ABSTRACT
Certain cytogenetic abnormalities (demonstrated by conventional metaphase cytogenetics) are diagnostic for MDS in patients with cytopenia even without morphologic features supporting the diagnosis, except for +8, del(20q), and −Y, which are not considered to be MDS-specic in the absence of morphologic features of dysplasia [15]. Similarly, the presence of MDS-associated mutations (SF3B1, TET3, SRSF2, ASXL1, DNMT3, RUNX1, U2AF1, TP53, and/or EZH2) alone is not considered diagnostic of MDS without morphologic or chromosomal changes typical for MDS [15]. ose mutational changes are classied as “clonal hematopoiesis of indeterminate potential” (CHIP) [15]. Patients who do not meet the minimal criteria for MDS and whose sustained cytopenia(s) (≥6 months) cannot be explained by other hematopoietic or nonhematopoietic disease are diagnosed with idiopathic cytopenia of undetermined signicance (ICUS). Initial investigations required to establish the diagnosis of ICUS include detailed clinical history (toxins, drugs, mutagenic events etc.), clinical evaluation with x-ray, dierential blood count and complete serum chemistry, BM histology with immunohistochemistry, BM smear including iron staining, ow cytometry of BM, chromosomal analysis (cytogenetics and uorescence in situ hybridization, FISH), exclusion of viral infections (HCV, HIV, CMV, EBV, others), and molecular tests. Patients with ICUS should be carefully monitored with repeated tests to exclude progression to MDS (blood count with dierential in 1-6 months’ intervals and BM analysis when appropriate). Patients
without signicant cytopenias but who have obvious dysplastic morphologic features are diagnosed with idiopathic dysplasia of undetermined signicance (IDUS). Although IDUS is rare, patients need to be followed as they may progress to frank myeloid malignancy.
