The role of morphology in diagnosing MDS with Non-clonal cytopenias

Myelodysplastic syndromes/neoplasms (MDS) are a heterogeneous group of blood disorders characterized by distinctive biological and clinical features. Diagnosis typically relies on bone marrow examination and cytogenetic/molecular analysis. However, a small subset of patients lacks detectable cytogenetic or genetic abnormalities, making diagnosis challenging and reliant solely on marrow dysplasia and cytopenia. Here, we conducted a multicenter retrospective study investigating the clinical and hematological features of patients with MDS lacking detectable cytogenetic or molecular alterations. From a cohort of 329 MDS patients who underwent genetic testing at our laboratory of “Diagnostica Avanzata Oncoematologica”, we selected 62 patients presenting with unexplained cytopenia, suspected MDS, and a non-informative cytogenomic profile. Of these, 26 were ultimately diagnosed with alternative conditions such as aplastic anemia, drug/radiation toxicity, multiple myeloma, and others. The patients with non-informative genetic profile had a median age of 60 years and a female predominance (67 %). Autoimmune diseases (AD) were the most frequently observed comorbidities (26 %), and neutropenia was the most common type of cytopenia (56 %), followed by thrombocytopenia (22 %), and anemia (19 %). Most patients had bi-lineage or tri-lineage dysplasia, and had low-risk disease according to IPSS-R and IPSS-M. Only one patient progressed to AML at a median follow-up of 12 months (IQR for the test cohort: 2–25). MDS lacking classical myeloid clonal alteration represent a unique clinical-biological subtype whereby marrow assessment along with a thorough clinical workup is crucial.