2016 WHO classification for MPNs
| 2016 WHO diagnostic criteria for PV (Diagnosis of PV requires meeting either all 3 major criteria, or the first 2 major criteria and the minor criterion) | |
| Major criteria | |
| Criterion 1 (clinical) | |
| Hb, or | >16.5 g/dL in men, >16.0 g/dL in women |
| Hematocrit, or | >49% in men, >48% in women |
| Red cell mass | Increased 25% above mean normal predicted value |
| Criterion 2 (morphologic) | |
| BM morphology* | Hypercellularity for age with trilineage growth (panmyelosis), including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature MKs (differences in size) |
| Criterion 3 (genetic) | |
| JAK2V617F, or | Presence |
| JAK2 exon 12 mutation | Presence |
| Minor criterion | |
| Serum Epo level | Subnormal |
| 2016 WHO diagnostic criteria for ET | |
| (Diagnosis of ET requires meeting all 4 major criteria, or the first 3 major criteria and the minor criterion) | |
| Major criteria | |
| Criterion 1 (clinical) | |
| Platelet count | >450 × 109/L |
| Criterion 2 (morphologic) | |
| BM morphology | Proliferation mainly of the MK lineage with increased numbers of enlarged, mature MKs with hyperlobulated nuclei. No significant increase or left-shift in neutrophil granulopoiesis or erythropoiesis, and very rarely minor (grade 1) increase in reticulin fibers |
| Criterion 3 (clinical) | |
| WHO criteria for BCR-ABL1 + CML, PV, PMF, MDS, or other myeloid neoplasms | Not meeting |
| Criterion 4 (genetic) | |
| JAK2, CALR, or MPL mutation | Presence |
| Minor criterion | |
| Clonal marker, or | Presence |
| Reactive thrombocytosis | Absence |
| 2016 WHO diagnostic criteria for prefibrotic/early PMF | |
| (Diagnosis of pre-PMF requires meeting all 3 major criteria, and at least 1 minor criterion) | |
| Major criteria | |
| Criterion 1 (morphologic) | |
| BM morphology | Megakaryocytic proliferation and atypia, without reticulin fibrosis > grade 1, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation, and often decreased erythropoiesis |
| Criterion 2 (clinical) | |
| WHO criteria for BCR-ABL1 + CML, PV, ET, MDS, or other myeloid neoplasms | Not meeting |
| Criterion 3 (genetic) | |
| JAK2, CALR or MPL mutation, or | Presence |
| Clonal marker,† or | Presence |
| Reactive BM reticulin fibrosis‡ | Absence |
| Minor criteria | |
| Anemia not attributed to a comorbid condition | Presence |
| Leukocyte count | ≥11 × 109/L |
| Spleen size | Palpable |
| Serum LDH | Increased to above upper normal limit of institutional reference range |
| 2016 WHO diagnostic criteria for PMF | |
| (Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criterion) | |
| Major criteria | |
| Criterion 1 (morphologic) | |
| BM morphology | Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3 |
| Criterion 2 (morphologic) | |
| WHO criteria for ET, PV, BCR-ABL1 + CML, MDS, or other myeloid neoplasms | Not meeting |
| Criterion 3 (genetic) | |
| JAK2, CALR, or MPL mutation, or | Presence |
| Clonal marker,† or | Presence |
| Reactive BM reticulin fibrosis‡ | Absence |
| Minor criteria | |
| Anemia not attributed to a comorbid condition | Presence |
| Leukocyte count | ≥11 × 109/L |
| Spleen size | Palpable |
| Serum LDH | Increased to above upper normal limit of institutional reference range |
| Leukoerythroblastosis | Presence |
| 2016 WHO diagnostic criteria for PV (Diagnosis of PV requires meeting either all 3 major criteria, or the first 2 major criteria and the minor criterion) | |
| Major criteria | |
| Criterion 1 (clinical) | |
| Hb, or | >16.5 g/dL in men, >16.0 g/dL in women |
| Hematocrit, or | >49% in men, >48% in women |
| Red cell mass | Increased 25% above mean normal predicted value |
| Criterion 2 (morphologic) | |
| BM morphology* | Hypercellularity for age with trilineage growth (panmyelosis), including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature MKs (differences in size) |
| Criterion 3 (genetic) | |
| JAK2V617F, or | Presence |
| JAK2 exon 12 mutation | Presence |
| Minor criterion | |
| Serum Epo level | Subnormal |
| 2016 WHO diagnostic criteria for ET | |
| (Diagnosis of ET requires meeting all 4 major criteria, or the first 3 major criteria and the minor criterion) | |
| Major criteria | |
| Criterion 1 (clinical) | |
| Platelet count | >450 × 109/L |
| Criterion 2 (morphologic) | |
| BM morphology | Proliferation mainly of the MK lineage with increased numbers of enlarged, mature MKs with hyperlobulated nuclei. No significant increase or left-shift in neutrophil granulopoiesis or erythropoiesis, and very rarely minor (grade 1) increase in reticulin fibers |
| Criterion 3 (clinical) | |
| WHO criteria for BCR-ABL1 + CML, PV, PMF, MDS, or other myeloid neoplasms | Not meeting |
| Criterion 4 (genetic) | |
| JAK2, CALR, or MPL mutation | Presence |
| Minor criterion | |
| Clonal marker, or | Presence |
| Reactive thrombocytosis | Absence |
| 2016 WHO diagnostic criteria for prefibrotic/early PMF | |
| (Diagnosis of pre-PMF requires meeting all 3 major criteria, and at least 1 minor criterion) | |
| Major criteria | |
| Criterion 1 (morphologic) | |
| BM morphology | Megakaryocytic proliferation and atypia, without reticulin fibrosis > grade 1, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation, and often decreased erythropoiesis |
| Criterion 2 (clinical) | |
| WHO criteria for BCR-ABL1 + CML, PV, ET, MDS, or other myeloid neoplasms | Not meeting |
| Criterion 3 (genetic) | |
| JAK2, CALR or MPL mutation, or | Presence |
| Clonal marker,† or | Presence |
| Reactive BM reticulin fibrosis‡ | Absence |
| Minor criteria | |
| Anemia not attributed to a comorbid condition | Presence |
| Leukocyte count | ≥11 × 109/L |
| Spleen size | Palpable |
| Serum LDH | Increased to above upper normal limit of institutional reference range |
| 2016 WHO diagnostic criteria for PMF | |
| (Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criterion) | |
| Major criteria | |
| Criterion 1 (morphologic) | |
| BM morphology | Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3 |
| Criterion 2 (morphologic) | |
| WHO criteria for ET, PV, BCR-ABL1 + CML, MDS, or other myeloid neoplasms | Not meeting |
| Criterion 3 (genetic) | |
| JAK2, CALR, or MPL mutation, or | Presence |
| Clonal marker,† or | Presence |
| Reactive BM reticulin fibrosis‡ | Absence |
| Minor criteria | |
| Anemia not attributed to a comorbid condition | Presence |
| Leukocyte count | ≥11 × 109/L |
| Spleen size | Palpable |
| Serum LDH | Increased to above upper normal limit of institutional reference range |
| Leukoerythroblastosis | Presence |
LDH, lactate dehydrogenase; MDS, myelodysplastic syndrome; MK, megakaryocyte.
*Criterion number 2 (BM biopsy) may not be required in cases with sustained absolute erythrocytosis: Hb 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.
†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, and 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.