Survival and Prognostic Factors of Adult Intracranial Ependymoma: A Single-institutional Analysis of 236 Patients.

Adult intracranial ependymomas (EPNs) are extremely rare brain tumors. Currently, clinical and molecular factors that could inform individualized treatment strategies are still lacking for EPNs in this age group. The aim of this study was to investigate potential prognostic indicators and rational therapeutic management in a large cohort of adult intracranial EPNs. Adult patients who underwent resection of World Health Organization (WHO) grade II or III intracranial EPNs were included. The demographic features, clinicopathologic manifestations, molecular subgroups, and outcomes were retrospectively analyzed. Overall survival and progression-free survival were calculated using the Kaplan-Meier analysis. Potential prognostic indicators were identified using multivariable Cox proportional hazards model. This cohort included 236 adult patients with a mean age of 36.2 years (range: 18 to 72 y) at diagnosis. The tumor location was supratentorial (ST) in 102 (43.2%) and infratentorial in 134 (56.8%). Pathologic analysis revealed 43.1% of ST-EPNs with RELA fusion and 88.1% of posterior fossa ependymomas (PF-EPNs) with positive H3K27me3 staining. Gross total removal was achieved in 169 cases (71.6%). During follow-up, 97 (41.1%) patients had disease progression and 39 (16.5%) died. Kaplan-Meier analysis showed that patients with H3K27me3-positive PF-EPN had excellent survival, whereas patients with RELA fusion-positive ST-EPN or H3K27me3-negative PF-EPN had poor prognosis (progression-free survival: P=1.3E-16, overall survival: P=2.5E-12). Multivariate analysis showed that molecular subgroup, extent of resection, and Ki-67 index were strong independent prognostic indicators. In conclusion, our study provides essential information on the prognostic prediction of adult intracranial EPNs that will assist in establishing appropriate risk stratification and individualized treatment strategies in future clinical trials.

RELA Fusion in Supratentorial Extraventricular Ependymomas: A Morphologic, Immunohistochemical, and Molecular Study of 43 Cases.

Supratentorial extraventricular ependymomas (STEEs) are relatively rare ependymomas, and their pathologic and genetic characteristics are still poorly understood. The aim of this study was to determine the histologic, immunohistochemical, and RELA fusion features, as well as to clarify in more detail the clinical courses of STEEs. Data from a total of 43 patients with STEEs was analyzed retrospectively. The status of RELA fusion was evaluated using fluorescence in situ hybridization. The expression levels of L1CAM, p65, cyclin D1, and p53 were assessed using immunohistochemistry. Progression-free survival and overall survival were calculated via Kaplan-Meier estimation using the log-rank test. Among all 43 STEEs, 65.1% (28/43) are positive for RELA fusion. Interestingly, almost half of the patients with RELA fusion-positive ependymomas are adults (13/28), and 89.3% (25/28) cases are anaplastic ependymomas, which suggests that RELA fusion testing is necessary in adults with STEEs. We investigated the immunohistochemical status of p65, L1CAM and CCND1 protein expression for their ability to predict RELA fusion status. RELA fusion-positive STEEs are frequently associated with expression of p65 (85.2%), L1CAM (85.2%), and CCND1 (81.5%). The accuracy of predicting RELA fusion status was much higher when the expression of p65 and L1CAM was combined, that is, when both were immunopositive. The status of RELA fusion, p53 overexpression, and extent of tumor resection are significantly associated with prognosis.

Epithelial-to-mesenchymal transition-related transcription factors are up-regulated in ependymomas and correlate with a poor prognosis.

Epithelial-to-mesenchymal transition (EMT) plays an important role in invasion and metastasis of various cancers including gliomas. EMT has also been linked to cancer stem cells and resistance to chemotherapy. An initial in-silico data mining in a published ependymoma (EPN) patient series (GSE21687) revealed up-regulation of EMT transcription factors in tumor samples. Furthermore, quantitative real-time polymerase chain reaction-based gene expression analysis of EMT transcription factors in 96 EPNs showed significant up-regulation of SNAI1, SNAI2, ZEB1, and TWIST1 as compared with normal brain, associated with up-regulation of CDH2/N-cadherin and down-regulation of CDH1/E-cadherin. Although this was observed in varying degrees in all clinicopathological-molecular subgroups of EPNs, it was most evident in supratentorial EPNs harboring fusions of RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) gene and in posterior fossa EPNs. Immunohistochemistry performed in 60 of the above cases corroborated with gene expression patterns, and immunopositivity for Snail, Slug, Zeb1, and Twist1 was observed in 80%, 80%, 81%, and 63% of all EPNs. Immunopositivity for N-cadherin and E-cadherin was observed in 76.6% and 2% of the cases, respectively. Univariate Cox regression analysis showed that low expression of CDH1/E-cadherin (P = .002) and high expression levels of CDH2/N-cadherin (P < .001), SNAI1/Snail (P = .023), SNAI2/Slug (P < .001), and ZEB1 (P < .001) were associated with shorter progression-free survival. Here, we report for the first time the existence of EMT-like phenotype in EPNs. These factors could represent new prognostic and therapeutic targets in EPN.

