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

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

Highly sensitive detection of TERT promoter mutations in recurrent glioblastomas using digital PCR
AbstractTelomerase reverse transcriptase promoter (TERTp) hotspot mutations are the most frequent mutations in primary glioblastomas (GBM). Previous studies have shown that the combination ofTERTp and isocitrate dehydrogenase (IDH) status may serve as a useful diagnostic marker for oligodendroglioma and glioblastoma. In oligodendrogliomas,TERTp andIDH mutations, along with the 1p/19q codeletion, usually coexist and are likely to be founder mutations. However, in contrast to oligodendroglioma, the role of theTERTp status in GBM remains obscure. Here, we used Sanger sequencing, pyrosequencing, and digital PCR (dPCR) to exami...
Source: Brain Tumor Pathology - August 3, 2020 Category: Neurology Source Type: research

A dedifferentiated intracranial solitary fibrous tumor with osteosarcoma components: rapid tumor progression and lethal clinical course
AbstractSolitary fibrous tumor/hemangiopericytoma is a mesenchymal tumor that originates from a commonNAB2 –STAT6 fusion gene and is known to very rarely demonstrate dedifferentiation in the pattern of local recurrence or distant metastasis. Here we describe for the first time a rare case of intracranial dedifferentiated solitary fibrous tumor/hemangiopericytoma with osteosarcoma components that developed in an 84-year-old man after frequent gamma knife radiosurgery over a 14-year period. We performed tumor-debulking and gamma knife radiosurgery, but unfortunately the patient died shortly after the development of ded...
Source: Brain Tumor Pathology - August 1, 2020 Category: Neurology Source Type: research

Primary central nervous system lymphomas associated with chronic inflammation: diagnostic pitfalls of central nervous system lymphomas
AbstractIn recent years, the features of lymphomas associated with chronic inflammation, referred to as diffuse large B-cell lymphoma (DLBCL) associated with chronic inflammation (DLBCL-CI), have been elucidated. DLBCL-CI is an aggressive lymphoma occurring in the context of long-standing chronic inflammation and showing an association with Epstein –Barr virus. Fibrin-associated diffuse large B-cell lymphoma (F-DLBCL) was suggested as a new and unusual form of DLBCL-CI in the most recent version of the World Health Organization classification. From the perspective of genetics, DLBCL-CI was associated with frequentTP5...
Source: Brain Tumor Pathology - July 4, 2020 Category: Neurology Source Type: research

Central nervous system neuroepithelial tumors with MN1 -alteration: an individual patient data meta-analysis of 73 cases
AbstractMN1 alteration characterizes a recently described group of neuroepithelial tumors with varied morphological features. In cIMPACT-NOW update 6, only those with astroblastoma morphology has been accepted as a newly recognized tumor type, whereas the rest of morphological variants are considered lesions sub-judice. We perform an individual patient data meta-analysis ofMN1-altered neuroepithelial tumors comprising a total of 73 cases, in order to study the survival data and predictive markers for better diagnosis and management of this rare molecular entity. The 5- and 10-year progression-free survival are 38% and 0%, ...
Source: Brain Tumor Pathology - June 28, 2020 Category: Neurology Source Type: research

Central nervous system ganglioneuroblastoma harboring MYO5A-NTRK3 fusion
AbstractCentral nervous system (CNS) ganglioneuroblastoma is a rare neuroectodermal neoplasm and little is known about its clinical and biological features. Herein, we report a pediatric case of CNS ganglioneuroblastoma harboringMYO5A-NTRK3 fusion. The patient, a 4-year-old boy, underwent a partial resection of a supratentorial tumor that was histopathologically diagnosed as a CNS ganglioneuroblastoma. Treatment with radiotherapy was started per the St Jude Medulloblastoma 03 (SJMB03) protocol; however, the tumor progressed rapidly and radiotherapy was temporally discontinued. Meanwhile, the patient underwent a second surg...
Source: Brain Tumor Pathology - June 17, 2020 Category: Neurology Source Type: research

