title: Metastatic sympathetic paraganglioma in a patient with loss of the SDHC gene.
abstract: Mutation of the genes encoding the succinate dehydrogenase (SDH) subunits A, B, C, or D, or the SDHAF2 protein, cause the SDHx-hereditary paraganglioma syndromes. Hereditary susceptibility to metastatic sympathetic pheochromocytomas and paragangliomas is most commonly due to germline mutations in the SDHB gene. Individuals with SDHD mutations occasionally present with metastatic disease, while conversely malignant paragangliomas are rarely observed in SDHC carriers. A 43 year-old woman presented with an abdominal paraganglioma metastatic to the skeleton and multiple lymph nodes. The tumor produced excessive amounts of noradrenaline causing hypertension and symptoms of catecholamine excess. The patient underwent surgical resection of the primary tumor and lymph node metastases. Loss of SDHB protein expression in the primary tumor was demonstrated by immunohistochemistry. Germline sequencing and deletion testing revealed a large allelic deletion of exons 1-6 in SDHC, and no mutations or deletions were detected in SDHB or SDHD. The patient's mother died because of kidney cancer. Hereditary pheochromocytomas and paragangliomas may be associated with a deletion of the SDHC gene. These patients may present with malignant sympathetic paragangliomas.
authors.affiliation: Myriad Genetic Laboratories, Salt Lake City, UT, USA.
authors.forename: Thereasa
authors.initials: T
authors.lastname: Rich
authors.affiliation: Clinical Cancer Genetics Department, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Jackson
authors.affiliation: Department of Endocrinology, Hospital San Vicente Fundacion, Universidad de Antioquia, Medellín, Colombia.|Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street Unit 1461, Houston, TX, 77030, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Roman-Gonzalez
authors.affiliation: Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Komal
authors.initials: K
authors.lastname: Shah
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street Unit 1461, Houston, TX, 77030, USA.
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Cote
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street Unit 1461, Houston, TX, 77030, USA. cjimenez@mdanderson.org.
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D010235:Paraganglioma / Q000235:genetics* / Q000556:secondary; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
chemical_list: D008565:Membrane Proteins; C108096:SDHC protein, human
keywords: Malignant paraganglioma; Paraganglioma; Pheochromocytoma; SDHC; SHDB