Skip to main content
SpringerLink
Log in
Book cover

Neoplastic Diseases of the Blood pp 71–89Cite as

Histopathology, Morphology and Immunophenotyping of CLL

  • Chapter
  • First Online:

  • 2796 Accesses

Abstract

Chronic lymphocytic leukaemia (CLL) is a low grade lymphoproliferative disorder (LPD) characterized by accumulation of monomorphic small mature lymphocytes in peripheral blood, bone marrow and lymphoid tissues. CLL was recognized as a separate clinical disorder towards the beginning of the twentieth century only, although leukaemia was first described in 1845. Even though in the early part of the century there were several case summaries and some mention about CLL in the text book published by Sir William Osler, The Principles and Practice of Medicine, the first comprehensive clinical reports on 80 patients with CLL were published by Minot and Isaacs in 1924 [1–3]. As with any other types of leukaemia, the diagnosis was initially purely based on morphology and over many years several diagnostic tests were introduced which helped to distinguish the various low grade LPDs with somewhat similar morphological appearance, which were originally all considered to be CLL. Currently the diagnosis of CLL can be made in a majority of patients by morphology and immunophenotyping of peripheral blood, but a minority of patients need an integrated approach including tissue histology and the analysis of chromosome deletions, duplications and translocations to make an accurate diagnosis. The distinction of CLL from other similar LPDs is important prognostically as well as increasingly in targeting specific therapies.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   269.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Osler W. The Principles and practice of medicine designed for the use of practitioners and students of medicine. 7th ed. New York; 1909.

    Google Scholar 

  2. Minot B, Isaacs R. Lymphatic Leukaemia:Age, incidence, duration and benefit derived from irradiation. Boston Med Surg J. 1924;191(1):1–9.

    Article  Google Scholar 

  3. Rai KR. 1 Progress in chronic lymphocytic leukaemia: A historical perspective. Baillière’s Clin Haematol. 1993;6(4):757–65.

    Article  CAS  Google Scholar 

  4. WHO classification of tumours of haematopoietic and lymphoid tissues: International Agency for Research on Cancer. 4th ed. WHO; 2008.

    Google Scholar 

  5. Hallek M, Cheson BD, Catovsky D et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008;111(12):5446.

    Google Scholar 

  6. Marti GE, Rawstron AC, Ghia P, et al. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol. 2005;130(3):325–32.

    Article  PubMed  Google Scholar 

  7. Rozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med. 1995;333(16):1052–7.

    Article  PubMed  CAS  Google Scholar 

  8. Phillips JK, Bass PS, Majumdar G, et al. Renal failure caused by leukaemic infiltration in chronic lymphocytic leukaemia. Br Med J. 1993;46(12):1131.

    CAS  Google Scholar 

  9. Kuse R, Lueb H. Gastrointestinal involvement in patients with chronic lymphocytic leukemia. Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, UK 1997;11:S50.

    Google Scholar 

  10. Garofalo Jr M, Murali R, Halperin I, et al. Chronic lymphocytic leukemia with hypothalamic invasion. Cancer. 2006;64(8):1714–6.

    Article  Google Scholar 

  11. Morrison C, Shah S, Flinn IW. Leptomeningeal involvement in chronic lymphocytic leukemia. Cancer Pract. 2001;6(4):223–8.

    Article  Google Scholar 

  12. Cerroni L, Zenahlik P, Höfler G, et al. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: a clinicopathologic and prognostic study of 42 patients. Am J Surg Pathol. 1996;20(8):1000.

    Article  PubMed  CAS  Google Scholar 

  13. Kaur P, Nazeer T. B-cell chronic lymphocytic leukemi-mall lymphocytic lymphoma presenting in the tonsil: a case report and review of literature. Am J Otolaryngol. 2004;25(2):121–5.

    Article  PubMed  Google Scholar 

  14. Currie JN, Lessell S, Lessell IM, et al. Optic neuropathy in chronic lymphocytic leukemia. Arch Ophthalmol. 1988;106(5):654.

