[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Endocrine system](https://durgical.com/en/general-pathology/areas/endocrine/) › Pheochromocytoma and paraganglioma # 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. Updated Nov 12, 2026 ## Key points - Classic triad of an attack: headache, sweating, palpitations, with hypertension. - Old «rule of 10s» is outdated: hereditary cases are about a third, and extra-adrenal tumours metastasise more often. - Germline genes: RET (MEN2), NF1, VHL, SDHB, SDHC, SDHD, EPAS1 (HIF-2-alpha), MAX, TMEM127. - Two signalling clusters: kinase signalling (RET, NF1, TMEM127, MAX) and pseudohypoxia (VHL, SDHx, EPAS1). - Micro: zellballen (nests) of chromaffin cells with sustentacular cells at the periphery; salt-and-pepper chromatin. - Diagnosis: plasma or urine metanephrines; malignancy only by metastasis (lymph nodes, liver, lung, bone). ## 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. ## Memory aid Pheochromocytoma is a balloon of adrenaline wrapped in zellballen: squeeze it and the pressure spikes; count the genes, not the 10s. ## 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). [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/pheochromocytoma-and-paraganglioma/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Catecholamines: synthesis and breakdown](https://durgical.com/en/biochemistry/topics/catecholamines-synthesis-and-breakdown/) - [The adrenal medulla and catecholamines](https://durgical.com/en/physiology/the-adrenal-medulla-and-catecholamines/) - [Adrenal gland: cortex from mesoderm, medulla from neural crest](https://durgical.com/en/embryology/adrenal-gland-cortex-from-mesoderm-medulla-from-neural-crest/) - [Adrenal cortex zones and medulla](https://durgical.com/en/histology/adrenal-cortex-zones-and-medulla/) - [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/) ## Connections ## Related 5 - [Multiple endocrine neoplasia (MEN) syndromes](https://durgical.com/en/general-pathology/multiple-endocrine-neoplasia-syndromes/) - [Neck cysts and paraganglioma](https://durgical.com/en/general-pathology/neck-cysts-and-paraganglioma/) - [Toxic and radiation injury of the myocardium](https://durgical.com/en/general-pathology/toxic-and-radiation-injury-of-the-myocardium/) - [Tumours of infancy and childhood](https://durgical.com/en/general-pathology/tumours-of-infancy-and-childhood/) - [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/) ## Related conditions 5 - [Phaeochromocytoma](https://durgical.com/en/conditions/phaeochromocytoma/) - [Multiple endocrine neoplasia (MEN 1, 2A, 2B)](https://durgical.com/en/conditions/multiple-endocrine-neoplasia/) - [Neurofibromatosis (types 1 and 2)](https://durgical.com/en/conditions/neurofibromatosis/) - [Neuroblastoma](https://durgical.com/en/conditions/neuroblastoma/) - [Renal cell carcinoma](https://durgical.com/en/conditions/renal-cell-carcinoma/) [← All of general pathology](https://durgical.com/en/general-pathology/) 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](https://www.ncbi.nlm.nih.gov/books/NBK589700/) (StatPearls (NCBI Bookshelf), 2025); [Hereditary paraganglioma-pheochromocytoma: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/hereditary-paraganglioma-pheochromocytoma/) (MedlinePlus, US National Library of Medicine, 2025); [Pheochromocytoma and Paraganglioma Treatment (PDQ®)–Health Professional Version](https://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq) (National Cancer Institute, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/pheochromocytoma-and-paraganglioma/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/pheochromocytoma-and-paraganglioma/