Ependymomas of the spinal region in adults: Clinical and pathological features and MYCN expression levels in spinal ependymomas and myxopapillary ependymomas.

BACKGROUND: Ependymomas (EPNs) of the spinal region are a heterogeneous group of tumors that account for 17.6 % in adults. Four types have been recognized: subependymoma, spinal ependymoma (Sp-EPN), myxopapillary ependymoma (MPE), and Sp-EPN-MYCN amplified, each with distinct histopathological and molecular features. METHODS: This study investigated the clinical and pathological characteristics and MYCN expression levels of 35 Sp-EPN and MPE cases diagnosed at a tertiary university hospital over a decade-long period. RESULTS: Twenty-five cases were Sp-EPN and 10 cases were MPE, and were graded as WHO grade 2, except for 1 Sp-EPN case with grade 3 features. The most common symptoms were lower back pain and difficulty in walking. Radiology showed different tumor sizes and locations along the spinal cord, with MPEs exclusively in the lumbosacral region. Surgery was the main treatment, and gross total resection was achieved in all cases except for one. Immunohistochemistry showed low Ki-67 proliferation indices in all cases, and no MYCN expression. During follow-up, 3 (8.6 %) cases recurred and/or metastasized and 5 cases (14.3 %) died. No significant difference was found in disease-free survival or overall survival between Sp-EPN and MPE cases. However, 3 cases with grade 2 histology demonstrated recurrence and/or metastasis, despite the lack of MYCN expression. CONCLUSION: Our results underscore the multifactorial nature of tumor aggressiveness in EPNs of the spinal region. This study enhances our knowledge of the clinical and pathological features of Sp-EPNs and MPEs and highlights the need for better diagnostic and prognostic markers in these rare tumors.

Bioinformatics analysis of microarray data reveals epithelial-mesenchymal-transition in pediatric ependymoma.

The objectives of this study were to explore the possible mechanisms of pediatric ependymoma using bioinformatics methods and provide potential genes and signaling pathways for pediatric ependymoma study. The data of GES74195 from Gene Expression Ominibus was analyzed by R language for pediatric ependymoma study. The differentially expressed genes were explored using gene set enrichment analysis, search tool for the retrieval of interacting genes, Cytoscape as well as other mainstream bioinformatics methods. Extracellular matrix-receptors interaction pathways and focal adhesion pathway were demonstrated as the key signaling pathway for pediatric ependymoma. The potential hub genes enriched in the two signaling pathways were regarded as final hub genes for this microarray analysis. The development and progression of pediatric ependymoma were associated with epithelial-mesenchymal-transition. Various potential hub genes and potential key signaling pathways in order to further explore their values in the diagnosis and treatment of this disease in the future.

Malignant transformation of NF1-associated spinal astrocytoma with loss of ATRX expression during the course: A case report.

Few cases of malignant transformation of supposedly low-grade gliomas were described in patients with neurofibromatosis type 1 (NF1). A 27-year-old man with NF1 presented with weakness of his lower extremities and was radiologically found to have a spinal intramedullary tumor primarily involving the Th11 level. The tumor histologically demonstrated features diagnosed as a low-grade astrocytoma, subtype indeterminate (WHO grade II). Immunohistochemically, GFAP was positive, and IDH1 R132H and BRAF V600E were negative. ATRX immunoreactivity was retained. Five years after the surgery, the intramedullary tumor extended to the levels from Th8 to L1 and was partially resected. It showed histologic features similar to those of the first tumor. Two years after the second surgery, the residual spinal cord tumor was found to widely involve the levels from Th5 to L3. Spinal cordectomy was subsequently undertaken and revealed anaplastic glial cells infiltrating diffusely into the spinal cord parenchyma, with prominent subarachnoid spreading and nerve root involvement. Both necrosis and microvascular proliferation were observed. This recurrent tumor was histologically indistinguishable from glioblastoma. Loss of ATRX was noted in the second and third surgical specimens. This is the first histologically proven case of malignant transformation of NF1-associated astrocytoma with ATRX loss during the course.

