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三级医疗体系中胶质瘤的组织病理学谱及其免疫组化相关性

Histopathological Spectrum of Gliomas and Its Immunohistochemical Correlation in a Tertiary Care Setup.

作者信息

Malla Srishti, Bavikar Rupali, Gore Charusheela, Chugh Ashish, Gurwale Sushama

机构信息

Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, IND.

Neurosurgery, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, IND.

出版信息

Cureus. 2024 Jul 21;16(7):e65036. doi: 10.7759/cureus.65036. eCollection 2024 Jul.

Abstract

Introduction Central nervous system (CNS) tumors pose significant diagnostic challenges due to their varied morphological and differentiating characteristics. Modern advancements in immunohistochemistry (IHC) and molecular pathology have greatly enhanced prognostication, screening, and therapeutic management. Gliomas, a type of tumor originating from glial cells in the CNS, can develop from astrocytes, oligodendrocytes, or ependymal cells. According to the 2021 update, the classification of diffuse gliomas is primarily based on the presence or absence of isocitrate dehydrogenase (IDH1/2) mutations. IDH-wildtype gliomas (glioblastomas) have a significantly poorer prognosis compared to IDH-mutant gliomas (astrocytomas and oligodendrogliomas). Gliomas are highly infiltrative and resistant to treatment, making them largely incurable regardless of their grade and prognosis. Objective This study aimed to determine the histopathological diversity of gliomas and its correlation with protein expressions of IDH, ATRX gene (α-thalassemia/mental retardation syndrome X-linked), Ki-67, and p53 mutations (tumor suppressor gene-53), according to the 2021 World Health Organization (WHO) Classification of CNS Tumors, Fifth Edition. Methods This descriptive cross-sectional study was carried out in the Department of Pathology at a tertiary care center, focusing on various types of gliomas received over a two-year period. A total of 54 specimens of gliomas received from the Department of Neurosurgery were subjected to histopathological examination. Sections were stained using hematoxylin and eosin (H&E), and IHC was performed using four markers (IDH, ATRX, p53, Ki-67) in each case. Results were analyzed according to the 2021 WHO Classification of CNS Tumors, Fifth Edition. Results The majority of individuals were between the age group of 40 and 60 years, showing a male predominance (65%). The most common site was the frontal lobe. Glioblastoma constituted the largest proportion (46.2%) of the total cases, followed by astrocytoma (20.3%), oligodendroglioma (18.5%), pilocytic astrocytoma (7.4%), and ependymoma (7.4%). All 11 cases of astrocytoma exhibited IDH mutation and ATRX loss, with p53 positive in the majority of cases. Strong nuclear p53 immunohistochemical positivity in >10% of tumor nuclei correlates with TP53 mutations. Among 25 cases of glioblastoma, IDH was negative, ATRX was retained in all cases, and 11 cases were positive for p53 mutation. For oligodendroglioma, out of 10 cases, IDH mutation was positive, and ATRX was retained in all cases. p53 mutation was not seen in any case. All cases of pilocytic astrocytoma were negative for IDH and p53 mutations, with ATRX retained in all cases. In all cases of ependymoma, IDH and p53 mutations were negative, and ATRX was retained in all cases. Glioblastomas exhibited the highest Ki-67 expression. Conclusion The 2021 WHO Classification of CNS Tumors, Fifth Edition, was updated, building on previously established concepts and continuing to evolve. The final diagnosis of gliomas relies on a comprehensive combination of clinical evaluation, neuroimaging, pathological examination, and molecular analysis. Nonetheless, histopathological examination, along with IHC, remains the cornerstone of diagnosis.

摘要

引言

中枢神经系统(CNS)肿瘤因其形态和分化特征多样,带来了重大的诊断挑战。免疫组织化学(IHC)和分子病理学的现代进展极大地改善了预后评估、筛查和治疗管理。胶质瘤是一种起源于中枢神经系统胶质细胞的肿瘤,可由星形胶质细胞、少突胶质细胞或室管膜细胞发展而来。根据2021年的更新内容,弥漫性胶质瘤的分类主要基于异柠檬酸脱氢酶(IDH1/2)突变的有无。与IDH突变型胶质瘤(星形细胞瘤和少突胶质细胞瘤)相比,IDH野生型胶质瘤(胶质母细胞瘤)的预后明显更差。胶质瘤具有高度浸润性且对治疗有抗性,无论其分级和预后如何,大多难以治愈。

目的

本研究旨在根据2021年世界卫生组织(WHO)中枢神经系统肿瘤分类第五版,确定胶质瘤的组织病理学多样性及其与IDH、ATRX基因(α地中海贫血/智力发育迟缓综合征X连锁)、Ki-67和p53突变(肿瘤抑制基因-53)蛋白表达的相关性。

方法

本描述性横断面研究在一家三级医疗中心的病理科进行,重点关注两年期间接收的各类胶质瘤。总共对从神经外科接收的54例胶质瘤标本进行了组织病理学检查。切片用苏木精和伊红(H&E)染色,每例均使用四种标志物(IDH、ATRX、p53、Ki-67)进行免疫组织化学检测。结果根据2021年WHO中枢神经系统肿瘤分类第五版进行分析。

结果

大多数患者年龄在40至60岁之间,男性占优势(65%)。最常见的部位是额叶。胶质母细胞瘤占总病例的比例最大(46.2%),其次是星形细胞瘤(20.3%)、少突胶质细胞瘤(18.5%)、毛细胞型星形细胞瘤(7.4%)和室管膜瘤(7.4%)。所有11例星形细胞瘤均表现出IDH突变和ATRX缺失,大多数病例p53呈阳性。肿瘤细胞核中>10%的强核p53免疫组织化学阳性与TP53突变相关。在25例胶质母细胞瘤中,IDH为阴性,所有病例中ATRX均保留,11例p53突变呈阳性。对于少突胶质细胞瘤,10例中有IDH突变阳性,所有病例中ATRX均保留。任何病例均未发现p53突变。所有毛细胞型星形细胞瘤病例的IDH和p53突变均为阴性,所有病例中ATRX均保留。在所有室管膜瘤病例中,IDH和p53突变均为阴性,所有病例中ATRX均保留。胶质母细胞瘤的Ki-67表达最高。

结论

2021年WHO中枢神经系统肿瘤分类第五版在先前确立的概念基础上进行了更新,并持续发展。胶质瘤的最终诊断依赖于临床评估、神经影像学、病理检查和分子分析的综合结合。尽管如此,组织病理学检查以及免疫组织化学仍然是诊断的基石。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d458/11335173/e2cd19c20e28/cureus-0016-00000065036-i01.jpg

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