Central nervous system neuroblastic tumor with FOXR2 activation presenting both neuronal and glial differentiation: a case report
AbstractA subset of central nervous system neuroblastomas (CNS NB), rare primary embryonal CNS tumors, has been encompassed in CNS NB withFOXR2 activation (CNS NB-FOXR2) and usually shows the primitive neuronal architecture and occasional neurocytic differentiation. Here, we report a rare case of 3-year-old female with uncommon morphology of CNS embryonal tumor withFOXR2 activation presenting bidirectional differentiation to neurocytic small primitive cells and astrocytic spindle cells both of which are positive for synaptophysin and GFAP. Ultrastructural study also showed that there were presynaptic structure and intermed...
Source: Brain Tumor Pathology - June 12, 2020 Category: Neurology Source Type: research

Prognostic role of H3K27M mutation, histone H3K27 methylation status, and EZH2 expression in diffuse spinal cord gliomas
The objective of this study is to clarify clinical significance of theH3F3A K27M mutation (H3K27M) and analyze the correlation between H3K27M, H3K27me3 status, and EZH2 expression and prognosis in spinal cord gliomas. Patients with spinal cord diffuse glioma regardless of World Health Organization (WHO) grade underwent genetic analysis forH3F3A, HIST1H3B,TERT promoter,IDH1/2, andBRAF. H3K27me3 status and EZH2 expression were analyzed through immunohistochemistry. Thereafter, the association between H3K27M, H3K27me3 status, and EZH2 expression and prognosis was retrospectively analyzed using the log-rank test. A total of 26...
Source: Brain Tumor Pathology - June 10, 2020 Category: Neurology Source Type: research

A rare case of oligodendroglioma with gangliocytic differentiation in a 31-year-old male: importance of genetic testing for IDH1/2
We report a rare case of oligodendroglioma with gangliocytic differentiation. A 31-year-old male without a past medical history was admitted with a sudden seizure. On magnetic resonance imaging, an approximately 7-cm mass with necrosis was noted in the right frontal lobe. The patient underwent surgical resection. On microscopy, two morphologically distinct areas with oligodendroglioma- and ganglioglioma-like features were found. Immunohistochemistry showed an absence of CD34 expression, whereas isocitrate dehydrogenase 1 (IDH1) was positive in the glial component. Moreover, IDH1 was positive in the ganglion-like cells as w...
Source: Brain Tumor Pathology - June 4, 2020 Category: Neurology Source Type: research

Intravascular carcinomatosis of the brain: a report of two cases
We report two cases of brain metastasis in which tumor cells were restricted to the vascular lumina without parenchymal involvement, resulting in ischemic lesions. The first patient is a previously healthy young woman who presented with symptoms of community-acquired pneumonia and progressed to respiratory failure. Computed tomography of the brain showed infarcts of differing ages. At autopsy, she was found to have widely metastatic cervical squamous cell carcinoma and cerebral tumor emboli with multifocal infarcts, mainly microinfarcts. The second patient is an elderly man with cognitive impairment and mild Parkinsonism w...
Source: Brain Tumor Pathology - May 31, 2020 Category: Neurology Source Type: research

Diffuse midline glioma of the cervical spinal cord with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma: a case report and review of the literature
AbstractHere, we report on a 28-year old male patient presenting with neck and shoulder pain, dysesthesia of all four limbs and hypesthesia of both hands, without motor deficits. Magnetic resonance imaging showed an intradural, intramedullary mass of the cervical spinal cord of 6.4  cm length and 1.7 cm diameter. The patient underwent surgical resection. Histological and immunohistochemical evaluation showed pleomorphic glial tumor cells, mitoses, calcifications, and atypical ganglioid cells compatible with the morphology of anaplastic ganglioglioma (WHO Grade III). Extensiv e molecular workup revealedH3F3A K27M,...
Source: Brain Tumor Pathology - May 24, 2020 Category: Neurology Source Type: research