    Article  PubMed  CAS  Google Scholar 

  15. Graff-Baker A, Sosa JA, Roman SA. Primary thyroid lymphoma: a review of recent developments in diagnosis and histology-driven treatment. Curr Opin Oncol. 2010;22(1):17–22.

    Article  PubMed  Google Scholar 

  16. Vega F, Padula A, Valbuena JR, et al. Lymphomas involving the pleura: A clinicopathologic study of 34 cases diagnosed by pleural biopsy. Arch Pathol Lab Med. 2006;130(10):1497–502.

    PubMed  Google Scholar 

  17. Benekli M, Büyükaşık Y, Haznedaroglu IC, Savas MC, Özcebe OE. Chronic lymphocytic leukemia presenting as acute urinary retention due to leukemic in filtration of the prostate. Ann Hematol. 1996;73(3):143–4.

    Article  PubMed  CAS  Google Scholar 

  18. Trisolini R, Agli LL, Poletti V. Bronchiolocentric pulmonary involvement due to chronic lymphocytic leukemia. Haematologica. 2000;85(10):1097.

    PubMed  CAS  Google Scholar 

  19. Assiri AH, Lamba M, Veinot JP. Chronic lymphocytic leukemia involving the coronary arteries with accompanying acute myocardial infarction. Cardiovasc Pathol. 2005;14(6):324–6.

    Article  PubMed  Google Scholar 

  20. The nature of the B lymphocyte in B-chronic lympho… [Blood Cells. 1993]—PubMed result. Available at: http://www.ncbi.nlm.nih.gov/sites/entrez [Accessed April 7, 2010].

  21. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group. J Clin Pathol. 1989;42(6):567.

    Article  PubMed  CAS  Google Scholar 

  22. Coffman RL, Cohn M. The class of surface immunoglobulin on virgin and memory B lymphocytes. J Immunol. 1977;118(5):1806–15.

    PubMed  CAS  Google Scholar 

  23. Kantor A. A new nomenclature for B cells. Immunol Today. 1991;12(11):388.

    Article  PubMed  CAS  Google Scholar 

  24. Dighiero G, Kipps T, Schroeder HW, et al. What is the CLL B-lymphocyte? Leuk Lymph. 1996;22(S2):13–39.

    Article  Google Scholar 

  25. Schena M, Larsson LG, Gottardi D, et al. Growth-and differentiation-associated expression of bcl-2 in B-chronic lymphocytic leukemia cells. Blood. 1992;79(11):2981.

    PubMed  CAS  Google Scholar 

  26. Chiorazzi N, Ferrarini M. B cell chronic lymphocytic leukemia: lessons learned from studies of the B cell antigen receptor. Annu Rev Immunol. 2003;21(1):841–94.

    Article  PubMed  CAS  Google Scholar 

  27. Ghiotto F, Fais F, Valetto A, et al. Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia. J Clin Invest. 2004;113(7):1008–16.

    PubMed  CAS  Google Scholar 

  28. Messmer BT, Albesiano E, Efremov DG, et al. Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J Exp Med. 2004;200(4):519.

    Article  PubMed  CAS  Google Scholar 

  29. Klein U, Tu Y, Stolovitzky GA, et al. Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J Exp Med. 2001;194(11):1625.

    Article  PubMed  CAS  Google Scholar 

  30. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. New Eng J Med. 2005;352(8):804.

    Article  PubMed  CAS  Google Scholar 

  31. Peters O, Thielemans C, Steenssens L, et al. Intracellular inclusion bodies in 14 patients with B cell lymphoproliferative disorders. Br Med J. 1984;37(1):45.

    CAS  Google Scholar 

  32. Djaldetti M. Intracytoplasmic inclusions in the peripheral blood lymphocytes of patients with chronic lymphatic leukemia. Virchows Archiv B Cell Pathol Zell-Pathologie. 1983;42(1):301–5.

    Article  Google Scholar 

  33. Ralfkiaer E, Hou-Jensen K, Geisler C, et al. Cytoplasmic inclusions in lymphocytes of chronic lymphocytic leukaemia. A report of 10 cases. Virchows Archiv A Pathol Anat Histol. 1982;395(2):227.

