Impact of World Health Organization (WHO) Revised Criteria-2016 on the Diagnosis of Polycythemia Vera

Abstract

The diagnosis of polycythemia vera (PV) requires the integration of clinical and laboratory findings, bone marrow morphologic features, and JAK2 analysis. JAK2V617F (exon 14) mutation is found in 95% of PV cases. In PV, addition of characteristic bone marrow morphology as one of three major diagnostic criteria allowed reduced hemoglobin/hematocrit threshold for diagnosis to 16.5 g/dL/49% in men and 16 g/dL/48% in women. JAK2 mutation is still the third major diagnostic criterion in PV. Low serum erythropoietin level is now considered as minor criterion in PV and is used to detect cases, which are negative for JAK2 mutation. In this retrospective study, cases diagnosed as PV from January 2013 to December 2015 were reclassified using WHO 2016 criteria. Their clinical and laboratory parameters along with treatment and outcome were studied. Out of 26 patients of previously diagnosed PV, either definitively or provisionally, twenty-one were found to comply with the new 2016 revision of the WHO Criteria. Median age was 55.5 years, with a male preponderance. The median values of hemoglobin, hematocrit and platelets were 17.5 gm/dL, 56.7% and 493 × 109/L, respectively. JAK2V617F was mutated in 17 cases. Bone marrow showed hypercellularity, panmyelosis and marked megakaryocyte dyspoiesis in all patients. All patients had normal oxygen saturation, confirming the primary nature of the disease. Our study, first of its kind in India, underscores the importance of the 2016 revision of the WHO document in detecting cases of masked PV.

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

References

  1. 1.

    Arber DA, Orazi A, Hasserjian R et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2406. https://doi.org/10.1182/blood-2016-03-643544

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114(5):937–951. https://doi.org/10.1182/blood-2009-03-209262

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Alvarez-larrán A, Ancochea A, Angona A et al (2012) Articles and brief reports red cell mass measurement in patients with clinically suspected diagnosis of polycythemia vera or essential thrombocythemia. Haematologica 97(11):9–12. https://doi.org/10.3324/haematol.2012.067348

    Article  Google Scholar 

  4. 4.

    Tefferi A, Barbui T (2017) Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol 92(1):94–108. https://doi.org/10.1002/ajh.24607

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Spivak JL (2002) Review article polycythemia vera: myths, mechanisms, and management. Blood 100(13):4272–4290. https://doi.org/10.1182/blood-2001-12-0349

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    James C, Ugo V, Le Couedic JP et al (2005) A unique clonal JAK2 mutation leading to constitutive signaling causes polycythaemia vera. Nature 434:1144–1148

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Lakey MA, Pardanani A, Hoyer JD et al (2017) Bone marrow morphologic features in polycythemia vera with JAK2 exon 12 mutations. Am J Clin Pathol 133:942–948. https://doi.org/10.1309/ajcp3z2akuwrgtnm

    Article  Google Scholar 

  8. 8.

    Tefferi A, Lasho TL, Schwager SM et al (2006) The clinical phenotype of wild-type, heterozygous, and homozygous JAK2 V617F in polycythemia vera. Cancer 106(3):631–635. https://doi.org/10.1002/cncr.21645

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Misawa K, Yasuda H, Araki M, Ochiai T, Morishita S, Nudejima M, Hironaka Y, Shirane S, Edahiro Y, Gotoh A, Ohsaka A (2017) The 2016 WHO diagnostic criteria for polycythemia vera renders an accurate diagnosis to a broader range of patients including masked polycythemia vera: comparison with the 2008 WHO diagnostic criteria. Am J Hematol. https://doi.org/10.1002/ajh.24752

    PubMed  Article  Google Scholar 

  10. 10.

    Iurlo A, Gianelli U, Cattaneo D, Thiele J, Orazi A (2017) Impact of the 2016 revised WHO criteria for myeloproliferative neoplasms, unclassifiable: comparison with the 2008 version. Am J Hematol. https://doi.org/10.1002/ajh.24657

    PubMed  Article  Google Scholar 

  11. 11.

    Ghai S, Rai S (2017) Megakaryocytic morphology in Janus kinase 2 V617F positive myeloproliferative neoplasm. South Asian J Cancer 6(2):75–78. https://doi.org/10.4103/2278-330X.208854

    PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Kvasnicka HM, Thiele J (2007) Classification of Ph-negative chronic myeloproliferative disorders: morphology as the yardstick of classification. Pathobiology 74:63–71

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Vytrva N, Stacher E, Regitnig P, Zinke-Cerwenka W, Hojas S, Hubmann E, Porwit A, Bjorkholm M, Hoefler G, Beham-Schmid C (2014) Megakaryocytic morphology and clinical parameters in essential thrombocythemia, polycythemia vera, and primary myelofibrosis with and without JAK2 V617F. Arch Pathol Lab Med 138(9):1203–1209. https://doi.org/10.5858/arpa.2013-0018-OA

    PubMed  Article  Google Scholar 

  14. 14.

    Chatterjee T, Ahuja A (2018) Summary and review of the abstracts on philadelphia-negative myeloproliferative neoplasms presented at haematocon 2017. Indian J Hematol Blood Transfus 34(2):227–232. https://doi.org/10.1007/s12288-017-0913-x

    PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Tiong IS, Casolari DA, Nguyen T et al (2016) Masked polycythaemia vera is genetically intermediate between JAK2V617F mutated essential thrombocythaemia and overt polycythaemia vera. Blood Cancer J 6(8):e459. https://doi.org/10.1038/bcj.2016.70

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Barbui T, Thiele J, Vannucchi AM, Tefferi A (2015) Rationale for revision and proposed changes of the WHO diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis. Blood Cancer J 5(8):e337. https://doi.org/10.1038/bcj.2015.64

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Barbui T, Thiele J, Gisslinger H et al (2014) Masked polycythemia vera (mPV): results of an international study. Am J Hematol 89:52–54

    CAS  PubMed  Article  Google Scholar 

Download references

Funding

This study has not received any funding from any agency.

Author information

Affiliations

Authors

Contributions

SN: reviewed slides, wrote the manuscript. SL: involved in initial diagnosis, jointly prepared manuscript and critically reviewed the manuscript and is the corresponding author, also reviewed data of all patients from laboratory archives and verified the accuarcy of the data. ST: collected data from patient records. SB, RK: faculty involved in initial diagnosis. CM: mentor guide for the project, reviewed slides and manuscript.

Corresponding author

Correspondence to Sindhura Lakshmi Koulmane Laxminarayana.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Standards

The study was reviewed and approved by institutional committee at Kasturba Medical College, Manipal. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nathany, S., Koulmane Laxminarayana, S.L., Tewari, S. et al. Impact of World Health Organization (WHO) Revised Criteria-2016 on the Diagnosis of Polycythemia Vera. Indian J Hematol Blood Transfus 36, 477–483 (2020). https://doi.org/10.1007/s12288-019-01202-w

Download citation

Keywords

  • Polycythemia vera
  • JAK2V617F mutation
  • World Health Organization revised criteria 2016
  • Serum erythropoietin
  • Abnormal megakaryopoiesis