Myeloid neoplasm with a novel cryptic PDGFRB rearrangement detected by next-generation sequencing

Rearrangements of PDGFRB are defining cytogenetic abnormalities seen in “Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB” and are generally evident by common cytogenetic methods. Here we present an unique case in which karyotyping and fluorescence in situ hybridization (FISH) analysis were negative, and the PDGFRB rearrangement was detected by next-generation sequencing (NGS) analysis. The patient presented with approximately one-year history of leukocytosis including neutrophilia, eosinophilia, basophilia and granulocytic left shift. Bone marrow biopsy revealed a hypercellular marrow with panmyelosis, eosinophilia and mast cell hyperplasia. Blasts were not increased. Ancillary studies revealed a normal karyotype and absence of BCR-ABL1 fusion gene. NGS identified AFAP1L1-PDGFRB fusion, which was confirmed by polymerase chain reaction amplification followed by direct Sanger sequencing. The patient was treated with imatinib and showed normalization of peripheral blood leukocytosis, which lasted for at least six months. This case highlights that cytogenetics/FISH study alone may be insufficient to detect all PDGFRB rearrangement, which is critical for the patient's management. We suggest that molecular analysis capable of detecting fusion genes should be performed in all similar cases.