Meningioma Tumor Research Articles

Primary central nervous system lymphoma – Presenting as a posterior fossa extradural mass lesion: A rare entity and literature review

Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin's lymphoma (NHL) confined to the brain, leptomeninges, eyes, or spinal cord. Primary NHL of the cranium with extra- and intracranial extension without systemic or skeletal manifestation in an immunocompetent patient is extremely rare. The prognosis of PCNSL is inferior to that of other NHL subtype. We describe a case of 49-year-old woman presented with occipital headache for 1 month, without any deficits. Imaging showed extradural mass lesion in the posterior fossa based at the trocula with minimal inner bony table changes mimicking primary bony tumor, meningioma, lymphoproliferative disorder, or metastatic tumor. We operated upon this patient, and histopathology was suggestive of B-cell NHL. On further evaluation, there was no systemic involvement. The patient was planned for radiotherapy followed by six cycles of chemotherapy with rituximab and bendamustine. There are case reports of cranial vault lymphomas involving frontoparietal/temporal region. So far, no posterior fossa extradural lesion reported till now.

Diagnostic role of MUC4 immunohistochemical expression in various subtypes of meningioma

Background Meningiomas exhibit a wide range of histological appearances, and they may show overlapping morphology with other nonmeningothelial tumors, and so the differential diagnosis may be challenging.Aim To examine the diagnostic role of MUC4 expression in various histological subtypes and grades of meningioma and some other nonmeningothelial tumors relevant to the potential diagnosis.Materials and methods The expression of MUC4 and epithelial membrane antigen was analyzed by immunohistochemical staining in various subtypes of meningiomas and other nonmeningothelial tumors that enter in the differential diagnosis (schwannoma, solitary fibrous tumors/hemangiopericytoma, glioblastoma, and hemangioblastoma).Results A statistically significant difference was detected between MUC4 expression in meningioma and other nonmeningothelial tumors (P<0.001). MUC4 was expressed in 83.3% of meningioma cases and was entirely negative in nonmeningothelial tumors, with 83.3% sensitivity and 100% specificity.Conclusion MUC4 is a possible novel adjunct diagnostic marker that can distinguish between confusing cases of meningioma and the tested nonmeningothelial tumors.

Constitutive activation of the EGFR-STAT1 axis increases proliferation of meningioma tumor cells.

BackgroundMeningiomas are the most frequent primary brain tumors of the central nervous system. The standard of treatment is surgery and radiotherapy, but effective pharmacological options are not available yet. The well-characterized genetic background stratifies these tumors in several subgroups, thus increasing diversification. We identified epidermal growth factor receptor–signal transducer and activator of transcription 1 (EGFR–STAT1) overexpression and activation as a common identifier of these tumors.MethodsWe analyzed STAT1 overexpression and phosphorylation in 131 meningiomas of different grades and locations by utilizing several techniques, including Western blots, qPCR, and immunocytochemistry. We also silenced and overexpressed wild-type and mutant forms of the gene to assess its biological function and its network. Results were further validated by drug testing.ResultsSTAT1 was found widely overexpressed in meningioma but not in the corresponding healthy controls. The protein showed constitutive phosphorylation not dependent on the JAK–STAT pathway. STAT1 knockdown resulted in a significant reduction of cellular proliferation and deactivation of AKT and ERK1/2. STAT1 is known to be activated by EGFR, so we investigated the tyrosine kinase and found that EGFR was also constitutively phosphorylated in meningioma and was responsible for the aberrant phosphorylation of STAT1. The pharmaceutical inhibition of EGFR caused a significant reduction in cellular proliferation and of overall levels of cyclin D1, pAKT, and pERK1/2.ConclusionsSTAT1–EGFR-dependent constitutive phosphorylation is responsible for a positive feedback loop that causes its own overexpression and consequently an increased proliferation of the tumor cells. These findings provide the rationale for further studies aiming to identify effective therapeutic options in meningioma.

