Review
Copyright ©2013 Baishideng. All rights reserved.
World J Hematol. Aug 6, 2013; 2(3): 71-88
Published online Aug 6, 2013. doi: 10.5315/wjh.v2.i3.71
PVSG and WHO vs European Clinical, Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms
Jan Jacques Michiels, Zwi Berneman, Wilfried Schroyens, King H Lam, Hendrik De Raeve
Jan Jacques Michiels, Zwi Berneman, Wilfried Schroyens, Department of Hematology, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Antwerp, Belgium
Jan Jacques Michiels, European Working Group on Myeloproliferative Neoplasms, Goodheart Institute, Erasmus Tower, Veenmos 13, 3069 AT, Rotterdam, The Netherlands
King H Lam, Department of Pathology, Erasmus University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Hendrik De Raeve, Department of Pathology OLV Hospital Aalst and University Hospital Brussels, OLV Ziekenhuis, Moorselbaan 164, B-9300 Aalst, Belgium
Author contributions: Michiels JJ and De Raeve H designed the study and wrote the manuscript; Michiels JJ, Berneman Z and Schroyens W collected and analysed the clinical features of myeloproliferative neoplasms (MPN); Lam KH and De Raeve H perfomed the pathology studies and interpreted the bone histology diagnotic findings in MPN of various molecular etiology.
Correspondence to: Jan Jacques Michiels, MD, PhD, Senior Internist, European Working Group on Myeloproliferative Neoplasms, Goodheart Institute, Erasmus Tower, Veenmos 13, 3069 AT, Rotterdam, The Netherlands. goodheartcenter@upcmail.nl
Telephone: +31-62-6970534
Received: January 11, 2013
Revised: June 14, 2013
Accepted: June 18, 2013
Published online: August 6, 2013
Abstract

The Polycythemia Vera Study Group (PVSG), World Health Organization (WHO) and European Clinical, Molecular and Pathological (ECMP) classifications agree upon the diagnostic criteria for polycythemia vera (PV) and advanced primary myelofibrosis (MF). Essential thrombocythemia (ET) according to PVSG and 2007/2008 WHO criteria comprises three variants of JAK2V617F mutated ET when the ECMP criteria are applied. These include normocellular ET, hypercellular ET with features of early PV (prodromal PV), and hypercellular ET due to megakaryocytic, granulocytic myeloproliferation (ET.MGM). Evolution of prodromal PV into overt PV is common. Development of MF is rare in normocellular ET (WHO-ET) but rather common in hypercellular ET.MGM. The JAK2V617F mutation burden in heterozygous mutated normocellular ET and in heterozygous/homozygous or homozygous mutated PV and ET.MGM is of major prognostic significance. JAK2/MPL wild type ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation (PMGM) is characterized by densely clustered immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are never seen in JAK2V617F mutated ET, and PV and also not in MPL515 mutated normocellular ET (WHO-ET). JAK2V617 mutation burden, spleen size, LDH, circulating CD34+ cells, and pre-treatment bone marrow histopathology are mandatory to stage the myeloproliferative neoplasms ET, PV, PMGM for proper prognosis assessment and therapeutic implications. MF itself is not a disease because reticulin fibrosis and reticulin/collagen fibrosis are secondary responses of activated polyclonal fibroblasts to cytokines released from the clonal myeloproliferative granulocytic and megakaryocytic progenitor cells in ET.MGM, PV and PMGM.

Keywords: Myeloproliferative neoplasms, Essential thrombocythemia, Prodromal polycythemia vera, Polycythemia vera, Myelofibrosis, JAK2V617F mutation, JAK2 wild type myeloproliferative neoplasm, Bone marrow pathology

Core tip: The integrated World Health Organization (WHO) and European Clinical, Molecular and Pathological classification of the myeloproliferative neoplasms include JAK2V617F mutated normocellular essential thrombocythemia (WHO-ET), prodromal polycythemia vera (PV), classical PV, and hypercellular ET due to megakaryocytic, granulocytic myeloproliferation. Evolution of prodromal PV into overt PV is common. JAK2/MPL wild hypercellular ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation is characterized by densely clustered immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are never seen in JAK2V617F mutated ET and PV, and also not in JAK2 wild type normocellular ET (WHO-ET) carrying the MPL515 mutation.