Neuropil-like islands (NIs) are a histologic hallmark of glioneuronal tumors with neuropil-like islands (GTNIs), but GTNIs are presently not considered a homogeneous entity. The essence of GTNI is likely its glial component, and NIs are now considered aberrant neuronal differentiation or metaplasia. The case we report herein is a 41-year-old woman who was synchronously affected by two brain tumors: one was a glioblastoma (glioblastoma multiforme, GBM), of isocitrate dehydrogenase (IDH)-wild type, with NIs in the left parietal lobe, and the other was histologically a composite gangliocytoma (GC)/anaplastic ganglioglioma (GG) with NIs in the right medial temporal lobe. While both tumors were genetically wild type for IDH, histone H3, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF), the former tumor, but not the latter, was mutated for telomerase reverse transcriptase promoter gene (TERT). A recent systematic study using DNA methylation profiling and next-generation sequencing showed that anaplastic GG separate into other WHO tumor types, including IDH-wild-type GBM. It suggested a diagnostic scheme where an anaplastic GG is likely an IDH-wild-type GBM if it is a BRAF wild type, IDH wild type, and TERT promoter mutant tumor. The likely scenario in this patient is that the GBM results from the progression of GC/anaplastic GG due to the superimposed TERT promoter mutation and the propagation of newly generated GBM cells in the contralateral hemisphere. A systematic analysis using DNA methylation profiling and next-generation sequencing was not available in this study, but the common presence of NIs histologically noted in the two tumors could support this scenario. Although a sufficient volume of molecular and genetic testing is sine qua non for the accurate understanding of brain tumors, the importance of histologic observation cannot be overemphasized.
{"title":"Neuropil-like islands are a possible pathogenetic link between glioblastoma and gangliocytoma/ganglioglioma in a case of synchronous bilateral brain tumors.","authors":"Keisuke Ishizawa, Jun-Ichi Adachi, Jun-Ichi Tamaru, Ryo Nishikawa, Kazuhiko Mishima, Atsushi Sasaki","doi":"10.1111/neup.12939","DOIUrl":"10.1111/neup.12939","url":null,"abstract":"<p><p>Neuropil-like islands (NIs) are a histologic hallmark of glioneuronal tumors with neuropil-like islands (GTNIs), but GTNIs are presently not considered a homogeneous entity. The essence of GTNI is likely its glial component, and NIs are now considered aberrant neuronal differentiation or metaplasia. The case we report herein is a 41-year-old woman who was synchronously affected by two brain tumors: one was a glioblastoma (glioblastoma multiforme, GBM), of isocitrate dehydrogenase (IDH)-wild type, with NIs in the left parietal lobe, and the other was histologically a composite gangliocytoma (GC)/anaplastic ganglioglioma (GG) with NIs in the right medial temporal lobe. While both tumors were genetically wild type for IDH, histone H3, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF), the former tumor, but not the latter, was mutated for telomerase reverse transcriptase promoter gene (TERT). A recent systematic study using DNA methylation profiling and next-generation sequencing showed that anaplastic GG separate into other WHO tumor types, including IDH-wild-type GBM. It suggested a diagnostic scheme where an anaplastic GG is likely an IDH-wild-type GBM if it is a BRAF wild type, IDH wild type, and TERT promoter mutant tumor. The likely scenario in this patient is that the GBM results from the progression of GC/anaplastic GG due to the superimposed TERT promoter mutation and the propagation of newly generated GBM cells in the contralateral hemisphere. A systematic analysis using DNA methylation profiling and next-generation sequencing was not available in this study, but the common presence of NIs histologically noted in the two tumors could support this scenario. Although a sufficient volume of molecular and genetic testing is sine qua non for the accurate understanding of brain tumors, the importance of histologic observation cannot be overemphasized.