Differential Diagnosis and Workup of Monocytosis: A Systematic Approach to a Common Hematologic Finding

Abstract

Purpose of review: Monocytosis is a frequently encountered clinical condition that needs appropriate investigation due to a broad range of differential diagnoses. This review is meant to summarize the latest literature in the diagnostic testing and interpretation and offer a stepwise diagnostic approach for a patient presenting with monocytosis.

Recent findings: Basic studies have highlighted the phenotypic and functional heterogeneity in the monocyte compartment. Studies, both translational and clinical, have provided insights into why monocytosis occurs and how to distinguish the different etiologies. Flow cytometry studies have illustrated that monocyte repartitioning can distinguish chronic myelomonocytic leukemia, a prototypical neoplasm with monocytosis from other reactive or neoplastic causes. In summary, we provide an algorithmic approach to the diagnosis of a patient presenting with monocytosis and expect this document to serve as a reference guide for clinicians.

Keywords: Chronic Myelomonocytic Leukemia; Classical; Intermediate; Monocytes; Monocytosis; Non-classical.

Fig. 1

The diverse functions of monocytes in humans. Monocytes are characterized by expression of several cell surface receptors. This figure highlights some of those receptors and the key monocyte-associated functions such as macrophage-associated phagocytosis, dendritic cell-mediated antigen presentation, wound healing, interactions with coagulation cascade, and regulation of inflammatory responses (created with BioRender.com)

Fig. 2

Bone marrow aspirate evaluation of a patient with chronic myelomonocytic leukemia. a Shows hematoxylin and eosin staining at × 1000 magnification. Arrow points to monocytes. b Shows dual staining of CMML bone marrow aspirate with alpha-naphthyl butyrate-esterase and naphthol AS-D chloroacetate esterase indicating increased monocytic cells (staining only alpha-naphthyl butyrate-esterase) for shown at × 1000 magnification (Courtesy: Kaaren K Reichard, MD)

Fig. 3

Figure showing flow cytometry-based monocyte repartioning patterns in normal individuals, reactive monocytosis and chronic myelomonocytic leukemia (CMML). In CMML, there is a preferential expansion of the classical (> 94%, MO1, CD14++, CD16−) monocyte fraction as opposed to intermediate (MO2, CD14⁺, CD16⁺) and non-classical fraction (MO3, CD14^dim, CD16⁺) (Courtesy: Michael M. Timm)

Fig. 4

Figure outlining a stepwise approach for a patient presenting with monocytosis. Abbreviations: CBC = complete blood count; CMML = chronic myelomonocytic leukemia