Asymptomatic patients — With the more widespread use of computed imaging and

genetic testing, an increasing number of pheochromocytoma patients are diagnosed in

the presymptomatic stage; eg, during the evaluation of an adrenal incidentaloma or on
germline pathogenic variant-based case detection. In approximately 60 percent of
patients, the tumor is discovered incidentally during computed tomography (CT) or
magnetic resonance imaging (MRI) of the abdomen for unrelated symptoms [8,9,24-26].
(See "Evaluation and management of the adrenal incidentaloma".)
In a study of 296 consecutive patients with pheochromocytoma treated from 2005 to
2016, 61 percent (180 of 296) were discovered as an incidental finding on cross-section
imaging (see 'Imaging' below), 27 percent (80 of 296) due to pheochromocytoma-
related symptoms, and 12 percent (36 of 296) on mutation-based testing [26]. The
germline pathogenic variant-based pheochromocytomas were smaller and required less
alpha-adrenergic blockade preoperatively (median cumulative phenoxybenzamine dose
270 versus 375 versus 450 mg for germline pathogenic variant-based, incidental-
finding, and symptomatic groups, respectively). In many patients, pheochromocytoma is
found only at autopsy [4,27].
Patients with familial pheochromocytoma — When pheochromocytoma is
associated with the multiple endocrine neoplasia type 2 (MEN2), symptoms are present
in only approximately one-half of patients, and only one-third have hypertension [28]. It
is not known whether this difference is due to screening for pheochromocytoma in
patients with MEN2 or a real difference in the clinical expression of the disease. A
similar finding has been observed with pheochromocytoma associated with von Hippel-
Lindau (VHL) disease as 35 percent of patients have no symptoms, a normal blood
pressure, and normal laboratory values for fractionated catecholamines and
metanephrines [29]. (See "Pheochromocytoma in genetic disorders".)
Tumor characteristics
Location — Approximately 95 percent of catecholamine-secreting tumors are in the
abdomen, 85 to 90 percent of which are intraadrenal (pheochromocytoma), and 5 to 10
percent are multiple [7,30]. Approximately 10 to 15 percent of catecholamine-secreting
tumors are extra-adrenal and are referred to as catecholamine-secreting
paragangliomas. (See "Paragangliomas: Epidemiology, clinical presentation, diagnosis,
and histology".)
Malignant potential — Approximately 10 percent of all catecholamine-secreting tumors
are metastatic (frequency ranges from 8.3 to 13 percent) [7,31-33]. Malignant
pheochromocytomas are histologically and biochemically the same as benign ones. The
only reliable clue to the presence of a malignant pheochromocytoma is local invasion
into surrounding tissues and organs (eg, kidney, liver) or distant metastases, which may
occur as long as 53 years after resection [32-34]. Thus, even when
pheochromocytomas or paragangliomas are considered "benign" on pathologic
examination, long-term follow-up is indicated in all patients to confirm that impression.
Patients with the succinate dehydrogenase (SDH) subunit B mutations are more likely
to develop metastatic disease [11,35,36].
A variety of immunohistochemical and other prognostic markers have been evaluated
for association with malignancy in adrenal pheochromocytomas [37,38], with mixed
results to date. According to the 2017 World Health Organization (WHO), all
pheochromocytomas have some metastatic potential [38]. This is also true for
paragangliomas. (See "Paragangliomas: Epidemiology, clinical presentation, diagnosis,
and histology", section on 'Histology and malignant potential'.)