IDH1突变型胶质母细胞瘤临床病理分析

曾英; 钟鹏; 朱祥风; 林俐; 杜娟; 肖华亮; 郭乔楠

doi:10.16016/j.1000-5404.201911013

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IDH1突变型胶质母细胞瘤临床病理分析

临床医学 | 更新时间：2026-01-09

- IDH1突变型胶质母细胞瘤临床病理分析
- Clinical and pathological features of IDH1-mutant glioblastoma: analysis of 10 cases
- 第三军医大学学报 2020年42卷第7期页码：734-743
- 作者机构：
  
  1.400037重庆，陆军军医大学(第三军医大学)第二附属医院病理科
  2.400042 重庆，陆军军医大学(第三军医大学)大坪医院病理科
- 作者简介：
  
  [ 肖华亮. E-mail:xhl616@hotmail.com XIAO Hualiang. E-mail:xhl616@hotmail.com
  [ 郭乔楠. E-mail:qiaonan85@263.net GUO Qiaonan. E-mail:qiaonan85@263.net
- 基金信息：
- DOI：10.16016/j.1000-5404.201911013
  中图分类号： R446.8;R730.264
- 收稿：2019-11-03，
  
  修回：2020-01-01，
  
  纸质出版：2020-04-15
- 稿件说明：
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曾英, 钟鹏, 朱祥风, 等. IDH1突变型胶质母细胞瘤临床病理分析[J]. 第三军医大学学报, 2020,42(7):734-743.

Ying ZENG, Peng ZHONG, Xiangfeng ZHU, et al. Clinical and pathological features of IDH1-mutant glioblastoma: analysis of 10 cases[J]. Journal of Third Military Medical University, 2020, 42(7): 734-743.
曾英, 钟鹏, 朱祥风, 等. IDH1突变型胶质母细胞瘤临床病理分析[J]. 第三军医大学学报, 2020,42(7):734-743. DOI： 10.16016/j.1000-5404.201911013.

Ying ZENG, Peng ZHONG, Xiangfeng ZHU, et al. Clinical and pathological features of IDH1-mutant glioblastoma: analysis of 10 cases[J]. Journal of Third Military Medical University, 2020, 42(7): 734-743. DOI： 10.16016/j.1000-5404.201911013.

摘要

目的

探讨IDH1突变型胶质母细胞瘤(glioblastoma IDH1-mutant

GBM IDH1-mut)的临床病理学特征。

方法

收集2014-2018年陆军军医大学大坪医院病理科10例GBM IDH1-mut患者临床及影像学资料，观察其病理学形态及免疫表型，检测其分子改变，并复习相关文献，探讨GBM IDH1-mut的临床病理特征及分子机制。

结果

GBM IDH1-mut患者10例，其中男性6例，女性4例；年龄28~63岁；7例累及额叶，以头昏、头痛为主要症状，5例有胶质瘤病史。显微镜下观察GBM IDH1-mut共同形态学特征为细胞密集，细胞呈圆形、梭形、多角形，细胞异型明显，核分裂象易见，微血管增生、坏死。微血管增生以肾小球样微血管增生为主，坏死表现为栅栏状坏死和凝固性缺血性坏死，根据累及范围分为大片和局灶。8例GBM IDH1-mut周围见WHOⅡ/Ⅲ胶质瘤成分。免疫组化结果:GFAP、Nestin、IDH1呈阳性表达，Olig-2可见不同程度表达(9/10)，P53呈弥漫阳性表达(9/10)；ATRX均不表达；Ki-67标记指数为10%~80%，而肿瘤细胞NeuN、NF、CD68、Syn、CD34均为阴性，CD34血管内皮细胞阳性。分子病理结果:10例均见IDH1R132H突变，9例MGMT启动子发生甲基化，1p/19q未缺失(0/4)，未检测到TERT突变和BRAFV600E突变(0/3)。

结论

GBM IDH1-mut少见，坏死局限和微血管增生不显著提示预后较好，坏死广泛和微血管显著增生提示预后较差。

Abstract

Objective

To investigate clinical and pathological features of IDH1-mutant glioblastoma (GBM IDH1-mut).

Methods

The clinical and radiological data of 10 patients with GBM IDH1-mut were collected

and their pathological

immunohistochemical

and molecular features were analyzed. The pathological diagnosis and molecular genetic features of GBM IDH1-mut were explored based on the findings in these cases and the previously reported cases.

Results

Of the 10 patients with GBM IDH1-mut (including 6 male and 4 female patients)

7 had temporal lobe involvement with headache and dizziness as the main symptoms. Pathological examination revealed that the tumors were highly cellular

and the tumor cells were pleomorphic (spherical

spindle-shaped and polygonal) with nuclear atypia and brisk mitotic activity. All the tumors showed microvascular proliferation and foci of necrosis. Microvascular hyperplasia was characterized mainly by a glomeruloid appearance; tumor necrosis

featured mostly by palisading necrosis and coagulative ischemic necrosis

could be either extensive or focal. The component of glioma (WHO Ⅱ/Ⅲ) was found in 8 cases. The tumor cells were immunohistochemically positive for GFAP

Nestin

and IDH1 in all the cases

and Olig-2 expression of varying intensity was found in 9 cases; diffuse expression of P53 was observed in 9 cases. ATRX was negative in all the cases. The tumor cells were negative for NeuN

CD68

Syn

and CD34

and the microvascular endothelial cells were positive for CD34. All the tumors showed IDH1R132H mutation. MGMT promoter methylation was detected in 9 cases

and none of the cases showed loss of 1p/19q (0/4); TERT mutation or BRAFV600E mutation (0/3) was detected in none of the cases.

