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

Table 2 2008 World Health Organization and European Clinical, Molecular and Pathological criteria for the diagnosis and classification of JAK2^V617F mutated essential thrombocythemia into 3 stags or phenotypes: important to differentiate because natural history differs

Clinical and molecular criteria	WHO bone marrow criteria
ET stage 1	Normocellular ET
Platelet count of > 350 × 109/L and the presence of large platelets in a blood smear in all stages of ET	Predominant proliferation of enlarged megakaryocytes with hyperlobulated nuclei and mature cytoplasm, lacking conspicuous morphological abnormalities. No increase, proliferation or immaturity of granulopoiesis or erythropoiesis
Presence of JAK2V617F mutation	No progression to post-ET myelofibrosis
ET stage 2	Prodromal PV
Platelet count of ≥ 350 × 109/L and normal hematocrit: male < 51%, female < 48%	Increased cellularity with trilineage myeloproliferation (i.e., panmyelosis). Proliferation and clustering of small to giant (pleomorphic) megakaryocytes
erythrocytes < 6 × 1012/L	No pronounced inflammatory reaction (plasmacytosis, cellular debris). Absence bone marrow features consistent with congenital polycythemia and secondary erythrocytosis
Presence of JAK2V617F mutation	Progression to overt PV during follow-up
Low serum EPO level and/or increased score for leukocyte alkaline phosphatase
Spontaneous EEC
ET stage 3	ET.MGM
Platelet count of ≥ 3500 × 109/L and no signs of leuko- erythroblastosis	Increased cellularity due to MGM and normal or relative reduction of erythroid precursors with various degrees pleiomorphic loosely clustered megakaryocytes containing dysmorphic (not cloud-like) nuclei and maturation defects
Erythrocytes < 6 × 1012/L	No or slight RF (RF 0 or 1)
Presence of JAK2V617F mutation	Progression to post ET myelofibrosis
Slight splenomegaly on ultrasound and no anemia Hb > 12 g/dL
No preceding or allied of CML, PV, RARS-T or MDS

Masked myeloproliferative neoplasms: normal platelets, leukocytes and hematocrit, but slight splenomegaly on echogram with the presence of JAK2^V617F mutation and/or a World Health Organization (WHO) bone marrow is rare (rather frequent in patients with splanchnic vein thrombosis and/or Budd Chiari syndrome). ET: Essential thrombocythemia; PV: Polycythemia vera; ET.MGM: ET due to megakaryocytic, granulocytic myeloproliferation; EEC: Endogenous erythroid colony; CML: Chronic myeloid leukemia; RARS-T: Thrombocythemia associated with refractory anemia with increased ringed sideroblasts; RF: Reticulin fibrosis.