Emerging glioneuronal and neuronal tumors: case-based review
AbstractGlioneuronal and neuronal tumors (GNTs) are rare heterogeneous central nervous system tumors characterized by slow growth and favorable outcomes, but are often associated with diagnostic difficulties. A thorough analysis of three rare and recently recognized GNTs was performed in the context of clinicopathological features and molecular genetic characterization. The current spinal diffuse leptomeningeal glioneuronal tumor (DLGNT) was characterized with oligodendroglioma-like tumor with chromosome 1p/19q codeletion withoutIDH mutations andKIAA1549:BRAF fusion. The current occipital multinodular and vacuolating neuro...
Source: Brain Tumor Pathology - January 20, 2022 Category: Neurology Source Type: research

Histopathological predictors of progression-free survival in atypical meningioma: a single-center retrospective cohort and meta-analysis
AbstractTo determine the prognostic significance of histopathological features included in the diagnostic criteria of atypical meningioma for progression-free survival (PFS). We performed a retrospective cohort study and meta-analysis. Brain invasion, mitotic index, spontaneous necrosis, sheeting, prominent nucleoli, high cellularity, and small cells were the histopathological features of interest. The data from 25 studies involving 3590 patients including our cohort (n = 262) were included. The pooled HR of mitotic index at a cutoff value of 4 showed no statical significance in the gross analysis (pooled HR,...
Source: Brain Tumor Pathology - January 15, 2022 Category: Neurology Source Type: research

A patient with two gliomas with independent oligodendroglioma and glioblastoma biology proved by DNA-methylation profiling: a case report and review of the literature
AbstractHere, we report on a patient presenting with two histopathologically distinct gliomas. At the age of 42, the patient underwent initial resection of a right temporal oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade II followed by adjuvant radiochemotherapy with temozolomide. 15  months after initial diagnosis, the patient showed right hemispheric tumor progression and an additional new left frontal contrast enhancement in the subsequent imaging. A re-resection of the right-sided tumor and resection of the left frontal tumor were conducted. Neuropathological work-up showed recurrence of the right-sided ...
Source: Brain Tumor Pathology - January 11, 2022 Category: Neurology Source Type: research

Role of proliferative marker index and KBTBD4 mutation in the pathological diagnosis of pineal parenchymal tumors
This study included 19 cases of PPTs [3 pineocytomas (PCs), 10 PPTs of intermediate differentiation (PPTID), and 6 pineoblastomas (PBs)]. Immunohistochemistry for Ki-67, PHH3, and DICER1, as well as Sanger sequencing analysis forKBTBD4 mutations, was performed using formalin-fixed paraffin-embedded tissue specimens that were resected during surgery. Tumor cell proliferation was quantified using an image analysis software. For the PHH3 and MIB-1 indices, a significant difference was observed between the PPTIDs and PBs (P 
Source: Brain Tumor Pathology - January 9, 2022 Category: Neurology Source Type: research

Timing of H3K27me3 loss in secondary anaplastic meningiomas
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - January 6, 2022 Category: Neurology Source Type: research

Correction to: Epithelioid inflammatory myofibroblastic sarcoma with VCL –ALK fusion of central nervous system: case report and brief review of the literature
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - January 4, 2022 Category: Neurology Source Type: research

Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas
We report the associations between histological findings, IHC, and genetic status. We performed IHC of IDH1-R132H, ATRX, and p53 in 76 lower-grade gliomas and discussed its validity based on the 2016 WHO and the upcoming 2021 WHO classification. The sensitivity and specificity of anti-ATRX, p53, and IDH1-R132H IHC were 40.9%/98.1%, 78.6%/85.4%, and 90.5%/84.6%, respectively. Among 21IDH1-mutant gliomas without 1p/19q codeletion, two gliomas (9.5%) mimicked the so-called classic for oligodendroglioma (CFO) in their morphology. Of the 42 gliomas with 1p/19q codeletion, four cases were difficult to diagnose as oligodendroglio...
Source: Brain Tumor Pathology - November 26, 2021 Category: Neurology Source Type: research

