Pheochromocytoma

Excerpt

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are neural crest-derived tumors. PHEOs are chromaffin cell tumors that produce, store, metabolize, and secrete catecholamines [1-3]. The 2004 World Health Organization classification of endocrine tumors defines pheochromocytoma as a tumor arising from catecholamine-producing chromaffin cells in the adrenal medulla, an intra-adrenal PGL. Closely related tumors of extra-adrenal paraganglia are classified as extra-adrenal PGL. While these definitions serve to distinguish the two types of tumor based on location, this does not take into account differences in functional characteristics related to other differences in cellular origin. More specifically, while extra-adrenal PGLs derived from sympathetic nervous system-associated chromaffin tissue almost always produce catecholamines and often lead to hypertension, those derived from parasympathetic tissue (mainly head and neck PGLs) rarely, in less than 20% of cases, produce significant amounts of catecholamines or their metabolites and usually do not cause hypertension; these tumors may be locally invasive but are rarely metastatic. These head and neck PGLs were formerly known as glomus tumor or carotid body tumors. It therefore seems likely that PHEOs will be continued to be defined as catecholamine-producing tumors of intra- and extra-adrenal chromaffin cells, with those derived from the latter types of chromaffin cells classified as extra-adrenal PHEOs. PHEOs typically occur in about 80-85% of cases from adrenal medullary chromaffin tissue and in about 15-20% of cases from extra-adrenal chromaffin tissues [4]. Extra-adrenal PHEOs in the abdomen most commonly arise from a collection of chromaffin tissue around the origin of the inferior mesenteric artery (the organ of Zuckerkandl) or aortic bifurcation [5, 6]. Most PHEOs represent sporadic tumors and about 35% of PHEOs are of familial origin [7]. Sporadic PHEOs are usually unicentric and unilateral while familial PHEOs are often multicentric and bilateral. Both adrenal and extra-adrenal PGLs display similar histopathological characteristics. Unusual sites in the abdomen and pelvis include kidney, bladder, urethra, prostate, spermatic cord, genital tract, and liver. About 4-10% of patients with PHEO present with adrenal incidentaloma, whereas approximately 5% are diagnosed at surgery [8-10]. Although metastases may be rare for adrenal (about 10%) and familial (less than 5%) PHEOs [11], the prevalence is up to 36-50% for extra-adrenal abdominal PHEOs or even higher in those with succinate dehydrogenase subunit B gene mutation [12-15]. Finally, up to 10% of intra-adrenal PHEOs recur locally [16, 17]. PHEOs occur in about 0.05% to 0.1% of patients with sustained hypertension. However, this probably accounts for only 50% of persons harboring PHEO, when it is considered that about half the patients with PHEO have only paroxysmal hypertension or are normotensive. Also, it must also be considered that the prevalence of sustained hypertension in the adult population of Western countries is between 15 to 20% [1, 5, 18]. Thus, in Western countries the prevalence of PHEO can be estimated at 1:2,500 to 1:6,500 patients, with an annual incidence in the United States of 500 to 1,100 cases per year. Despite this low incidence, PHEO must always be considered because if identified, it can be cured in about 90% cases, whereas left untreated, the tumor is likely to be fatal due catecholamine-induced malignant hypertension, heart failure, myocardial infarction, stroke, ventricular arrhythmias, or metastatic disease.