Virchows Archiv A

, Volume 406, Issue 1, pp 105–124 | Cite as

Histological, immunohistological and autopsy findings in lymphogranulomatosis X (including angio-immunoblastic lymphadenopathy)

  • H. Knecht
  • E. -W. Schwarze
  • K. Lennert


172 cases of lymphogranulomatosis X (LgX) were studied by light microscopy. In 53 cases immunohistological techniques for detecting intracytoplasmic immunoglobulins were applied. In the lymph nodes of all cases the nodal architecture was found to be effaced. Active germinal centres were absent, and there was a generalized, markedly increased proliferation of epithelioid venules. A polymorphic infiltrate was present in all cases. It was dominated by immunoblasts in 14%, by plasma cells in 16%, by epithelioid cells in 23% and by lymphocytes in 6% of the cases. In the remaining 41% of the cases no special type of cell predominated (mixed cell type of LgX). The clusters of clear cells present in some cases with immunoblastic predominance did not stain for intracytoplasmic immunoglobulins; in contrast, the basophilic immunoblasts exhibited a polyclonal Ig pattern. In some of the cases with lymphocytic predominance most of the lymphocytes showed abundant cytoplasm with azurophil granules.

Transformation into malignant lymphoma was proven at autopsy in 5 of 38 cases (13.2%). Malignant transformation (biopsy and autopsy material) was confirmed in a total of 11 of 172 cases (6.4%) and suspected in an additional 7%. Among the malignant lymphomas were one immunologically proven B-immunoblastic lymphoma, one peripheral T cell lymphoma and 5 cases of Hodgkin's disease. An association between LgX and carcinoma was histologically verified in 7 cases. 26 cases with active germinal centres and 11 cases with only locally pronounced vascularization but with histological and cytological changes that were otherwise similar to LgX were designated as hyperimmune reactions (HR). These cases had a significantly better prognosis. Two cases that presented as HR with active germinal centres later developed into LgX. It is suggested that the disappearance of active germinal centres is important in the pathogenesis of LgX. The possibility that this may correspond morphologically to an alteration of different components of the T-cell system is discussed.

Key words

Lymphogranulomatosis X (Angio)-immunoblastic lymphadenopathy Immunohistology Malignant transformation Prognostic factors 


