Skip to main content
Log in

Is it justified to perform a bone marrow biopsy examination in sustained erythrocytosis?

  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

The diagnostic criteria of the Polycythemia Vera Study Group do not consider bone marrow histopathology, nor do they recognize the dynamics of polycythemia vera (PV). Precursor stages, when accompanied by an elevated platelet count, may clinically mimic essential thrombocythemia. Significantly extending former descriptions of bone marrow features, a trilineage myeloproliferation (panmyelosis) with a pleomorphous appearance (differences in size) of megakaryopoiesis is a characteristic histopathologic finding in PV. Differentiation from secondary polycythemia is accomplished by also considering the conspicuously expressed stromal changes (perivascular plasmacytosis, eosinophils, cell debris, and iron deposits). A clear-cut discrimination is possible, even in the initial (latent) stages of PV, which do not fulfill all the conventional diagnostic criteria. Advanced stages (spent phases) of PV show an increased left-shifted granulocytic proliferation accompanied by reduction of erythroid precursors and progressive myelofibrosis (postpolycythemic myeloid metaplasia). Finally, an increase in dysplastic changes and immaturity of cell lineages signals a transition into blastic crisis.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. StreiffMB, Smith B, Spivak JL: The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members’ practice patterns. Blood 2002, 99:1144–1149. This comprehensive study elegantly describes the state of art regarding diagnosis and management of polycythemia vera (PV) in the United States.

    Article  PubMed  CAS  Google Scholar 

  2. TefferiA, Spivak JL: Polycythemia vera: scientific advances and current practice. Semin Hematol 2005, 42:206–220. A very recent review of basic scientific and clinical aspects of PV, including a critical attitude towards the determination of the red cell mass as the major diagnostic feature and the performance of a bone marrow biopsy examination.

    Article  PubMed  CAS  Google Scholar 

  3. SpivakJL: Polycythemia vera: myths, mechanisms, and management. Blood 2002, 100:4272–4290. An outstanding and thorough review of the multiple aspects of PV, with a critical discussion of the diagnostic value of bone marrow biopsies.

    Article  PubMed  CAS  Google Scholar 

  4. Murphy S: Diagnostic criteria and prognosis in polycythemia vera and essential thrombocythemia. Semin Hematol 1999, 36:9–13.

    PubMed  CAS  Google Scholar 

  5. Berlin NI: Diagnosis and classification of the polycythemias. Semin Hematol 1975, 12:339–351.

    PubMed  CAS  Google Scholar 

  6. Bilgrami S, Greenberg BR: Polycythemia rubra vera. Semin Oncol 1995, 22:307–326.

    PubMed  CAS  Google Scholar 

  7. Pearson TC: Diagnosis and classification of erythrocytoses and thrombocytoses. Baillieres Clin Haematol 1998, 11:695–720.

    Article  PubMed  CAS  Google Scholar 

  8. Pearson TC: Evaluation of diagnostic criteria in polycythemia vera. Semin Hematol 2001, 38:21–24.

    Article  PubMed  CAS  Google Scholar 

  9. Pierre R, Imbert M, Thiele J, et al.: Polycythemia vera. In WHO Classification of Tumours: Tumours of Hematopoietic and Lymphoid Tissue. Edited by Jaffe ES, Harris NL, Stein H, et al. Lyon, France: IARC Press; 2001:32–38. This chapter includes the new World Health Organization (WHO) classification of PV in which, for the first time, bone marrow morphology is regarded as a minor criterion.

    Google Scholar 

  10. Michiels JJ, Thiele J: Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). Int J Hematol 2002, 76:133–145. This paper reviews clinical as well as morphologic findings in chronic myeloproliferative disorders, including PV. In confirmation and extension of the WHO diagnostic guidelines (see reference 9), the paper introduces the so-called European clinicopathological criteria.

    Article  PubMed  Google Scholar 

  11. Ellis JT, Silver RT, Coleman M, et al.: The bone marrow in polycythemia vera. Semin Hematol 1975, 12:433–444.

    PubMed  CAS  Google Scholar 

  12. Peterson P, Ellis TJ: The bone marrow in polycythemia vera. In Polycythemia Vera and the Myeloproliferative Disorders. Edited by Wasserman LR, Berk PD, Berlin NI, Philadelphia: WB Saunders; 1995:31–53.