Molecular subtyping of ependymoma and prognostic impact of Ki-67
In this study, we propose a cost-effective schematic diagnostic flow of EPNs by the anatomical location, three biomarkers (L1CAM, H3K27me3, and EZHIP), and a cut-off of a 7% Ki-67 labeling index. (Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - November 23, 2021 Category: Neurology Source Type: research

Central nervous system ALK-negative anaplastic large cell lymphoma with IRF4/DUSP22 rearrangement
We report what may be the first case of ALK-negative ALCL withIRF4/DUSP22 rearrangement involving the brain in a 55-year-old man. Magnetic resonance imaging demonstrated signal abnormalities in the periventricular region, corpus callosum and cingulate gyrus. Biopsy revealed a diffuse parenchymal and angiocentric infiltrate of CD30-positive cells that showedIRF4/DUSP22 rearrangement by fluorescence in situ hybridization. We also review the clinical and pathologic features of primary CNS ALK-negative ALCLs in the literature and highlight the need for awareness of this entity to optimize appropriate management. (Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - November 18, 2021 Category: Neurology Source Type: research

Epithelioid inflammatory myofibroblastic sarcoma with VCL –ALK fusion of central nervous system: case report and brief review of the literature
AbstractEpithelioid inflammatory myofibroblastic sarcomas are an aggressive variant of inflammatory myofibroblastic tumor described primarily in the abdomen and less commonly in pulmonary location. The anaplastic lymphoma kinase (ALK) fusion partners described in this tumor includeRANB2, RRBP1and EML4. While rare examples of inflammatory myofibroblastic tumors have been described in the central nervous system, the epithelioid variant has never been described. TheALK –VCL fusion has been described in renal cell carcinoma, high-grade glioma and epithelioid fibrous histiocytoma but has not been described in epithelioid ...
Source: Brain Tumor Pathology - November 6, 2021 Category: Neurology Source Type: research

Insights in primary central nervous system lymphoma: a role for glymphatics?
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - September 17, 2021 Category: Neurology Source Type: research

Revisiting vimentin: a negative surrogate marker of molecularly defined oligodendroglioma in adult type diffuse glioma
AbstractVimentin is a marker of epithelial-mesenchymal transformation and indicates poor prognosis in various cancers, but its role in diffuse gliomas remains unknown. We investigated the vimentin expression of diffuse gliomas according to the upcoming 2021 WHO classification, its variations due to mutational status, and its prognostic effects. We analyzed vimentin immunohistochemistry in 315 gliomas: a test set (n = 164) and a validation set (n = 151). RNA-seq and mutational information from The Cancer Genome Atlas (TCGA,n = 422) were also used for validation. Vimentin was diffuse...
Source: Brain Tumor Pathology - August 2, 2021 Category: Neurology Source Type: research

Spinal cord astroblastoma with EWSR1-BEND2 fusion classified as HGNET-MN1 by methylation classification: a case report
AbstractThe most recurrent fusion of central nervous system high-grade neuroepithelial tumor withMN1 alteration (HGNET-MN1) isMN1 rearrangement. Here, we report the case of a 36-year-old man with spinal cord astroblastoma showingEwing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1)-BEN domain-containing 2 (BEND2) fusion. The patient presented with back pain, gait disturbance and dysesthesia in the lower extremities and trunk. Magnetic resonance imaging showed an intramedullary tumor at the T3 –5 level, displaying homogeneous gadolinium enhancement. Partial tumor removal was performed with laminectomy. H...
Source: Brain Tumor Pathology - July 27, 2021 Category: Neurology Source Type: research

Preface
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - July 23, 2021 Category: Neurology Source Type: research

Association between IDH mutational status and tumor-associated epilepsy or venous thromboembolism in patients with grade II and III astrocytoma
We examined the relationship between IDH mutations in grade II/III astrocytomas and TAE/VTE according to the 2016 World Health Organization classification. The clinical data of patients with newly diagnosed grade II/III gliomas who were treated at Tohoku University Hospital from January 2010 to December 2018 were reviewed. Associations between TAE or VTE and the clinical/biological characteristics, histology, and IDH1/2 mutational status in patients with grade II/III gliomas were evaluated. Of the initial 137 patients (290 hospitalizations), 117 patients (203 hospitalizations) were included in the TAE group and 124 patient...
Source: Brain Tumor Pathology - July 16, 2021 Category: Neurology Source Type: research

