LEMS Tied to Rare Skin Cancer Successfully Treated: Case Study
About 50% of LEMS cases associated with an underlying cancer
Lambert-Eaton myasthenic syndrome (LEMS) arose in association with a rare type of aggressive skin cancer called Merkel cell carcinoma (MCC), a case study reported for the first time.
The patient was successfully treated with a combination of radiotherapy, chemotherapy, and immunotherapy, which may be a suitable strategy for those with MCC combined with LEMS, its authors noted. The researchers also recommended that a LEMS diagnosis should be accompanied by a thorough cancer screening, even if patients test negative for lung cancer, the type of cancer most commonly associated with LEMS.
The case study, “Combined treatment with radiotherapy, chemotherapy and avelumab results in regression of metastatic Merkel cell carcinoma and improvement of associated Lambert‑Eaton myasthenic syndrome: A case report,” was published in Oncology Letters.
About 50% of LEMS cases are associated with an underlying cancer. The immune response to cancer, rather than the tumor itself, triggers the autoimmune attack on nerve cell endings that eventually lead to the onset of LEMS. Although small cell lung cancer accounts for most of these cases, other cancer types have been linked to LEMS.
For the first time, researchers in Sweden described the case of a 67-year-old man diagnosed with LEMS caused by MCC. “To the best of our knowledge, the present report is the first to describe MCC with associated LEMS,” they wrote.
Lead-up to a LEMS diagnosis
At the beginning of 2018, the man reported involuntary weight loss and progressive muscle weakness, most prominently in the lower limbs, that had begun a year ago. He had been using a wheelchair for a few months.
The man also had dry mouth, erectile dysfunction, and constipation. The researchers noted these indicated problems with the autonomic system, a part of the nervous system that regulates various bodily processes independent of conscious thought, consistent with LEMS. He had no previous cancer history, but was an ex-smoker, was obese, and had high blood pressure.
He had high antibody levels against voltage-gated calcium channels (VGCCs), the proteins in nerve cell endings that are mistakenly targeted and damaged in LEMS, examinations showed. He was diagnosed with LEMS and prescribed pyridostigmine and Firdapse (amifampridine).
Because LEMS is associated with cancer, the patient underwent a series of CT scans to look for tumors. No tumors were found on the skin, but prominent nodes were seen in the right groin area and slightly enlarged nodes were found in the left armpit and chest area. Four regions with increased metabolism — a sign of cancer growth — were detected in both the right groin and and pelvic lymph nodes.
A series of staining tests in tissues isolated from a node in his groin suggested MCC. This wasn’t confirmed, however, since staining results didn’t follow established patterns.
He soon had difficulty breathing, but CT scans showed no signs of lung cancer or lung conditions. But the largest groin node had gotten bigger. The man underwent local radiation therapy, which eased some symptoms, though muscle weakness persisted.
By the middle of the year, his muscle weakness gradually eased and VGCC-antibody levels dropped.
While CT scans showed improvement, the results were not considered satisfactory and the patient required further treatment. An initial round of chemotherapy didn’t ease his LEMS symptoms sustainably, his shortness of breath returned, and a pulmonary embolism, a blood clot in an artery in the lung, was detected.
Avelumab, an immunotherapy for MCC sold under the brand name Bavencio, was prescribed. By the end of the year, he saw further improvements in muscle strength and after five months he could walk without aids. Eight months after starting avelumab, imaging tests showed a marked reduction in tumor size.
One year after starting avelumab infusions, he was diagnosed with suspected therapy-induced hypothyroidism, a condition wherein the thyroid gland doesn’t make enough thyroid hormones. He was treated for it and continued on avelumab. Ten weeks later, CT scans showed no signs of active cancer, but inflammation was consistent with medication side effects. Avelumab was stopped and he continued with LEMS medications.
More than two years after his last avelumab dose, no signs of recurrence were seen. Although a new pulmonary embolism had arisen during follow-up, he was healthy with few signs of muscle weakness. Follow-up clinical and imaging tests are ongoing.
“Signs indicative of LEMS should always form the basis for a thorough malignancy screening even if lung examinations appear normal,” the researchers wrote. “The effect of the combined treatment with radiotherapy, chemotherapy, and avelumab, as well as the tolerance in our patient suggests that this might be a suitable treatment strategy for other patients with MCC combined with LEMS.”