Spectrochemical differentiation of meningioma tumours based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy

Meningiomas are the commonest types of tumours in the central nervous system (CNS). It is a benign type of tumour divided into three WHO grades (I, II and III) associated with tumour growth rate and likelihood of recurrence, where surgical outcomes and patient treatments are dependent on the meningioma grade and histological subtype. The development of alternative approaches based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy could aid meningioma grade determination and its biospectrochemical profiling in an automated fashion. Herein, ATR-FTIR in combination with chemometric techniques is employed to distinguish grade I, grade II and grade I meningiomas that re-occurred. Ninety-nine patients were investigated in this study where their formalin-fixed paraffin-embedded (FFPE) brain tissue samples were analysed by ATR-FTIR spectroscopy. Subsequent classification was performed via principal component analysis plus linear discriminant analysis (PCA-LDA) and partial least squares plus discriminant analysis (PLS-DA). PLS-DA gave the best results where grade I and grade II meningiomas were discriminated with 79% accuracy, 80% sensitivity and 73% specificity, while grade I versus grade I recurrence and grade II versus grade I recurrence were discriminated with 94% accuracy (94% sensitivity and specificity) and 97% accuracy (97% sensitivity and 100% specificity), respectively. Several wavenumbers were identified as possible biomarkers towards tumour differentiation. The majority of these were associated with lipids, protein, DNA/RNA and carbohydrate alterations. These findings demonstrate the potential of ATR-FTIR spectroscopy towards meningioma grade discrimination as a fast, low-cost, non-destructive and sensitive tool for clinical settings.Graphical abstractAttenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was used to discriminate meningioma WHO grade I, grade II and grade I recurrence tumours.

Brain Tumor Classification Using Deep Learning Technique - A Comparison between Cropped, Uncropped, and Segmented Lesion Images with Different Sizes

Deep Learning is the newest and the current trend of the machine learning field that paid a lot of the researchers' attention in the recent few years. As a proven powerful machine learning tool, deep learning was widely used in several applications for solving various complex problems that require extremely high accuracy and sensitivity, particularly in the medical field. In general, brain tumor is one of the most common and aggressive malignant tumor diseases which is leading to a very short expected life if it is diagnosed at higher grade. Based on that, brain tumor grading is a very critical step after detecting the tumor in order to achieve an effective treating plan. In this paper, we used Convolutional Neural Network (CNN) which is one of the most widely used deep learning architectures for classifying a dataset of 3064 T1 weighted contrast-enhanced brain MR images for grading (classifying) the brain tumors into three classes (Glioma, Meningioma, and Pituitary Tumor). The proposed CNN classifier is a powerful tool and its overall performance with accuracy of 98.93% and sensitivity of 98.18% for the cropped lesions, while the results for the uncropped lesions are 99% accuracy and 98.52% sensitivity and the results for segmented lesion images are 97.62% for accuracy and 97.40% sensitivity.

CSIG-02. TARGETING CONSTITUTIVE ACTIVATION OF THE EGFR-STAT1 AXIS DECREASES PROLIFERATION OF MENINGIOMA TUMOUR CELLS

Abstract Meningiomas are the most frequent primary brain tumours of the central nervous system. The standard of treatment is surgery and radiotherapy, but the lack of knowledge of their tumorigenesis contributes to delay the development of additional therapeutic options. We found STAT1 widely overexpressed in meningioma tumours and in patient-derived meningioma cells but not in the corresponding healthy controls. The protein showed a constitutive phosphorylation on both phosphosites (Y701 and S727), which was not dependent on the JAK/STAT pathway. STAT1 knocked down resulted in a significant reduction of cellular proliferation, showed as a decrease in Ki67-positive cells and Cyclin D1, and deactivation of AKT and ERK 1/2. By studying STAT1 binding partners we isolated a complex composed by STAT1, STAT2, PRMT5 and MEP50. As PRMT5 is known to interact with EGFR, we tested the tyrosine kinase and found that EGFR was constitutively active in meningioma and was responsible for the aberrant phosphorylation of STAT1 on both phosphosites. We tested different drugs inhibiting of EGFR phosphorylation, Canertinib was most effective. It caused a significant reduction in meningioma cells proliferation and a reduction of overall levels of Cyclin D1, phospho- AKT and phospho-ERK 1/2. Hence, STAT1 constitutive phosphorylation, initiated by EGFR activation, is responsible for inducing a positive feedback loop causing its own overexpression and consequently an increased proliferation of the tumour cells. These findings underline a pivotal role of the EGFR and STAT1 axis in meningioma and provides the rationale for further studies aiming to identify novel and effective therapeutic options.

