. Pirker R, Schwarzmeier JD, Radaszkiewicz T, Lenzhofer R, Konrad K, Bettelheim P, Bauer K, Prischl F . B-immunoblastic lymphoma arising in angioimmunoblastic lymphadenopathy Acta Haematol 1986 75: 105–109

    Article  CAS  PubMed  Google Scholar 

  11. Hodges E, Quin CT, Wright DH, Smith JL . Oligoclonal populations of T and B cells in a case of angioimmunoblastic T-cell lymphoma predominantly infiltrated by T cells of the VB5.1 family Mol Pathol 1997 50: 15–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ho JW, Ho FC, Chan AC, Liang RH, Srivastava G . Frequent detection of Epstein–Barr virus-infected B cells in peripheral T-cell lymphomas J Pathol 1998 185: 79–85

    Article  CAS  PubMed  Google Scholar 

  13. Bornkamm GW, Stein H, Lennert K, Ruggeberg F, Bartels H, zur Hausen H . Attempts to demonstrate virus-specific sequences in human tumors. IV. EB viral DNA in European Burkitt lymphoma and immunoblastic lymphadenopathy with excessive plasmacytosis Int J Cancer 1976 17: 177–181

    Article  CAS  PubMed  Google Scholar 

  14. Anagnostopoulos I, Hummel M, Finn T, Tiemann M, Kobjuhn P, Dimmler C, Gatter K, Dallenbach F, Parwaresch MR, Stein H . Heterogeneous Epstein–Barr virus infection patterns in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type Blood 1992 80: 1804–1812

    CAS  PubMed  Google Scholar 

  15. Borisch B, Caioni M, Hurwitz N, Dommann-Scherrer C, Odermatt B, Waelti E, Laeng RH, Kraft R, Laissue J . Epstein–Barr virus subtype distribution in angioimmunoblastic lymphadenopathy Int J Cancer 1993 55: 748–752

    Article  CAS  PubMed  Google Scholar 

  16. Kon S, Sato T, Onodera K, Satoh M, Kikuchi K, Imai S, Osato T . Detection of Epstein–Barr virus DNA and EBV-determined nuclear antigen in angioimmunoblastic lymphadenopathy with dysproteinemia type T-cell lymphoma Pathol Res Pract 1993 189: 1137–1144

    Article  CAS  PubMed  Google Scholar 

  17. Ohshima K, Takeo H, Kikuchi M, Kozuou M, Uike N, Masuda Y, Yoneda S, Takeshita M, Shikata T, Akamastsu M . Heterogeneity of Epstein–Barr virus infection in angioimmunoblastic lymphadenopathy type T-cell lymphoma Histopathology 1994 25: 569–579

    Article  CAS  PubMed  Google Scholar 

  18. Weiss LM, Jaffe ES, Liu X, Chen Y, Shibata D, Medeiros LJ . Detection and localization of Epstein–Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma Blood 1992 79: 1789–1795

    CAS  PubMed  Google Scholar 

  19. Aubin J, Davi F, Nguyen-Salomon F, Leboeuf D, Debert C, Taher M, Valensi F, Canioni D, Brousse N, Varet B . Description of a novel FR1 IgH PCR strategy and its comparison with three other strategies for the detection of clonality in B cell malignancies Leukemia 1995 9: 471–479

    CAS  PubMed  Google Scholar 

  20. Landman-Parker J, Aubin J, Delabesse E, Tabone MD, Adam M, Millien C, Leboeuf D, Buzyn-Veil A, Dollfus C, Leverger G, MacIntyre E . Simplified strategies for minimal residual disease detection in B-cell precursor acute lymphoblastic leukaemia Br J Haematol 1995 95: 281–290

    Article  Google Scholar 

  21. Delabesse E, Burtin ML, Millien C, Madonik A, Arnulf B, Beldjord K, Valensi F, MacIntyre E . Rapid, mutifluorescent TCRγ Vγ and Jγ typing: application to T-cell acute lymphoblastic leukemia and to the detection of minor clonal populations Leukemia 2000 14: 1143–1152