Molecular, functional, and histopathological classification of the pituitary neuroendocrine neoplasms
AbstractIn 2017, WHO published an updated classification of the pituitary adenomas according to the lineages defined by the transcription factors, PIT1, SF1 and TPIT. Nomenclature of the pituitary tumors follows the mature cell types such as somatotroph (GH), lactotroph (LH), thyrotroph, corticotroph, and gonadotroph (FSH, LH). Null cell adenomas are defined by the absence of expression of any hormones and transcription factors. Not infrequently, the pituitary adenomas are invasive to the adjacent structures and are designated as aggressive adenomas. Knosp grading is often used to define the aggressiveness of the tumor. Sp...
Source: Brain Tumor Pathology - July 16, 2021 Category: Neurology Source Type: research

Clinical implications of molecular analysis in diffuse glioma stratification
In this study, we evaluated the molecular alterations for consecutive 300 diffuse glioma cases (grade 2, 56; grade 3, 62; grade 4, 182) based on this classification. Mutations in the isocitrate dehydrogenase (IDH) genes were common in lower grade glioma (LGG: grade2 –3), and when combined with 1p/19q status, LGGs could be stratified into three groups except for four cases (Astrocytoma, IDH-mutant: 44; Oligodendroglioma, IDH-mutant and 1p/19q codeleted: 37; Astrocytoma,IDH-wildtype: 33). 1p/19q-codeleted oligodendrogliomas were clinically the most favorable subgroup even with upfront chemotherapy. In contrast,IDH-wild...
Source: Brain Tumor Pathology - July 15, 2021 Category: Neurology Source Type: research

Primary central nervous system lymphoma: clinicopathological and genomic insights for therapeutic development
AbstractPrimary central nervous system lymphoma (PCNSL) is a highly aggressive, extra-nodal non-Hodgkin lymphoma that is confined to the central nervous system (CNS) and the eyes. Most PCNSLs arise in immunocompetent older patients and less frequently in immunocompromised patients with Epstein-Barr virus infection. Although a patient ’s initial response to chemotherapy and radiation therapy is favorable, the clinical outcome of PCNSL remains poor compared to that of systemic lymphoma. Radiation-induced neurotoxicity is also a critical problem for patients with PCNSL. Therefore, a novel therapeutic strategy is require...
Source: Brain Tumor Pathology - July 13, 2021 Category: Neurology Source Type: research

Combination of p38 MAPK inhibitor with PD-L1 antibody effectively prolongs survivals of temozolomide-resistant glioma-bearing mice via reduction of infiltrating glioma-associated macrophages and PD-L1 expression on resident glioma-associated microglia
AbstractCurrent conventional treatment strategies for glioblastoma (GBM) have limited efficacy due to the rapid development of resistance to temozolomide (TMZ). It is particularly urgent to develop novel therapeutic strategies that can overcome TMZ resistance and provide patients with better prognoses. Here, a TMZ-resistant GBM cell strain and a mouse model of TMZ resistance are established as valuable tools to explore novel therapeutic strategies against TMZ resistance. Experimentally, p38MAPK inhibitor reduces the accumulation of F4/80+/CD11b+ macrophages/microglia in glioma and prolongs the survivals of glioma-bearing m...
Source: Brain Tumor Pathology - July 6, 2021 Category: Neurology Source Type: research

Predicting BRAF V600E mutation in glioblastoma: utility of radiographic features
AbstractDetection of BRAF V600E mutation in glioblastomas (GBMs) is important because of potential therapeutic implications. Still, the relative paucity of these mutations makes molecular detection in all GBMs controversial. In the present study, we analyzed clinical, radiographic and pathologic features of 12 BRAF V600E-mutant GBMs and 12 matched controls from 2 institutions. We found that a majority of BRAF V600E-mutant GBMs displayed a combination of well-circumscribed lesions, large cystic components with thin walls and solid cortical component on MRI, but with some overlap with matchedBRAF wildtype controls (p ...
Source: Brain Tumor Pathology - July 3, 2021 Category: Neurology Source Type: research