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"126-134"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10114170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Compared with those involving the central nervous system, lymphomas involving the peripheral nervous system, namely neurolymphomatosis, are extremely rare. Neurolymphomatosis is classified as primary or secondary; the former is much rarer than the latter. Herein, we present an autopsied case of primary cauda equina lymphoma (PCEL), a type of primary neurolymphomatosis, with a literature review of autopsied cases of PCEL as well as primary neurolymphomatosis other than PCEL (non-PCEL primary neurolymphomatosis). A 70-year-old woman presented with difficulty walking, followed by paraplegia and then bladder and bowel disturbance. On magnetic resonance imaging, the cauda equina was diffusely enlarged and enhanced with gadolinium. The brainstem and cerebellum were also enhanced with gadolinium along their surface. The differential diagnosis of the patient included meningeal tumors (other than lymphomas), lymphomas, or sarcoidosis. The biopsy of the cauda equina was planned for a definite diagnosis, but because the patient deteriorated so rapidly, it was not performed. Eventually, she was affected by cranial nerve palsies. With the definite diagnosis being undetermined, the patient died approximately 1.5 years after the onset of disesase. At autopsy, the cauda equina was replaced by a bulky mass composed of atypical B-lymphoid cells, consistent with diffuse large B-cell lymphoma (DLBCL). The spinal cord was heavily infiltrated, as were the spinal/cranial nerves and subarachnoid space. There was metastasis in the left adrenal. The patient was finally diagnosed postmortem as PCEL with a DLBCL phenotype. To date, there have been a limited number of autopsied cases of PCEL and non-PCEL primary neurolymphomatosis (nine cases in all, including ours). The diagnosis is, without exception, B-cell lymphoma including DLBCL, and the histology features central nervous system parenchymal infiltration, nerve root involvement, and subarachnoid dissemination (lymphomatous meningitis). Metastases are not uncommon. All clinicians and pathologists should be aware of lymphomas primarily involving the peripheral nervous system.
与累及中枢神经系统的淋巴瘤相比,累及周围神经系统的淋巴瘤(即神经淋巴瘤病)极为罕见。神经淋巴瘤病分为原发性和继发性两种,前者比后者罕见得多。在此,我们将介绍一例原发性马尾淋巴瘤(PCEL)(原发性神经淋巴瘤病的一种)的尸检病例,并对 PCEL 和 PCEL 以外的原发性神经淋巴瘤病(非 PCEL 原发性神经淋巴瘤病)的尸检病例进行文献综述。一名 70 岁的妇女出现行走困难,随后出现截瘫,接着是膀胱和肠道功能紊乱。磁共振成像显示,马尾呈弥漫性肿大,钆增强。脑干和小脑表面也有钆增强。患者的鉴别诊断包括脑膜肿瘤(淋巴瘤除外)、淋巴瘤或肉样瘤病。原计划对马尾进行活检以明确诊断,但由于患者病情急剧恶化,活检未能进行。最后,她出现了颅神经麻痹。由于无法确诊,患者在发病约 1.5 年后死亡。尸检发现,马尾被一个由非典型 B 淋巴细胞组成的肿块取代,与弥漫大 B 细胞淋巴瘤(DLBCL)一致。脊髓、脊神经/颅神经和蛛网膜下腔均被严重浸润。左肾上腺也有转移。患者死后最终被诊断为具有 DLBCL 表型的 PCEL。迄今为止,PCEL 和非 PCEL 原发性神经淋巴瘤病的尸检病例数量有限(共 9 例,包括我们的病例)。诊断结果无一例外都是 B 细胞淋巴瘤(包括 DLBCL),组织学特征为中枢神经系统实质浸润、神经根受累和蛛网膜下腔播散(淋巴瘤性脑膜炎)。转移并不少见。所有临床医生和病理学家都应了解主要累及周围神经系统的淋巴瘤。
{"title":"Primary cauda equina lymphoma confirmed by autopsy: A case report.","authors":"Keisuke Ishizawa, Takashi Komori, Rui Shimazaki, Yasuhiro Nakata, Jun-Ichi Tamaru, Atsushi Sasaki, Kazushi Takahashi","doi":"10.1111/neup.12941","DOIUrl":"10.1111/neup.12941","url":null,"abstract":"<p><p>Compared with those involving the central nervous system, lymphomas involving the peripheral nervous system, namely neurolymphomatosis, are extremely rare. Neurolymphomatosis is classified as primary or secondary; the former is much rarer than the latter. Herein, we present an autopsied case of primary cauda equina lymphoma (PCEL), a type of primary neurolymphomatosis, with a literature review of autopsied cases of PCEL as well as primary neurolymphomatosis other than PCEL (non-PCEL primary neurolymphomatosis). A 70-year-old woman presented with difficulty walking, followed by paraplegia and then bladder and bowel disturbance. On magnetic resonance imaging, the cauda equina was diffusely