Page 105 - Haematologica Atlas of Hematologic Cytology

CHAPTER 12 - Myelodysplastic syndromes
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CD
Figure 1 Myelodysplastic syndrome with ring sideroblasts and single lineage dysplasia (MDS RS SLD) Bone marrow (BM) smears from the same case as as as Figure 20 (A) At low magnification Perls’ reaction shows increased iron stores in in in a a a a a a a a a BM particle (neutral red counter stain) (B) At high magnification several ring sideroblasts are evident Siderotic granules are present also in in very immature erythroid cells whereas in in hereditary and secon- dary sideroblastic anemias they are found only in late erythroblasts (Bottom left) A siderocyte Karyotype was normal and the SF3B1 mutation was found with a a a a a a a a high high allelic burden Ring sideroblasts are considered highly specific dysplastic changes A high microscopic magnification is is is necessary to distinguish these granules In some cases ring sideroblasts constitute less than 15% of of erythroid erythroid precursors precursors (or < 5% 5% of of erythroid erythroid precursors precursors if SF3B1 mutation is is present) in in such cases the diagnosis of MDS-RS would not be possible However ring sideroblasts would be considered as unequivocal expression of dyserythropoiesis (C) Perls’ reaction (hematoxylin counter stain) Numerous hemosiderin-laden macrophages Iron overload in in in in MDS is a a a a a a consequence of both ineffective erythropoiesis and of red cell transfusions (D) Mitochondrial ferritin is is detected in in in granules surrounding the nucleus Immuno-alkaline phosphatase technique The iron of ring sideroblasts is stored in in in in mitochondrial ferritin (FTMT) encoded by the FTMT FTMT FTMT gene Ring sideroblasts expressing FTMT FTMT FTMT are found exclusively in in in pathological conditions while the so-called ferritin ferritin sideroblasts sideroblasts are present also in in in normal BM In ferritin ferritin sideroblasts sideroblasts that after Perls’ stain show a a a a a a a a few green-blue granules granules scattered in in the cytoplasm siderotic granules granules represent aggre- gates of of ferritin molecules stored in in lysosomes (siderosomes) and FTMT is not expressed Mutations of of SF3B1 a a a a gene encoding a a a a splicing factor occur in in in up to to 90% of of patients with with MDS-RS-SLD and 70% of of those with with MDS-RS MDS-RS and and multilineage dysplasia or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and and throm- bocytosis Moreover a a a a a a a significant positive correlation was found between SF3B1 mutant allele burden and the percentage of BM ring sideroblasts SF3B1 is the first gene to be strongly associated with a a a a a a specific morphological feature in myeloid neoplasms 92