EPID-03. HISTOLOGY-SPECIFIC BRAIN TUMOR INCIDENCE AND SURVIVAL VARIES BY SEX

Abstract BACKGROUND Significant sex differences exist in cancer, and males have higher incidence and lower survival compared to females for most cancers. No large-scale studies have systematically examined sex differences in incidence and survival across all primary brain histologies. We performed a comprehensive investigation of the differences in incidence and survival in patients diagnosed with primary malignant brain and other CNS tumors by specific histologies. METHODS Age-adjusted incidence rate ratios (IRR) and 95% confidence intervals (945% CI) were generated from the United States Cancer Statistics (USCS) Public Use Database. Data from the Surveillance, Epidemiology, and End-Results (SEER) program were used to calculate overall survival. Data was restricted to patients with histologically or radiologically confirmed, primary malignant tumors diagnosed between 2001 and 2015. Histological groupings were categorized based on the Central Brain Tumor Registry of the United States (CBTRUS). Cox proportional hazards models were used to calculate hazard ratios (HR) adjusted for age for males as compared to females. RESULTS Males exhibited higher incidence than females in all brain histologies except meningioma (IRR=0.83; 95% CI 0.73–0.93) and other neuroepithelial tumors (i.e. polar spongioblastomas and astroblastomas) (IRR=0.48; 95% CI 0.26–0.88). Males experienced better overall survival in germ cell tumors, cysts and heterotopias (HR=0.68; 95% CI 0.49–0.94) compared to females, but were observed to have lower survival in all other histologies. Survival was lowest for males among patients with nerve sheath tumors (HR=2.32; 95% CI 1.31–4.12) and other neoplasms related to the meninges (e.g. chondrosarcomas and chordomas) (HR=2.23; 95% CI 1.24–3.99). Survival in meningioma patients was significantly higher in females (HR=1.49; 95% CI 1.25–1.77). Patients with glioblastomas, had a slightly worse survival outcome in males (HR=1.02, 95% CI 1.00–1.05). CONCLUSION Understanding the role of sex differences is critical for addressing sex based inequalities and needs to be taken into account in clinical paradigms.

GENE-61. METHYLATION-BASED LIQUID BIOPSY OF MENINGIOMA PRIMARY AND RECURRENT SAMPLES

Abstract Meningiomas are mostly benign CNS tumors, however a subset of these tumors may become atypical or malignant. The standard of care to monitor patients after diagnosis requires serial MRI assessments, which have limited value in distinguishing malignant tumors from benign disease. Therefore the discovery of non-invasive methodologies that reflect meningioma tumor burden and its dynamic evolution in real-time is highly desirable. Liquid biopsy (LB) could be used to fine-tune surveillance and treatment with minimal risk to patients. Evidence of circulating tumor cells and cell-free (cf) tumor DNA in the blood has been shown in several tumor types, however limited progress has been made for brain tumors with known biomarkers; possibly due to the unlikelihood of capturing point mutations in circulating DNA fragments. On the other hand, DNA methylation signatures are maintained even in small DNA fragments, which suggests that DNA methylation is an attractive marker to be studied in liquid biopsy of brain cancers. In order to identify DNA methylation-based biomarkers using archival serum and tissue specimens, we analyzed the epigenome (Illumina Human EPIC array) of patients with primary (n=10) and recurrent (n=4) meningiomas and epileptic patients (n=5) as control. cfDNA fragment size distribution revealed peaks with 150~200bp on average. We identified 482 CpGs (p-value&lt; 0.001) differentially methylated between primary meningiomas and controls, which 294 (61%) show a DNA methylation profile similar to the matched tumor tissue. Overall, we observed that recurrent samples are hypermethylated (56%) compared to primary. From this pilot data, we were able to investigate the LB methylome of meningioma patients and identify potential markers to detect tumor cells in the serum of these patients, which could eventually allow clinicians to monitor impending disease progression and recurrence.

Canine Primary Intracranial Cancer: A Clinicopathologic and Comparative Review of Glioma, Meningioma, and Choroid Plexus Tumors.

