Mowrey Kate, Northrup Hope, Rougeau Peyton, Hashmi S Shahrukh, Krueger Darcy A, Ebrahimi-Fakhari Daniel, Towbin Alexander J, Trout Andrew T, Capal Jamie K, Franz David Neal, Rodriguez-Buritica David
Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States.
Department of Pediatrics, Pediatric Research Center, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Neurol. 2021 Apr 9;12:627672. doi: 10.3389/fneur.2021.627672. eCollection 2021.
Tuberous sclerosis complex (TSC) is a genetic condition that causes benign tumors to grow in multiple organ systems. Nonfunctional pancreatic neuroendocrine tumors (PNETs) are a rare clinical feature of TSC with no specific guidelines outlined for clinical management at this time. Our purpose is to calculate the frequency of nonfunctional PNETs as well as characterize the presentation, current clinical management, and assess the impact of systemic mammalian target of rapamycin (mTOR) on nonfunctional PNETs in TSC. This retrospective chart review was performed by a query of the TS Alliance's Natural History Database and the Cincinnati Children's Hospital TSC Database for patients with nonfunctional PNET. Clinical data from these two groups was summarized for patients identified to have a nonfunctional PNET and compared to previously reported cases with TSC and nonfunctional PNETs. Our calculated frequency of nonfunctional PNETs is 0.65%. We identified 16 individuals, nine males and seven females, with a median age of 18.0 years (interquartile range: -15.5 to 25.5). Just over half (56.3%, = 9) of the patients provided results from genetic testing. Six had pathogenic variants in whereas three had pathogenic variants in . The average age at PNET diagnosis was 15.0 years (range: 3-46 years). Almost all individuals were diagnosed with a PNET during routine TSC surveillance, 56.3% ( = 9) by MRI, 12.5% ( = 2) by CT, 25% ( = 4) by ultrasound, and 6.2% ( = 1) through a surgical procedure. Follow up after diagnosis involved 68.8% ( = 11) having serial imaging and nine of the sixteen individuals proceeding with surgical removal of the PNET. Eight individuals had a history of using systemic mTOR inhibitors. Tumor growth rate was slightly less in individuals taking an mTOR inhibitor (-0.8 mm/yr, IQR: -2.3 to 2.2) than those without (1.6 mm/yr; IQR: -0.99 to 5.01, > 0.05). Nonfunctional PNETs occurred at younger ages in our TSC cohort and more commonly compared to ages and prevalence reported for the general population. PNETs in patients on systemic mTOR inhibitors had lower rates of growth. The outcome of this study provides preliminary evidence supporting the use of mTOR inhibitor therapy in conjunction with serial imaging as medical management for nonfunctional PNETs as an alternative option to invasive surgical removal.
结节性硬化症（TSC）是一种遗传性疾病，可导致多个器官系统出现良性肿瘤。无功能胰腺神经内分泌肿瘤（PNETs）是TSC的一种罕见临床特征，目前尚无针对其临床管理的具体指南。我们的目的是计算无功能PNETs的发生率，并对其临床表现、当前临床管理进行描述，以及评估全身性哺乳动物雷帕霉素靶蛋白（mTOR）对TSC中无功能PNETs的影响。通过查询TS联盟的自然病史数据库和辛辛那提儿童医院的TSC数据库，对患有无功能PNETs的患者进行了这项回顾性病历审查。对这两组中被确定患有无功能PNETs的患者的临床数据进行了总结，并与先前报道的TSC和无功能PNETs病例进行了比较。我们计算出的无功能PNETs发生率为0.65%。我们确定了16例患者，9例男性和7例女性，中位年龄为18.0岁（四分位间距：15.5至25.5岁）。略超过一半（56.3%，n = 9）的患者提供了基因检测结果。6例在[基因名称1]中有致病变异，而3例在[基因名称2]中有致病变异。PNET诊断时的平均年龄为15.0岁（范围：3至46岁）。几乎所有个体都是在常规TSC监测期间被诊断出患有PNET，56.3%（n = 9）通过MRI诊断，12.5%（n = 2）通过CT诊断，25%（n = 4）通过超声诊断，6.2%（n = 1）通过手术程序诊断。诊断后的随访包括68.8%（n = 11）进行了系列影像学检查，16例中有9例进行了PNET的手术切除。8例患者有使用全身性mTOR抑制剂的病史。服用mTOR抑制剂的个体肿瘤生长速度略低于未服用者（-0.8 mm/年，四分位间距：-2.3至2.2）（1.6 mm/年；四分位间距：-0.99至5.01，P>0.05）。在我们的TSC队列中，无功能PNETs在较年轻的年龄出现，并且与一般人群报道的年龄和患病率相比更为常见。接受全身性mTOR抑制剂治疗的患者中PNETs的生长速度较低。本研究结果提供了初步证据，支持将mTOR抑制剂治疗与系列影像学检查联合使用，作为无功能PNETs的医学管理方法，作为侵入性手术切除的替代选择。
