PVSG and WHO vs European Clinical, Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms

Table 3 The 2008 World Health Organization and European Clinical, Molecular and Pathological criteria for the diagnosis of polycythemia vera and diagnostic differentiation between polycythemia vera and congenital or acquired erythrocytosis

Clinical and molecular criteria	Pathological criteria (WHO)
Major PV criteria	P1. Early PV
A0. Early PV. Hematocrit in the upper limit of normal: Ht: 0.45 to 0.51 in male and 0.43 to 0.48 in female, Erythrocytes < 6 × 1012/L A1. Classical WHO defined PV: Hematocrit > 0.51/> 0.48 in male/ female, Erythrocytes > 6 × 1012/L A2. Presence of JAK2V617F mutation (sensitivity 95%) or exon 12 mutation A3. Low serum EPO level and/or spontaneous endogenous erythroid colony formation	Increased cellularity of bone marrow predominantly due to increased erythropoiesis and loose clusters of large megakaryocytes with hyperlobulated nuclei. No or slight increase of granulopoiesis and RF
	P2. Overt PV
	Hypercellular (75%-100%) bone marrow due to trilinear increase of erythropoiesis, megakaryopoiesis and granulopoiesis and clustering of small to giant (pleomorph) megakaryocytes with hyperlobulated nuclei. Absence of stainable iron
Minor MPD criteria	P3. Erythrocytosis
B1. Persistent increase of platelet count: grade I: 400-1500, grade II: > 1500 B2. Granulocytes > 10 × 109/L or Leukocytes > 12 × 109/L and/or raised LAP-score or increased PRV-1 expression in the absence of fever or infection	Selective increase of erythropoiesis, normal granulopoiesis and megakaryocytes of normal size, morphology and no clustering of megakaryocytes in primary or secondary erythrocytosis
	Grading of RF (RF 0, 1, 2, 3)
B3. Splenomegaly on palpation or on ultrasound echogram (> 12 cm length in diameter)	Grading of reticulin and collagen fibrosis; myelofibrosis MF grade 1, 2 and 3

World Health Organization (WHO) and European Clinical, Molecular and Pathological (ECMP) criteria criteria for early and overt polycythemia vera (PV). A0, A2, B1 and P1 establish prodromal PV (ET stage 2) PV ECMP stage 0, or masked PV; A1, A2, P1 and none of B establish so-called idiopathic erythrocytosis or polycythemic PV ECMP stage 1. A1, A2, P2 and one or more of B establish WHO defined classic and advanced PV ECMP stage 2 and 3. A1 and P3 with normal or increased values of serum EPO is consistent with congenital or secondary erythrocytosis. A3 confirms early and overt PV without the need of red cell mass measurement for clinicians who do not have access to a hematopathologist expert in myeloproliferative neoplasms. MPD: Myeloproliferative disorders; LAP: Leukocyte alkaline phosphatase; MF: Myelofibrosis; RF: Reticulin fibrosis.