Clinical and pathologic challenges of clonal cytopenia of undetermined significance

Unexplained blood cytopenias, in particular anemia, are often found in older individuals. The relationship between these cytopenias and myeloid neoplasms like myelodysplastic syndromes is currently poorly defined. Terminology used to describe patients with unexplained cytopenias and with clonally restricted hematopoiesis can be confusing and is evolving. This review uses a complex clinical case with borderline morphology and somatic mutations with high variant allele frequencies to illustrate a diagnostic approach to clonal cytopenias, and differentiation from myeloid neoplasms with a focus on appropriate ancillary testing. Testing for somatic mutations and variant allele frequency is helpful in assessing risk for progression to myeloid malignancy. The interpretation of mutation profiles in patients with cytopenia has been challenging, as some of these genes are commonly detected in elderly adults showing a normal blood count as well as in individuals with nonmalignant bone marrow failure syndromes. For patients with unexplained cytopenias, longitudinal follow-up including monitoring of blood counts may also be appropriate.