Asian Hematology Research Journal

Histiocytic sarcoma is a rare haematopoietic neoplasm with aggressive clinical behaviour and limited standardised treatment guidance. Its occurrence in association with acute lymphoblastic leukaemia is uncommon and may create significant diagnostic and therapeutic challenges. This case report describes a 25-year-old woman who was diagnosed with B-cell acute lymphoblastic leukaemia after presenting with fever and generalised tiredness. Initial evaluation showed blast involvement in the peripheral blood and bone marrow, with flow cytometry supporting B-cell lineage disease. Cytogenetic testing by FISH was negative for BCR-ABL, ETV6-RUNX1, KMT2A, and TCF3 rearrangements, and there was no central nervous system involvement at diagnosis. The patient received HyperCVAD chemotherapy and achieved measurable residual disease-negative remission after the first cycle. During subsequent therapy, she developed persistent fever despite negative infectious and haemophagocytic lymphohistiocytosis work-ups. Repeat bone marrow biopsy and PET-CT revealed a multifocal process, including metabolically active breast nodules and skeletal lesions. Core biopsy of the right breast lesion showed large histiocytoid cells with diffuse CD68 and CD4 positivity, weak LCA and TdT expression, absence of other myeloid and lymphoid lineage markers, a Ki-67 index of 15–20%, and negative BRAF V600E staining. These findings supported a diagnosis of histiocytic sarcoma involving the breast and bone marrow. The patient’s condition deteriorated despite further therapy, and palliative care was initiated. This case highlights the need for careful clinicopathological correlation when atypical lesions emerge during treatment for acute lymphoblastic leukaemia.