Discussion: Pheochromocytomas may arise sporadically, which is more common than other presentations, or it may be a part of syndromes such as multiple endocrine neoplasia (MEN) syndrome types IIA and IIB, von Hippel-Lindau disease, tuberous sclerosis, neurofibromatosis, Carney syndrome, and Sturge-Weber syndrome, among others. Pheochromocytomas may be inherited, as they are in 10% of patients. Familial cases these tend to occur in younger patients.
The location and tendency to involve multiple sites vary in incidence depending on whether the tumor is part of a syndrome. Thus, bilateral adrenal pheochromocytomas are seen more commonly in the MEN syndromes, although they may be seen in approximately 10% of sporadic cases. Furthermore, the presence of adrenal medullary hyperplasia preceding the occurrence of pheochromocytomas is highly suggestive of an underlying MEN syndrome. Establishing the diagnosis is important for the patient and family because the risk of other tumors involves the entire family, and early detection of the other components of the syndrome is important for successful management.
Usually, tumors are larger than 3 cm when seen. They are highly vascular, and larger tumors are prone to hemorrhage and necrosis, even when they are benign.
Approximately 10% of pheochromocytomas are malignant. Some authors believe that the size of the tumor is poorly correlated with its malignancy. The diagnosis of a benign versus a malignant pheochromocytoma cannot be accurately determined by the histologic appearance; it depends on the presence or absence of metastasis. Metastases have been reported in the lymphatic tissue, lung, liver, bones, and brain. Vascular invasion, local or distant metastasis, and a DNA ploidy pattern (DNA diploidy is more benign that other patterns) affect the prognosis. The risk of malignancy is lower in patients with familial tumors than in patients with sporadic tumors.
The most severe complication is pheochromocytoma crisis, which includes any manifestation of obtundation, shock, disseminated intravascular coagulopathy, seizures, rhabdomyolysis, acute renal failure, and death.
The high risk of provoking a hypertensive crisis during the manipulation of an adrenal gland is well known.
CT and MRI have higher sensitivity in detecting pheochromocytomas, compared with nuclear medicine scanning with iodine-131 meta-iodobenzylguanidine (131I-MIBG), although 131I-MIBG uptake is more specific. Some authors prefer to use metaiodobenzylguanidine (MIBG) uptake scanning as the initial screening modality because it enables whole-body imaging, which makes it useful for detection of extra-adrenal tumors and metastatic deposits.
Once an adrenal or extra-adrenal tumor is detected, CT or MRI of the region may be performed for anatomic localization prior to surgical removal. If 131I-MIBG uptake is negative but the clinical findings suggest pheochromocytoma, CT or MRI of the chest or abdomen may be performed because the false-negative rate of MIBG scintigraphy is 10%.
The "rule of 10's" applies to pheochromocytomas -- 10% are malignant, 10% are bilateral, 10% are extra-adrenal, and 10% are inherited.
The primary differential diagnosis of an adrenal pheochromocytoma includes adrenal adenoma, adrenal carcinoma, and metastatic disease; the appropriate history and laboratory findings strongly suggest the diagnosis.
MEN-II Syndrome is a familial cancer syndrome which includes pheochromocytomas (approximately 50% of patients, and bilateral 60-80% of the time), medullary thyroid cancer (virtually 100% of patients, and typically bilateral and multicentric), and parathyroid hyperplasia (approximately 50% of patients).
