Pheochromocytoma and functional paraganglioma syndrome: no longer the 10% tumor.
Pheochromocytomas and abdominal paragangliomas are catecholamine-producing tumors of the sympathetic nervous system, while head and neck paragangliomas are non-secreting tumors of parasympathetic origin. Recent developments in clinical and molecular research on these tumor forms have significantly clarified their genetic backgrounds and challenged the view of "pheochromocytoma as the 10% rule tumor." Firstly, a larger proportion of these tumors are today discovered in normotensive patients during imaging carried out for other reasons than suspicion of pheochromocytoma. Secondly, although the differential diagnosis between malignant and benign tumors remains a challenge, the risk of malignancy well exceeds the classical 10% in patients with extra-adrenal disease, and/or carriers of germ-line SDHB mutations. Finally, up to a third of patients carry a germ-line mutation in a gene predisposing to pheochromocytoma and/or paraganglioma. Identification of a constitutional mutation in RET, VHL, SDHD, or SDHB has implications for clinical screening and follow-up for both the patient and for relatives at risk who can be identified by screening for the same mutation. Genetic testing in apparently sporadic cases is therefore regarded as beneficial, especially in patients diagnosed before 50 years of age, and in patients with bilateral, multifocal, malignant and/or extra-adrenal disease.
Elder
Elisabeth Edström
EE
Department of Surgical Sciences, Karolinska University Hospital, Stockholm, Sweden. e.elder@bigpond.net.au
Elder
Grahame
G
Larsson
Catharina
C
D000008:Abdominal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009456:Neurofibromatosis 1 / Q000235:genetics; D010236:Paraganglioma, Extra-Adrenal / Q000175:diagnosis / Q000235:genetics*; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics*; D013385:Succinate Dehydrogenase; D025521:Tumor Suppressor Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics
D008565:Membrane Proteins; C491545:SDHD protein, human; D025521:Tumor Suppressor Proteins; D013385:Succinate Dehydrogenase; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human