A-260 Role of the clinical laboratory in guiding the diagnostic workup of chronic myelomonocytic leukemia: a case report

Abstract

Chronic myelomonocytic leukemia (CMML) is a rare myeloid neoplasm defined by the World Health Organization (WHO) by persistent peripheral blood monocytosis, dysplastic hematopoiesis, and a heterogeneous clinical course. In routine practice, CMML may initially present with non-specific cytopenias and subtle dysgranulopoiesis that can be overlooked or attributed to reactive etiologies, and total leukocyte counts may remain within reference limits. Diagnosis requires correlation between clinical findings, complete blood count (CBC) morphology, and immunophenotypic profiling. The clinical laboratory is often the first setting in which suggestive abnormalities are recognized, and timely escalation to the treating physician can direct the choice of complementary tests such as flow cytometry. The aim of this case report was to illustrate how expert morphology review documented in the CBC report, combined with proactive communication of critical findings, can guide complementary testing to support the diagnostic workup of suspected CMML. This observational, descriptive case report describes a 77-year-old male evaluated at a private clinical laboratory. Initial assessment included automated CBC analysis and differential leukocyte counting. Peripheral blood smear review was performed by optical microscopy, with qualitative evaluation of erythrocyte morphology, platelet estimate, leukocyte differential, immature granulocytes, and dysplastic features in neutrophils and monocytes. After identification of marked monocytosis with left shift and dysplastic morphology, the laboratory contacted the attending physician by telephone to communicate results and recommend flow cytometry. Flow cytometry was performed on K3-EDTA–anticoagulated peripheral blood using an internally validated monoclonal antibody panel optimized for myeloid and lymphoid characterization, using internally validated protocols aligned with CLSI guidance. Analysis included monocyte gating and subset distribution (classical/intermediate/non-classical), evaluation of T-, B, and NK-cell populations for abnormal immunophenotype or clonality, estimation of myeloid progenitors (blasts), and integration of morphology plus monocyte repartitioning to distinguish reactive monocytosis from a clonal myeloid process. CBC and morphology revealed hemoglobin below reference intervals with red blood cell indices consistent with normocytic normochromic anemia, polychromasia, and mild thrombocytopenia. Total leukocyte counts were within normal limits; however, significant monocytosis and a left shift extending to the myelocyte stage were observed. Smear review demonstrated dysplastic features, including nuclear maturation asynchrony, cytoplasmic asymmetry, and aberrant granulation affecting both monocytes and neutrophils. These findings were promptly communicated to the physician. Flow cytometry demonstrated predominance of mature monocytes (59.29% of total events). Within this population, 98% exhibited a classical monocyte phenotype, while the non-classical fraction represented 0.5%. T-, B-, and NK-cell compartments showed preserved distribution with no evidence of clonality. Myeloid progenitors (blasts) were 0.02%. The constellation of hematologic and immunophenotypic findings was highly suggestive of CMML and supported a CMML-focused differential diagnosis. This case underscores the clinical laboratory’s proactive role in guiding CMML investigation through integrated interpretation of CBC parameters and smear morphology, structured reporting, and timely clinician communication. Recognition of monocytosis coupled with dysplastic changes enabled directed flow cytometry, strengthening diagnostic confidence by demonstrating monocyte predominance and subset skewing, excluding alternative lymphoid clonal processes, and confirming low blast burden. This escalation pathway can accelerate hematology referral and help prioritize confirmatory investigations in patient-centered care.