Al-Saleem T, Wessner L L, Scheithauer B W, Patterson K, Roach E S, Dreyer S J, Fujikawa K, Bjornsson J, Bernstein J, Henske E P
Department of Pathology Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Cancer. 1998 Nov 15;83(10):2208-16.
The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, skin, and kidney. Malignant tumors also can occur in patients with tuberous sclerosis, particularly in the kidney, although they occur less frequently than benign tumors. The types of malignancy that occur in TSC have not been characterized fully.
Clinical and pathologic features of 8 malignant tumors from 6 TSC patients ranging in age from 22 months to 21 years are reviewed. Six tumors were renal, one was from the inguinal region, and one was from the brain. The tumors were analyzed for loss of heterozygosity (LOH) in the chromosomal regions of the TSC1, TSC2, and VHL genes.
Three patients (ages 7, 8, and 20 years) had renal cell carcinomas (RCCs). Two of these patients had multifocal RCCs. All three patients with RCC also had prominent multifocal dysplasia of renal cyst epithelium. Two patients (ages 20 and 21 years) had malignant angiomyolipomas (1 renal and 1 inguinal). One patient (age 22 months) had a Grade 4 giant cell astrocytoma (glioblastoma multiforme). LOH in the region of the TSC2 gene was found, either in the malignant tumor or in benign tumors, in all five patients whose DNA could be analyzed.
Children with TSC, as well as adults with the disease, are at risk for developing malignant tumors. Two types of renal malignancy occur in TSC: RCC, which appears to arise from dysplastic renal cyst epithelial cells, and malignant angiomyolipoma. Tumors cytologically similar to malignant angiomyolipomas also may occur at extrarenal sites. LOH analyses suggest that the majority of patients with TSC who develop malignant tumors have germline TSC2, rather than TSC1, gene mutations.
结节性硬化症（TSC）是一种常染色体显性疾病，其特征为癫痫发作、智力迟钝以及脑、心脏、皮肤和肾脏的良性肿瘤。恶性肿瘤也可发生于结节性硬化症患者，尤其是肾脏，但发生频率低于良性肿瘤。TSC中发生的恶性肿瘤类型尚未完全明确。
回顾了6例年龄从22个月至21岁的TSC患者的8例恶性肿瘤的临床和病理特征。6例肿瘤为肾脏肿瘤，1例来自腹股沟区，1例来自脑部。对肿瘤进行了TSC1、TSC2和VHL基因染色体区域杂合性缺失（LOH）分析。
3例患者（年龄分别为7岁、8岁和20岁）患有肾细胞癌（RCC）。其中2例患者有多灶性RCC。所有3例RCC患者还伴有明显的肾囊肿上皮多灶性发育异常。2例患者（年龄分别为20岁和21岁）患有恶性血管平滑肌脂肪瘤（1例肾脏，1例腹股沟区）。1例患者（年龄22个月）患有4级巨细胞星形细胞瘤（多形性胶质母细胞瘤）。在所有5例可分析DNA的患者中，无论是在恶性肿瘤还是良性肿瘤中均发现了TSC2基因区域的LOH。
患有TSC的儿童以及成人都有发生恶性肿瘤的风险。TSC中发生两种类型的肾脏恶性肿瘤：RCC，似乎起源于发育异常的肾囊肿上皮细胞；以及恶性血管平滑肌脂肪瘤。细胞学上与恶性血管平滑肌脂肪瘤相似的肿瘤也可能发生于肾外部位。LOH分析表明，大多数发生恶性肿瘤的TSC患者具有种系TSC2基因突变，而非TSC1基因突变。
