Diversity of Affected Genes and Genetic Variants among Patients with Malignant Paragangliomas of the Head and Neck at a Single Institution

Background: There are limited data to guide management of malignant paragangliomas of the head and neck, in part because of their rarity. Here, we sought to characterize the clinical and genetic features of patients with this rare malignancy at our institution.

Methods: Retrospective chart review over the past 20 years was used to identify patients with malignant paragangliomas of the head and neck treated at a tertiary medical center.

Results: Eleven patients with malignant paragangliomas of the head and neck were identified. All tumors originated in the carotid body. Patients had a median age of 32 (range: 17–76), were mostly male (seven patients), and all were of non-Hispanic ethnicity and white race. Most patients had unilateral disease with more cases occurring on the right side (six patients). Two patients had bilateral neck disease. Eight patients had genetic assessment records in the EMR. Genes with variants detected included SDHD (three patients), SDHB (three patients), SDHC (one patient with c.43C>T), and PALB2 (one patient with c.3508C>T). Among those with SDHB mutations, each patient had a different variant (c.649C>T, c.418G>T, and a deletion of exons 2–6). Among those with SDHD mutations, two patients had variant c.242C>T. Notably, these two patients were second-degree relatives carrying the same genetic variant. Data on the specific variant for other subject documented to have a SDHD mutation was not available. The most common location of mets was regional lymph nodes in the neck (six patients), followed by cranial nerves (four patients), skull base (three patients), other nerves of the neck (two patients), the mediastinum (two patients), lung (one patient), and brain (one patient). Patients were all managed surgically. In addition to surgery, five patients received adjuvant radiation, two patients received adjuvant Sandostatin, and two patients received embolization ahead of surgery. At the time of this study, 10 patients were alive at last follow-up, and one patient had died from their disease.

Conclusion: Our review found diversity in both the affected genes and the genetic variants among patients with malignant head and neck paragangliomas at our institution. Further prospective research, ideally at multiple institutions, will be needed to better characterize patterns in specific genetic variants as they relate to patient outcomes and treatment regimens.

Publication History

Article published online:
12 February 2021