Objectives: 1) Classify succinate dehydrogenase subunit (SDHx) germline mutations associated with malignant head and neck (HN) paragangliomas. 2) Evaluate time from diagnosis to malignancy. 3) Describe locations of metastases and the functional status of malignant HN paragangliomas.
Methods: A prospective cohort study of patients diagnosed with a paraganglioma between the years 1963-2018 was completed. All patients were enrolled in the Huntsman Cancer Institute at the University of Utah. Data regarding diagnosis, gene/mutation, and tumor characteristics were reviewed.
Results: A total of 70 patients diagnosed with a paraganglioma were included in the study, of which 17 were found to have malignant tumors, with 6 malignant tumors being isolated to the HN. Among those with malignant tumors of the HN, all but one had mutations of the SDHB gene, with the following mutations identified: R230L, P197R, R230H, R242C, and 423+1G>A. Another patient diagnosed at 16 years had no identifiable mutation found. Non-HN malignancies had mutations associated with the genes SDHA (9.0%), SDHB (72.7%), and SDHD (18.3%). Benign paragangliomas were associated with mutations in the genes SDHB (54.7%), SDHC (5.7%), and SDHD (39.6%). The average age of diagnosis for malignant HN tumors was 35 years (range 16-65), while benign tumors demonstrated an average age of 36 years (range 32-41). Only 1 patient had a diagnosis of malignancy upon diagnosis, with an average time to malignancy of 1 year. Locations of malignant tumors in the HN included paracervical (n=1), glomus vagale (n=2), carotid body (n=2), and connective tissue (n=1). All patients with malignant HN tumors underwent excision with selective neck dissection. Positive lymph nodes were found in 5 patients, with another found to have lymph node involvement upon recurrence. Two patients were known to have regional spread prior to surgery, while 4 were found at the time of selective neck dissection. Distant bony metastases were found in 3 malignant HN paraganglioma patients. Among patients with malignant HN tumors, 83.3% were provided adjuvant radiation (n=5) and 16.6% were provided adjuvant chemotherapy (n=1). Only 1 malignant HN tumor was found to be functional, positive for Chromogranin A. One patient had mortality associated with their disease and 2 patients had disease recurrence after initial treatment.
Conclusions: Due to the paucity of literature on malignant HN paragangliomas, we present our prospective cohort of patients, with some patients followed for over 50 years. Malignant paragangliomas are rare entities that are difficult to diagnose, typically identified by the presence of regional/distant metastasis. Our study found the prevalence of malignant HN paragangliomas to be 8.6%. Our data supports performing a selective neck dissection at the time of tumor excision. Furthermore, we provide a detailed discussion of the mutations associated with malignant HN paragangliomas. All patients but one patient had SDHB gene mutations. The patient with no mutation fits into the 10% of patients under the age of 20 who may have no identifiable mutation. Ultimately, all patients with a paraganglioma benefit from counseling on hereditary paragangliomas and malignancy risk with genetic counselors regardless of the disease site.