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  1. Bensa J-C, Faure J, Martin H, Sotto J-J, Schaerer R (1976) Levamisole in angioimmunoblastic lymphadenopathy. Lancet 1976/I:1081Google Scholar
  2. Bluming AZ, Cohen HG, Saxon A (1979) Angioimmunoblastic lymphadenopathy with dysproteinemia. A pathogenetic link between physiologic lymphoid proliferation and malignant lymphoma. Am J Med 67:421–428Google Scholar
  3. Bornkamm GW, Stein H, Lennert K, Rüggeberg F, Bartels H, Zur Hausen H (1976) 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 17:177–181Google Scholar
  4. Boros L, Bhaskar AG, D'Souza JP (1981) Monoclonal evolution of angioimmunoblastic lymphadenopathy. Am J Clin Pathol 75:856–860Google Scholar
  5. Brouet J-C, Rabian C, Gisselbrecht C, Flandrin G (1984) Clinical and immunological study of non-Hodgkin T-cell lymphomas (cutaneous and lymphoblastic lymphomas excluded). Br J Haematol 57:315–327Google Scholar
  6. Brynes RK, Chart WC, Spira TJ, Ewing EP, Chandler FW (1983) Morphologic features of the unexplained lymphadenopathy of homosexual man. Lab Invest 48:11AGoogle Scholar
  7. Cibull ML, Seligson GR, Mouradian JA, Fialk MA, Pasmantier M (1978) Immunoblastic lymphadenopathy and adenocarcinoma of the pancreas. A case report. Cancer 42:1883–1885Google Scholar
  8. Congdon CC, Makinodan T (1961) Splenic white pulp alteration after antigen injection: Relation to time of serum antibody production. Am J Pathol 39:697–709Google Scholar
  9. Cullen MH, Stansfeld AG, Oliver RT, Lister TA, Malpas JS (1979) Angioimmunoblastic lymphadenopathy: report of ten cases and review of the literature. QJ Med 48:151–177Google Scholar
  10. De Waele M, Thielemans C, Van Camp BKG (1981) Characterisation of immunoregulatory T cells in EBV-induced infectious mononucleosis by monoclonal antibodies. N Engl J Med 304:460–462Google Scholar
  11. Dorfman RF, Wamke R (1974) Lymphadenopathy simulating the malignant lymphomas. Hum Pathol 5:519–550Google Scholar
  12. Dumont J, Liabeuf A, Henle W, Ferchal F, Feingold N, Kourilsky FM (1979) Anticorps dirigés contre li virus d'Epstein Barr. Etude comparative au cours des lymphosarcomes et des adènopathies angio-immunoblastiques. Bull Cancer (Paris) 66:373–381Google Scholar
  13. Dvoretsky P, Wood GS, Levy R, Warnke RA (1982) T-lymphocyte subsets in follicular lymphomas compared with those in non-neoplastic lymph nodes and tonsils. Hum Pathol 13:618–625Google Scholar
  14. Ellegaard J, Boesen AM (1976) Restoration of defective cellular immunity by Levamisole in a patient with immunoblastic lymphadenopathy. Scand J Haematol 17:36–43Google Scholar
  15. Fisher RI, Jaffe ES, Braylan RC, Andersen JC, Tan HK (1976) Immunoblastic lymphadenopathy. Evolution into a malignant lymphoma with plasmacytoid features. Am J Med 61:553–559Google Scholar
  16. Flandrin G (1978) Angioimmunoblastic lymphadenopathy. Clinical, biologic, and follow-up study of 14 cases. In: Mathé G, Seligmann M, Tubiana M (eds) Lymphoid neoplasias I. Recent results in cancer research, vol 64. Springer, Berlin Heidelberg New York, pp 247–262Google Scholar
  17. Flandrin G, Daniel MT, El Yafi G, Chelloul N (1972) Sarcomatoses ganglionnaires diffuses ä différenciation plasmocytaire avec anémie hémolytique auto-immune. Actualités Hémat 6:25–41Google Scholar
  18. Forster G, Moeschlin S (1954) Extramedulläres, leukämisches Plasmacytom mit Dysproteinämie und erworbener hämolytischer Anämie. Schweiz Med Wochenschr 84:1106–1110Google Scholar
