Best Practice & Research Clinical Haematology
Volume 19, Issue 3 , Pages 413-437 , September 2006

Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: A forgotten pearl

  • J. Thiele, Dr med. (Professor)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +49 0221 4785008; Fax: +49 0221 4786360.
    • ,
  • H.M. Kvasnicka, Dr med. (Assistant Professor)

References 

  1. Dickstein JI, Vardiman JW. Hematopathologic findings in the myeloproliferative disorders. Seminars in Oncology. 1995;22:355–373
  2. Vardiman JW, Pierre R, Thiele J & Imbert M. Chronic myeloproliferative disorders. In Jaffe ES, Harris NL, Stein H& Vardiman JW (eds) WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues., pp 16-59. Lyon: IARC Press, 2001.
  3. Georgii T, Vykoupil KF, Buhr T, Choritz H. myeloproliferative disorders in bone marrow biopsies. Pathology, Research and Practice. 1990;186:3–27
  4. Buhr T, Choritz H, Georgii A. The impact of megakaryocyte proliferation of the evolution of myelofibrosis. Histological follow-up study in 186 patients with chronic myeloid leukaemia. Virchows Archiv A Pathology Anatomy Histopathology. 1992;420:473–478
  5. Bartl R, Frisch B, Wilmanns W. Potential of bone marrow biopsy in chronic myeloproliferative disorders (MPD). European Journal of Haematology. 1993;50:41–52
  6. Dickstein JI, Vardiman JW. Issues in the pathology and diagnosis of the chronic myeloproliferative disorders and the myelodysplastic syndromes. American Journal of Clinical Pathology. 1993;99:513–525
  7. Georgii A, Buesche G, Kreft A. The histopathology of chronic myeloproliferative diseases. Baillieres Clinical Haematology. 1998;11:721–749
  8. Thiele J, Kvasnicka HM, Fischer R. Histochemistry and morphometry on bone marrow biopsies in chronic myeloproliferative disorders - aids to diagnosis and classification. Annals of Hematology. 1999;78:495–506
  9. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Zirbes TK, et al. Bone marrow features and clinical findings in chronic myeloid leukemia-a comparative, multicenter, immunohistological and morphometric study on 614 patients. Leukemia & Lymphoma. 2000;36:295–308
  10. Buesche G, Hehlmann R, Hecker H, Heimpel H, et al. Marrow fibrosis, indicator of therapy failure in chronic myeloid leukemia - prospective long-term results from a randomized-controlled trial. Leukemia. 2003;17:2444–2453
  11. Sokal JE, Sheerin KA. Decreased stainable marrow iron in chronic granulocytic leukemia. The American Journal of Medicine. 1986;81:395–399
  12. Hayhoe FG, Flemans RJ, Cowling DC. Acquired lipidosis of marrow macrophages: birefringent blue crystals and Gaucher-like cells, sea-blue histiocytes, and grey-green crystals. Journal of Clinical Pathology. 1979;32:420–428
  13. Kelsey PR, Geary CG. Sea-blue histiocytes and Gaucher cells in bone marrow of patients with chronic myeloid leukaemia. Journal of Clinical Pathology. 1988;41:960–962
  14. Schmid C, Frisch B, Beham A, Jager K, et al. Comparison of bone marrow histology in early chronic granulocytic leukemia and in leukemoid reaction. European Journal of Haematology. 1990;44:154–158
  15. Thiele J, Kvasnicka HM, Fischer R. Bone marrow histopathology in chronic myelogenous leukemia (CML)–evaluation of distinctive features with clinical impact. Histology and Histopathology. 1999;14:1241–1256
  16. Lazzarino M, Morra E, Castello A, Inverardi D, et al. Myelofibrosis in chronic granulocytic leukaemia: clinicopathologic correlations and prognostic significance. British Journal of Haematology. 1986;64:227–240
  17. Dekmezian R, Kantarjian HM, Keating MJ, Talpaz M, et al. The relevance of reticulin stain-measured fibrosis at diagnosis in chronic myelogenous leukemia. Cancer. 1987;59:1739–1743
  18. Kvasnicka HM, Thiele J, Schmitt-Graeff A, Diehl V, et al. Prognostic impact of bone marrow erythropoietic precursor cells and myelofibrosis at diagnosis of Ph1+ chronic myelogenous leukaemia-a multicentre study on 495 patients. British Journal of Haematology. 2001;112:727–739
  19. Wilhelm M, Bueso-Ramos C, O'Brien S, Pierce S, et al. Effect of interferon-alpha therapy on bone marrow fibrosis in chronic myelogenous leukemia. Leukemia. 1998;12:65–70
  20. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Spohr M, et al. Effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukaemia: a comparative retrospective multicentre histological and clinical study. British Journal of Haematology. 2000;108:64–71
  21. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Bundschuh S, et al. Effects of chemotherapy (busulfan-hydroxyurea) and interferon-alfa on bone marrow morphologic features in chronic myelogenous leukemia. Histochemical and morphometric study on sequential trephine biopsy specimens with special emphasis on dynamic features. American Journal of Clinical Pathology. 2000;114:57–65
  22. Kvasnicka HM, Thiele J, Schmitt-Graeff A, Diehl V, et al. Bone marrow features improve prognostic efficiency in multivariate risk classification of chronic-phase Ph1+ chronic myelogenous leukemia: a multicenter trial. Journal of Clinical Oncology 2001; 19: 2994-3009.
