Department of Neuropathology, Research Institute for Brain and Blood Vessels, Akita Cerebrospinal and Cardiovascular Center, Akita, Japan.
Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Neuropathology. 2021 Feb;41(1):58-64. doi: 10.1111/neup.12700. Epub 2020 Nov 12.
Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disorder caused by mutations in either TSC1 on chromosome 16 or TSC2 on chromosome 9, clinically characterized mainly by facial angiofibroma, epilepsy, and intellectual disability. Cortical dysplasias, subependymal nodules, and subependymal giant cell astrocytoma are characteristic central nervous system lesions among 11 major features in the current clinical diagnostic criteria for TSC. We encountered an unusual case of genetically confirmed TSC1 presenting with symptomatic West syndrome due to an isolated cortical dysplasia in the left occipital lobe of a six-month-old male infant who did not meet the clinical diagnostic criteria for TSC. The patient underwent left occipital lesionectomy at age 11 months and has been seizure-free for nearly six years since then. Histological examination of the resection specimen revealed cortical neuronal dyslamination with abundant dysmorphic neurons and ballooned cells, consistent with focal cortical dysplasia (FCD) type IIb. However, the lesion was also accompanied by unusual features, including marked calcifications, dense fibrillary gliosis containing abundant Rosenthal fibers, CD34-positive glial cells with abundant long processes confined to the dysplastic cortex, and multiple nodular lesions occupying the underlying white matter, consisting exclusively of ballooned cell and/or balloon-like astrocytes with focal calcifications. Genetic testing for TSC1 and TSC2 using the patient's peripheral blood revealed a germline heterozygous mutation in exon 7 (NM_000368.5: c.526dupT, p.Tyr176fs) in TSC1. Isolated FCD with unusual features such as calcification, dense fibrillary gliosis, Rosenthal fibers and/or subependymal nodule-like lesions in the white matter may indicate the possibility of a cortical tuber even without a clinical diagnosis of TSC. Identification of such histopathological findings has significant implications for early and accurate diagnosis and treatment of TSC, and is likely to serve as an important supplementary feature for the current clinical diagnostic criteria for TSC.
结节性硬化症（TSC）是一种常染色体显性遗传性疾病，由染色体 16 上的 TSC1 或染色体 9 上的 TSC2 突变引起，临床上主要表现为面部血管纤维瘤、癫痫和智力障碍。皮质发育不良、室管膜下结节和室管膜下巨细胞星形细胞瘤是 TSC 目前临床诊断标准中 11 个主要特征之一的中枢神经系统病变。我们遇到了一例不常见的 TSC1 基因突变病例，表现为左侧枕叶孤立性皮质发育不良引起的症状性 West 综合征，而该男婴 6 个月大，不符合 TSC 的临床诊断标准。患儿在 11 个月大时接受了左侧枕叶病变切除术，此后近 6 年无癫痫发作。切除标本的组织学检查显示皮质神经元排列紊乱，伴有大量畸形神经元和气球样细胞，符合局灶性皮质发育不良（FCD）Ⅱb 型。然而，病变还伴有不常见的特征，包括明显的钙化、富含 Rosenthal 纤维的密集纤维状神经胶质增生、CD34 阳性的长突胶质细胞局限于发育不良的皮质、以及多个占据白质的结节性病变，仅由气球样细胞和/或气球样星形细胞组成，伴有局灶性钙化。对患儿外周血进行 TSC1 和 TSC2 的基因检测显示 TSC1 外显子 7（NM_000368.5：c.526dupT，p.Tyr176fs）存在种系杂合突变。孤立性 FCD 伴有钙化、密集纤维状神经胶质增生、Rosenthal 纤维和/或白质内室管膜下结节样病变等不常见特征，即使没有 TSC 的临床诊断，也可能提示存在皮质结节。识别这些组织病理学发现对 TSC 的早期和准确诊断和治疗具有重要意义，可能成为 TSC 目前临床诊断标准的重要补充特征。