enlarged and enhanced with gadolinium. The brainstem and cerebellum were also enhanced with gadolinium along their surface. The differential diagnosis of the patient included meningeal tumors (other than lymphomas), lymphomas, or sarcoidosis. The biopsy of the cauda equina was planned for a definite diagnosis, but because the patient deteriorated so rapidly, it was not performed. Eventually, she was affected by cranial nerve palsies. With the definite diagnosis being undetermined, the patient died approximately 1.5 years after the onset of disesase. At autopsy, the cauda equina was replaced by a bulky mass composed of atypical B-lymphoid cells, consistent with diffuse large B-cell lymphoma (DLBCL). The spinal cord was heavily infiltrated, as were the spinal/cranial nerves and subarachnoid space. There was metastasis in the left adrenal. The patient was finally diagnosed postmortem as PCEL with a DLBCL phenotype. To date, there have been a limited number of autopsied cases of PCEL and non-PCEL primary neurolymphomatosis (nine cases in all, including ours). The diagnosis is, without exception, B-cell lymphoma including DLBCL, and the histology features central nervous system parenchymal infiltration, nerve root involvement, and subarachnoid dissemination (lymphomatous meningitis). Metastases are not uncommon. All clinicians and pathologists should be aware of lymphomas primarily involving the peripheral nervous system.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"147-153"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10484363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-07-31DOI: 10.1111/neup.12938
Arenn F Carlos, Shunsuke Koga, Neill R Graff-Radford, Matthew C Baker, Rosa Rademakers, Owen A Ross, Dennis W Dickson, Keith A Josephs
Transactive response DNA-binding protein 43 (TDP-43) pathological inclusions are found in frontotemporal lobar degeneration (FTLD-TDP) and Alzheimer's disease (AD-TDP). While clinically different, TDP-43 inclusions in FTLD-TDP and AD can have similar morphological characteristics. However, TDP-43 colocalizing with tau and forming "apple-bite" or "flame-shaped" neuronal cytoplasmic inclusions (NCI) are only found in AD-TDP. Here, we describe a case with AD and neuritic plaque-associated TDP-43. The patient was a 96-year-old right-handed Caucasian woman who had developed a slowly progressive amnestic syndrome compatible with typical AD at age 80. Genetic testing revealed APOE ε3/ε4, GRN r5848 CT, and MAPT H1/H2 genotype. Consistent with the old age at onset and long disease duration, limbic-predominant AD was found at autopsy, with high hippocampal yet low cortical neurofibrillary tangle (NFT) counts. Hippocampal and amygdala sclerosis were present. Immunohistochemistry for phospho-TDP-43 showed NCIs, dystrophic neurites, and rare neuronal intranuclear inclusions consistent with FTLD-TDP type A, as well as tau NFT-associated TDP-43 inclusions. These were frequent in the amygdala, entorhinal cortex, hippocampus, occipitotemporal gyrus, and inferior temporal gyrus but sparse in the mid-frontal cortex. Additionally, there were TDP-43-immunoreactive inclusions forming plaque-like structures in the molecular layer of the dentate fascia of the hippocampus. The presence of neuritic plaques in the same region was confirmed using thioflavin-S fluorescent microscopy and immunohistochemistry for phospho-tau. Double labeling immunofluorescence showed colocalization of TDP-43 and tau within neuritic plaques. Other pathologies included mild Lewy body pathology predominantly affecting the amygdala and olfactory bulb, aging-related tau astrogliopathy, and mixed small vessel disease (arteriolosclerosis and amyloid angiopathy) with several cortical microinfarcts. In conclusion, we have identified TDP-43 colocalizing with tau in neuritic plaques in AD, which expands the association of TDP-43 and tau in AD beyond NFTs. The clinical correlate of this plaque-associated TDP-43 appears to be a slowly progressive amnestic syndrome.