  23. Thiele J, Kvasnicka HM, Niederle N, Zirbes TK, et al. The impact of interferon versus busulfan therapy on the reticulin stain-measured fibrosis in CML-a comparative morphometric study on sequential trephine biopsies. Annals of Hematology. 1995;70:121–128
  24. Straetmans N, Ma DD, Nevell DF, Arthur C. Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy. Hematopathology and Molecular Hematology. 1996;10:213–222
  25. Sacchi S. The role of alpha-interferon in essential thrombocythaemia, polycythaemia vera and myelofibrosis with myeloid metaplasia (MMM): a concise update. Leukemia & Lymphoma. 1995;19:13–20
  26. Bachleitner-Hofmann T & Gisslinger H. The role of interferon-alpha in the treatment of idiopathic myelofibrosis. Annals of Hematology 1999; 78: 533-538.
  27. Kreft A, Nolde C, Busche G, Buhr T, et al. Polycythaemia vera: bone marrow histopathology under treatment with interferon, hydroxyurea and busulphan. European Journal of Haematology. 2000;64:32–41
  28. Beham-Schmid C, Apfelbeck U, Sill H, Tsybrovsky O, et al. Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis. Blood. 2002;99:381–383
  29. Hasserjian RP, Boecklin F, Parker S, Chase A, et al. ST1571 (imatinib mesylate) reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response. American Journal of Clinical Pathology. 2002;117:360–367
  30. Bueso-Ramos CE, Cortes J, Talpaz M, O'Brien S, et al. Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia. Cancer. 2004;101:332–336
  31. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Kriener S, et al. Effects of the tyrosine kinase inhibitor Imatinib mesylate (STI571) on bone marrow features in patients with chronic myelogenous leukemia. Histology and Histopathology. 2004;19:1277–1288
  32. Kvasnicka HM, Thiele J, Staib P, Schmitt-Graeff A, et al. Reversal of bone marrow angiogenesis in chronic myeloid leukemia following imatinib mesylate (STI571) therapy. Blood. 2004;103:3549–3551
  33. Kvasnicka HM, Thiele J, Schmitt-Graeff A, Diehl V, et al. Impact of bone marrow morphology on multivariate risk classification in chronic myelogenous leukemia. Acta Haematologica 2003; 109: 53-56.
  34. Thiele J, Kvasnicka HM, Beelen DW, Zirbes TK, et al. Relevance and dynamics of myelofibrosis regarding hematopoietic reconstitution after allogeneic bone marrow transplantation in chronic myelogenous leukemia-a single center experience on 160 patients. Bone Marrow Transplantation. 2000;26:275–281
  35. Pearson TC. Diagnosis and classification of erythrocytoses and thrombocytoses. Baillieres Clinical Haematology. 1998;11:695–720
  36. Pierre R, Imbert M, Thiele J, Vardiman JW, et al. Polycythaemia vera. In Jaffe ES, Harris NL, Stein H& Vardiman JW (eds) WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues., pp 32-38. Lyon: IARC Press, 2001.
