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. 1984 Nov;50(5):587–599. doi: 10.1038/bjc.1984.225

Lymphocytic lymphoma/B-chronic lymphocytic leukaemia--an immunohistopathological study of peripheral B lymphocyte neoplasia.

S H Swerdlow, L J Murray, J A Habeshaw, A G Stansfeld
PMCID: PMC1976971  PMID: 6388614

Abstract

Twenty seven patients with malignant lymphoma of lymphocytic type/B-chronic lymphocytic leukaemia (ML, L/B-CLL, Kiel classification) diagnosed from lymph node and splenectomy specimens were studied histologically and immunologically. Lymph node biopsies showed a diffuse effacement of normal architecture by small round lymphocytes usually with scattered proliferation centres (PC). A1 spleens showed white pulp with or without red pulp involvement, sometimes with tumour nodules present. PC-like cells or PC were only found in the white pulp or tumour nodules. Studies of 13 specimens using the ABC immunoperoxidase technique on frozen sections with a large panel of monoclonal antibodies showed that although a part of the monoclonal B cell neoplasm, the proliferation centres or splenic white pulp have a different phenotype from the surrounding cells. Some of these phenotypic changes are similar to those reported with in vitro induction of "maturation" of ML, L/B-CLL cells. The implications for normal B-cell development are discussed. In contrast to reported peripheral blood findings, T cells, predominantly of T helper phenotype in lymph nodes, were present but usually not numerous.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abramson C. S., Kersey J. H., LeBien T. W. A monoclonal antibody (BA-1) reactive with cells of human B lymphocyte lineage. J Immunol. 1981 Jan;126(1):83–88. [PubMed] [Google Scholar]
  2. Braylan R. C., Jaffe E. S., Burbach J. W., Frank M. M., Johnson R. E., Berard C. W. Similarities of surface characteristics of neoplastic well-differentiated lymphocytes from solid tissues and from peripheral blood. Cancer Res. 1976 May;36(5):1619–1625. [PubMed] [Google Scholar]
  3. Caligaris-Cappio F., Gobbi M., Bofill M., Janossy G. Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia. J Exp Med. 1982 Feb 1;155(2):623–628. doi: 10.1084/jem.155.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Charron D. J., McDevitt H. O. Analysis of HLA-D region-associated molecules with monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6567–6571. doi: 10.1073/pnas.76.12.6567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cherchi M., Catovsky D. Mouse RBC rosettes in chronic lymphocytic leukaemia: different expression in blood and tissues. Clin Exp Immunol. 1980 Feb;39(2):411–415. [PMC free article] [PubMed] [Google Scholar]
  6. Dick F. R., Maca R. D. The lymph node in chronic lymphocytic leukemia. Cancer. 1978 Jan;41(1):283–292. doi: 10.1002/1097-0142(197801)41:1<283::aid-cncr2820410140>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  7. Evans H. L., Butler J. J., Youness E. L. Malignant lymphoma, small lymphocytic type: a clinicopathologic study of 84 cases with suggested criteria for intermediate lymphocytic lymphoma. Cancer. 1978 Apr;41(4):1440–1455. doi: 10.1002/1097-0142(197804)41:4<1440::aid-cncr2820410432>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  8. Fialkow P. J., Najfeld V., Reddy A. L., Singer J., Steinmann L. Chronic lymphocytic leukaemia: Clonal origin in a committed B-lymphocyte progenitor. Lancet. 1978 Aug 26;2(8087):444–446. doi: 10.1016/s0140-6736(78)91444-7. [DOI] [PubMed] [Google Scholar]
