Objectives: Primary myelofibrosis (PMF) is a BCR/ABL1-negative myeloproliferative neoplasm (MPN) with a shorter overall survival and a higher leukemic transformation than other BCR/ABL1-negative MPNs. Diagnosis of PMF can be challenging given its clinical, morphologic, molecular overlap with other myeloid neoplasms also associated with myelofibrosis, and reactive conditions.
Methods: We summarize and discuss the clinical, morphologic, and molecular features useful for diagnosing PMF as well as salient features helpful in distinguishing PMF from myelodysplastic syndrome with associated fibrosis and autoimmune myelofibrosis using a case-based approach.
Results: PMF in both its prefibrotic and fibrotic stages, the latter characterized by reticulin/collagen marrow fibrosis, is characterized by a proliferation of predominantly abnormal megakaryocytes and granulocytes in the bone marrow. Driver mutations in JAK2, CALR, or MPLare seen in approximately 90% of PMF cases. In triple-negative cases, the presence of cytogenetic abnormalities and other somatic mutations identified by next-generation sequencing can help establish a diagnosis of PMF in the appropriate clinical and morphologic context.
Conclusions: Given the significant difference in prognosis and treatment, integration of clinical, morphological, and molecular/genetic findings is essential in distinguishing PMF from other etiologies that can demonstrate myelofibrosis.
Keywords: Autoimmune myelofibrosis; Myelodysplastic syndrome with associated fibrosis; Myeloproliferative neoplasm; Primary myelofibrosis.
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