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Case history

image A 64-year-old man presented with a 4 week history of haematuria. His medical history included hypertension, type 2 diabetes mellitus and ischaemic heart disease. Investigations revealed a large exophytic mass in the left kidney consistent with renal cell carcinoma (RCC). CT body staging was unremarkable. He underwent laparoscopic left nephrectomy; the final postoperative staging was pT3a left grade 2 clear cell RCC. Since this was high-risk disease, his follow-up was according to the high-risk protocol, which involved 3 monthly clinic review and 6 monthly CT imaging.

Two years into his follow-up, a solitary enlarging lung nodule was seen on the surveillance CT, which was treated with radiofrequency ablation, with confirmed response on subsequent imaging.

Subsequently he developed left arm pain. Shoulder MRI confirmed metastatic disease in the left proximal humerus. He underwent metastasectomy followed by postoperative short course radiotherapy.

During his postoperative recovery, he experienced an episode of left-sided facial weakness and was diagnosed with Bell's palsy. Symptoms resolved following a 7 day course of low-dose oral prednisolone prescribed by his GP.

He continued on watchful waiting. Four years from the diagnosis he developed multiple lobulated lung lesions, consistent with metastases, and an enlarged right adrenal gland. He was commenced on 800 mg oral pazopanib once daily and had an initial response at 3 months; however, progression developed in the known sites of disease at 6 months. In view of the disease progression, pazopanib was stopped and he started nivolumab 3 mg/kg every 2 weeks. He experienced grade 1 fatigue; random cortisol and thyroid function were within the normal range.

After cycle 5 of nivolumab he developed a second episode of left-sided facial weakness. On examination he had a left-sided facial droop with forehead sparing and weakness of left eye closure. Symptoms were consistent with left lower motor neurone facial nerve palsy. Examination of the remainder of the cranial nerves and neurological system was unremarkable. There was no ear pain or evidence of infection on otoscopy.

Head MRI showed no evidence of intracranial metastatic disease but some mild small vessel disease. A CT scan of the chest, abdomen and pelvis revealed progression at known sites of disease.

Nivolumab was stopped and following specialist neurology consultation the patient was commenced on 60 mg oral prednisolone (1 mg/kg per day), with a plan to wean by 10 mg per week. Following 4 weeks of corticosteroid treatment, he had only partial resolution of his symptoms, so his weaning regimen was modified to 5 mg per week. He was then started on cabozantinib for the progressing RCC.

At 8 weeks post-presentation his symptoms had resolved, corticosteroids were stopped and he was tolerating cabozantinib well.

What are the most likely differential diagnoses in this patient?

What tests would you perform to exclude the likely differentials?

How should neurological immune-related adverse events (irAEs) be managed?

How should refractory or worsening neurological symptoms be managed?

What are the concerns with use of corticosteroids in this patient?

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