Next-Generation Sequencing of a Glioblastoma with True Epithelial Differentiation.
Next-Generation Sequencing of a Glioblastoma with True Epithelial Differentiation.
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具有真正上皮分化的胶质母细胞瘤的下一代测序。
DOI：
10.1093/jnen/nlab114
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发表时间：
2022
影响因子：
3.2
通讯作者：
Horbinski,Craig
中科院分区：
文献类型：
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作者：
Larkin,CollinJ;Jennings,LawrenceJ;Heimberger,AmyB;Horbinski,Craig
致编辑：一位65岁的左撇子男子提出了局灶性癫痫发作，轻度头痛，恶心，呕吐，和人格改变有关的颅内肿块。患者无相关既往病史，也无恶性肿瘤个人或家族史，既往从未接受过此类评价。影像学检查显示左侧颞叶有一囊性/坏死性环状强化肿块，结节直径达6.9 cm（图1A，B）。入院时，他的神经系统检查结果为非病灶性。他在全身麻醉下接受了一次顺利的左颞部颅骨切开术，进行了整块完全切除。术中神经病理诊断为胶质母细胞瘤（GBM）。显微镜检查显示切除的肿块呈双相性（图1C），其中大部分肿瘤为典型的胶质母细胞瘤（图1D），但散在的肿瘤细胞岛为上皮细胞，在某些区域甚至呈腺样（图1 E-G）。这些形态上不同的区域在化学上也不同。当胶质细胞出现的成分对GFAP、OLIG 2和突触素呈阳性时（图1H-J），上皮腺体区域对CAM 5呈阳性。2、CK 7、CK 19和CK 20（图1 M-P）。两个区域均显示细胞核p53积聚（图1 K），尽管在上皮-腺体区域更明显。同样，Ki-67标记在上皮-腺细胞中更突出，接近100%，而在神经胶质区中约为15-20%。考虑到该切除术中明显的组织学和免疫组织化学差异，将代表性的神经胶质和上皮区域分别从组织块中显微解剖出来，然后进行下一代测序（NGS）和全基因组拷贝数阵列。两个区域具有完全相同的分子改变（表）。基于分子特征分析，最终综合诊断为“胶质母细胞瘤，IDH野生型，WHO 4级”。近世纪来，“多形性胶质母细胞瘤”被用来描述现在简称为“胶质母细胞瘤”，尽管“GBM”仍然是官方缩写（1）。像目前这样的病例强调了为什么“多形性”最初被纳入诊断，因为这些肿瘤可以显示出巨大的组织学范围，
To the Editor: A 65-year-old left-handed man presented with focal seizures, mild headache, nausea, vomiting, and personality changes concerning for an intracranial mass. The patient had no relevant past medical history nor personal or family history of malignancy and had never been evaluated for this in the past. Imaging revealed a cystic/necrotic, ring-enhancing mass with nodularity in the left temporal lobe measuring up to 6.9 cm in diameter (Fig. 1A, B). His neurological exam was non-focal upon admission. He underwent an uneventful left temporal craniotomy for an en bloc complete resection under general anesthesia. Intraoperative neuropathologic diagnosis was a glioblastoma (GBM).The resected mass appeared biphasic on microscopic examination (Fig. 1C), wherein most of the tumor was a typical glioblastoma (Fig. 1D), but scattered islands of tumor cells were epithelial, even appearing glandular in some areas (Fig. 1E–G). These morphologically distinct regions were also distinct immunohistochemically. While the glial-appearing elements were positive for GFAP, OLIG2, and synaptophysin (Fig. 1H–J), the epithelialglandular areas were variably positive for CAM5. 2, CK7, CK19, and CK20 (Fig. 1M–P). Both regions showed nuclear p53 accumulation (Fig. 1K), although it was more pronounced in the epithelial-glandular regions. Likewise, Ki-67 labeling was more prominent in the epithelial-glandular cells, approaching 100% versus approximately 15–20% in the glial areas. Given the stark histologic and immunohistochemical differences within this resection, representative glial and epithelial regions were each microdissected out of a tissue block, and then subjected to next-generation sequencing (NGS) and whole genome copy number array. Both regions shared the exact same molecular alterations (Table). Based on molecular profiling, the final integrated diagnosis was “glioblastoma, IDH wildtype, WHO grade 4.” For nearly a century,“glioblastoma multiforme” was used to describe what are now simply referred to as “glioblastomas,” even though “GBM” remains the official abbreviation (1). Cases like the current one underscore why “multiforme” was originally incorporated into the diagnosis, because these tumors can show a tremendous range of histo-