Endocrine Genetics Unit (LIM-25) (T.D.G., R.A.T., T.S., S.P.A.T., D.M.L.), Endocrinology Division (T.D.G., R.A.T., T.S., A.G., M.D.B., M.A.A.P., S.P.A.T., D.M.L.), Endoscopy Division (S.E.M., F.M.F.), Radiology Division (M.S.R.), Pathology Division (S.A.C.S.), and Department of Gastroenterology, Surgical Division (T.B., M.C.C.M.), Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo 01246-903, Brazil; and Department of Gastroenterology, Surgical Division (T.B., R.J.), and Endocrine Oncology Division, Cancer Institute of São Paulo (D.M.L.), São Paulo 01246-000, Brazil.
J Clin Endocrinol Metab. 2014 Jan;99(1):E89-96. doi: 10.1210/jc.2013-1768. Epub 2013 Dec 20.
Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. A potential positive correlation between tumor size and malignancy (2-3 cm, 18%; >3 cm, 43%) has greatly influenced the management of MEN1 adults with NF-PETs.
The aim of the study was to estimate the penetrance of NF-PETs, insulinomas, and gastrinomas in young MEN1 carriers.
The data were obtained from a screening program (1996-2012) involving 113 MEN1 patients in a tertiary academic reference center.
Nineteen MEN1 patients (aged 12-20 y; 16 patients aged 15-20 y and 3 patients aged 12-14 y) were screened for NF-PETs, insulinomas, and gastrinomas.
Magnetic resonance imaging/computed tomography and endoscopic ultrasound (EUS) were performed on 10 MEN1 carriers, magnetic resonance imaging/computed tomography was performed on five patients, and four other patients underwent an EUS.
The overall penetrance of PETs during the second decade of life was 42% (8 of 19). All eight PET patients had NF-PETs, and half of those tumors were multicentric. One-fifth of the screened patients (21%; 4 of 19) harbored at least one large tumor (>2.0 cm). Insulinoma was detected in two NF-PET patients (11%) at the initial screening; gastrinoma was not present in any cases. Six of the 11 (54%) screened patients aged 15-20 years who underwent an EUS had NF-PETs. Potential false-positive EUS results were excluded based on EUS-guided biopsy results, the reproducibility of the NF-PET findings, or the observation of increased tumor size during follow-up. Distal pancreatectomy and the nodule enucleation of pancreatic head tumors were conducted on three patients with large tumors (>2.0 cm; T2N0M0) that were classified as grade 1 neuroendocrine tumors (Ki-67<2%).
Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group.
多发性内分泌腺瘤病 1 型（MEN1）相关无功能性胰腺神经内分泌肿瘤（NF-PET）和胰岛素瘤在年轻的 MEN1 患者中的发生率数据很少。肿瘤大小与恶性程度之间存在潜在的正相关（2-3cm，18%；>3cm，43%），这极大地影响了 MEN1 成人中 NF-PET 的治疗。
本研究旨在评估年轻的 MEN1 携带者中 NF-PET、胰岛素瘤和胃泌素瘤的外显率。
数据来自于一个三级学术参考中心的筛查项目（1996-2012 年），涉及 113 名 MEN1 患者。
19 名 MEN1 患者（年龄 12-20 岁；16 名年龄 15-20 岁，3 名年龄 12-14 岁）接受了 NF-PET、胰岛素瘤和胃泌素瘤的筛查。
对 10 名 MEN1 携带者进行磁共振成像/计算机断层扫描和内镜超声（EUS）检查，对 5 名患者进行磁共振成像/计算机断层扫描，对 4 名其他患者进行 EUS 检查。
在人生的第二个十年，PET 的总外显率为 42%（19 例中的 8 例）。所有 8 例 PET 患者均患有 NF-PET，其中一半的肿瘤为多中心性。筛查患者中有五分之一（21%；19 例中的 4 例）存在至少一个大肿瘤（>2.0cm）。在最初的筛查中，2 名 NF-PET 患者（11%）中发现了胰岛素瘤；没有发现胃泌素瘤。在接受 EUS 检查的 15-20 岁的 11 名筛查患者中，有 6 名（54%）患有 NF-PET。根据 EUS 引导活检结果、NF-PET 结果的可重复性或随访中观察到肿瘤大小增加，排除了潜在的假阳性 EUS 结果。对 3 名大肿瘤（>2.0cm；T2N0M0）患者进行了远端胰腺切除术和胰腺头部肿瘤的结节切除术，这些肿瘤被归类为 1 级神经内分泌肿瘤（Ki-67<2%）。
我们的数据表明，15-20 岁的 MEN1 患者中 NF-PET 的外显率较高。很大一部分患者符合单独进行 NF-PET 或 NF-PET/胰岛素瘤手术的共识标准，这表明在该年龄组定期监测这些肿瘤可能具有潜在益处。