  37. Spivak JL. Polycythemia vera: myths, mechanisms, and management. Blood. 2002;100:4272–4290
  38. Najean Y, Triebel F, Dresch C. Pure erythrocytosis: reappraisal of a study of 51 cases. American Journal of Hematology. 1981;10:129–136
  39. Westwood N, Dudley JM, Sawyer B, Messinezy M, et al. Primary polycythaemia: diagnosis by non-conventional positive criteria. European Journal of Haematology. 1993;51:228–232
  40. Messinezy M, Sawyer B, Westwood NB, Pearson TC. Idiopathic erythrocytosis–additional new study techniques suggest a heterogenous group. European Journal of Haematology. 1994;53:163–167
  41. Ruggeri M, Tosetto A, Frezzato M, Rodeghiero F. The rate of progression to polycythemia vera or essential thrombocythemia in patients with erythrocytosis or thrombocytosis. Annals of Internal Medicine. 2003;139:470–475
  42. Gruppo Italiano Studio Policitemia. Polycythemia vera: the natural history of 1213 patients followed for 20 years. Annals of Internal Medicine 1995; 123: 656-664.
  43. Ellis JT, Peterson P, Geller SA, Rappaport H. Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies. Seminars in Hematology. 1986;23:144–155
  44. Najean Y, Dresch C, Rain JD. The very-long-term course of polycythaemia: a complement to the previously published data of the Polycythaemia Vera Study Group. British Journal of Haematology. 1994;86:233–235
  45. Bilgrami S & Greenberg BR. Polycythemia rubra vera. Seminars in Oncology 1995; 22: 307-326.
  46. Passamonti F, Malabarba L, Orlandi E, Barate C, et al. Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia. Haematologica. 2003;88:13–18
  47. Georgii A, Buhr T, Buesche G, Kreft A, et al. Classification and staging of Ph-negative myeloproliferative disorders by histopathology from bone marrow biopsies. Leukemia & Lymphoma. 1996;22(Suppl 1):15–29
  48. Thiele J, Kvasnicka HM, Muehlhausen K, Walter S, et al. Polycythemia rubra vera versus secondary polycythemias. A clinicopathological evaluation of distinctive features in 199 patients. Pathology, Research and Practice. 2001;197:77–84
  49. Michiels JJ, Thiele J. Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). International Journal of Hematology. 2002;76:133–145
  50. Thiele J, Kvasnicka HM. Diagnostic impact of bone marrow histopathology in polycythemia vera (PV). Histology and Histopathology. 2005;20:317–328
  51. Ellis JT, Silver RT, Coleman M, Geller SA. The bone marrow in polycythemia vera. Seminars in Hematology. 1975;12:433–444
  52. Ellis JT, Peterson P. The bone marrow in polycythemia vera. Pathology Annual. 1979;14(Pt 1):383–403
  53. Thiele J, Kvasnicka HM, Zankovich R, Diehl V. The value of bone marrow histology in differentiating between early stage polycythemia vera and secondary (reactive) polycythemias. Haematologica. 2001;86:368–374
  54. Thiele J, Schneider G, Hoeppner B, Wienhold S, et al. Histomorphometry of bone marrow biopsies in chronic myeloproliferative disorders with associated thrombocytosis-features of significance for the diagnosis of primary (essential) thrombocythaemia. Virchows Archiv A Pathology Anatomy Histopathology. 1988;413:407–417
  55. Buhr T, Georgii A, Schuppan O, Amor A, et al. Histologic findings in bone marrow biopsies of patients with thrombocythemic cell counts. Annals of Hematology. 1992;64:286–291
  56. Thiele J, Kvasnicka HM, Diehl V, Fischer R, et al. Clinicopathological diagnosis and differential criteria of thrombocythemias in various myeloproliferative disorders by histopathology, histochemistry and immunostaining from bone marrow biopsies. Leukemia & Lymphoma. 1999;33:207–218
  57. Thiele J, Kvasnicka HM & Diehl V. Standardization of bone marrow features - does it work in hematopathology for histological discrimination of different disease patterns? Histology and Histopathology 2005: 90: 1129–1133.