Multi-omics analysis of intertumoral heterogeneity within medulloblastoma uncharted-pathway subtypes
AbstractMedulloblastoma is a common pediatric malignant brain tumor. There were four consensus molecular subgroups (WNT, SHH, Group3 and Group4). Group 3 and Group 4 tumors exhibited a great degree of transcriptional overlap, and were neither derived from exact pathway aberration. We investigated transcriptional and chromatin accessibility of medulloblastoma by multi-omics single-cell analysis. Our work identified inter- and intra-tumoral heterogeneity within the Group 3, Group 4 and Group 3/4 intermediate subgroups. Unsupervised cluster of each tumor identified 9 cell clusters with transcriptional profiles and 6 cell clus...
Source: Brain Tumor Pathology - June 28, 2021 Category: Neurology Source Type: research

Metabolic, immunohistochemical, and genetic profiling of a cerebellar liponeurocytoma with spinal dissemination: a case report and review of the literature
AbstractCerebellar liponeurocytoma (cLNC), categorized as a World Health Organization grade II tumor, is a rare neoplasm characterized by advanced neuronal/neurocytic differentiation and focal lipid accumulation in neuroepithelial tumor cells. However, the expression and genetic profiling of cLNC have been poorly studied. A 44-year-old woman with a three-year history of cerebellar ataxia and numbness in lower extremities underwent radiological examination revealing multiple contrast-enhancing tumors at the floor of the fourth ventricle and in the lower vermis, and spinal dissemination. The high uptake of 11 C-methionine in...
Source: Brain Tumor Pathology - June 17, 2021 Category: Neurology Source Type: research

Droplet digital PCR assay for detecting TERT promoter mutations in patients with glioma
In this report, we described a novel droplet digital PCR (ddPCR) assay to evaluateTERT hot spot mutations in fresh frozen and formalin-fixed paraffin-embedded (FFPE) specimens of glioma and verified the difference in results from the Sanger DNA sequencing results. We obtained the mutant allele fraction forTERT mutations of in a single ddPCR run in all cases, including the micro-dissected FFPE sections. On the contrary, up to twice the DNA sequences were required from fresh frozen tissue to obtain the results, consistent with ddPCR assay. When FFPE specimens were used, more time was required to evaluateTERT mutations throug...
Source: Brain Tumor Pathology - June 14, 2021 Category: Neurology Source Type: research

Anti-angiogenic and macrophage-based therapeutic strategies for glioma immunotherapy
AbstractAs a new concept of glioma therapy, immunotherapy combined with standard therapies is a promising modality to improve glioma patient survival. VEGF and its signaling pathway molecules not only inhibit angiogenesis but also may reinforce the immunosuppressive tumor microenvironment, including promotion of the accumulation of immunosuppressive tumor-associated macrophages (TAMs). In this review, we discuss VEGF-targeted therapy as a new treatment option of the TAM-targeted therapy for high-grade gliomas, as well as other TAM-targeted therapies. The authors also discuss the potential of these therapies combined with c...
Source: Brain Tumor Pathology - May 11, 2021 Category: Neurology Source Type: research

Unique pathological findings of astroblastoma with MN1 alteration in a patient with late recurrence
We report a late recurrence ofMN1-altered astroblastoma with unique pathological findings. A 24-year-old woman presented with seizures due to a left frontal lobe tumor. Gross total resection (GTR) was achieved, and the diagnosis wasMN1-altered astroblastoma, which presented cell wrapping, i.e., presence of tumor cells enveloping one another. She received local radiotherapy (50  Gy). However, the tumor recurred after 12 years, and its size increased rapidly. The second surgery achieved GTR and confirmed increasing anaplasia. The patient was tumor-free for 1 year without any neurological deficits. This case im...
Source: Brain Tumor Pathology - April 28, 2021 Category: Neurology Source Type: research