在额颞叶变性(FTLD-TDP)和阿尔茨海默病(AD-TDP)中发现了转录反应DNA结合蛋白43(TDP-43)病理包涵体。虽然临床表现不同,但 FTLD-TDP 和 AD 中的 TDP-43 包涵体可能具有相似的形态特征。然而,TDP-43与tau共聚焦并形成 "苹果咬合 "或 "火焰形 "神经元胞浆包涵体(NCI)仅见于AD-TDP。在此,我们描述了一例 AD 和神经斑块相关 TDP-43 的病例。患者是一名 96 岁的右撇子高加索女性,80 岁时出现了与典型 AD 相似的缓慢进展性失忆综合征。基因检测显示她患有 APOE ε3/ε4、GRN r5848 CT 和 MAPT H1/H2 基因型。与发病年龄大、病程长相一致的是,尸检时发现了以边缘为主的AD,海马计数高而皮质神经纤维缠结(NFT)计数低。存在海马和杏仁核硬化。磷酸化-TDP-43免疫组化显示出NCIs、萎缩性神经元、与FTLD-TDP A型一致的罕见神经元核内包涵体以及与tau NFT相关的TDP-43包涵体。在杏仁核、内视网膜皮层、海马、枕颞回和颞下回等部位经常出现这些包涵体,但在额叶中层皮层则很少见。此外,在海马齿状筋膜的分子层中存在 TDP-43 免疫反应性包涵体,形成斑块样结构。使用硫黄素-S荧光显微镜和磷酸化-tau免疫组化法证实了同一区域存在神经斑块。双标记免疫荧光显示,TDP-43和tau在神经斑块内共定位。其他病变包括主要影响杏仁核和嗅球的轻度路易体病变、与衰老相关的tau星形胶质细胞病变以及伴有数个皮质微梗塞的混合性小血管疾病(动脉硬化和淀粉样血管病)。总之,我们在 AD 的神经斑块中发现了 TDP-43 与 tau 的共聚焦,这将 TDP-43 与 tau 在 AD 中的关联扩展到了 NFTs 之外。这种斑块相关的TDP-43的临床相关性似乎是一种缓慢进展的失忆综合征。
{"title":"Senile plaque-associated transactive response DNA-binding protein 43 in Alzheimer's disease: A case report spanning 16 years of memory loss.","authors":"Arenn F Carlos, Shunsuke Koga, Neill R Graff-Radford, Matthew C Baker, Rosa Rademakers, Owen A Ross, Dennis W Dickson, Keith A Josephs","doi":"10.1111/neup.12938","DOIUrl":"10.1111/neup.12938","url":null,"abstract":"<p><p>Transactive response DNA-binding protein 43 (TDP-43) pathological inclusions are found in frontotemporal lobar degeneration (FTLD-TDP) and Alzheimer's disease (AD-TDP). While clinically different, TDP-43 inclusions in FTLD-TDP and AD can have similar morphological characteristics. However, TDP-43 colocalizing with tau and forming \"apple-bite\" or \"flame-shaped\" neuronal cytoplasmic inclusions (NCI) are only found in AD-TDP. Here, we describe a case with AD and neuritic plaque-associated TDP-43. The patient was a 96-year-old right-handed Caucasian woman who had developed a slowly progressive amnestic syndrome compatible with typical AD at age 80. Genetic testing revealed APOE ε3/ε4, GRN r5848 CT, and MAPT H1/H2 genotype. Consistent with the old age at onset and long disease duration, limbic-predominant AD was found at autopsy, with high hippocampal yet low cortical neurofibrillary tangle (NFT) counts. Hippocampal and amygdala sclerosis were present. Immunohistochemistry for phospho-TDP-43 showed NCIs, dystrophic neurites, and rare neuronal intranuclear inclusions consistent with FTLD-TDP type A, as well as tau NFT-associated TDP-43 inclusions. These were frequent in the amygdala, entorhinal cortex, hippocampus, occipitotemporal gyrus, and inferior temporal gyrus but sparse in the mid-frontal cortex. Additionally, there were TDP-43-immunoreactive inclusions forming plaque-like structures in the molecular layer of the dentate fascia of the hippocampus. The presence of neuritic plaques in the same region was confirmed using thioflavin-S fluorescent microscopy and immunohistochemistry for phospho-tau. Double labeling immunofluorescence showed colocalization of TDP-43 and tau within neuritic plaques. Other pathologies included mild Lewy body pathology predominantly affecting the amygdala and olfactory bulb, aging-related tau astrogliopathy, and mixed small vessel disease (arteriolosclerosis and amyloid angiopathy) with several cortical microinfarcts. In conclusion, we have identified TDP-43 colocalizing with tau in neuritic plaques in AD, which expands the association of TDP-43 and tau in AD beyond NFTs. The clinical correlate of this plaque-associated TDP-43 appears to be a slowly progressive amnestic syndrome.