Prognostic value of H3K27me3 in children with ependymoma.

OBJECTIVE: To investigate the expression of H3K27me3 in different anatomical sites and analyze its prognostic value in children with ependymoma. METHODS: A total of 188 children diagnosed with ependymoma were admitted to the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, between 2012 and 2017, and regular follow-up was conducted. Expression of H3K27me3 was analyzed by immunohistochemistry and scored semiquantitatively. The prognostic correlation was analyzed by Kaplan-Meier and Cox regression survival analyses. RESULTS: Of the 188 children with ependymoma, 61.7% were male, and the median and average age was five years (0-17 years) and 6.26 years, respectively. There were 65 cases of supratentorial ependymoma, 115 cases of infratentorial ependymoma, and 8 cases of spinal cord ependymoma. The median follow-up time was 39.95 months (0.3-90.19 months). Five-year progression-free survival (PFS) and overall survival (OS) were 48.5% and 61.4%, respectively. Kaplan-Meier univariate survival analysis showed that H3K27me3 expression had significant effects on PFS (P = 0.0003) and OS (P < 0.0001) in infratentorial ependymoma, but only affected OS (P = 0.03) in supratentorial ependymoma. CONCLUSION: In Chinese children, infratentorial ependymoma with incomplete resection and no adjuvant radiotherapy is associated with poor OS. On the other hand, low expression of H3K27me3 indicates poor prognosis of infratentorial ependymoma, but it has no significant prognostic value for supratentorial ependymoma. In addition, high expression of H3K27me3 in spinal ependymoma may indicate a better prognosis.

Spinal Cord Tumor Microenvironment.

Intramedullary spinal cord tumors (IMSCT) are rare entities for which there currently exist no standardized treatment paradigms. Consequently, patients usually receive treatment modalities that were established for intracerebral tumors; these approaches, however, typically result in functional impairment, recurrent tumor growth, and short overall survival. There is a distinct lack of promising research efforts in this field, which raises questions about whether spinal cord tumor microenvironment (TME) might promote the development, progression, and treatment resistance of IMSCT. In this review, we aim to examine spinal cord biology, compare spinal cord and brain microenvironments, and discuss mutual interactions between IMSCT and TME. Manipulating these pathways may provide new treatment approaches for future patient groups.

Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation.

Primary high-grade infiltrating gliomas of the spinal cord are rare, with prior series including limited numbers of cases and reporting poor outcomes. Additionally, the molecular profile of high-grade infiltrating gliomas of the spinal cord has not been well characterized. We identified 13 adult patients whose surgery had been performed at our institution over a 26-year-period. Radiologically, nine cases harbored regions of post-contrast enhancement. Existing slides were reviewed, and when sufficient tissue was available, immunohistochemical stains (IDH1-R132H, H3-K27M, H3K27-me3, ATRX, p53 and BRAF-V600E), and a targeted 150-gene neuro-oncology next-generation sequencing panel were performed. The 13 patients included 11 men and 2 women with a median age of 38 years (range = 18-69). Histologically, all were consistent with an infiltrating astrocytoma corresponding to 2016 WHO grades III (n = 5) and IV (n = 8). By immunohistochemistry, six cases were positive for H3K27M, all showing concomitant loss of H3K27-me3. Next-generation sequencing was successfully performed in ten cases. Next-generation sequencing studies were successfully performed in four of the cases positive for H3K27M by immunohistochemistry, and all were confirmed as H3F3A K27M-mutant. Additional recurrent mutations identified included those of TERT promoter (n = 3), TP53 (n = 5), PPM1D (n = 3), NF1 (n = 3), ATRX (n = 2), and PIK3CA (n = 2). No HIST1H3B, HIST1H3C, IDH1, IDH2, or BRAF mutations were detected. Ten patients have died since first surgery, with a median survival of 13 months and 1 year of 46%. Median survival was 48.5 months for H3K27M-positive cases, compared to 1 month for those with TERT promoter mutation and 77 months for those harboring neither (p = 0.019). Median survival for cases with TP53 mutations was 11.5 months and for those with PPM1D mutations was 84 months. Our findings suggest that high-grade infiltrating gliomas of the spinal cord in adults represent a heterogeneous group of tumors, with variable outcomes possibly related to their molecular profiles.

