Diagnosis: Primary Myelofibrosis or Post-Polycythemia Vera Myelofibrosis
The combination of absolute neutrophilia with teardrop cells (dacrocytes) and elliptocytes strongly suggests primary myelofibrosis (PMF) or post-polycythemia vera myelofibrosis (post-PV MF), requiring immediate bone marrow biopsy with reticulin staining to confirm marrow fibrosis and assess blast percentage. 1, 2
Diagnostic Workup
Immediate Laboratory Evaluation
- Bone marrow biopsy with reticulin/trichrome staining is essential to document fibrosis grade and exclude blast transformation 1
- JAK2 V617F mutation testing should be performed, as this mutation is present in the majority of myeloproliferative neoplasms 1
- Complete blood count with differential to quantify the absolute neutrophil count and assess for other cytopenias 1
- Peripheral blood smear review to quantify teardrop cells, immature myeloid cells, and nucleated red blood cells 2
- Cytogenetic analysis to identify high-risk abnormalities and guide prognosis 1
Key Morphologic Features
- Teardrop cells (dacrocytes) in the setting of neutrophilia indicate extramedullary hematopoiesis and altered marrow architecture from myelofibrosis 3
- Elliptocytes combined with teardrop cells suggest membrane stress from splenic sequestration and extramedullary hematopoiesis 3, 4
- Leukoerythroblastic picture (immature myeloid cells and nucleated RBCs) supports myelofibrosis diagnosis 2
Distinguishing Post-PV Myelofibrosis
The research evidence shows that persistent neutrophilic leukocytosis ≥13 × 10⁹/L developing at or around progression to post-PV myelofibrosis is associated with more aggressive disease and shorter overall survival 2. Look for:
- History of polycythemia vera (elevated hemoglobin/hematocrit previously)
- Current or recent splenomegaly
- Transition from erythrocytosis to anemia
- JAK2 mutation positivity 2
Treatment Approach
Risk Stratification
Calculate IPSS-R score using cytogenetics, blast percentage, hemoglobin, platelet count, and absolute neutrophil count to determine risk category and guide treatment intensity 1
Treatment Based on Risk Category
Higher-Risk Disease (IPSS-R Intermediate-2 or High)
- Ruxolitinib (JAK1/2 inhibitor) is first-line therapy for symptomatic splenomegaly or constitutional symptoms, with response defined as ≥35% spleen volume reduction by imaging 1
- Allogeneic stem cell transplantation should be considered for eligible patients without major comorbidities, as this is the only curative option 1
- Clinical trial enrollment should be pursued when available 1
Lower-Risk Disease with Symptomatic Neutrophilia
- Hydroxyurea can be used to control elevated white blood cell counts and reduce splenomegaly 1
- Observation with regular monitoring if asymptomatic, with CBC every 3-6 months 1
Management of Cytopenias
If neutropenia develops during treatment:
- Hold therapy when ANC <1.0 × 10⁹/L, resume at reduced dose when ANC ≥1.5 × 10⁹/L 1
- G-CSF support can be considered for persistent grade 3-4 neutropenia, though evidence for improved outcomes is limited 1
Monitoring for Progression
- Assess for blast transformation with bone marrow biopsy if peripheral blasts ≥10% or clinical deterioration 1
- Monitor for thrombotic complications, as neutrophilia at disease onset is associated with increased thrombosis risk 2
- Serial spleen assessments by palpation or imaging to track disease progression 1
Critical Pitfalls to Avoid
Do not attribute neutrophilia solely to infection or inflammation without excluding myeloproliferative neoplasm, especially when teardrop cells are present 2, 3. The combination is pathognomonic for marrow fibrosis with extramedullary hematopoiesis.
Do not delay bone marrow biopsy in patients with this presentation, as early identification of blast percentage and fibrosis grade is essential for treatment planning 1.
Do not assume elliptocytes indicate hereditary elliptocytosis when accompanied by neutrophilia and teardrop cells; this combination suggests acquired pathology from myelofibrosis 3, 5.