Primary spinal intramedullary Ewing-like sarcoma harboring CIC - DUX4 translocation: a similar cytological appearance as its soft tissue counterpart but no lobulation in association with desmoplastic stroma
We report a rare case of primary spinal intramedullary Ewing-like sarcoma harboringCIC-DUX4 translocation. A 23-year-old man presented with weakness in the extremities. Magnetic resonance imaging revealed a large intramedullary tumor spanning C3 –C5 with heterogeneous enhancement following gadolinium administration. Histologically, most of the tumor displayed dense myeloid proliferation composed of medium- to slightly small-sized primitive cells. Postoperatively, he received local adjuvant radiation therapy without tumor progression for 1 0 months. Target RNA sequencing analysis revealed theCIC-DUX4 fusion gene....
Source: Brain Tumor Pathology - May 23, 2020 Category: Neurology Source Type: research

Placental alkaline phosphatase in cerebrospinal fluid as a biomarker for optimizing surgical treatment strategies for pineal region germ cell tumors
AbstractPineal region germ cell tumors are a heterogenous group of tumors; of these, pure germinoma shows high sensitivity to adjuvant therapy, and the timing and sequence of surgical intervention and adjuvant/neoadjuvant therapy are important for devising a treatment strategy for intracranial germ cell tumors (IGCT). Biopsy is diagnostically useful, but is often insufficient because only a limited amount of specimen can be obtained. In the present study, we aimed to determine the value of cerebrospinal fluid placental alkaline phosphatase (PLAP) levels, reflecting the presence of germinoma, as a reliable indicator to dete...
Source: Brain Tumor Pathology - May 4, 2020 Category: Neurology Source Type: research

Molecular characteristics and clinical outcomes of elderly patients with IDH -wildtype glioblastomas: comparative study of older and younger cases in Kansai Network cohort
AbstractAging is a known negative prognostic factor in glioblastomas (GBM). Whether particular genetic backgrounds are a factor in poor outcomes of elderly patients with GBM warrants investigation. We aim to elucidate any differences between older and younger adult patients withIDH-wildtype GBM regarding both molecular characteristics and clinical outcomes. We collected adult cases diagnosed withIDH-wildtype GBM from the Kansai Network. Clinical and pathological characteristics were analyzed retrospectively and compared between older ( ≥ 70 years) and younger (≤ 50 years) cases. Included were ...
Source: Brain Tumor Pathology - May 1, 2020 Category: Neurology Source Type: research

Preface
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - April 27, 2020 Category: Neurology Source Type: research

Malignant transformation of a dysembryoplastic neuroepithelial tumor verified by a shared copy number gain of the tyrosine kinase domain of FGFR1
AbstractDysembryoplastic neuroepithelial tumors (DNTs) are regarded as benign glioneuronal neoplasms because of their excellent outcomes; however, rare DNTs show malignant transformation. We herein described a case of DNT showing malignant transformation. The patient had intractable epilepsy caused by a tumor at 1  year of age and partial resection was performed. After surgery, the residual tumor showed regrowth and surgery was performed again at 4 years of age. The resected tumor showed the typical histological features of DNT, such as specific glioneuronal elements and alveolar structures. Tumor regrowth was de...
Source: Brain Tumor Pathology - April 14, 2020 Category: Neurology Source Type: research

Correlation between IDH , ATRX , and TERT promoter mutations in glioma
This study analyzedIDH,ATRX, andTERT promoter mutations, and the correlation between them. Immortalized cells overcome the telomere-related crisis by activating telomerase or ALT. In glioma, telomerase is mainly activated byTERT promoter mutation, while ALT is usually associated withATRX mutation. Although the mechanism of howATRX mutation induces ALT remains unclear, ATRX loss alone is believed to be insufficient to induce ALT. Treatments targeting telomere maintenance are promising. (Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - March 28, 2020 Category: Neurology Source Type: research