MicroRNA regulating stanniocalcin-1 is a metastasis and dissemination promoting factor in glioblastoma.

BACKGROUND: MicroRNAs (miRs) regulate many biological processes, such as invasion, angiogenesis, and metastasis. Glioblastoma (GBM) patients with metastasis/metastatic dissemination have a very poor prognosis; therefore, inhibiting metastasis/metastatic dissemination has become an important therapeutic strategy for GBM treatment. METHODS: Using 76 GBM tissues, we examined the expression levels of 23 GBM-related miRs and compared the miRs' expression levels between GBMs with metastasis/metastatic dissemination and GBMs without metastasis/metastatic dissemination. Using the bioinformatics web site, we searched the target genes of miRs. To analyze the function of target gene, several biological assays and survival analysis by the Kaplan-Meier method were performed. RESULTS: We found that eight miRs were significantly decreased in GBM with metastasis/metastatic dissemination. By the bioinformatics analysis, we identified stanniocalcin-1 (STC1) as the most probable target gene against the combination of these miRs. Four miRs (miR-29B, miR-34a, miR-101, and miR-137) have predictive binding sites in STC1 mRNA, and mRNA expression of STC1 was downregulated by mimics of these miRs. Also, mimics of these miRs and knockdown of STC1 by siRNA suppressed invasion in GBM cells. GBM with metastasis/metastatic dissemination had significantly higher levels of STC1 than GBM without metastasis/metastatic dissemination. Finally, Kaplan-Meier analysis demonstrated that GBMs with high STC1 level had significantly shorter survival than GBMs with low STC1 level. CONCLUSIONS: STC1 may be a novel metastasis/metastatic dissemination promoting factor regulated by several miRs in GBM. Because STC1 is a secreted glycoprotein and functions via the autocrine/paracrine signals, inhibiting STC1 signal may become a novel therapeutic strategy for GBM.

Analysis of PD-L1 expression and T cell infiltration in different molecular subgroups of diffuse midline gliomas.

Diffuse midline gliomas (DMGs) are rare and devastating tumors with limited therapeutic options. Programmed death-ligand 1 (PD-L1) expression represents a potential predictive biomarker for immunotherapy. One hundred and twenty-six DMGs (89 adult and 37 pediatric) were assessed for immune profile (PD-L1, cluster of differentiation (CD3, CD8) and genetic markers (mutation in 27th amino acid of histone H3 (H3K27M), alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase 1 (IDH1), p53) by immunohistochemistry. Sanger sequencing was done for IDH1 and H3K27M. The thalamus was the commonest site. Four molecular subgroups of DMGs were identified. H3K27M mutation was more frequent in children (P = 0.0001). The difference in median overall survival (OS) was not significant in any of the four molecular subgroups (P > 0.05). PD-L1 expression was significantly higher in H3K27M/IDH1 double-negative adult glioblastomas (GBMs) (P = 0.002). Strong PD-L1 expression was more frequent in grade IV tumors and thalamic location, although the difference was not significant (P = 0.14 and P = 0.19 respectively). Positive PD-L1 expression was significantly associated with high tumor-infiltrating lymphocytes count (P < 0.05). There was no significant difference in median OS in PD-L1-positive versus negative cases among four genetic subgroups (P > 0.05). On univariate analysis, there was no direct correlation of PD-L1 with any genetic alteration, except H3K27M mutation (P = 0.01). CD3 infiltration was similar in both adults and pediatric ages (84.3% and 78.4%, respectively) while CD8 expression was significantly greater in adults compared to children (74.1% vs 37.8%, P = 0.0001). This is the first comprehensive analysis highlighting molecular and immune profiles of DMGs. Despite molecular and clinicopathological diversity, overall survival in DMGs remains dismal. Multicentric studies with larger numbers of cases should be undertaken for stratifying DMGs according to their age, immune and molecular profiles, to develop effective immunotherapies.

