Myopathy in Metastatic Salivary Duct Carcinoma during Neurotrophic Tyrosine Receptor Kinase Inhibitor Treatment: A Case Report.

Case Diagnosis: A 66-year-old male with metastatic salivary duct carcinoma presents with proximal limb myopathy.

Case Description or Program Description: The patient presented with progressive painless proximal limb weakness over the past 3 years. He was diagnosed with salivary duct carcinoma 7 years prior and underwent right parotidectomy and chemoradiotherapy due to metastasis to the lungs and ribs. He remained on palliative treatment with neurotrophic tyrosine receptor kinase (NTRK) inhibitors, first Larotrectinib followed by Entrectinib for the past 3 years. Initially, he reported myalgias which gradually improved, however, he developed weakness as his treatment transitioned. Oncology noted symptom improvement during treatment interruptions. Discontinuation was avoided due to overall survival exceeding the anticipated 7-month prognosis now 7 years later.

Setting: Outpatient - Cancer Rehabilitation

Assessment/Results: Initial strength examination revealed symmetric 4/5 strength in the shoulder abductors and hip flexors. Laboratory results showed elevated levels of Creatine Kinase, Aldolase, and Lactate Dehydrogenase, though creatine kinase remained below 10 times the upper limit of normal. Inflammatory markers (ESR, CRP), thyroid studies (TSH, Free T4), voltage-gated calcium channel (VGCC) antibodies, and urine myoglobin were within normal limits. An electrodiagnostic study indicated abnormal findings in the right iliopsoas muscle, consistent with myopathic etiology. A referral for rheumatologic evaluation was made for further diagnosis and treatment recommendations.

Discussion (relevance): This appears to be the first reported case of proximal limb myopathy associated with NTRK inhibitor therapy in metastatic salivary duct carcinoma. Common adverse reactions to NTRK inhibitors include gastrointestinal symptoms, mood disturbances, weight gain, cognitive impairment, dizziness, fatigue, and increased fracture risk. A multidisciplinary approach involving oncological, rehabilitative, and rheumatologic evaluations is crucial for accurate diagnosis and management. Oncogenic or neuromuscular disorders should be considered when initiating treatment.

Conclusions: Rehabilitative physicians should maintain a high clinical suspicion for myopathy in patients treated with NTRK inhibitors who experience functional decline involving proximal limb muscles.