Simultaneous occurrence of germline mutations of SDHB and TP53 in a patient with metastatic pheochromocytoma

Abstract

Context. We describe a patient with metastatic malignant pheochromocytoma who was found to have germline SDHB and TP53 mutations occurring together. Case Description. A 39-year-old male presented with neck pain. Magnetic resonance imaging of the neck revealed a C3 vertebral body collapse and an underlying C3 lesion. Computed tomography (CT) of the thorax, abdomen, and pelvis showed multiple skeletal lesions, a sternal mass, bilateral pulmonary nodules, bilateral adrenal masses, and an aortocaval lymph node conglomerate. He underwent biopsy of the sternal mass, which revealed metastatic pheochromocytoma and subsequent blood work showed serum epinephrine levels of 200 pg/ mL (normal 10-200 pg/mL), norepinephrine 28 241 pg/mL (normal 80-520 pg/mL), and dopamine 250 pg/mL (normal 0-20 pg/mL). Genetic testing revealed both SDHB and TP53 germline mutations. He was started on α- and β-blockers and calcium channel blockers to control hypertension and tachycardia. Two months after the diagnosis, a CT of the abdomen and pelvis showed progression of disease, with enlargement of the right adrenal mass as well as the aortocaval conglomeration. His plasma metanephrines were significantly elevated. He was started on systemic chemotherapy with cyclophosphamide, dacarbazine, and vincristine. He required several antihypertensive agents, including metyrosine, to control his blood pressure in preparation for chemotherapy. Conclusion. This is the first reported case of simultaneous SDHB and TP53 germline mutations occurring in an individual with a highly aggressive clinical course of pheochromocytoma. We speculate that the simultaneous occurrence of these 2 oncogenic mutations may have led to an aggressive tumor progression.