Long Non-Coding RNA LINC01260 Inhibits the Proliferation, Migration and Invasion of Spinal Cord Glioma Cells by Targeting CARD11 Via the NF-κB Signaling Pathway.

BACKGROUND/AIMS: Spinal cord glioma is a highly aggressive malignancy that commonly results in high mortality due to metastasis, high recurrence and limited treatment regimens. This study aims to elucidate the effects of long non-coding RNA LINC01260 (LINC01260) on the proliferation, migration and invasion of spinal cord glioma cells by targeting Caspase recruitment domain family, member 11 (CARD11) via nuclear factor kappa B (NF-κB) signaling. METHODS: The Multi Experiment Matrix (MEM) website was used for target gene prediction, and the DAVID database was used for analysis of the relationship between CARD11 and the NF-κB pathway. In total, 60 cases of glioma tissues and adjacent normal tissues were collected. Human U251 glioma cells were grouped into blank, negative control (NC), LINC01260 vector, CARD11 vector, siRNA-LINC01260, siRNA-CARD11, LINC01260 vector + CARD11 vector and LINC01260 + siRNA-CARD11 groups. A dual-luciferase reporter assay was conducted to verify the target relationship between LINC01260 and CARD11. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were employed to assess expression of LINC01260, E-cadherin, p53, CARD11, Ki67, N-cadherin, matrix metalloproteinase (MMP)-9, NF-κBp65 and NF-κBp50. MTT, flow cytometry, wound-healing and Transwell assays were performed to examine cell viability, the cell cycle, apoptosis, invasion and migration. Tumor growth was assessed through xenografts in nude mice. RESULTS: CARD11 was confirmed to be a target gene of LINC01260 and was found to be involved in regulating the NF-κB pathway. Compared with adjacent normal tissues, glioma tissues showed reduced expression of LINC01260 and elevated expression of CARD11 and genes related to apoptosis, invasion and migration; activation of NF-κB signaling was also observed. In contrast to the blank and NC groups, an elevated number of cells arrested in G1 phase, increased apoptosis and reduced cell proliferation, invasion and number of cells arrested in S and G2 phases, as well as tumor growth were found for the LINC01260 vector and siRNA-CARD11 groups. CONCLUSIONS: Our findings demonstrate that overexpression of LINC01260 inhibits spinal cord glioma cell proliferation, migration and invasion by targeting CARD11 via NF-κB signaling suppression.

A pilot study on the use of cerebrospinal fluid cell-free DNA in intramedullary spinal ependymoma.

Cerebrospinal fluid (CSF) represents a promising source of cell-free DNA (cfDNA) for tumors of the central nervous system. A CSF-based liquid biopsy may obviate the need for riskier tissue biopsies and serve as a means for monitoring tumor recurrence or response to therapy. Spinal ependymomas most commonly occur in adults, and aggressive resection must be delicately balanced with the risk of injury to adjacent normal tissue. In patients with subtotal resection, recurrence commonly occurs. A CSF-based liquid biopsy matched to the patient's spinal ependymoma mutation profile has potential to be more sensitive then surveillance MRI, but the utility has not been well characterized for tumors of the spinal cord. In this study, we collected matched blood, tumor, and CSF samples from three adult patients with WHO grade II intramedullary spinal ependymoma. We performed whole exome sequencing on matched tumor and normal DNA to design Droplet Digital™ PCR (ddPCR) probes for tumor and wild-type mutations. We then interrogated CSF samples for tumor-derived cfDNA by performing ddPCR on extracted cfDNA. Tumor cfDNA was not reliably detected in the CSF of our cohort. Anatomic sequestration and low grade of intramedullary spinal cord tumors likely limits the role of CSF liquid biopsy.

