What is monocytosis?

Monocytosis Definition and Management

Monocytosis is defined as an absolute monocyte count greater than 1×10^9/L in peripheral blood. 1

Diagnostic Criteria

• Persistent peripheral blood monocytosis is defined as an absolute monocyte count exceeding 1×10^9/L 1, 2
• This elevation must be persistent over time to be clinically significant, with some guidelines recommending confirmation over a 3-month period 1, 2
• Monocytosis can be either reactive (secondary to other conditions) or neoplastic (part of a hematologic malignancy) 2, 3

Differential Diagnosis

Reactive Causes of Monocytosis

• Infections (particularly chronic infections such as tuberculosis, endocarditis) 2, 4
• Inflammatory conditions and autoimmune disorders 2, 5
• Recovery from bone marrow suppression 2
• Solid tumors 2

Neoplastic Causes of Monocytosis

• Chronic Myelomonocytic Leukemia (CMML) - the prototypical neoplasm with monocytosis 1, 2
• Other myelodysplastic/myeloproliferative neoplasms 2, 6
• Acute myeloid leukemia with monocytic differentiation 2, 6

Diagnostic Approach

Initial Evaluation

• Complete blood count with differential to confirm absolute monocytosis 2, 5
• Peripheral blood smear examination to assess for dysplastic features and presence of immature cells 1, 2
• Patient history to exclude reactive causes of monocytosis 1, 2
• Physical examination with attention to spleen size and lymphadenopathy 1, 2

Further Workup for Persistent Unexplained Monocytosis

• Bone marrow aspiration and biopsy to assess for:
  • Presence of dysplasia in one or more myeloid lineages 1
  • Percentage of blasts (including myeloblasts, monoblasts, and promonocytes) 1
  • Marrow cellularity and fibrosis 1, 2
• Conventional cytogenetic analysis to detect clonal abnormalities 1, 2
• Molecular testing to exclude:
  • BCR-ABL1 fusion gene (Philadelphia chromosome) 1
  • PDGFRA or PDGFRB rearrangements (especially in cases with eosinophilia) 1

Specific Diagnostic Criteria for CMML

According to the WHO classification, CMML diagnosis requires all of the following 1:

1. Persistent peripheral blood monocytosis (>1×10^9/L)
2. No Philadelphia chromosome or BCR-ABL1 fusion gene
3. No rearrangement of PDGFRA or PDGFRB
4. Less than 20% blasts in peripheral blood and bone marrow
5. At least one of the following:
   • Dysplasia in one or more cell lines
   • An acquired clonal cytogenetic or molecular genetic abnormality
   • Persistence of monocytosis for at least 3 months with exclusion of other causes

Clinical Significance

• Persistent monocytosis warrants investigation as it may indicate underlying serious conditions 2, 7
• Monocytosis has been associated with increased 30-day mortality and longer hospital stays in emergency department patients 4
• In primary care settings, while monocytosis increases the relative risk of hematological malignancies (particularly CMML), the absolute risk remains low 7
• Sustained monocytosis (present on multiple tests over time) significantly increases the risk of CMML, though the absolute risk is still only about 0.1% 7

Common Pitfalls to Avoid

• Failing to distinguish between relative and absolute monocytosis 2, 5
• Not confirming persistence of monocytosis over time 1, 2
• Missing underlying infections or malignancies that may cause reactive monocytosis 2, 5
• Overlooking the need for bone marrow evaluation in cases of persistent unexplained monocytosis 1, 2

When monocytosis is identified, a systematic approach to diagnosis is essential to distinguish between reactive and neoplastic causes, with particular attention to excluding CMML and other hematologic malignancies 2, 3.