    Google Scholar 

  13. Ellis JT, Peterson P: The bone marrow in polycythemia vera. Pathol Annu 1979, 14:383–403.

    PubMed  Google Scholar 

  14. Iland HJ, Laszlo J, Case DC, Jr., et al.: Differentiation between essential thrombocythemia and polycythemia vera with marked thrombocytosis. Am J Hematol 1987, 25:191–201.

    Article  PubMed  CAS  Google Scholar 

  15. Georgii A, Buesche G, Kreft A: The histopathology of chronic myeloproliferative diseases. Baillieres Clin Haematol 1998, 11:721–749. This review thoroughly describes bone marrow findings in chronic myeloproliferative disorders, including PV.

    Article  PubMed  CAS  Google Scholar 

  16. Thiele J, Kvasnicka HM: Diagnostic impact of bone marrow histopathology in polycythemia vera (PV). Histol Histopathol 2005, 20:317–328. This review article on bone marrow morphology in all stages of PV is based on a large cohort of patients and tries to elucidate the dynamics of the disease process.

    PubMed  CAS  Google Scholar 

  17. Thiele J, Kvasnicka HM, Orazi A: Bone marrow histopathology in myeloproliferative disorders—current diagnostic approach. Semin Hematol 2005, 42:184–195.

    Article  PubMed  Google Scholar 

  18. Thiele J, Kvasnicka HM, Zankovich R, et al.: The value of bone marrow histology in differentiating between early stage polycythemia vera and secondary (reactive) polycythemias. Haematologica 2001, 86:368–374. This is the first paper discriminating early initial stages of PV from secondary polycythemia based on histomorphologic criteria evaluated in a blinded and independent fashion.

    PubMed  CAS  Google Scholar 

  19. Thiele J, Kvasnicka HM, Diehl V: Standardization of bone marrow features—does it work in hematopathology for histological discrimination of different disease patterns? Histol Histopathol 2005, 20:633–644.

    PubMed  CAS  Google Scholar 

  20. Thiele J, Kvasnicka HM, Fischer R: Histochemistry and morphometry on bone marrow biopsies in chronic myeloproliferative disorders—aids to diagnosis and classification. Ann Hematol 1999, 78:495–506.

    Article  PubMed  CAS  Google Scholar 

  21. Thiele J, Kvasnicka HM, Diehl V: Bone marrow features of diagnostic impact in erythrocytosis. Ann Hematol 2005, 84:362–367.

    Article  PubMed  Google Scholar 

  22. Thiele J, Kvasnicka HM, Muehlhausen K, et al.: Polycythemia rubra vera versus secondary polycythemias. A clinicopathological evaluation of distinctive features in 199 patients. Pathol Res Pract 2001, 197:77–84.

    Article  PubMed  CAS  Google Scholar 

  23. Gruppo Italiano Studio Policitemia: Polycythemia vera: the natural history of 1213 patients followed for 20 years. Ann Intern Med 1995, 123:656–664.

    Google Scholar 

  24. Messinezy M, Pearson TC: The classification and diagnostic criteria of the erythrocytoses (polycythaemias). Clin Lab Haematol 1999, 21:309–316.

    Article  PubMed  CAS  Google Scholar 

  25. Berglund S, Zettervall O: Incidence of polycythemia vera in a defined population. Eur J Haematol 1992, 48:20–26.

    Article  PubMed  CAS  Google Scholar 

  26. Messinezy M, Sawyer B, Westwood NB, et al.: Idiopathic erythrocytosis—additional new study techniques suggest a heterogenous group. Eur J Haematol 1994, 53:163–167.

    Article  PubMed  CAS  Google Scholar 

  27. Najean Y, Triebel F, Dresch C: Pure erythrocytosis: reappraisal of a study of 51 cases. Am J Hematol 1981, 10:129–136.

    Article  PubMed  CAS  Google Scholar 

  28. Pearson TC, Wetherley-Mein G: The course and complications of idiopathic erythrocytosis. Clin Lab Haematol 1979, 1:189–196.

    Article  PubMed  CAS  Google Scholar 

  29. Ruggeri M, Tosetto A, Frezzato M, et al.: The rate of progression to polycythemia vera or essential thrombocythemia in patients with erythrocytosis or thrombocytosis. Ann Intern Med 2003, 139:470–475. This remarkable epidemiologic study of a large Italian city population is focused on the incidence of idiopathic erythrocytosis and evolving PV, according to the PVSG criteria, after a follow-up of about 5 years.