    Article  CAS  Google Scholar 

  34. Dorion RP, Shaw JH. Intracytoplasmic filamentous inclusions in the peripheral blood of a patient with chronic lymphocytic leukemia. Arch Pathol Lab Med. 2003;127(5):618–20.

    PubMed  Google Scholar 

  35. Den Ottolander GJ, Brederoo P, Schuurman RK, et al. Intracellular immunoglobulin G ‘Pseudocrystals’ in a patient with chronic B-cell leukemia. Cancer. 2006;58(1):43–51.

    Article  Google Scholar 

  36. Matutes E, Oscier D, Garcia-Marco J, et al. Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients. Br J Haematol. 2003;92(2):382–8.

    Article  Google Scholar 

  37. Cordone I, Matutes E, Catovsky D. Monoclonal antibody Ki-67 identifies B and T cells in cycle in chronic lymphocytic leukemia: correlation with disease activity. Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, UK 1992;6(9):902.

    Google Scholar 

  38. Criel A, Wlodarska I, Meeus P, et al. Trisomy 12 is uncommon in typical chronic lymphocytic leukaemias. Br J Haematol. 2008;87(3):523–8.

    Article  Google Scholar 

  39. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848.

    PubMed  CAS  Google Scholar 

  40. Rozman C, Montserrat E, Rodriguez-Fernandez J, et al. Bone marrow histologic pattern—the best single prognostic parameter in chronic lymphocytic leukemia: a multivariate survival analysis of 329 cases. Blood. 1984;64(3):642–8.

    PubMed  CAS  Google Scholar 

  41. Campbell JK, Matthews JP, Seymour JF, Wolf MM, Juneja SK. Optimum trephine length in the assessment of bone marrow involvement in patients with diffuse large cell lymphoma. Ann Oncol. 2003;14(2):273–6.

    Article  PubMed  CAS  Google Scholar 

  42. Bishop PW, McNally K, Harris M. Audit of bone marrow trephines. J Clin Pathol. 1992;45(12):1105–8.

    Article  PubMed  CAS  Google Scholar 

  43. Byrd JC, Flinn IW, Grever MR. Introduction: chronic lymphocytic leukemia. Semin Oncol. 1998;25(1):4–5.

    PubMed  CAS  Google Scholar 

  44. Kipps TJ, Carson DA. Autoantibodies in chronic lymphocytic leukemia and related systemic autoimmune diseases. Blood. 1993;81(10):2475.

    PubMed  CAS  Google Scholar 

  45. Nieto LH, Raya Sanchez JM, Arguelles HA, Brito Barroso ML, Gonzalez BG. A case of chronic lymphocytic leukemia overwhelmed by rapidly progressive idiopathic myelofibrosis. Haematologica. 2000;85(9):973.

    PubMed  CAS  Google Scholar 

  46. Yoo D, Pierce LE, Lessin LS. Acquired pure red cell aplasia ­associated with chronic lymphocytic leukemia. Cancer. 1983;51(5):844–50.

    Article  PubMed  CAS  Google Scholar 

  47. Thiele J, Zirbes TK, Kvasnicka HM, Fischer R. Focal lymphoid aggregates (nodules) in bone marrow biopsies: differentiation between benign hyperplasia and malignant lymphoma—a practical guideline. J Clin Pathol. 1999;52(4):294–300.

    Article  PubMed  CAS  Google Scholar 

  48. Schade U, Bock O, Vornhusen S, et al. Bone marrow infiltration pattern in B-cell chronic lymphocytic leukemia is related to immunoglobulin heavy-chain variable region mutation status and expression of 70-kd [zeta]-associated protein (ZAP-70). Human Pathol. 2006;37(9):1153–61.

    Article  CAS  Google Scholar 

  49. Harris NL. The International Lymphoma Study Group, A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Curr Diagnostic Pathol. 1995;2(1):58–9.

    Article  Google Scholar 

  50. Jaffe ES, Harris NL, Stein H, Vardiman JW. WHO classification. Tumours of haematopoietic and lymphoid tissues. Lyon; 2001.

