Malignant paragangliomas associated with mutations in the succinate dehydrogenase D gene.
BACKGROUND
Malignant paragangliomas have been well described in carriers of mutations of the succinate dehydrogenase B (SDHB) gene, but have rarely been associated with mutations in the succinate dehydrogenase D (SDHD) gene.


OBJECTIVE
The aim of the study was to report the different clinical expression patterns of malignant paragangliomas in five patients with SDHD (D92Y) mutations observed in approximately 200 SDHD (D92Y) mutation carriers followed in our institution.


RESULTS
Metastasis and/or local tumor invasion was documented 0 (n=2), 1, 18, and 30 yr after the initial diagnosis of paraganglioma. Malignancy was proven by paraganglioma bone metastases (n=2), intrathoracic paraganglioma with lymph node metastases, locally invasive head-and-neck paraganglioma with destruction of the petrosal bone, and locally invasive paraganglioma of the bladder with lymph node metastases. Four of the five patients developed catecholamine excess during follow-up due to intraadrenal paraganglioma (pheochromocytoma) (n=1), extra adrenal paraganglioma (n=2), and presumed subclinical disease (n=1).


CONCLUSIONS
SDHD mutations (D92Y) are associated with malignant paragangliomas and catecholamine excess with remarkable interindividual variations despite the same mutation. We estimate that the prevalence of malignancy in carriers of D92Y mutations is at least 2.5%.
Havekes
B
B
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. b.havekes@lumc.nl
Corssmit
E P M
EP
Jansen
J C
JC
van der Mey
A G L
AG
Vriends
A H J T
AH
Romijn
J A
JA
D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002345:Carotid Body Tumor / Q000235:genetics; D005260:Female; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000235:genetics*; D012888:Skull Neoplasms / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics*; D013704:Temporomandibular Joint
D007506:Iron-Sulfur Proteins; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase