What is the meaning of monocytic predominance?

Monocytic Predominance: Definition and Clinical Significance

Monocytic predominance refers to an elevated proportion or absolute number of monocytes in the blood or bone marrow, typically defined as monocytes comprising >10% of white blood cells or an absolute monocyte count >1×10⁹/L, which can indicate either reactive inflammatory conditions or clonal hematologic malignancies, most critically chronic myelomonocytic leukemia (CMML). 1, 2

Core Definition

Monocytic predominance describes a shift in the cellular composition of blood or bone marrow toward increased monocytic cells. This can manifest as: 1, 2

• Absolute monocytosis: Monocyte count >1×10⁹/L in peripheral blood 3, 1
• Relative monocytosis: Monocytes comprising >10% of total white blood cells 4
• Monocytic-MDSC (M-MDSC): A subset of myeloid-derived suppressor cells characterized by CD11b+ Ly6C+ Ly6G- phenotype in mice, representing pathologically activated monocytic cells distinct from mature monocytes 3

Clinical Context and Significance

Two Major Categories of Causes

Reactive (Benign) Conditions: 2, 5

• Chronic infections (tuberculosis, bacterial endocarditis, Listeria monocytogenes) 2
• Inflammatory conditions (inflammatory bowel disease, rheumatoid arthritis) 2
• Adult-onset Still's disease (often with WBC >15×10⁹/L) 2, 5
• Cardiovascular disease (atherosclerosis, coronary artery disease) 2, 5
• Tissue injury and chronic inflammation 5

Clonal Hematologic Malignancies: 1, 2

• Chronic myelomonocytic leukemia (CMML): The most critical diagnosis to exclude in persistent monocytosis 1, 2
• Myelodysplastic syndromes with monocytic component 4
• Acute myeloid leukemia with monocytic differentiation 4

CMML-Specific Context

In CMML, monocytic predominance is a defining feature with specific WHO 2008 diagnostic criteria: 3, 1

• Persistent peripheral blood monocytosis (>1×10⁹/L) 3, 1
• No Philadelphia chromosome or BCR-ABL1 fusion gene 3
• <20% blasts in peripheral blood and bone marrow 3
• Dysplasia in one or more cell lines or acquired clonal abnormality 3

The distinction between myelodysplastic (MD-CMML) and myeloproliferative (MP-CMML) variants uses a WBC cutoff of 13×10⁹/L, which has therapeutic implications despite WHO not maintaining this distinction officially. 3

Monocyte Subsets and Heterogeneity

Monocytes are heterogeneous and consist of three phenotypically distinct subpopulations: 6, 7

• Classical monocytes (CD14+CD16- in humans; Ly6Chi in mice): Critical for initial inflammatory response 7
• Intermediate monocytes (CD14+CD16+ in humans; Ly6C+Treml4+ in mice) 7
• Nonclassical monocytes (CD14-CD16+ in humans; Ly6Clo in mice): Maintain vascular homeostasis and provide first-line pathogen defense 7

Diagnostic Approach to Monocytic Predominance

Initial Evaluation 1, 2

• Complete blood count with differential to confirm absolute monocyte count 1, 2
• Peripheral blood smear examining monocyte morphology, dysgranulopoiesis, promonocytes, and blasts 1, 2
• Comprehensive metabolic panel 2
• Assessment for reactive causes (infections, inflammatory conditions, autoimmune disorders) 1

When to Pursue Advanced Workup 1, 2

Bone marrow evaluation is indicated for: 1, 2

• Persistent unexplained monocytosis without clear reactive cause 1, 2
• Absolute monocyte count ≥1×10⁹/L sustained over 3 months 1, 5
• Concurrent cytopenias or other blood count abnormalities 1
• Constitutional symptoms or organomegaly 1
• Dysplastic features on peripheral smear 1

Comprehensive Bone Marrow Assessment 1, 2

• Bone marrow aspiration and biopsy to assess cellularity, dysplasia, and blast percentage (including myeloblasts, monoblasts, promonocytes) 1, 2
• Gomori's silver impregnation staining for fibrosis 1, 2
• Conventional cytogenetic analysis to exclude t(9;22) Philadelphia chromosome, BCR-ABL1 fusion gene, and t(5;12) translocations 1, 2
• Molecular testing for mutations in TET2, SRSF2, ASXL1, and RAS genes 1, 5

Prognostic Implications

Patients with myelodysplastic syndromes showing monocytic predominance represent a distinct disease subset characterized by: 4

• Multilineage dysplasia 4
• Higher incidence of karyotype aberrations (11/13 patients with monocytosis showed clonal changes versus 19/41 without monocytosis) 4
• Relatively higher leukocyte and granulocyte counts 4
• Hypercellular bone marrow 4
• Particularly high incidence of evolution to CMML (34.5%) and AML with monocytic component (17.2%) 4
• Relatively poor prognosis 4

Critical Pitfalls to Avoid

• Failing to distinguish absolute from relative monocytosis can lead to unnecessary workup 2
• Not performing comprehensive bone marrow evaluation in persistent unexplained monocytosis delays CMML diagnosis 2
• Missing underlying infections or malignancies by attributing monocytosis to benign causes without adequate investigation 2
• Overlooking molecular testing to exclude specific myeloid neoplasms in persistent cases 2
• Ignoring that monocytes are highly sensitive to activation state and expression of surface markers can change during cell isolation, requiring unbiased functional analysis in whole blood when possible 8

Special Considerations in Cancer and Inflammation

In the context of myeloid-derived suppressor cells (MDSC), monocytic predominance takes on additional meaning: 3

• M-MDSC are phenotypically and morphologically distinct from PMN-MDSC with unique functional characteristics 3
• M-MDSC can be distinguished from tumor-associated macrophages (TAM) by increased relative expression of F4/80, low-to-intermediate Ly6C expression, and low/undetectable S100A9 protein 3
• Cells with inflammatory monocyte phenotype (CD11b+ Ly6Chi Ly6G-) in tumors typically have potent immune-suppressive activity and can be attributed to M-MDSC 3
• In humans, M-MDSC are typically identified as CD14+ HLA-DRlow cells 3