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SEGA-like circumscribed astrocytoma in a non-NF1 patient, harboring molecular profile of GBM. A case report. 非NF1患者的SEGA样局限性星形细胞瘤,具有GBM的分子特征。病例报告。
IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY Pub Date : 2024-06-01 Epub Date: 2023-11-02 DOI: 10.1111/neup.12948
Seiji Yamada, Motoki Tanikawa, Yuko Matsushita, Ryota Fujinami, Hiroshi Yamada, Kaishi Sakomi, Tomohiro Sakata, Hidehito Inagaki, Hideaki Yokoo, Koichi Ichimura, Mitsuhito Mase

Subependymal giant cell astrocytoma (SEGA) is a low-grade periventricular tumor that is closely associated with tuberous sclerosis complex (TSC). SEGA typically arises during the first two decades of life and rarely arises after the age of 20-25 years. Nevertheless, it has also been reported that glioma histologically resembling SEGA, so-called SEGA-like astrocytoma, can arise in neurofibromatosis type 1 (NF1) patients, even in the elderly. Herein, we report a case of SEGA-like circumscribed astrocytoma arising in the lateral ventricle of a 75-year-old woman. Whole-exome sequencing revealed a somatic variant of NF1. Methylation array analysis led to a diagnosis of "methylation class glioblastoma, IDH-wildtype, mesenchymal-type (GBM, MES)" with a high calibrated score (0.99). EGFR amplification, CDKN2A/B homozygous deletion, chromosomal +7/-10 alterations, and TERT promoter mutation, typical molecular abnormalities usually found in GBM, were also observed. While most reported cases of SEGA-like astrocytoma have arisen in NF1 patients, the patient was neither TSC nor NF1. Near total removal was accomplished with endoscopic cylinder surgery. At the 36-month follow-up, there was no tumor recurrence without adjuvant therapies. This clinical behavior did not match GBM. SEGA-like astrocytoma of the elderly is rare, and this is the oldest case reported so far. In addition, high-grade molecular features found in circumscribed tumor remain unclear. Further investigations among larger series are needed for clarifying the underlying molecular mechanisms.

室管膜下巨细胞星形细胞瘤(SEGA)是一种与结节性硬化综合征(TSC)密切相关的低级别室周肿瘤。SEGA通常发生在生命的前二十年,很少发生在20-25岁之后 年。然而,也有报道称,在组织学上类似SEGA的神经胶质瘤,即所谓的SEGA样星形细胞瘤,可能出现在1型神经纤维瘤病(NF1)患者中,甚至在老年人中。在此,我们报告了一例发生在一名75岁女性侧脑室的SEGA样局限性星形细胞瘤。全外显子组测序揭示了NF1的体细胞变体。甲基化阵列分析诊断为“甲基化类胶质母细胞瘤,IDH野生型,间充质型(GBM,MES)”,评分高(0.99)。还观察到EGFR扩增、CDKN2A/B纯合缺失、染色体+7/-10改变和TERT启动子突变,这是GBM中常见的典型分子异常。虽然大多数报告的SEGA样星形细胞瘤病例发生在NF1患者中,但该患者既不是TSC也不是NF1。内窥镜圆柱体手术几乎完全切除。在36个月的随访中,在没有辅助治疗的情况下没有肿瘤复发。这种临床行为与GBM不匹配。老年人的SEGA样星形细胞瘤是罕见的,这是迄今为止报道的最古老的病例。此外,在局限性肿瘤中发现的高级分子特征尚不清楚。需要在更大的系列中进行进一步的研究,以阐明潜在的分子机制。
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引用次数: 0
A rare encounter: Comprehensive case review of myxoid meningiomas with a representative case. 罕见的偶遇:一例典型的黏液样脑膜瘤的综合病例回顾。
IF 1.3 4区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2023-11-12 DOI: 10.1111/neup.12955
Norris C Talbot, Carlie Proctor, Hidehiro Takei, Jamie B Toms

Meningiomas are the most diagnosed primary central nervous system tumor. Currently, 15 different subtypes of meningioma exist with various characteristics. One extremely rare subtype is myxoid meningioma, which is a World Health Organization grade 1 benign meningioma. These specific meningiomas have only been reported 12 times in the literature. In this representative case, we present a 46-year-old female patient with a left frontal myxoid meningioma, describe the findings on imaging, and provide the histopathological features that are needed for diagnosis. Furthermore, this report discusses the other existing myxoid meningioma case reports found throughout the literature.