Cerebellar ependymoma with overlapping features of clear-cell and tanycytic variants mimicking hemangioblastoma: a case report and literature review.

BACKGROUND: Imaging and histology of clear-cell ependymoma and cerebellum-based hemangioblastoma are similar; distinguishing between them is a diagnostic challenge. CASE PRESENTATION: A 62-year-old Chinese woman presented with an intermittent headache of 8 years' duration. Computed tomography and magnetic resonance imaging revealed a mass in the cerebellum. Neurological imaging suggested hemangioblastoma (HB). Histologically, the tumor included cellular and paucicellular areas, in which cells were arranged in nests or diffusely distributed; and a highly vascular area, in which tumor cells were arranged in clusters and separated by capillaries. At low magnification, the tumor mimicked cellular HB, but at high magnification, tumor cells showed clear cytoplasm instead of the vacuolated cytoplasm typically observed in HB. Moreover, spindly, bipolar elements resembling tanycytes were observed within the nest structures. Although these features indicated the possibility of ependymoma, neither true ependymal rosettes nor an ependymal-lined profile was observed. The tumor was characterized by prominent vascularity, but glomeruloid formation was absent. We saw pleomorphism in foci of some tumor giant cells, but pathologic mitosis and palisaded necrosis were absent. Most tumor cells were positive for glial fibrillary acidic protein and S100. Epithelial membrane antigen was expressed with a paranuclear dot-like or a ring-like pattern. The Ki-67 index was approximately 2%. Considering the patient's symptom, neurological imaging, and pathological findings, she was diagnosed as cerebellar ependymoma (WHO grade II). CONCLUSIONS: Here, we report a case of ependymoma with overlapping clear-cell and tanycytic features, and review the literature to evaluate its real incidence. Pathologists should consider this rare diagnosis when confronted with a similar presentation.

Ependymoma with diffuse signet-ring features: report of a case and review of the literature.

Signet-ring cell ependymoma is a rare variant of ependymoma with only seven cases described in literature. Biological behavior and prognosis of this entity are not well-known until now. We present a case of a 49-year-old female with a history of headache and gait instability. Magnetic resonance imaging showed an upper cervical tumor with cystic component and mural nodule. The patient underwent surgery. Microscopically some cells displayed an eccentric nucleus compressed to the periphery by vacuolated cytoplasm. Perivascular pseudorosettes and ependymal rosettes were seen only focally. The cells were positive for glial fibrillary acidic protein and epithelial membrane antigen. The diagnosis was ependymoma with diffuse signet-ring features, grade II according to the World Health Organization. It may be difficult to diagnose this unusual variant of ependymoma especially on small biopsies or frozen sections. A complete examination of the specimen is recommended with immunohistochemical confirmation to rule out potential morphologic mimics, such as metastatic adenocarcinomas and gliomas in the differential diagnosis.

Temozolomide Treatment for Pediatric Refractory Anaplastic Ependymoma with Low MGMT Protein Expression.

The benefit of postoperative chemotherapy for anaplastic ependymoma remains unknown. We report two pediatric patients with refractory anaplastic ependymoma treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT protein expression was low. With TMZ treatment, one patient had a 7-month complete remission; the other, stable disease for 15 months. Three other patients did not respond to TMZ; two had high and one low MGMT expression, and two showed no MGMT promoter methylation. These findings suggest that TMZ may be effective for pediatric refractory anaplastic ependymoma with low MGMT protein expression.

A rare case of malignant pediatric ectomesenchymoma arising from the cerebrum.

Malignant ectomesenchymoma is a rare tumor that contains both ectodermal and mesenchymal elements. So far, only 7 patients with a manifestation in the cerebrum (with confirmed clinicopathological data) have been reported. A 4-year-old girl was present at our hospital with a 3-week history of intermittent sudden dizzy with no apparent cause. MRI showed an irregular enhanced lesion in the left frontal-parietal lobe and lateral ventricle with peripheral gadolinium-enhancement with a significant surrounding edema. Total removal of the tumor was performed. Histological examination of the resected tumor revealed a mixed astrocytoma and anaplastic ependymoma component with undifferentiated mesenchymal spindle cell component. Generally speaking, the main malignant part in most cases of malignant ectomesenchymoma (MEM) is the mesenchymal component. In the present case, the malignant component was both in the mesenchymal and ectodermal part. In particular, the mesenchymal part was mainly composed of spindle cells, and the ectodermal part primarily consisted of gliomatous component and anaplastic ependymoma component. The patient was then treated with chemotherapy and as regard to the prognosis, there was no evidence of tumor recurrence at the 5 months' follow-up. The long term follow-up is still in progress.