  58. Shih LY, Lee CT. Identification of masked polycythemia vera from patients with idiopathic marked thrombocytosis by endogenous erythroid colony assay. Blood. 1994;83:744–748
  59. Jantunen R, Juvonen E, Ikkala E, Oksanen K, et al. Development of erythrocytosis in the course of essential thrombocythemia. Annals of Hematology. 1999;78:219–222
  60. Murphy S, Peterson P, Iland H, Laszlo J. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Seminars in Hematology. 1997;34:29–39
  61. Laszlo J. Myeloproliferative disorders (MPD): myelofibrosis, myelosclerosis, extramedullary hematopoiesis, undifferentiated MPD, and hemorrhagic thrombocythemia. Seminars in Hematology. 1975;12:409–432
  62. Wolf BC, Neiman RS. Myelofibrosis with myeloid metaplasia: pathophysiologic implications of the correlation between bone marrow changes and progression of splenomegaly. Blood. 1985;65:803–809
  63. Buhr T, Georgii A, Choritz H. Myelofibrosis in chronic myeloproliferative disorders. Incidence among subtypes according to the Hannover Classification. Pathology, Research and Practice. 1993;189:121–132
  64. Barosi G. Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. Journal of Clinical Oncology. 1999;17:2954–2970
  65. Tefferi A. Myelofibrosis with myeloid metaplasia. The New England Journal of Medicine. 2000;342:1255–1265
  66. Dingli D, Mesa RA, Tefferi A. Myelofibrosis with myeloid metaplasia: new developments in pathogenesis and treatment. Internal Medicine. 2004;43:540–547
  67. Thiele J, Zankovich R, Steinberg T, Fischer R, et al. Agnogenic myeloid metaplasia (AMM) - correlation of bone marrow lesions with laboratory data: a longitudinal clinicopathological study on 114 patients. Hematological Oncology. 1989;7:327–343
  68. Thiele J, Kvasnicka HM, Boeltken B, Zankovich R, et al. Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF) - a clinicopathological study. Leukemia. 1999;13:1741–1748
  69. Thiele J & Kvasnicka HM. Prefibrotic chronic idiopathic myelofibrosis-a diagnostic enigma? Acta Haematologica 2004; 111: 155-159.
  70. Buhr T, Buesche G, Choritz H, Langer F, et al. Evolution of myelofibrosis in chronic idiopathic myelofibrosis as evidenced in sequential bone marrow biopsy specimens. American Journal of Clinical Pathology. 2003;119:152–158
  71. Thiele J, Kvasnicka HM, Schmitt-Gräff A, Diehl V. Dynamics of fibrosis in chronic idiopathic (primary) myelofibrosis during therapy: a follow-up study on 309 patients. Leukemia & Lymphoma. 2003;44:549–553
  72. Thiele J, Kvasnicka HM, Facchetti F, Franco V et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 2005; 90: 1128–1132.
  73. Thiele J, Hoeppner B, Zankovich R, Fischer R. Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia)-correlations between clinical and morphological features. Virchows Archiv A Pathology Anatomy Histopathology. 1989;415:191–202
  74. Thiele J, Imbert M, Pierre R, Vardiman JW, et al. Chronic idiopathic myelofibrosis. In Jaffe ES, Harris NL, Stein H& Vardiman JW (eds) WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues., pp 35-38. Lyon: IARC Press, 2001.
  75. Kreft A, Buche G, Ghalibafian M, Buhr T et al. The incidence of myelofibrosis in essential thrombocytaemia vera and chronic idiopathic myelofibrosis: a restrospective of evaluation of sequential bone marrow biopsies. Acta Haematol 2005; 113: 137–143.
  76. Cervantes F, Barosi G, Demory JL, Reilly J, et al. Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. British Journal of Haematology. 1998;102:684–690
  77. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Diehl V. Bone marrow histopathology following cytoreductive therapy in chronic idiopathic myelofibrosis. Histopathology. 2003;43:470–479
  78. Thiele J, Rompcik V, Wagner S, Fischer R. Vascular architecture and collagen type IV in primary myelofibrosis and polycythaemia vera: an immunomorphometric study on trephine biopsies of the bone marrow. British Journal of Haematology. 1992;80:227–234
  79. Kvasnicka HM, Thiele J. Bone marrow angiogenesis: methods of quantification and changes evolving in chronic myeloproliferative disorders. Histology and Histopathology. 2004;19:1245–1260
  80. Mesa RA, Hanson CA, Rajkumar SV, Schroeder G, et al. Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia. Blood. 2000;96:3374–3380
  81. Arora B, Ho CL, Hoyer JD, Mesa RA, et al. Bone marrow angiogenesis and its clinical correlates in myelofibrosis with myeloid metaplasia. Haematologica. 2004;89:1454–1458
  82. Van Dyke D, Parker H, Anger HO, McRae J, et al. Markedly increased bone blood flow in myelofibrosis. Journal of Nuclear Medicine. 1971;12:506–512
  83. Lundberg LG, Lerner R, Sundelin P, Rogers R, et al. Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity. American Journal of Pathology. 2000;157:15–19
  84. Visani G, Finelli C, Castelli U, Petti MC, et al. Myelofibrosis with myeloid metaplasia: clinical and haematological parameters predicting survival in a series of 133 patients. British Journal of Haematology 1990; 75: 4-9.
