Clinical and pathological features of clonal cytopenia of undetermined significance presenting with isolated thrombocytopenia (CCUS‐IT)

Abstract

AbstractBackgroundClonal cytopenia of undetermined significance (CCUS) is defined as somatic mutations of myeloid malignancy‐associated genes in the blood or bone marrow with one or more persistent unexplained cytopenias that do not meet diagnostic criteria for a defined myeloid neoplasm. CCUS with isolated thrombocytopenia (CCUS‐IT) is rare.MethodsThis is a retrospective case series of patients with prolonged isolated thrombocytopenia, a pathogenic mutation on a myeloid molecular panel, and a bone marrow biopsy with morphologic atypia below the WHO‐defined diagnostic threshold for dysplasia.ResultsFive male patients were identified with a median age at CCUS‐IT diagnosis of 61 years (56–74). Median duration of thrombocytopenia prior to CCUS‐IT diagnosis was 4 years (3–12), and median platelet count at CCUS‐IT diagnosis was 41 × 103/μL (26–80). All patients had megakaryocytic hyperplasia and megakaryocytes with hyperchromasia and high nuclear‐cytoplasmic ratio. Pathogenic SRSF2 mutations were identified in all 5 patients with median variant allele frequency of 36% (28%–50%). Three patients were treated with IVIg and/or steroids with no response; one of three responded to thrombopoietin receptor agonists. Three patients progressed to MDS and one to AML.DiscussionWe describe the clinicopathological features of CCUS‐IT which can mimic immune thrombocytopenia.