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Clinical Characteristics of Pheochromocytoma Patients With Germline Mutations in SDHD

From the Department of Pathology, Josephine Nefkens Institute, Erasmus MC, University Medical Center, Rotterdam; Department of Pathology, St Radboud University Medical Center, Nijmegen, the Netherlands; and Institute of Pathology, Hospital Baden, Baden, Switzerland

Address reprint requests to Winand N.M. Dinjens, PhD, Department of Pathology, Josephine Nefkens Institute, Erasmus MC, University Medical Center, PO Box 1738, 3000 DR Rotterdam, the Netherlands; e-mail: w.dinjens{at}erasmusmc.nl

PURPOSE: We examined the value of SDHD mutation screening in patients presenting with apparently sporadic and familial pheochromocytoma for the identification of SDHD-related pheochromocytomas.

PATIENTS AND 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.

CONCLUSION: 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.

Supported by the Vanderes Foundation (grant No. 60), Breda, the Netherlands.

H.D. and F.H.v.N. contributed equally to this work.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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