Small cell lung cancer detected 9 years after LEMS in man, 61

Case report highlights need for cancer checks in LEMS beyond 2 years

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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It can take as long as nine years for doctors to be able to detect a small cell lung cancer (SCLC) in people with Lambert-Eaton myasthenic syndrome (LEMS), as evidenced by a new case report from Italy.

The report describes a man, 61, who was tested every six months for cancer following his LEMS diagnosis. Despite such regular scans, by the time the tumor was found, the patient’s cancer had spread to his airways.

While the current guidelines state that “cancer screening in LEMS should be performed for 2 years,” the treating clinicians noted that “in our patient the underlying tumour remained undetectable much longer, despite the strict surveillance that was extended beyond the recommended time limits.”

According to the team, this case stresses the value of regularly checking for the presence of cancer beyond the currently recommended two years, as the interval between the onset of symptoms and tumor detection can be lengthy.

The report, “Cancer detection after a 9-year course of Lambert-Eaton Myasthenic Syndrome complicated by anti-Hu associated Limbic Encephalitis,” was published in the journal Neuromuscular Disorders.

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In LEMS, antibodies produced by the body’s immune system mistakenly attack voltage-gated calcium channel (VGCC) proteins at the junction where nerves and muscles meet. Nerves and muscles then fail to communicate with one another, resulting in symptoms that include muscle weakness, fatigue, and lack of reflexes.

In roughly half of cases, the disorder occurs with small cell lung cancer or SCLC, a usually fast-growing disease that forms in the lungs. This is because cancer cells also have these VGCC proteins at their surface and the immune system will produce antibodies against them to defend the body from harm. 

LEMS typically manifests before cancer can be detected, and guidelines recommend screening for cancer every 4-6 months for the first two years. However, it can happen that cancer is not detected soon enough. Sometimes, detection comes too late for proper and effective treatment.

Now, researchers describe the case of an older man who experienced weakness in his legs, which gradually spread to his arms over a period of three months. The man was a heavy smoker and also had difficulty swallowing, called dysphagia, a dry mouth, known as xerostomia, and problems with erectile function.

A neurological exam revealed absent reflex response, which improved after brief muscle contraction. In LEMS, muscle weakness often is relieved temporarily after exercise; this phenomenon is called post-exercise facilitation and can help in the diagnosis of LEMS.

When nerves were repeatedly stimulated, at a frequency of 3 Hz, the muscle electrical response became weaker over time; however, at a faster rate of 50 Hz, the response was increased, again suggesting post-exercise facilitation.

Blood testing was positive for anti-VGCC antibodies, and a diagnosis of LEMS was made. The man was started on the corticosteroid prednisone and 3,4-diaminopyridine, also called amifampridine, Firdapse’s active ingredient. His symptoms eased.

Testing came back negative for anti-SOX1 antibodies, a biomarker of paraneoplastic syndrome, which refers to a set of symptoms that occur due to a cancer.

However, the man’s Dutch-English Tumor Association Prediction (DELTA-P) score, a tool considered highly sensitive for estimating the risk of a person with LEMS having small cell lung cancer, was 4. This indicated a high risk (93.5%) of SCLC.

A positron emission tomography (PET) scan, done along with a CT scan, did not detect any signs of cancer. The PET/CT scan was repeated after three months, and then every six months, always with negative results.

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Patient deemed ‘not eligible’ for cancer treatment

Two years after the first symptoms of LEMS, the man was diagnosed with another disease called anti-Hu limbic encephalitis. This is a rare form of brain inflammation associated with an underlying cancer. It also can occur due to self-reactive antibodies.

Among its potential symptoms are cognitive impairment, seizures, and changes in behavior.

A high dose of the corticosteroid methylprednisolone was started, along with anti-seizure medications. This resulted in “good control of seizures despite the persistence of cognitive impairment,” the researchers wrote.

The man also received intravenous (into-the-vein) immunoglobulin to provide extra antibodies to the body. It is believed that these extra antibodies have the effect of distracting the immune system and preventing it from mistakenly attack the body’s own cells.

Doctors continued to closely watch the man for the presence of cancer, with PET/CT done regularly every six months.

When there is an increased risk of cancer, the researchers noted, “cancer screening should be prolonged beyond the current recommendations.”

It was not until nine years after the onset of LEMS that the doctors detected a mass in the left lung. The mass was located in the hilus, an area where the airways, blood vessels, and nerves enter and exit the lungs.

Further studies are needed to improve tumour screening strategies … to foster the probability of [an] earlier cancer diagnosis.

An additional CT scan revealed that the cancer was rapidly spreading and entering into the airways and blood vessels, a characteristic of SCLC. The prognosis, or outlook, was poor, the scientists noted.

Moreover, the man had a low performance status, or level of functioning in terms of day-to-day activities, so he “was deemed not eligible for active cancer treatment,” the researchers wrote.

Per the team, this was “the first case” in which the reported interval between the onset of LEMS and tumor detection “was as prolonged as nine years.”

“Further studies are needed to improve tumour screening strategies … to foster the probability of earlier cancer diagnosis considering risk-based patient stratification,” the team concluded.