脑膜瘤是诊断最多的原发性中枢神经系统肿瘤。目前,脑膜瘤有15种不同的亚型,具有不同的特征。粘液样脑膜瘤是一种极为罕见的亚型,是世界卫生组织一级良性脑膜瘤。这些特殊的脑膜瘤在文献中只报道过12次。在这个具有代表性的病例中,我们报告了一位46岁的女性左额部黏液样脑膜瘤患者,描述了其影像学表现,并提供了诊断所需的组织病理学特征。此外,本报告还讨论了文献中发现的其他现有黏液样脑膜瘤病例报告。
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引用次数: 0
Ependymoma-like tumor with mesenchymal differentiation (ELTMD) with ZFTA:NCOA1 fusion: A diagnostic challenge. ZFTA:NCOA1融合的间充质分化Ependymoma样肿瘤:诊断挑战。
IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY Pub Date : 2024-06-01 Epub Date: 2023-11-06 DOI: 10.1111/neup.12952
Pranav Dorwal, Christine White, Anna Fn Goh, Amit Kumar, Jane McEniery, Rick Walker, Thomas Robertson

Ependymal tumors are classified based on their location, histology, and molecular characteristics. Supratentorial ependymomas (ST-EPNs) are a group of circumscribed supratentorial gliomas, which usually have pathogenic fusions involving either zinc finger translocation associated (ZFTA) (formerly C11orf95) or YAP1. A subtype of ependymoma was recently described and labeled ependymoma-like tumors with mesenchymal differentiation (ELTMDs). We describe a case of a 5-year-old boy who presented with a right frontal tumor. The diagnosis was challenging, and a correct diagnosis could only be reached after reanalysis of methylation data with a more recent version of the classifier and RNA fusion testing, which revealed ZFTA:NCOA1 (nuclear receptor coactivator 1) fusion. There are only a handful of cases of this entity, which is being reported for its rarity and the diagnostic challenge it poses.

Ependymal肿瘤根据其位置、组织学和分子特征进行分类。幕上室管膜瘤(ST-EPNs)是一组局限性幕上神经胶质瘤,通常具有致病性融合,涉及锌指易位相关(ZFTA)(以前为C11orf95)或YAP1。室管膜瘤的一种亚型最近被描述并标记为具有间充质分化的室管膜样肿瘤(ELTMDs)。我们描述了一个5岁男孩的病例,他表现为右额肿瘤。诊断具有挑战性,只有在用最新版本的分类器和RNA融合测试重新分析甲基化数据后才能得出正确的诊断,该测试揭示了ZFTA:NCOA1(核受体共激活因子1)融合。这种实体只有少数病例,由于其罕见性及其带来的诊断挑战而被报道。
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引用次数: 0
ASK1 activation in glial cells in post-mortem multiple sclerosis tissue. 多发性硬化症死后组织神经胶质细胞中的 ASK1 激活。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-05-22 DOI: 10.1111/neup.12978
Erika Seki, Xiaoli Guo, Kazuhiko Namekata, Takashi Komori, Hiroyuki Hayashi, Nobutaka Arai, Takayuki Harada

Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice. To further investigate its clinical significance, in the present study, we examined the activation of ASK1 in the post-mortem brain of MS patients. ASK1 activation was found in active lesions of the corpus callosum in both microglia/macrophages and astrocytes. Moreover, ASK1 activation in astrocytes was higher than that in microglia/macrophages, which was in line with our findings in EAE mice. Our results suggest an important role of ASK1 in glial cells, indicating that ASK1 might be a good therapeutic target for MS.

