{"title":"Tectal glioma: clinical, radiological, and pathological features, and the importance of molecular analysis.","authors":"Ryoji Imoto, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Naoya Kemmotsu, Yasuki Suruga, Ryo Mizuta, Yasuhito Kegoya, Yohei Inoue, Tsuyoshi Umeda, Madoka Hokama, Kana Washio, Hiroyuki Yanai, Shota Tanaka, Kaishi Satomi, Koichi Ichimura, Isao Date","doi":"10.1007/s10014-024-00494-9","DOIUrl":"https://doi.org/10.1007/s10014-024-00494-9","url":null,"abstract":"<p><p>Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5 years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation.</p>","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Double-hit primary central nervous system lymphoma with histogenetically proven bone marrow infiltration: a case report and a review of the literature.","authors":"Koki Onodera, Mitsuaki Shirahata, Reina Mizuno, Masayoshi Fukuoka, Tomonari Suzuki, Tsugumi Satoh, Taku Homma, Naoki Takahashi, Kazuhiko Mishima","doi":"10.1007/s10014-024-00490-z","DOIUrl":"10.1007/s10014-024-00490-z","url":null,"abstract":"<p><p>Double-hit lymphoma (DHL) formerly referred to high-grade B-cell lymphoma with concurrent MYC and BCL2 or BCL6 rearrangements, however, the updated 2022 World Health Organization Classification (5th edition online) excludes those with MYC and BCL 6 rearrangements from the high-grade category. DHL confined to the central nervous system (CNS), known as double-hit primary CNS lymphoma (DH-PCNSL), is rare with poorly understood clinical features. Here, we report a case of a 64-year-old man with multiple brain tumors diagnosed with DH-PCNSL who showed bone marrow (BM) infiltration early in the clinical course. The histological diagnosis was high-grade B-cell lymphoma with MYC and BCL6 rearrangements. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal accumulation except in the CNS. The patient received whole-brain radiotherapy following the failure of high-dose methotrexate. After completion of radiotherapy, the patient developed thrombocytopenia, and BM biopsy showed infiltration of DHL cells, which were not detected by repeated FDG-PET. This is the first report of DH-PCNSL where identical gene rearrangements were confirmed in both the resected CNS tumor and BM tissue. Patients with DH-PCNSL require careful follow-up because they may be at a potential risk of BM infiltration, which may be undetectable by FDG-PET, particularly early in the disease course.</p>","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel case of ependymoma-like tumor with mesenchymal differentiation harboring ZFTA::RELA fusion in an adult.","authors":"Hirohisa Yajima, Shunsaku Takayanagi, Hirokazu Takami, Shota Tanaka, Masashi Nomura, Kaishi Satomi, Masako Ikemura, Sumihito Nobusawa, Ryuta Saito, Akihide Kondo, Nobuhito Saito","doi":"10.1007/s10014-024-00489-6","DOIUrl":"10.1007/s10014-024-00489-6","url":null,"abstract":"<p><p>High-grade supratentorial tumors harboring ZFTA::NCOA1/2 fusion in infants presenting with mixed histology of embryonal-appearing components resembling ependymoma and mesenchymal sarcomatous components have recently been reported as ependymoma-like tumors with mesenchymal differentiation (ELTMDs). In contrast, we describe herein a pathologically similar case with a novel ZFTA::RELA fusion in an adult. A frontal lobe lesion was resected from a 30-year-old woman and displayed mixed components on pathological examination, showing ependymoma-like and sarcomatous parts. The absence of perivascular pseudorosettes was inconsistent with a diagnosis of ependymoma. Fluorescence in situ hybridization analysis confirmed ZFTA::RELA fusion. The DKFZ methylation classifier (v12.8) did not categorize this case among established methylation classes. In addition, t-distributed stochastic neighbor embedding analysis using DNA methylation data revealed that the present case was distant from ependymomas but close to two previously reported cases of ELTMD involving ZFTA::NCOA1/2 fusion. Taken together, we concluded that this tumor should be considered under the entity of ELTMD. This represents the first description of an adult patient with ELTMD harboring ZFTA::RELA fusion analyzed by DNA methylation profiling, supporting the establishment of ELTMD as a possible new tumor type.