    Google Scholar 

  51. Moreton P, O’Connor SJ, Blythe D, Hillmen P, Jack AS. The proliferating cells in. CLL have a unique immunophenotype. Blood. 2003;102(1):187a. abstract 652.

    Google Scholar 

  52. Lampert IA, Wotherspoon A, Van Noorden S, Hasserjian RP. High expression of CD23 in the proliferation centers of chronic lymphocytic leukemia in lymph nodes and spleen. Human Pathol. 1999;30(6):648–54.

    Article  CAS  Google Scholar 

  53. Cheuk W, Wong KOY, Wong CSC, Chan JKC. Consistent immunostaining for cyclin D1 can be achieved on a routine basis using a newly available rabbit monoclonal antibody. Am J Surg Pathol. 2004;28(6):801–7.

    Article  PubMed  Google Scholar 

  54. Sschmid C, Isaacson P. Proliferation centres in B-cell malignant lymphoma, lymphocytic (B-CLL): an immunophenotypic study. Histopathology. 1994;24(5):445–51.

    Article  Google Scholar 

  55. Granziero L, Ghia P, Circosta P, et al. Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia. Blood. 2001;97(9):2777–83.

    Article  PubMed  CAS  Google Scholar 

  56. Narang S, Wolf BC, Neiman RS. Malignant lymphoma presenting with prominent splenomegaly a clinicopathologic study with special reference to intermediate cell lymphoma. Cancer. 1985;55(9):1948–57.

    Article  PubMed  CAS  Google Scholar 

  57. Van Krieken J, Feller AC, Te Velde J. The distribution of non-Hodgkin’s lymphoma in the lymphoid compartments of the human spleen. Am J Surg Pathol. 1989;13(9):757.

    Article  PubMed  Google Scholar 

  58. Tsimberidou A, Keating MJ. Richter syndrome. Cancer. 2005;103(2):216–28.

    Article  PubMed  CAS  Google Scholar 

  59. Rossi D, Cerri M, Capello D, et al. Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome. Br J Haematol. 2008;142(2):202–15.

    Article  PubMed  CAS  Google Scholar 

  60. Cherepakhin V, Baird SM, Meisenholder GW, Kipps TJ. Common clonal origin of chronic lymphocytic leukemia and high-grade lymphoma of Richter’s syndrome. Blood. 1993;82(10):3141.

    PubMed  CAS  Google Scholar 

  61. Matolcsy A, Inghirami G, Knowles DM. Molecular genetic demonstration of the diverse evolution of Richter’s syndrome (chronic lymphocytic leukemia and subsequent large cell lymphoma). Blood. 1994;83(5):1363.

    PubMed  CAS  Google Scholar 

  62. Varghese AM, Sayala H, Evans PAS, et al. Development of EBV-associated diffuse large B-cell lymphoma in Waldenstrom macroglobulinemia and mantle cell lymphoma. Leuk Lymph. 2008;49(8):1618–9.

    Article  Google Scholar 

  63. Dojcinov SD, Venkataraman G, Raffeld M, Pittaluga S, Jaffe ES. EBV positive mucocutaneous ulcer—a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol. 2010;34(3):405–17.

    Article  PubMed  Google Scholar 

  64. Mao Z, Quintanilla-Martinez L, Raffeld M, et al. IgVH mutational status and clonality analysis of Richter’s transformation: diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution. Am J Surg Pathol. 2007;31(10):1605.

    Article  PubMed  Google Scholar 

  65. Koziner B, Kempin S, Passe S, et al. Characterization of B-cell leukemias: A tentative immunomorphological scheme. Blood. 1980;56(5):815.

    PubMed  CAS  Google Scholar 

  66. Wang CY, Good RA, Ammirati P, Dymbort G, Evans RL. Identification of a p69, 71 complex expressed on human T cells sharing determinants with B-type chronic lymphatic leukemic cells. J Exp Med. 1980;151(6):1539.

    Article  PubMed  CAS  Google Scholar 

  67. Dillman RO, Beauregard JC, Lea JW, et al. Chronic lymphocytic leukemia and other chronic lymphoid proliferations: surface marker phenotypes and clinical correlations. J Clin Oncol. 1983;1(3):190.