多发性硬化症(MS)是青壮年致残的主要原因,是一种以局部脱髓鞘区域为特征的中枢神经系统炎症性疾病。凋亡信号调节激酶1(ASK1)是一种丝裂原活化蛋白激酶,已被证明与多发性硬化症小鼠模型--实验性自身免疫性脑脊髓炎(EAE)的发病机制有关。有趣的是,ASK1 信号调节神经胶质细胞的相互作用,并驱动 EAE 小鼠的神经炎症。为了进一步研究其临床意义,我们在本研究中检测了多发性硬化症患者死后大脑中 ASK1 的激活情况。在胼胝体活动性病变中的小胶质细胞/巨噬细胞和星形胶质细胞中都发现了 ASK1 的活化。此外,星形胶质细胞中的ASK1活化高于小胶质细胞/巨噬细胞,这与我们在EAE小鼠中的发现一致。我们的研究结果表明,ASK1在神经胶质细胞中起着重要作用,这表明ASK1可能是多发性硬化症的一个很好的治疗靶点。
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引用次数: 0
Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine. 拉丁美洲-伊比利亚髓母细胞瘤体细胞突变谱分析及驱动基因的临床影响:迈向精准医疗。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-05-12 DOI: 10.1111/neup.12979
Letícia Ganem Rillo Paz Barateiro, Rodrigo de Oliveira Cavagna, Mariana Bisarro Dos Reis, Flávia Escremim de Paula, Gustavo Ramos Teixeira, Daniel Antunes Moreno, Murilo Bonatelli, Iara Santana, Fabiano Pinto Saggioro, Luciano Neder, João Norberto Stavale, Suzana Maria Fleury Malheiros, Hernan Garcia-Rivello, Silvia Christiansen, Susana Nunes, Maria João Gil da Costa, Jorge Pinheiro, Carlos Almeida Júnior, Bruna Minniti Mançano, Rui Manuel Reis

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MBSHH, 13.0% MBWNT, 7.3% MBGrp3, and 13.0% MBGrp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MBSHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MBSHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.

髓母细胞瘤(MB)是儿童中最常见的恶性脑肿瘤,因其异质性和治疗相关毒性而闻名,目前亟需新的治疗靶点。我们使用 Illumina TruSight Tumor 15 面板分析了 69 例拉丁美洲-伊比利亚分子特征髓母细胞瘤中 15 个驱动基因的体细胞突变情况。我们根据变异的临床影响和致癌性对其进行了分类。在患者中,66.7% 为 MBSHH,13.0% 为 MBWNT,7.3% 为 MBGrp3,13.0% 为 MBGrp4。在发现的 63 个变异中,54% 被归类为 I 级/II 级,31.7% 被归类为致癌/可能致癌。我们观察到 33.3% 的病例至少携带一种变异。TP53(23.2%,16/69)是突变最多的基因,其次是PIK3CA(5.8%,4/69)、KIT(4.3%,3/69)、PDGFRA(2.9%,2/69)、表皮生长因子受体(1.4%,1/69)、ERBB2(1.4%,1/69)和NRAS(1.4%,1/69)。约41%的MBSHH肿瘤出现基因突变,TP53(32.6%)是最常见的突变基因。I/II级和致癌/可能致癌的TP53变异与复发、病情进展和生存率降低有关。此外,还发现了 PIK3CA 和 KIT 基因中可能具有可操作性的变异。拉丁美洲-伊比利亚髓母细胞瘤,尤其是MBSHH,比其他人群表现出更高的变异频率。我们证实TP53基因突变状态是一个重要的预后因素,而PIK3CA和KIT则是潜在的治疗靶点。
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引用次数: 0
An autopsy case of type A FTLD-TDP with a GRN mutation presenting with the logopenic variant of primary progressive aphasia at onset and with corticobasal syndrome subsequently. 一例带有 GRN 突变的 A 型 FTLD-TDP 尸检病例,发病时表现为原发性进行性失语的对数开放变异型,随后出现皮质基底综合征。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-05-07 DOI: 10.1111/neup.12980
Takafumi Tomenaga, Shinobu Minatani, Hiroto Namba, Akitoshi Takeda, Takahito Yoshizaki, Joji Kawabe, Nazere Keyoumu, Hiroyuki Morino, Makoto Higuchi, Tomoyasu Matsubara, Hiroyuki Hatsuta, Masato Hasegawa, Shigeo Murayama, Yoshiaki Itoh

A 68-year-old woman presented with difficulty finding words and writing characters. Neurological examination led to clinical diagnosis at onset of the logopenic variant of primary progressive aphasia accompanied with ideomotor apraxia, visuospatial agnosia on the right, and Gerstmann syndrome. Bradykinesia and rigidity on the right with shuffling gait developed after one year. Treatment with L-dopa had no effect. The patient was diagnosed with corticobasal syndrome (CBS). Brain magnetic resonance imaging revealed diffuse