Interpret this CBC with differential: WBC 17.3 ×10⁹/L (neutrophils 73.5%, absolute neutrophils 12.8 ×10⁹/L), immature granulocytes 1.8% (0.3 ×10⁹/L), lymphocytes 8.5% (1.5 ×10⁹/L), monocytes 9.2% (1.6 ×10⁹/L), eosinophils 6.1% (1.1 ×10⁹/L), basophils 0.9% (0.2 ×10⁹/L), nucleated red blood cells 1.7% (0.3 ×10⁹/L); RBC 2.90 ×10¹²/L, hemoglobin 8.1 g/dL, hematocrit 26.3%, MCV 90.7 fL, MCH 27.9 pg, MCHC 30.8 g/dL, RDW 18.6%, platelets 233 ×10⁹/L, MPV 9.4 fL.

CBC Interpretation: Concerning for Hematologic Malignancy Requiring Urgent Evaluation

This CBC demonstrates leukocytosis with left shift, immature granulocytes, nucleated RBCs, normocytic anemia with elevated RDW, and relative lymphopenia—a constellation highly suspicious for a myeloproliferative neoplasm, most likely chronic myeloid leukemia (CML), requiring immediate peripheral smear review, BCR-ABL1 testing, and hematology consultation. 1, 2

Critical Abnormalities Identified

White Blood Cell Abnormalities

• WBC 17.3 × 10⁹/L with neutrophilia (73.5%, absolute 12.8 × 10⁹/L): This moderate leukocytosis with neutrophil predominance falls below the typical CML threshold of >25 × 10⁹/L but exceeds normal limits and warrants investigation 2, 3
• Immature granulocytes 1.8% (0.3 × 10⁹/L absolute): The presence of immature granulocytes in peripheral blood is abnormal and indicates either severe physiologic stress or an underlying myeloproliferative neoplasm 2
• Nucleated RBCs 1.7% (0.3 × 10⁹/L absolute): This is a critical finding suggesting bone marrow stress, extramedullary hematopoiesis, or marrow infiltration 2
• Relative lymphopenia (8.5%, absolute 1.5 × 10⁹/L): The disproportionately low lymphocyte percentage in the setting of leukocytosis suggests a myeloid-predominant process 4

Red Blood Cell Abnormalities

• Severe normocytic anemia: Hemoglobin 8.1 g/dL, hematocrit 26.3%, RBC 2.90 × 10¹²/L with normal MCV (90.7 fL) indicates anemia of chronic disease or bone marrow failure 5
• Elevated RDW 18.6%: This suggests heterogeneous red cell populations, consistent with ongoing marrow stress or dysplasia 4

Other Findings

• Monocytosis: Absolute monocyte count 1.6 × 10⁹/L (≥1.0 × 10⁹/L threshold) requires evaluation for chronic myelomonocytic leukemia (CMML) or other myeloid neoplasms 6
• Eosinophilia: Absolute eosinophil count 1.1 × 10⁹/L is elevated and may accompany CML 2
• Basophilia: Absolute basophil count 0.2 × 10⁹/L—while only mildly elevated, basophilia ≥200/mm³ strongly suggests CML rather than reactive causes 2

Differential Diagnosis

Primary Concern: Chronic Myeloid Leukemia

CML is the leading diagnosis based on the following features 1, 2:

• Left shift with immature granulocytes representing the full spectrum of myeloid maturation 2
• Basophilia and eosinophilia accompanying the leukocytosis 2
• Nucleated RBCs indicating marrow stress 2
• Normocytic anemia consistent with CML presentation 5

Key distinguishing features from the typical CML presentation 1:

• WBC is only 17.3 × 10⁹/L rather than the characteristic >100 × 10⁹/L seen in most CML cases
• However, CML can present with lower WBC counts, and the qualitative findings (immature granulocytes, basophilia, eosinophilia, nucleated RBCs) are more diagnostically significant than the absolute WBC count 5, 2