    PubMed  CAS  Google Scholar 

  68. Harwood NE, Batista FD. New insights into the early molecular events underlying B cell activation. Immunity. 2008;28(5):609–19.

    Article  PubMed  CAS  Google Scholar 

  69. Catovsky D, Cherchi M, Brookss D, Bradely J, Zola H. Heterogeneity of B-cell leukemias demonstrated by the monoclonal antibody FMC7. Blood. 1981;58(2):406.

    PubMed  CAS  Google Scholar 

  70. Zola H, Neoh SH, Potter A, et al. Markers of differentiated B cell leukaemia: CD22 antibodies and FMC7 react with different molecules. Dis Markers. 1987;5(4):227.

    PubMed  CAS  Google Scholar 

  71. Serke S, Schwaner I, Yordanova M, Szczepek A, Huhn D. Monoclonal antibody FMC7 detects a conformational epitope on the CD20 molecule: evidence from phenotyping after rituxan therapy and transfectant cell analyses. Cytometry B Clin Cytom. 2001;46(2):98–104.

    Article  CAS  Google Scholar 

  72. Hübl W, Iturraspe J, Braylan RC. FMC7 antigen expression on normal and malignant B-cells can be predicted by expression of CD20. Cytometry B Clin Cytom. 1998;34(2):71–4.

    Article  Google Scholar 

  73. McCarron KF, Hammel JP, Hsi ED. Usefulness of CD79b expression in the diagnosis of B-cell chronic lymphoproliferative disorders. Am J Clin Pathol. 2000;113(6):805–13.

    Article  PubMed  CAS  Google Scholar 

  74. Thompson AA, Talley JA, Do HN, et al. Aberrations of the B-cell receptor B29 (CD79b) gene in chronic lymphocytic leukemia. Blood. 1997;90(4):1387.

    PubMed  CAS  Google Scholar 

  75. Alfarano A, Indraccolo S, Circosta P, et al. An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in B-chronic lymphocytic leukemia. Blood. 1999;93(7):2327.

    PubMed  CAS  Google Scholar 

  76. Bomberger C, Singh-Jairam M, Rodey G, et al. Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors. Blood. 1998;91(7):2588–600.

    PubMed  CAS  Google Scholar 

  77. Bennett F, Rawstron A, Plummer M, et al. B-cell chronic ­lymphocytic leukaemia cells show specific changes in membrane protein expression during different stages of cell cycle. Br J Haematol. 2007;139(4):600–4.

    Article  PubMed  Google Scholar 

  78. Delespesse G, Suter U, Mossalayi D, et al. Expression, structure, and function of the CD23 antigen. Adv Immunol. 1991;49:149–91.

    Article  PubMed  CAS  Google Scholar 

  79. Kolb J, Roman V, Mentz F, et al. Contribution of nitric oxide to the apoptotic process in human B cell chronic lymphocytic leukaemia. Leuk Lymph. 2001;40(3):243.

    Article  CAS  Google Scholar 

  80. Reinisch W, Willheim M, Hilgarth M, et al. Soluble CD23 reliably reflects disease activity in B-cell chronic lymphocytic leukemia. J Clin Oncol. 1994;12(10):2146.

    PubMed  CAS  Google Scholar 

  81. Sarfati M, Bron D, Lagneaux L, et al. Elevation of IgE-binding factors in serum of patients with B cell-derived chronic lymphocytic leukemia. Blood. 1988;71(1):94.

    PubMed  CAS  Google Scholar 

  82. Lampert IA, Wotherspoon A, Van Noorden S, Hasserjian RP. High expression of CD23 in the proliferation centers of chronic lymphocytic leukemia in lymph nodes and spleen. Hum Pathol. 1999;30(6):648–54.

    Article  PubMed  CAS  Google Scholar 

  83. Dyer MJ, Zani VJ, Lu WZ, et al. BCL2 translocations in leukemias of mature B cells. Blood. 1994;83(12):3682.

    PubMed  CAS  Google Scholar 

  84. Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood. 1993;82(6):1820.