  19. Frizzera G, Moran EM, Rappaport H (1974) Angio-immunoblastic lymphadenopathy with dysproteinaemia. Lancet 1974/I:1070–1073Google Scholar
  20. Frizzera G, Moran EM, Rappaport H (1975) Angio-immunoblastic lymphadenopathy. Diagnosis and clinical course. Am J Med 59:803–818Google Scholar
  21. Gindhart TD, Greenspan JS (1980) Angioimmunoblastic lymphadenopathy with dysproteinemia. Animal model: Preneoplastic lymphoid hyperplasia in autoimmune New Zealand Mice. Am J Pathol 99:805–808Google Scholar
  22. Goedde-Salz E, Schwarze EW, Stein H, Lennert K, Grote W (1981) Cytogenetic findings in T-zone lymphoma. J Cancer Res Clin Oncol 101:81–89Google Scholar
  23. Goedde-Salz E (1983) Über die Bedeutung von Chromosomenaberrationen bei Lymphomen und lymphomähnlichen Erkrankungen. Habilitationsschrift. Universität KielGoogle Scholar
  24. Gottlieb MS, Schroff R, Schanker HM, Weismann JD, Peng DO, Fan T, Wolf RA, Saxon A (1981) Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men. New Engl J Med 305:1425–1430Google Scholar
  25. Guarda LA, Butler JJ, Mansell P, Hersh EM, Reuben J, Newell GR (1983) Lymphadenopathy in homosexual man. Morbid anatomy with clinical and immunologic correlations. Am J Clin Pathol 79:559–568Google Scholar
  26. Habeshaw JA, Catley PF, Stansfeld AG, Brearly RL (1979) Surface phenotyping, histology and the nature of non-Hodgkin lymphoma in 157 patients. Br J Cancer 40:11–34Google Scholar
  27. Hanna MG, Jr (1965) Germinal center changes and plasma cell reaction during the primary immune response. Int Arch Allergy 26:230–251Google Scholar
  28. Hanna MG, Jr Congdon CC, Wust CJ (1966) Effect of antigen dose on lymphatic tissue germinal center changes. Proc Soc Exp Biol Med 121:286–290Google Scholar
  29. Hossfeld DK, Höffgen K, Schmidt CG, Diedrichs H (1976) Chromosome abnormalities in angioimmunoblastic lymphadenopathy. Lancet I:198Google Scholar
  30. Jacobson EB, Caporale LH, Thorbecke GJ (1974) Effect of thymus cell injections on germinal center formation in lymphoid tissues of nude (thymusless) mice. Cell Immunol 13:416–430Google Scholar
  31. Jones DB, Castleden M, Smith JL, Mepham BL, Wright DH (1978) Immunopathology of angioimmunoblastic lymphadenopathy. Br J Cancer 37:1053–1062Google Scholar
  32. Kaneko Y, Larson RA, Variakojis D, Haren JM, Rowley JD (1982) Nonrandom chromosome abnormalities in angioimmunoblastic lymphadenopathy. Blood 60:877–887Google Scholar
  33. Klajman A, Yaretsky A, Schneider M, Holoshitz Y, Shneur A, Griffel B (1981) Angioimmunoblastic lymphadenopathy with paraproteinemia. A T- and B-cell disorder. Cancer 48:2433–2437Google Scholar
  34. Knecht H, Lennert K (1981 a) Vorgeschichte und klinisches Bild der Lymphogranulomatosis X (einschließlich [angio] immunoblastischer Lymphadenopathie) Schweiz Med Woschenchr 111:1108–1121Google Scholar
  35. Knecht H, Lennert K (1981 b) Verlauf, Therapie und maligne Transformation der Lymphogranulomatosis X (einschließlich [angio]immunoblastischer Lymphadenopathie) Schweiz Med Wochenschr 111:1122–1130Google Scholar
  36. Knecht H, Lennert K (1981 c) Ultrastructural findings in lymphogranulomatosis X ([angio]immunoblastic lymphadenopathy). Virchows Arch [Cell Pathol] 37:29–47Google Scholar
  37. Kornfeld H, Vande Stouwe RA, Lange M, Reddy MM, Grieco MH (1982) T-lymphocyte subpopulations in homosexual men. N Engl J Med 307:729–731Google Scholar
  38. Kosmidis PA, Axelrod AR, Palacas C, Stahl M (1978) Angioimmunoblastic lymphadenopathy. A T-cell deficiency. Cancer 42:447–452Google Scholar
