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Invasion of brain tissue by meningiomas has been identified as one key factor for meningioma recurrence. The identification of meningioma tumor tissue surrounded by brain tissue in neurosurgical samples has been touted as a criterion for atypical meningioma (CNS WHO grade 2), but is only rarely seen in the absence of other high‐grade features, with brain‐invasive otherwise benign (BIOB) meningiomas remaining controversial. While post‐surgery irradiation therapy might be initiated in brain‐invasive meningiomas to prevent recurrences, specific treatment approaches targeting key molecules involved in the invasive process are not established. Here we have compiled the current knowledge about mechanisms supporting brain tissue invasion by meningiomas and summarize preclinical models studying targeted therapies with potential inhibitory effects. [ABSTRACT FROM AUTHOR]

Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) gliosarcomas, but not in glial areas ( P < 0.0001). Nuclear Twist expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) gliosarcomas, but glial tumor areas were largely negative except in four cases ( P < 0.0001). Expression of MMP-2 and MMP-9 was also significantly more extensive in mesenchymal than in glial tumor areas. None of 20 ordinary glioblastomas showed Slug or Twist expression in >10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in gliosarcomas. [ABSTRACT FROM AUTHOR]

Abstract: Amyloidomas are rare amyloid‐containing lesions, which may also occur in the central nervous system. Etiology, pathogenesis and clinical course are poorly understood. To gain more insight into the biology of cerebral amyloidoma, they aimed to characterize its histopathological, molecular and clinical features in a retrospective series of seven patients. FFPE tissue specimens were examined using immunohistochemistry, chromogenic in situ hybridization (CISH) for light chains kappa and lambda as well as an IgH gene clonality analysis. Follow‐up information was gathered by reviewing patient records and imaging results. Median age of the three males and four females was 50 years (range: 35–53 years). All cerebral amyloidomas were located supratentorially and were classified as lambda light chain amyloidosis (AL‐λ; n = 6) and kappa light chain amyloidosis (AL‐κ; n = 1) on immunohistochemistry and CISH. B‐cell clonality was confirmed by IgH gene clonality assay in all cases examined. After a median follow‐up of 21 months, all patients were alive and showed stable disease. No progression to systemic disease was observed. In conclusion, their data suggest that cerebral amyloidoma is a local disease characterized by B‐cell clonality and associated with a stable clinical course. [ABSTRACT FROM AUTHOR]

Glioblastoma may develop rapidly without evidence for precursor lesions (primary glioblastomas), or progress from diffuse or anaplastic astrocytomas (secondary glioblastomas). Despite having distinct genetic profiles, these glioblastoma subtypes have similar histological features. We hypothesized that the highly malignant phenotype of glioblastoma may be attributable to genetic alterations that are common to both glioblastoma subtypes. In the present study, we first searched for commonly (>35%) amplified genes in glioblastomas with IDH1 mutation (a hallmark of secondary glioblastoma) and those without IDH1 mutation (typical for primary glioblastoma) in data from The Cancer Genome Atlas ( TCGA). A total of 25 genes were identified, of which 21 were located at 7q31-34. We then screened 264 gliomas (70 glioblastomas, 112 diffuse astrocytomas, 82 oligodendrogliomas) for gain of the MET at 7q31.2 with quantitative polymerase chain reaction ( PCR). MET gain was detected in primary glioblastomas (47%) and secondary glioblastomas (44%), suggesting that this genetic alteration plays a role in the pathogenesis of both glioblastoma subtypes. MET gain was also common in diffuse astrocytomas (38%), but less frequent in oligodendrogliomas (16%). MET gain in diffuse astrocytomas was associated with shorter survival (median, 43.0 vs. 70.7 months; P = 0.004), suggesting that MET gain is a useful prognostic marker for diffuse astrocytomas. [ABSTRACT FROM AUTHOR]

Chromosomal 7q34 duplication and BRAF-KIAA1549 fusion is a characteristic genetic alteration in pilocytic astrocytomas. 7q34 gain appears to be common in diffuse astrocytomas, but its significance is unclear. We assessed BRAF gain and BRAF mutations in 123 low-grade diffuse gliomas, including 55 diffuse astrocytomas, 18 oligoastrocytomas and 50 oligodendrogliomas. Quantitative polymerase chain reaction (PCR) revealed BRAF gain in 17/50 (34%) oligodendrogliomas, a significantly higher frequency than in diffuse astrocytomas (7/55; 13%; P = 0.0112). BRAF gain was common in low-grade diffuse gliomas with 1p/19q loss (39%) and those lacking any of the genetic alterations analyzed (31%), but was rare in those with TP53 mutations (2%). Logistic regression analysis showed a significant positive association between 1p/19q loss and BRAF gain ( P = 0.0032) and a significant negative association between TP53 mutations and BRAF gain ( P = 0.0042). Fluorescence in situ hybridization (FISH) analysis of 26 low-grade diffuse gliomas with BRAF gain additionally revealed BRAF-KIAA1549 fusion in one oligodendroglioma. Sequencing of cDNA in 17 low-grade diffuse gliomas showed BRAF-KIAA1549 fusion in another oligodendroglioma. A BRAFV600E mutation was also detected in one oligodendroglioma, and a BRAFA598V in one diffuse astrocytoma. These results suggest that low-grade diffuse gliomas with 1p/19q loss have frequent BRAF gains, and a small fraction of oligodendrogliomas may show BRAF-KIAA1549 fusion. [ABSTRACT FROM AUTHOR]

We recently reported that the vast majority (>90%) of low-grade diffuse gliomas (diffuse astrocytoma, oligoastrocytoma and oligodendroglioma) carry at least one of the following genetic alterations: IDH1/2 mutation, TP53 mutation or 1p/19q loss. Only 7% of cases were triple-negative (ie, lacking any of these alterations). In the present study, array comparative genomic hybridization (CGH) in 15 triple-negative WHO grade II gliomas (eight diffuse astrocytomas and seven oligodendrogliomas) showed loss at 9p21 ( p14ARF, p15INK4b, p16INK4a loci) and 13q14-13q32 (containing the RB1 locus) in three and two cases, respectively. Further analyses in 31 triple-negative cases as well as a total of 160 non-triple-negative cases revealed that alterations in the RB1 pathway (homozygous deletion and promoter methylation of the p15INK4b, p16INK4a and RB1 genes) were significantly more frequent in triple-negative (26%) than in non-triple-negative cases (11%; P = 0.0371). Multivariate analysis after adjustment for age, histology and treatment showed that RB1 pathway alterations were significantly associated with unfavorable outcome for patients with low-grade diffuse glioma [hazard ratio, 3.024 (1.279-6.631); P = 0.0057]. These results suggest that a fraction of low-grade diffuse gliomas lacking common genetic alterations may develop through a distinct genetic pathway, which may include loss of cell-cycle control regulated by the RB1 pathway. [ABSTRACT FROM AUTHOR]