In the dog, primary intracranial neoplasia represents ~2–5% of all cancers and is especially common in certain breeds including English and French bulldogs and Boxers. The most common types of primary intracranial cancer in the dog are meningioma, glioma, and choroid plexus tumors, generally occurring in middle aged to older dogs. Much work has recently been done to understand the characteristic imaging and clinicopathologic features of these tumors. The gross and histologic landscape of these tumors in the dog compare favorably to their human counterparts with many similarities noted in histologic patterns, subtype, and grades. Data informing the underlying molecular abnormalities in the canine tumors have only begun to be unraveled, but reveal similar pathways are mutated between canine and human primary intracranial neoplasia. This review will provide an overview of the clinicopathologic features of the three most common forms of primary intracranial cancer in the dog, delve into the comparative aspects between the dog and human neoplasms, and provide an introduction to current standard of care while also highlighting novel, experimental treatments that may help bridge the gap between canine and human cancer therapies.

Deep neural network with generative adversarial networks pre-training for brain tumor classification based on MR images

In this paper, a new deep learning method for tumor classification in MR images is presented. A deep neural network is first pre-trained as a discriminator in a generative adversarial network (GAN) on different datasets of MR images to extract robust features and to learn the structure of MR images in its convolutional layers. Then the fully connected layers are replaced and the whole deep network is trained as a classifier to distinguish three tumor classes. The deep neural network classifier has six layers and about 1.7 million weight parameters. Pre-training as a discriminator of a GAN together with other techniques such as data augmentations (image rotation and mirroring) and dropout prevent the network from overtraining on a relatively small dataset. This method is applied to an MRI data set consists of 3064 T1-CE MR images from 233 patients, 13 images from each patient on average, with three different brain tumor types: meningioma (708 images), glioma (1426 images), and pituitary tumor (930 images). 5-Fold cross-validation is used to evaluate the performance of overall design, achieving the highest accuracy as compared to state-of-art methods.

Efficient ADCC killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK.

Meningiomas are the most common adult primary tumor of the central nervous system, but there are no known effective medical therapies for recurrent meningioma, particularly for World Health Organization grade II and III tumors. Meningiomas arise from the meninges, located outside the blood-brain barrier, and therefore may be directly targeted by antibody-mediated immunotherapy. We found that programmed cell death ligand 1 (PD-L1) was highly expressed in multiple human malignant meningioma cell lines and patient tumor samples. PD-L1 was targeted with the anti-PD-L1 antibody avelumab and directed natural killer cells to mediate antibody-dependent cellular cytotoxicity (ADCC) of PD-L1-expressing meningioma tumors both in vitro and in vivo. ADCC of meningioma cells was significantly increased in target cells that upregulated PD-L1 expression and, conversely, abrogated in tumor cells that were depleted of PD-L1. Additionally, the high-affinity natural killer cell line, haNK, outperformed healthy donor NK cells in meningioma ADCC. Together, these data support a clinical trial designed to target PD-L1 with avelumab and haNK cells, potentially offering a novel immunotherapeutic approach for patients with malignant meningioma.

Determination of meningioma brain tissue grades using Raman hyperspectral imaging

Abstract Raman spectroscopy is a powerful tool used to analyse biological materials, where spectral biomarkers such as proteins (1500–1700 cm-1), carbohydrates (470–1200 cm-1) and phosphate groups of DNA (980, 1080–1240 cm-1) can be detected. A major advantage is that it is reagent-free and unaffected by water interference, which is ideal for biological applications. Raman hyperspectral imaging combines the chemical sensitivity of this spectrochemical technique with spatially distributed information. Herein, Raman microspectroscopy imaging (50 × 50 μm tissue area, 50× magnification, 50% laser power, 0.1 ms exposure time, 780–1858 cm-1 spectral range) was used to investigate 79 brain tissue samples (sourced from the Brain Tumour North West) in order to differentiate meningioma Grade I (n=55) versus Grade II (n=24). Meningioma is the commonest type of brain tumour with the majority of them being benign tumours (Grade I) whilst a few are aggressive or malignant (Grade II). Grade II tumours have a poor prognosis by their nature, hence new sensitive diagnostic tools are essential. Using partial least squares discriminant analysis (PLS-DA) with 20 LVs (99% explained variance), we were able to differentiate Grade I versus Grade II meningioma with a classification accuracy of 99% in an internal validation set of 23 samples (16 Grade I, seven Grade II); this was with an accuracy of 85% for an external test set of similar size. These findings highlight the potential of Raman hyperspectral imaging for differentiation of meningioma tumours.

