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. Immunohistochemistry ...
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 express...
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 two...
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. The tum...
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 par...
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 could assess t...
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