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"115-125"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We report a case of pediatric glioma with uncommon imaging, morphological, and genetic features. A one-year-old boy incidentally presented with a tumor in the fourth ventricle. The tumor was completely resected surgically and investigated pathologically. The mostly circumscribed tumor had piloid features but primitive and anaplastic histology, such as increasing cellularity and mitosis. The Ki-67 staining index was 25% at the hotspot. KIAA1549::BRAF fusion and KIAA1549 partial deletions were detected by direct PCR, supported by Sanger sequencing. To the best of our knowledge, this is the first report of a glioma with both deletion of KIAA1549 p.P1771_P1899 and fusion of KIAA1549::BRAF. The tumor could not be classified using DNA methylome analysis. The present tumor fell into the category of pilocytic astrocytoma with histological features of anaplasia (aPA). Further studies are needed to establish pediatric aPA.
{"title":"A case of a pilocytic astrocytoma with histological features of anaplasia and unprecedent genetic alterations.","authors":"Mayuko Moritsubo, Takuya Furuta, Tetsuya Negoto, Hideo Nakamura, Yusuke Uchiyama, Motohiro Morioka, Koichi Oshima, Yasuo Sugita","doi":"10.1111/neup.12946","DOIUrl":"10.1111/neup.12946","url":null,"abstract":"<p><p>We report a case of pediatric glioma with uncommon imaging, morphological, and genetic features. A one-year-old boy incidentally presented with a tumor in the fourth ventricle. The tumor was completely resected surgically and investigated pathologically. The mostly circumscribed tumor had piloid features but primitive and anaplastic histology, such as increasing cellularity and mitosis. The Ki-67 staining index was 25% at the hotspot. KIAA1549::BRAF fusion and KIAA1549 partial deletions were detected by direct PCR, supported by Sanger sequencing. To the best of our knowledge, this is the first report of a glioma with both deletion of KIAA1549 p.P1771_P1899 and fusion of KIAA1549::BRAF. The tumor could not be classified using DNA methylome analysis. The present tumor fell into the category of pilocytic astrocytoma with histological features of anaplasia (aPA). Further studies are needed to establish pediatric aPA.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"161-166"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-06-29DOI: 10.1111/neup.12931
Mitsuhiro Anan, Rolando Fausto Del Maestro, Nobuhiro Hata, Minoru Fujiki
Glioblastoma (GBM) remains a treatment-resistant malignant brain tumor in large part because of its genetic heterogeneity and epigenetic plasticity. In this study, we investigated the epigenetic heterogeneity of GBM by evaluating the methylation status of the O6 -methylguanine methyltransferase (MGMT) promoter in individual clones of a single cell derived from GBM cell lines. The U251 and U373 GBM cell lines, from the Brain Tumour Research Centre of the Montreal Neurological Institute, were used for the experiments. To evaluate the methylation status of the MGMT promoter, pyrosequencing and methylation-specific PCR (MSP) were used. Moreover, mRNA and protein expression levels of MGMT in the individual GBM clones were evaluated. The HeLa cell line, which hyper-expresses MGMT, was used as control. A total of 12 U251 and 12 U373 clones were isolated. The methylation status of 83 of 97 CpG sites in the MGMT promoter were evaluated by pyrosequencing, and 11 methylated CpG sites and 13 unmethylated CpG sites were evaluated by MSP. The methylation status by pyrosequencing was relatively high at CpG sites 3-8, 20-35, and 7-83, in both the U251 and U373 clones. Neither MGMT mRNA nor protein was detected in any clone. These findings demonstrate tumor heterogeneity among individual clones derived from a single GBM cell. MGMT expression may be regulated, not only by methylation of the MGMT promoter but by other factors as well. Further studies are needed to clarify the mechanisms underlying the epigenetic heterogeneity and plasticity of GBM.