</p>","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MAPK pathway alterations in polymorphous low-grade neuroepithelial tumor of the young: diagnostic considerations.","authors":"Shilpa Rao, Aditi Goyal, Allen Johnson, Nishanth Sadashiva, Karthik Kulanthaivelu, Vikas Vazhayil, Vani Santosh","doi":"10.1007/s10014-024-00487-8","DOIUrl":"10.1007/s10014-024-00487-8","url":null,"abstract":"<p><p>Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently recognised tumor type with indolent behaviour with characteristic imaging and histomolecular features. We describe the clinical, imaging, histo-molecular features of 15 cases diagnosed as low-grade glioma suggestive of PLNTY, over a period of 3 years. Immunohistochemistry (IHC) and fluorescence in situ hybridisation were used to assess molecular alterations. The tumors were seen predominantly in children (range 5-65 years). Most of the patients presented with history of seizures. Imaging revealed cortical-subcortical well demarcated solid-cystic tumor with intratumoral calcification. Histopathology revealed a low-grade tumor with oligodendroglia-Iike cells admixed with astrocytic cells immunopositive for CD34. BRAF p.V600E mutations and FGFR2 breakapart were observed in six cases each, while three showed FGFR3 breakapart. FGFR2 breakapart positive PLNTY were seen in children exclusively. The majority of cases were seizure free post-surgery, except two patients who succumbed to the illness. PLNTY, needs to be considered as a prime differential diagnosis in a solid-cystic tumor in a young patient with history of seizures. Characteristic clinical features, radiology, histomorphology with an IHC panel of OLIG2, GFAP and CD34 correlates with one of the MAPK alterations in PLNTY (BRAF p.V600E, FGFR2/3 gene rearrangement). In a resource limited setting, this limited panel may be sufficient for a correlative diagnosis.</p>","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain Tumor PathologyPub Date : 2024-10-01Epub Date: 2024-09-24DOI: 10.1007/s10014-024-00493-w
Naohide Fujita, Andrew Bondoc, Sergio Simoes, Joji Ishida, Michael S Taccone, Amanda Luck, Dilakshan Srikanthan, Robert Siddaway, Adrian Levine, Nesrin Sabha, Stacey Krumholtz, Akihide Kondo, Hajime Arai, Christian Smith, Paul McDonald, Cynthia Hawkins, Shoukat Dedhar, James Rutka
{"title":"Combination treatment with histone deacetylase and carbonic anhydrase 9 inhibitors shows therapeutic potential in experimental diffuse intrinsic pontine glioma.","authors":"Naohide Fujita, Andrew Bondoc, Sergio Simoes, Joji Ishida, Michael S Taccone, Amanda Luck, Dilakshan Srikanthan, Robert Siddaway, Adrian Levine, Nesrin Sabha, Stacey Krumholtz, Akihide Kondo, Hajime Arai, Christian Smith, Paul McDonald, Cynthia Hawkins, Shoukat Dedhar, James Rutka","doi":"10.1007/s10014-024-00493-w","DOIUrl":"10.1007/s10014-024-00493-w","url":null,"abstract":"<p><p>Diffuse intrinsic pontine glioma (DIPG) remains a significant therapeutic challenge due to the lack of effective and safe treatment options. This study explores the potential of combining histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors in treating DIPG. Analysis of RNA sequencing data and tumor tissue from patient samples for the expression of the carbonic anhydrase family and hypoxia signaling pathway activity revealed clinical relevance for targeting CA9 in DIPG. A synergy screen was conducted using CA9 inhibitor SLC-0111 and HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. The combination of SLC-0111 and pyroxamide demonstrated the highest synergy and was selected for further analysis. Combining SLC-0111 and pyroxamide effectively inhibited DIPG cell proliferation, reduced cell migration and invasion potential, and enhanced histone acetylation, leading to decreased cell population in S Phase. Additionally, the combination therapy induced a greater reduction in intracellular pH than either agent alone. Data from this study suggest that the combination of SLC-0111 and pyroxamide holds promise for treating experimental DIPG, and further investigation of this combination therapy in preclinical models is warranted to evaluate its potential as a viable treatment for DIPG.</p>","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analyses of immune cells and alpha-smooth muscle actin-positive cells under the immunological microenvironment between with and without dense fibrosis in primary central nervous system lymphoma.","authors":"Jun Takei, Miku Maeda, Nei Fukasawa, Masaharu Kawashima, Misayo Miyake, Kyoichi Tomoto, Shohei Nawate, Akihiko Teshigawara, Tomoya Suzuki, Yohei Yamamoto, Hiroyasu Nagashima, Ryosuke Mori, Ryoko Fukushima, Satoshi Matsushima, Hiroyoshi Kino, Ai Muroi, Takao Tsurubuchi, Noriaki Sakamoto, Kaichi Nishiwaki, Shingo Yano, Yuzuru Hasegawa, Yuichi Murayama, Yasuharu Akasaki, Masayuki Shimoda, Eiichi Ishikawa, Toshihide Tanaka","doi":"10.1007/s10014-024-00488-7","DOIUrl":"10.1007/s10014-024-00488-7","url":null,"abstract":"<p><p>Histopathologic examinations of primary