LAUSR

Abstract Background: Metastatic pheochromocytomas are rare neuroendocrine tumors that carry a poor prognosis. There are no curative treatments; however, current therapeutic strategies to control tumor burden include surgery, radiation, ablative therapy, chemoembolization, and systemic therapies. We describe an interesting case of a patient with metastatic pheochromocytoma misdiagnosed as renal cell carcinoma (RCC) started on axitinib and pembrolizumab, who achieved a partial response to treatment, despite lack of approved indications for these therapies in metastatic pheochromocytoma. Clinical Case: A 64-year-old man presented to the emergency department (ED) with uncontrolled hypertension and severe headache. A 12 cm left-sided pheochromocytoma was diagnosed 11 years ago, which was surgically resected via adrenalectomy. After surgery, the patient was followed in the endocrine clinic for five years with pheochromocytoma serum biochemical markers and declared free of disease. 2 months before hospital admission, he was worked-up for flank pain and at that time, CT abdomen showed a 3 cm mass in the liver and exophytic solid mass measuring 4.2 cm off the left kidney. Subsequently, a CT guided biopsy of the left renal mass was performed and revealed grade II renal cell carcinoma (RCC). He was referred to oncology and was started on a combination of IV pembrolizumab, an immune checkpoint inhibitor against PD-1/PD-L1, and oral axitinib, a selective VEGF receptor inhibitor. He received 3 cycles of immunotherapy treatment; however, he became significantly hypertensive with intermittent headaches, so he was started on atenolol 25 mg once daily. Despite this, he continued to have uncontrolled hypertension, worsening headaches, and flushing, which prompted him to undergo evaluation in the ED. On arrival, BP was 210/90. Labs were remarkable for Hgb 17.2, WBC count of 17.1, and glucose of 178 mg/dL. CT head was negative for any acute intracranial process. Due to suspected recurrence of pheochromocytoma, atenolol was stopped, adrenal workup was conducted, and the patient was started on doxazosin. Urine metanephrines came back elevated at 1097 (RR: 55-320 μg/24 hrs), urine norepinephrine of 260 (RR: 14-120 μg/24 hrs), and urine normetanephrine of 3305 (RR: 114-865 μg/24 hrs). Re-evaluation of pathology opinion was obtained, which indicated that biopsy stained positive for chromogranin A and synaptophysin markers, consistent with metastatic pheochromocytoma. FDG PET/CT was performed following discharge, which revealed the left renal mass decreased to 2.4 cm and the liver mass shrunk to 1.5 cm. Conclusion: To our knowledge, this is the first case report outside of a clinical trial highlighting partial response to axitinib and pembrolizumab in metastatic pheochromocytoma. Emerging preliminary phase II clinical trial data are currently investigating these medications as future treatment modalities.