A novel SF3B1 variant in a patient with MDS with ring sideroblasts.

Abstract

An 80-year-old male was investigated for anemia. Complete blood counts showed WBC of 4.0 × 109/L, hemoglobin of 92 g/L, hematocrit of 27.2%, mean corpuscular volume of 103.7 fl, red cell distribution width of 19.7%, and platelets of 140 × 109/L. Aspirate smears showed 4% blasts, decreased myeloid to erythroid ratio (0.7:1), and megaloblastoid erythroid elements (>10%; Figure 1, panel A, original magnification 1000×, Wright–Giemsa stain). The iron stain showed ∼94% ring sideroblasts (Figure 1, panel B, original magnification 1000×, iron stain). The bone marrow biopsy showed a 60% cellular marrow with occasional hypolobulated megakaryocytes (>10%; Figure 1, panel C, original magnification 200×, hematoxylin and eosin stain; Figure 1, panel D, original magnification 400×, Wright–Giemsa stain). A custom next-generation sequencing panel (45 genes, RainDance/Illumina) showed SF3B1 c.1862A>T, p.D621V at 39.9% variant allele frequency (VAF) and TET2 c.1862A>T, p.S1898F at 3.6% VAF. Cytogenetics showed a normal karyotype. The diagnosis of myelodysplastic syndrome (MDS) with ring sideroblasts (RS) and multilineage dysplasia (MLD) was rendered. To our knowledge, SF3B1 c.1862A>T, p.D621V identified in this case has never been reported to be pathogenic. This case highlights how the morphologic findings (i.e., ring sideroblasts) were very important to guide the interpretation of this novel SF3B1 variant as pathogenic. And, in turn, the molecular evidence of an SF3B1 mutation permitted definitive diagnosis and classification of the morphologic findings. The authors declare no conflict of interest. This study received no specific funding. The authors agree for data sharing and the journal policy.