儿童颅底SMARCB1/INI1缺失性差分化脊索瘤5例临床病理学观察

Pediatric SMARCB1/INI1-deficient poorly differentiated chordoma of the skull base:report of five cases and review of literature

目的探讨儿童颅底SMARCB1/INI1缺失性差分化脊索瘤(poorly differentiated chordoma,PDC)的临床病理特点及鉴别诊断。方法整理2017年3月至2021年3月首都医科大学三博脑科医院诊断的脊索瘤139例,其中5例诊断为SMARCB1/INI1缺失性的PDC,收集此5例患者的临床影像学资料,进行HE和免疫组织化学染色、DNA甲基化测序检测,并复习相关文献。结果5例PDC均发生在中颅底斜坡,平均年龄6.4岁(3~16岁);3例女性,2例男性。形态学上,缺乏脊索瘤的典型形态学特征,表现为成片或巢片状分布的上皮样或梭形肿瘤细胞,核分裂象活跃,均见坏死,可见肿瘤浸润周围组织。免疫表型特征上,表达脊索瘤常见免疫标志物广谱细胞角蛋白(CKpan)、上皮细胞膜抗原(EMA)、波形蛋白及brachyury,同时SMARCB1/INI1核表达缺失。2例S-100蛋白阳性,Ki-67阳性指数高(20%~50%),均存在p53过表达。需要与儿童颅底发生的SMARCB1/INI1缺失性肿瘤或具有上皮样和梭形细胞形态学特征的肿瘤进行鉴别。其中3例的甲基化特征不同于任何儿童非典型畸胎样/横纹肌样肿瘤亚组,构成独立的DNA甲基化特征簇。本组5例患者临床预后均很差,总体生存时间2~17个月。结论PDC属于新认识的SMARCB1/INI1缺失性的特殊类型脊索瘤,多见于儿童,常累及颅底;表现为上皮样或梭形细胞的形态特征,具有脊索瘤的典型免疫表型特征,同时存在SMARCB1/INI1表达缺失,并具有独特的表观遗传特征。

Objective To investigate the clinicopathological characteristics and differential diagnosis of pediatric SMARCB1/INI1-deficient poorly differentiated chordoma(PDC)of the skull base.Methods Five cases of SMARCB1/INI1-deficient PDC were identified in 139 cases of chordoma diagnosed in Sanbo Brain Institute,Capital Medical University,Beijing,China from March 2017 to March 2021.The clinical and imaging data of the 5 PDCs were collected.H&E and immunohistochemical staining,and DNA methylation array were used,and the relevant literatures were reviewed.Results All 5 PDCs were located at the clivus.The average age of the patients was 6.4 years,ranging from 3 to 16 years.Three patients were female and two were male.Morphologically,in contrast with classical chordomas,they presented as epithelioid or spindle tumor cells organized in sheets or nests,with necrosis,active mitoses,and infiltration into surrounding tissue.All cases showed positivity of CKpan,EMA,vimentin and brachyury(nuclear stain),and loss of nuclear SMARCB1/INI1 expression.S-100 protein expression was not frequent(2/5).Ki-67 proliferative index was high(20%-50%).All cases had over-expressed p53.It was necessary to differentiate SMARCB1/INI1-dificient PDC from SMARCB1/INI1-dificient tumors occurring at skull base of children or the tumors with epithelial and spindle cell morphological features.The 3 PDCs with DNA methylation testing showed the methylation profiles different from the pediatric atypical teratoid/rhabdoid tumors.They formed an independent methylation profile cluster.The clinical prognosis of the 5 patients was poor,and the overall survival time was 2-17 months.Conclusions PDC is a special subtype of chordoma,which often affects children and occurs in the clivus.The PDC shares epithelioid or spindle cell morphologic features which are different from the classic chordoma.Besides the typical immunohistochemical profile of chordoma,PDC also has loss of nuclear SMARCB1/INI1 expression and distinct epigenetic characteristics.