Characterization of Malignant Head and Neck Paragangliomas at a Single Institution Across Multiple Decades
Hilary C. McCrary, MD, MPH1; Eric Babajanian, MD1; Matias Calquin, BS2; et al Patrick Carpenter, MD1; Geoffrey Casazza, MD1; Anne Naumer, MS3; Samantha Greenberg, MS, MPH3; Wendy Kohlmann, MS3; Richard Cannon, MD1; Marcus M. Monroe, MD1; Jason P. Hunt, MD1; Luke Buchmann, MD1
Author Affiliations
JAMA Otolaryngol Head Neck Surg. Published online June 13, 2019. doi:10.1001/jamaoto.2019.1110
Key Points
Question  What are the genetic trends associated with malignant paragangliomas, and what are the roles of surgery, irradiation, and chemotherapy in the treatment of these tumors?

Findings  In this cohort study of 70 patients with paragangliomas at any body site, 17 had malignant paragangliomas, and 5 were found to have succinate dehydrogenase subunit B mutations. Surgery is the mainstay of therapy, with 4 patients found to have malignant disease after selective neck dissection.

Meaning  Genetic evaluation should be integrated into the care of patients with paragangliomas, and a selective neck dissection should be performed at the time of initial resection owing to the inability to detect malignant disease prior to surgery.

Abstract
Importance  Malignant head and neck paragangliomas (HNPGLs) are rare entities, and there are limited data regarding optimal treatment recommendations to improve clinical outcomes.

Objective  To classify succinate dehydrogenase (SDH) germline mutations associated with malignant HNPGLs, evaluate time from diagnosis to identification of malignant tumor, describe locations of metastases and the functional status of malignant HNPGLs, and determine the role of selective neck dissection at the time of initial surgical resection.

Design, Setting, and Participants  A retrospective cohort study was completed of patients diagnosed with paragangliomas on various sites on the body at an academic tertiary cancer hospital between the years 1963 and 2018. A subanalysis of HNPGLs was also completed. Data regarding diagnosis, gene and mutation, tumor characteristics and location, and treatments used were reviewed between February 2017 and March 2018.

Main Outcomes and Measures  Mutations of SDH genes associated with benign and malignant HNPGLs, treatments used, time to the discovery of malignancy, and location of metastasis.

Results  Of the 70 patients included in the study, 40 (57%) were male, and the mean (SD) age was 47 (21.1) years. Of patients with tumors isolated to the head and neck, 38 (54%) had benign HNPGLs, which were associated with mutations in the genes SDH subunit B (SDHB) (n = 18; 47%), SDH subunit C (n = 2; 5%), and SDH subunit D (n = 18; 47%). Among those with malignant HNPGLs, all but 1 patient had mutations in SDHB (n = 5; 83%); 1 patient had no mutation associated with their disease. The average age at diagnosis for malignant HNPGLs was 35 years, while benign tumors were diagnosed at an average age at 36 years. All patients with malignant disease underwent surgery. Four patients were found to have metastasis at the time of selective neck dissection. Among patients with malignant HNPGLs, 5 (83%) were treated with adjuvant radiation, and 1 (17%) was treated with adjuvant chemotherapy.

Conclusions and Relevance  Malignant HNPGLs are rare entities that are difficult to diagnose and are typically identified by the presence of regional or distant metastasis. The results of this study found the prevalence of malignant HNPGLs to be 9%. These data suggest that it is beneficial to perform a selective neck dissection at the time of tumor excision. All patients with malignant HNPGLs but 1 had SDHB mutations.