Pheochromocytomas are located in the adrenal glands in about 80 to 85% of cases, specifically in the inner layer called the adrenal medulla. The remaining 15 to 20% grow outside the adrenal glands at various points along the nervous system, and these are technically called paragangliomas. Understanding the full range of possible locations matters because it affects how the tumor behaves, how it’s found, and how it’s treated.
The Adrenal Medulla: The Primary Site
Your two adrenal glands sit on top of your kidneys. Each gland has an outer layer (the cortex) and an inner core (the medulla). Pheochromocytomas grow from specialized cells in the medulla called chromaffin cells, which normally produce adrenaline and related stress hormones. When a tumor develops in these cells, it can pump out excessive amounts of those hormones, causing episodes of high blood pressure, rapid heartbeat, headaches, and sweating.
Most adrenal pheochromocytomas appear on one side only. In one surgical series, about 50% were right-sided and 41% left-sided, with only 3% occurring in both adrenal glands simultaneously. The median tumor size at diagnosis is around 35 mm, though they can range from as small as 15 mm to 90 mm or larger.
Bilateral Tumors and Genetic Links
Between 7 and 10% of pheochromocytomas show up in both adrenal glands, either at the same time or years apart. This bilateral pattern is a strong signal of an inherited genetic condition. In one long-term study of 112 surgical patients, 12.5% had tumors in both adrenals, and 78.5% of those patients carried a known gene mutation, most commonly associated with MEN2A syndrome or von Hippel-Lindau (VHL) disease.
The old “Rule of 10s,” which taught that only 10% of pheochromocytomas are hereditary, has been overturned by modern genetic testing. Roughly a quarter of patients with seemingly random, non-familial tumors actually carry gene mutations. This is why genetic testing has become a routine part of the workup.
Extra-Adrenal Locations Along the Sympathetic Chain
When pheochromocytomas grow outside the adrenal glands, they most often appear along the sympathetic nervous system, the network of nerves running alongside the spine that controls your fight-or-flight response. These tumors can technically arise anywhere along that chain, from the base of the skull down to the bladder and prostate, but about 98% of sympathetic paragangliomas are found below the diaphragm.
The single most common extra-adrenal site is a cluster of nerve tissue called the Organ of Zuckerkandl. This is a group of chromaffin cells located in the abdomen between the aorta and the vena cava (the body’s two largest blood vessels), roughly between the kidneys and the point where the aorta splits to supply the legs. Other frequent abdominal locations include areas near the major nerve clusters that supply the gut and pelvic organs.
Extra-adrenal location is clinically significant beyond just anatomy. It’s one of the strongest predictors of more aggressive tumor behavior and is associated with mutations in the SDHB gene. Patients with tumors in these locations are monitored more closely for potential spread.
Head and Neck Locations
A smaller group of these tumors arise along the parasympathetic nerves in the head and neck, which follow the paths of the vagus and glossopharyngeal nerves. Head and neck paragangliomas make up about 3% of all paragangliomas and tend to behave differently from their abdominal counterparts. Most are non-functional, meaning they don’t pump out excess hormones, so they don’t cause the classic symptoms of sweating, racing heart, and blood pressure spikes.
The most common head and neck site is the carotid body, a tiny sensor at the fork of the carotid artery in the neck. Carotid body tumors account for up to 60% of all head and neck paragangliomas. They typically present as a painless, rubbery lump just below the angle of the jaw, sometimes with a noticeable pulse. A doctor may hear a bruit (a whooshing sound) over the mass in 30 to 40% of cases. Familial cases are nearly six times more common in carotid body tumors than in paragangliomas at other sites.
Other head and neck sites include the middle ear and jugular region (jugulotympanic paragangliomas), along the vagus nerve, in the larynx, and rarely in the orbit of the eye.
Rare and Unusual Sites
Small clusters of the same type of nerve tissue exist in organs throughout the body, which means paragangliomas occasionally turn up in unexpected places. The urinary bladder and gallbladder both contain tiny paraganglia and can, rarely, develop these tumors. Bladder paragangliomas sometimes cause a distinctive symptom: episodes of high blood pressure triggered by urination, because the bladder contracting squeezes the tumor and releases a burst of hormones. Cardiac and pulmonary paragangliomas have also been documented, though they are exceedingly rare.
Where Malignant Tumors Spread
About 10 to 15% of pheochromocytomas are malignant, meaning they spread beyond their original site. There is no reliable way to determine malignancy from the tumor’s appearance under a microscope alone; the diagnosis is confirmed only when tumor cells are found in locations where chromaffin tissue doesn’t normally exist.
The most common sites of metastatic spread, based on a study of 41 patients with confirmed malignant disease, are lymph nodes (66%), liver (49%), bone (49%), and lungs (34%). A smaller number spread to the mediastinum, the central compartment of the chest.
How These Tumors Are Localized
Finding a pheochromocytoma starts with blood or urine tests that detect excess hormone production, but pinpointing the tumor’s exact location requires imaging. CT and MRI are the first-line tools, with sensitivities of about 90% and 93% respectively. Both are excellent at spotting adrenal tumors but can occasionally miss small or extra-adrenal ones.
For tumors that don’t show up on standard scans, or when doctors need to confirm that a mass is truly a pheochromocytoma, a specialized nuclear medicine scan using a radioactive tracer called MIBG is used. This tracer is absorbed specifically by chromaffin cells, so it lights up pheochromocytomas and paragangliomas wherever they are in the body. MIBG scintigraphy has a 100% positive predictive value in studies, meaning that when it flags a mass, it’s essentially always correct. Combining MRI with MIBG scanning reaches 100% sensitivity and positive predictive value, making it the most reliable approach for patients with confirmed biochemical disease. PET-CT scans using similar hormone-targeting tracers are increasingly used as well, particularly for detecting metastatic or extra-adrenal disease.