Histiocytic sarcoma (HS) is a rare, aggressive malignancy of monocyte–macrophage lineage, typically presenting with extranodal disease and lacking B- or T-cell markers [1]. Because of its rarity, there is no standard treatment, though salvage regimens such as ICE (ifosfamide, carboplatin, etoposide) have demonstrated some benefit. Ifosfamide, a DNA-alkylating prodrug metabolized by hepatic CYP3A4 and CYP2B6, is associated with central nervous system (CNS) toxicity in 10–30% of patients [2,3]. Encephalopathy is the most common presentation, while catatonia—characterized by stupor, mutism, negativism, posturing, and waxy flexibility—is rarely reported in oncology patients [4].

A 27-year-old male with stage IV HS, confirmed by biopsy of an 80 × 70 mm terminal ileum mass, was admitted for ICE chemotherapy. On day three, he developed acute psychomotor symptoms including stupor, mutism, and negativism. The Bush–Francis Catatonia Rating Scale (score 7) and Kanner Catatonia Screening Instrument (score 4) confirmed retarded-type catatonia. Neurological evaluation (cranial CT, diffusion-weighted MRI) and laboratory studies were unremarkable. Vital signs remained stable. He was treated with intravenous diazepam 10 mg every 8 hours (two doses total), leading to full resolution of catatonic symptoms. The patient was discharged clinically stable.

Discussion Ifosfamide-induced neurotoxicity typically appears within 48–72 hours, mediated by toxic metabolites such as chloroacetaldehyde that disrupt mitochondrial function and neurotransmission [2,3]. While encephalopathy is well-documented, catatonia is extremely rare and underrecognized. In this case, the temporal relationship to ifosfamide, absence of structural CNS pathology, and rapid benzodiazepine response strongly support ifosfamide-induced catatonia. Similar observations have been described rarely; Gupta et al. [5] reported an analogous case in lymphoma. Benzodiazepines remain first-line therapy, often producing rapid resolution, even in drug-induced catatonia [6].Conclusion This case highlights catatonia as a rare neuropsychiatric complication of ifosfamide. Recognition of such unusual adverse effects is critical, as early diagnosis and benzodiazepine treatment can prevent delays in cancer therapy and improve outcomes.