Diagnosis and classification of myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDSs) are neoplastic myeloid proliferations characterized by ineffective hematopoiesis resulting in peripheral blood cytopenias. MDS is distinguished from non-neoplastic clonal myeloid proliferations by the presence of morphologic dysplasia and from acute myeloid leukemia (AML) by a blast threshold of 20%. The diagnosis of MDS can be challenging due to the myriad other causes of cytopenias: accurate diagnosis requires the integration of clinical features with bone marrow and peripheral blood morphology, immunophenotyping, and genetic testing. MDS has historically been subdivided into several subtypes by classification schemes, the most recent of which are the International Consensus Classification (ICC) and 5th edition WHO Classification (WHO5), both published in 2022. The aim of MDS classification is to identify entities with shared genetic underpinnings and molecular pathogenesis, and the specific subtype can inform clinical decision making alongside prognostic risk categorization. The current MDS classification schemes incorporate morphologic features (bone marrow and blood blast percentage, degree of dysplasia, ring sideroblasts, bone marrow fibrosis, and bone marrow hypocellularity) and also recognize three entities defined by genetics: isolated del(5q) cytogenetic abnormality, SF3B1 mutation, and TP53 mutation. It is anticipated that with advancing understanding of the genetic basis of MDS pathogenesis, future MDS classification will be based increasingly on genetic classes. Nevertheless, morphologic features in MDS reflect the phenotypic expression of the underlying abnormal genetic pathways, and will undoubtedly retain importance to inform prognosis and guide treatment.

Latest Insights and Therapeutic Advances in Myelodysplastic Neoplasms

“…MDS diagnosis traditionally relies on clinical and morphologic characterization, as well as genetic criteria [29,30]. The recognition of dysplastic features is crucial for MDS diagnosis, with the recommended threshold for dysplasia set at 10% for all lineages [2].…”

“…In this regard, CD34, CD117, CD33, myeloperoxidase, and lysozyme staining can assist in quantifying myeloid blasts [33]. In addition, a useful accuracy in blast counting, other than valuable findings on the pathological immunophenotype features of MDS cell populations, can be provided by multiparametric flow cytometry (MFC), although this methodology has still only a complementary role [29] in this field and it is not yet widely used in MDS diagnosis [41]. Although cytogenetic analysis maintains a fundamental role in the diagnosis and especially prognosis of MDS patients [35,36], with about half of them carrying one karyotype alteration [4,34], recent genomic advances have provided remarkable improvement in this setting [5,42].…”

Parallel genomic analysis from paired bone marrow and peripheral blood samples of 200 cytopenic patients

“…S14 ). When clonality is detected in PB, current guidelines recommend a BM examination for diagnosing a myeloid neoplasm [ 9 ] and assessing prognostic scores [ 10 ]. BM examination at diagnosis might be replaced in the future by PB monitoring in certain clinical settings (e.g., small/stable clone, low-risk mutation like sole DNMT3A [ 11 ], no therapeutic indication) [ 12 – 14 ].…”

Immunophenotype of myeloid granulocytes in Chinese patients with BCR::ABL1-negative myeloproliferative neoplasms

“…For example, the assessment of minimal residual disease (MRD) has increasingly become a cornerstone of the clinical management of haematological malignancies. Myeloid cell immunophenotyping is an important tool for the diagnosis of myeloid dysplasia in MDS [ 18 ], which can be accompanied by a variety of myeloid cell immunophenotypic abnormalities characterised by abnormal granulocyte CD13/CD16 phenotypes, abnormal expression of CD56 by monocytes and decreased expression of CD71 by erythrocytes [ 19 , 20 ]. It has been shown that monocytes in patients with MPN abnormally express CD56 and have an increase in intermediate and non-classical monocytes [ 21 ], furthermore, granulocytes in patients with PMF also show abnormal features such as an abnormal CD13/CD16 phenotype and expression of CD56 [ 22 ].…”