  39. Krmpotic E, Georgii A, Thiele J, Stünkel K, Vykoupil KF (1978) Chromosomenuntersuchungen yon Non-Hodgkin-Lymphomen und angioimmunoblastischer Lymphadenopathie. (Abtract) Blut 37:164Google Scholar
  40. Lennert K (1973) Pathologisch-histologische Klassifizierung der malignen Lymphome. In: Stacher A (ed) Leukämien und maligne Lymphome. Urban & Schwarzenberg, München Berlin Wien, pp 181–194Google Scholar
  41. Lennert K (1981) Lymphocytisches Lymphom vom T-Zonentyp: T-Zonenlymphom. In: Lennert K (ed) Histopathologie der Non-Hodgkin-Lymphome (nach der Kiel-Klassifikation). Springer, Berlin Heidelberg New York, pp 41–44Google Scholar
  42. Lennert K, Knecht H (1981) Lymphogranulomatosis X. Einschließlich (angio)immunoblastiche Lymphadenopathie. Dtsch Aerztebl 78:601–605Google Scholar
  43. Lennert K, Knecht H, Burkert M (1979) Vorstadien maligner Lymphome. Verb Dtsch Ges Pathol 63:170–196Google Scholar
  44. Lennert K, Mestdagh J (1968) Lymphogranulomatosen mit konstant hohem Epitheloidzellgehalt. Virchows Arch [Pathol Anat] 344:1–20Google Scholar
  45. Lennert K, Mohri N (1974) Histologische Klassifizierung und Vorkommen des M. Hodgkin. Internist 15:57–65Google Scholar
  46. Lukes RJ, Tindle BH (1975) Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin's disease. N Engl J Med 292:1–8Google Scholar
  47. Lukes RJ, Tindle BH (1978) Immunoblastic lymphadenopathy. A prelymphomatous state of immunoblastic sarcoma. In: Mathé G, Seligmann M, Tubiana M (eds) Lymphoid neoplasias I, Recent results in cancer research, vol. 64. Springer, Berlin Heidelberg New York, pp 241–246Google Scholar
  48. McKenna RW, Parkin J, Gail-Peczalska KJ, Kersey JH, Brunning RD (1977) Ultrastructural, cytochemical, and membrane surface marker characteristics of the atypical lymphocytes in infectious mononucleosis. Blood 50:505–515Google Scholar
  49. Modlin RL, Meyer PR, Hofman FM, Mehlmauer M, Levy NB, Lukes RJ, Parker JW, Ammann J, Conant MA, Rea TH, Taylor CR (1983) T-lymphocyte subsets in lymph nodes from homosexual men. JAMA 250:1302–1305Google Scholar
  50. Moore SB, Harrison EG, Weiland LH (1976) Angioimmunoblastic lymphadenopathy. Mayo Clin Proc 51:273–280Google Scholar
  51. Nathwani BN, Rappaport H, Moran EM, Pangalis GA, Kim H (1978) Malignant lymphoma arising in angio-immunoblastic lymphadenopathy. Cancer 41:578–606Google Scholar
  52. Neiman RS, Dervan P, Haudenschild C, Jaffe R (1978) Angioimmunoblastic lymphadenopathy. An ultrastructural and immunologic study with review of the Literature. Cancer 41:507–518Google Scholar
  53. Noel H, Helbron D, Lennert K (1979) Die epitheloidzellige Lymphogranulomatose (sogenanntes “Lennert's lymphoma”). In: Stacher A, Höcker P (eds) Lymphknotentumoren. Urban & Schwarzenberg, München, pp 40–45Google Scholar
  54. Palutke M, Khilanani P, Weise R (1976) Immunologic and electron microscopic characteristics of a case of immunoblastic lymphadenopathy. Am J Clin Pathol 65:929–941Google Scholar
  55. Pangalis GA, Moran EM, Rappaport H (1978) Blood and bone marrow findings in angioimmunoblastic lymphadenopathy. Blood 51:71–83Google Scholar
  56. Polkowska-Kulesza E, Hyjek E, Wozniak L, Pluzanska A, Krykowski E, Mazurowa A (1981) Observations on angioimmunoblastic lymphodenopathy. Acta Med Pol 22:81–95Google Scholar
  57. Poppema S, Bahn AK, Reinherz EL, McCluskey RT, Schlossmann SF (1981) Distribution of T cell subsets in human lymph nodes. J Exp Med 153:30–41Google Scholar
  58. Radaszkiewicz T, Lennert K (1975) Lymphogranulomatosis X. Klinisches Bild, Therapie und Prognose. Dtsch med Wochenschr 100:1157–1163Google Scholar
