Hereditary and clinical insights into paraganglioma and pheochromocytoma

Background Approximately 30–40% of paragangliomas (PGLs) and pheochromocytomas (PCCs) harbor an underlying hereditary cause. Early identification of at-risk individuals is imperative given the early onset, aggressiveness of tumors, and other tumor/cancer risks associated with hereditary PGLs/PCCs. T...

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Published in:	Endocrine oncology Vol. 4; no. 1; pp. e240029 - 9
Main Authors:	Mauer Hall, Caitlin B, Watson, Elise M, Prasad, Tanushree, Myers, Chandler L, Mersch, Jacqueline A
Format:	Journal Article
Language:	English
Published:	Bristol Bioscientifica Ltd 01-11-2024 Bioscientifica
Subjects:	hereditary predisposition incidental findings paraganglioma pheochromocytoma sdhx
Online Access:	Get full text
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Summary:	Background Approximately 30–40% of paragangliomas (PGLs) and pheochromocytomas (PCCs) harbor an underlying hereditary cause. Early identification of at-risk individuals is imperative given the early onset, aggressiveness of tumors, and other tumor/cancer risks associated with hereditary PGLs/PCCs. This study analyzes the clinical presentations and genetic histories of patients with PGL/PCC and/or hereditary risk to contribute to the expanding knowledge in this rare population. Methods A retrospective chart review identified two cohorts of patients seen in cancer genetics clinics at an academic medical center and a safety-net hospital between August 2016 and December 2022. Cohort 1 consisted of patients with likely pathogenic variants (LPVs)/pathogenic variants (PVs) in hereditary PGL/PCC predisposition genes. Cohort 2 consisted of patients with a personal history of a PGL/PCC. Demographics, personal/family history, and genetic testing outcomes were analyzed. Results A total of 560 patients met the study criteria (Cohort 1, n = 364; Cohort 2, n = 269). In Cohort 1, 77 (21.1%) patients had an incidental LPV/PV in a PGL/PCC gene. Nearly half ( n = 36, 46.8%) were in SDHx genes, with a majority in SDHA ( n = 21). In Cohort 2, 86 patients tested positive for 87 LPV/PV in a hereditary cancer predisposition gene. The SDHx genes were most likely to have an LPV/PV identified ( SDHB n = 24, SDHD n = 23). Conclusions Multigene panels identify patients at risk for hereditary PGL/PCC, many of whom are incidentally found. While SDHA LPV/PVs were the most frequent incidental finding, they were less common in patients with PGL/PCC, indicating the need for longitudinal studies to better understand the prevalence and penetrance of these tumors.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2634-4793 2634-4793
DOI:	10.1530/EO-24-0029