Myeloid neoplasm with PDGFRA rearrangement presenting in blast-phase with basophilia

An adult man, from Southern Africa, presented to a public health centre with symptoms of progressive fatigue. Peripheral blood morphology showed marked basophilia and 21% myeloblasts, confirmed by flow cytometry, suggesting acute myeloid leukaemia with basophilia. Bone marrow biopsy revealed increased mast cells, raising systemic mastocytosis as a differential. However, next-generation sequencing identified a PDGFRA fusion, establishing the diagnosis of blast phase of a myeloid/lymphoid neoplasm with PDGFRA rearrangement. The presence of cells with abnormal basophilic granulation and absence of peripheral blood eosinophilia, together with lengthy turnaround times (TAT) for specialised tests in the public health sector contributed to the delayed diagnosis. This case highlights the diagnostic challenges posed by overlapping morphological features and underscores the critical role of molecular testing in identifying rare but clinically significant tyrosine kinase fusion-driven haematological malignancies, which are highly responsive to targeted therapy.