Conclusion

GBM IDH1-mut is rare. About half of the patients with GBM IDH1-mut have favorable prognoses

which may be related to focal necrosis and mild microvascular proliferation; the other half of the patients have poor prognoses possibly due to extensive necrosis and significant microvascular proliferation.

关键词

Keywords

references

LOUIS D N, OHGAKI H, WIESTLER O D, et al . WHO classification of the tumors of the central nervous system[M ] . 2016: 52-56.

RICHARDSON T E, SNUDERL M, SERRANO J, et al . Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis[J ] . J Neurooncol, 2017, 133(1): 183-192. DOI:10.1007/s11060-017-2431-y.

RICHARDSON T E, SATHE A A, KANCHWALA M, et al . Genetic and epigenetic features of rapidly progressing IDH-mutant astrocytomas[J ] . J Neuropathol Exp Neurol, 2018, 77(7): 542-548. DOI:10.1093/jnen/nly026.

OHNO M, NARITA Y, MIYAKITA Y, et al . Glioblastomas with IDH1/2 mutations have a short clinical history and have a favorable clinicaloutcome[J ] . Jpn J Clin Oncol, 2016, 46(1): 31-39. DOI:10.1093/jjco/hyv170.

YAN W, ZHANG W, YOU G, et al . Correlation of IDH1 mutation with clinicopathologic factors and prognosis in primary glioblastoma: a report of 118 patients from China[J ] . PLoS ONE, 2012, 7(1): e30339. DOI:10.1371/journal.pone.0030339.

LAI A, KHARBANDA S, POPE W B, et al . Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin[J ] . J Clin Oncol, 2011, 29(34): 4482-4490. DOI: 10.1200/jco.2010.33.8715.

PALDOR I, DRUMMOND K J, KAYE A H. IDH1 mutation may not be prognostically favorable in glioblastoma when controlled for tumor location: a case-controlstudy[J]. J Clin Neurosci, 2016, 34: 117-120. DOI: 10.1016/j.jocn.2016.05.016.

OHGAKI H, KLEIHUES P. The definition of primary and secondaryglioblastoma[J]. Clin Cancer Res, 2013, 19(4): 764-772. DOI: 10.1158/1078-0432.ccr-12-3002.

HATA N, HATAE R, YOSHIMOTO K, et al . Insular primary glioblastomas with IDH mutations: Clinical and biologicalspecificities[J ] . Neuropathology, 2017, 37(3): 200-206. DOI: 10.1111/neup.12362.

KORSHUNOV A, CASALINI B, CHAVEZ L, et al . Integrated molecular characterization of IDH-mutantglioblastomas[J ] . Neuropathol Appl Neurobiol, 2019, 45(2): 108-118. DOI:10.1111/nan.12523.

WANG P F, LIU N, SONG H W, et al . IDH-1R132H mutation status in diffuse glioma patients: implications for classification[J ] . Oncotarget, 2016, 7(21): 31393-31400. DOI: 10.18632/oncotarget.8918.

HA S Y, KANG S Y, DO I G, et al . Glioblastoma with oligodendroglial component represents a subgroup of glioblastoma with high prevalence of IDH1 mutation and association with youngerage[J ] . J Neurooncol, 2013, 112(3): 439-448. DOI:10.1007/s11060-013-1073-y.

TURKALP Z, KARAMCHANDANI J, DAS S. IDH mutation in glioma: new insights and promises for the future[J]. JAMANeurol, 2014, 71(10): 1319-1325. DOI: 10.1001/jamaneurol.2014.1205.

MILLER J J, SHIH H A, ANDRONESI O C, et al . Isocitrate dehydrogenase-mutant glioma: Evolving clinical and therapeuticimplications[J ] . Cancer, 2017, 123(23): 4535-4546. DOI: 10.1002/cncr.31039.

胡慧敏, 王政, 江涛.异柠檬酸脱氢酶1突变的原发性胶质母细胞瘤差异表达基因的生物学功能分析[J].中华神经外科杂志, 2016, 32(5): 502-505. DOI: 10.3760/cma.j.issn.1001-2346.2016.05.019.

HU H M, WANG Z, JIANG T. Biological function analysis of differentially expressed genes of primary glioblastomas of isocitrate dehydrogenase 1 mutation[J]. Chin J Neurosurg, 2016, 32(5): 502-505. DOI: 10.3760/cma.j.issn.1001-2346.2016.05.019.

BERGHOFF A S, KIESEL B, WIDHALM G, et al . Correlation of immune phenotype with IDH mutation in diffuse glioma[J ] . Neuro-oncology, 2017, 19(11): 1460-1468. DOI: 10.1093/neuonc/nox054.

POON C C, GORDON P M K, LIU K, et al . Differential microglia and macrophage profiles in human IDH-mutant and -wild type glioblastoma[J ] . Oncotarget, 2019, 10(33): 3129-3143. DOI: 10.18632/oncotarget.26863.

SHIRAHATA M, ONO T, STICHEL D, et al . Novel, improved grading system(s) for IDH-mutant astrocyticgliomas[J ] . Acta Neuropathol, 2018, 136(1): 153-166. DOI: 10.1007/s00401-018-1849-4.

HU H M, WANG Z, LIU Y W, et al . Genome-wide transcriptional analyses of Chinese patients reveal cell migration is attenu ated in IDH1-mutant glioblastomas[J ] . Cancer Lett, 2015, 357(2): 566-574. DOI:10.1016/j.canlet.2014.12.018.

KICKINGEREDER P, SAHM F, RADBRUCH A, et al . IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma[J ] . Sci Rep, 2015, 5: 16238. DOI: 10.1038/srep16238.

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