  9. Forbes I. J., Zalewski P. D., Valente L., Murray A. W. Loss of receptor activity for mouse erythrocytes precedes tumour promoter-induced maturation of chronic lymphocytic leukaemia cells. Cancer Lett. 1981 Nov;14(2):187–192. doi: 10.1016/0304-3835(81)90129-4. [DOI] [PubMed] [Google Scholar]
  10. Gahrton G., Robèrt K. H., Friberg K., Zech L., Bird A. G. Nonrandom chromosomal aberrations in chronic lymphocytic leukemia revealed by polyclonal B-cell-mitogen stimulation. Blood. 1980 Oct;56(4):640–647. [PubMed] [Google Scholar]
  11. Gathings W. E., Kubagawa H., Cooper M. D. A distinctive pattern of B cell immaturity in perinatal humans. Immunol Rev. 1981;57:107–126. doi: 10.1111/j.1600-065x.1981.tb00444.x. [DOI] [PubMed] [Google Scholar]
  12. Godal T., Funderud S. Human B-cell neoplasms in relation to normal B-cell differentiation and maturation processes. Adv Cancer Res. 1982;36:211–255. doi: 10.1016/s0065-230x(08)60426-1. [DOI] [PubMed] [Google Scholar]
  13. Gordon J., Aman P., Mellstedt H., Biberfeld P., Klein G. In vitro differentiation of chronic lymphocytic leukaemia cells with a small pre-B-like phenotype. Leuk Res. 1983;7(2):133–138. doi: 10.1016/0145-2126(83)90003-6. [DOI] [PubMed] [Google Scholar]
  14. Gordon J., Mellstedt H., Aman P., Biberfeld P., Björkholm M., Klein G. Phenotypes in chronic B-lymphocytic leukemia probed by monoclonal antibodies and immunoglobulin secretion studies: identification of stages of maturation arrest and the relation to clinical findings. Blood. 1983 Oct;62(4):910–917. [PubMed] [Google Scholar]
  15. Greaves M. F., Verbi W., Kemshead J., Kennett R. A monoclonal antibody identifying a cell surface antigen shared by common acute lymphoblastic leukemias and B lineage cells. Blood. 1980 Dec;56(6):1141–1144. [PubMed] [Google Scholar]
  16. Guglielmi P., Preud'homme J. L., Ciorbaru-Barot R., Seligmann M. Mitogen-induced maturation of chronic lymphocytic leukemia B lymphocytes. J Clin Immunol. 1982 Jul;2(3):186–196. doi: 10.1007/BF00915221. [DOI] [PubMed] [Google Scholar]
  17. Guy K., Van Heyningen V., Dewar E., Steel C. M. Enhanced expression of human Ia antigens by chronic lymphocytic leukemia cells following treatment with 12-O-tetradecanoylphorbol-13-acetate. Eur J Immunol. 1983 Feb;13(2):156–159. doi: 10.1002/eji.1830130212. [DOI] [PubMed] [Google Scholar]
  18. Habeshaw J. A., Bailey D., Stansfeld A. G., Greaves M. F. The cellular content of non Hodgkin lymphomas: a comprehensive analysis using monoclonal antibodies and other surface marker techniques. Br J Cancer. 1983 Mar;47(3):327–351. doi: 10.1038/bjc.1983.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Habeshaw J. A., Lister T. A., Stansfeld A. G., Greaves M. F. Correlation of transferrin receptor expression with histological class and outcome in non-Hodgkin lymphoma. Lancet. 1983 Mar 5;1(8323):498–501. doi: 10.1016/s0140-6736(83)92191-8. [DOI] [PubMed] [Google Scholar]
  20. Han T., Ozer H., Bloom M., Sagawa K., Minowada J. The presence of monoclonal cytoplasmic immunoglobulins in leukemic B cells from patients with chronic lymphocytic leukemia. Blood. 1982 Feb;59(2):435–438. [PubMed] [Google Scholar]
  21. Holm G., Mellstedt H., Pettersson D., Biberfeld R. Idiotypic immunoglobulin structures on blood lymphocytes in human plasma cell myeloma. Immunol Rev. 1977;34:139–164. doi: 10.1111/j.1600-065x.1977.tb00371.x. [DOI] [PubMed] [Google Scholar]
  22. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  23. Kay N. E., Howe R. B., Douglas S. D. Effect of therapy on T cell subpopulations in patients with chronic lymphocytic leukemia. Leuk Res. 1982;6(3):345–348. doi: 10.1016/0145-2126(82)90096-0. [DOI] [PubMed] [Google Scholar]