    PubMed  CAS  Google Scholar 

  85. Jung G, Eisenmann J, Thiebault S, Henon P. Cell surface CD43 determination improves diagnostic precision in late B-cell diseases. Br J Haematol. 2003;120(3):496–9.

    Article  PubMed  Google Scholar 

  86. Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94(6):1840.

    PubMed  CAS  Google Scholar 

  87. Krober A, Seiler T, Benner A, et al. VH mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood. 2002;100(4):1410.

    PubMed  CAS  Google Scholar 

  88. Ibrahim S, Keating M, Do KA, et al. CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia. Blood. 2001;98(1):181.

    Article  PubMed  CAS  Google Scholar 

  89. Jelinek DF, Tschumper RC, Geyer SM, et al. Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status in relation to clinical outcome for B-chronic lymphocytic leukaemia. Br J Haematol. 2001;115(4):854–61.

    Article  PubMed  CAS  Google Scholar 

  90. Hamblin TJ, Orchard JA, Ibbotson RE, et al. CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood. 2002;99(3):1023.

    Article  PubMed  CAS  Google Scholar 

  91. Matrai Z, Lin K, Dennis M, et al. CD38 expression and Ig VH gene mutation in B-cell chronic lymphocytic leukemia. Blood. 2001;97(6):1902.

    Article  PubMed  CAS  Google Scholar 

  92. Vasconcelos Y, Davi F, Levy V, et al. Binet’s staging system and VH genes are independent but complementary prognostic indicators in chronic lymphocytic leukemia. J Clin Oncol. 2003;21(21):3928.

    Article  PubMed  CAS  Google Scholar 

  93. Ghia P, Guida G, Stella S, et al. The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. Blood. 2003;101(4):1262.

    Article  PubMed  CAS  Google Scholar 

  94. Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. New Engl J Med. 2005;353(17):1793.

    Article  PubMed  CAS  Google Scholar 

  95. Crespo M, Bosch F, Villamor N, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. New Engl J Med. 2003;348(18):1764.

    Article  PubMed  CAS  Google Scholar 

  96. D\ürig J, N\ückel H, Cremer M, et al. ZAP-70 expression is a prognostic factor in chronic lymphocytic leukemia. Leukemia. 2003;17(12):2426–34.

    Article  CAS  Google Scholar 

  97. Rassenti LZ, Huynh L, Toy TL, et al. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. New Engl J Med. 2004;351(9):893.

    Article  PubMed  CAS  Google Scholar 

  98. Piette J, Neel H, Marechal V. Mdm2: keeping p53 under control. Oncogene. 1997;15(9):1001.

    Article  PubMed  CAS  Google Scholar 

  99. Bártek J, Bártková J, Vojtĕsek B, et al. Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene. 1991;6(9):1699–703.

    PubMed  Google Scholar 

  100. Lepelley P, Preudhomme C, Vanrumbeke M, et al. Detection of p53 mutations in hematological malignancies: comparison between immunocytochemistry and DNA analysis. Leukemia. 1994;8(8):1342–9.

    PubMed  CAS  Google Scholar 

  101. Carter A, Lin K, Sherrington PD, Pettitt AR. Detection of p53 dysfunction by flow cytometry in chronic lymphocytic leukaemia. Br J Haematol. 2004;127(4):425–8.

    Article  PubMed  CAS  Google Scholar 

  102. Schlette EJ, Admirand J, Wierda W, et al. p53 expression by immunohistochemistry is an important determinant of survival in patients with chronic lymphocytic leukemia receiving frontline chemo-immunotherapy. Leuk Lymph. 2009;50(10):1597–605.

    Article  CAS  Google Scholar 

  103. Cordone I, Masi S, Mauro FR, et al. p53 expression in B-cell chronic lymphocytic leukemia: a marker of disease progression and poor prognosis. Blood. 1998;91(11):4342.

    PubMed  CAS  Google Scholar 

  104. Matutes E, Owusu-Ankomah K, Morilla R et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, UK 1994;8(10):1640.

    Google Scholar 

  105. Rawstron AC, Villamor N, Ritgen M, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia. 2007;21(5):956–64.

    PubMed  CAS  Google Scholar 

  106. Argatoff LH, Connors JM, Klasa RJ, Horsman DE, Gascoyne RD. Mantle cell lymphoma: a clinicopathologic study of 80 cases. Blood. 1997;89(6):2067.