Brain-invasive meningiomas: molecular mechanisms and potential therapeutic options
AbstractMeningiomas are the most commonly diagnosed benign intracranial adult tumors. Subsets of meningiomas that present with extensive invasion into surrounding brain areas have high recurrence rates, resulting in difficulties for complete resection, substantially increased mortality of patients, and are therapeutically challenging for neurosurgeons. Exciting new data have provided insights into the understanding of the molecular machinery of invasion. Moreover, clinical trials for several novel approaches have been launched. Here, we will highlight the mechanisms which govern brain invasion and new promising therapeutic...
Source: Brain Tumor Pathology - April 26, 2021 Category: Neurology Source Type: research

A case of a rosette-forming glioneuronal tumor with clinicopathological features of a dysembryoplastic neuroepithelial tumor and fibroblast growth factor receptor 1 internal tandem duplication
AbstractRosette-forming glioneuronal tumors (RGNTs) are benign WHO grade 1 tumors that occur in the ventricular system, particularly the fourth ventricle. RGNTs and dysembryoplastic neuroepithelial tumors (DNTs) are both categorized as neuronal and mixed neuronal-glial tumors and may be difficult to distinguish. Coexistence of the two tumor types has been reported. Here, we report a pediatric case of RGNT with DNT-like features showing intraventricular dissemination. The tumor occurred in the medial temporal lobe and presented with specific pathological glioneuronal elements including floating neurons, which are typical in...
Source: Brain Tumor Pathology - April 9, 2021 Category: Neurology Source Type: research

A case of central nervous system lesion pathologically characterized by angiocentric, T-cell-rich lymphoid cell infiltrates: a case report and literature review
We report the case of a 37-year-old man with CNS lesion pathologically characterized by angiocentric, T-cell-rich lymphoid cell infiltrates that resembled CNS-LYG. The lesion was clinically aggressive with subacute onset and irregular ring-like enhancement on MRI. The resected specimen showed no cytological atypia, EBV-infected cells, or monoclonality for IgH and TCR gene rearrangements. Considering the possibility of latent malignancy, the patient was successfully treated with corticosteroid and chemoradiotherapy with high-dose methotrexate. The present case and the literature suggest that EBV-negative CNS lesions with an...
Source: Brain Tumor Pathology - March 30, 2021 Category: Neurology Source Type: research

Topoisomerase II β immunoreactivity (IR) co-localizes with neuronal marker-IR but not glial fibrillary acidic protein-IR in GLI3-positive medulloblastomas: an immunohistochemical analysis of 124 medulloblastomas from the Japan Children’s Cancer Group
AbstractWe previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase II β (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population. We divided 124 medulloblastomas into three groups (NM−/GFAP−, NM +/GFAP&minus...
Source: Brain Tumor Pathology - March 11, 2021 Category: Neurology Source Type: research

Aberrant expression of thyroid transcription factor-1 in meningeal solitary fibrous tumor/hemangiopericytoma
In conclusion, our study suggested that a large proportion of meningeal SFT/HPC was positive to TTF-1, while very few extra CNS SFT/HPC cases and no meningiomas were stained. So TTF-1 has value as an auxiliary diagnostic marker for meningeal SFT/HPC. (Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - March 5, 2021 Category: Neurology Source Type: research

Concomitant KIAA1549-BRAF fusion and IDH mutation in Pediatric spinal cord astrocytoma: a case report and literature review
AbstractPrimary tumors of the spinal cord are rare, accounting for 3 –6% of tumors in the central nervous system, particularly in children. KIAA1549-BRAF fusion is more common in pilocytic astrocytoma (PA) and IDH1 R132H mutation is rare in infratentorial tumors. Here, we report a 10-year-old male patient who presented with weakness in lower limbs that progressed t o difficulty walking. Magnetic resonance imaging (MRI) revealed an intramedullary solid-cystic lesion from the medulla oblongata to the thoracic spin 4 level, with the expansion of the spinal cord. The lesion exhibited patchy enhancement at C4-T1, indicati...
Source: Brain Tumor Pathology - February 28, 2021 Category: Neurology Source Type: research

