What is the appropriate management for an adult patient with no significant past medical history presenting with neutrophilia, normal leukocyte count, and monocytosis?

Management of Neutrophilia with Normal Leukocyte Count and Monocytosis

The immediate priority is to exclude reactive causes—particularly chronic infections, autoimmune disorders, and solid tumors—through targeted history, physical examination, and peripheral blood smear review before pursuing bone marrow evaluation for chronic myelomonocytic leukemia (CMML) or other myeloid neoplasms. 1

Initial Diagnostic Approach

Critical History Elements

• Travel exposure to tuberculosis-endemic areas, parasitic infections, or tick-borne illnesses (ehrlichiosis presents with monocytosis, leukopenia, thrombocytopenia, and morulae visible in monocytes) 1
• Recurrent infections suggesting HIV, hepatitis C, or endocarditis 1
• Constitutional symptoms including fever, night sweats, weight loss, or arthralgias (Adult-onset Still's disease demonstrates monocytosis with fever spikes, sore throat, and rash in 51-87% of cases) 2
• Autoimmune symptoms such as photosensitivity, oral ulcers, or joint pain (systemic lupus erythematosus and rheumatoid arthritis frequently cause monocytosis) 1
• Family history of hematologic malignancies 1
• Recent bone marrow suppression or chemotherapy (recovery phase causes transient monocytosis) 1

Physical Examination Priorities

• Splenomegaly (present in 14-65% of CMML cases and suggests clonal disorder) 2
• Cutaneous lesions (vasculitic purpuric rash or salmon-colored evanescent rash suggests Adult-onset Still's disease) 2
• Lymphadenopathy (present in 32-74% of CMML) 2
• Signs of organ infiltration 2

Mandatory Laboratory Evaluation

Peripheral Blood Smear Review

Manual differential is essential—automated analyzers miss critical morphologic features. 1, 3

Look specifically for:

• Dysgranulopoiesis (pseudo-Pelger-Huët anomaly, hypogranulation) suggesting myelodysplastic syndrome or CMML 1
• Promonocytes and blasts (>1% blasts or promonocytes raises concern for CMML) 2
• Neutrophil precursors (left shift) 1
• Morulae in monocytes (diagnostic of ehrlichiosis) 1
• Rouleaux formation (suggests plasma cell dyscrasia) 1

Confirmatory Testing

• Absolute monocyte count calculation to confirm true monocytosis (>0.8-1.0 × 10⁹/L) 1
• Comprehensive metabolic panel including calcium, albumin, creatinine, liver function tests 1
• Erythrocyte sedimentation rate and C-reactive protein (virtually always elevated in Adult-onset Still's disease and CMML) 2
• Serum protein electrophoresis with immunofixation if rouleaux or hypercalcemia present 1

When to Pursue Bone Marrow Evaluation

Bone marrow aspiration and biopsy are indicated when: 2, 1

• Absolute monocyte count ≥1 × 10⁹/L persists for >3 months without identified reactive cause
• Concurrent cytopenias (anemia, thrombocytopenia) develop
• Dysplastic features appear on peripheral smear
• Constitutional symptoms or organomegaly present
• No infectious, inflammatory, or malignant cause identified after comprehensive workup

Bone Marrow Workup Components

• Morphological examination for dysplasia in erythroid, granulocytic, or megakaryocytic lineages 2
• Blast percentage (CMML requires <20% blasts; ≥20% indicates acute myeloid leukemia) 2
• Conventional cytogenetic analysis to identify clonal abnormalities (chromosome 7 abnormalities, trisomy 8, complex karyotype occur in CMML) 2
• Molecular assays to exclude BCR-ABL fusion gene (chronic myeloid leukemia) and PDGFRA/PDGFRB rearrangements 2
• Gomori's silver impregnation for bone marrow fibrosis 2
• Store bone marrow cells for potential molecular analysis (TET2, SRSF2, ASXL1, RAS mutations found in 93% of CMML patients) 2

Critical Clinical Pitfalls

Do not confuse relative and absolute monocytosis—calculate absolute monocyte count from total WBC and differential percentage to avoid unnecessary workup or missed diagnoses. 1

Do not attribute persistent monocytosis to inflammation without excluding infection—tuberculosis, endocarditis, and parasitic infections require specific treatment and can mimic inflammatory conditions. 1

Do not delay bone marrow evaluation beyond 3 months in unexplained monocytosis—CMML has poor prognosis (median age at diagnosis 65-75 years) and early identification allows consideration of allogeneic stem cell transplantation in appropriate candidates. 2

Do not rely solely on automated differential—manual peripheral smear review is mandatory to identify dysplasia, promonocytes, and other morphologic abnormalities that automated analyzers miss. 1, 3

Special Consideration: Post-Treatment Lymphocytosis Pattern

Transient neutrophilia, monocytosis, and eosinophilia can occur during immune response initiation and are typically not clinically significant, though persistent or progressive changes warrant evaluation for autoimmune causes. 2