{"title":"O<sup>6</sup> -methylguanine methyltransferase promoter methylation status of glioblastoma cell line clonal population.","authors":"Mitsuhiro Anan, Rolando Fausto Del Maestro, Nobuhiro Hata, Minoru Fujiki","doi":"10.1111/neup.12931","DOIUrl":"10.1111/neup.12931","url":null,"abstract":"<p><p>Glioblastoma (GBM) remains a treatment-resistant malignant brain tumor in large part because of its genetic heterogeneity and epigenetic plasticity. In this study, we investigated the epigenetic heterogeneity of GBM by evaluating the methylation status of the O<sup>6</sup> -methylguanine methyltransferase (MGMT) promoter in individual clones of a single cell derived from GBM cell lines. The U251 and U373 GBM cell lines, from the Brain Tumour Research Centre of the Montreal Neurological Institute, were used for the experiments. To evaluate the methylation status of the MGMT promoter, pyrosequencing and methylation-specific PCR (MSP) were used. Moreover, mRNA and protein expression levels of MGMT in the individual GBM clones were evaluated. The HeLa cell line, which hyper-expresses MGMT, was used as control. A total of 12 U251 and 12 U373 clones were isolated. The methylation status of 83 of 97 CpG sites in the MGMT promoter were evaluated by pyrosequencing, and 11 methylated CpG sites and 13 unmethylated CpG sites were evaluated by MSP. The methylation status by pyrosequencing was relatively high at CpG sites 3-8, 20-35, and 7-83, in both the U251 and U373 clones. Neither MGMT mRNA nor protein was detected in any clone. These findings demonstrate tumor heterogeneity among individual clones derived from a single GBM cell. MGMT expression may be regulated, not only by methylation of the MGMT promoter but by other factors as well. Further studies are needed to clarify the mechanisms underlying the epigenetic heterogeneity and plasticity of GBM.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"41-46"},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9687082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-06-26DOI: 10.1111/neup.12930
Merve Aktan Suzgun, Elif Everest, Selin Kucukyurt, Melih Tutuncu, Ugur Uygunoglu, Ahmet Emre Eskazan, Ugur Ture, Herbert Budka, Aydin Sav, Aksel Siva
Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.
{"title":"Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature.","authors":"Merve Aktan Suzgun, Elif Everest, Selin Kucukyurt, Melih Tutuncu, Ugur Uygunoglu, Ahmet Emre Eskazan, Ugur Ture, Herbert Budka, Aydin Sav, Aksel Siva","doi":"10.1111/neup.12930","DOIUrl":"10.1111/neup.12930","url":null,"abstract":"<p><p>Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"59-67"},"PeriodicalIF":2.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A 76-year-old female with no apparent immunosuppressive conditions and no history of exposure to freshwater and international travel presented with headache and nausea 3 weeks before the presentation. On admission, her consciousness was E4V4V6. Cerebrospinal fluid analysis showed pleocytosis with mononuclear cell predominance, elevated protein, and decreased glucose. Despite antibiotic and antiviral therapy, her consciousness and neck stiffness gradually worsened, right eye-movement restriction appeared, and the right direct light reflex became absent. Brain magnetic resonance imaging revealed hydrocephalus in the inferior horn of the left lateral ventricle and meningeal enhancement around the brainstem and cerebellum. Tuberculous meningitis was suspected, and pyrazinamide, ethambutol, rifampicin, isoniazid, and dexamethasone were started. In addition, endoscopic biopsy was performed from the white matter around the inferior horn of the left lateral ventricle to exclude brain tumor. A brain biopsy specimen revealed eosinophilic round cytoplasm with vacuoles around blood vessels, and we diagnosed with amoebic encephalitis. We started azithromycin, flucytosine, rifampicin, and fluconazole, but her symptoms did not improve. She died 42 days after admission. In autopsy, the brain had not retained its structure due to autolysis. Hematoxylin and eosin staining of her brain biopsy specimen showed numerous amoebic cysts in the perivascular brain tissue. Analysis of the 16S ribosomal RNA region of amoebas from brain biopsy and autopsy specimens revealed a sequence consistent with Balamuthia mandrillaris. Amoebic meningoencephalitis can present with features characteristic of tuberculous meningitis, such as cranial nerve palsies, hydrocephalus, and basal meningeal enhancement. Difficulties in diagnosing amoebic meningoencephalitis are attributed to the following factors: (1) excluding tuberculous meningitis by microbial testing is difficult, (2) amoebic meningoencephalitis has low incidence and can occur without obvious exposure history, (3) invasive brain biopsy is essential in diagnosing amoebic meningoencephalitis. We should recognize the possibility of amoebic meningoencephalitis when evidence of tuberculosis meningitis cannot be demonstrated.