[Glioneuronal tumor with neuropil-like island: report of four cases and review of literature].

OBJECTIVE: To investigate the clinicopathologic features of glioneuronal tumor with neuropil-like island (GTNI). METHODS: Four cases of intracranial and spinal GTNI, including three cases of WHO grade Ⅲ, and one case of WHO grade Ⅱ with grade Ⅲ recurrence. HE and immunohistochemical (IHC) staining were used for pathologic analysis. Fluorescence in situ hybridization (FISH) was used to detect tumor genetic changes. Related literatures were reviewed. RESULTS: Microscopically, neuropil-like islands of varying sizes were seen within a background of glial proliferation, which showed features of astrocytoma or oligoastrocytoma. Neuropil-like islands were focal or circumscribed oval islands of varying sizes. Focally ganglion-like cells were seen. IHC staining revealed that in neuropil-like island area, the neuronal nuclei (Neu-N) as well as the cells around the neuropil-like island expressed oligodendrocyte lineage transcription factor-2 (Olig-2), and synaptophysin. The background glioma cells expressed S-100, glial fibrillary acidic protein (GFAP), vimentin and Olig-2, and the number of p53 positive cells was 10%-50%.In the neuropil-like island area, the Ki-67 labeling index was less than 3%, while in the astrocytoma area it was around 10%-25%.By FISH testing, four cases were no deletion of 1p/19q and PTEN, also no amplification of epidermal growth factor receptor. CONCLUSIONS: GTNI is more common in adults. 1p/19q deletions are uncommon in GTNI, only seen in a few cases with background oligodendroglioma. The prognosis is related to WHO grading. GTNI often recurs locally, and the prognosis is not good, especially in the spinal cord GTNI. The recommended treatment includes tumor resection combined with radiotherapy and chemotherapy.

Unique microenvironmental responses to PDGF stimulation in brain and spinal cord gliomas determine tumor phenotype.

Injection of a PDGF-B expressing retrovirus into the subcortical white matter of adult rats induces the rapid formation of brain tumors that have the histological features of glioblastoma. In contrast, when the same retrovirus is injected into the spinal cord of adult rats the resulting tumors are more indolent and display a unique histology characterized by nests of tumor cells separated by a dense vascular network without areas of necrosis. To study whether these differences are determined by the tumor cell of origin or due to microenvironmental influences, we conducted a series of transplantation experiments. Cells were independently isolated from PDGF-induced brain and cord tumors then subsequently transplanted into naive rat forebrains and spinal cords. The resulting tumors were characterized by histological analysis, marker expression profiling, PDGFR subtyping, and latency to tumor-induced morbidity. Tumor phenotypes were found to be consistently predicted by the tissue into which they were transplanted rather than by the tissue of origin. These results suggest that tumor microenvironment rather than the tumor cell of origin may be the primary determinant of glioma phenotype in the model presented.

Retinol dehydrogenase 10 promotes epithelial-mesenchymal transition in spinal cord gliomas via PI3K/AKT pathway.

Background: Spinal cord glioma (SCG), a rare subset of central nervous system (CNS) glioma, represents a complex challenge in neuro-oncology. There has been research showing that Retinol Dehydrogenase 10 (RDH10) may be a tumor promoting factor in brain glioma, but the biological effects of RDH10 remain undefined in SCG. Methods: We performed gene set enrichment analysis (GSEA) and unsupervised clustering analysis to investigate the roles of EMT (epithelial-mesenchymal transition) in glioma. DEG (differently expressed gene) screening and correlation analysis were conducted to filter the candidate genes which were closely associated with EMT process in SCG. Enrichment analysis and GSVA (Gene Set Variation Analysis) were conducted to investigate the potential mechanism of RDH10 for SCG. Trans-well and healing assay were performed to explore the role of RDH10 in the invasion of SCG. Western blotting was performed to evaluate the levels of markers in PI3K-AKT and EMT pathway. In vivo tests were conducted to verify the role of RDH10 in EMT process. Results: Bioinformatic analysis demonstrated the EMT pathway was associated with dismal prognosis of glioma. Further analysis demonstrated that RDH10 showed the strongest correlation with the EMT process. Retinol Dehydrogenase 10 expression was significantly increased in SCG tissues, correlating with advanced tumor grade and unfavorable prognosis. Functional analysis indicated that decreasing RDH10 levels impeded the invasive and migratory abilities of SCG cells, whereas increasing RDH10 levels augmented them. Enrichment analysis and western blot revealed that RDH10 regulated EMT process of SCG by PI3K-AKT pathway. We observed that the enhanced invasion ability and increased EMT-related protein induced by RDH10 overexpression can be suppressed by PI3K-AKT pathway inhibitor (LY294002). Conclusion: Our research found that RDH10 was an effective biomarker associated with tumor grade and prognosis of SCG. RDH10 could regulate EMT process of SCG through PI3K-AKT pathway.