Intracranial extra-axial ependymoma involving the petroclival region: a rare case report.

Intracranial extraaxial ependymomas (IEAEs) are very rare, and extra-axial petroclival ependymoma (EAPE) has not been reported in the reviewed English-language literature by now. We present a male patient with EAPE misdiagnosed as a petroclival meningioma preoperatively, and involved recurrence at 4th months after operation though totally resection. Thereafter, we report this case and discuss the clinical characteristics of the disease by briefly review.

Evaluation of the expression of C-kit (CD117) in ependymomas and oligodendrogliomas.

C-kit is a proto-oncogene located on the long arm of chromosome 4. Its product, CD117, is a specific immunohistochemical (IHQ) marker that is associated with response to a potent tyrosine kinase inhibitor therapy with STI-571 (Gleevec®) in chronic myelogenous leukemia and GISTs. In our study, we aimed to evaluate the expression of CD117 in glial tumors as this finding may guide therapeutic approaches for these brain tumors. Ependymomas and oligodendrogliomas, in formalin fixed and paraffin embedded blocks were assayed for CD117 immunoreactivity using anti-c-kit (CD117, DAKO). GISTs were used as positive control. We observed immunoreactivity of CD117 protein in 25.5% of tumors in both histological types. In oligodendrogliomas, there was an association between older age at diagnosis and positivity for CD117 (P=0.039). In addition, we observed an association between higher tumor grade (grade III) and positivity for CD117 (P=0.007). No clinical association was observed in ependymomas (P>0.05). This study encourages further investigations, considering that CD117 may be a possible oncogenic factor in some glial tumors. In this case, tumors that express this marker may eventually benefit from a therapy with selective inhibitors of receptor kinases.

A case of anaplastic clear-cell ependymoma presenting with high erythropoietin concentration and 1p/19q deletions.

We describe a 19-year-old woman with onset of epileptic seizure, and a small mural nodule and multicystic lesions with severe brain edema located in the right frontal lobe. At surgery, the tumor and a clear margin was removed, and symptoms improved postoperatively. Extended local radiotherapy (60 Gy) was performed. Histopathological examination revealed oligodendroglioma-like tumor cells with a perinuclear halo. The tumor cells extended processes toward CD34-positive proliferating vessels, which resemble a basement membrane. These proliferating vessels formed a tumor membrane so that there was a clear margin between the tumor and brain tissue. Tumor cells were positive for epithelial membrane antigen in a dot-like pattern. MIB-1 staining index was 50.6%. Electron microscopy showed cilia and zipper-like junctions, and anaplastic clear-cell ependymoma grade III was diagnosed. A characteristic of the case was formation of a tumor membrane by proliferating tumor blood vessels. Fluorescence in situ hybridization showed 1p/19q deletions, and the concentration of erythropoietin in the cyst fluid was abnormally high, at 1,859.4 mIU/ml. Erythropoietin and erythropoietin receptors were verified with immunohistochemical staining.

Podoplanin is a potential marker for the diagnosis of ependymoma: a comparative study with epithelial membrane antigen (EMA).

Podoplanin is a mucin-type transmembrane sialoglycoprotein that is characteristically expressed in lymphatic endothelia. It is also expressed in the ependyma of the central nervous system as well as in ependymomas. Particularly, membrane-bound structures along the luminal surface, ring-like structures, and dot-like structures in the cytoplasm, all of which were originally reported for epithelial membrane antigen (EMA) immunohistochemistry in ependymoma, were also reported for podoplanin immunohistochemistry in ependymoma. This study was undertaken to evaluate podoplanin as compared with EMA as a marker of ependymoma. A total of 16 ependymomas (WHO Grade (G) II, 9 cases; GIII, 4; myxopapillary, 2; GIII clear cell, (1) were immunohistochemically studied using antibodies against podoplanin (clones D2-40 and NZ-1) as well as an antibody against EMA (clone E29). In all cases, D2-40 and NZ-1 excellently labeled linear signals along the luminal surface of ependymal canals/rosettes, dot-like structures, and/or ringlike structures, as did E29. These structures were generally more abundant in GII ependymomas than in GIII ependymomas. A semiquantitative analysis between the immunopositive structures of D2-40 or NZ-1 and E29 was conducted with a focus on the dot-like structures and the ring-like structures in the cases of GII and GIII ependymoma. The result showed that there was no statistical difference between D2-40 or NZ-1 and E29. Our study suggests that podoplanin is a potential marker for the diagnosis of ependymoma that corresponds to EMA. Anti-podoplanin antibodies and anti-EMA antibodies could cooperate with each other for the diagnostic immunohistochemistry of ependymoma.