  24. Kersey J. H., LeBien T. W., Abramson C. S., Newman R., Sutherland R., Greaves M. P-24: a human leukemia-associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody. J Exp Med. 1981 Mar 1;153(3):726–731. doi: 10.1084/jem.153.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lukes R. J., Collins R. D. Immunologic characterization of human malignant lymphomas. Cancer. 1974 Oct;34(4 Suppl):suppl–suppl:1503. doi: 10.1002/1097-0142(197410)34:8+<1488::aid-cncr2820340822>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  26. Marti G. E., Kuo M. C., Shaw S., Chang C. C., Demars R., Sogn J. A., Coligan J. E., Kindt T. J. A novel HLA-D/DR-like antigen specific for human B lymphoid cells. Biochemical evidence for similarity to but nonidentity with known HLA-D/DR antigens. J Exp Med. 1983 Dec 1;158(6):1924–1937. doi: 10.1084/jem.158.6.1924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Martin P. J., Hansen J. A., Siadak A. W., Nowinski R. C. Monoclonal antibodies recognizing normal human T lymphocytes and malignant human B lymphocytes: a comparative study. J Immunol. 1981 Nov;127(5):1920–1923. [PubMed] [Google Scholar]
  28. McCubrey J., Risser R. Genetic interactions in the spontaneous production of endogenous murine leukemia virus in low leukemic mouse strains. J Exp Med. 1982 Aug 1;156(2):337–349. doi: 10.1084/jem.156.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mills K. H., Cawley J. C. Suppressor T cells in B-cell chronic lymphocytic leukaemia: relationship to clinical stage. Leuk Res. 1982;6(5):653–657. doi: 10.1016/0145-2126(82)90081-9. [DOI] [PubMed] [Google Scholar]
  30. Murray L. J., Swerdlow S. H., Habeshaw J. A. Distribution of B lymphocyte subsets in normal lymphoid tissue. Clin Exp Immunol. 1984 May;56(2):399–406. [PMC free article] [PubMed] [Google Scholar]
  31. Nadler L. M., Ritz J., Hardy R., Pesando J. M., Schlossman S. F., Stashenko P. A unique cell surface antigen identifying lymphoid malignancies of B cell origin. J Clin Invest. 1981 Jan;67(1):134–140. doi: 10.1172/JCI110005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nanba K., Jaffe E. S., Braylan R. C., Soban E. J., Berard C. W. Alkaline phosphatase-positive malignant lymphoma. A subtype of B-cell lymphomas. Am J Clin Pathol. 1977 Nov;68(5):535–542. doi: 10.1093/ajcp/68.5.535. [DOI] [PubMed] [Google Scholar]
  33. Newell D. G., Harris A. H., Smith J. L. The ultrastructural localization of immunoglobulin in chronic lymphocytic lymphoma cells: changes in light and heavy chain distribution induced by mitogen stimulation. Blood. 1983 Mar;61(3):511–519. [PubMed] [Google Scholar]
  34. Okamura J., Gelfand E. W., Letarte M. Heterogeneity of the response of chronic lymphocytic leukemia cells to phorbol ester. Blood. 1982 Nov;60(5):1082–1088. [PubMed] [Google Scholar]
  35. Papadimitriou C. S., Müller-Hermelink U., Lennert K. Histologic and immunohistochemical findings in the differential diagnosis of chronic lymphocytic leukemia of B-cell type and lymphoplasmacytic/lymphoplasmacytoid lymphoma. Virchows Arch A Pathol Anat Histol. 1979;384(2):149–158. doi: 10.1007/BF00427252. [DOI] [PubMed] [Google Scholar]
  36. Platsoucas C. D., Galinski M., Kempin S., Reich L., Clarkson B., Good R. A. Abnormal T lymphocyte subpopulations in patients with B cell chronic lymphocytic leukemia: an analysis by monoclonal antibodies. J Immunol. 1982 Nov;129(5):2305–2312. [PubMed] [Google Scholar]
  37. Preud'homme J. L., Seligmann M. Surface bound immunoglobulins as a cell marker in human lymphoproliferative diseases. Blood. 1972 Dec;40(6):777–794. [PubMed] [Google Scholar]
