Update from the latest WHO classification of MPNs: a user's manual

Abstract

The 2016 multiparameter World Health Organization (WHO) classification for Philadelphia-negative myeloproliferative neoplasms (MPNs) integrates clinical features, morphology, and genetic data to diagnose polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The main novelties are: (1) the reduction of the hemoglobin (Hb) level threshold to diagnose PV, now established at 16.5 g/dL for men and 16 g/dL for women (based on the identification of MPN patients with PV-consistent bone marrow [BM] features and a Hb level lower than that established in the 2008 WHO classification for PV); (2) the recognition of prefibrotic/early PMF, distinguishable from ET on the basis of BM morphology, an entity having a higher tendency to develop overt myelofibrosis or acute leukemia, and characterized by inferior survival; (3) the central role of BM morphology in the diagnosis of ET, prefibrotic/early PMF, PMF, and PV with borderline Hb values; megakaryocyte number and morphology (typical in ET, atypical in both PMF forms) accompanied by a new distinction of reticulin fibrosis grade in PMF (grade 1 in prefibrotic/early PMF and grade 2-3 in PMF) constitute diagnostic criteria; and (4) the inclusion of all mutually exclusive MPN driver mutations (JAK2, CALR, and MPL) as major diagnostic criteria in ET and PMF; 10% to 15% of these patients are triple negative, and in these cases the search for an additional clonal marker (eg, mutations in ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, and SF3B1) is warranted.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

© 2016 by The American Society of Hematology. All rights reserved.

Figures

Figure 1.

Algorithm for evaluation of MPN phenotype with erythrocytosis. *Test JAK2 V617F first and exon 12 JAK2 mutations if V617F is negative. CML, chronic myeloid leukemia; Epo, erythropoietin; F, female; M, male; MK, megakaryocytes; PLT, platelet; WBC, white blood cell.

Figure 2.

Algorithm for evaluation of MPN phenotype without erythrocytosis. *Test JAK2 V617F first, CALR mutations if V617F is negative, and MPL mutations if JAK2 and CALR are negative. **Evaluate for MPN, MDS, MDS/MPN, or other myeloid malignancies.

Figure 3.

Illustrations of BM reticulin fibers and osteosclerosis. MF-0: scattered linear reticulin fibers with no intersections (internal control is represented by the reticulin fiber around the vessel; MF-1: loose network of reticulin fibers with many intersections, especially in perivascular areas; MF-2: diffuse and dense increase in reticulin fibers, with extensive intersections and occasionally with focal bundles of collagen (arrows); and MF-3: diffuse and dense increase in reticulin fibers, with extensive intersections and coarse bundles of collagen (arrows).