Abstract
The significance of T-cell proliferations in angioimmunoblastic lymphoma (AILD) is still enigmatic. Although classified as a malignant T-cell lymphoma in the World Health Organisation lymphoma classification, some cases of AILD lack dominant T-cell clones. In a previous study, based on single-cell polymerase chain reaction (PCR), we obtained similar results as studies of AILD using Southern blot or conventional PCR: some cases of AILD contained large T-cell clones, and, in other cases, T-cell clones were undetectable. As in single-cell studies, only a limited number of cells could be investigated; thus, we wanted to gain more insight into the amount and distribution of tumour cells. By applying triple immunofluorescent staining with antibodies directed against T-cell receptor Vβ-family-specific epitopes, we investigated T-cell populations in AILD and their localisation in the tissue in relation to B cells (CD20) and follicular dendritic cells (CD21). In two of five cases investigated, only a minority of the T-cells compartment belonged to the tumour clone. Neoplastic T cells were found throughout the tissue, including areas dominated by B cells.
Similar content being viewed by others
References
Bräuninger A, Küppers R, Spieker T, Siebert R, Strickler JG, Schlegelberger B, Rajewsky K, Hansmann ML (1999) Molecular analysis of single B cells from T-cell-rich B-cell lymphoma shows the derivation of the tumor cells from mutating germinal center B cells and exemplifies means by which immunoglobulin genes are modified in germinal center B cells. Blood 8:2679–2687
Bräuninger A, Spieker T, Willenbrock K, Gaulard P, Wacker HH, Rajewsky K, Hansmann ML, Küppers R (2001) Survival and clonal expansion of mutating “forbidden” (immunoglobulin receptor-deficient) Epstein–Barr virus-infected B cells in angioimmunoblastic T cell lymphoma. J Exp Med 7:927–940
Feller AC, Griesser H, Schilling CV, Wacker HH, Dallenbach F, Bartels H, Kuse R, Mak TW, Lennert K (1988) Clonal gene rearrangement patterns correlate with immunophenotype and clinical parameters in patients with angioimmunoblastic lymphadenopathy. Am J Pathol 3:549–556
Foss HD, Anagnostopoulos I, Herbst H, Grebe M, Ziemann K, Hummel M, Stein H (1995) Patterns of cytokine gene expression in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type. Blood 10:2862–2869
Frizzera G, Moran EM, Rappaport H (1974) Angio-immunoblastic lymphadenopathy with dysproteinaemia. Lancet 866:1070–1073
Jaffe ES, Ralfkiaer E (2001) Angioimmunoblastic T-cell lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) Pathology and genetics of tumours of haematopoetic and lymphoid tissues. IARC Press, Lyon, France, pp 225–226
Kanzler H, Küppers R, Hansmann ML, Rajewsky K (1996) Hodgkin and Reed–Sternberg cells in Hodgkin’s disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med 4:1495–1505
Kneba M, Bolz I, Linke B, Bertram J, Rothaupt D, Hiddemann W (1994) Characterization of clone-specific rearrangement T-cell receptor gamma-chain genes in lymphomas and leukemias by the polymerase chain reaction and DNA sequencing. Blood 2:574–581
Knecht H, Schwarze EW, Lennert K (1985) Histological, immunohistological and autopsy findings in lymphogranulomatosis X (including angio-immunoblastic lymphadenopathy). Virchows Arch 1:105–124
Küppers R, Zhao M, Hansmann ML, Rajewsky K (1993) Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J 13:4955–4967
Küppers R, Rajewsky K, Zhao M, Simons G, Laumann R, Fischer R, Hansmann ML (1994) Hodgkin disease: Hodgkin and Reed–Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci U S A 23:10962–10966
Linke B, Bolz I, Fayyazi A, von Hofen M, Pott C, Bertram J, Hiddemann W, Kneba M (1997) Automated high resolution PCR fragment analysis for identification of clonally rearranged immunoglobulin heavy chain genes. Leukemia 7:1055–1062
Lorenzen J, Li G, Zhao-Höhn M, Wintzer C, Fischer R, Hansmann ML (1994) Angioimmunoblastic lymphadenopathy type of T-cell lymphoma and angioimmunoblastic lymphadenopathy: a clinicopathological and molecular biological study of 13 Chinese patients using polymerase chain reaction and paraffin-embedded tissues. Virchows Arch 6:593–600
Lukes RJ, Tindle BH (1975) Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin’s disease. N Engl J Med 1:1–8
O’Connor NT, Crick JA, Wainscoat JS, Gatter KC, Stein H, Falini B, Mason DY (1986) Evidence for monoclonal T lymphocyte proliferation in angioimmunoblastic lymphadenopathy. J Clin Pathol 11:1229–1232
Ohshima KS, Suzumiya J, Kawasaki C, Kanda M, Kikuchi M (2000) Cytoplasmic cytokines in lymphoproliferative disorders: multiple cytokine production in angioimmunoblastic lymphadenopathy with dysproteinemia. Leuk Lymphoma 5–6:541–545
Radaszkiewicz T, Lennert K (1975) Lymphogranulomatosis X (immunoblastic adenopathy): clinical features, treatment and prognosis. Dtsch Med Wochenschr 21:1157–1163
Roers A, Montesinos-Rongen M, Hansmann ML, Rajewsky K, Küppers R (1998) Amplification of TCRbeta gene rearrangements from micromanipulated single cells: T cells rosetting around Hodgkin and Reed-Sternberg cells in Hodgkin’s disease are polyclonal. Eur J Immunol 8:2424–2431
Roers A, Hansmann ML, Rajewsky K, Küppers R (2000) Single-cell PCR analysis of T helper cells in human lymph node germinal centers. Am J Pathol 3:1067–1071
Smith JL, Hodges E, Quin CT, McCarthy KP, Wright DH (2000) Frequent T and B cell oligoclones in histologically and immunophenotypically characterized angioimmunoblastic lymphadenopathy. Am J Pathol 2:661–669
Weiss LM, Strickler JG, Dorfman RF, Horning SJ, Warnke RA, Sklar J (1986) Clonal T-cell populations in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma. Am J Pathol 3:392–397
Willenbrock K, Roers A, Seidl C, Wacker HH, Küppers R, Hansmann ML (2001) Analysis of T-cell Subpopulations in T-cell non-Hodgkin’s lymphoma of angioimmunoblastic lymphadenopathy with dysproteinemia type by single target gene amplification of T cell receptor-beta gene rearrangements. Am J Pathol 5:1851–1857
Acknowledgements
We thank Prof. Dr. med. Reza Parwaresch and Prof. Dr. med. Hans-Heinrich Wacker for contributing tissue of AILD cases, Prof. Dr. rer. nat. Ralf Küppers for helpful discussion and Ekaterini Hadzoglou for excellent technical support. This work was supported by the Deutsche Krebshilfe, Dr. Mildred Scheel Stiftung.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Willenbrock, K., Renné, C., Gaulard, P. et al. In angioimmunoblastic T-cell lymphoma, neoplastic T cells may be a minor cell population. A molecular single-cell and immunohistochemical study. Virchows Arch 446, 15–20 (2005). https://doi.org/10.1007/s00428-004-1114-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-004-1114-1