Diagnostic Criteria for Myelodysplastic Syndromes (MDS)

Essential Diagnostic Features

The diagnosis of MDS requires meeting specific morphological and clinical criteria, including blood cytopenias, bone marrow examination showing dysplasia in ≥10% of cells in one or more myeloid lineages, and blast percentage in bone marrow must be documented (<5% for lower-risk subtypes, 5-19% for RAEB) 1, 2, 3, 4, 5
Blood cytopenias must be present (anemia, neutropenia, and/or thrombocytopenia) with persistent duration over at least several months, according to the National Comprehensive Cancer Network 3
Cytogenetic analysis of bone marrow cells is mandatory to identify characteristic abnormalities and aid in risk stratification, as recommended by the European Society for Medical Oncology 1, 2

The "classic" MDS presentation typically includes an elderly patient (median age ~70 years, though >10% are younger than 50), hypercellular bone marrow with ineffective hematopoiesis despite peripheral cytopenias, and morphologic dysplasia showing megaloblastoid erythropoiesis, nucleocytoplasmic asynchrony in early myeloid/erythroid precursors, and dysmorphic megakaryocytes 1, 2, 3

Before confirming MDS, it is necessary to systematically exclude alternative diagnoses, including nutritional deficiencies, medication effects, other disorders, and secondary causes, as recommended by the National Comprehensive Cancer Network and the European Society for Medical Oncology 1, 2, 3

If MDS is confirmed, classify according to WHO criteria to guide prognosis and treatment, including lower-risk subtypes (refractory cytopenia with unilineage dysplasia, refractory anemia with ring sideroblasts, and some cases of refractory cytopenia with multilineage dysplasia) and higher-risk subtypes (refractory anemia with excess blasts-1 and RAEB-2) 4, 5

Once MDS is confirmed, calculate the Revised International Prognostic Scoring System (IPSS-R) score using marrow blast percentage, number and severity of cytopenias, and cytogenetic abnormalities, as recommended by the International Working Group for Prognosis in MDS 1, 2

The raised MCV reflects the underlying megaloblastoid erythropoiesis that characterizes MDS bone marrow morphology, which is fundamentally different from true megaloblastic anemia, with dysplastic erythroid precursors exhibiting nucleocytoplasmic asynchrony, creating larger cells with increased volume 6
This occurs despite normal vitamin B12 and folate levels, distinguishing it from nutritional megaloblastic anemia, with the National Comprehensive Cancer Network noting the importance of this distinction 7

The American Society of Hematology suggests that MCV elevation serves as an important diagnostic clue for MDS, particularly in elderly patients with unexplained cytopenias, with a significant elevation in MCV compared to other causes of cytopenia, and the European Hematology Association recommends considering MDS in patients with elevated MCV and cytopenias 7

The National Comprehensive Cancer Network recommends excluding nutritional causes first by checking B12, folate, and iron studies, and reviewing medication history, particularly chemotherapy, immunosuppressants, and alcohol, before proceeding to bone marrow examination if MDS is suspected 7
The International Working Group for Myelodysplastic Syndromes suggests examining the peripheral smear for dysplastic features in multiple cell lines, and proceeding to bone marrow examination to assess for ≥10% dysplasia in one or more lineages, enumerate blasts, and perform cytogenetic analysis 7