Table 3.

Diagnostic criteria for early/pre-fibrotic and overt primary myelofibrosis (PMF) according to the International Consensus Classification¹

	Early/pre-fibrotic—PMF	Overt—PMF
Major criteria	1. Bone marrow biopsy showing megakaryocytic proliferation and atypiaa), bone marrow fibrosis grade < 2, increased age-adjusted BM cellularity, granulocytic proliferation, and (often) decreased erythropoiesis	1. Bone marrow biopsy showing megakaryocytic proliferation and atypiaa, accompanied by reticulin and/or collagen fibrosis grades 2 or 3
	2. JAK2, CALR, or MPL mutationb or presence of another clonal markerc or absence of reactive bone marrow reticulin fibrosisd	2. JAK2, CALR, or MPL mutationb or presence of another clonal markerc or absence of reactive bone marrow reticulin fibrosisd
	3. Diagnostic criteria for BCR::ABL1 positive chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelodysplastic syndromes, or other myeloid neoplasmse are not met	3. Diagnostic criteria for BCR::ABL1 positive chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelodysplastic syndromes, or other myeloid neoplasmse are not met
Minor criteria	1. Anemia not attributed to a comorbid condition	1. Anemia not attributed to a comorbid condition
	2. Leukocytosis ≥ 11 × 109/L	2. Leukocytosis ≥ 11 × 109/L
	3. Palpable splenomegaly	3. Palpable splenomegaly
	4. Lactate dehydrogenase level above the reference range	4. Lactate dehydrogenase level above the reference range
		5. 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

^aMorphology 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)

^bIt is recommended to use highly sensitive assays for JAK2 V617F (sensitivity level < 1%) and CALR and MPL (sensitivity level 1−3%)—in negative cases, consider searching for non-canonical JAK2 and MPL mutations.

^cAssessed by cytogenetics or sensitive NGS techniques; detection of mutations associated with myeloid neoplasms (e.g., ASXL1, EZH2, IDH1, IDH2, SF3B1, SRSF2, and TET2 mutations) supports the clonal nature of the disease

^dMinimal 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

^eMonocytosis 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