Elsevier

Surgery

Volume 150, Issue 6, December 2011, Pages 1194-1201
Surgery

American Association of Endocrine Surgeon
Is genetic screening indicated in apparently sporadic pheochromocytomas and paragangliomas?

https://doi.org/10.1016/j.surg.2011.09.024Get rights and content

Background

Pheochromocytoma (Pheo) is usually considered a sporadic disease. Recently, an increasing rate of genetically based tumors has been reported. However, the need for systematic screening of unsuspected germline mutations in apparently sporadic forms is still debated. This study aimed to assess the effective rate of germline mutations causing Pheo and Paraganglioma (PGL), and the role of systematic genetic screening.

Methods

Demographics, clinical, and genetic evaluation were performed in a series of 71 patients with Pheo and/or PGL.

Results

Twelve patients had evident inherited/familial disease at presentation: NF1 (n = 4); MEN2 (n = 4), and familial Pheo/PGL (n = 4). Among 59 patients with apparently sporadic disease, unsuspected germline mutations occurred in 8 cases: TMEM127 (n = 4), SDHB (n = 2), VHL (n = 1), SDHC (n = 1). No differences were found between hereditary and sporadic disease concerning age, sex, and tumor size; bilateral Pheo and/or PGL and recurrences occurred most often in hereditary disease.

Conclusion

Hereditary Pheo and/or PGL are frequent (28.2%). Inheritance is evident at presentation only in 16.9% of cases; 13.6% of apparently sporadic variants are genetically determined. Despite increased costs, systematic genetic screening might be useful because it might lead to a stricter follow-up, early diagnosis of recurrences in index cases and presymptomatic detection of disease in relatives.

Section snippets

Methods

Between 1985 and 2010, 109 consecutive patients with Pheo and/or secreting sympathetic thoraco-abdominal PGL were investigated and treated at the Endocrine Surgery Department of the University of Padua, Italy. The diagnosis of Pheo or functional PGL was determined by the presence of an adrenal or an extra-adrenal thoraco-abdominal tumor associated with a high level of 24-hour urinary catecholamines or catabolites. For every patient, the diagnosis was confirmed by histological examination after

Results

Complete follow-up and genetic test results were available from 71 patients (34 male, 37 female; mean age 44.8; range, 15–80 years), at a median follow-up of 126 months (range, 6–300) after initial surgery. Sixty-six patients presented at initial diagnosis with Pheo only (bilateral in 6 cases), 3 with PGL only, and 2 with both Pheo and PGL. Surgery was performed by open approach in 49 cases, by laparoscopic approach in 21 cases, and the remaining patient, who had a malignant invasive

Discussion

Our study confirmed that hereditary Pheo and/or PGL are frequent (28.2% of cases), suggesting the need for systematic genetic counseling in all patients.4, 6, 7, 9 This finding is concordant with the results of the review of the most recent literature: to date, a rate of 33.7% of genetically determined variants can be identified among the 2204 published cases.5, 6, 7, 8

However, the effective prevalence of hereditary disease is difficult to assess: most findings have been reported by tertiary

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