Cerebral Aspergillosis in a Patient on Ibrutinib: A Case of Diagnostic Ambiguity and Multidisciplinary Care.

This case report describes the challenging diagnosis and management of cerebral aspergillosis in a patient with chronic lymphocytic leukaemia undergoing treatment with a BTK inhibitor. The initial presentation was deceptively unspecific, comprising cognitive changes, receptive aphasia, gait instability and mild neurological deficits without fever or significant systemic inflammation. The combination of a muted and non-indicative clinical picture and a broad differential diagnosis reflects the evolving complexity of CNS infections in patients treated with targeted haematological therapies. Neuroimaging played a central role in directing attention toward an intracranial pathological process but did not resolve the ambiguity. CT suggested a space-occupying lesion, while MRI revealed multiple enhancing foci with mixed signal characteristics that could represent fungal, bacterial or neoplastic processes. Diagnosis was only established after neurosurgical intervention, when resection of the dominant lesion provided tissue for definitive identification of Aspergillus fumigatus. Once the diagnosis was confirmed, long-term voriconazole therapy was initiated and adjusted with therapeutic drug monitoring, while ibrutinib was discontinued to prevent interactions and further immunosuppression. The patient's clinical trajectory gradually stabilised, with radiological follow-up showing resolution of lesions and no recurrence. Overall, this case illustrates the importance of maintaining a high index of suspicion for fungal CNS infections in patients receiving modern immunomodulatory treatments. The interplay between subtle and non-specific neurological clinical signs, atypical imaging and altered immune responses can delay diagnosis unless the clinical team actively integrates therapeutic background and invasive modalities into its reasoning. The favourable outcome achieved here underscores the value of early multidisciplinary involvement, timely pursuit of tissue diagnosis and careful coordination of antifungal therapy.