Small cell lung cancer with anti-SOX1 paraneoplastic limbic encephalitis: fatal autopsy case

What happened, in summary

This 69-year-old man, who had lived with schizophrenia for more than 20 years, was hospitalized after 1 day of fever, altered mental status, and a 5-minute generalized seizure. He had smoked about 10 cigarettes per day and had no previous history of epilepsy. Initial tests showed mild inflammation, low sodium, markedly elevated creatine kinase, and chest CT findings that looked like pneumonia with hilar lymph node enlargement. Brain MRI was initially unrevealing, but on hospital day 8 his consciousness worsened and recurrent seizures became difficult to control. A repeat brain MRI showed abnormal signal in both hippocampi, and spinal-fluid testing showed mild inflammation without viral infection or malignant cells. His breathing then worsened, requiring mechanical ventilation for 2 weeks. The diagnostic workup shifted toward a paraneoplastic neurologic syndrome. ProGRP was markedly elevated at 667 pg/mL, sputum cytology suggested small cell lung cancer, and paraneoplastic antibody testing was strongly positive for anti-SOX1 antibody. Because his condition continued to deteriorate and responsiveness remained poor, a palliative approach was chosen. Seizures were controlled with levetiracetam and phenobarbital, but his consciousness did not recover. He died on hospital day 115. Autopsy found a right hilar small cell lung cancer with neuroendocrine marker positivity and Ki-67 of 46%. The brain showed severe limbic injury, especially hippocampal neuronal loss, gliosis, and cytotoxic T-cell infiltration, consistent with anti-SOX1 paraneoplastic limbic encephalitis. The diagnosis rested on several converging clues: recurrent seizures, hippocampal MRI changes, inflammatory spinal-fluid findings, strongly positive anti-SOX1 antibody, elevated ProGRP, and small cell carcinoma confirmed in the right hilum at autopsy.