Large Invasive Adrenal Cortical Carcinoma in a Patient With Neurofibromatosis Type I

Abstract

Background: Adrenal cortical carcinoma is a rare neoplasm. Adrenal cortical carcinoma has previously been reported in less than 10 cases of patients with Neurofibromatosis Type I. Clinical Case: A 44-year-old Hispanic man with Neurofibromatosis Type I (NF1) presented with progressive hypoxia, tachypnea and abdominal pain. Intubation was required with 100% FiO2. CT angiogram of the chest and abdomen showed a 9.5 cm left adrenal mass with tumor thrombus in the left adrenal vein, distal left renal vein, IVC extending into the right atrium, suggestive of an adrenocortical carcinoma. Café-au-spots, neurofibromas and Lisch nodules were seen on physical exam but no signs suggestive of a functional adrenal cortical carcinoma. Transthoracic echocardiogram demonstrated a large well circumscribed echo-dense mass filling the right atrial cavity. Hemodynamically he was unstable with labile blood pressures due to right atrium thrombus burden. He was supported pending pheochromocytoma investigation. Biochemical work up revealed an elevated 24-hour free cortisol concentration of 95.9 ug/d (<=60ug/d) with a normal 24-hour urine metanephrine and normetanephrine [140ug/d (55-320ug/d) and 448 ug/d (114-865ug/d]. Plasma free metanephrine level was normal 0.43 (0.00-0.49nmol/L) and the normetanephrine levels was increased at 2.7 (0.00-0.89nmol/L) consistent with stress response. Serum aldosterone level and renin activity with potassium and DHEA-S levels were normal. Once pheochromocytoma was ruled out, he successfully underwent a left nephrectomy, left adrenalectomy, IVC thrombectomy, right atrium thrombectomy under a multidisciplinary team of surgeons. Surgery was well tolerated and he was discharged home 11 days later. Pathology confirmed adrenal cortical carcinoma, stage 4, with involvement of endocardium and left renal vein with mitotic count greater than 20/50 high-power fields, consistent with a high-grade tumor. Summary: Patients with NF1 have a higher predilection to develop tumors including pheochromocytoma, paraganglioma, gastrointestinal stromal tumor, and pancreatic neuroendocrine tumor. NF1 association with adrenal tumors is well known, most commonly pheochromocytomas which occur in 0.1–5.7% of patients with NF1. However, based on a literature search there have been less than 10 case reports which postulate an association between NF1 and ACC. Genetic analysis of these reported cases suggest a loss of heterozygosity at the NF1 locus as a possible explanation of development of ACC in patients with NF1. Conclusion: Adrenal cortical carcinoma is rare but should be considered in a patient with NF1 and adrenal mass when plasma/urine metanephrines are not suggestive of pheochromocytoma.