Diagnostic criteria for primary myelofibrosis (PMF)
| PMF, early/prefibrotic stage (pre-PMF) . | PMF, overt fibrotic stage . |
|---|---|
| Major criteria 1. Bone marrow biopsy showing megakaryocytic proliferation and atypia,* bone marrow fibrosis grade < 2, increased age-adjusted BM cellularity, granulocytic proliferation, and (often) decreased erythropoiesis 2. JAK2, CALR, or MPL mutation† or presence of another clonal marker‡ or absence of reactive bone marrow reticulin fibrosis§ 3. Diagnostic criteria for BCR::ABL1-positive CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms are not met | Major criteria 1. Bone marrow biopsy showing megakaryocytic proliferation and atypia,* accompanied by reticulin and/or collagen fibrosis grades 2 or 3 2. JAK2, CALR, or MPL mutation† or presence of another clonal marker‡ or absence of reactive myelofibrosis§ 3. Diagnostic criteria for ET, PV, BCR::ABL1-positive CML, myelodysplastic syndrome, or other myeloid neoplasmsǁ are not met |
| Minor criteria • Anemia not attributed to a comorbid condition • Leukocytosis ≥ 11 × 109/L • Palpable splenomegaly • Lactate dehydrogenase level above the above the reference range | Minor criteria • Anemia not attributed to a comorbid condition • Leukocytosis ≥ 11 × 109/L • Palpable splenomegaly • Lactate dehydrogenase level above the above the reference range • Leukoerythroblastosis |
| The diagnosis of pre-PMF or overt PMF requires all 3 major criteria and at least 1 minor criterion confirmed in 2 consecutive determinations | |
| PMF, early/prefibrotic stage (pre-PMF) . | PMF, overt fibrotic stage . |
|---|---|
| Major criteria 1. Bone marrow biopsy showing megakaryocytic proliferation and atypia,* bone marrow fibrosis grade < 2, increased age-adjusted BM cellularity, granulocytic proliferation, and (often) decreased erythropoiesis 2. JAK2, CALR, or MPL mutation† or presence of another clonal marker‡ or absence of reactive bone marrow reticulin fibrosis§ 3. Diagnostic criteria for BCR::ABL1-positive CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms are not met | Major criteria 1. Bone marrow biopsy showing megakaryocytic proliferation and atypia,* accompanied by reticulin and/or collagen fibrosis grades 2 or 3 2. JAK2, CALR, or MPL mutation† or presence of another clonal marker‡ or absence of reactive myelofibrosis§ 3. Diagnostic criteria for ET, PV, BCR::ABL1-positive CML, myelodysplastic syndrome, or other myeloid neoplasmsǁ are not met |
| Minor criteria • Anemia not attributed to a comorbid condition • Leukocytosis ≥ 11 × 109/L • Palpable splenomegaly • Lactate dehydrogenase level above the above the reference range | Minor criteria • Anemia not attributed to a comorbid condition • Leukocytosis ≥ 11 × 109/L • Palpable splenomegaly • Lactate dehydrogenase level above the above the reference range • Leukoerythroblastosis |
| The diagnosis of pre-PMF or overt PMF requires all 3 major criteria and at least 1 minor criterion confirmed in 2 consecutive determinations | |
Morphology of megakaryocytes in pre-PMF and overt PMF usually demonstrates a higher degree of megakaryocytic atypia than in any other MPN subtype; distinctive features of megakaryocytes include small to giant megakaryocytes with a prevalence of severe maturation defects (cloud-like, hypolobulated, and hyperchromatic nuclei) and presence of abnormal large dense clusters (mostly > 6 megakaryocytes lying strictly adjacent).
It is recommended to use highly sensitive assays for JAK2 V617F (sensitivity level < 1%) and CALR and MPL (sensitivity level 1% to 3%); in negative cases, consider searching for noncanonical JAK2 and MPL mutations.
Assessed by cytogenetics or sensitive NGS techniques; detection of mutations associated with myeloid neoplasms (eg, ASXL1, EZH2, IDH1, IDH2, SF3B1, SRSF2, and TET2 mutations) supports the clonal nature of the disease.
Minimal reticulin fibrosis (grade 1) secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukemia or another lymphoid neoplasm, metastatic malignancy, or toxic (chronic) myelopathies.
Monocytosis can be present at diagnosis or develop during the course of PMF; in these cases, a history of MPN excludes CMML, whereas a higher variant allelic frequency for MPN-associated driver mutations is supporting the diagnosis of PMF with monocytosis rather than CMML.