The proteomic analysis shows enrichment of RNA surveillance pathways in adult SHH and extensive metabolic reprogramming in Group 3 medulloblastomas
AbstractMedulloblastoma, a common malignant brain tumor in children, comprises four molecular subgroups WNT, SHH, Group 3, and Group 4. In the present study, we performed a deep proteome-based investigation of SHH, Group 3 and Group 4 tumors. The adult SHH medulloblastomas were found to have a distinct proteomic profile. Several RNA metabolism-related pathways including mRNA splicing, 5 ′ to 3′ RNA decay, 3′ to 5′ RNA decay by the RNA exosome, and the N6-methyladenosine modification of RNA were enriched in adult SHH tumors. The heightened expression of the RNA surveillance pathways is likely to be e...
Source: Brain Tumor Pathology - January 12, 2021 Category: Neurology Source Type: research

Intracranial angiomatoid fibrous histiocytoma with rhabdoid features: a mimic of rhabdoid meningioma
AbstractAngiomatoid fibrous histiocytoma (AFH) is an uncommon soft-tissue neoplasm that arises mostly in the extremities of young people and generally carries a good prognosis. Intracranial location is unusual and frequently associated with myxoid change.EWSR1 gene fusions with members of theCREB family (CREB1, ATF1, andCREM) are well-established events in AFH. These fusions have also been described in other neoplasms including intracranial myxoid mesenchymal tumor, and it is still uncertain whether the latter is a distinct entity or if it represents a myxoid variant of AFH. Here, we describe a rare falcine AFH presenting ...
Source: Brain Tumor Pathology - January 12, 2021 Category: Neurology Source Type: research

Correction to: EZH2 inhibitory protein (EZHIP/Cxorf67) expression correlates strongly with H3K27me3 loss in posterior fossa ependymomas and is mutually exclusive with H3K27M mutations
In the original publication of the article, the middle name was missing in corresponding author ’s name. (Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - January 9, 2021 Category: Neurology Source Type: research

Prognostic significance of brain invasion in meningiomas: systematic review and meta-analysis
AbstractThe WHO 2016 classification introduced brain invasion as a standalone criterion for grade II meningioma (GIIM). We systematically reviewed studies published after 2000 and performed a PRISMA-compliant meta-analysis of the hazard ratios (HRs) for progression-free survival (PFS) between brain-invasive and noninvasive meningiomas. In five studies that included both benign and higher-grade meningiomas, brain invasion was a significant risk factor for recurrence (HR  = 2.45,p = 0.0004). However, in 3 studies comparing “brain-invasive meningioma with otherwise benign histology (BIOB)&rdq...
Source: Brain Tumor Pathology - January 6, 2021 Category: Neurology Source Type: research

The molecular framework of pediatric-type diffuse gliomas: shifting toward the revision of the WHO classification of tumors of the central nervous system
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - January 5, 2021 Category: Neurology Source Type: research

Ependymoma with C11orf95-MAML2 fusion: presenting with granular cell and ganglion cell features
AbstractC11orf95-RELA fusion or, less frequently,YAP1 fusion is recurrently detected in most cases of supratentorial ependymoma. Other fusions have rarely been reported in some cases of supratentorial ependymoma, and little is known about their pathological or clinical features. Here, we present a case of supratentorial ependymoma with unusual pathological findings andC11orf95-MAML2 fusion. A 23-year-old man was admitted to our hospital because of headache and vomiting. Magnetic resonance imaging revealed a cystic lesion in the right frontal lobe, and gross total resection of the tumor was performed. Pathologically, the tu...
Source: Brain Tumor Pathology - November 22, 2020 Category: Neurology Source Type: research

