LEMS and Cancer

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune condition in which the immune system mistakenly attacks the nerve cell endings and blocks communication between the nerve cells and muscles, leading to symptoms such as progressive muscle weakness.

About 60% of LEMS cases are associated with small cell lung cancer (SCLC), an aggressive form of cancer that affects the lungs. Other types of malignant tumors may be present in about 10% of LEMS patients.

What causes LEMS?

Nerve cells function by releasing a neurotransmitter or cell-signaling molecule called acetylcholine, which transmits the nerve impulses to the muscles. A protein called voltage-gated calcium channels (VGCC) present in the nerve cell endings controls the flow of calcium inside the nerve cells and the release of acetylcholine into the neuromuscular junction — the point where nerve cells and muscles meet.

LEMS is caused by the immune system producing autoantibodies that mistakenly target the VGCC and block their function. This results in a shortage of acetylcholine and the symptoms associated with LEMS.

LEMS and SCLC

SCLC is a form of cancer that affects the lung tissues. The immune system produces antibodies against neuronal protein that are expressed in SCLC tumors to fight the cancer. These antibodies may cross-react with the VGCC in the neuromuscular junction, triggering the clinical manifestations of LEMS.

Some SCLC-specific antibodies may attack the SOX family of DNA-binding proteins that play an essential role in the development of the nervous system. These antibodies produced in response to SCLC may cause the neuronal damage seen in patients with LEMS. Patients with LEMS without SCLC rarely test positive for these autoantibodies, and therefore they can help discriminate between LEMS with and without underlying SCLC.

Due to a high degree of association between LEMS and SCLC, a diagnosis of LEMS is usually followed by tests to detect underlying cancer.

In LEMS patients with underlying SCLC, chemotherapy and radiation therapy directed toward SCLC have proven beneficial in treating lung cancer as well as alleviating LEMS symptoms.

LEMS and other types of cancer

Although SCLC is the leading type of cancer associated with LEMS, other types of cancer have also been reported. For example, researchers have published a case study of a LEMS patient with adenocarcinoma of the lungs.

LEMS has also been associated with malignant and non-malignant thymoma (cancer of the thymus gland, acute lymphocytic leukemia (cancer that starts in bone marrow), prostate cancer, throat cancer, and breast and cervix cancer. Rare instances of LEMS with cancer in the colon, stomach, and bladder have also been reported.

 

Last updated: July 27, 2019

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