Myelofibrosis is a myeloproliferative neoplasm which is characterised by the proliferation of abnormal cells of the megakaryocytic and granulocytic series. This results in a reactive deposition of fibrous tissue in the bone marrow and extramedullary haematopoiesis.

The vast majority of cases are characterised by mutations in JAK2 (50-60%), CALR (20-25%) or MPL (8%)., while a minority are negative for all three classical driver mutations (Tefferi et a., 2014).

Diagnostic criteria (WHO 2016)

All three major criteria and at least one minor criteria are required for diagnosis.

Major criteria:

  • Megakaryocytic proliferation and atypia with grade 2 or 3 reticulin or collagen fibrosis.
  • WHO criteria for CML, MDS, PV, ET or other myeloid neoplasms are not met.
  • Presence of JAK2/CALR/MPL or other clonal mutation, or absence of reactive myelofibrosis.

Minor criteria:

  • Anaemia not attributed to another condition.
  • Leukocytosis ≥ 11×109/L
  • Palpable splenomegaly
  • Lactate dehydrogenase above upper limit of reference range
  • Leukoerythroblastosis
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Blood film features:

  • Leukoerythroblastic picture
  • Teardrop poikilocytes
  • “Stubby” elliptocytes
  • Leukocytosis and thrombocytosis in proliferative MF
  • Platelet anisocytosis 

Other features to look for:

  • Hydroxyurea therapy (macrocytosis, stomatocytes, hypersegmented neutrophils on a background of leukoerythroblastosis)
  • Hyposplenism (old practice for MF – splenectomy)
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Bone marrow features:

  • Pre-fibrotic MF
    • Increased cellularity.
    • Increased myeloid:erythroid ratio.
    • Frequent, dense clusters of megakaryocytes adjacent to bone marrow vascular sinuses and bone trabeculae.
    • Variable megakaryocyte size.
    • Bulbous/hypolobated megakaryocytes.
    • Nuclear atypia in megakaryocytes (including clumped chromatin and abnormal nuclear:cytoplasmic ratios).
    • May have grade 1 reticulin fibrosis.
  • Fibrotic stage
    • Blasts ususally <10% of nucleated cell count.
    • Normo- or hypocellular marrow.
    • Clear-cut reticulin or collagen fibrosis (grade 2 or 3).
    • Normo- or hypocellular with islands of haematopoiesis interspersed with fibrotic tissue or fat.
    • Sheets or large clusters of atypical megakaryocytes within dilated vascular sinuses.
    • Osteosclerosis with new bone formation, resulting in irregular trabeculae which can occupy large proportions of bone marrow space.
    • Vascular proliferation with intrasinusoidal haematopoiesis.

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