Reynolds Rebecca A, Aum Diane J, Gonzalez-Gomez Ignacio, Wong Michael, Roberts Kaleigh, Dahiya Sonika, Rodriguez Luis F, Roland Jarod L, Smyth Matthew D
1Division of Pediatric Neurosurgery, Johns Hopkins All Children's Hospital, St. Petersburg, Florida.
Departments of2Neurosurgery.
J Neurosurg Pediatr. 2023 Jun 9;32(3):351-357. doi: 10.3171/2023.5.PEDS23108. Print 2023 Sep 1.
Tuberous sclerosis is a rare genetic condition caused by TSC1 or TSC2 mutations that can be inherited, sporadic, or the result of somatic mosaicism. Subependymal giant-cell astrocytoma (SEGA) is a major diagnostic feature of tuberous sclerosis complex (TSC). This study aimed to present a series of cases in which a pathological diagnosis of SEGA was not diagnostic of tuberous sclerosis.
The authors retrospectively reviewed a clinical case series of 5 children who presented with a SEGA tumor to Johns Hopkins All Children's Hospital and St. Louis Children's Hospital between 2010 and 2022 and whose initial genetic workup was negative for tuberous sclerosis. All patients were treated with craniotomy for SEGA resection. TSC genetic testing was performed on all SEGA specimens.
The children underwent open frontal craniotomy for SEGA resection from the ages of 10 months to 14 years. All cases demonstrated the classic imaging features of SEGA. Four were centered at the foramen of Monro and 1 in the occipital horn. One patient presented with hydrocephalus, 1 with headaches, 1 with hand weakness, 1 with seizures, and 1 with tumor hemorrhage. Somatic TSC1 mutation was present in the SEGA tumors of 2 patients and TSC2 mutation in 1 patient. Germline TSC mutation testing was negative for all 5 cases. No patient had other systemic findings of tuberous sclerosis on ophthalmological, dermatological, neurological, renal, or cardiopulmonary assessments and thus did not meet the clinical criteria for tuberous sclerosis. The average follow-up was 6.7 years. Recurrence was noted in 2 cases, in which 1 patient underwent radiosurgery and 1 was started on a mammalian target of rapamycin (mTOR) inhibitor (rapamycin).
There may be intracranial implications of somatic mosaicism associated with tuberous sclerosis. Children who are diagnosed with SEGA do not necessarily have a diagnosis of tuberous sclerosis. Tumors may carry a TSC1 or TSC2 mutation, but germline testing can be negative. These children should continue to be followed with serial cranial imaging for tumor progression, but they may not require the same long-term monitoring as patients who are diagnosed with germline TSC1 or TSC2 mutations.
结节性硬化症是一种罕见的遗传性疾病，由TSC1或TSC2基因突变引起，可遗传、散发或由体细胞镶嵌现象导致。室管膜下巨细胞星形细胞瘤（SEGA）是结节性硬化症复合体（TSC）的主要诊断特征。本研究旨在呈现一系列病例，其中SEGA的病理诊断未能确诊结节性硬化症。
作者回顾性分析了2010年至2022年间在约翰·霍普金斯儿童医院和圣路易斯儿童医院就诊的5例患有SEGA肿瘤的儿童临床病例系列，这些患儿最初的基因检测结果显示结节性硬化症为阴性。所有患者均接受了开颅手术以切除SEGA。对所有SEGA标本进行了TSC基因检测。
这些儿童接受了开颅手术以切除SEGA，年龄在10个月至14岁之间。所有病例均表现出SEGA的典型影像学特征。4例以室间孔为中心，1例位于枕角。1例患者出现脑积水，1例头痛，1例手部无力，1例癫痫发作，1例肿瘤出血。2例患者的SEGA肿瘤中存在体细胞TSC1突变，1例患者存在TSC2突变。所有5例患者的生殖系TSC突变检测均为阴性。在眼科、皮肤科、神经科、肾脏或心肺评估中，没有患者有结节性硬化症的其他全身表现，因此不符合结节性硬化症的临床标准。平均随访时间为6.7年。2例患者出现复发，其中1例接受了放射外科治疗，1例开始使用雷帕霉素哺乳动物靶点（mTOR）抑制剂（雷帕霉素）。
与结节性硬化症相关的体细胞镶嵌现象可能存在颅内影响。被诊断为SEGA的儿童不一定患有结节性硬化症。肿瘤可能携带TSC1或TSC2突变，但生殖系检测可能为阴性。这些儿童应继续通过系列头颅影像学检查随访以监测肿瘤进展，但他们可能不需要像被诊断为生殖系TSC1或TSC2突变的患者那样进行同样长期的监测。
