Myelodysplastic syndromes: aspects of hematopathologic diagnosis

Myelodysplastic syndromes (MDS) are a heterogenous group of clonal stem cel l disorders which generally occur in older adults but may also affect child ren. Primary MDS should be distinguished from secondary MDS associated with antineoplastic or immunosuppressive therapy (t-MDS), exposure to toxic com pounds, or genetic disorders. The establishment of a neoplastic clone is re flected by dysplastic features and impaired function which may affect all t hree hematopoietic cell lineages. The ineffective hematopoiesis which cause s bone marrow failure is accompanied by peripheral blood cytopenia and is c onsidered to result from increased apoptosis, at least in the less advanced MDS stages. The elucidation of the molecular pathogenesis of MDS has provi ded evidence that chromosomal abnormalities are present in about 50% of pat ients with primary MDS. They include numerical aberrations such as monosomy 5 or 7,trisomy 8, loss of the Y-chromosome and structural abnormalities su ch as deletion of the long arm of chromosome 5 (5q-syndrome), 7, or 8. Base d on the percentage of blasts (<5%, 5-20%, 20-30%) and the presence of >15% ringed sideroblasts for marrows with <5% blasts, the French-American-Briti sh (FAB) classifies MDS into 4 morphologic categories:refractory anemia (RA ), refractory anemia with excess of blasts (RAEB), refractory anemia with e xcess of blasts in transformation (RAEB-t), and refractory anemia with ring ed sideroblasts. The fifth morphologic type is chronic myelomonocytic leuke mia characterized by peripheral blood monocytosis (>1x10(9)/l). However, a modification of this classification will be proposed by the World Health Or ganization, with the intention of lowering the threshold for the diagnosis of AMI from 30% to 20% blast cells. ln patients presenting with cytopenias suggesting impaired hematopoiesis, the initial diagnosis depends mainly on the cytological evaluation of bane marrow and blood smears and the histolog ical findings of trephine bone marrow biopsy. in a retrospective analysis w e evaluated the occurrence of the distinct FAB-categories as percentage of the total number of MDS cases diagnosed at the Institute of Pathology of th e University of Freiburg. A total of 63% fullfilled the criteria of RA/RARS , 17% of RAEB, 14% of RAEB-t and 6% of CMML. A fibrotic variant of MDS was observed in 7.67% of all cases, ranging from 2.34% in RA up to 15.42-15.84% in the categories which did not show significant differences with regard t o myelofibrosis. The histologic evaluation of a trephine bone marrow biopsy is of critical importance for the evaluation of fibrotic or hypocellular M DS since these patterns are not reflected by the cytological examination. T he combined cytological and histological diagnosis of bone marrow and perip heral blood is a reliable tool for the initial diagnosis of MDS. ln additio n, cytogenetic and molecular analysis should be performed. Presently, the r isk of leukemic transformation is evaluated using the International Prognos tic Scoring System for MDS, which is the sum of the scores of bone marrow b lasts, karyotypes and cytopenia. In the context of clinical trials therapeu tic modalities should be considerd according to the age and the general per formance state and the prognostic scores of individual patients.