  38. Ritz J., Nadler L. M., Bhan A. K., Notis-McConarty J., Pesando J. M., Schlossman S. F. Expression of common acute lymphoblastic leukemia antigen (CALLA) by lymphomas of B-cell and T-cell lineage. Blood. 1981 Sep;58(3):648–652. [PubMed] [Google Scholar]
  39. Semenzato G., Pezzutto A., Agostini C., Albertin M., Gasparotto G. T-lymphocyte subpopulations in chronic lymphocytic leukemia: a quantitative and functional study. Cancer. 1981 Nov 15;48(10):2191–2197. doi: 10.1002/1097-0142(19811115)48:10<2191::aid-cncr2820481013>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  40. Stashenko P., Nadler L. M., Hardy R., Schlossman S. F. Characterization of a human B lymphocyte-specific antigen. J Immunol. 1980 Oct;125(4):1678–1685. [PubMed] [Google Scholar]
  41. Stein H., Bonk A., Tolksdorf G., Lennert K., Rodt H., Gerdes J. Immunohistologic analysis of the organization of normal lymphoid tissue and non-Hodgkin's lymphomas. J Histochem Cytochem. 1980 Aug;28(8):746–760. doi: 10.1177/28.8.7003001. [DOI] [PubMed] [Google Scholar]
  42. Stein H., Gerdes J., Mason D. Y. The normal and malignant germinal centre. Clin Haematol. 1982 Oct;11(3):531–559. [PubMed] [Google Scholar]
  43. Stein H., Staudinger M., Tolksdorf G., Lennert K. Immunologic markers in the differential diagnosis of non-Hodgkin's lymphomas. J Cancer Res Clin Oncol. 1981;101(1):29–42. doi: 10.1007/BF00405061. [DOI] [PubMed] [Google Scholar]
  44. Stevenson F. K., Hamblin T. J., Stevenson G. T. The nature of the immunoglobulin G on the surface of B lymphocytes in chronic lymphocytic leukemia. J Exp Med. 1981 Dec 1;154(6):1965–1969. doi: 10.1084/jem.154.6.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stevenson F. K., Hamblin T. J., Stevenson G. T., Tutt A. L. Extracellular idiotypic immunoglobulin arising from human leukemic B lymphocytes. J Exp Med. 1980 Dec 1;152(6):1484–1496. doi: 10.1084/jem.152.6.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Swerdlow S. H., Habeshaw J. A., Murray L. J., Dhaliwal H. S., Lister T. A., Stansfeld A. G. Centrocytic lymphoma: a distinct clinicopathologic and immunologic entity. A multiparameter study of 18 cases at diagnosis and relapse. Am J Pathol. 1983 Nov;113(2):181–197. [PMC free article] [PubMed] [Google Scholar]
  47. Swerdlow S. H., Murray L. J. Natural killer (Leu 7+) cells in reactive lymphoid tissues and malignant lymphomas. Am J Clin Pathol. 1984 Apr;81(4):459–463. doi: 10.1093/ajcp/81.4.459. [DOI] [PubMed] [Google Scholar]
  48. Tubbs R. R., Fishleder A., Weiss R. A., Savage R. A., Sebek B. A., Weick J. K. Immunohistologic cellular phenotypes of lymphoproliferative disorders. Comprehensive evaluation of 564 cases including 257 non-Hodgkin's lymphomas classified by the International Working Formulation. Am J Pathol. 1983 Nov;113(2):207–221. [PMC free article] [PubMed] [Google Scholar]
  49. Tötterman T. H., Nilsson K., Sundström C. Phorbol ester-induced differentiation of chronic lymphocytic leukaemia cells. Nature. 1980 Nov 13;288(5787):176–178. doi: 10.1038/288176a0. [DOI] [PubMed] [Google Scholar]
  50. Yasuda N., Kanoh T., Shirakawa S., Uchino H. Intracellular immunoglobulin in lymphocytes from patients with chronic lymphocytic leukemia: an immunoelectron microscopic study. Leuk Res. 1982;6(5):659–667. doi: 10.1016/0145-2126(82)90082-0. [DOI] [PubMed] [Google Scholar]
  51. Yunis J. J., Oken M. M., Kaplan M. E., Ensrud K. M., Howe R. R., Theologides A. Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma. N Engl J Med. 1982 Nov 11;307(20):1231–1236. doi: 10.1056/NEJM198211113072002. [DOI] [PubMed] [Google Scholar]

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