  59. Reinherz EL, O'Brien C, Rosenthal P, Schlossmann SF (1980) The cellular basis for viral induced immunodeficiency: Analysis by monoclonal antibodies. J Immunol 125:1269–1274Google Scholar
  60. Reinherz EL, Parkman R, Rappaport J, Rosen FS, Schlossmann SF (1979a) Aberrations of suppressor T cells in human graft-versus-host disease. N Engl J Med 300:1061–1068Google Scholar
  61. Reinherz EL, Rubinstein A, Geha RS, Strelkauskas AJ, Rosen FS, Schlossmann SF (1979a) Abnormalities of immunoregulatory T cells in disorders of immune function. N Engl J Med 301:1018–1022Google Scholar
  62. Rice L, Abramson SL, Laughter AH, Wheeler TM, Twomey JJ (1982) Angioimmunoblastic lymphadenopathy with hypogammaglobulinemia. Possible role of monocyte suppression. Am J Med 72:998–1004Google Scholar
  63. Rubinstein A, Dauber LG (1983) Lymphoma of cytotoxic/suppressor T cell phenotype (T8) following angioimmunoblastic lymphadenopathy. Oncology 40:195–199Google Scholar
  64. Schnaidt U, Vykoupil KF, Thiele J, Georgii A (1980) Angio immunoblastic lymphadenopathy: Histopathology of bone marrow involvement. Virchows Arch [Pathol Anat] 389:369–380Google Scholar
  65. Shimoyama M, Minato K, Saito H, Takenaka T, Watanabe S, Nagatani T, Naruto M (1979) Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma. Jpn J Clin Oncol 9 (Suppl):347–356Google Scholar
  66. Shimoyama M, Tobinai K, Minato K, Watanabe S (1982) Immunoblastic lymphadenopathy (IBL)-like T cell lymphoma. GANN Monogr Cancer Res 28:121–134Google Scholar
  67. Skibin A, Yeremiyahu T, Keynan A, Quastel MR (1980) Immunological studies in angioimmunoblastic lymphadenopathy. Clin Exp Immunol 39:386–394Google Scholar
  68. Stein H, Bonk A, Tolksdorf G, Lennert K, Rodt H, Gerdes J (1980) Immunohistologic analysis of the organisation of normal lymphoid tissue and non-Hodgkin's lymphomas. J Histochem Cytochem 28:746–760Google Scholar
  69. Sternberger LA, Hardy PH, Cuculis JJ, Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333Google Scholar
  70. Suchi T (1974) Atypical lymph node hyperplasia with fatal outcome - a report on the histopathological, immunological and clinical investigations of the cases. Recent Adv RES Res 14:13–34Google Scholar
  71. Thabaut A, Cristau P, Saliou P, Durosoir JL, Larroque D, Roue R, Combemale P, Duriez R (1979) Evolution histologique polymorphe d'une adénopathie angio-immunoblastique. Ann Mé Interne 130:541–545Google Scholar
  72. Tosato G, Magrath J, Koski I, Dooley N, Blaese M (1979) Activation of suppressor T cells during Epstein-Barr-Virus induced infectious mononucleosis. N Engl J Med 301:1133–1137Google Scholar
  73. Tosi P, Auteri A, Cintorino M, Pasini FL, Luzi P (1979) Angioimmunoblastic lymphadenopathy with dysproteinemia complicated by Kaposi's sarcoma. Tumori 65:363–371Google Scholar
  74. Volk SLR, Monteleone PL, Knight WAK (1975) Chromosomes in AILD. N Engl J Med 292:975Google Scholar
  75. Watanabe S, Shimosato Y, Shimoyama M, Minato K, Suzuki M, Abe M, Nagatani T (1980) Adult T cell lymphoma with hypergammaglobulinemia. Cancer 46:2472–2483Google Scholar
  76. Yataganas X, Papadimitriou C, Pangalis G, Loukopoulos D, Fessas P, Papacharalampous N (1977) Angio-immunoblastic lymphadenopathy terminating as Hodgkin's disease. Cancer 39:2183–2189Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • H. Knecht
    • 1
  • E. -W. Schwarze
    • 1
  • K. Lennert
    • 1
  1. 1.Lymph Node Registry, Institute of PathologyChristian Albrecht UniversityKielGermany

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