Diagnostic workup of suspected myelodysplastic syndromes. The diagnostic approach to suspected MDS begins with the exclusion of the secondary causes of cytopenias. If no cause for the cytopenia(s) is identified based on history, physical examination, and screening blood tests, a bone marrow examination is recommended for diagnostic evaluation. Recent studies have explored the feasibility and reliability of somatic mutation analysis on DNA from peripheral blood cells (dotted line) to screen individuals with unexplained anemia for the likelihood of MDS. The absence of somatic mutations has a high negative predictive value for ruling out a diagnosis of myeloid neoplasm, whereas in individuals harboring hematologic clone(s), the clone metrics, (number of mutations, VAF, and mutation patterns) are predictive of the likelihood of a myeloid neoplasm. AA, aplastic anemia; ACD, anemia of chronic disease; BM, bone marrow; cBMF, constitutional bone marrow failure; LGL, large granular lymphocytic leukemia; MD-CMML, myelodysplastic-type chronic myelomonocytic leukemia; PMF, primary myelofibrosis. Professional illustration by Somersault18:24.