cortical atrophy dominantly on the left, especially in the temporal, parietal, and occipital lobes. Positron emission tomography did not reveal any significant accumulation of amyloid β or tau protein. She died five years later. Neuropathological examination revealed diffuse cortical atrophy with severe neuronal loss and fibrous gliosis in the cortex. Neuronal cytoplasmic inclusions, short dystrophic neurites, and, most notably, neuronal intranuclear inclusions, all immunoreactive for phosphorylated TDP-43, were observed. Western blotting revealed a full length and fragments of phosphorylated TDP-43 at 45 and 23 kDa, respectively, confirming the pathological diagnosis of type A FTLD-TDP. Whole exome sequencing revealed a pathogenic mutation in GRN (c.87dupC). FTLD-TDP should be included in the differential diagnosis of CBS.

一名 68 岁的妇女因找不到单词和书写汉字而就诊。通过神经系统检查,临床诊断为原发性进行性失语的对数开放变异型,伴有意念运动障碍、右侧视觉空间缺失和格斯特曼综合征。一年后出现右侧运动迟缓和僵直,步态不稳。左旋多巴治疗没有效果。患者被诊断为皮质基底综合征(CBS)。脑磁共振成像显示,弥漫性皮质萎缩以左侧为主,尤其是颞叶、顶叶和枕叶。正电子发射断层扫描没有发现淀粉样蛋白β或tau蛋白的明显积聚。她在五年后去世。神经病理学检查显示,她的大脑皮层弥漫性萎缩,神经元严重缺失,皮层出现纤维胶质增生。观察到神经元胞浆包涵体、短小的萎缩性神经元,最明显的是神经元核内包涵体,它们对磷酸化的TDP-43均有免疫反应。Western 印迹显示,磷酸化 TDP-43 的全长和片段分别为 45 kDa 和 23 kDa,证实了 A 型 FTLD-TDP 的病理诊断。全外显子组测序显示,GRN存在致病突变(c.87dupC)。FTLD-TDP应包括在CBS的鉴别诊断中。
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引用次数: 0
A case of myxopapillary ependymoma with predominant giant cell morphology: A rare entity with comprehensive genomic profiling and review of literature 一例以巨细胞形态为主的肌乳头状上皮瘤:罕见病例的全面基因组分析和文献综述
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-04-19 DOI: 10.1111/neup.12977
Bryan Morales‐Vargas, Hassan Saad, Daniel Refai, Matthew Schniederjan, Zied Abdullaev, Kenneth Aldape, Malak Abedalthagafi
In the evolving landscape of ependymoma classification, which integrates histological, molecular, and anatomical context, we detail a rare case divergent from the usual histopathological spectrum. We present the case of a 37‐year‐old man with symptomatic spinal cord compression at the L3–L4 level. Neuroradiological evaluation revealed an intradural, encapsulated mass. Histologically, the tumor displayed atypical features: bizarre pleomorphic giant cells, intranuclear inclusions, mitotic activity, and a profusion of eosinophilic cytoplasm with hyalinized vessels, deviating from the characteristic perivascular pseudorosettes or myxopapillary patterns. Immunohistochemical staining bolstered this divergence, marking the tumor cells positive for glial fibrillary acidic protein and epithelial membrane antigen with a characteristic ring‐like pattern, and CD99 but negative for Olig‐2. These markers, alongside methylation profiling, facilitated its classification as a myxopapillary ependymoma (MPE), despite the atypical histologic features. This profile underscores the necessity of a multifaceted diagnostic process, especially when histological presentation is uncommon, confirming the critical role of immunohistochemistry and molecular diagnostics in classifying morphologically ambiguous ependymomas and exemplifying the histological diversity within MPEs.
