Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes

Abstract

The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.

An exploratory clinical trial of bortezomib in patients with lower risk myelodysplastic syndromes

“…Bone marrow characteristics are summarized in Table . Bone marrow aspirates were reviewed to evaluate cellularity, blast count, iron immunohistochemistry stain for ring sideroblasts (RS), dysplasia (defined by MDS dysplasia score as described by Della porta et al), and nuclear factor kappa B (NF‐κB) activity as measured by phosphorylated P65 (pp65) immunofluorescence. These characteristics were compared between the BM sample at the beginning of the clinical trial and the last BM during treatment.…”

Altered chemotactic response to CXCL12 in patients carrying GATA2 mutations

“…The potential relationship between GATA2 mutations and CXCR4 dysfunctions and its association with MDS needs to be addressed in future experiments, notably including longitudinal studies to follow a patient's evolution, and comparative analyses with sporadic MDS. Because MDS is a highly heterogeneous syndrome [65], such a study will demand a discriminative choice of the sporadic MDS cases to establish a group comparable in age and clinical manifestations with patients with GATA2 deficiency.…”

HBME-1 is expressed by erythroid precursors in early maturation stage and can be a valuable tool for evaluation of dyserythropoiesis in bone marrow core biopsy specimens

“…Although morphological erythroid changes are commonly observed in different reactive or neoplastic conditions, a recent study has shown that dyserythropoiesis was one of the minimal marrow dysplasia-defining criteria which provides, in combination with clonal cytogenetic abnormality, a conclusive diagnosis of myelodysplastic syndrome (MDS) 9. However, the identification of dyserythropoietic features in cytology specimens is poorly reproducible,10 and in the setting of histology, this identification is much more difficult, hence the need for additional diagnostic tools.…”