Clear Discrepancy in Neurofibromin Expression between NF1 Pheochromocytoma Cells and Non-Tumorous Adrenal Medullary Cells

Neurofibromatosis type 1 (NF1) is a common inherited disorder with an autosomal dominant trait. We encountered an NF1 patient who showed adrenal pheochromocytoma, and analyzed expression of neurofibromin in an excised specimen. A 54-year-old man showing multiple neurofibromas and cafe-au-lait spots in the skin was pointed out to have a right adrenal tumor by ultrasonography. Abdominal CT also revealed a right adrenal tumor. He was diagnosed with neurofibromatosis type 1 with no family history. Urine catecholamines, metanephrine, and normetanephrine levels were elevated. MIBG scintigraphy showed positive right adrenal uptake, and so pheochromocytoma was also diagnosed. The patient underwent laparoscopic right adrenalectomy. The excised adrenal specimen of this patient was stained with anti-neurofibromin polyclonal antibody. The NF1 pheochromocytoma was completely negative for neurofibromin protein expression, while the NF1 non-pheochromocytomatous adrenal medulla was neurofibromin-positive in the cytoplasm and nucleus. The clear discrepancy in neurofibromin expression between pheochromocytoma cells and “normal” adrenal medullary cells of the patient may well be explained by Knudson’s two-hit hypothesis.