在综合组织学、分子学和解剖学背景的不断发展的脑外胶质瘤分类中,我们详细介绍了一例不同于常见组织病理学范围的罕见病例。我们介绍了一例 37 岁男子的病例,他的 L3-L4 水平有症状性脊髓压迫。神经放射学评估显示其为硬膜内包裹性肿块。组织学上,肿瘤显示出非典型特征:奇异的多形性巨细胞、核内包涵体、有丝分裂活动、大量嗜酸性细胞质和透明化血管,偏离了特征性的血管周围假乳头状或肌乳头状形态。免疫组化染色证实了这一差异,标记为胶质纤维酸性蛋白和上皮膜抗原阳性的肿瘤细胞具有特征性环状模式,CD99阳性,但Olig-2阴性。尽管组织学特征不典型,但这些标记物以及甲基化分析有助于将其归类为肌乳头状上皮瘤(MPE)。这一特征强调了多方面诊断过程的必要性,尤其是在组织学表现不常见的情况下,这也证实了免疫组化和分子诊断在形态学上模糊的上皮瘤分类中的关键作用,并体现了MPE的组织学多样性。
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引用次数: 0
Acute respiratory failure caused by brainstem demyelinating lesions in an older patient with an atypical relapsing autoimmune disorder 一名患有非典型复发性自身免疫性疾病的老年患者因脑干脱髓鞘病变导致急性呼吸衰竭
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-04-07 DOI: 10.1111/neup.12976
Shoko Hongo, Hiroshi Shimizu, Etsuji Saji, Akihiro Nakajima, Kouichirou Okamoto, Izumi Kawachi, Osamu Onodera, Akiyoshi Kakita
An 84‐year‐old man presented with somnolence, dysphagia, and right hemiplegia, all occurring within a month, approximately one year after initial admission due to subacute, transient cognitive decline suggestive of acute disseminated encephalomyelitis involving the cerebral white matter. Serial magnetic resonance imaging (MRI) studies over that period revealed three high‐intensity signal lesions on fluid‐attenuated inversion recovery images, appearing in chronological order in the left upper and left lower medulla oblongata and left pontine base. Despite some clinical improvement following methylprednisolone pulse therapy, the patient died of respiratory failure. Autopsy revealed four fresh, well‐defined lesions in the brainstem, three of which corresponded to the lesions detected radiologically. The remaining lesion was located in the dorsal medulla oblongata and involved the right solitary nucleus. This might have appeared at a later disease stage, eventually causing respiratory failure. Histologically, all four lesions showed loss of myelin, preservation of axons, and infiltration of lymphocytes, predominantly CD8‐positive T cells, consistent with the histological features of autoimmune demyelinating diseases, particularly the confluent demyelination observed in the early and acute phases of multiple sclerosis (MS). In the cerebral white matter, autoimmune demyelination appeared superimposed on ischemic changes, consistent with the cerebrospinal fluid (CSF) and MRI findings on initial admission. No anti‐AQP4 or MOG antibodies or those potentially causing autoimmune encephalitis/demyelination were detected in either the serum or CSF. Despite several similarities to MS, such as the relapsing–remitting disease course and lesion histology, the entire clinicopathological picture in the present patient, especially the advanced age at onset and development of brainstem lesions in close proximity within a short time frame, did not fit those of MS or other autoimmune diseases that are currently established. The present results suggest that exceptionally older individuals can be affected by an as yet unknown inflammatory demyelinating disease of the CNS.
