2022 International Consensus Classification diagnostic criteria for PV and ET
| Essential thrombocythemia . | Polycythemia vera . |
|---|---|
| Major criteria | |
| 1. Platelet count ≥450 × 109/L | 1. Elevated hemoglobin concentration or elevated hematocrit or increased red blood cell massf |
| 2. BM biopsy showing proliferation mainly of the megakaryocytic lineage, with increased numbers of enlarged, mature megakaryocytes with hyperlobulated staghorn-like nuclei, infrequently dense clustersa; no significant increase or left shift in neutrophil granulopoiesis or erythropoiesis; no relevant BM fibrosisb | 2. Presence of JAK2 V617F or JAK2 exon 12 mutationg |
| 3. Diagnostic criteria for BCR-ABL1-positive CML, PV, PMF, or other myeloid neoplasms are not met | 3. BM biopsy showing age-adjusted hypercellularity with trilineage proliferation (panmyelosis), including prominent erythroid and granulocytic and increased pleomorphic, mature megakaryocytes without atypia |
| 4. JAK2, CALR, or MPL mutationc | |
| Minor criterion | |
| Presence of a clonal markerd or absence of evidence of reactive thrombocytosise | Subnormal serum erythropoietin level |
| The diagnosis of ET requires either all 4 major criteria or the first 3 major criteria plus the minor criterion | The diagnosis of PV requires either all 3 major criteria or the first 2 major criteria plus the minor criterionh |
| Essential thrombocythemia . | Polycythemia vera . |
|---|---|
| Major criteria | |
| 1. Platelet count ≥450 × 109/L | 1. Elevated hemoglobin concentration or elevated hematocrit or increased red blood cell massf |
| 2. BM biopsy showing proliferation mainly of the megakaryocytic lineage, with increased numbers of enlarged, mature megakaryocytes with hyperlobulated staghorn-like nuclei, infrequently dense clustersa; no significant increase or left shift in neutrophil granulopoiesis or erythropoiesis; no relevant BM fibrosisb | 2. Presence of JAK2 V617F or JAK2 exon 12 mutationg |
| 3. Diagnostic criteria for BCR-ABL1-positive CML, PV, PMF, or other myeloid neoplasms are not met | 3. BM biopsy showing age-adjusted hypercellularity with trilineage proliferation (panmyelosis), including prominent erythroid and granulocytic and increased pleomorphic, mature megakaryocytes without atypia |
| 4. JAK2, CALR, or MPL mutationc | |
| Minor criterion | |
| Presence of a clonal markerd or absence of evidence of reactive thrombocytosise | Subnormal serum erythropoietin level |
| The diagnosis of ET requires either all 4 major criteria or the first 3 major criteria plus the minor criterion | The diagnosis of PV requires either all 3 major criteria or the first 2 major criteria plus the minor criterionh |
Three or more megakaryocytes lying adjacent without other BM cells in between; in most of these rare clusters, 6 or fewer megakaryocytes may be observed. An increase in huge clusters (>6 cells) accompanied by granulocytic proliferation is a morphological hallmark of pre-PMF.
Very rarely, a minor increase in reticulin fibers may occur at initial diagnosis (grade 1).
It is recommended that highly sensitive assays be used for JAK2 V617F (sensitivity level <1%) and CALR and MPL (sensitivity level 1% to 3%); in negative cases, consider a search for noncanonical JAK2 and MPL mutations.
Assessed by cytogenetics or sensitive next-generation sequencing techniques.
Reactive causes of thrombocytosis include a variety of underlying conditions like iron deficiency, chronic infection, chronic inflammatory disease, medication, neoplasia, or history of splenectomy.
Diagnostic thresholds: hemoglobin level above 16.5 g/dL in men and 16.0 g/dL in women; hematocrit above 49% in men and 48% in women; red blood cell mass 25% above mean normal predicted value.
A BM biopsy may not be required in patients with sustained absolute erythrocytosis (hemoglobin concentrations above 18.5 g/dL in men or 16.5 g/dL in women and hematocrit values above 55.5% in men or 49.5% in women) and the presence of a JAK2 V617F or JAK2 exon 12 mutation.
Highly sensitive assays for JAK2 V617F (sensitivity level <1%) are recommended; in negative cases, consider searching for noncanonical or atypical JAK2 mutations in exons 12 to 15.
CML, chronic myelogenous leukemia; PMF, primary myelofibrosis.