Reduced Risk of Corporal Tumors in Patients With Head and Neck Paragangliomas With p.Pro81Leu Mutations.

Objective: Patients with head and neck paragangliomas who are positive for the SDHD p.Pro81Leu (P81L) mutation are thought to have a distinct phenotype from other SDHx mutations, but few studies have focused on this mutation. The objective of this study was to determine the hazard of developing a second primary, metastatic, or recurrent paraganglioma in SDHx patients with or without P81L.

Study Design: Retrospective chart review of 60 patients with head and neck paragangliomas and genetic testing, followed for a median of 9 years.

Setting: Single academic medical center.

Methods: Univariable Cox proportional hazards regression evaluated second primary and recurrent paragangliomas in patients with SDHD P81L, SDHx non-P81L, and nonhereditary paraganglioma.

Results: This series comprised 31 patients without SDHx, 14 with SDHD P81L, and 15 with other SDHx mutations. At a median 9 years of follow-up, corporal (not head and neck) second primary paragangliomas occurred in 31% of patients with SDHx non-P81L mutations, compared with 0% and 4% of patients with SDHD P81L and without SDHx mutations, respectively. Second corporal paragangliomas were more likely in patients with SDHx non-P81L mutations than in those without a mutation (hazard ratio = 5.461, 95% confidence interval: 0.596-50.030, p = .13).

Conclusion: This is the first study to report a lower likelihood of corporal tumors for patients with head and neck paragangliomas with SDH mutations positive for P81L. Larger studies are needed to determine if head and neck paraganglioma patients with P81L qualify for less intensive imaging surveillance to screen for second primary paragangliomas outside the head and neck.