    PubMed  CAS  Google Scholar 

  107. Cohen PL, Kurtin PJ, Donovan KA, Hanson CA. Bone marrow and peripheral blood involvement in mantle cell lymphoma. Br J Haematol. 1998;101(2):302–10.

    Article  PubMed  CAS  Google Scholar 

  108. Jennings CD, Foon KA. Recent advances in flow cytometry: application to the diagnosis of hematologic malignancy. Blood. 1997;90(8):2863.

    PubMed  CAS  Google Scholar 

  109. Medeiros LJ, Van Krieken JH, Jaffe ES, Raffeld M. Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation. Blood. 1990;76(10):2086.

    PubMed  CAS  Google Scholar 

  110. Williams ME, Westermann CD, Swerdlow SH. Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus. Blood. 1990;76(7):1387.

    PubMed  CAS  Google Scholar 

  111. Palumbo GA, Parrinello N, Fargione G, et al. CD200 expression may help in differential diagnosis between mantle cell lymphoma and B-cell chronic lymphocytic leukemia. Leuk Res. 2009;33(9):1212–6.

    Article  PubMed  CAS  Google Scholar 

  112. Fernàndez V, Salamero O, Espinet B, et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res. 2010;70(4):1408–18.

    Article  PubMed  CAS  Google Scholar 

  113. Mozos A, Royo C, Hartmann E, et al. SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica. 2009;94(11):1555–62.

    Article  PubMed  CAS  Google Scholar 

  114. Galton DAG, Goldman JM, Wiltshaw E, et al. Prolymphocytic leukaemia. Br J Haematol. 2008;27(1):7–23.

    Article  Google Scholar 

  115. Matutes E, Morilla R, Owusu-Ankomah K, Houlihan A, Catovsky D. The immunophenotype of splenic lymphoma with villous ­lymphocytes and its relevance to the differential diagnosis with other B-cell disorders. Blood. 1994;83(6):1558.

    PubMed  CAS  Google Scholar 

  116. Berinstein NL, Reis MD, Ngan BY, et al. Detection of occult lymphoma in the peripheral blood and bone marrow of patients with untreated early-stage and advanced-stage follicular lymphoma. J Clin Oncol. 1993;11(7):1344.

    PubMed  CAS  Google Scholar 

  117. Lambrechts AC, Hupkes PE, Dorssers LC, Van’t Veer MB. Translocation (14; 18)-positive cells are present in the circulation of the majority of patients with localized (stage I and II) follicular non-Hodgkin’s lymphoma. Blood. 1993;82(8):2510.

    PubMed  CAS  Google Scholar 

  118. Medeiros LJ, Carr J. Overview of the role of molecular methods in the diagnosis of malignant lymphomas. Arch Pathol Lab Med. 1999;123(12):1189–207.

    PubMed  CAS  Google Scholar 

  119. Matutes E, Wotherspoon A, Catovsky D. The variant form of hairy-cell leukaemia. Best Pract Res Clin Haematol. 2003;16(1):41–56.

    Article  PubMed  CAS  Google Scholar 

  120. Matutes E. Immunophenotyping and differential diagnosis of hairy cell leukemia. Hematol Oncol Clin North Am. 2006;20(5):1051–63.

    Article  PubMed  Google Scholar 

  121. Gordon DS, Jones BM, Browning SW, Spira TJ, Lawrence DN. Persistent polyclonal lymphocytosis of B lymphocytes. New Engl J Med. 1982;307(4):232.

    Article  PubMed  CAS  Google Scholar 

  122. Mossafa H, Malaure H, Maynadie M, et al. Persistent polyclonal B lymphocytosis with binucleated lymphocytes: a study of 25 cases. Br J Haematol. 2002;104(3):486–93.

