The Significance of Detecting an Unusual Myeloblast Immunophenotype in a Presumptive Clinical Diagnosis of Myelodysplastic Syndromes.

Abstract

Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS. To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance. More than 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded. Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but 31 patients (4%) had unusual blasts that were either completely or partially negative for CD34. Of the latter, recurrent genetic abnormalities were identified in 13 (42%) including 10 with nucleophosmin 1 (NPM1) mutation, 1 with lysine methyltransferase 2A (KMT2A) rearrangement, and 2 with t(3;5)(q25.3;q35.1)/NPM1::myeloid leukemia factor 1 (MLF1). These cases were classified as MDS prior to the 2022 classifications, but 9 of 13 (69%) and 7 of 13 (54%) cases would be reclassified as AML according to the 5th edition of the World Health Organization classification and the International Consensus Classification, respectively. Eight cases (26%) had multihit tumor protein p53 (TP53) mutation, and 6 of them were ultimately diagnosed as or quickly evolved to pure erythroid leukemia. Of the remaining 10 cases, 4 uncharacteristically had no detectable molecular genetic abnormalities. Our data show that if a presumptive MDS shows a nonprimitive blast phenotype, caution is needed to rule out AML with recurrent genetic abnormality with an oligoblastic presentation, high-risk myeloid neoplasms with double-hit TP53 mutation with abnormal erythroid proliferation, and MDS with molecular-genetic and clinical features more akin to AML.