Case Reports

Lambert-Eaton Myasthenic Syndrome and Merkel Cell Carcinoma

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Lambert-Eaton myasthenic syndrome (LEMS) is an antibody-mediated disorder of the neuromuscular junction that is most commonly diagnosed in association with small cell lung carcinoma (SCLC). Small cell lung carcinoma is histologically similar to the aggressive cutaneous neuroendocrine malignancy Merkel cell carcinoma (MCC). We provide a full report and longitudinal clinical follow-up of a case of LEMS occurring with MCC. We also review the literature on paraneoplastic syndromes associated with MCC and other nonpulmonary small cell carcinomas.

Practice Points

  • Approximately 50% to 60% of patients with Lambert-Eaton myasthenic syndrome (LEMS) have an underlying tumor, most commonly small cell lung carcinoma.
  • A thorough search for an underlying malignancy is highly recommended in patients with diagnosed LEMS without clear cause; to this end, a screening protocol comprising computed tomography and total-body fludeoxyglucose positron emission tomography has been established.
  • Because Merkel cell carcinoma (MCC) can present as occult lymph node involvement with primary cutaneous findings absent, it is recommended that MCC be considered in the differential diagnosis of an underlying malignancy in a LEMS patient.
  • Early identification and treatment of the primary tumor can lead to improvement of neurologic symptoms.


 

References

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy of the skin that is thought to arise from neural crest cells. It has an estimated annual incidence of 0.6 per 100,000 individuals, typically occurs in the elderly population, and is most common in white males.1 The tumor presents as a rapidly growing, violaceous nodule in sun-exposed areas of the skin; early in the course, it can be mistaken for a benign entity such as an epidermal cyst.2 Merkel cell carcinoma has a propensity to spread to regional lymph nodes, and in some cases, it occurs in the absence of skin findings.3 Histologically, MCC is nearly indistinguishable from small cell lung carcinoma (SCLC).4 The overall prognosis for patients with MCC is poor and largely dependent on the stage at diagnosis. Patients with regional and distant metastases have a 5-year survival rate of 26% to 42% and 18%, respectively.3

Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic or autoimmune disorder of the neuromuscular junction that is found in 3% of cases of SCLC.4 Reported cases of LEMS in patients with MCC are exceedingly rare.5-8 We provide a full report and longitudinal clinical follow-up of a case that was briefly discussed by Simmons et al,8 and we review the literature regarding paraneoplastic syndromes associated with MCC and other extrapulmonary small cell carcinomas (EPSCCs).

Case Report

A 63-year-old man was evaluated in the neurology clinic due to difficulty walking, climbing stairs, and performing push-ups over the last month. Prior to the onset of symptoms, he was otherwise healthy, walking 3 miles daily; however, at presentation he required use of a cane. Leg weakness worsened as the day progressed. In addition, he reported constipation, urinary urgency, dry mouth, mild dysphagia, reduced sensation below the knees, and a nasal quality in his speech. He had no ptosis, diplopia, dysarthria, muscle cramps, myalgia, or facial weakness. He denied fevers, chills, and night sweats but did admit to an unintentional 10- to 15-lb weight loss over the preceding few months.

The neurologic examination revealed mild proximal upper extremity weakness in the bilateral shoulder abductors, infraspinatus, hip extensors, and hip flexors (Medical Research Council muscle scale grade 4). All deep tendon reflexes, except the Achilles reflex, were present. Despite subjective sensory concerns, objective examination of all sensory modalities was normal. Cranial nerve examination was normal, except for a slight nasal quality to his voice.

A qualitative assay was positive for the presence of P/Q-type voltage-gated calcium channel (VGCC) antibodies. Other laboratory studies were within reference range, including acetylcholine-receptor antibodies (blocking, binding, and modulating) and muscle-specific kinase antibodies.

Lumbar and cervical spine magnetic resonance imaging revealed multilevel neuroforaminal stenosis without spinal canal stenosis or myelopathy. Computed tomography (CT) of the chest was notable for 2 pathologically enlarged lymph nodes in the left axilla and no evidence of primary pulmonary malignancy. Nerve-conduction studies (NCSs) in conjunction with other clinical findings were consistent with the diagnosis of LEMS.

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