Abstract
Diagnosing a myelodysplastic syndrome (MDS) can be challenging. Somatic mutations are common in MDS and might have diagnostic utility in patients with idiopathic cytopenias of undetermined significance (ICUS). However, using mutations to diagnose MDS is complicated by several issues: (1) no gene is mutated in most cases, (2) no mutated gene is highly specific for MDS, (3) clonal hematopoiesis is common in older individuals without disease, and (4) we lack outcome data for ICUS patients with clonal cytopenias of undetermined significance (CCUS). Despite these caveats, genetic sequencing can inform the diagnosis of MDS. CCUS patients more closely resemble patients with MDS than age matched controls with somatic mutations. Genetic testing can identify alternative diagnoses in cytopenic patients and help risk stratify those with proven MDS. While we cannot include somatic mutations in the diagnostic definition of MDS now, testing to recognize CCUS will help characterize outcomes in these diagnostically challenging patients.
Highlights
For several of reasons, myelodysplastic syndromes (MDS) are often challenging to diagnose
Current evidence does not support the use of somatic mutations as presumptive evidence of MDS absent traditional diagnostic criteria [42]
As with the del(5q) chromosomal abnormality, some gene mutations may be strongly associated with clinical features and be used to help classify MDS subtypes in patients that meet the classical diagnostic criteria
Summary
Myelodysplastic syndromes (MDS) are often challenging to diagnose. Somatic mutations are indicative of clonal hematopoiesis, a defining feature of MDS, they identify the molecular drivers responsible for its pathogenesis These facts, and our experience with diagnostic molecular tests in related myeloid disorders, suggest that mutations could readily be incorporated into the diagnostic criteria for MDS [21, 22]. Diagnostic utility of somatic mutations in MDS is complicated by several issues These include concerns about poor specificity, the range of genetic variability present in MDS, and a poor understanding about the implications of mutations in patients who do not meet current diagnostic criteria. Several clonal conditions that share clinical features with MDS, including AML, MPN, and AA, must be excluded in order to make the diagnosis (Fig. 1).
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