EZH2 inhibitory protein (EZHIP/Cxorf67) expression correlates strongly with H3K27me3 loss in posterior fossa ependymomas and is mutually exclusive with H3K27M mutations
AbstractThe PFA molecular subgroup of posterior fossa ependymomas (PF-EPNs) shows poor outcome. H3K27me3 (me3) loss by immunohistochemistry (IHC) is a surrogate marker for PFA wherein its loss is attributed to overexpression of Cxorf67/EZH2 inhibitory protein (EZHIP), C17orf96, and ATRX loss. We aimed to subgroup PF-EPNs using me3 IHC and study correlations of the molecular subgroups  with other histone related proteins, 1q gain, Tenascin C and outcome. IHC for me3, acetyl-H3K27, H3K27M, ATRX, EZH2, EZHIP, C17orf96, Tenascin-C, and fluorescence in-situ hybridisation for chromosome 1q25 locus were performed on an ...
Source: Brain Tumor Pathology - November 1, 2020 Category: Neurology Source Type: research

Genetic characterization of an aggressive optic nerve pilocytic glioma
AbstractOptic nerve glioma (ONG) is a rare, typically slow-growing WHO I grade tumor that affects the visual pathways. ONG is most commonly seen in the pediatric population, in association with neurofibromatosis type 1 syndrome. However, sporadic adult cases may also occur and may clinically behave more aggressively, despite benign histopathology. Genetic characterization of these tumors, particularly in the adult population, is lacking. A 39-year-old female presented with 1 month of progressive left-sided visual loss secondary to a enhancing mass along the left optic nerve sheath. Initial empiric management with focal rad...
Source: Brain Tumor Pathology - October 24, 2020 Category: Neurology Source Type: research

Clinicopathologic significance of MYD88 L265P mutation and expression of TLR4 and P-STAT3 in primary central nervous system diffuse large B-cell lymphomas
AbstractPatients with primary central nervous system lymphoma (PCNSL) have a prognosis poorer than that of systemic lymphoma patients. In patients with this condition, TLR4/STAT3 pathway alterations and the MYD88 L265P mutation may be viable targets for therapeutic intervention. The present study was, therefore, designed to identify clinicopathologic correlates of MYD88 mutations and TLR4/STAT3 pathway alterations in PCNSL. We detected TLR4 and p-STAT3 in 41.5% (22/53) and 43.4% (23/53) of PCNSL patients, respectively, while 60.4% of these patients (32/53) were found to harbor the MYD88 L265P mutation. TLR4 expression was ...
Source: Brain Tumor Pathology - October 20, 2020 Category: Neurology Source Type: research

Masked malignant phenotype with a benign appearance: beat-up copy number profile may be the key for hemangioblastoma dissemination
AbstractDissemination of histologically benign hemangioblastoma is rare; approximately 30 cases have previously been reported, and all cases occurred several months to years after surgical resection. Herein, we report a case of hemangioblastoma in which leptomeningeal dissemination occurred 2  years after hypofractionated radiation therapy (39 Gy/13 fractions). The tumor was treated primarily with radiation without surgical resection. Biopsy of the disseminated lesion confirmed histological diagnosis as histologically benign hemangioblastoma. Ki67 index was not remarkably elevated for hemangioblastomas. In additi...
Source: Brain Tumor Pathology - October 18, 2020 Category: Neurology Source Type: research

Masked malignant phenotype with a benign appearance beat-up copy number profile may be the key for hemangioblastoma dissemination
AbstractDissemination of histologically benign hemangioblastoma is rare; approximately 30 cases have previously been reported, and all cases occurred several months to years after surgical resection. Herein, we report a case of hemangioblastoma in which leptomeningeal dissemination occurred 2  years after hypofractionated radiation therapy (39 Gy/13 fractions). The tumor was treated primarily with radiation without surgical resection. Biopsy of the disseminated lesion confirmed histological diagnosis as histologically benign hemangioblastoma. Ki67 index was not remarkably elevated for hemangioblastomas. In additi...
Source: Brain Tumor Pathology - October 18, 2020 Category: Neurology Source Type: research

Methylation profiling-based diagnosis of radiologically suspected congenital glioma
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - October 16, 2020 Category: Neurology Source Type: research

H3 G34-mutant high-grade glioma
In conclusion,H3.3 G34-mutant gliomas were unique HGGs with uniform genetic and epigenetic abnormalities, which suggested a single phylogenic origin. The median survival ofH3.3 G34-mutant HGGs was better than those ofIDH-wildtype GBMs andH3 K27M-mutant DMGs, but worse than that ofIDH-mutant GBM. The tumor-infiltrating area and resectability may be the crucial parameters for the prognosis of the patients. (Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - September 28, 2020 Category: Neurology Source Type: research