{"title":"Balamuthia mandrillaris amoebic encephalitis mimicking tuberculous meningitis.","authors":"Yoya Ono, Kazuhiro Higashida, Kanako Yamanouchi, Shusuke Nomura, Yuki Hanamatsu, Chiemi Saigo, Nobuyuki Tetsuka, Takayoshi Shimohata","doi":"10.1111/neup.12932","DOIUrl":"10.1111/neup.12932","url":null,"abstract":"<p><p>A 76-year-old female with no apparent immunosuppressive conditions and no history of exposure to freshwater and international travel presented with headache and nausea 3 weeks before the presentation. On admission, her consciousness was E4V4V6. Cerebrospinal fluid analysis showed pleocytosis with mononuclear cell predominance, elevated protein, and decreased glucose. Despite antibiotic and antiviral therapy, her consciousness and neck stiffness gradually worsened, right eye-movement restriction appeared, and the right direct light reflex became absent. Brain magnetic resonance imaging revealed hydrocephalus in the inferior horn of the left lateral ventricle and meningeal enhancement around the brainstem and cerebellum. Tuberculous meningitis was suspected, and pyrazinamide, ethambutol, rifampicin, isoniazid, and dexamethasone were started. In addition, endoscopic biopsy was performed from the white matter around the inferior horn of the left lateral ventricle to exclude brain tumor. A brain biopsy specimen revealed eosinophilic round cytoplasm with vacuoles around blood vessels, and we diagnosed with amoebic encephalitis. We started azithromycin, flucytosine, rifampicin, and fluconazole, but her symptoms did not improve. She died 42 days after admission. In autopsy, the brain had not retained its structure due to autolysis. Hematoxylin and eosin staining of her brain biopsy specimen showed numerous amoebic cysts in the perivascular brain tissue. Analysis of the 16S ribosomal RNA region of amoebas from brain biopsy and autopsy specimens revealed a sequence consistent with Balamuthia mandrillaris. Amoebic meningoencephalitis can present with features characteristic of tuberculous meningitis, such as cranial nerve palsies, hydrocephalus, and basal meningeal enhancement. Difficulties in diagnosing amoebic meningoencephalitis are attributed to the following factors: (1) excluding tuberculous meningitis by microbial testing is difficult, (2) amoebic meningoencephalitis has low incidence and can occur without obvious exposure history, (3) invasive brain biopsy is essential in diagnosing amoebic meningoencephalitis. We should recognize the possibility of amoebic meningoencephalitis when evidence of tuberculosis meningitis cannot be demonstrated.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"68-75"},"PeriodicalIF":2.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10071537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-07-04DOI: 10.1111/neup.12933
Abigale D MacLellan, Alexander S Easton, Rufus Alubankudi, Gwynedd E Pickett
Intracranial capillary hemangiomas in adults are rare, and diagnosis can be challenging. Hemangiomas, in general (and particularly in the skin), are more often noted in the pediatric population. Due to the lack of imaging undertaken in the presymptomatic phase, the literature provides few clues on the rate of growth of these unusual tumors. Therefore, we report a case of a 64-year-old man with a medical history of Lyme disease who presented with exhaustion and confusion. Imaging demonstrated an intra-axial lesion with vascularity in the posterior right temporal lobe, raising the possibility of a glioma. Imaging two years prior revealed a very small lesion in the same location. The patient underwent a craniectomy, total resection of the lesion was completed, and his symptoms of confusion resolved. Biopsy revealed a capillary hemangioma composed of small vascular channels lined by endothelial cells and pericytes without smooth muscle. Features of glioma, vascular neoplasms or neuroborreliosis (cerebral Lyme disease) were not identified. Our case documents the growth over two years of a rare intracranial capillary hemangioma in an older adult male.
