Document resource
Background/Objectives Paraneoplastic neurological syndromes (PNS) are rare, immune-mediated disorders associated with malignancy, often preceding a cancer diagnosis. Lambert-Eaton Myasthenic Syndrome (LEMS) and paraneoplastic peripheral neuropathies can be early manifestations of malignancies, particularly small cell lung cancer and lymphoproliferative disorders. We present a 73-year-old male with progressive lower limb weakness, ultimately diagnosed with synchronous metastatic melanoma and diffuse large B-cell lymphoma (DLBCL), with a suspected paraneoplastic lower motor neuron (LMN) neuropathy. Methods The patient presented with progressive lower limb weakness, falls, and bladder disturbance over several weeks. Clinical examination revealed a flaccid paraparesis with intact reflexes. EMG/NCS: Lower motor neuron pattern, suggestive of a paraneoplastic syndrome.MRI spine: No compression or cauda equina involvement, but incidental right lower lobe lung mass.CT-guided biopsy: Confirmed metastatic melanoma (previous skin resection several years prior).Sinonasal biopsy: Identified DLBCL (non-GCB subtype).Autoimmune panel: Negative VGCC antibodies, positive anti-Titin antibody.Results Paraneoplastic LMN neuropathy presumed secondary to DLBCL.DLBCL treatment: Initiated R-CHOP chemotherapy, resulting in moderate neurological improvement.Autonomic dysfunction: Orthostatic hypotension improved with beta-blockers and IV hydration.Rehabilitation: Physiotherapy commenced, and mobilization improved.Metastatic Melanoma: Planned initiation of immunotherapy.Conclusion This case highlights the diagnostic challenge of paraneoplastic neuropathies, particularly in the context of dual malignancies. Unlike LEMS, this patient presented with progressive LMN neuropathy with intact reflexes and positive anti-Titin antibodies, more commonly associated with myasthenia gravis than lymphoma. Early recognition and comprehensive oncological workup are critical to guiding treatment and optimizing patient outcomes.