central nervous system lymphoma (PCNSL) reveal concentric accumulation of lymphocytes in the perivascular area with fibrosis. However, the nature of this fibrosis in \"stiff\" PCNSL remains unclear. We have encountered some PCNSLs with hard masses as surgical findings. This study investigated the dense fibrous status and tumor microenvironment of PCNSLs with or without stiffness. We evaluated by silver-impregnation nine PCNSLs with stiffness and 26 PCNSLs without stiffness. Six of the nine stiff PCNSLs showed pathological features of prominent fibrosis characterized by aggregation of reticulin fibers, and collagen accumulations. Alpha-smooth muscle actin (αSMA)-positive spindle cells as a cancer-associated fibroblast, the populations of T lymphocytes, and macrophages were compared between fibrous and control PCNSLs. Fibrous PCNSLs included abundant αSMA-positive cells in both intra- and extra-tumor environments (5/6, 87% and 3/6, 50%, respectively). Conversely, only one out of the seven control PCNSL contained αSMA-positive cells in the intra-tumoral area. Furthermore, the presence of extra-tumoral αSMA-positive cells was associated with infiltration of T lymphocytes and macrophages. In conclusion, recognizing the presence of dense fibrosis in PCNSL can provide insights into the tumor microenvironment. These results may help stratify patients with PCNSL and improve immunotherapies for these patients.</p>","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Astroblastoma with MN1::BEND2 in an elderly patient: A case report and review of the literature","authors":"Hirotaka Tsukamoto, Ryu Saito, Takahiro Shirakura, Takuma Nakashima, Ryo Yamamoto, Hirofumi Kazama, Mitsuto Hanihara, Hiromichi Suzuki, Sumihito Nobusawa, Hiroyuki Kinouchi","doi":"10.1007/s10014-024-00491-y","DOIUrl":"https://doi.org/10.1007/s10014-024-00491-y","url":null,"abstract":"","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive genomic analysis reveals clonal origin and subtype-specific evolution in a case of sporadic multiple meningiomas","authors":"Maki Sakaguchi, Masafumi Horie, Yukinobu Ito, Shingo Tanaka, Keishi Mizuguchi, Hiroko Ikeda, Etsuko Kiyokawa, Mitsutoshi Nakada, Daichi Maeda","doi":"10.1007/s10014-024-00486-9","DOIUrl":"https://doi.org/10.1007/s10014-024-00486-9","url":null,"abstract":"<p>Meningioma is the most common primary intracranial tumor in adults, with up to 10% manifesting as multiple tumors. Data on the genomic and molecular changes in sporadic multiple meningiomas are scarce, leading to ongoing debates regarding their evolutionary processes. A comprehensive genetic analysis of a large number of lesions, including precursor lesions, is necessary to explore these two possible origins: clonal and independent. In the present study, we performed whole-exome sequencing and analyzed somatic single-nucleotide variants (SNVs), insertions/deletions (INDELs), and copy number alterations (CNAs) in a patient with sporadic multiple meningiomas. These meningiomas included two mass-forming lesions of different histological subtypes (transitional and chordoid) and two small meningothelial nests. Genetic analysis revealed CNAs on chromosomes 22q and Y as common abnormalities in the two largest tumors. Furthermore, we identified SNV/INDELs unique to each focus, with <i>NF2</i> mutation prevalent in the transitional meningioma and <i>CREBBP</i> mutation in the chordoid meningioma. Loss of chromosome 22 was detected in two small meningothelial nests. Overall, we elucidated the clonal origin and subtype-specific evolution of multiple meningiomas in this case. CNAs may serve as the initial driving event in meningioma development.</p>","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141779949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment","authors":"Taketo Ezaki, Toshihide Tanaka, Ryota Tamura, Kentaro Ohara, Yohei Yamamoto, Jun Takei, Yukina Morimoto, Ryotaro Imai, Yuki Kuranai, Yasuharu Akasaki, Masahiro Toda, Yuichi Murayama, Keisuke Miyake, Hikaru Sasaki","doi":"10.1007/s10014-024-00481-0","DOIUrl":"https://doi.org/10.1007/s10014-024-00481-0","url":null,"abstract":"<p>Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (<i>p</i> = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (<i>p</i> = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (<i>p</i> = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (<i>p</i> = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.</p>","PeriodicalId":9226,"journal":{"name":"Brain Tumor Pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140576873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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