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. 2019 Jul 29;63(4):369-375.
doi: 10.20945/2359-3997000000145.

Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance

Ana Milena Gómez  1 , Diogo Cordeiro Soares  2 , Alexandre André Balieiro Costa  2 , Daniele Paixão Pereira  2 , Maria Isabel Achatz  3 , Maria Nirvana Formiga  2
Affiliations

Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance

Ana Milena Gómez et al. Arch Endocrinol Metab. .

Abstract

Objective: Paraganglioma (PGL) and pheochromocytoma (PCC) are rare neuroendocrine tumors that were considered to be predominantly sporadic. However, with the identification of novel susceptibility genes over the last decade, it is currently estimated that up to 40% of cases can occur in the context of a hereditary syndrome. We aimed to characterize PGL/PCC families to exemplify the different scenarios in which hereditary syndromes can be suspected and to emphasize the importance for patients and their families of making an opportune genetic diagnosis.

Materials and methods: Retrospective analysis of patients diagnosed with PGL/PCC. Germline mutations were studied using next-generation sequencing panels including SDHA, SDHB, SDHC and SDHD. Clinical data were collected from clinical records, and all patients received genetic counseling.

Results: We describe 4 families with PGL/PCC and germline mutations in SDH complex genes. 2 families have SDHB mutations and 2 SDHD mutations. The clinical presentation of the patients and their families was heterogeneous, with some being atypical according to the literature.

Conclusions: PGL/PCC are more commonly associated with a germline mutation than any other cancer type, therefore, all individuals with these types of tumors should undergo genetic risk evaluation. NGS multigene panel testing is a cost-effective approach given the overlapping phenotypes. Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical and imaging surveillance and their families should undergo genetic counseling. For all these reasons, it is critical that all medical staff can suspect and diagnose these inherited cancer predisposition syndromes.

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Conflict of interest statement

Disclosure: the study authors had no financial support for the development of this work, contributed within their areas of expertise, and had no conflicts of interest.

Figures

Figure 1
Figure 1. Pedigree of family with mutation in SDHB gene
Figure 2
Figure 2. Pedigree of family with mutation in SDHD gene
See this image and copyright information in PMC

References

    1. Baysal BE. Hereditary paraganglioma targets diverse paraganglia. J Med Genet. 2002;39(9):617-22. - PMC - PubMed
    1. Kirmani S, Young WF. Hereditary Paraganglioma-Pheochromocytoma Syndromes. In: Pagon RA, Adam MP, Ardinger HH, et al. (eds): Seattle (WA): GeneReviews(R); 2014.
    1. Mannelli M, Castellano M, Schiavi F, Filetti S, Giacchè M, Mori L, et al. Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. J Clin Endocrinol Metab. 2009;94(5):1541-7. - PubMed
    1. Buffet A, Venisse A, Nau V, Roncellin I, Boccio V, Le Pottier N, et al. A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma. Horm Metab Res. 2012;44(5):359-66. - PubMed
    1. Fishbein L, Merrill S, Fraker DL, Cohen DL, Nathanson KL. Inherited mutations in pheochromocytoma and paraganglioma: why all patients should be offered genetic testing. Ann Surg Oncol. 2013;20(5):1444-50. - PMC - PubMed