The impact of cytomorphology, cytogenetics, molecular genetics, and immunophenotyping in a comprehensive diagnostic workup of myelodysplastic syndromes

Abstract

Because of limited reproducibility of morphologic features, the morphological categorization of initial myelodysplastic syndromes (MDS) cases remains a major task in a diagnostic setting. To further evaluate the role of additional diagnostic methods for suspected early MDS, the authors analyzed 1965 cases with unclear cytopenia where at least cytomorphology and immunophenotyping were performed in parallel, combined with cytogenetics and molecular genetics. In 353 patients, both methods diagnosed malignant/nonmalignant disease other than MDS, and 557 patients had MDS-refractory anemia with excess of blasts/chronic myelomonocytic leukemia. The remaining 1055 patients (53.7%), where early MDS/reactive cytopenia had to be assumed, were categorized into 6 groups depending on cytomorphology/immunophenotyping results for or against MDS. In 659 of 1055 cases (62.4%) with suspected initial MDS, cytomorphology and immunophenotyping were concordant in the categorization of MDS/non-MDS. Cytogenetics, available in 951 of 1055 patients, revealed the highest frequency of aberrant karyotypes when both cytomorphology and immunophenotyping proposed MDS (63 of 227; 27.8%). But also in the groups where either cytomorphology or immunophenotyping showed evidence of MDS, aberrant karyotypes were found in 6% to 14% of patients. Even when both morphology and immunophenotyping showed no MDS, 11 of 208 (5.3%) had cytogenetic aberrations. RUNX1/AML1 mutation screening was positive in 15% in the latter group. NRAS, MLL-PTD, NPM1, and JAK2V617F were detected in low frequencies, confirming MDS diagnosis in the respective cases. This report outlines the power of a combined diagnostic approach for suspected initial cases of MDS including immunophenotyping, cytogenetics, and molecular genetics with selected markers in addition to cytomorphology. Diagnostic algorithms should be developed, and immunophenotyping should be further validated for this specific indication.