Myelodysplastic syndromes/neoplasms presenting with isolated thrombocytopenia: a poorly understood pathophysiology, difficult to diagnose, and challenging to treat entity

INTRODUCTION: Myelodysplastic syndromes/neoplasms (MDS) usually present with anemia or multilineage cytopenias, whereas isolated thrombocytopenia is uncommon and may closely mimic immune thrombocytopenia (ITP). In lower-risk MDS (LR-MDS) without increased blasts, thrombocytopenia may be the sole or predominant abnormality, leading to diagnostic delay and unnecessary exposure to immune-directed therapies. AREAS COVERED: A narrative literature search was undertaken using terms related to MDS, isolated thrombocytopenia, ITP, clonal cytopenia of undetermined significance (CCUS), del(20q), and treatment. This review examines the clinical phenotype, pathophysiology, diagnostic evaluation, prognosis, and management of MDS with isolated thrombocytopenia (MDS-IT), emphasizing differentiation from ITP and CCUS and the roles of marrow morphology, cytogenetics, molecular testing, and longitudinal assessment. Particular attention is given to isolated del(20q), which is often associated with platelet-predominant disease, low blast burden, and relatively indolent behavior, although coexisting mutations such as ASXL1, TP53, and spliceosome-gene alterations may worsen prognosis. Supportive care remains foundational; thrombopoietin receptor agonists provide the strongest prospective evidence in selected lower-risk patients, whereas evidence for hypomethylating agents remains indirect. EXPERT OPINION: MDS-IT is a biologically heterogeneous clinical phenotype rather than a formal subtype. Accurate diagnosis and individualized management require integrated clinical, morphologic, cytogenetic, molecular, and bleeding-risk assessment.