  85. Rupoli S, Da Lio L, Sisti S, Campanati G, et al. Primary myelofibrosis: a detailed statistical analysis of the clinicopathological variables influencing survival. Annals of Hematology. 1994;68:205–212
  86. Dupriez B, Morel P, Demory JL, Lai JL, et al. Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood. 1996;88:1013–1018
  87. Reilly JT. Idiopathic myelofibrosis: pathogenesis, natural history and management. Blood Reviews. 1997;11:233–242
  88. Kvasnicka HM, Thiele J, Werden C, Zankovich R, et al. Prognostic factors in idiopathic (primary) osteomyelofibrosis. Cancer. 1997;80:708–719
  89. Kvasnicka HM, Thiele J, Regn C, Zankovich R, et al. Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis. Annals of Hematology. 1999;78:65–72
  90. Thiele J & Kvasnicka HM. Diagnostic differentiation of essential thrombocythaemia from thrombocythaemias associated with chronic idiopathic myelofibrosis by discriminate analysis of bone marrow features-a clinicopathological study on 272 patients. Histology and Histopathology 2003; 18: 93-102.
  91. Thiele J, Kvasnicka HM, Zankovich R & Diehl V. Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis. Haematologica 2000; 85: 1126-1134.
  92. Thiele J & Kvasnicka HM. Chronic myeloproliferative disorders with thrombocythemia: a comparative study of two classification systems (PVSG, WHO) on 839 patients. Annals of Hematology 2003; 82: 148-152.
  93. Imbert M, Pierre R, Thiele J, Vardiman JW, et al. Essential thrombocythaemia. In Jaffe ES, Harris NL, Stein H& Vardiman JW (eds) WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues., pp 39–41. Lyon: IARC Press, 2001.
  94. Florena AM, Tripodo C, Iannitto E, Porcasi R, et al. Value of bone marrow biopsy in the diagnosis of essential thrombocythemia. Haematologica. 2004;89:911–919
  95. Annaloro C, Lambertenghi Deliliers G, Oriani A, Pozzoli E, et al. Prognostic significance of bone marrow biopsy in essential thrombocythemia. Haematologica. 1999;84:17–21
  96. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Zankovich R, et al. Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients. American Journal of Hematology. 2002;70:283–291
  97. Cervantes F, Alvarez-Larran A, Talarn C, Gomez M, et al. Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. British Journal of Haematology. 2002;118:786–790
  98. Radaelli F, Mazza R, Curioni E, Ciani A, et al. Acute megakaryocytic leukemia in essential thrombocythemia: an unusual evolution?. European Journal of Haematology. 2002;69:108–111
  99. Petrides PE. Anagrelide: a decade of clinical experience with its use for the treatment of primary thrombocythaemia. Expert Opinion on Pharmacotherapy. 2004;5:1781–1798
  100. Dingli D & Tefferi A. Anagrelide: an update on its mechanisms of action and therapeutic potential. Expert Review of Anticancer Therapy 2004; 4: 533-541.
  101. Birgegard G, Bjorkholm M, Kutti J, Larfars G, et al. Adverse effects and benefits of two years of anagrelide treatment for thrombocythemia in chronic myeloproliferative disorders. Haematologica. 2004;89:520–527
  102. Tomer A. Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia. Blood. 2002;99:1602–1609
  103. Thiele J, Kvasnicka HM, Fuchs N, Brunnbauer K, et al. Anagrelide-induced bone marrow changes during therapy of chronic myeloproliferative disorders with thrombocytosis - an immunohistochemical and morphometric study of sequential trephine biopsies. Haematologica. 2003;88:1130–1138

PII: S1521-6926(05)00102-7

doi: 10.1016/j.beha.2005.07.015

Best Practice & Research Clinical Haematology
Volume 19, Issue 3 , Pages 413-437 , September 2006

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