1. Pheochromocytoma Maria E. Ferris, MD, MPH

2. Epidemiology Mean Age in children: 11 years Male 2:1 female Bilateral in 20% of cases 35 Malignant

3. PATHOLOGY It is a tumor of neuroendocrine origin first described by Frankel in 1886. In the 5th gestational week, neuroblasts migrate from the thoracic neural crest to form the sympathetic chains and preaortic ganglia (thought to be the precursors of neuroblastomas and ganglioneuromas.

4. Pathology (2) In the 7th week, a second migration of cells (chromaffin cells) occurs to form the adrenal medullae to: –the sympathetic ganglia, the vagus nerve, paraganglia of the carotid arteries, the arch of the aorta, and the abdominal aorta. –Less commonly to the wall of the urinary bladder, the prostate, behind the liver, the hepatic and renal hila, and near the rectum and the gonads. Pheochromocytomas and paragangliomas arise from these chromaffin cells.

5. Nomenclature Paraganglioma is any extra-adrenal tumor of the paraganglion system. Tumors in the head, neck, and paravagal region are usually nonfunctioning. Tumors around the aorta and sympathetic chain and visceral tumors, such as bladder tumors, usually elaborate catecholamines

6. Tumor Location 50% arise in the adrenal medulla. Most extra-adrenal pheochromocytomas (functional paragangliomas) occur in the abdomen along the great vessels -most commonly in the upper periaortic region from the diaphragm to the lower poles of the kidneys- Extra-adrenal tumors may also occur at the base of the brain, in the chest (including the heart and pericardium), or paratesticularly

7. Characteristics Size from 2 to 3600 g. and are typically not encapsulated. Microscopically, they are composed of nests or cords of polyhedral cells separated by a fibrovascular stroma. Nuclear pleomorphism does not correlate with malignant behavior

8. Malignancy Malignancy is Dx’d clinically based on the presence of extensive local invasion or metastatic disease. Metastases must be distinguished from multifocal tumors occurring elsewhere in areas of neural crest tissue.

9. Presentation and Dx Usualc/o related to catecholamine production. Patients have  stores of catecholamines in sympathetic nerves & norepinephrine released from these terminals has easier access to receptors on the effector cells.

10. Presentation and Dx (2) The catecholamine-induced symptoms are mediated by the normal sympathetic neural pathway and not primarily by serum catecholamines. Any direct stimulus to the sympathetic nervous system can induce a crisis without a large rise in serum catecholamine levels. Blood pressure may sometimes be normal despite high serum levels of catecholamines.