Intracranial myxoid mesenchymal tumor with EWSR1 – CREB1 gene fusion: a case report and literature review
Abstract Intracranial myxoid mesenchymal tumors harboringEWSR1 fusions withCREB transcriptional factor gene families were recently described in several case reports and a few case series and this tumor closely resembles the myxoid variant of angiomatoid fibrous histiocytoma. We herein present an intracranial mesenchymal myxoid tumor arising in the third ventricle of a middle-aged woman. The tumor displayed prominent myxoid features consisting of mildly atypical oval to round cells, arranged in reticular and cord-like structures, with starburst-like amianthoid fibers, whereas it lacked pseudoangiomatoid spaces, pseudocaps...
Source: Brain Tumor Pathology - March 24, 2020 Category: Neurology Source Type: research

Updating the grading criteria for adult diffuse gliomas: beyond the WHO2016CNS classification
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - February 13, 2020 Category: Neurology Source Type: research

Infiltration of CD163-positive macrophages in glioma tissues after treatment with anti-PD-L1 antibody and role of PI3K γ inhibitor as a combination therapy with anti-PD-L1 antibody in in vivo model using temozolomide-resistant murine glioma-initiating cells
AbstractAlthough chemoimmunotherapy often lengthens glioblastoma (GBM) survival, early relapses remain problematic as immunosuppressive M2 macrophages (M ϕ) that function via inhibitory cytokine and PD-L1 production cause immunotherapy resistance. Here, we detail anti-PD-L1 antibody effects on the tumor microenvironment, including Mϕ infiltration, using a temozolomide (TMZ)-treated glioma model. In addition, we tested combinations of anti-PD-L1 ant ibody and the M2Mϕ inhibitor IPI-549 on tumor growth. We simulated late TMZ treatment or relapse stage, persistent GBM cells by generating TMZ-resistant TS (TMZRTS) cells. M2...
Source: Brain Tumor Pathology - January 23, 2020 Category: Neurology Source Type: research

Cells with ganglionic differentiation frequently stain for VE1 antibody: a potential pitfall
AbstractMitogen-activated protein kinase (MAPK) pathway plays a major role in pediatric low-grade gliomas (pLGGs). Immunohistochemistry with mutant-specific antibody, VE1, has appeared to be the most affordable and rapidly deployable method to identify tumors with aberrant MAPK signaling pathway, by highlighting tumor withBRAFV600E mutation. Nonetheless, positive staining cases but not associated withBRAFV600E mutation are also seen. We analyzed 62 pLGGs for the two commonest genetic aberrations in MAPK pathway:KIAA1549-BRAF fusion, using reverse-transcriptase polymerase chain reaction, andBRAFV600E mutation, using VE1 ant...
Source: Brain Tumor Pathology - December 8, 2019 Category: Neurology Source Type: research

Giant cell glioblastoma is a distinctive subtype of glioma characterized by vulnerability to DNA damage
AbstractGiant cell glioblastoma (GC-GBM) consists of large cells with pleomorphic nuclei. As a contrast to GC-GBM, we defined monotonous small GBM (MS-GBM) as GBM that consists of small cells with monotonous small nuclei, and compared the DNA damage as well as other pathological features. GC-GBM showed minimal invasion (
Source: Brain Tumor Pathology - October 25, 2019 Category: Neurology Source Type: research

Ventricle-predominant primary CNS lymphomas: clinical, radiological and pathological evaluation of five cases and review of the literature
AbstractPrimary central nervous system lymphomas (PCNSLs) are typically intraparenchymal. A subset of PCNSLs predominantly arises in the ventricles, with minimal parenchymal involvement. We review the clinical, radiological, and pathological features of ventricle-predominant PCNSLs (VP-PCNSLs) in 40 previously reported cases and report 5 additional cases. Including all cases of VP-PCNSLs (n = 45), 38% were diffuse large B-cell lymphomas (DLBCL), 11% were Burkitt lymphomas, 7% were MALT lymphomas, 4% were T-cell lymphomas, and 40% were lymphomas, not otherwise classified. VP-PCNSLs show rapid clinical progress...
Source: Brain Tumor Pathology - October 18, 2019 Category: Neurology Source Type: research

Reviewers in 2019
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - September 11, 2019 Category: Neurology Source Type: research

