Primary Myelofibrosis Differential Diagnoses

Updated: Feb 02, 2021
  • Author: Asheesh Lal, MBBS, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Diagnostic Considerations

Primary myelofibrosis must be differentiated from conditions in which marrow fibrosis is a secondary development. For example, in patients with carcinoma or lymphoma, bone marrow involvement may be associated with marrow fibrosis, which reverses after effective treatment of the underlying disease. Similarly, in histoplasmosis and tuberculosis, marrow fibrosis may result in granulomatous involvement of the bone marrow. 

Performing testing for bcr:abl gene rearrangements is important to exclude chronic myelogenous leukemia (CML). JAK2V617F mutation can be detected in approximately 50–60% of patients with primary myelofibrosis. [21, 22, 23]

World Health Organization diagnostic criteria for primary myelofibrosis include three major criteria and four minor criteria. Diagnosis requires meeting all three major criteria and at least two minor criteria. [6] The major criteria are as follows:

  1. Megakaryocyte proliferation and atypia accompanied by reticulin and/or collagen fibrosis or, in the absence of reticulin fibrosis, the megakaryocyte changes accompanied by increased marrow cellularity, granulocytic proliferation and oftenndecreased erythropoiesis (ie, pre-fibrotic primary myelofibrosis)
  2. Not meeting WHO criteria for chronic myeloid leukemioa, polycythemia vera, myelodysplastic syndrome, or other myeloid neoplasm
  3. Demonstration of JAK2V617F or other clonal marker, or no evidence of reactive bone marrow fibrosis

Minor criteria are as follows:

  1. Leukoerythroblastosis
  2. Elevated serum lactate dehydrogenase level
  3. Anemia
  4. Palpable splenomegaly

The International Working Group for Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) has established diagnostic criteria for post–polycythemia vera myelofibrosis (PPV-MF) and post–essential thrombocythaemia myelofibrosis (PET-MF). [24] For both disorders, cases must meet the following two criteria:

  • Documentation of a previous diagnosis of PV or PET, as defined by the 2008 WHO criteria
  • Bone marrow fibrosis grade 2–3 (on a 0–3 scale) or grade 3–4 (on a 0–4 scale)

In addition, cases must meet at least two further criteria. For PVV-MF, the additional criteria are as follows:

  • Anemia or sustained loss of requirement for phlebotomy in the absence ofcytoreductive therapy
  • Leukoerythroblastic peripheral blood picture
  • Increasing splenomegaly - Either an increase in palpable splenomegaly of ≥5 cm from the left costal margin or the appearance of a newly palpable splenomegaly
  • Development of one or more constitutional symptoms (>10% weight loss in 6 months, night sweats, unexplained fever >37.5°C)

For PET-MF, the additional criteria are as follows:

  • Anemia and a decrease in hemoglobin level of 2 g/dL or more from baseline
  • Leukoerythroblastic peripheral blood picture
  • Increasing splenomegaly - Either an increase in palpable splenomegaly of ≥5 cm from the left costal margin or the appearance of a newly palpable splenomegaly
  • Development of more than one constitutional symptoms (>10% weight loss in 6 months, night sweats, unexplained fever >37.5°C)
  • Increased lactate dehydrogenase concentration

Differential Diagnoses