Selumetinib as an Effective Therapy of Histiocytic Sarcoma Evolving From a B-Cell Acute Lymphoblastic Leukaemia.
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INTRODUCTION: Histiocytic sarcoma (HS) is a rare neoplasm derived from non-Langerhans histiocytic cells, exceptionally arising from B-ALL. METHODS: We present the case of a child with high-risk B-ALL with PAX5 P80R mutation. RESULTS: Despite initial remission, a chemoresistant paravertebral mass was identified as HS. A shared IGK/TCRB rearrangements and PAX5 alterations between the leukaemic and histiocytic clones suggested transdifferentiation driven by PAX5. A somatic MAP2K1 mutation in the HS component prompted selumetinib treatment, leading to a rapid response. CONCLUSION: This case underscores the role of PAX5 in lineage plasticity and highlights the potential of targeted MEK inhibition in MAPK-driven HS arising from B-ALL. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.