    Article  CAS  PubMed  Google Scholar 

  22. Beishuizen A, Verhoeven MA, Mol EJ, Breit TM, Wolvers-Tettero IL, van Dongen JJ . Detection of immunoglobulin heavy-chain gene rearrangements by Southern blot analysis: recommendations for optimal results Leukemia 1993 7: 2045–2053

    CAS  PubMed  Google Scholar 

  23. Raab-Traub N, Flynn K . The structure of the termini of Epstein–Barr virus as a marker of clonal cellular proliferation Cell 1986 47: 883–889

    Article  CAS  PubMed  Google Scholar 

  24. Gulley ML, Raab-Traub N . Detection of Epstein–Barr virus in human tissues by molecular genetic techniques Arch Pathol Lab Med 1993 117: 1115–1120

    CAS  PubMed  Google Scholar 

  25. Toyonaga B, Yoshikai Y, Vadasz V, Chin B, Mak TW . Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta-chain Proc Natl Acad Sci USA 1985 82: 8624–8628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tunnacliffe A, Kefford R, Milstein C, Forster A, Rabbitts TH . Sequence and evolution of the human T-cell antigen receptor beta-chain genes Proc Natl Acad Sci USA 1985 82: 5068–5072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gisselbrecht C, Gaulard P, Lepage E, Coiffier B, Brière J, Haioun C, Cazals-Haiem D, Booly A, Xerri L, Tilly H, Berger F, Bouhabdallah R, Diebold J . Prognostic significance of T-cell phenotype in aggressive Non-Hodgkin's lymphomas. Groupe d'Etude des Lymphomes de l'Adulte (GELA) Blood 1998 92: 76–82

    CAS  PubMed  Google Scholar 

  28. Frizzera G . Atypical Lymphoproliferative Disorders. In: Knowles DM (ed.) Neoplastic Hematopathology Williams & Wilkins: Baltimore 1992 459–495

    Google Scholar 

  29. Theodorou I, Bigorgne C, Delfau MH, Lahet C, Cochet G, Vidaud M, Raphael M, Gaulard P, Farcet JP . VJ rearrangements of the TCR gamma locus in peripheral T-cell lymphomas: analysis by polymerase chain reaction and denaturing gradient gel electrophoresis J Pathol 1996 178: 303–310

    Article  CAS  PubMed  Google Scholar 

  30. Diss TC, Watts M, Pan LX, Burke M, Linch D, Isaacson PG . The polymerase chain reaction in the demonstration of monoclonality in T cell lymphomas J Clin Pathol 1995 48: 1045–1050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Knecht H, Odermatt BF, Hayoz D, Kuhn L, Bachmann F . Polyclonal rearrangements of the T-cell receptor beta-chain in fatal angioimmunoblastic lymphadenopathy Br J Haematol 1989 73: 491–496

    Article  CAS  PubMed  Google Scholar 

  32. Araki A, Taniguchi M, Mikata A . T cell receptor V beta repertoires of angioimmunoblastic lymphadenopathy-like T-cell lymphoma Leuk Lymphoma 1994 16: 135–140

    Article  CAS  PubMed  Google Scholar 

  33. Sheibani K, Wu A, Ben-Ezra J, Stroup R, Rappaport H, Winberg C . Rearrangement of kappa-chain and T cell receptor beta-chain genes in malignant lymphomas of ‘T-cell’ phenotype Am J Pathol 1987 129: 201–207

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Smith JL, Hodges E, Quin CT, McCarty KP, Wright DH . Frequent T and B cell oligoclones in histologically and immunophenotypically characterized angioimmunoblastic lymphadenopathy Am J Pathol 2000 56: 661–669

    Article  Google Scholar 

  35. Attygalle A, Aljehani R, Diss TC, Munson P, Liu HX, Du MQ, Isaacson PG, Dogan A . Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10 Blood 2002 99: 627–633

    Article  CAS  PubMed  Google Scholar 

  36. Quintanilla-Martinez L, Fend F, Moguel RL, Spilove L, Beaty MW, Kingma DW, Raffeld M, Jaffe ES . Peripheral T-cell lymphoma with Reed–Sternberg-like cells of B-cell phenotype and genotype associated with Epstein–Barr virus infection Am J Surg Pathol 1999 23: 1233–1240

