Pheochromocytoma and paraganglioma
- Lesion
A tumour of the adrenal medulla that pours out adrenaline-like hormones, causing attacks of high blood pressure, headache and sweating.
What it is
Pheochromocytomas are tumours of chromaffin cells of the adrenal medulla; their extra-adrenal counterparts are paragangliomas. They secrete catecholamines and cause sustained or paroxysmal hypertension, a surgically curable form. A large fraction, around a third, carry germline mutations, so genetic testing is offered to everyone. All are considered to have metastatic potential, and metastasis, not histology, defines malignancy.
Structure
- Gross: from small to large, well demarcated; cut surface yellow-tan, darkening to brown with dichromate (chromaffin reaction); larger ones haemorrhagic and cystic.
- Micro: polygonal or spindle chromaffin cells in nests separated by a rich vascular network.
- Sustentacular cells around the nests are S100 and SOX10 positive.
- Pleomorphism, giant cells and even capsular invasion do not prove malignancy.
- SDHB immunostain loss flags SDH-deficient tumours (germline testing).
Step by step
- A germline or somatic mutation activates kinase signalling or stabilises HIF (pseudohypoxia).
- Chromaffin cells proliferate and store large amounts of catecholamines.
- Release, spontaneous or triggered by pressure, drugs or anaesthesia, causes surges of noradrenaline and adrenaline.
- Vasoconstriction and tachycardia: hypertensive crisis, arrhythmia, stroke.
- Chronic excess injures the heart (catecholamine cardiomyopathy, contraction-band necrosis).
Markers
- Chromogranin A
- Synaptophysin
- Tyrosine hydroxylase
- S100 (sustentacular)
- GATA3
- SDHB loss
Clinical notes
- Up to one in ten tumours are found without hypertension.
- Alpha-blockade before surgery prevents intraoperative crisis.
- Paragangliomas of the head and neck (carotid body) are often parasympathetic and non-secretory.
Test yourself
Think of the answer, then tap the question to see it.
What defines a malignant (metastatic) pheochromocytoma?
The presence of metastases to sites where chromaffin tissue is not normally found; histologic features do not reliably predict behaviour.
What are zellballen?
Nests of chromaffin cells surrounded by sustentacular cells and a delicate vascular network.
Which three genes, when mutated in the germline, commonly cause pheochromocytoma?
RET, VHL and NF1 (also SDHB, SDHD, SDHC, EPAS1, MAX, TMEM127).
Elsewhere in DurgiPedia
- Catecholamines: synthesis and breakdown
- The adrenal medulla and catecholamines
- Adrenal gland: cortex from mesoderm, medulla from neural crest
- Adrenal cortex zones and medulla
- Hereditary cancer syndromes: the table to know
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Pheochromocytoma (StatPearls (NCBI Bookshelf), 2025); Hereditary paraganglioma-pheochromocytoma: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Pheochromocytoma and Paraganglioma Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).
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Representative model, for educational purposes only.