The Pathogenesis of Pheochromocytomas: Of Mice and Men

Pheochromocytomas are neuro‐endocrine tumors that arise from the neural crest derived adrenal medullary chromaffin cells, and produce catecholamines. The first description of a patient with pheochromocytomas was done by Fränkel in 1886, but the term pheochromocytoma was invented by the pathologists Ludwig Pick in 1912, after the Greek words phaios, meaning dark or dusky, and chroma, meaning color, which refers to the dark discoloration of the tumor cells in the chromium‐salt reaction. During embryonic development, cells of the neural crest migrate along preprogrammed pathways, and differentiate into a variety of cell types, such as the intraadrenal and extra‐adrenal chromaffin cells, and the autonomic ganglion cells. The adrenal medulla is composed of chromaffin cells, which are arranged in clusters, enclosed by sustentacular cells and a stromal network. Apart from these structures, the medulla is highly vascularized, and this is also seen in pheochromocytomas. In general, chromaffin cells are thought to store either adrenalin or noradrenalin, but cells containing both catecholamines have been reported in mice. Pheochromocytomas can produce dopamine, adrenalin, noradrenalin, or a combination, depending on their genetic background. Catecholamine production results in sustained, labile or paroxysmal hypertension, and if patients are not treated appropriately, pheochromocytomas will almost always cause fatal cardiovascular events or other devastating complications. Pheochromocytomas occur in approximately 1 or 2 per 100,000 adults in the USA per year (0.001‐0.002%), but the exact incidence is not precisely known. The true incidence of pheochromocytomas is probably higher (towards 0.05%) as one in twenty cases of the incidentally‐found adrenal masses during autopsy, magnetic resonance imaging (MRI), computed tomography (CT), or abdominal ultrasonography, is a pheochromocytoma.

• View at Worldcat

Free Full Text ( Final Version , 3mb )