Reactivation of an anti-Hu paraneoplastic syndrome in a patient with small-cell lung cancer treated with immunotherapy: a diagnostic and therapeutic challenge

Introduction: The objective of this study is to describe a reactivation of anti-Hu paraneoplastic syndrome in a patient with small- cell lung cancer treated with immunotherapy, highlighting the diagnostic and therapeutic challenges involved. Case presentation: The case is a 69-year-old man, former smoker, with a prior history of anti-Hu-positive sensory neuropathy and lung cancer (cT2N3M0, stage IIIB) initially managed with chemoradiotherapy, followed by atezolizumab. After developing new neurological symptoms (ataxia, dysphonia, dysarthria, and weight loss), immunotherapy was discontinued, and extensive evaluations (including neuroimaging, PET/CT, blood tests, and cerebrospinal fluid [CSF] analysis) were performed, ruling out tumor progression or infection. The CSF showed positivity for anti-Hu antibodies, suggesting reactivation of paraneoplastic syndrome. Treatment with methylprednisolone pulses and intravenous immunoglobulin was initiated, resulting in partial improvement of speech and dysphonia, though gait instability persisted. Discussion: Findings highlight the diagnostic complexity in distinguishing immune-related toxicity, tumor progression, and paraneoplastic relapse. The absence of tumor evidence and partial response to immunomodulatory therapy support the latter hypothesis. Conclusions: It is concluded that in patients with anti-Hu antibodies, the emergence of new neurological symptoms should include, in the differential diagnosis, suspicion of paraneoplastic reactivation, even during immunotherapy. The originality of this report lies in demonstrating the potential interaction between immunotherapy and paraneoplastic reactivation, carrying significant clinical implications.