    Article  Google Scholar 

  123. Troussard X, Valensi F, Debert C, et al. Persistent polyclonal lymphocytosis with binucleated B lymphocytes: a genetic predisposition. Br J Haematol. 2008;88(2):275–80.

    Article  Google Scholar 

  124. Costello C, Catovsky D, O’Brien M, Galton DAG. Prolymphocytic leukaemia: an ultrastructural study of 22 cases. Br J Haematol. 2008;44(3):389–94.

    Article  Google Scholar 

  125. Ruchlemer R, Parry-Jones N, Brito-Babapulle V, et al. B-prolymphocytic leukaemia with t(11;14) revisited: a splenomegalic form of mantle cell lymphoma evolving with leukaemia. Br J Haematol. 2004;125(3):330–6.

    Article  PubMed  Google Scholar 

  126. Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87(12):4990.

    PubMed  CAS  Google Scholar 

  127. Nieto WG, Almeida J, Romero A, et al. Increased frequency (12%) of circulating CLL-like B-cell clones in healthy individuals using a high-sensitive multicolor flow cytometry approach. Blood. 2009;114:33–7.

    Article  PubMed  CAS  Google Scholar 

  128. Enno A, Catovsky D, O’brien M, et al. ‘Prolymphocytoid’ transformation of chronic lymphocytic leukaemia. Br J Haematol. 2008;41(1):9–18.

    Article  Google Scholar 

  129. Rawstron AC, Bennett FL, O’Connor SJ, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. New Engl J Med. 2008;359(6):575.

    Article  PubMed  CAS  Google Scholar 

  130. Shim YK, Vogt RF, Middleton D, et al. Prevalence and natural history of monoclonal and polyclonal B-cell lymphocytosis in a residential adult population. Cytometry B Clin Cytom. 2007;72(5):344–53.

    PubMed  Google Scholar 

  131. Ghia P, Prato G, Scielzo C, et al. Monoclonal CD5+ and CD5-B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood. 2004;103(6):2337.

    Article  PubMed  CAS  Google Scholar 

  132. Dagklis A, Fazi C, Sala C, et al. The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis is different from CLL: diagnostic implications for clinical monitoring. Blood. 2009;114(1):26–32.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, St. James’s Institute of Oncology, Leeds, LS97TF, UK

    Abraham M. Varghese M.B.B.S., M.R.C.P.

  2. Hematological Malignancy Diagnostic Service, St. James’s Institute of Oncology, Leeds, LS97TF, UK

    Andy C. Rawstron Ph.D., Roger G. Owen M.B.B.Ch., M.R.C.P., F.R.C.Path., M.D. & Peter Hillmen M.B.Ch.B., F.R.C.P., F.R.C.Path, Ph.D.

Authors
  1. Abraham M. Varghese M.B.B.S., M.R.C.P.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andy C. Rawstron Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roger G. Owen M.B.B.Ch., M.R.C.P., F.R.C.Path., M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Hillmen M.B.Ch.B., F.R.C.P., F.R.C.Path, Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abraham M. Varghese M.B.B.S., M.R.C.P. .

Editor information

Editors and Affiliations

  1. Beth Israel Hospital, Cancer Center, St. Lukes-Roosevelt Hospital Center, 10th Avenue 1000, New York, 10019, New York, USA

    Peter H. Wiernik

  2. , Department of Hematology, Imperial College of London, Du Cane Road 150, London, W12 0NN, United Kingdom

    John M. Goldman

  3. Continuum Cancer Centers, Department of Medicine, St. Luke's-Roosevelt Hospital Center, 10th Avenue 1000, New York, 10019, New York, USA

    Janice P. Dutcher

  4. , Division of Hematology, Mayo Clinic, First Street SW. 200, Rochester, 55905, Minnesota, USA

    Robert A. Kyle

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Varghese, A.M., Rawstron, A.C., Owen, R.G., Hillmen, P. (2013). Histopathology, Morphology and Immunophenotyping of CLL. In: Wiernik, P., Goldman, J., Dutcher, J., Kyle, R. (eds) Neoplastic Diseases of the Blood. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3764-2_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-3764-2_7

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3763-5

  • Online ISBN: 978-1-4614-3764-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation