(0620) Clinical and Genetic Characteristics of Malignant Paragangliomas of the Head and Neck

Introduction: There is limited data to guide management of malignant paragangliomas of the head and neck (MHNPGL), in part because of their rarity. Here, we sought to characterize the clinical and genetic traits of patients with this rare malignancy at our institution.

Methods: Retrospective chart review of a 10 year window (2013-23) was used to identify patients with MHNPGL treated at a tertiary medical center. Clinical, pathologic, and outcome data were collected.

Results: In total, 20 patients with MHNPGL were identified. Most of these tumors originated in the carotid body. There were 6 glomus vagale and one glomus jugulare. One patient had a malignant sympathetic paraganglioma. One patient had multifocal disease in the head and neck with both bilateral carotid body tumors as well as a glomus vagale. Patients had a median age of 51.5 (Range: 17-81), were mostly male (11/20), and all were of non-Hispanic ethnicity and White race. Most patients had unilateral disease with more cases occurring on the right side (10/20). Of the total, 3 patients had bilateral neck disease, and 10 patients had genetic assessment records in the EMR. Genes with variants detected included SDHD (3/10), SDHB (3/10), SDHC (2/10), VHL (1/10), and PALB2 (1/10). 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. The most common location of mets was regional lymph nodes in the neck (11/20), followed by cranial nerves (7/10), skull base (5/20), other nerves of the neck (3/20), the mediastinum (2/20), lung (3/20), and brain (3/20). Most patients were managed surgically, and 2 received only radiation therapy. At the time of this study, 18 patients were alive at last follow-up, and two patient had died from their disease.

Conclusions: To our knowledge, this is the largest single institution series of MHNPGL and demonstrates diversity in both the genes and variants. Further prospective research at multiple institutions will be needed to better characterize this condition and genetic variants as they relate to patient outcomes.