Page 91 - Haematologica Atlas of Hematologic Cytology

CHAPTER 12 - Myelodysplastic syndromes
Chapter 12. MYELODYSPLASTIC SYNDROMES
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis due to premature apoptosis. This phenomenon results in the apparent paradox of peripheral cyto- penia in one or more cell lineages associated with hypercellular bone marrow (BM). The risk of leukemic evolution is variable and the clinical outcome is widely heterogeneous (Table 1).
Table 1. haracteris c features of myelodysplas c syndromes at diagnosis.
one marrow cellularity
Increased, occasionally normal or reduced
one marrow blasts
Normal or increased; <20%
Matura on
Present
Morphology
Dysplasia in one or more myeloid lineages
Hematopoiesis
Ine ec ve
lood counts
Cytopenia(s)
rganomegaly
Uncommon
Once all other hematopoietic or non-hematopoietic disorders have been excluded as the primary reason for the cytopenia/dysplasia, persistent (at least 4 months) peripheral blood (PB) cytopenia (hemoglobin <10 g/dL and/or platelet count <100x109/L and/or absolute neutrophil count <1.8x109/L) should give rise to suspicion of MDS.
Major criteria for diagnosis include the presence of specific alterations in the BM, i.e. one or more of the fol- lowing characteristics: dysplasia in at least 10% of all cells in one of the erythroid, neutrophilic, megakaryocytic lineages in the BM smear; at least 15% ring sideroblasts or at least 5% ring sideroblasts in the presence of SF3B1 mutation; 5-19% myeloblasts on BM smears or 2-19% myeloblasts on blood smears; typical chromosome abnor- mality(ies) by conventional karyotyping or fluorescence in situ hybridization (FISH) (Hasserjian et al., 2017; Valent et al., 2017). Other investigations such as flow cytometry, histological and/or immunohistochemical studies of BM biopsy sections and molecular sequencing studies revealing MDS-related mutations should integrate, but not replace, morphological analysis.
The current reference classification of MDS is that of the World Health Organization (WHO), published in 2001 and up-dated in 2008 and 2016 (Vardiman et al., 2002; Vardiman et al., 2009; Arber et al., 2016). This classifi- cation system is based on an integrated multidisciplinary approach that uses all available information, including molecular findings, to define clinically relevant entities with different prognoses (Table 2). While in advanced forms the detection of increased blasts may facilitate the diagnosis, in the early forms, especially with modest morphological abnormalities, a correct diagnosis is mainly based on the exclusion of other hematologic and non-hematologic diseases (Table 3).
The diagnosis of MDS is essentially based on morphological findings in the PB and BM. Morphological exa- mination has several advantages: it is simple, technically easy, not expensive, and gives quick results. The ma- terial to be examined should be of high quality and well stained. Slides should be made from freshly obtained specimens; specimens exposed to anticoagulants for more than two hours are not satisfactory. No case of MDS should be reclassified while the patient is on growth factor therapy. On BM aspirate smears and/or biopsy tou- ch preparations, May-Grünwald Giemsa (MGG) or similar staining, and iron staining could be supplemented by: cytochemical dyes such as myeloperoxidase and Sudan black to detect myeloid cells and better identify Auer rods, periodic acid Schiff (PAS) to detect abnormal erythroid cells by staining cytoplasmic glycogen, or esterases to distinguish myelocytic from monocytic cells. On PB smears, a differential count of 200 leukocytes and a qua- litative evaluation of white and red cells and platelets are recommended. On BM aspirates, the blast cell count should be performed on 500 nucleated cells with exclusion of megakaryocytes, macrophages, osteoblasts and stromal cells; at least 200 erythroblasts, 200 granulocytic cells and 30 megakaryocytes should be evaluated for dysplasia. A BM trephine biopsy provides information on cellularity and stroma, and is essential for the identifi- cation of MDS with fibrosis and hypoplastic MDS.
An accurate blast count is extremely important in the diagnosis and prognosis of MDS. An increase in blast cel- ls has to be considered a sign of myelodysplasia. According to the WHO, 20% of BM or PB blasts is the threshold for the diagnosis of acute myeloid leukemia (AML), whereas according to the revised International Prognostic
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