No abstract

Myelodysplastic syndromes are hematological neoplasias in which immunohistologic examination of bone marrow trephines is important for a definite diagnosis. Unequivocal distinction from reactive bone marrow changes is, however, sometimes difficult. Because neoplastic clones in myelodysplastic syndrome carry mutations in recurrent genes, mutation detection by targeted next-generation sequencing may be a useful support for differential diagnosis. To elucidate the accuracy of this approach in the clinical diagnostic setting, we analyzed single and consecutive bone marrow trephines processed for immunohistologic examination from 145 patients by targeted next-generation sequencing of 12 genes recurrently mutated in myelodysplastic syndromes. Of 110 patients with immunohistologic unequivocal diagnosis, 41 of 47 with myelodysplastic syndrome carried mutations. In 14 consecutive samples available from these patients, remissions were accompanied by loss of mutations and ongoing disease with persisting mutations. Of 35 samples with indefinite immunohistologic appearance, 22 developed clinical unequivocal myelodysplastic syndrome in the further course, and 19 carried mutations already in the initial biopsy, which persisted in consecutive samples available from 13 patients. No mutation was detected in any initial and consecutive sample of 13 patients with indefinite immunohistologic appearance without clinical unequivocal myelodysplastic syndrome in the further course. We conclude that targeted next-generation sequencing is an accurate tool for differential diagnosis of myelodysplastic syndrome in the clinical diagnostic setting.