    Article  CAS  PubMed  Google Scholar 

  37. Higgins JPT, van de Rijn M, Jones CD, Zehnder JL, Warnke RA . Peripheral T-cell lymphoma complicated by a proliferation of Large B cells Am J Clin Pathol 2001 114: 236–247

    Article  Google Scholar 

  38. Osborne BM, Butler JJ, Pubgh WC . T-cell-rich B-cell large-cell lymphomas. The value of immunophenotyping on paraffin sections in the identification Am J Surg Pathol 1990 14: 933–938

    Article  CAS  PubMed  Google Scholar 

  39. Abruzzo LV, Griffith LM, Nandedkar M, Aguiera NS, Tanbenberger JK, Raffeld M, Stass SA, Abbondanzo SL, Jaffe ES . Histologically discordant lymphomas with B-cell and T-cell components Am J Clin Pathol 1997 108: 316–323

    Article  CAS  PubMed  Google Scholar 

  40. Hu E, Weiss LM, Warnke R, Sklar J . Non-Hodgkin's lymphoma containing both B and T-cell clones Blood 1987 70: 287–292

    CAS  PubMed  Google Scholar 

  41. Foss HD, Anagnostopoulos L, Herbst H, Grebe M, Zieman K, Hummel M, Stein H . Patterns of cytokine gene expression in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type Blood 1995 85: 2862–2869

    CAS  PubMed  Google Scholar 

  42. Estrov Z, Kurzrock R, Pocsik E, Pathak S, Kantarjian HM, Zipf TF, Harris D, Talpaz M, Aggarwal BB . Lymphotoxin is an autocrine growth factor for Epstein–Barr virus-infected B cell lines J Exp Med 1993 177: 763–774

    Article  CAS  PubMed  Google Scholar 

  43. Kehrl JH, Alvarez-Mon M, Delsing GA, Fauci AS . Lymphotoxin is an important T cell-derived growth factor for human B-cells Science 1987 238: 1144–1146

    Article  CAS  PubMed  Google Scholar 

  44. Hsu SM, Waldron JA Jr, Fink L, King C, Xie SS, Mansouri A, Barlogia B . Pathogenic significance of interleukin-6 in angioimmunoblastic lymphadenopathy-type T-cell lymphoma Hum Pathol 1993 24: 126–131

    Article  CAS  PubMed  Google Scholar 

  45. Yokoi T, Miyawaki T, Yachie A, Kato K, Kasahara Y, Taniguchi N . Epstein–Barr virus immortalized B cells produce IL-6 as an autocrine growth factor Immunology 1990 70: 100–105

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Mamzer-Bruneel MF, Bourquelot P, Hermine O, Legendre C, Kreis H . Treatment and prognosis of post-transplant lymphoproliferative disease Ann Transplant 1997 2: 42–48

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology (EA 219, University Paris V), Hôpital Necker-Enfants Malades, Paris, France

    C Lome-Maldonado, D Canioni, D Damotte & N Brousse

  2. Department of Hematology and CNRS UMR 8603, Hôpital Necker-Enfants Malades, Paris, France

    O Hermine

  3. Department of Hematology Biology, Hôpital Necker-Enfants Malades, Paris, France

    E Delabesse & E Macintyre

  4. Centre Hayem, Hôpital Saint Louis, Paris, France

    E Raffoux

  5. Department of Pathology, Hôpital Henri Mondor, Créteil, France

    P Gaulard

Authors
  1. C Lome-Maldonado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Canioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O Hermine
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Delabesse
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Damotte
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Raffoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Gaulard
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E Macintyre
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N Brousse
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

The French Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lome-Maldonado, C., Canioni, D., Hermine, O. et al. Angio-immunoblastic T cell lymphoma (AILD-TL) rich in large B cells and associated with Epstein–Barr virus infection. A different subtype of AILD-TL?. Leukemia 16, 2134–2141 (2002). https://doi.org/10.1038/sj.leu.2402642

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402642

Keywords

This article is cited by

Search

Advanced search

Quick links