2016 WHO diagnostic criteria for PV, ET, prefibrotic PMF, and overt PMF
| . | Major criteria . | Minor criteria . | Diagnosis requires . |
|---|---|---|---|
| PV | 1. Hemoglobin >16.5 g/dL in men or >16.0 g/dL in women, OR hematocrit >49% in men or >48% in women, OR increased red cell mass (>25% above mean normal predicted value) 2. BM biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size) 3. Presence of JAK2 (V617F) or JAK2 exon 12 mutation | Subnormal serum erythropoietin level | Diagnosis of PV requires meeting all 3 major criteria or the first 2 major criteria and the minor criterion. Note: Criterion number 2 (BM biopsy) may not be required in cases with sustained absolute erythrocytosis: hemoglobin levels >18.5 g/dL in men (hematocrit, 55.5%) or >16.5 g/dL in women (hematocrit, 49.5%) if major criterion 3 and the minor criterion are present. However, initial myelofibrosis (present in up to 20% of patients) can only be detected by performing a BM biopsy; this finding may predict a more rapid progression to overt myelofibrosis (post-PV myelofibrosis) |
| ET | 1. Platelet count ≥450 × 109/L 2. BM biopsy showing proliferation mainly of the megakaryocyte 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+ CML, PV, PMF, myelodysplastic syndromes, or other myeloid neoplasms 4. Presence of JAK2, CALR, or MPL mutation | 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. |
| Prefibrotic PMF | 1. Megakaryocytic proliferation and atypia, without reticulin fibrosis >grade 1, accompanied by increased age-adjusted bone marrow cellularity, granulocytic proliferation, and often decreased erythropoiesis 2. Not meeting WHO criteria for BCR-ABL1+ CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms 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 BM reticulin fibrosis (minor reticulin fibrosis secondary to infection, autoimmune disorder, or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, or toxic myelopathies) | Presence of at least 1 of the following, confirmed in 2 consecutive determinations: • Anemia not attributed to a comorbid condition • Leukocytosis (WBC count ≥11 × 109/L) • Palpable splenomegaly • LDH level increased to above upper normal limit of institutional reference range | Diagnosis of prefibrotic myelofibrosis requires meeting all 3 major criteria, and at least 1 minor criterion. Note: In the absence of any of the 3 major clonal mutations, the search for the most frequent accompanying mutations (eg, ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1) are of help in determining the clonal nature of the disease. |
| Overt PMF | 1. Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3 2. Not meeting WHO criteria for BCR-ABL1+ CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms 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 BM reticulin fibrosis (minor reticulin fibrosis secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, or toxic myelopathies) | Presence of at least 1 of the following, confirmed in 2 consecutive determinations: • Anemia not attributed to a comorbid condition • Leukocytosis (WBC count ≥11 × 109/L) • Palpable splenomegaly • LDH level increased to above upper normal limit of institutional reference range • Leukoerythroblastosis | Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criterion. Note: In the absence of any of the 3 major clonal mutations, the search for the most frequent accompanying mutations (eg, ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1) are of help in determining the clonal nature of the disease. |
| . | Major criteria . | Minor criteria . | Diagnosis requires . |
|---|---|---|---|
| PV | 1. Hemoglobin >16.5 g/dL in men or >16.0 g/dL in women, OR hematocrit >49% in men or >48% in women, OR increased red cell mass (>25% above mean normal predicted value) 2. BM biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size) 3. Presence of JAK2 (V617F) or JAK2 exon 12 mutation | Subnormal serum erythropoietin level | Diagnosis of PV requires meeting all 3 major criteria or the first 2 major criteria and the minor criterion. Note: Criterion number 2 (BM biopsy) may not be required in cases with sustained absolute erythrocytosis: hemoglobin levels >18.5 g/dL in men (hematocrit, 55.5%) or >16.5 g/dL in women (hematocrit, 49.5%) if major criterion 3 and the minor criterion are present. However, initial myelofibrosis (present in up to 20% of patients) can only be detected by performing a BM biopsy; this finding may predict a more rapid progression to overt myelofibrosis (post-PV myelofibrosis) |
| ET | 1. Platelet count ≥450 × 109/L 2. BM biopsy showing proliferation mainly of the megakaryocyte 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+ CML, PV, PMF, myelodysplastic syndromes, or other myeloid neoplasms 4. Presence of JAK2, CALR, or MPL mutation | 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. |
| Prefibrotic PMF | 1. Megakaryocytic proliferation and atypia, without reticulin fibrosis >grade 1, accompanied by increased age-adjusted bone marrow cellularity, granulocytic proliferation, and often decreased erythropoiesis 2. Not meeting WHO criteria for BCR-ABL1+ CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms 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 BM reticulin fibrosis (minor reticulin fibrosis secondary to infection, autoimmune disorder, or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, or toxic myelopathies) | Presence of at least 1 of the following, confirmed in 2 consecutive determinations: • Anemia not attributed to a comorbid condition • Leukocytosis (WBC count ≥11 × 109/L) • Palpable splenomegaly • LDH level increased to above upper normal limit of institutional reference range | Diagnosis of prefibrotic myelofibrosis requires meeting all 3 major criteria, and at least 1 minor criterion. Note: In the absence of any of the 3 major clonal mutations, the search for the most frequent accompanying mutations (eg, ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1) are of help in determining the clonal nature of the disease. |
| Overt PMF | 1. Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3 2. Not meeting WHO criteria for BCR-ABL1+ CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms 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 BM reticulin fibrosis (minor reticulin fibrosis secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, or toxic myelopathies) | Presence of at least 1 of the following, confirmed in 2 consecutive determinations: • Anemia not attributed to a comorbid condition • Leukocytosis (WBC count ≥11 × 109/L) • Palpable splenomegaly • LDH level increased to above upper normal limit of institutional reference range • Leukoerythroblastosis | Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criterion. Note: In the absence of any of the 3 major clonal mutations, the search for the most frequent accompanying mutations (eg, ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1) are of help in determining the clonal nature of the disease. |
The information is from Arber et al.3
BM, bone marrow.