一名 84 岁的男性因亚急性、一过性认知能力下降入院,入院约一年后,在一个月内出现嗜睡、吞咽困难和右侧偏瘫,提示为急性播散性脑脊髓炎累及脑白质。在此期间进行的连续磁共振成像(MRI)检查发现,在流体增强反转恢复图像上有三个高强度信号病灶,按时间顺序出现在左侧延髓上部和左侧延髓下部以及左侧桥脑底部。尽管经过甲基强的松龙脉冲治疗后临床症状有所好转,但患者还是死于呼吸衰竭。尸检发现脑干有四个新鲜、界限清楚的病灶,其中三个与放射学检测到的病灶一致。其余一个病灶位于延髓背侧,累及右侧孤核。这可能出现在疾病的后期,最终导致呼吸衰竭。从组织学角度看,所有四个病灶均显示髓鞘缺失、轴突保留和淋巴细胞浸润,主要是 CD8 阳性 T 细胞,这与自身免疫性脱髓鞘疾病的组织学特征一致,尤其是多发性硬化症(MS)早期和急性期的融合性脱髓鞘。在脑白质中,自身免疫性脱髓鞘与缺血性改变相叠加,与最初入院时的脑脊液(CSF)和核磁共振成像结果一致。血清或脑脊液中均未检测到抗AQP4或MOG抗体或可能导致自身免疫性脑炎/脱髓鞘的抗体。尽管与多发性硬化症有几处相似之处,如复发-缓解病程和病变组织学,但该患者的整个临床病理特征,尤其是高龄发病和在短时间内脑干病变相邻发展的特征,与多发性硬化症或目前已确定的其他自身免疫性疾病的特征并不相符。本研究结果表明,年龄特别大的人也可能患上一种尚不为人知的中枢神经系统炎症性脱髓鞘疾病。
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引用次数: 0
Rare dual‐genotype IDH mutant glioma: Review of previously reported cases and two new cases of true “oligoastrocytoma” 罕见的双基因型IDH突变胶质瘤:回顾先前报告的病例和两例新的真性 "寡细胞瘤 "病例
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-04-06 DOI: 10.1111/neup.12975
Isabella Sutherland, John DeWitt, Alissa Thomas
In 2016, the World Health Organization (WHO) eliminated “oligoastrocytoma” from the classification of central nervous system (CNS) tumors, in favor of an integrated histologic and molecular diagnosis. Consistent with the 2016 classification, in the 2021 classification, oligodendrogliomas are defined by mutations in isocitrate dehydrogenase (IDH) with concurrent 1p19q codeletion, while astrocytomas are IDH mutant tumors, usually with ATRX loss. In 2007, a 24‐year‐old man presented with a brain tumor histologically described as astrocytoma, but with molecular studies consistent with an oligodendroglioma, IDH mutant and 1p19q‐codeleted. Years later, at resection, pathology revealed an astrocytoma, with variable ATRX expression and mutations of IDH, ATRX, TP53, and TERT by DNA sequencing. Fluorescence in situ hybridization studies confirmed 1p19q codeletion in sections of the tumor shown to histologically retain ATRX expression. Separately, in 2017, a 36‐year‐old woman presented with a frontal brain tumor with pathology consistent with an oligodendroglioma, IDH mutant and 1p19q‐codeleted. Two years later, pathology revealed an astrocytoma, IDH1 mutant, with ATRX loss. These two cases likely represent the rare occurrence of dual‐genotype IDH mutant infiltrating glioma. Nine cases of dual‐genotype IDH mutant glioma were previously reported in the literature. We present two cases in which this distinct molecular phenotype is present in a tumor in the same location with surgeries at two points in time, both with 1p19q codeletion and ATRX loss at the time of resection. Whether this represents a true “collision tumor” or genetic switching over time is not known, but the co‐occurrence of these hybrid mutations supports a diagnosis of dual‐genotype IDH mutant glioma.