Circulating Tumor Biomarkers in Meningiomas Reveal a Signature of Equilibrium Between Tumor Growth and Immune Modulation.

Meningiomas are primary central nervous system (CNS) tumors that originate from the arachnoid cells of the meninges. Recurrence occurs in higher grade meningiomas and a small subset of Grade I meningiomas with benign histology. Currently, there are no established circulating tumor markers which can be used for diagnostic and prognostic purposes in a non-invasive way for meningiomas. Here, we aimed to identify potential biomarkers of meningioma in patient sera. For this purpose, we collected preoperative (n = 30) serum samples from the meningioma patients classified as Grade I (n = 23), Grade II (n = 4), or Grade III (n = 3). We used a high-throughput, multiplex immunoassay cancer panel comprising of 92 cancer-related protein biomarkers to explore the serum protein profiles of meningioma patients. We detected 14 differentially expressed proteins in the sera of the Grade I meningioma patients in comparison to the age- and gender-matched control subjects (n = 12). Compared to the control group, Grade I meningioma patients showed increased serum levels of amphiregulin (AREG), CCL24, CD69, prolactin, EGF, HB-EGF, caspase-3, and decreased levels of VEGFD, TGF-α, E-Selectin, BAFF, IL-12, CCL9, and GH. For validation studies, we utilized an independent set of meningioma tumor tissue samples (Grade I, n = 20; Grade II, n = 10; Grade III, n = 6), and found that the expressions of amphiregulin and Caspase3 are significantly increased in all grades of meningiomas either at the transcriptional or protein level, respectively. In contrast, the gene expression of VEGF-D was significantly lower in Grade I meningioma tissue samples. Taken together, our study identifies a meningioma-specific protein signature in blood circulation of meningioma patients and highlights the importance of equilibrium between tumor-promoting factors and anti-tumor immunity.

P09.07 Constitutive activation of the EGFR-STAT1 axis increases proliferation of meningioma tumour cells

Abstract BACKGROUND Meningiomas are the most frequent primary brain tumours of the central nervous system. The standard of treatment is (radio)surgery, but the lack of knowledge of their tumorigenesis contributes to delay the development of additional therapeutic options. MATERIAL AND METHODS We used a variety of differen model systems and cell biology techniques RESULTS We found STAT1 widely overexpressed in meningioma tumours and in patient-derived meningioma cells but not in the corresponding healthy controls. The protein showed a constitutive phosphorylation on both phosphosites (Y701 and S727), which was not dependent on the JAK/STAT pathway. STAT1 knocked down resulted in a significant reduction of cellular proliferation, showed as a decrease in Ki67-positive cells and Cyclin D1, and deactivation of AKT and ERK 1/2. By studying STAT1 binding partners we isolated a complex composed by STAT1, STAT2, PRMT5 and MEP50. As PRMT5 is known to interact with EGFR, we tested the tyrosine kinase and found that EGFR was constitutively active in meningioma and was responsible for the aberrant phosphorylation of STAT1 on both phosphosites. We tested different drugs inhibiting of EGFR phosphorylation, Canertinib was most effective. It caused a significant reduction in meningioma cells proliferation and a reduction of overall levels of Cyclin D1, phospho- AKT and phospho-ERK 1/2. Hence, STAT1 constitutive phosphorylation, initiated by EGFR activation, is responsible for inducing a positive feedback loop causing its own overexpression and consequently an increased proliferation of the tumour cells. CONCLUSION These findings underline a pivotal role of the EGFR and STAT1 axis in meningioma and provides the rationale for further studies aiming to identify novel and effective therapeutic options.

Metabolomic profiling of blood plasma in patients with primary brain tumours: Basal plasma metabolites correlated with tumour grade and plasma biomarker analysis predicts feasibility of the successful statistical discrimination from healthy subjects - a preliminary study.

