Purpose: Multiple Endocrine Neoplasia Type-1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Hereby, we aimed to describe the frequency, the incidence and specific clinical and histological features of CNS tumors in the MEN1 population (except pituitary tumors). Experimental design: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed-up in the French MEN1 national cohort. Standardized incidence rate (SIR) was calculated based on the French Gironde CNS tumors registry. Genomic analyses were performed on somatic DNA from 7 CNS tumors including meningiomas and ependymomas from MEN1 patients, then in 50 sporadic meningiomas and ependymomas. Results: Twenty-nine CNS tumors were found among the 1498 symptomatic patients (2%) (incidence=47.4/100’000 person-years; SIR=4.5), including 12 meningiomas (0.8%) (incidence=16.2/100’000; SIR=2.5), 8 ependymomas (0.5%) (incidence=10.8/100’000; SIR=17.6), 5 astrocytomas (0.3%) (incidence=6.7/100’000; SIR=5.8), and 4 schwannomas (0.3%) (incidence=5.4/100’000; SIR=12.7). Meningiomas in MEN1 patients were benign, mostly meningothelial, with 11 years earlier onset compared to the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified WHO grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from the MEN1 patients, whereas MEN1 deletion in one allele was present in respectively 3/41 and 0/9 sporadic meningiomas and ependymomas. Conclusions: Incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas.

中文翻译：

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1 型多发性内分泌肿瘤中枢神经系统肿瘤的队列研究

目的：1 型多发性内分泌肿瘤 (MEN1) 被认为会增加脑膜瘤和室管膜瘤的风险。在此，我们的目的是描述MEN1人群（垂体瘤除外）中CNS肿瘤的频率、发病率以及具体的临床和组织学特征。实验设计：研究人群包括 1990 年后诊断为 MEN1 综合征的中枢神经系统肿瘤患者，并在法国 MEN1 国家队列中进行随访。标准化发病率（SIR）是根据法国吉伦特省中枢神经系统肿瘤登记处计算的。对来自 MEN1 患者的 7 个 CNS 肿瘤（包括脑膜瘤和室管膜瘤）的体细胞 DNA 进行了基因组分析，然后对 50 个散发性脑膜瘤和室管膜瘤进行了基因组分析。结果：1498 名有症状患者中发现 29 例中枢神经系统肿瘤（2%）（发病率=47.4/100'000 人年；SIR=4.5），其中包括 12 例脑膜瘤（0.8%）（发病率=16.2/100'000 人年） ；SIR=2.5)、8 例室管膜瘤 (0.5%)（发病率=10.8/100'000；SIR=17.6）、5 例星形细胞瘤 (0.3%)（发病率=6.7/100'000；SIR=5.8）和 4 例神经鞘瘤（ 0.3%）（发生率=5.4/100'000；SIR=12.7）。 MEN1 患者的脑膜瘤是良性的，大部分为脑膜上皮瘤，与散发人群相比发病时间早 11 年，F/M 比为 1/1。脊髓和颅脑室管膜瘤大多被分类为 WHO 2 级。在 MEN1 患者中，4/5 的室管膜瘤和 1/2 的脑膜瘤中观察到双等位基因 MEN1 失活，而 3/41 和 0/9 的散发性患者中分别存在一个等位基因 MEN1 缺失。脑膜瘤和室管膜瘤。结论：MEN1 人群中每种 CNS 肿瘤的发病率均高于法国普通人群。脑膜瘤和室管膜瘤应被视为 MEN1 综合征的一部分，但缺乏体细胞分子数据来得出星形细胞瘤和神经鞘瘤的结论。