Disseminated spinal cord astrocytoma with features of gliofibroma: a review of the literature.

Gliofibromas represent a relativel rare variant of astrocytoma marked by a mixture of astrocytoma and a benign mesenchymal component, usually fibroblastic with collagen deposition. The exact nature of these tumors, due to their rarity, is still uncertain. This paper reports a case of spinal cord gliofibroma arising in a 19-year-old female who presented with headaches. Imaging studies suggested widespread, multifocal tumor. Histologically, the tumor was marked by a low grade astrocytoma component (GFAP and S-100 positive) intermixed with bands of collagen. A Ki-67 labeling index of 1.9% was observed. The literature on gliofibromas arising in the spinal cord is reviewed.

Low-dose zoledronic acid reduces spinal cord metastasis in pulmonary adenocarcinoma with neuroendocrine differentiation.

Zoledronic acid (ZOL), a nitrogen-containing compound, is effective in the treatment of skeletal disorders, but its long-term use in high doses gives rise to complications such as osteonecrosis. We aimed to investigate the effect of low-dose ZOL on the expression of the neural cell adhesion molecule (NCAM), which may be correlated with tumor growth and spinal cord metastasis in lung adenocarcinoma with neuroendocrine differentiation. First, we used the small hairpin RNA technique to directly knock down NCAM expression in cells of a murine lung adenocarcinoma line, line 1 cells, and found that the tumor cells generated showed lower invasive capacity, slower tumor growth, and lesser tendency for spinal cord metastasis than control cells. Further, ZOL decreased NCAM expression and invasiveness in line 1 tumor cells in vitro. Line 1/lacZ cells, a stable clone tagged with the lacZ gene, were introduced into mice, followed by ZOL treatment (1 µg/kg/weekly). Low-dose ZOL significantly reduced spinal cord metastasis probably through reduced NCAM expression in vivo. These findings indicated that NCAM is involved in tumor growth and spinal cord metastasis of lung adenocarcinoma with neuroendocrine differentiation. Treatment with low-dose ZOL can reduce NCAM expression that may contribute toward reduced spinal cord metastasis, suggesting that NCAM is an alternative therapeutic target and that the low-dose ZOL treatment protocol is a reasonable approach for its treatment.

Platelet-derived growth factor receptor (PDGFR) expression in primary spinal cord gliomas.

Abnormal signaling through the platelet-derived growth factor receptor (PDGFR) has been proposed as a possible mechanism of spinal cord glioma initiation and progression. However, the extent of PDGFR expression in human spinal cord gliomas remains unknown. In this study we perform immunohistochemical analysis of PDGFRα expression in a series of 33 primary intramedullary spinal cord gliomas of different types and grades. PDGFRα was seen to be expressed in a significant subset of these tumors across all major glioma types including ependymoma, oligodendroglioma, pilocytic astrocytoma, astrocytoma, and glioblastoma. These results support the hypothesis that growth factor signaling through the PDGFR may be important for the development of at least a subset of human spinal cord gliomas. Further studies investigating the prognostic significance of PDGFR expression as well as the role of PDGF signaling on the development of intramedullary spinal cord gliomas are warranted.

