Myelodysplastic Syndrome and Peripheral Leukocytosis

Introduction to MDS and Leukocytosis

Myelodysplastic syndrome (MDS) can cause peripheral leukocytosis, particularly in specific MDS subtypes such as chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML), which are classified as MDS/myeloproliferative neoplasms, according to the National Comprehensive Cancer Network 1

MDS represents a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis with peripheral blood cytopenias and hypercellular bone marrow, as noted by the journal Blood 3
Dysplasia in one or more cell lineages (erythroid, granulocytic, megakaryocytic) is a key characteristic of MDS, as reported by Annals of Oncology 4, 5
Increased risk of transformation to acute myeloid leukemia (AML) is a concern in MDS patients, according to Blood 3

Classic MDS typically presents with neutropenia, anemia, and/or thrombocytopenia, as stated by Annals of Oncology 5, 6
MDS/MPN overlap syndromes (particularly CMML) can present with monocytosis and leukocytosis, according to the Journal of the National Comprehensive Cancer Network 1
Atypical CML (aCML) presents with neutrophilia and leukocytosis, as noted by the Journal of the National Comprehensive Cancer Network 1
MDS with ring sideroblasts and thrombocytosis (MDS-RS-T) can present with elevated platelet counts, as reported by the Journal of the National Comprehensive Cancer Network 1

Chronic Myelomonocytic Leukemia (CMML) features peripheral blood monocytosis (>1 × 10^9/L) and can be divided into subtypes based on blast percentage, as classified by the Journal of the National Comprehensive Cancer Network 1
Atypical Chronic Myeloid Leukemia (aCML) presents with neutrophilia similar to chronic neutrophilic leukemia but with distinct molecular features, according to the Journal of the National Comprehensive Cancer Network 1
MDS-RS-T features thrombocytosis (platelet counts ≥450 × 10^9/L) with ring sideroblasts, as reported by the Journal of the National Comprehensive Cancer Network 1

Complete blood count with differential is essential to characterize the specific cell types contributing to leukocytosis, as stated by Annals of Oncology 5
Peripheral blood smear examination should look for dysplastic features such as pseudo Pelger-Huet cells, abnormal chromatin clumping, and hypo-/degranulation in granulocytes, as noted by Annals of Oncology 4, 6
Bone marrow examination is required for definitive diagnosis, including aspiration and biopsy with iron stain, as reported by Annals of Oncology 5 and Blood 8
Cytogenetic analysis is essential as chromosomal abnormalities are observed in up to 80% of MDS patients, according to Annals of Oncology 4, 6
Molecular testing is necessary for mutations commonly associated with MDS/MPN overlap syndromes, such as JAK2 mutations in cases with thrombocytosis, as noted by Praxis Medical Insights 2

The presence of leukocytosis does not exclude MDS, especially in MDS/MPN overlap syndromes, as stated by the Journal of the National Comprehensive Cancer Network 1
Careful distinction between reactive leukocytosis and clonal proliferation is essential, as reported by Annals of Oncology 5
Peripheral blood findings must be correlated with bone marrow morphology for accurate diagnosis, according to Blood 8