{"title":"Documented growth of an intracranial capillary hemangioma: A case report.","authors":"Abigale D MacLellan, Alexander S Easton, Rufus Alubankudi, Gwynedd E Pickett","doi":"10.1111/neup.12933","DOIUrl":"10.1111/neup.12933","url":null,"abstract":"<p><p>Intracranial capillary hemangiomas in adults are rare, and diagnosis can be challenging. Hemangiomas, in general (and particularly in the skin), are more often noted in the pediatric population. Due to the lack of imaging undertaken in the presymptomatic phase, the literature provides few clues on the rate of growth of these unusual tumors. Therefore, we report a case of a 64-year-old man with a medical history of Lyme disease who presented with exhaustion and confusion. Imaging demonstrated an intra-axial lesion with vascularity in the posterior right temporal lobe, raising the possibility of a glioma. Imaging two years prior revealed a very small lesion in the same location. The patient underwent a craniectomy, total resection of the lesion was completed, and his symptoms of confusion resolved. Biopsy revealed a capillary hemangioma composed of small vascular channels lined by endothelial cells and pericytes without smooth muscle. Features of glioma, vascular neoplasms or neuroborreliosis (cerebral Lyme disease) were not identified. Our case documents the growth over two years of a rare intracranial capillary hemangioma in an older adult male.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"76-82"},"PeriodicalIF":2.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9754243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-09-20DOI: 10.1111/neup.12943
{"title":"Correction to \"MicroRNA-221 targeting PI3-K/Akt signaling axis induces cell proliferation and BCNU resistance in human glioblastoma\".","authors":"","doi":"10.1111/neup.12943","DOIUrl":"10.1111/neup.12943","url":null,"abstract":"","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"83"},"PeriodicalIF":2.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41124861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the central nervous system (CNS), a large group of glial cells called astrocytes play important roles in both physiological and disease conditions. Astrocytes participate in the formation of neurovascular units and interact closely with other cells of the CNS, such as microglia and neurons. Stroke is a global disease with high mortality and disability rate, most of which are ischemic stroke. Significant strides in understanding astrocytes have been made over the past few decades. Astrocytes respond strongly to ischemic stroke through a process known as activation or reactivity. Given the important role played by reactive astrocytes (RAs) in different spatial and temporal aspects of ischemic stroke, there is a growing interest in the potential therapeutic role of astrocytes. Currently, interventions targeting astrocytes, such as mediating astrocyte polarization, reducing edema, regulating glial scar formation, and reprogramming astrocytes, have been proven in modulating the progression of ischemic stroke. The aforementioned potential interventions on astrocytes and the crosstalk between astrocytes and other cells of the CNS will be summarized in this review.
{"title":"Astrocytes in ischemic stroke: Crosstalk in central nervous system and therapeutic potential.","authors":"Jueling Liu, Yuying Guo, Yunsha Zhang, Xiaoxiao Zhao, Rong Fu, Shengyu Hua, Shixin Xu","doi":"10.1111/neup.12928","DOIUrl":"10.1111/neup.12928","url":null,"abstract":"<p><p>In the central nervous system (CNS), a large group of glial cells called astrocytes play important roles in both physiological and disease conditions. Astrocytes participate in the formation of neurovascular units and interact closely with other cells of the CNS, such as microglia and neurons. Stroke is a global disease with high mortality and disability rate, most of which are ischemic stroke. Significant strides in understanding astrocytes have been made over the past few decades. Astrocytes respond strongly to ischemic stroke through a process known as activation or reactivity. Given the important role played by reactive astrocytes (RAs) in different spatial and temporal aspects of ischemic stroke, there is a growing interest in the potential therapeutic role of astrocytes. Currently, interventions targeting astrocytes, such as mediating astrocyte polarization, reducing edema, regulating glial scar formation, and reprogramming astrocytes, have been proven in modulating the progression of ischemic stroke. The aforementioned potential interventions on astrocytes and the crosstalk between astrocytes and other cells of the CNS will be summarized in this review.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"3-20"},"PeriodicalIF":2.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10029808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}