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Weakness and Myalgia in a Patient With Hepatocellular Carcinoma Undergoing Checkpoint Inhibitor Therapy

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 59-year-old man with nonalcoholic steatohepatitis was found to have a 12.4-cm liver mass, with imaging characteristics concerning for malignant neoplasm (Figure, A). A biopsy was performed, and pathology results were consistent with a well-differentiated hepatocellular carcinoma. He enrolled in a phase 1 clinical trial (NCT03299946) using neoadjuvant cabozantinib plus nivolumab followed by definitive resection for patients with locally advanced disease.

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D. Myasthenia gravis and myositis syndrome

Myasthenia gravis (MG) is an autoimmune condition caused by autoantibodies targeting acetylcholine receptors in the neuromuscular junction. There are 2 clinical forms of MG. Ocular MG presents with fluctuating ptosis, ophthalmoparesis, and diplopia. Generalized MG can also affect extraocular muscles but is characterized by proximal muscle weakness that worsens with muscle use. Although all the conditions in the differential diagnosis have been reported as adverse effects of immune checkpoint inhibitor (ICI) therapy, the combination of ophthalmoparesis, ptosis, acetylcholine receptor antibodies (AChR-Abs), and abnormal jitter on single-fiber electromyography is characteristic of MG.13 Lambert-Eaton syndrome also presents with weakness, but it typically improves with muscle use and is caused by antibodies against presynaptic P/Q-type voltage-gated calcium channels. Miller Fisher syndrome is caused by autoantibodies against GQ1b, a ganglioside found in nerves. Guillain-Barré syndrome typically presents with ascending weakness and diminished deep tendon reflexes.

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Article Information

Corresponding Author: Mark Yarchoan, MD, Johns Hopkins University, Baltimore, MD (mark.yarchoan@jhmi.edu).

Published Online: August 29, 2019. doi:10.1001/jamaoncol.2019.2304

Conflict of Interest Disclosures: Dr Yarchoan reports grants and personal fees from Exelixis and Eisai and grants from Bristol-Myers Squibb and Merck & Co outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
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Padua  L, Caliandro  P, Di Iasi  G, Pazzaglia  C, Ciaraffa  F, Evoli  A.  Reliability of SFEMG in diagnosing myasthenia gravis: sensitivity and specificity calculated on 100 prospective cases.  Clin Neurophysiol. 2014;125(6):1270-1273. doi:10.1016/j.clinph.2013.11.005PubMedGoogle ScholarCrossref
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