Calculating the optimal surveillance for head and neck paraganglioma in SDHB-mutation carriers

Karin Eijkelenkamp,Robin P F Dullaart,Michiel N Kerstens,Wim J Sluiter,Thamara E Osinga,Mirjam M De Jong,Thera P Links,Anouk N A Van Der Horst-Schrivers

doi:10.1007/s10689-016-9923-3

Karin Eijkelenkamp, Robin P F Dullaart + Show 6 more

Open Access

https://doi.org/10.1007/s10689-016-9923-3

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Abstract

Germline mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to head-and-neck-paraganglioma (HNPGL), sympathetic PGL, pheochromocytoma and renal cell carcinoma for which regular surveillance is required. SDHB-associated tumors harbor germline and somatic mutations, consistent with Knudson’s two-hit hypothesis. To assess the penetrance and optimal surveillance for different manifestations of SDHB mutation carriers. This study included all SDHB mutation carriers who were followed at the Department of Endocrinology at the University Medical Center of Groningen. Kaplan–Meier curves were used to assess the penetrance. Poisson process was used to assess the optimal age to start surveillance and intervals. Ninety-one SDHB-mutation carriers (38 men and 53 women) were included. Twenty-seven mutation carriers (30 %) had manifestations, with an overall penetrance 35 % at the age of 60 years. We calculated that optimal surveillance for HNPGL could start from an age of 27 years with an interval of 3.2 years. This study underscores the relatively low penetrance of disease in SDHB mutation carriers. Use of the Poisson approach provides a more accurate estimation of the age to initiate surveillance and length of intervals for HNPGL. These results may give rise to reconsider the current guidelines regarding the screening of these mutation carriers.

Highlights

The succinate dehydrogenase subunit B (SDHB) gene is one of the 15 [1] susceptibility genes that have been linked to familial paraganglioma (PGL) and pheochromocytoma (PCC) [2]
This is the first study using the Poisson distribution model to calculated the time to detect the first and subsequent head and neck paragangliomas (HNPGLs) in SDHB mutation carriers. This mathematical model provides a rationale to assess the optimal age to start surveillance at 27 years and subsequent follow-up intervals at 3 years. This approach has been recently applied to calculate the optimal surveillance in patients with a mutation in the von Hippel Lindau (VHL)-gene [18]
The outcome is compatible with the assumption of the two-hit hypothesis used in our model, which is a statistical proof that the Poisson distribution model is a valid method to use

Summary

Introduction

The succinate dehydrogenase subunit B (SDHB) gene is one of the 15 [1] susceptibility genes that have been linked to familial paraganglioma (PGL) and pheochromocytoma (PCC) [2]. Germline mutations in this gene predispose to head and neck paragangliomas (HNPGLs), sympathetic PGLs and PCCs. HNPGLs are mainly nonsecretory tumors of the parasympathetic paraganglia in the head and neck region, whereas sympathetic PGLs and PCCs are known for overproduction of catecholamines. SDHB mutation carriers have been associated with an increased risk of developing other neoplasms, including renal cell carcinoma, gastrointestinal stromal tumors (GISTs) and papillary thyroid cancer [9]. The Dutch national guideline advises to screen SDHB mutation carries as early as from the age of

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