Criteria

Several diagnostic criteria for primary myelofibrosis (PMF) have been proposed.

The 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms[2]

The WHO classification divides PMF into prefibrotic/early stage PMF and overt fibrotic stage PMF, and each has a different diagnostic criteria.

Prefibrotic/early stage PMF requires meeting all of the following major criteria and at least one minor criterion (confirmed in 2 consecutive determinations):

  • Major criteria:

    1. Presence of megakaryocyte proliferation and atypia, without reticulin fibrosis grades 2 or 3*, accompanied by increased age-adjusted bone marrow cellularity, granulocytic proliferation, and often decreased erythropoiesis.

    2. Not meeting the WHO criteria for BCR::ABL1ᐩ chronic myeloid leukaemia (CML), polycythaemia vera (PV), essential thrombocythaemia (ET), myelodysplastic syndromes (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 (e.g., ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1) or absence of minor (grade 1) reactive bone marrow reticulin fibrosis (e.g., secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukaemia or other lymphoid neoplasm, metastatic malignancy, or toxic [chronic] myelopathies).

  • Minor criteria:

    • Anaemia not attributed to a comorbid condition

    • Leukocytosis ≥11 × 10⁹/L

    • Palpable splenomegaly

    • LDH increased to above upper normal limit of institutional reference range

Overt fibrotic stage PMF requires meeting all of the following major criteria and at least one minor criterion (confirmed in 2 consecutive determinations):

  • Major criteria:

    1. Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3*.

    2. Not meeting WHO criteria for ET, PV, BCR::ABL1ᐩ CML, 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 (e.g., ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1), or absence of reactive myelofibrosis (e.g., bone marrow fibrosis secondary to infection, autoimmune disorder, or other chronic inflammatory conditions, hairy cell leukaemia or other lymphoid neoplasm, metastatic malignancy, or toxic [chronic] myelopathies).

  • Minor criteria:

    • Anaemia not attributed to a comorbid condition

    • Leukocytosis ≥11 × 10⁹/L

    • Palpable splenomegaly

    • LDH increased to above upper normal limit of institutional reference range

    • Leukoerythroblastosis

*Reticulin fibrosis grade 2: diffuse and dense increase in reticulin with extensive intersections, occasionally with focal bundles of thick fibres mostly consistent with collagen, and/or focal osteosclerosis. Reticulin fibrosis grade 3: diffuse and dense increase in reticulin with extensive intersections and coarse bundles of thick fibres consistent with collagen, usually associated with osteosclerosis.

International Consensus Classification of myeloid neoplasms and acute leukaemias[3]

The International Consensus Classification (ICC) divides PMF into early/prefibrotic stage PMF and overt fibrotic stage PMF, and each has a different diagnostic criteria.

Early/prefibrotic stage PMF requires meeting all of the following major criteria and at least one minor criterion (confirmed in 2 consecutive determinations):

  • Major criteria:

    1. Bone marrow biopsy showing megakaryocytic proliferation and atypia, bone marrow fibrosis grade <2, increased age-adjusted bone marrow cellularity, granulocytic proliferation, and (often) decreased erythropoiesis

    2. JAK2, CALR, or MPL mutation, or presence of another clonal marker (e.g., ASXL1, EZH2, IDH1, IDH2, SF3B1, SRSF2, and TET2 mutations), or absence of reactive bone marrow reticulin fibrosis (e.g., minimal reticulin fibrosis [grade 1] secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukaemia or another lymphoid neoplasm, metastatic malignancy, or toxic [chronic] myelopathies)

    3. Diagnostic criteria for BCR::ABL1-positive CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms are not met.

  • Minor criteria:

    • Anaemia not attributed to a comorbid condition

    • Leukocytosis ≥11 × 10⁹/L

    • Palpable splenomegaly

    • Lactate dehydrogenase level above the reference range

Overt fibrotic stage PMF requires meeting all three major criteria and at least one minor criterion confirmed in two consecutive determinations:

  • 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 (e.g., ASXL1, EZH2, IDH1, IDH2, SF3B1, SRSF2, and TET2 mutations), or absence of reactive myelofibrosis (e.g., minimal reticulin fibrosis [grade 1] secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukaemia or another lymphoid neoplasm, metastatic malignancy, or toxic [chronic] myelopathies)

    3. Diagnostic criteria for ET, PV, BCR::ABL1-positive CML, myelodysplastic syndrome, or other myeloid neoplasms are not met.

  • Minor criteria:

    • Anaemia not attributed to a comorbid condition

    • Leukocytosis ≥11 × 10⁹/L

    • Palpable splenomegaly

    • Lactate dehydrogenase level above the reference range

    • Leukoerythroblastosis

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