Summary of the criteria for the diagnosis of myeloproliferative neoplasm (MPN) in the WHO (5th edition) and ICC4,5
| WHO . | ICC . |
|---|---|
| PV . | PV . |
| Major criteria 1. Hemoglobin >16.5 g/dL in men and >16.0 g/dL in women or hematocrit >49% in men and >48% in women 2. Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis), including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes 3. Presence of JAK2-p.V617F or JAK2 exon 12 mutation Minor criterion - Subnormal serum erythropoietin level Diagnosis of PV requires meeting either all 3 major criteria, or the first 2 major criteria and the minor criterion | Major criteria 1. Elevated hemoglobin concentration (>16.5 g/dL in men and >16.0 g/dL in women) or elevated hematocrit (hematocrit >49% in men and >48% in women) or increased red blood cell mass (>25% above mean normal predicted value) 2. Presence of JAK2-p.V617F or JAK2 exon 12 mutation 3. Bone marrow biopsy showing age-adjusted hypercellularity with trilineage proliferation (panmyelosis), including prominent erythroid, granulocytic, and increase in pleomorphic, mature megakaryocytes without atypia Minor criterion - Subnormal serum erythropoietin level The diagnosis of PV requires either all 3 major criteria or the first 2 major criteria plus the minor criterion |
| ET | ET |
| Major criteria 1. Platelet count ≥450 × 109/L 2. Bone marrow biopsy showing proliferation mainly of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibers. 3. Not meeting WHO criteria for BCR::ABL1-positive CML, PV, PMF, myelodysplastic syndromes, or other myeloid neoplasms 4. Presence of JAK2, CALR, or MPL mutation Minor criterion - Presence of a clonal marker or absence of evidence for reactive thrombocytosis Diagnosis of ET requires meeting all 4 major criteria or the first 3 major criteria and the minor criterion | Major criteria 1. Platelet count ≥450 × 109/L 2. Bone marrow biopsy showing proliferation mainly of the megakaryocytic lineage, with increased numbers of enlarged, mature megakaryocytes with hyperlobulated staghorn-like nuclei, infrequently dense clusters; no significant increase or left shift in neutrophil granulopoiesis or erythropoiesis; no relevant bone marrow fibrosis 3. Diagnostic criteria for BCR::ABL1-positive CML, PV, PMF, or other myeloid neoplasms are not met 4. JAK2, CALR, or MPL mutation Minor criteria - Presence of a clonal marker or absence of evidence of reactive thrombocytosis The diagnosis of ET requires either all major criteria or the first 3 major criteria plus the minor criteria |
| WHO and ICC | WHO and ICC |
| Prefibrotic PMF | Overt PMF |
| Major criteria 1. Megakaryocytic proliferation and atypia, without reticulin fibrosis >grade 1, increased age-adjusted bone marrow cellularity, granulocytic proliferation, and often decreased erythropoiesis 2. Diagnostic criteria for BCR::ABL1-positive CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms are not met 3. Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal marker, or absence of minor reactive bone marrow reticulin fibrosis Minor criteria Presence of at least 1 of the following, confirmed in 2 consecutive determinations: a. Anemia not attributed to a comorbid condition b. Leukocytosis ≥11 × 109/L c. Palpable splenomegaly d. LDH increased to above upper normal limit of institutional reference range Diagnosis of prePMF requires meeting all 3 major criteria, and at least 1 minor criterion | Major criteria 1. Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3 2. Diagnostic criteria for ET, PV, BCR::ABL-1 positive CML, myelodysplastic syndrome, or other myeloid neoplasms are not met 3. Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal marker, or absence of reactive myelofibrosis Minor criteria Presence of at least 1 of the following, confirmed in 2 consecutive determinations: a. Anemia not attributed to a comorbid condition b. Leukocytosis ≥11 × 109/L c. Palpable splenomegaly d. LDH increased above the reference range e. Leukoerythroblastosis Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criterion |
| WHO . | ICC . |
|---|---|
| PV . | PV . |
| Major criteria 1. Hemoglobin >16.5 g/dL in men and >16.0 g/dL in women or hematocrit >49% in men and >48% in women 2. Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis), including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes 3. Presence of JAK2-p.V617F or JAK2 exon 12 mutation Minor criterion - Subnormal serum erythropoietin level Diagnosis of PV requires meeting either all 3 major criteria, or the first 2 major criteria and the minor criterion | Major criteria 1. Elevated hemoglobin concentration (>16.5 g/dL in men and >16.0 g/dL in women) or elevated hematocrit (hematocrit >49% in men and >48% in women) or increased red blood cell mass (>25% above mean normal predicted value) 2. Presence of JAK2-p.V617F or JAK2 exon 12 mutation 3. Bone marrow biopsy showing age-adjusted hypercellularity with trilineage proliferation (panmyelosis), including prominent erythroid, granulocytic, and increase in pleomorphic, mature megakaryocytes without atypia Minor criterion - Subnormal serum erythropoietin level The diagnosis of PV requires either all 3 major criteria or the first 2 major criteria plus the minor criterion |
| ET | ET |
| Major criteria 1. Platelet count ≥450 × 109/L 2. Bone marrow biopsy showing proliferation mainly of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibers. 3. Not meeting WHO criteria for BCR::ABL1-positive CML, PV, PMF, myelodysplastic syndromes, or other myeloid neoplasms 4. Presence of JAK2, CALR, or MPL mutation Minor criterion - Presence of a clonal marker or absence of evidence for reactive thrombocytosis Diagnosis of ET requires meeting all 4 major criteria or the first 3 major criteria and the minor criterion | Major criteria 1. Platelet count ≥450 × 109/L 2. Bone marrow biopsy showing proliferation mainly of the megakaryocytic lineage, with increased numbers of enlarged, mature megakaryocytes with hyperlobulated staghorn-like nuclei, infrequently dense clusters; no significant increase or left shift in neutrophil granulopoiesis or erythropoiesis; no relevant bone marrow fibrosis 3. Diagnostic criteria for BCR::ABL1-positive CML, PV, PMF, or other myeloid neoplasms are not met 4. JAK2, CALR, or MPL mutation Minor criteria - Presence of a clonal marker or absence of evidence of reactive thrombocytosis The diagnosis of ET requires either all major criteria or the first 3 major criteria plus the minor criteria |
| WHO and ICC | WHO and ICC |
| Prefibrotic PMF | Overt PMF |
| Major criteria 1. Megakaryocytic proliferation and atypia, without reticulin fibrosis >grade 1, increased age-adjusted bone marrow cellularity, granulocytic proliferation, and often decreased erythropoiesis 2. Diagnostic criteria for BCR::ABL1-positive CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms are not met 3. Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal marker, or absence of minor reactive bone marrow reticulin fibrosis Minor criteria Presence of at least 1 of the following, confirmed in 2 consecutive determinations: a. Anemia not attributed to a comorbid condition b. Leukocytosis ≥11 × 109/L c. Palpable splenomegaly d. LDH increased to above upper normal limit of institutional reference range Diagnosis of prePMF requires meeting all 3 major criteria, and at least 1 minor criterion | Major criteria 1. Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3 2. Diagnostic criteria for ET, PV, BCR::ABL-1 positive CML, myelodysplastic syndrome, or other myeloid neoplasms are not met 3. Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal marker, or absence of reactive myelofibrosis Minor criteria Presence of at least 1 of the following, confirmed in 2 consecutive determinations: a. Anemia not attributed to a comorbid condition b. Leukocytosis ≥11 × 109/L c. Palpable splenomegaly d. LDH increased above the reference range e. Leukoerythroblastosis Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criterion |