Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications.
Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications.
复制标题
DOI：
10.1007/s00401-014-1319-6
复制
发表时间：
2014-10
影响因子：
12.7
通讯作者：
Hawkins C
中科院分区：
文献类型：
--
作者：
Buczkowicz P;Bartels U;Bouffet E;Becher O;Hawkins C
弥漫性桥脑胶质瘤（DIPG）是儿童脑肿瘤相关死亡的主要原因。在大多数情况下，诊断是基于临床和MRI结果，导致可用于研究的治疗前标本稀缺。我们的小组已经开发了一种基于尸检的协议，以调查DIPG的组织学和生物学谱。这也使我们能够研究疾病的终末模式，并更好地了解我们在治疗DIPG时面临的挑战。在这里，我们回顾了72例DIPG病例，有充分的临床病史和分子数据，并描述了这种疾病的病理特征与临床和遗传特征的关系。53份样本为尸检材料（7份为治疗前），19份为治疗前活检/手术标本。在组织学检查中，62例患者患有高级别星形细胞瘤（18例WHO III级和44例WHO IV级患者），8例患有WHO II级星形细胞瘤，2例具有原始神经外胚层肿瘤（PNET）的特征。K27 M-H3突变仅见于WHO II-IV级星形细胞瘤组织学的肿瘤。K27 M-H3.1和ACVR 1突变以及ALT表型仅见于WHO III-IV级星形细胞瘤，而PIK 3CA突变和PDGFRA获得/扩增见于WHO II-IV级星形细胞瘤。大约1/3的DIPG患者的肿瘤发生了软脑膜扩散。此外，脑干、脊髓和丘脑的弥漫性侵犯很常见，有些病例显示扩散至额叶。这些发现表明，局部放射可能是不充分的，其中一些患者。重要的是，我们发现临床上经典的DIPG代表了不同的组织学谱，包括符合WHO II级星形细胞瘤标准的多个病例，这些病例在临床上表现为高级别星形细胞瘤，并含有组蛋白K27 M-H3.3突变。这表明，目前的WHO星形细胞瘤分级方案可能无法适当预测儿童脑干胶质瘤的结局。本文的在线版本（doi：10.1007/s 00401 -014-1319-6）包含补充材料，可供授权用户使用。
Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related death in children. In the majority of cases diagnosis is based on clinical and MRI findings, resulting in the scarcity of pre-treatment specimens available to study. Our group has developed an autopsy-based protocol to investigate the histologic and biologic spectrum of DIPG. This has also allowed us to investigate the terminal pattern of disease and gain a better understanding of what challenges we are facing in treating DIPG. Here, we review 72 DIPG cases with well documented clinical history and molecular data and describe the pathological features of this disease in relation to clinical and genetic features. Fifty-three of the samples were autopsy material (7 pre-treatment) and 19 were pre-treatment biopsy/surgical specimens. Upon histological review, 62 patients had high-grade astrocytomas (18 WHO grade III and 44 WHO grade IV patients), 8 had WHO grade II astrocytomas, and 2 had features of primitive neuroectodermal tumour (PNET). K27M-H3 mutations were exclusively found in tumours with WHO grade II–IV astrocytoma histology. K27M-H3.1 and ACVR1 mutations as well as ALT phenotype were only found in WHO grade III–IV astrocytomas, while PIK3CA mutations and PDGFRA gains/amplifications were found in WHO grade II–IV astrocytomas. Approximately 1/3 of DIPG patients had leptomeningeal spread of their tumour. Further, diffuse invasion of the brainstem, spinal cord and thalamus was common with some cases showing spread as distant as the frontal lobes. These findings suggest that focal radiation may be inadequate for some of these patients. Importantly, we show that clinically classic DIPGs represent a diverse histologic spectrum, including multiple cases which would fit WHO criteria of grade II astrocytoma which nevertheless behave clinically as high-grade astrocytomas and harbour the histone K27M-H3.3 mutation. This suggests that the current WHO astrocytoma grading scheme may not appropriately predict outcome for paediatric brainstem gliomas. The online version of this article (doi:10.1007/s00401-014-1319-6) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
45.3
作者：
Paugh, Barbara S.;Broniscer, Alberto;Baker, Suzanne J.
通讯作者：
Baker, Suzanne J.
影响因子：
45.3
作者：
Paugh, Barbara S.;Qu, Chunxu;Baker, Suzanne J.
通讯作者：
Baker, Suzanne J.
影响因子：
--
作者：
Herbert, Brittney-Shea;Shay, Jerry W;Wright, Woodring E
通讯作者：
Wright, Woodring E
影响因子：
30.8
作者：
Wu, Gang;Broniscer, Alberto;McEachron, Troy A.;Lu, Charles;Paugh, Barbara S.;Becksfort, Jared;Qu, Chunxu;Ding, Li;Huether, Robert;Parker, Matthew;Zhang, Junyuan;Gajjar, Amar;Dyer, Michael A.;Mullighan, Charles G.;Gilbertson, Richard J.;Mardis, Elaine R.;Wilson, Richard K.;Downing, James R.;Ellison, David W.;Zhang, Jinghui;Baker, Suzanne J.
通讯作者：
Baker, Suzanne J.
影响因子：
50.3
作者：
Bender, Sebastian;Tang, Yujie;Pfister, Stefan M.
通讯作者：
Pfister, Stefan M.