Department of Nuclear Medicine, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
Service de Génétique AP-HP, Hôpital Européen Georges Pompidou, Paris, France.
J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1301-e1315. doi: 10.1210/clinem/dgaa888.
When an SDHx mutation is identified in a patient with a pheochromocytoma (PCC) or a paraganglioma (PGL), predictive genetic testing can detect mutation carriers that would benefit from screening protocols.
To define the tumor detection rate in a large cohort of asymptomatic SDHX mutation carriers.
Retrospective multicentric study in 6 referral centers.
Between 2005 and 2019, 249 asymptomatic SDHx (171 SDHB, 31 SDHC, 47 SDHD) mutation carriers, with at least 1 imaging work-up were enrolled.
Initial work-up, including anatomical (98% of subjects [97-100% according to center]) and/or functional imaging (67% [14-90%]) detected 48 tumors in 40 patients. After a negative initial work-up, 124 patients benefited from 1 to 9 subsequent follow-up assessments (mean: 1.9 per patient), with a median follow-up time of 5 (1-13) years. Anatomical (86% [49-100 %]) and/or functional imaging (36% [7-60 %]) identified 10 new tumors (mean size: 16 mm [4-50]) in 10 patients. Altogether, 58 tumors (55 paraganglioma [PGL], including 45 head and neck PGL, 2 pheochromocytoma [PCC], 1 gastrointestinal stromal tumor [GIST]), were detected in 50 patients (22 [13%] SDHB, 1 [3.2%] SDHC, and 27 [57%] SDHD), with a median age of 41 years old [11-86], 76% without catecholamine secretion and 80% during initial imaging work-up.
Imaging screening enabled detection of tumors in 20% of asymptomatic SDHx mutation carriers, with a higher detection rate in SDHD (57%) than in SDHB (13%) and SDHC (3%) mutation carriers, arguing for a gene-by-gene approach. Prospective studies using well-defined protocols are needed to obtain strong and useful data.
当患有嗜铬细胞瘤（PCC）或副神经节瘤（PGL）的患者中发现 SDHx 突变时，预测性基因检测可以发现突变携带者，从而使他们受益于筛查方案。
在一个大型无症状 SDHX 突变携带者队列中定义肿瘤检出率。
在 6 个转诊中心进行的回顾性多中心研究。
2005 年至 2019 年，纳入了 249 名无症状 SDHx（171 名 SDHB、31 名 SDHC、47 名 SDHD）突变携带者，这些患者至少进行了一次影像学检查。
初始检查，包括解剖学（98%的患者[根据中心为 97-100%]）和/或功能影像学（67%[14-90%]）检测到 40 名患者中的 48 个肿瘤。初始检查结果为阴性后，124 名患者进行了 1 至 9 次后续评估（平均每位患者 1.9 次），中位随访时间为 5（1-13）年。解剖学（86%[49-100%]）和/或功能影像学（36%[7-60%]）在 10 名患者中发现了 10 个新肿瘤（平均大小：16 毫米[4-50]）。总共，在 50 名患者（22 名[13%]SDHB、1 名[3.2%]SDHC 和 27 名[57%]SDHD）中发现了 58 个肿瘤（55 个副神经节瘤[PGL]，包括 45 个头颈部 PGL、2 个嗜铬细胞瘤[PCC]和 1 个胃肠道间质瘤[GIST]），中位年龄为 41 岁[11-86]，76%无儿茶酚胺分泌，80%在初始影像学检查时。
影像学筛查使 20%的无症状 SDHx 突变携带者发现了肿瘤，SDHD（57%）的检出率高于 SDHB（13%）和 SDHC（3%）突变携带者，这表明基因检测是必要的。需要使用明确的方案进行前瞻性研究，以获得有力且有用的数据。
