European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

Table 8 2015 World Health Organization clinical molecular and pathobiological criteria for diagnosis of JAK2^V617F mutated essential throbocythemia[77,78]

CM criteria	Bone marrow pathology (P) criteria (WHO)
ET	Normocellular ET
(1) Platelet count of > 350 × 109/L and the presence of large platelets in a blood smear	Proliferation and clustering of enlarged mature pleomorphic megakaryocytes with hyperlobulated nuclei and mature cytoplasm, lacking conspicuous morphological abnormalities
(2) Heterozygous JAK2V617F mutation, and low JAK2 allele mutation load	Normocellular bone marrow (< 60%) and no proliferation or immaturity of granulopoiesis or erythropoiesis
(3) Normal erythrocytes < 5.8 × 1012/L males, < 5.6 × 1012/L females	RF 0 or 1
(4) Hb and ht normal or in the upper range of normal
Prodromal PV	ET with bone marrow features of PV
(1) Platelet count of > 350 × 109/L Hb and Ht normak or in the upper range of normal, normal erythrocyte < 5.8 × 1012/L males, < 5.6 × 1012/L females	Increased cellularity (60%-80%) due to increased erytropoiesis or trilineage myeloproliferation (i.e., panmyelosis). Proliferation and clustering of medium sized to large (pleomorphic) mature megakaryocytes
(2) Presence of JAK2V617F mutation and variable JAK mutation load	Absence bone marrow features consistent with congenital polycythemia and secondary erythrocytosis
(3) Low serum EPO level and increased LAP score	RF 0 or 1
(4) Spontaneous EEC
Prefibrotic hypercellular ET	EMGM
(1) Platelet count of > 350 × 109/L	Hypercellular ET due to chronic megakaryocytic and EMGM and normal or reduced erythroid precursors
(2) Presence of JAK2V617F mutation and high JAK2 mutation load	Loose to dense clustering of more pleiomorphic megakaryocytes with hyperploid or clumpsy nuclei (not or some cloud-like)
(3) Slight or moderate splenomegaly on ultrasound or on palpation
(4) No preceding or allied CML, PV, PMGM, RARS-T or MDS
Clinical stage 1: No anemia with Hb and Ht in the normal or low normal range: hb > 12 g/dL, normal LDH and CD34+	Grading of reticulin fibrosis and MF in EMGM
Clinical stage 2: Slight anemia Hb < 12 to > 10 g/dL, LDH↑, and splenomegaly	Prefibrotic: RF 0/1 = MF 0, no/minor splenomegaly
Clinical stage 3: Anemia, Hb < 10 g/dL, LDH↑↑, CD34+, leukoerythroblastose and, tear drop	Early fibrotic EMGM: RF 2 = MF 1 and minor or moderate splenomegaly
	Fibrotic EMGM: RF 3, RCF = MF 2 and overt splenomegaly
	Post-ET MF: RF 3/4 = MF 2/3 (WHO criteria)

ET: Essential thrombocythemia; MF: Myelofibrosis; EPO: Erythropoetin; CM: Clinical and molecular; Hb: Hemoglobin; ht: Hematocrit; WHO: World Health Organization; PV: Polycythemia vera; EPO: Erythropoetin; EEC: Endogenous erythroid colony; CML: Chronic myeloid leukemia; PMGM: Primary megakaryocytic granulocytic myeloproliferation; MDS: Myelodysplastic syndrome; EMGM: ET with hypercellular megakaryocytic-granulocytic myeloproliferation; RF: Reticuline fibrosis; LDH: Lactodehydrogenase; RCF: Reticulin collagen fibrosis.