Clinical characteristics of pheochromocytoma patients with germline mutations in SDHD.
OBJECTIVE
We examined the value of SDHD mutation screening in patients presenting with apparently sporadic and familial pheochromocytoma for the identification of SDHD-related pheochromocytomas.


METHODS
This retrospective study involved 126 patients with adrenal or extra-adrenal pheochromocytomas, including 24 patients with a family history of multiple endocrine neoplasia 2, von Hippel-Lindau disease, neurofibromatosis type 1, or paraganglioma (PGL). Conformation-dependent gel electrophoresis and sequence determination analysis of germline and tumor DNA were used to identify SDHD alterations. The clinical and molecular characteristics of sporadic and hereditary tumors were compared. We reviewed the literature and compared our results with those from previously published studies.


RESULTS
Pathogenic germline SDHD mutations were identified in three patients: two (2.0%) of the 102 apparently sporadic pheochromocytoma patients and one patient with a family history of PGL. These patients presented with multifocal disease (two of three multifocal patients) or with a single adrenal tumor (one of 82 patients). In the literature, mutations are mostly found in patients </= 35 years of age or presenting with multifocal or extra-adrenal disease. All patients with an SDHD mutation developed extra-adrenal tumors (pheochromocytomas or PGLs) at presentation or during follow-up.


CONCLUSIONS
SDHD gene mutations in patients presenting with apparently sporadic adrenal pheochromocytoma are rare. We recommend SDHD mutation screening for patients presenting with a family history of pheochromocytoma or PGL, multiple tumors, isolated adrenal or extra-adrenal pheochromocytomas, and age </= 35 years. Analysis of SDHD can also help to distinguish synchronous primary tumors from abdominal metastases.
Dannenberg
Hilde
H
Department of Pathology, Josephine Nefkens Institute, Erasmus MC, University Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
van Nederveen
Francien H
FH
Abbou
Mustaffa
M
Verhofstad
Albert A
AA
Komminoth
Paul
P
de Krijger
Ronald R
RR
Dinjens
Winand N M
WN
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase
D008565:Membrane Proteins; C491545:SDHD protein, human; D013385:Succinate Dehydrogenase