Two cases of primary supratentorial intracranial rhabdomyosarcoma with DICER1 mutation which may belong to a “spindle cell sarcoma with rhabdomyosarcoma-like feature, DICER1 mutant”
AbstractRhabdomyosarcoma is the most common soft-tissue sarcoma affecting children and adolescents. It is defined as a malignant neoplasm characterized by morphologic, immunohistochemical, ultrastructural, or molecular genetic evidence of primary skeletal muscle differentiation, usually in the absence of any other pattern of differentiation. Primary intracranial rhabdomyosarcoma (PIRMS) is an extremely rare neoplasm, with only 60 cases reported in the literature, and generally has poor prognosis with an overall survival of only 9.1  months. TheDICER1 gene encodes an RNA endoribonuclease that plays a key role in gene e...
Source: Brain Tumor Pathology - September 4, 2019 Category: Neurology Source Type: research

First autopsy analysis of the efficacy of intra-operative additional photodynamic therapy for patients with glioblastoma
AbstractThe study aim to demonstrate the therapeutic tissue depth of photodynamic therapy (PDT) using the photosensitizer talaporfin sodium and semiconductor laser for malignant glioma from an autopsy finding. Three patients diagnosed with glioblastoma by pre-operative imaging (1 newly diagnosed patient and 2 patients with recurrence) were treated with intra-operative additional PDT and adjuvant therapy such as post-operative radiotherapy or chemotherapy. All three patients died of brain stem dysfunction owing to cerebrospinal fluid dissemination or direct invasion of the tumor cells from 13, 18, or 20  months after P...
Source: Brain Tumor Pathology - September 4, 2019 Category: Neurology Source Type: research

Clinicopathological evaluation of PD-L1 expression and cytotoxic T-lymphocyte infiltrates across intracranial molecular subgroups of ependymomas: are these tumors potential candidates for immune check-point blockade?
AbstractImmune check-point blockade (ICB) targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has created paradigm shift in cancer treatment. ‘ST-RELA’ and ‘PF-A’ molecular subgroups of ependymomas (EPN) show poor outcomes. We aimed to understand the potential candidature of EPNs for ICB. Supratentorial (ST) Grade II/III EPNs were classified into ST-RELA, ST-YAP, and ST-not otherwise specified (NOS), based onRELA/YAP1 fusion transcripts and/or L1CAM and p65 protein expression. Posterior fossa (PF) EPNs were classified into PF-A and PF-B based on H3K27me3 expression. Immun...
Source: Brain Tumor Pathology - August 5, 2019 Category: Neurology Source Type: research

Anaplastic pleomorphic xanthoastrocytoma associated with an H3G34 mutation: a case report with review of literature
AbstractHere, we report a rare case of anaplastic pleomorphic xanthoastrocytoma (PXA) associated with an H3G34 mutation. A 12-year-old male presented with loss of appetite, vomiting, headache, and a generalized seizure, and CT revealed a 9.0  cm left frontal lobe mass with some septal walls and a localized high-density area suggestive of hemorrhage or calcification, causing severe midline shift. He emergently underwent subtotal resection and the tumor was morphologically diagnosed as anaplastic PXA. DNA sequencing identified an H3F3A G 34R mutation and a TP53 R273H mutation, and immunohistochemically, ATRX nuclear exp...
Source: Brain Tumor Pathology - July 25, 2019 Category: Neurology Source Type: research

Clinical, histopathological, and molecular analyses of IDH -wild-type WHO grade II –III gliomas to establish genetic predictors of poor prognosis
This study analyzed the genetic and other features ofIDH-wt LGGs to develop a subclassification that can be used to predict their prognosis. Clinical, histopathological, and genetic features of 35 cases of diffuseIDH-wt astrocytoma andIDH-wt anaplastic astrocytoma were analyzed. The following genetic factors were examined: mutations ofB-rapidly accelerated fibrosarcoma,telomerase reverse transcriptase promoter (TERTp),histone 3 family 3A, andalpha-thalassemia/mental retardation syndrome,X-linked; and copy number aberrations. In the univariate analysis, the following factors were associated with poor overall survival (OS): ...
Source: Brain Tumor Pathology - July 18, 2019 Category: Neurology Source Type: research

