摘要：

目的 总结1 例以胶质母细胞瘤为临床表现的Li-Fraumeni 综合征患者的临床病理学特点。方法与结果 女性患者，33 岁，以无明显诱因的左侧肢体抽搐发病，头部MRI显示右侧额顶叶交界区占位性病变，增强扫描病灶呈“花环”样强化征象，行右侧顶叶占位性病变切除术。术中切开右侧顶叶皮质2.50 cm，其下即见肿瘤组织，呈椭圆形，大小约5 cm × 4 cm × 3 cm，质地柔软，紫红色，边界清晰，血供丰富，分块全切除肿瘤。组织学形态，胶质细胞异型性增生明显，部分区域呈梭形伴大量瘤巨细胞；免疫组织化学染色，肿瘤细胞胞质表达胶质纤维酸性蛋白、胞核弥漫性表达P53 蛋白，Ki-67 抗原标记指数为25%；网织纤维染色呈阴性；分子病理学检查未检测到异柠檬酸脱氢酶1/2（IDH1/2）基因外显子4 突变、端粒酶逆转录酶（TERT）基因启动子突变和O₆-甲基鸟嘌呤DNA 甲基转移酶（MGMT）基因甲基化，荧光原位杂交未检测到染色体1p/19q 共缺失。病理诊断为（右侧顶叶）胶质母细胞瘤，IDH-野生型（WHOⅣ级）。患者共住院15 d，出院后随访至2016 年，死亡。详细追问家族史得知患者家系有肿瘤病史：其姊罹患右侧乳腺癌，其父因胃癌死亡，祖母因乳腺癌死亡，叔父因肺癌死亡，伯父因造血系统肿瘤死亡。进一步对患者胶质母细胞瘤标本和右侧乳腺浸润性导管癌标本行TP53 基因检测，均未检测到突变；对冻存的血液标本行全外显子测序，TP53 基因存在c.1009C > T（p.Arg337Cys）杂合致病性突变，为错义突变。最终诊断为Li-Fraumeni综合征，该家系诊断为Li-Fraumeni综合征家系。结论 Li-Fraumeni综合征是遗传性肿瘤综合征，呈常染色体显性遗传，以乳腺癌、骨与软组织肉瘤、中枢神经系统肿瘤和肾上腺皮质肿瘤等高肿瘤发病风险为特征，TP53 基因是最常见的Li-Fraumeni综合征相关致病基因。

关键词: Li-Fraumeni综合征, 胶质母细胞瘤, 免疫组织化学, 病理学, 遗传学

Abstract:

Objective To investigate the clinicopathological features of Li - Fraumeni syndrome (LFS) manifested as glioblastoma. Methods and Results A 33 - year -old female patient presented hyperspasmia of left extremities. Head MRI showed space - occupying lesion on the right fronto - parietal junction, and contrast - enhanced scanning revealed "garland" enhancement of the lesion. The patient underwent surgical resection. During the operation, an oval tumor was visible after the right parietal cortex was cut open for 2.50 cm, which was about 5 cm × 4 cm × 3 cm in size. The tumor was soft and purple, with clear boundary and rich blood supply, and was totally removed through piecemeal resection. Microscopic examination found obvious dysplasia of glial cells, spindle shape in some areas, and a large number of giant tumor cells. Immunohistochemical staining showed that the tumor cells expressed glial fibrillary acidic protein (GFAP) in cytoplasm and P53 protein in nuclei. Ki-67 labeling index was 25%. Reticular fiber staining was negative. Molecular pathological examination did not detect isocitrate dehydrogenase 1/2 (IDH1/2) gene exon 4 mutation, telomerase reverse transcriptase (TERT) promoter mutation, or methylation of O₆-methylguanine-DNA methyltransferase (MGMT). Fluorescence in situ hybridization (FISH) analysis did not reveal codeletion of 1p/19q. The integrated diagnosis was (right parietal) glioblastoma, IDH - wild type (WHO grade Ⅳ). The patient was hospitalized for 15 d and died in 2016. Previous family medical history showed her older sister suffered from right breast cancer, her father died of gastic cancer, her grandmother died of breast cancer, her uncles died of lung cancer and hematopoietic system tumor. Samples from the patient's glioblastoma and right mammary gland invasive duct carcinoma were collected for TP53 gene detection, but no mutation was found. Further, whole exome sequencing (WES) on the patient's freezing blood samples showed TP53 gene c.1009C > T (p.Arg337Cys) pathogenic heterozygous mutation (missense mutation). Combined with the family cancer history, a clinical diagnosis of the patient was Li-Fraumeni syndrome, and her family was Li-Fraumeni syndrome pedigree. Conclusions Li-Fraumeni syndrome is a hereditary tumor syndrome with autosomal dominant inheritance, characterized by high risk of breast cancer, bone and soft tissue sarcoma, brain tumor and adrenocortical cancer, and TP53 gene is the most common gene associated with Li-Fraumeni syndrome.

Key words: Li-Fraumeni syndrome, Glioblastoma, Immunohistochemistry, Pathology, Genetics