Myelofibrosis diagnosis, WHO 2008

Diagnostic criteria for primary myelofibrosis (World Health Organisation, 2008)

Diagnosis requires all three major criteria PLUS two minor criteria

Major criteria (all three required)
  1. Megakaryocyte proliferation and atypia, usually with either reticulin and/or collagen fibrosis (a)
  2. Does NOT meet WHO criteria for any of the following: polycythemia vera (b), BCR-ABL1-chronic myelogenous leukemia (c), myelodysplastic syndrome (d), another myeloid neoplasm
  3. Presence of JAK2 V617F or other clonal marker (eg MPL W515K/L), OR in absence of a clonal marker, no evidence that the marrow fibrosis or other changes are reactive (e)
Minor criteria (at least two required)
  1. Leukoerythroblastosis (f)
  2. Increase in serum LDH (f)
  3. Anemia (f)
  4. Splenomegaly (f)
Notes
(a) Small to large megakaryocytes with aberrant N:C ratio and hyperchromatic, bulbous or irregularly-folded nuclei and dense clustering. In absence of significant reticulin fibrosis, the megakaryocyte changes must be accompanied by increased bone marrow cellularity characterized by granulocytic proliferation and often decreased erythropoiesis (ie prefibrotic cellular-phase disease)
(b) if serum ferritin reduced, WHO guidelines state exclusion of polycythemia requires failure of iron replacement to raise the hemoglobin to the polycythemia vera range (PV exclusion based on hemoglobin and hematocrit levels - red cell mass measurement not required)
(c) BCR-ABL1 must be absent
(d) dyserythropoiesis and dysgranulopoiesis must be absent
(e) Causes of reactive bone marrow fibrosis include: infection, autoimmune disorder or other chronic inflammatory condition, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, toxic (chronic) myelopathy
(f) May be borderline or marked

These World Health Organistation (WHO) criteria for the diagnosis of primary myelofibrosis (PMF; also chronic idiopathic myelofibrosis, agnogenic myeloid metaplasia) were proposed in 2007,1 and published in the fourth edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.2