A long-term survivor of pediatric midline glioma with H3F3A K27M and BRAF V600E double mutations
We report a case of 2-year-old female with lateral ventricular glioma harboring bothH3F3A K27M andBRAF V600E mutations. By the methylation analysis, the tumor was classified as a diffuse midline glioma H3 K27M mutant, WHO grade IV. However, the tumor was pathologically low-grade and likely localized rather than diffusely infiltrating. Further, the patient has survived more than 8  years after gross total resection of the tumor. Whereas bothH3F3A K27M andBRAF V600E have been reported as poor prognostic markers in pediatric glioma, our case, along with several other reported cases, suggests that the coexistence of these...
Source: Brain Tumor Pathology - June 27, 2019 Category: Neurology Source Type: research

MN1 rearrangement in astroblastoma: study of eight cases and review of literature
AbstractAstroblastomas are unique tumours with unresolved issues in terms of their origin, molecular biology, clinical behaviour, and response to treatment. To decipher the characteristics of this tumour, we reviewed cases histologically diagnosed as astroblastoma in our institute over the past 8  years, with immunohistochemistry, and performed fluorescence in situ hybridisation (FISH), for the newly emergedMN1 rearrangement which was reported in central nervous system high-grade neuroepithelial tumours. The mean age at diagnosis was 18.6  years with all cases seen in females and with supratentorial localisation....
Source: Brain Tumor Pathology - May 19, 2019 Category: Neurology Source Type: research

High-grade glioneuronal tumor with an ARHGEF2 – NTRK1 fusion gene
AbstractHere, we report a highly unusual case of high-grade glioneuronal tumor with aneurotrophic tropomyosin receptor kinase (NTRK) fusion gene. A 13-year-old girl presented with headache and vomiting and MRI detected two cystic lesions bilaterally in the frontal areas with surrounding edema. The left larger tumor was removed by left frontal craniotomy. The tumor was diagnosed as a high-grade glioneuronal tumor, unclassified. Methylation profiling classified it as a diffuse leptomeningeal glioneuronal tumor (DLGNT) with low confidence. This tumor showed genotypes frequently found in DLGNT such as 1p/19q codeletion without...
Source: Brain Tumor Pathology - April 21, 2019 Category: Neurology Source Type: research

Clinicopathological characteristics of circumscribed high-grade astrocytomas with an unusual combination of BRAF V600E, ATRX , and CDKN2A/B alternations
We report four cases of high-grade astrocytoma with aBRAF V600E mutation,ATRX inactivation, andCDKN2A/B homozygous deletion. Children to young adults aged 3 –46 presented with a well demarcated contrast-enhancing mass in the supratentorial area. Pathological examination revealed packed growth of short spindle to round polygonal cells including some pleomorphic cells. The tumors had less ability to infiltrate into the adjacent brain parenchyma and pres ented a circumscribed growth pattern. Mitosis was readily found, accompanied by focal necrosis and/or microvascular proliferation. Tumors were histologically similar in...
Source: Brain Tumor Pathology - April 9, 2019 Category: Neurology Source Type: research

Novel concept of the border niche: glioblastoma cells use oligodendrocytes progenitor cells (GAOs) and microglia to acquire stem cell-like features
AbstractGlioblastoma (GBM) is a major malignant brain tumor developing in adult brain white matter, characterized by rapid growth and invasion. GBM cells spread into the contralateral hemisphere, even during early tumor development. However, after complete resection of tumor mass, GBM commonly recurs around the tumor removal cavity, suggesting that a microenvironment at the tumor border provides chemo-radioresistance to GBM cells. Thus, clarification of the tumor border microenvironment is critical for improving prognosis in GBM patients. MicroRNA (miRNA) expression in samples from the tumor, tumor border, and peripheral r...
Source: Brain Tumor Pathology - April 8, 2019 Category: Neurology Source Type: research

