My Strangest Case: The Man With a Heavy Tongue

Meera Mohan, MD, MS; Paulette Mehta, MD, MPH


August 04, 2020

Eight months later, the patient presented with new-onset dysarthria and heaviness of the tongue. Focal neurologic examination was remarkable for a tongue deviation. MRI of the skull base was suggestive of an infiltrative metastatic lesion that involved the clivus and bilateral occipital condyles, with involvement of both hypoglossal canals. The patient underwent 10 sessions of local radiation therapy, with dramatic improvement in his symptoms. On the basis of anecdotal evidence from preclinical and small clinical studies, the patient was started on lenvatinib, a multi–tyrosine kinase inhibitor (TKI). Interim CT scans demonstrated stable disease with no disease progression.

Around the same time, the patient developed new lytic bone lesions, mainly in his thoracic spine. He was started on zoledronic acid, which was later switched to denosumab owing to breakthrough lesions despite bisphosphonate therapy. He had stable disease on lenvatinib. Overall treatment was well tolerated, except for hypertension that required a combination of calcium-channel blocker and angiotensin-converting enzyme inhibitors.

Tumor tissue was sent for next-generation sequencing to identify a targetable mutation. Results were unrevealing, except for a missense mutation in NTRK1 G18E in exon 1. Nine months later, the patient experienced disease relapse, with an incidental new lytic lesion that compromised weight-bearing on the left femur. He underwent open intramedullary fixation, followed by local radiation therapy for 10 sessions. We proceeded with larotrectinib for NTRK alternations, despite existing literature that reported minimal benefit in this setting. A radioactive iodine scan showed no uptake, suggesting an undifferentiated component at the metastatic sites.

Overall, his disease remained stable for 5 months. The patient later presented with a worsening bone lesion and new mediastinal lymph node compression in the right-side bronchi. CT revealed a 4.1 × 3.1 cm bulky subcarinal nodal mass, with mass effect on the right main pulmonary artery and approximately 40% loss of luminal diameter in the right main pulmonary artery. He had ongoing severe pain due to the pelvic lytic lesion. Local radiation therapy was administered for symptom relief. We proceeded with therapy with pembrolizumab as a fourth-line option in this patient with extremely limited treatment choices.


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