    PubMed  Google Scholar 

  30. Thiele J, Kvasnicka HM, Diehl V: Initial (latent) polycythemia vera with thrombocytosis mimicking essential thrombocythemia. Acta Haematol 2005, 113:213–219. This is a systematic clinicopathologic study of latent (initial) PV presenting as ET, based on a large cohort of patients.

    Article  PubMed  Google Scholar 

  31. Murphy S, Peterson P, Iland H, et al.: Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Semin Hematol 1997, 34:29–39.

    PubMed  CAS  Google Scholar 

  32. Jantunen R, Juvonen E, Ikkala E, et al.: Development of erythrocytosis in the course of essential thrombocythemia. Ann Hematol 1999, 78:219–222.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    PubMed  CAS  Google Scholar 

  34. Griesshammer M, Klippel S, Strunck E, et al.: PRV-1 mRNA expression discriminates two types of essential thrombocythemia. Ann Hematol 2004, 83:364–370.

    Article  PubMed  CAS  Google Scholar 

  35. Goerttler PS, Steimle C, Marz E, et al.: The Jak2V617F mutation, PRV-1 overexpression, and EEC formation define a similar cohort of MPD patients. Blood 2005, 106:2862–2864.

    Article  PubMed  CAS  Google Scholar 

  36. Imbert M, Pierre R, Thiele J, et al.: Essential thrombocythaemia. In WHO Classification of Tumours: Tumours of Hematopoietic and Lymphoid Tissue. Edited by Jaffe ES, Harris NL, Stein H, et al. Lyon, France: IARC Press; 2001:39–41.

    Google Scholar 

  37. Thiele J, Schneider G, Hoeppner B, 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 Arch A Pathol Anat Histopathol 1988, 413:407–417.

    Article  PubMed  CAS  Google Scholar 

  38. Buhr T, Georgii A, Schuppan O, et al.: Histologic findings in bone marrow biopsies of patients with thrombocythemic cell counts. Ann Hematol 1992, 64:286–291.

    Article  PubMed  CAS  Google Scholar 

  39. Georgii A, Buhr T, Buesche G, et al.: Classification and staging of Ph-negative myeloproliferative disorders by histopathology from bone marrow biopsies. Leuk Lymphoma 1996, 22(Suppl 1):15–29.

    Article  PubMed  Google Scholar 

  40. Thiele J, Kvasnicka HM, Diehl V, et al.: Clinicopathological diagnosis and differential criteria of thrombocythemias in various myeloproliferative disorders by histopathology, histochemistry and immunostaining from bone marrow biopsies. Leuk Lymphoma 1999, 33:207–218.

    PubMed  CAS  Google Scholar 

  41. Bartl R, Frisch B, Wilmanns W: Potential of bone marrow biopsy in chronic myeloproliferative disorders (MPD). Eur J Haematol 1993, 50:41–52.

    Article  PubMed  CAS  Google Scholar 

  42. Dickstein JI, Vardiman JW: Issues in the pathology and diagnosis of the chronic myeloproliferative disorders and the myelodysplastic syndromes. Am J Clin Pathol 1993, 99:513–525.

    PubMed  CAS  Google Scholar 

  43. Ellis JT, Peterson P, Geller SA, et al.: Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies. Semin Hematol 1986, 23:144–155.

    PubMed  CAS  Google Scholar 

  44. Buhr T, Georgii A, Choritz H: Myelofibrosis in chronic myeloproliferative disorders. Incidence among subtypes according to the Hannover Classification. Pathol Res Pract 1993, 189:121–132.

    PubMed  CAS  Google Scholar 

  45. Kreft A, Buche G, Ghalibafian M, et al.: The incidence of myelofibrosis in essential thrombocythaemia, polycythaemia vera and chronic idiopathic myelofibrosis: a retrospective evaluation of sequential bone marrow biopsies. Acta Haematol 2005, 113:137–143.

    Article  PubMed  Google Scholar 

  46. Thiele J, Kvasnicka HM, Facchetti F, et al.: European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 2005, 90:1128–1132.

    PubMed  Google Scholar 

  47. Kreft A, Nolde C, Busche G, et al.: Polycythaemia vera: bone marrow histopathology under treatment with interferon, hydroxyurea and busulphan. Eur J Haematol 2000, 64:32–41.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Juergen Thiele MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thiele, J., Kvasnicka, H.M. Is it justified to perform a bone marrow biopsy examination in sustained erythrocytosis?. Curr Hematol Malig Rep 1, 87–92 (2006). https://doi.org/10.1007/s11899-006-0028-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-006-0028-1

Keywords

Navigation