Preface
(Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - April 7, 2019 Category: Neurology Source Type: research

Pilomyxoid astrocytomas: a short review
AbstractPilomyxoid astrocytoma is a variant of pilocytic astrocytoma and the clinical, histological and molecular data point to a very close relationship as well as a more aggressive biological behavior for the former. WHO 2016 classification does not provide a specific grade for these neoplasms, but there is sufficient evidence in the literature that pilomyxoid astrocytoma has slightly worse prognosis than typical pilocytic astrocytoma. There is increasing evidence that in addition to the MAPK pathway alterations, pilomyxoid astrocytomas harbor genetic alterations that distinguish them from typical pilocytic astrocytoma (...
Source: Brain Tumor Pathology - April 2, 2019 Category: Neurology Source Type: research

Overview of DNA methylation in adult diffuse gliomas
AbstractAdult diffuse gliomas form a heterogeneous group of tumors of the central nervous system that vary greatly in histology and prognosis. A significant advance during the last decade has been the identification of a set of genetic lesions that correlate well with histology and clinical outcome in diffuse gliomas. Most characteristic driver mutations consist ofisocitrate dehydrogenase 1 (IDH1) andIDH2, andH3 histone family member 3A, which are strongly associated with DNA and histone methylation patterns. A well-characterized DNA methylation aberration is on the O6-methylguanine-DNA methyltransferase promoter. This abe...
Source: Brain Tumor Pathology - March 31, 2019 Category: Neurology Source Type: research

Molecular genetics and therapeutic targets of pediatric low-grade gliomas
AbstractPediatric low-grade gliomas (PLGGs) have relatively favorable prognosis and some resectable PLGGs, such as cerebellar pilocytic astrocytoma, can be cured by surgery alone. However, many PLGG cases are unresectable and some of them undergo tumor progression. Therefore, a multidisciplinary approach is necessary to treat PLGG patients. Recent genomic analysis revealed a broad genomic landscape underlying PLGG. Notably, the majority of PLGGs present MAPK pathway-associated genomic alterations and MAPK signaling-dependent tumor progression. Following preclinical evidence, many clinical trials based on molecular target t...
Source: Brain Tumor Pathology - March 29, 2019 Category: Neurology Source Type: research

Review of ependymomas: assessment of consensus in pathological diagnosis and correlations with genetic profiles and outcome
This study indicated that the expert consensus pathological diagnosis could correlate well with the molecular classifications in EPNs. ST EPNs should be diagnosed more carefully by histological and molecular analyses. (Source: Brain Tumor Pathology)
Source: Brain Tumor Pathology - March 29, 2019 Category: Neurology Source Type: research

The emerging clinical potential of circulating extracellular vesicles for non-invasive glioma diagnosis and disease monitoring
AbstractDiffuse gliomas (grades II –IV) are amongst the most frequent and devastating primary brain tumours of adults. Currently, patients are monitored by clinical examination and radiographic imaging, which can be challenging to interpret and insensitive to early signs of treatment failure and tumour relapse. While brain biopsy a nd histologic analysis can evaluate disease progression, serial biopsies are invasive and impractical given the cumulative surgical risk, and may not capture the complete molecular landscape of an evolving tumour. The availability of a minimally invasive ‘liquid biopsy’ that co...
Source: Brain Tumor Pathology - March 10, 2019 Category: Neurology Source Type: research

Pathologic and molecular aspects of anaplasia in circumscribed gliomas and glioneuronal tumors
AbstractMany breakthroughs have been made in the past decade regarding our knowledge of the biological basis of the diffuse gliomas, the most common primary central nervous system (CNS) tumors. These tumors as a group are aggressive, associated with high mortality, and have a predilection for adults. However, a subset of CNS glial and glioneuronal tumors are characterized by a more circumscribed pattern of growth and occur more commonly in children and young adults. They tend to be indolent, but our understanding of anaplastic changes in these tumors continues to improve as diagnostic classifications evolve in the era of m...
Source: Brain Tumor Pathology - March 10, 2019 Category: Neurology Source Type: research