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

Context.—: 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.

Objective.—: To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.

Design.—: Over 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.

Results.—: 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 (52%) 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.

Conclusions.—: 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.