Alternative Considerations

Chronic Myelomonocytic Leukemia (CMML): The monocytosis (1.6 × 10⁹/L) raises concern for CMML, which requires persistent monocytosis with dysplasia and <20% blasts 6

Reactive Leukocytosis: Less likely given the combination of immature granulocytes, nucleated RBCs, and multiple cell line abnormalities 3, 7

• Infections typically cause leukocytosis with toxic granulations but not nucleated RBCs 3
• Adult-onset Still's disease can cause WBC >15 × 10⁹/L with neutrophilia but would not explain the immature granulocytes and nucleated RBCs 5, 6

Acute Myeloid Leukemia (AML): Less likely because AML typically presents with circulating blasts, more severe cytopenias, and lacks the orderly myeloid maturation seen here 1

Immediate Diagnostic Workup Required

Urgent Laboratory Studies

1. Manual peripheral blood smear review to confirm automated differential, assess myelocyte proportion, evaluate for dysplasia, and identify any blasts 2, 4
2. BCR-ABL1 testing by RT-PCR: This is diagnostic for CML and must be performed immediately 5, 2
3. Repeat CBC with manual differential to document percentages of all immature forms (blasts, promyelocytes, myelocytes, metamyelocytes) 2

Bone Marrow Evaluation

Bone marrow aspiration and biopsy are mandatory given the constellation of findings 2, 6:

• Assess marrow cellularity and blast percentage 6
• Conventional cytogenetic analysis to detect Philadelphia chromosome t(9;22) 5, 2
• FISH for BCR-ABL1 if cytogenetics cannot be analyzed 5
• Gomori silver staining to assess for reticulin fibrosis (present in 30% of CML cases) 5

Additional Testing

• Molecular testing: If BCR-ABL1 is negative, test for PDGFRA/PDGFRB rearrangements (given eosinophilia) and mutations in TET2, SRSF2, ASXL1, and RAS genes to evaluate for CMML 6

Clinical Context Assessment

History to Obtain

• Constitutional symptoms: Weight loss, night sweats, fever, fatigue (present in 40-50% of CML cases) 1
• Splenomegaly symptoms: Early satiety, left upper quadrant fullness (splenomegaly in 40-50% of CML) 1
• Bleeding or bruising: Suggests thrombocytopenia or coagulopathy 5
• Infection symptoms: To exclude reactive causes 3
• Medication history: Corticosteroids, lithium, beta-agonists can cause reactive leukocytosis 7

Physical Examination

• Splenomegaly: Most consistent finding in CML, present in 40-50% at diagnosis 1
• Hepatomegaly: Less common but characteristic 1
• Lymphadenopathy: Evaluate for lymphoproliferative disorders 6

Red Flags for Disease Progression

The following findings would indicate accelerated or blast phase CML 5:

• Blasts 15-29%: Accelerated phase by European LeukemiaNet criteria 2
• Blasts ≥30%: Blast phase 2
• Basophils >20%: Suggests progression 5, 2
• Platelets <100 × 10⁹/L unrelated to therapy: Accelerated phase criterion 5

Urgent Hematology Consultation Indicated

Immediate hematology referral is mandatory based on 2, 4:

• Immature granulocytes with WBC >15 × 10⁹/L
• Nucleated RBCs in peripheral blood
• Concurrent basophilia and eosinophilia
• Unexplained normocytic anemia with elevated RDW
• Monocytosis requiring evaluation for CMML

Common Pitfalls to Avoid

1. Do not attribute this to infection alone: While infections cause leukocytosis, the presence of nucleated RBCs, immature granulocytes, and basophilia suggests a primary marrow disorder 3, 4
2. Do not delay BCR-ABL1 testing: This is the definitive diagnostic test for CML and should be ordered immediately 5, 2
3. Do not rely solely on WBC count: The qualitative findings (cell types present) are more important than the absolute WBC count for diagnosing myeloproliferative neoplasms 2, 4
4. Do not miss CMML: The monocytosis requires specific evaluation with bone marrow examination if it persists 6