Primary Myelofibrosis
Definition
- Myeloproliferative neoplasm characterized by panmyelosis, clustered hyperchromatic megakaryocyte proliferation and development of bone marrow fibrosis
Alternate/Historical Names
- Agnogenic myeloid metaplasia
- Chronic idiopathic myelofibrosis
- Myelofibrosis with myeloid metaplasia
Diagnostic Criteria
- All three major and two minor criteria required for diagnosis
- Major
- Atypical densely clustered megakaryocytic hyperplasia with either:
- Fibrosis (MF-2 or 3) (fibrotic phase) OR
- Hypercellular marrow with granulocytic hyperplasia (cellular phase)
- Does not meet criteria for PV, CML, MDS or other myeloid neoplasm
- Jak2V617F or other clonal marker (MPL W515K/L), OR
- If no clonal marker, exclusion of secondary causes of fibrosis (see Differential Diagnosis)
- Minor
- Splenomegaly
- Leukoerythroblastosis
- Anemia
- Increase in serum LDH
- Cellular / prefibrotic phase is characterized by hypercellularity but absent or minimal reticulin fibrosis
- MF-0 or 1 (European consensus grading system, Thiele 2005)
- Peripheral blood may show only marked thrombocytosis
- Hypercellular marrow
- Prominent megakaryocytic hyperplasia with dense clustering
- Increased M:E ratio
- Pleomorphic megakaryocytes
- Hyperchromasia and coarse lobulations
- Increased N:C ratio
- Anisocytosis
- Fibrotic phase is characterized by marrow fibrosis
- Leukoerythroblastic peripheral blood findings
- RBC may show teardrops
- Anemia with mild reticulocytosis and nucleated RBCs
- Variable platelet count with giant hypogranular bizarre forms
- Circulating megakaryocytes and/or bare nuclei can be seen
- Leukocytosis, 15-30 x 103/μL
- Left shift with 1-10% myeloblasts
- Basophilia, eosinophilia in 10-30% of cases
- Can present with isolated thrombocytosis
- Marrow fibrosis
- MF-2 or 3 (European consensus grading system, Thiele 2005)
- May include collagen fibrosis
- Loss of hematopoiesis, except for megakaryocytes
- Osteosclerosis can be dramatic and occupy >50% of marrow
- May lead to massive splenomegaly with extramedullary hematopoiesis
- Dilated sinuses with intravascular hematopoiesis
Dita Gratzinger MD PhD
Tracy I George MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting: 10/23/11
