Genetic Testing in Head and Neck Paragangliomas: Who, What, and Why?

Objective: Understand the role of genetic testing in patients with paragangliomas (PG), we studied a cohort of patients treated at a single institution and characterized the patterns of treatment and genetic mutations. Method: A retrospective review was performed of all patients with paraganglioma who were evaluated at MD Anderson Cancer Center from 1970 to present. Patient demographics, disease patterns, outcomes, and genetic mutations were analyzed. Results: We identified 177 patients with head and neck paragangliomas (HNPG). Genetic testing was performed on 26 patients, of whom 16 had mutations. SDHD accounted for 75% of the mutations, of which P81L [ProlineàLeucine] accounted for 75%. The remainder had SDHB mutations. Of patients with mutations, average age was 39.5 years (vs 48.4 years in those without mutation), 63% (vs 40%) had multiple tumors, 94% (60%) had at least one carotid body tumor, and family history was positive in 38% (20%). Concurrent sites outside the head and neck included adrenal pheochromocytoma, mediastinum, retroperitoneum, and spinal metastasis. Conclusion: Our results suggest patients suspected of heritable HNPG should undergo testing first at the SDHD and SDHB loci, unlike familial PGs at other sites, which are also associated with VHL mutations. Our findings have implications for long-term monitoring for secondary tumors, counseling family members, and cost-efficient mutational screening.