Pheochromocytomas are an uncommon tumour of the adrenal gland, with characteristic clinical, and to a lesser degree, imaging features. The tumours are said to follow a 10% rule:
- ~10% are extra-adrenal
- ~10% are bilateral
- ~10% are malignant
- ~10% are found in children
- ~10% are familial
- ~10% are not associated with hypertension
The estimated prevalence of pheochromocytomas in hypertensive adults is thought to range around 0.1-0.6%. The incidence in the general population is thought to be around 0.05% based on autopsy series 9.
The majority of cases are sporadic. In 5-10% of cases, a pheochromocytoma is a manifestation of an underlying condition including 1-4,6:
- multiple endocrine neoplasia type II (MEN II): both MEN IIa and MEN IIb
- account for 3% of all pheochromocytomas
- almost never extra-adrenal
- almost always bilateral 4
- von Hippel-Lindau disease
- von Recklinghausen disease (neurofibromatosis type I)
- Sturge-Weber syndrome
- Carney triad: for extra-adrenal pheochromocytoma
- tuberous sclerosis
- familial phaeochomocytoma
It is rare, but classical cause, of uncontrolled secondary hypertension. A minority of patients will present with hypertensive crises. In addition to severe paroxysmal hypertension, patients may present with cardiac dysfunction (myocardial infarction, pulmonary oedema) or neurological events (severe headache, visual disturbance, haemorrhagic strokes) 5.
The first investigation in cases where pheochromocytoma is suspected is usually urinary catecholamines. When those results are positive then imaging is performed to try and localise the tumour.
Pheochromocytomas are a type of paraganglioma. They are catecholamine-secreting tumors derived from chromaffin cells. They typically demonstrate a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumour cells containing eosinophilic cytoplasm separated by fibrovascular stroma.
They most frequently arise from the chromaffin cells of the adrenal medulla.
Extra adrenal locations
Approximately 10% of all pheochromocytomas are not located in the adrenal glands. Extra-adrenal tumours are more likely to be malignant and metastasise 4.
As a general rule tumours in the adrenal region tend to be large at presentation, usually > 3 cm, with an average size of ~5 cm. When confined to the adrenal glands, and especially if suspected clinically, the diagnosis is readily made. Small extra-adrenal tumours can however be a challenge to find. Overall 98% of tumours are in the abdomen, and 90% are confined to the adrenal glands 6.
It is also important to note that it is not possible to distinguish malignant from benign pheochromocytomas merely on the direct appearance of the mass. Rather, the distinction is made on demonstrating evidence of direct tumour invasion into adjacent organs/structures or the presence of metastases 4.
Can have a variable appearance ranging from solid to mixed cystic and solid to cystic 9.
CT is the first imaging modality to be used, with an overall sensitivity of 89%. This is on account of 98% of tumours being located within the abdomen and 90% limited to the adrenal glands 6.
On CT pheochromocytomas are large usually heterogeneous masses with areas of necrosis and cystic change. They typically enhance avidly 8 and up to 7% demonstrate areas of calcification 4.
It should be noted, that in patients with suspected phaeochromocytomas contrast may be contraindicated as it could precipitate a hypertensive crisis.
MRI is the most sensitive modality for identification of pheochromocytomas, and is particularly useful in cases of extra-adrenal location. The overall sensitivity is said to be 98% 6.
- slightly hypointense to the remainder of the adrenal
- if necrotic and/or haemorrhagic then signal will be more heterogeneous
- markedly hyperintense (lightbulb sign): this is a helpful feature
- areas of necrosis/haemorrhage/calcification will alter signal
T1 C+ (Gd)
- heterogenous enhancement
- enhancement is prolonged, persisting for as long as 50 minutes 4
A number of agents can be used to attempt to image pheochromocytomas, and are especially useful in trying to locate an extra-adrenal tumour (when CT of the abdomen is negative) or metastatic deposits. Unfortunately these agents are not very specific for pheochromocytomas, and have limited spatial resolution, usually requiring the tumour to be >1 cm in diameter.
Octreotide (somatostatin) scans
Over 70% of tumours express somatostatin receptors. Imaging is obtained 4 hours (+/- 24/48 hours) after an intravenous infusion. Unfortunately the kidney also has somatostatin receptors, as do areas of inflammation, mammary glands, liver, spleen, bowel, gallbladder, thyroid gland and salivary glands. As such interpretation can be difficult 5.
Octreotide is usually labeled with either 111In-DTPA (Octreoscan) or (less commonly) 123I-Tyr3-DTPA 5.
As many tumours demonstrate uptake with MIBG, it is not specific for phaeochromocytoma. Overall sensitivity is ~ 81% 6.
18F Dopa PET is thought to be highly sensitive according to initial results 3.
Treatment and prognosis
Definitive treatment is surgical, and if complete resection is achieved, without metastases, then surgery is curative, and hypertension usually resolves.
Preoperative medical management is essential in reducing the risk of intraoperative hypertensive crises and typically consists of non-competitive alpha adrenergic blockade (e.g. phenoxybenzamine). Later, but never before 7-10 days of alpha blockade, a beta blocker may need to be added to control tachycardia or some arrhythmias 5-6.
Metastases from malignant pheochromocytomas are typically to lung, bone and liver 4.
When located in the adrenal gland, the differential is essentially that of an adrenal tumour, and includes:
In large tumours, especially if malignant, differentiating them from renal cell carcinomas can be difficult, especially on CT.
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