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

Table 5 The 2002 European Clinical and Pathological criteria for the diagnosis of "true" essential thrombocythemia and chronic idiopathic myelofibrosis or primary megakaryocytic granulocytic myeloproliferation according to Michiels et al[91]

Clinical ECP criteria of "true" ET	Pathological ECP criteria of "true" ET
A1 Persistent increase of platelet count grade 1 400-1500 × 109/L, grade 2 > 1500 × 109/L	B1 Predominant proliferation of enlarged to giant megakaryocytes wit hyperlobulated staghorn-like nuclei and mature cytoplasm, lacking conspicious cytological abnormalities
A2 Normal spleen or only minor splenomegaly on echogram	B2 No proliferation or immaturity of granulopoisis or erythropoiesis
A3 Normal LAP score, normal ESR and increased MPV	B3 No or only borderline increase in reticulin fibers
A4 Spontaneous megakaryocyte colony formation (CFU-Meg)	The combination of A1 and B1 + B2 establish "true" ET. Any other criterion confirms ET
A5 No signs or cause of reactive thrombocytosis
A6 No preceding or allied other subtype of MPN, PV, MDS or CML
A7 Absence of Philadelphia chromosome
Clinical ECP criteria of CIMF or PMGM	Pathological ECP criteria of CIMF or PMGM
A1 No preceding or allied other subtype of MPN, PV, CML or MDS	B1 PMGM and relative or absolute reduction of erythropoiesis (erythroid precursors). Abnormal clustering and increase of atypical immature medium-sized large to giant megakaryocyte containing (Cloud-like) hypolobulated nucle and definitive maturation defects
Early clinical stage	Staging of myelofibrosis: MF in ET, PV and PMGM
Normal hemoglobin, or anemia grade 1: Hemoglobin	MF 0 No reticulin fibrosis RF 0/1
> 12 g/dL, slight or moderate splenomegaly on palpation	MF 1 Slight reticulin fibrosis RF 2
or > 11 cm on ultrasound or CT. Thrombocythemia	MF 2 Marked increase RF grade 3 and slight to moderate collagen fibrosis
around 1000 × 109/L	MF 3 Advanced collagen fibrosis-osteosclerosis (endophytic bone formation)
Intermediate clinical stage
Anemia grade 2, hemoglobin > 10 g/dL, definitive leuko-erythroblastic blood picture and/or tear-drop erythrocytes. Splenomegaly on palpation, no adverse signs
Advance clinical stage
Anemia grade 3, hemoglobin < 10 g/dL, significant splenomegaly and one or more adverse signs

ECP: European Clinical and Pathological; CIMF: Chronic idiopathic myelofibrosis; PMGM: Primary megakaryocytic granulocytic myeloproliferation; ET: Essential thrombocythemia; LAP: Leukocyte alkaline phosphatase; ESR: Erythrocyte sedimentation rate; MPV: Mean platelet volume; MPN: Myeloproliferative neoplasm; PV: Polycythemia vera; MDS: Myelodysplastic syndrome; RF: Reticulin fibrosis; CML: Chronic myeloid leukemia.