Cancer Found After Death of LEMS Patient with Rare Immune-mediated Disorder

A positive SOX1 antibody test led to a post-mortem small-cell lung carcinoma (SCLC) diagnosis in a man with paraneoplastic cerebellar degeneration (PCD) and Lambert-Eaton myasthenic syndrome (LEMS), a case study reports.

“To our knowledge, this is the first reported case of PCD-LEMS with positive SOX-1 antibodies,” the investigators wrote, adding that the case highlights the importance of SCLC evaluation in patients with PCD-LEMS and SOX1 antibodies.

The case report, “Paraneoplastic Cerebellar Degeneration and Lambert-Eaton Myasthenic Syndrome with SOX-1 Antibodies,” appeared in the journal Internal Medicine.

LEMS is caused by autoantibodies attacking a protein called voltage-gated calcium channel (VGCC) found at the neuromuscular junctions, the site where nerve cells connect and transmit signals to muscles. The resulting disruption in nerve-muscle communication causes muscle weakness, primarily in the limbs.

About 10% of LEMS patients develop limb ataxia — difficulty making coordinated limb movements — resulting from paraneoplastic cerebellar degeneration, a condition in which antibodies against tumor cells attack healthy cells in the cerebellum, a motor-controlling brain structure. Most PCD-LEMS cases are associated with small cell lung cancer, an aggressive type of lung cancer most common in smokers.

Antibodies against the protein SOX1 are common in people with SCLC, including a case reported last year in a man with LEMS.

The present case study describes a 69-year-old man with PCD-LEMS who was eventually diagnosed with SCLC due to the presence of anti-SOX1 antibodies.

He was admitted to the hospital with progressive gait abnormalities. Seven months prior, he began experiencing difficulty walking that worsened with time. Within five months, he was unsteady when walking and required a handrail to use the stairs. The patient had a medical history of altered levels of blood lipids (fat) and had been a smoker.

At admission, he had low blood pressure and a normal body temperature. An examination revealed several neurological features including slurred speech, muscle weakness in both legs, and limb ataxia along with a clumsy, staggering gait. 

Nerve-muscle analysis showed signs of damage in the forearm and lower legs. A strong voluntary contraction of the patient’s right forearm muscle generated a response (i.e. transmission of an electrical signal between the nerve and muscle), but repetitive stimulation of the nerve generated a decreasing response, indicative of muscle fatigue and weakness.

On the second day of his hospitalization, the patient had a chest CT scan that revealed a mass in the lungs, suggesting pneumonia caused by breathing in food, saliva, liquids, or vomit into the lungs or airways. He was diagnosed with PCD-LEMS and treated with 60 mg/day of pyridostigmine from day five. His respiratory condition continued to deteriorate due to pneumonia, and he died nine days after admission.

A post-mortem blood test detected antibodies against VGCC, indicative of PCD-LEMS, as well as SOX1 antibodies, suggestive of SCLC. An autopsy confirmed the presence of a tumor in the lungs that had not been detected by CT scan and was later determined to be SCLC. 

“Our patient died within a short period, but we believe that additional examinations … would have been useful for SCLC detection because his blood examination revealed SOX-1 antibodies,” the scientists wrote. “The potential presence of SCLC should be more carefully assessed in patients with PCD-LEMS who test positive for SOX-1 antibodies, even if no mass lesion suggesting malignancy is detected by CT.”