LITERATURE UPDATE


Phaeochromocytoma and paraganglioma: testing for rare neuroendocrine tumours


Phaeochromocytomas and paragangliomas develop from neuroendocrine chromaffin cells. Tumours developing from such cells are called phaeochromocytomas if found in the medulla of the adrenal gland, or paragangliomas if growing elsewhere in the body. Here, Pathology in Practice Science Editor Brian Nation looks at a selection of current research in the literature.


Update on the diagnosis of the pheochromocytoma Achote E, Arroyo Ripoll OF, Araujo- Castro M. Hipertens Riesgo Vasc. 2025 Jan-Mar; 42 (1): 43–51. doi: 10.1016/ j.hipert.2024.08.001. Epub 2024 Oct 10.


Phaeochromocytoma is a rare neuroendocrine tumour that develops from chromaffin cells in the adrenal medulla and is characterised by the excessive production of catecholamines and their metabolites. Diagnostic confirmation is performed by detecting elevated levels of catecholamines and/or their metabolites in plasma or 24-h urine. In the case of moderate elevations


of normetanephrine, the clonidine suppression test may be useful to differentiate between endogenous hypersecretion and false-positive results. Once the biochemical diagnosis is performed, the tumour localisation is carried out using imaging techniques and sometimes with nuclear medicine imaging tests.


Furthermore, in all patients with


phaeochromocytomas it is recommended to perform a genetic study to identify hereditary disorders that may be present in more than 30% of cases and to perform a cardiological evaluation to rule out the presence of cardiovascular involvement secondary to the catecholamine hypersecretion.


Biochemical Assessment of Pheochromocytoma and Paraganglioma Eisenhofer G, Pamporaki C, Lenders JWM. Endocr Rev. 2023 Sep 15; 44 (5): 862– 909. doi: 10.1210/endrev/bnad011.


Phaeochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimise associated morbidity and mortality. Once considered, appropriate


56


Adrenal phaeochromocytoma. The tumour is sharply demarcated by a fibrous capsule from the surrounding adrenal cortex, part of which is seen in the upper part of the image (haematoxylin and eosin [H&E] stain).


biochemical testing is key to diagnosis. Advances in understanding


catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis. These metabolites, normetanephrine and metanephrine, produced respectively from norepinephrine and epinephrine, can be measured in plasma or urine, with choice according to available methods or presentation of patients. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity than urinary metanephrines for patients screened due to an incidentaloma or genetic predisposition, particularly for small tumours or in patients with an asymptomatic presentation.


Additional measurements of plasma methoxytyramine can be important for some tumours, such as paragangliomas, and for surveillance of patients at risk of metastatic disease. Avoidance of false- positive test results is best achieved by plasma measurements with appropriate reference intervals and preanalytical precautions, including sampling blood in the fully supine position. Follow-up of positive results, including optimisation of preanalytics for repeat tests or whether


to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the test results, which can also suggest likely size, adrenal versus extra-adrenal location, underlying biology, or even metastatic involvement of a suspected tumour.


Modern biochemical testing now makes diagnosis of PPGL relatively simple. Integration of artificial intelligence into the process should make it possible to fine-tune these advances.


Pheochromocytoma: an updated scoping review from clinical presentation to management and treatment


Saavedra TJS, Nati-Castillo HA, Valderrama Cometa LA et al. Front Endocrinol (Lausanne). 2024 Dec 13; 15: 1433582. doi: 10.3389/ fendo.2024.1433582. eCollection 2024.


Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours derived from chromaffin cells, with 80-85% originating in the adrenal medulla and 15-20% from extra-adrenal chromaffin tissues (paragangliomas). Approximately 30-40% of PPGLs have a hereditary component, making them one of the most genetically predisposed tumour types. Recent advances in genetic research have classified PPGLs into three molecular clusters: pseudohypoxia-related, kinase- signalling, and WNT-signalling pathway variants. Specifically, the detection of SDHB-related tumours indicates an increased risk of metastatic disease, which


DECEMBER 2025 WWW.PATHOLOGYINPRACTICE.COM


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