The brain tumours represent a complex tissue that has its own characteristic metabolic features and is interfaced with the whole organism. We investigated changes in basal blood plasma metabolites in the presence of primary brain tumour, their correlation with tumour grade, as well as the feasibility of statistical discrimination based on plasma metabolites. Together 60 plasma samples from patients with clinically defined glioblastoma, meningioma, oligodendrioglioma, astrocytoma, and non-specific glial tumour and plasma samples from 28 healthy volunteers without any cancer history were measured by NMR spectroscopy. In blood plasma of primary brain tumour patients, we found significantly increased levels of glycolytic metabolites glucose and pyruvate, and significantly decreased level of glutamine and also metabolites participating in tricarboxylic acid (TCA) cycle, citrate and succinate, when compared with controls. Further, plasma metabolites levels: tyrosine, phenylalanine, glucose, creatine and creatinine correlated significantly with tumour grade. In general, observed changes are parallel to the biochemistry expected for tumourous tissue and metabolic changes in plasma seem to follow the similar rules in all primary brain tumours, with very subtle variations among tumour types. Only two plasma metabolites tyrosine and phenylalanine were increased exclusively in blood plasma of patients with glioblastoma. Based on metabolite levels, an excellent discrimination between plasma from patient's tumours and controls was attainable. The metabolites creatine, pyruvate, glucose, formate, creatinine and citrate were of the highest discriminatory power.

5-ALA fluorescence on tumors different from malignant gliomas. Review of the literature and our experience.

Fluorescence guided surgery with 5-aminolevulinic acid (5-ALA) is a well-established technique for improving resection of malignant cerebral glioma. In recent years, this technique is being increasingly applied off label to other brain tumor entities such as Low-grade glioma, meningioma, metastases, lymphoma and other central nervous system tumors. In this paper We collected all the data of 5-ALA guided surgery in "not malignant glioma" in literature compared to our experience. We searched the PubMed/Medline database all clinical series reporting 5-ALA guided-surgery in not malignant glioma. We reviewed all data also showing our experience. Fluorescence guided surgery with 5-ALA might be helpful not only in high-grade glioma but also in other brain tumor especially in Low grade glioma with a suspect of anaplastic spot, meningioma with bone invasion or parenchymal infiltration, ependymoma, lymphoma and pediatric tumors. Due to the relatively few number or clinical studies, prospective clinical trials are needed to increase the overall level of evidence concerning the usage of 5-ALA in CNS tumors different from high-grade glioma. Furthermore, a greater us of new tools such as, spectroscopy or confocal microscope or the use of combination of other fluorescence could make more effective this technique.

Diversity in tumor territory of meningioma: Protein expression in vascular endothelial growth factor and epidermal growth factor

Background: Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are involved in tumor development and progression. But, the classified-based data of protein expression (PE) in meningiomas is unavailable. Therefore, we aimed to explore the PE of VEGF and EGF in meningiomas by considering evolutionary strategy and the regional tumor-based assay. Methods: PE was assayed using immunofluorescence (IF) within the peripheral, central, and basal sections of four meningioma tumors, and a lung metastatic brain tumor as a positive control. Results: Diverse characteristics and harmonic cross-talk in the individual sections and between different tumor sections were traced. The mode of PE was puzzling and personalized issue. Co-expression had a key impact on tumor evolution and diverse PE profiles led to draw the heterogenic classification, as the personalized/complementary insight in the functional behavior of VEGF and EGF. D1853N polymorphism of ATM gene was mosaics in two patients with meningiomas. Conclusion: The classified heterogeneity, harmonic co-expression, and diverse functional information in different regions of tumors may lead to predict the aggressiveness mode of tumors as a translational insight to the clinical managements including therapy in brain tumors.

Canine Ependymoma: Diagnostic Criteria and Common Pitfalls.

Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in the lateral ventricle, tumors can occur anywhere in the ventricular system and in extraventricular locations. Rosettes and pseudorosettes are a common histologic feature; however, these features can be mimicked by other CNS neoplasms. Thirty-seven potential ependymoma cases were identified in a retrospective database search of 8 institutions, and a histologic review of all cases was conducted. Of 37 cases, 22 candidate cases were further subjected to a consensus histologic and immunohistochemical review, and only 5 of 37 (13.5%) were conclusively identified as ependymoma. The neuroanatomic locations were the lateral ventricle (3/5), third ventricle (1/5), and mesencephalic aqueduct (1/5). Subtypes were papillary (4/5) and tanycytic (1/5). Histologic features included rosettes (5/5), pseudorosettes (5/5), ependymal canals (2/5), tanycytic differentiation (1/5), blepharoplasts (1/5), ciliated cells (1/5), and high nuclear to cytoplasmic ratio (5/5). Immunolabeling for GFAP (4/4) and CKAE1/3 (3/4) was found in pseudorosettes, rosettes, and scattered individual neoplastic cells. Diffuse but variably intense cytoplasmic S100 immunolabeling was detected in 3 of 4 cases. Olig2 intranuclear immunolabeling was observed in less than 1% of the neoplastic cells (3/3). Tumors that had pseudorosettes and mimicked ependymoma included oligodendroglioma, choroid plexus tumor, pituitary corticotroph adenoma, papillary meningioma, and suprasellar germ cell tumor. These findings indicate that canine ependymoma is an extremely rare neoplasm with histomorphologic features that overlap with other primary CNS neoplasms.

Brain tumor classification using deep CNN features via transfer learning

Brain tumor classification is an important problem in computer-aided diagnosis (CAD) for medical applications. This paper focuses on a 3-class classification problem to differentiate among glioma, meningioma and pituitary tumors, which form three prominent types of brain tumor. The proposed classification system adopts the concept of deep transfer learning and uses a pre-trained GoogLeNet to extract features from brain MRI images. Proven classifier models are integrated to classify the extracted features. The experiment follows a patient-level five-fold cross-validation process, on MRI dataset from figshare. The proposed system records a mean classification accuracy of 98%, outperforming all state-of-the-art methods. Other performance measures used in the study are the area under the curve (AUC), precision, recall, F-score and specificity. In addition, the paper addresses a practical aspect by evaluating the system with fewer training samples. The observations of the study imply that transfer learning is a useful technique when the availability of medical images is limited. The paper provides an analytical discussion on misclassifications also.

Correlations between the expression of hTERT and α and β splice variants in human brain tumors.

Astrocytomas are diffusible infiltrative and aggressive brain tumors that are extensive and heterogeneous clusters of neoplastic growths in the central nervous system (CNS). Meningioma tumors are commonly benign but may demonstrate an invasive pattern with frequent recurrences. Human telomerase reverse transcriptase (hTERT) is an unfavorable prognostic factor for several types of cancers, and there are controversies about its role. In the present study, we investigated the relative expression of hTERT splice variants in 2 groups of brain tumors compared to non-tumor samples. The mRNA of 40 brain tumor samples and 4 control samples was extracted; mRNA expression of hTERT α-deletion and β-deletion variants, as well as the wild type isoform, was quantified using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The α-deletion variant was significantly expressed in primary benign meningeal tumors (p = 0.01). The results indicate a positive correlation between the relative expression of hTERT mRNA transcript and α-deletion and β-deletion variants in both groups of tumors (meningiomas and astrocytomas). A strong association between the expression of the full-length splice variant and the β-deletion variant was observed in astrocytoma tumors (p = 0.045). The most significant correlations were found between the hTERT full-length and β-deletion variants in high-grade meningiomas (p = 0.018, correlation coefficient (CC) = 0.964) and grade II astrocytomas (p = 0.015; CC = 0.580). In addition, in low grades of both types of tumors, the hTERT full-length variant and especially the α-deletion variant were the predominant isoforms. The overexpression of hTERT and β-deletion variants in high grades of these tumors was statistically significant. Our findings indicate that α-deletion and β-deletion isoforms are associated with high levels of full-length hTERT mRNA in both groups of brain tumor patients. Changes in the splicing pattern of hTERT splice variants in brain tumors and their correlation with pathological alterations in cells could be applied as diagnostic or prognostic biomarkers, or possibly as targets for cancer therapy. However, the function and biological role of hTERT splice variants remain to be clarified.