Selumetinib as an Effective Therapy of Histiocytic Sarcoma Evolving From a B‐Cell Acute Lymphoblastic Leukaemia

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