A histopathological diagnostic marker for human spinal astrocytoma: expression of glial fibrillary acidic protein-δ.

Although histopathological diagnosis of spinal cord astrocytomas is important for postoperative treatment planning and prognosis, there is a lack of reliable immunohistochemical markers. The purpose of our study was to assess the expression pattern of GFAP-δ in spinal cord astrocytomas in human patients and to evaluate the utility of GFAP-δ as an immunohistochemical diagnostic marker. A total of 22 patients with spinal cord astrocytic tumors were included in this study. Patients were classified according to the WHO designation of human astrocytic tumors; three patients had grade 1 astrocytomas, 14 had grade 2, and five had Grade 3. Normal control spinal cord tissues were obtained at autopsy from the cervical spinal cords of ten patients with no history of cervical trauma or neurological disease. We evaluated BRAF, IDH1, GFAP, and GFAP-δ immunoreactivity in control tissues and astrocytomas. In normal control tissues, GFAP immunoreactivity was detected in astrocytes whereas GFAP-δ immunoreactivity was observed in very few astrocytes adjacent to the subpial layer of the spinal cord. GFAP-δ immunoreactivity was significantly correlated with spinal cord astrocytoma grade in astrocytomas compared to that in normal control tissues. The optical density of GFAP-δ increased significantly with astrocytoma grade (correlation coefficient, R (2) = 0.680). Also, BRAF and IDH1 immunoreactivity were detected in astrocytoma. We suggest that GFAP-δ may be an additional, reliable histopathological diagnostic marker for spinal cord astrocytomas.

Mixed schwannoma with meningioma - report on 2 cases of unusual tumor with review of literature.

We present 2 rare cases of mixed schwannoma with meningioma. The first case was sporadic, in a 38-year-old female in cervical spine (C2). The second case was a 24-year-old female, associated with NF-2, involving bilateral cerebellopontine angle with extension into the left cavernous sinus, sellar region with erosion of the petrous ridge and multiple intradural extramedullary lesions in the spinal cord suggestive of neurofibromas. To date only 12 cases of such tumors are documented in the literature. To the best of our knowledge this is the first case of sporadic mixed schwannoma with meningioma in cervical spine (C2).

Solitary fibrous tumor of the central nervous system: a 15-year literature survey of 220 cases (August 1996-July 2011).

We reviewed the world literature on solitary fibrous tumors of the central nervous system from August 1996 to July 2011, focusing on both clinicopathological features and diagnostic findings. The anatomical distribution of the 220 cases reported so far reveals that most are intracranial and just over one-fifth are intraspinal. In decreasing frequency, intracranial tumors involve the supratentorial and infratentorial compartments, the pontocerebellar angle, the sellar and parasellar regions, and the cranial nerves. Intraspinal tumors are mainly located in the thoracic and cervical segments. Although most solitary fibrous tumors of the central nervous system are dural based, a small subset presents as subpial, intraparenchymal, intraventricular, or as tumors involving the nerve rootlets with no dural connection. Preoperative imaging and intraoperative findings suggest meningioma, schwannoma or neurofibroma, hemangiopericytoma, or pituitary tumors. Immunohistochemistry is critical to establish a definitive histopathological diagnosis. Vimentin, CD34, BCL2, and CD99 are the most consistently positive markers. The usual histologic type generally behaves in a benign manner if complete removal is achieved. Recurrence is anticipated when resection is subtotal or when the tumor exhibits atypical histology. The proliferative index as assessed by MIB1 labeling is of prognostic significance. Occasionally, tumors featuring conventional morphology may recur, perhaps because of minimal residual disease left behind during surgical extirpation. Rare extracranial metastases and tumor-related deaths are on record. Surgery is the treatment of choice. Stereotactic and external beam radiation therapy may be indicated for postsurgical tumor remnants and for unresectable recurrences. Long-term active surveillance of the patients is mandatory.