What is the diagnosis and treatment for a patient with leukopenia (low polymorphonuclear cells), lymphocytosis (high lymphocytes), eosinophilia (high eosinophils), elevated RDW (Red Cell Distribution Width), and elevated MCH-CV (Mean Corpuscular Hemoglobin Concentration)?

Diagnostic Approach to Low Polymorphs, High Lymphocytes, High Eosinophils, Elevated RDW and MCH

This constellation of findings—low polymorphonuclear cells (neutropenia), lymphocytosis, eosinophilia, and elevated RDW—requires immediate molecular and cytogenetic testing to exclude myeloid/lymphoid neoplasms with tyrosine kinase fusion genes, particularly PDGFRA/PDGFRB rearrangements, which are life-threatening if untreated but highly responsive to targeted therapy. 1

Immediate Priority: Rule Out Life-Threatening Hematologic Malignancies

The combination of eosinophilia with lymphocytosis raises concern for several specific entities that require urgent identification:

Test for Tyrosine Kinase Fusion Genes First

• Order FISH or RT-PCR for PDGFRA rearrangements (especially FIP1L1-PDGFRA fusion) immediately, as this predicts dramatic response to imatinib and is associated with life-threatening cardiac complications including endomyocardial fibrosis and cardiogenic shock if left untreated 1
• Test for PDGFRB, FGFR1, JAK2, FLT3, and ABL1 rearrangements to define specific myeloid/lymphoid neoplasms with eosinophilia that require targeted therapy 1
• Exclude BCR-ABL fusion gene (Philadelphia chromosome) through cytogenetics and RT-PCR, as chronic myeloid leukemia can present with eosinophilia and basophilia 2

Assess for Organ Damage Urgently

• Obtain echocardiogram and serum troponin immediately if eosinophilia is present with any tyrosine kinase fusion gene, as patients are at high risk for endomyocardial fibrosis 1
• Monitor for fever, cardiac symptoms (chest pain, dyspnea), and respiratory status daily if symptomatic 1

Differential Diagnosis Based on Cell Pattern

Chronic Myelomonocytic Leukemia (CMML) Considerations

The combination of lymphocytosis with eosinophilia could suggest CMML with eosinophilia:

• Verify persistent peripheral blood monocytosis (>1×10⁹/L) as this is required for CMML diagnosis 2
• Confirm absence of Philadelphia chromosome or BCR-ABL1 fusion gene 2
• Specifically exclude PDGFRA or PDGFRB rearrangements in cases with eosinophilia, as these are classified separately as myeloid/lymphoid neoplasms with eosinophilia 2
• Check blast percentage in peripheral blood and bone marrow (must be <20% for CMML) 2
• Note that higher lymphocyte counts have been associated with shorter survival in CMML 2

Chronic Lymphocytic Leukemia (CLL) Considerations

Lymphocytosis with low polymorphs could represent CLL:

• Confirm sustained lymphocytosis ≥5×10⁹/L with predominance of small, morphologically mature lymphocytes 2
• Perform immunophenotyping: CD5+, CD19+, CD20+ (low), CD23+, sIg low, CD79b low, FMC7– distinguishes CLL from other CD5+ B-cell lymphomas 2
• Obtain FISH for cytogenetic abnormalities (del17p, del11q, trisomy 12, del13q) as these have prognostic value 2
• However, eosinophilia is not typical of CLL and should prompt consideration of other diagnoses

Chronic Myeloid Leukemia (CML) Considerations

• Look for basophilia in addition to eosinophilia, as CML characteristically shows leukocytosis with basophilia and immature granulocytes 2
• Eosinophils may be prominent in CML bone marrow 2
• Confirm with cytogenetics showing t(9;22)(q3.4;q1.1) and RT-PCR for BCR-ABL transcripts 2

Anemia Workup (Elevated RDW and MCH)

The elevated RDW suggests heterogeneous red cell populations:

• High RDW is an indicator of iron deficiency, even when MCV is normal due to coexisting conditions 2
• Elevated MCH (assuming you meant MCHC - Mean Corpuscular Hemoglobin Concentration) is important as it alerts to spurious results and should prompt review of the blood smear 3
• Check serum ferritin, transferrin saturation, and CRP as minimum workup for anemia 2
• Consider reticulocyte count to assess bone marrow response 2
• In inflammatory conditions or hematologic malignancies, anemia of chronic disease may coexist with iron deficiency 2

Essential Diagnostic Steps

Peripheral Blood Smear Review

• Manual review of peripheral smear is mandatory to confirm automated differential and identify immature cells, dysplasia, or circulating blasts 2, 4, 5
• Look for toxic granulations, uniformity of white blood cells, and maturity of cells 5

Bone Marrow Examination

• Bone marrow biopsy with aspirate is indicated if malignancy cannot be excluded or if cytopenias persist without clear etiology 2
• Assess cellularity, blast percentage, dysplasia in cell lines, and perform cytogenetics 2

Additional Laboratory Tests

• Complete metabolic panel including LDH (elevated in hematologic malignancies) 2
• Serum protein electrophoresis to exclude paraprotein 2
• Vitamin B12 and folate levels as macrocytosis can mask microcytosis, resulting in normal MCV with high RDW 2

Treatment Approach If Tyrosine Kinase Fusion Identified

• Imatinib 100-400 mg daily is definitive treatment for PDGFRA/PDGFRB-rearranged neoplasms, producing dramatic responses in >90% of patients 1
• Monitor for tumor lysis syndrome risk: correct dehydration and treat hyperuricemia before starting therapy 1
• Weekly CBC initially to track response and monitor for cytopenia 1
• Molecular monitoring at 3,6, and 12 months to assess cytogenetic and molecular response 1

Common Pitfalls to Avoid

• Do not dismiss eosinophilia as allergic or parasitic without first excluding clonal hematologic disorders, especially if accompanied by other cytopenias or lymphocytosis 1
• Do not delay cardiac assessment in patients with eosinophilia and suspected myeloid neoplasm, as cardiac damage can be rapidly progressive and fatal 1
• Spurious counts can occur: EDTA-dependent agglutination can cause falsely low WBC counts, and various technical factors can affect RBC indices 3
• Do not use MCV alone to classify anemia when RDW is elevated, as mixed deficiencies can neutralize each other 2
• Lymphocytosis in adults requires different evaluation than in children, where viral illnesses commonly cause lymphocytosis 5, 6

When to Refer to Hematology/Oncology

Immediate referral is indicated if:

• Molecular testing reveals tyrosine kinase fusion genes 1
• Blast cells are present in peripheral blood 2
• Persistent unexplained cytopenias after initial workup 7
• Immunophenotyping confirms clonal lymphoproliferative disorder 2
• Symptoms suggest malignancy (fever, weight loss, night sweats, bruising, fatigue) 5