2016 年,世界卫生组织(WHO)将 "少突胶质细胞瘤 "从中枢神经系统(CNS)肿瘤分类中删除,转而采用组织学和分子诊断相结合的方法。与 2016 年的分类法一致,在 2021 年的分类法中,少突胶质瘤的定义是异柠檬酸脱氢酶(IDH)突变,同时伴有 1p19q 编码缺失,而星形细胞瘤是 IDH 突变肿瘤,通常伴有 ATRX 缺失。2007 年,一名 24 岁的男子出现脑瘤,组织学描述为星形细胞瘤,但分子研究结果与少突胶质细胞瘤一致,IDH 突变且 1p19q 缺失。多年后,在切除手术中,病理结果显示为星形细胞瘤,ATRX表达不稳定,DNA测序显示IDH、ATRX、TP53和TERT突变。荧光原位杂交研究证实,在组织学显示保留ATRX表达的肿瘤切片中,存在1p19q编码缺失。另外,2017 年,一名 36 岁女性出现额叶脑瘤,病理符合少突胶质细胞瘤、IDH 突变和 1p19q 编码缺失。两年后,病理显示为星形细胞瘤,IDH1 突变,ATRX 缺失。这两个病例很可能代表了罕见的双基因型 IDH 突变浸润性胶质瘤。此前有文献报道了9例双基因型IDH突变胶质瘤。我们介绍了两个病例,这两个病例在同一部位的肿瘤中出现了这种不同的分子表型,而且在两个时间点进行了手术,切除时均有1p19q编码缺失和ATRX缺失。这究竟是真正的 "碰撞瘤 "还是随时间发生的基因转换尚不清楚,但这些混合突变的共同出现支持双基因型 IDH 突变胶质瘤的诊断。
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引用次数: 0
Association between hypothalamic Alzheimer's disease pathology and body mass index: The Hisayama study 下丘脑阿尔茨海默病病理变化与体重指数之间的关系:久山研究
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-04-02 DOI: 10.1111/neup.12974
Kaoru Yagita, Hiroyuki Honda, Tomoyuki Ohara, Sachiko Koyama, Hideko Noguchi, Yoshinao Oda, Ryo Yamasaki, Noriko Isobe, Toshiharu Ninomiya
The hypothalamus is the region of the brain that integrates the neuroendocrine system and whole-body metabolism. Patients with Alzheimer's disease (AD) have been reported to exhibit pathological changes in the hypothalamus, such as neurofibrillary tangles (NFTs) and amyloid plaques (APs). However, few studies have investigated whether hypothalamic AD pathology is associated with clinical factors. We investigated the association between AD-related pathological changes in the hypothalamus and clinical pictures using autopsied brain samples obtained from deceased residents of a Japanese community. A total of 85 autopsied brain samples were semi-quantitatively analyzed for AD pathology, including NFTs and APs. Our histopathological studies showed that several hypothalamic nuclei, such as the tuberomammillary nucleus (TBM) and lateral hypothalamic area (LHA), are vulnerable to AD pathologies. NFTs are observed in various neuropathological states, including normal cognitive cases, whereas APs are predominantly observed in AD. Regarding the association between hypothalamic AD pathologies and clinical factors, the degree of APs in the TBM and LHA was associated with a lower body mass index while alive, after adjusting for sex and age at death. However, we found no significant association between hypothalamic AD pathology and the prevalence of hypertension, diabetes, or dyslipidemia. Our study showed that a lower BMI, which is a poor prognostic factor of AD, might be associated with hypothalamic AP pathology and highlighted new insights regarding the disruption of the brain–whole body axis in AD.
下丘脑是大脑中整合神经内分泌系统和全身新陈代谢的区域。据报道,阿尔茨海默病患者的下丘脑会出现病理变化,如神经纤维缠结(NFT)和淀粉样蛋白斑块(AP)。然而,很少有研究探讨下丘脑AD病理变化是否与临床因素有关。我们利用从一个日本社区的已故居民身上获得的尸检脑样本,研究了下丘脑中与AD相关的病理变化与临床症状之间的关联。我们对85份尸检脑样本进行了半定量分析,以确定AD病理变化,包括NFT和AP。我们的组织病理学研究表明,下丘脑的几个核区,如结节锤状核(TBM)和下丘脑外侧区(LHA),很容易发生AD病变。在包括正常认知病例在内的各种神经病理状态中都可观察到NFT,而AP则主要在AD中观察到。关于下丘脑AD病变与临床因素之间的关系,在调整了性别和死亡时的年龄后,TBM和LHA的AP程度与生前体重指数较低有关。然而,我们发现下丘脑AD病变与高血压、糖尿病或血脂异常的发病率之间没有明显的关联。我们的研究表明,较低的体重指数(AD的不良预后因素)可能与下丘脑AP病变有关,并强调了关于AD中脑-全身轴破坏的新见解。
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Neuropathology
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