Idiopathic neutropenia with fewer than 5% dysplasia may be a distinct entity of idiopathic cytopenia of undetermined significance

Abstract

Dear Editor, A condition marked by fewer than 10% of dysplastic cells and fewer than 5% of blasts in the bone marrow (BM) is now categorized as idiopathic cytopenia of undetermined significance (ICUS); if clonal cytogenetic changes are detectable in ICUS patients, the diagnosis can be changed to myelodysplastic syndrome (MDS) [1]. This categorization is very practical and clear-cut in separating MDS from those with low-grade dysplasia [1], and it thus became possible to analyze the clinical and hematologic features to differentiate refractory cytopenia with unilineage dysplasia (RCUD) from ICUS. However, only a single report dealing with possible ICUS with dysplastic features in each cell lineage appears to exist, that by Wimazal et al. [2]. We therefore focused on cytopenia patients with fewer than 5% of BM blasts and reassessed the dysplastic features, in combination with the cytogenetic results, to shed light on low-grade dysplasia. From 1994 to 2008, we performed BM examinations with cytogenetic studies in 445 patients with cytopenia, 237 of whom were given diagnoses of MDS or suspected MDS. As well as we could, we used the initial BM examination to rule out the possibility of other underlying disorders inducing cytopenia, and as a result, 137 patients with fewer than 5% marrow blasts were enrolled in this study. Of these 137 patients, 56 who were followed for more than 6 months and for whom specimens were available for reanalyzable marrow films (200 cells being examined in each cell lineage) were used in this study [3, 4]; two patients with hypoplastic BM without cytogenetic changes were excluded from this study since we could not completely rule out the possibility of low-grade aplastic anemia. In this study, we reassessed the bone marrow films for 16 patients with ICUS (Electronic supplementary materials, File 1), 16 with RCUD (Electronic supplementary materials, File 2), and 22 patients with refractory cytopenia with multilineage dysplasia (RCMD; Electronic supplementary materials, File 3). No particular difference in the peripheral blood data was found among patients with ICUS, RCUD, and RCMD. RCUD patients had more dysgranulopoietic cells than those with ICUS (16.7± 19.4% vs 3.5±3.3%, P=0.0116) because of the presence of hypogranular neutrophils or pseudo-Pelger anomaly, while no significant difference in percentages of dyserythropoietic cells was noted (P=0.1809; Electronic supplementary materials, File 4). This indicates that ICUS patients can usually be diagnosed from the absence of prominent dysgranulopoiesis. We then separated the ICUS patients into two groups according to the percentages of dysplastic cells (Table 1). ICUS patients with fewer than 5% dysplastic cells in at least one cell lineage had a significantly lower absolute neutrophil count than those with 5% to 9% of dysplastic Electronic supplementary material The online version of this article (doi:10.1007/s00277-009-0845-0) contains supplementary material, which is available to authorized users. K. Ando : T. Iwabuchi :K. Ohyashiki (*) The First Department of Internal Medicine (Hematology Division), Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan e-mail: ohyashik@rr.iij4u.or.jp