Diagnostic criteria for the chronic phase of PV and ET and for prefibrotic PMF: revised 2016 WHO criteria
| 2016 WHO Criteria . | PV . | ET . | Early/Pre-PMF . |
|---|---|---|---|
| Major | 1. Hb (>16.5 g/dL in men; >16.0 g/dL in women) or hematocrit (>49% in men; >48% in women) or increased RCM* 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 JAK2V617F or JAK2 exon 12 mutation | 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-ABL11 CML, PV, PMF, MDSs, or other myeloid neoplasms 4. Presence of JAK2, CALR, or MPL mutation. | 1. Megakaryocytic proliferation and atypia, without reticulin fibrosis >grade 1, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation, and often decreased erythropoiesis 2. Not meeting the WHO criteria for BCR-ABL + CML, PV, ET, MDS, 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 | Subnormal serum erythropoietin level | Presence of a clonal marker or absence of evidence for reactive thrombocytosis | a. Anemia not attributed to a comorbid condition b. Leukocytosis ≥11 × 109/L c. Palpable splenomegaly d. LDH increased to above upper normal range |
| Criteria required for diagnosis | All 3 major or the first 2 major and the minor criterion | All 4 major criteria or the first 3 major and the minor criterion | All 3 major criteria, and at least 1 minor criterion |
| 2016 WHO Criteria . | PV . | ET . | Early/Pre-PMF . |
|---|---|---|---|
| Major | 1. Hb (>16.5 g/dL in men; >16.0 g/dL in women) or hematocrit (>49% in men; >48% in women) or increased RCM* 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 JAK2V617F or JAK2 exon 12 mutation | 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-ABL11 CML, PV, PMF, MDSs, or other myeloid neoplasms 4. Presence of JAK2, CALR, or MPL mutation. | 1. Megakaryocytic proliferation and atypia, without reticulin fibrosis >grade 1, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation, and often decreased erythropoiesis 2. Not meeting the WHO criteria for BCR-ABL + CML, PV, ET, MDS, 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 | Subnormal serum erythropoietin level | Presence of a clonal marker or absence of evidence for reactive thrombocytosis | a. Anemia not attributed to a comorbid condition b. Leukocytosis ≥11 × 109/L c. Palpable splenomegaly d. LDH increased to above upper normal range |
| Criteria required for diagnosis | All 3 major or the first 2 major and the minor criterion | All 4 major criteria or the first 3 major and the minor criterion | All 3 major criteria, and at least 1 minor criterion |
BM, bone marrow; CML, chronic myeloid leukemia; ET, essential thrombocythemia; Hb, hemoglobin; LDH, lactate dehydrogenase; MDS, myelodysplastic syndrome; MF, myelofibrosis; PMF, primary myelofibrosis; PV, polycythemia vera; RCM, red cell mass; WHO, World Health Organization.
More than 25% above mean normal predicted value.
BM biopsy may not be required in cases with sustained absolute erythrocytosis defined as 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 MF can only be detected by performing a BM biopsy; this finding may predict a more rapid progression to overt MF (post-PV MF).
In the absence of any of the 3 driver 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.
Minor (grade 1) reticulin fibrosis secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, or toxic (chronic) myelopathies.