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The WHO 2008 classification of Ph-myeloproliferative disorders: statement of the Czech MPD Working Group

Leukemia volume 22, pages 2118–2119 (2008)Cite this article

The recently published WHO 2008 criteria for Ph-myeloproliferative disorders (MPD)1 have, in the opinion of the Czech MPD Working Group, several pitfalls.

James et al.2 and many groups thereafter have suggested that JAK2V617F mutation and increased values of the red blood cell parameters (or possibly, increased total red cell mass) suffice for the diagnosis of polycythemia vera (PV). However, the WHO criteria1 introduce additional ‘minor’ criteria: (a) histopathology; (b) erythropoietin (Epo) values and (c) endogenous erythroid colony formation (EEC). In JAK2 mutated cases, one minor criterion is demanded, and in unmutated cases, two of them. The authors1 advocate fulfilling the minor criteria as they fear of false JAK2V617F positivity. However, if allelic discrimination assays are employed, this is extremely unlikely to happen: a discordant result was obtained in 0/261 samples screened by two alternative tests.3 The minor criteria (b) and (c) may not be met at least in the early stages of PV—at this stage, Epo is quite frequently within the lower normal range and the EEC assay may be unavailable or falsely negative as it is technically rather difficult to perform (in the lab of one of us, EEC growth was demonstrated in only 79% of otherwise typical JAK2V617F-positive MPDs; unpublished). In case, when two of the minor criteria (Epo and EEC) are missed, performing the (otherwise unnecessary) biopsy would be mandatory. However, the histological distinction of PV from essential thrombocythemia (ET) on the one hand and from primary myelofibrosis (PMF) on the other is sometimes not easy even for an experienced pathologist. Conversely, two minor criteria (Epo and EEC) may be occassionally met in cases of JAK2V617F-negative idiopathic erythrocytosis.1 One of the major criteria of the WHO 2008 for PV is the presence of JAK2V617F or JAK2 exon 12 mutation.1 This may lead to substantial overlap and diagnostic confusion of the different entities, that is, true JAK2V617F-positive PV and idiopathic erythrocytosis with JAK2 exon 12 mutation. Moreover, the cases with exon 12 mutation (as the major criterion1) cannot be confirmed by histopathology (a minor criterion1) because in cases with exon 12 mutation, the picture is far different from the typical PV ‘panmyelosis’.4 We would prefer omitting the minor criteria whatsoever. The risk of ‘false’ negativity of the minor criteria (lack of both elevated Epo and EEC growth) by far overweights the possibility of an erroneous JAK2V617F result. We agree with the authors1 that histopathological evaluation should be obligatory when JAK2V617F-negative PV is suspected.

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Authors and Affiliations

  1. Clinical Section, Institute of Hematology and Blood Transfusion, Prague, Czechia

    J Schwarz

  2. Department of Clinical Hematology, Masaryk University Faculty Hospital, Brno, Czechia

    M Penka

  3. Department of Internal Medicine-Hematooncology, Palacký University Faculty Hospital, Olomouc, Czechia

    K Indrák

  4. Department of Pediatrics, Palacký University Faculty Hospital, Olomouc, Czechia

    D Pospís̆ilová

  5. Ist Department of Internal Medicine, Charles University General Hospital, Prague, Czechia

    R Pytlík

  6. IInd Department of Internal Medicine-Clinical Hematology, Charles University, Faculty Hospital, Hradec Kr, á, lové, Czechia

    P Dulíc̆ek

  7. IInd Department of Internal Medicine-Hematooncology, Masaryk University Faculty Hospital, Brno, Czechia

    M Doubek

  8. Department of Pathology, Masaryk University Faculty Hospital, Brno, Czechia

    L Křen

  9. Institute of Pathological Anatomy, Faculty Hospital Motol, Charles University, Prague, Czechia

    V Campr

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Schwarz, J., Penka, M., Indrák, K. et al. The WHO 2008 classification of Ph-myeloproliferative disorders: statement of the Czech MPD Working Group. Leukemia 22, 2118–2119 (2008). https://doi.org/10.1038/leu.2008.93

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