Minimal diagnostic criteria for myelodysplastic syndromes and separation from ICUS and IDUS: update and open questions

Abstract

Although a classification for myelodysplastic syndromes (MDS) has been proposed by several working groups and by the World Health Organization (WHO), with criteria useful to discriminate between disease variants, the important issue of minimal diagnostic criteria of MDS has only recently been addressed. In the current article, proposed minimal diagnostic criteria for MDS are discussed together with two conditions that do not meet these criteria, although cytopenia or dysplasia is present. These two conditions, idiopathic cytopenia of unknown significance and idiopathic dysplasia of unknown significance should be kept in mind as a provisional (potential) diagnosis in patients with suspected MDS. Both conditions can progress to frank MDS over time. Therefore, once diagnosed, these patients should have a haematological follow-up. The diagnosis MDS, on the other hand, needs to be based on robust criteria and exclusion of all other causes of cytopenia and dysplasia, which requires detailed and sometimes extensive investigations, including a bone marrow biopsy, cytogenetic analyses, molecular studies and flow cytometry.

New challenges in evaluating anemia in older persons in the era of molecular testing

“…Current WHO diagnostic criteria for MDS require the presence of one or more cytopenias and either 10% dysplastic cells in one or more hematopoietic lineages, 5% to 19% marrow myeloid blast cells, or a recurrent MDS-associated clonal chromosomal abnormality. [26][27][28] A few karyotypic changes that lack diagnostic specificity (ie, -Y, 18, del(20q)) are not sufficient by themselves to diagnose MDS. 28 Although a diagnosis of MDS using WHO guidelines requires subjective assessment of the degree of hematopoietic cell dysplasia, dysplasia assessment has a low interoperator reproducibility.…”

Assessment of dysplastic hematopoiesis: lessons from healthy bone marrow donors

“…In the absence of cytopenias, it has been proposed that marked dysplasia (> 10%) in one or more major cell lineages should be defined as 'IDUS' ('idiopathic dysplasia of undetermined significance'). 29 Several of our donors would meet these criteria, but the term and its significance should be questioned in this setting.…”

Standards and Impact of Hematopathology in Myelodysplastic Syndromes (MDS)

“…If this is not the case, a provisional diagnosis should be established: in those with marked and persistent cytopenia (hemoglobin <10 g/dL and/or neutrophils <1,000/µL and/or platelets <100,000/µL) but no evident dysplasia (<10% of cells in major BM lineages) the diagnosis Idiopathic Cytopenia of Undetermined (Uncertain) Significance (ICUS) is established [7,57]. In those patients who have marked dysplasia (≥10% in at least one major lineage) with or without an MDS-related karyotype but no or only mild cytopenia, the term Idiopathic Dysplasia of Undetermined (Uncertain) Significance (IDUS) should be applied (Table 4) [57]. By definition the presence of both ICUS and IDUS is exclusive since coexistence of these conditions is diagnostic and meets criteria for MDS [57].…”

“…In those patients who have marked dysplasia (≥10% in at least one major lineage) with or without an MDS-related karyotype but no or only mild cytopenia, the term Idiopathic Dysplasia of Undetermined (Uncertain) Significance (IDUS) should be applied (Table 4) [57]. By definition the presence of both ICUS and IDUS is exclusive since coexistence of these conditions is diagnostic and meets criteria for MDS [57]. Some of these IDUS patients progress to frank MDS over time, whereas others may progress to a myelodysplastic/ myeloproliferative neoplasm.…”

“…In several of these patients, FISH may reveal the presence of a small population of clonal cells carrying an MDS-related cytogenetic defect [57]. Sometimes, when recorded over time, the size of the clone (number of "FISH-positive" cells) may increase, BM function (i.e.…”