Reduced H3K27me3 levels in diffuse gliomas: association with 1p/19q codeletion and difference from H3K27me3 loss in malignant peripheral nerve sheath tumors
AbstractTrimethylation of histone H3 at lysine 27 (H3K27me3) acts as a transcriptional repressor of target genes. Recent immunohistochemical studies have reported a loss of H3K27me3 modification in diffuse (especially 1p/19q-codeleted) gliomas. However, we did not observe H3K27me3 loss in diffuse gliomas using routine immunostaining conditions for the detection of H3K27me3 loss in malignant peripheral nerve sheath tumors (MPNSTs). Therefore, we conducted immunohistochemical analysis of surgically resected specimens to understand the differences in the H3K27me3 status in MPNSTs and diffuse gliomas and evaluate the diagnosti...
Source: Brain Tumor Pathology - September 27, 2020 Category: Neurology Source Type: research

Central nervous system high grade neuroepithelial tumor with BCOR immunopositivity: Is there a molecular heterogeneity?
We describe four cases of high grade neuroepithelial tumor with BCOR immunopositivity which were diagnosed over a period of one year at our institute. Amongst these, only one tumor revealed BCOR-ITD on sequencing. SATB2 immunopositivity which is a sensitive marker of BCOR-ITD, BCOR fusions and YWHAE fusions was noted in three out of four cases. Our study suggests that BCOR immunopositive CNS high grade tumors are molecularly heterogeneous and could harbour genetic alterations other than BCOR-ITD (Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - September 26, 2020 Category: Neurology Source Type: research

Frequency of mismatch repair protein deficiency and PD-L1 in high-grade gliomas in adolescents and young adults (AYA)
AbstractCentral nervous system tumors in adolescents and young adults (AYA) are rarely reported in the literature. The association with cancer predisposition syndrome is not established. Programmed death ligand 1 (PD-L1) can predict the potential response of patients to immunotherapy. A link between mismatch repair protein deficiency (MMRP-D) and response to immunotherapy is established. P53 is reported to be positive in MMRD-D cases. We aim to investigate the frequency of MMRP-D in AYA with high-grade glioma and any potential association with PD-L1. A total of 96 cases were tested including 49 (51.0%) cases of glioblastom...
Source: Brain Tumor Pathology - September 7, 2020 Category: Neurology Source Type: research

Reviewers in 2020
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - September 2, 2020 Category: Neurology Source Type: research

Glioblastomas harboring gene fusions detected by next-generation sequencing
AbstractOncogenic gene fusions have been reported in diffuse gliomas and may serve as potential therapeutic targets. Here, using next-generation sequencing analysis (Illumina TruSight Tumor 170 panel), we analyzed a total of 356 diffuse gliomas collected from 2017 to 2019 to evaluate clinical, pathological, and genetic features of gene fusion. We found 53 cases of glioblastomas harboring the following oncogenic gene fusions:MET (n = 18),EGFR (n = 14),FGFR (n = 12),NTRK (n = 5),RET (n = 2),AKT3 (n = 1), andPDGFRA fusions (n = 1...
Source: Brain Tumor Pathology - August 5, 2020 Category: Neurology Source Type: research

RELA fusion-positive ependymoma accompanied by extensive desmoplasia: a case report
We report a case of 33-year-old Japanese male who presented with a headache and visual disturbances. Magnetic resonance imaging revealed a large tumor in the left frontal lobe, measuring 7  cm in diameter, which was diagnosed as supratentorial anaplastic ependymoma accompanied by extensive desmoplasia. The patient underwent a gross total resection. Histologically, the tumor cells had oval or short, spindle-shaped nuclei, and proliferating cells in perivascular pseudorosettes with anu cleate zones and mitotic figures. Desmoplasia with abundant collagen fibers among the tumor cells was detected at numerous sites, and pe...
Source: Brain Tumor Pathology - August 3, 2020 Category: Neurology Source Type: research