Diagnostic Considerations

Primary myelofibrosis (PMF) should be distinguished from other myeloid neoplasms including chronic myeloid leukemia (CML), PV, ET, MDS, and chronic myelomonocytic leukemia (CMML). The presence of dwarf megakaryocytes raises the possibility of CML and should be pursued with BCR‐ABL1 cytogenetic or molecular testing.^[21]

Patients who otherwise fulfill the diagnostic criteria for PV should be labeled as “PV” even if they display substantial bone marrow fibrosis.^[21]

Prefibrotic PMF can mimic ET in its presentation and mutation profile (both can express JAK2, CALR or MPL mutations) and careful morphologic examination is necessary for distinguishing the two; megakaryocytes in ET are large and mature‐appearing whereas those in prefibrotic PMF display abnormal maturation with hyperchromatic and irregularly folded nuclei.^[21]

MDS should be suspected in the presence of dyserythropoiesis or dysgranulopoiesis. CMML is a possibility in the presence of peripheral blood monocyte count of greater than 1 × 109/L. Patients with acute myelofibrosis (either acute panmyelosis with myelofibrosis or acute megakaryoblastic leukemia) usually present with severe constitutional symptoms, pancytopenia, mild or no splenomegaly, and increased circulating blasts.^[21]

Differential Diagnoses

Workup

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Media Gallery

Peripheral smear of a patient with chronic myelogenous leukemia (CML) shows leukocytosis with extreme left shift and basophilia.
Peripheral smear of a patient with chronic myelogenous leukemia (CML) in blastic phase shows several blasts.
Peripheral smear of a patient with essential thrombocythemia (ET) shows markedly increased number of platelets. Some of the platelets are giant (arrow).
Peripheral smear of a patient with agnogenic myeloid metaplasia (myelofibrosis) shows leukoerythroblastosis. This photomicrograph also shows giant platelets.
Photomicrograph of a peripheral smear of a patient with agnogenic myeloid metaplasia (myelofibrosis) shows findings of leukoerythroblastosis, giant platelets, and few teardrop cells.

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FAB	WHO
Chronic myelogenous leukemia	Chronic myelogenous leukemia, BCR/ABL1 positive
Polycythemia vera	Polycythemia vera
Essential thrombocythemia	Essential thrombocythemia
Agnogenic myeloid metaplasia/myelofibrosis	Primary myelofibrosis*
...	Chronic neutrophilic leukemia, not otherwise specified
...	MPN, unclassified
*The 2016 WHO classification system distinguishes prefibrotic (prePMF) from overtly fibrotic PMF ^[4]

Myeloproliferative Disease Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

References

Tables

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