Comparative analysis of annexin-1 in neuroepithelial tumors shows altered expression with the grade of malignancy but is not associated with survival.

In various types of cancer, the expression of members of the annexin family of calcium- and phospholipid-binding anti-inflammatory proteins is dysregulated. Annexin-1 (ANXA1, lipocortin-1) is involved in proliferation, differentiation and apoptosis. It serves as a substrate for the epidermal growth factor receptor (EGFR), which is frequently amplified in primary gliomas. It is unclear how annexin-1 is expressed in various neuroepithelial tumors, and whether there is any association with tumor malignancy or survival. We studied annexin-1 expression in 394 glial neoplasms of all grades of malignancy and 81 normal brain samples by immunohistochemistry using tissue microarrays. The results were validated using western blot and reverse transcription-PCR (RT-PCR). In the normal human brain, the expression of annexin-1 is limited to ependymal cells and subependymal astrocytes, but is also upregulated in reactive astrocytes. Ependymomas and astrocytomas showed significantly higher mean annexin-1 expression levels in the cytoplasm compared with oligodendrogliomas (both: P<0.0001). In addition, nuclear staining of annexin-1 in oligodendroglial tumor cells was significantly reduced (P=0.0002), which may be used as a diagnostic tool for differentiating between astrocytomas and oligodendrogliomas. Although annexin-1 expression in ependymomas decreased with the grade of malignancy, diffuse astrocytomas showed a significant increase in cytoplasmic annexin-1-positive tumor cells. However, survival analysis showed that the expression of annexin-1 is not associated with patient survival. Similar to the EGFR amplification profile, primary glioblastomas had a higher annexin-1 expression level compared with secondary glioblastomas. Thus, annexin-1 upregulation in astrocytomas may contribute to tumor progression and its expression profile is similar to its substrate, EGFR, suggesting a possible regulation thereof.

Distribution of 4-hydroxynonenal-protein conjugates as a marker of lipid peroxidation and parameter of malignancy in astrocytic and ependymal tumors of the brain.

AIMS AND BACKGROUND: Lipid peroxidation (LPO) is an autocatalytic process caused by oxidative stress. It results in the production of 4-hydroxynonenal (HNE), which plays a crucial role in hypoxic brain injury, neuronal degeneration and apoptosis. The aim of this study was to evaluate the expression of HNE in 120 astrocytic and 40 ependymal tumors in relation to tumor type, grade of malignancy, angiogenesis, and presence of necrosis and apoptosis. METHODS: Immunohistochemical staining was performed using a monoclonal antibody for the detection of HNE-modified proteins. RESULTS: HNE-protein adducts were found in all tumors. The incidence of HNE-immunopositive tumor cells increased with increasing grades of malignancy. Significantly higher HNE expression was found in tumor cells of glioblastomas multiforme than in cells of pilocytic astrocytomas (P < 0.005), and in anaplastic ependymomas than in benign ependymomas (P < 0.01). HNE-immunopositive tumor cells were distributed more diffusely than in perivascular locations (P < 0.05). Pronounced HNE-protein adducts were detected in mitotic, necrotic, and apoptotic cells. HNE was expressed in the endothelium of almost all tumor vessels, but its expression in the walls of the vessels was significantly higher in diffuse and anaplastic astrocytomas than in pilocytic astrocytomas and glioblastomas multiforme (P < 0.05). The number of microvessels containing HNE in their endothelium and walls was significantly associated with the grade of malignancy in both astrocytic (P < 0.001) and ependymal tumors (P < 0.05), although microvessels in pilocytic astrocytomas were significantly more numerous (P < 0.05) than in diffuse astrocytomas. CONCLUSIONS: LPO seems to be a common pathological process in astrocytic and ependymal glial tumors, proportional to the level of malignancy and neovascularization. Therefore, HNE might be involved in the damage of brain cells and the induction of malignancy.

Ependymoma of the sella turcica: a variant of pituicytoma.

A broad spectrum of neoplasms affects the sellar region. Among these, gliomas are rare, most being tumors of pituicytes such as granular cell tumor and pituicytoma. Only 4 ependymomas of the human sellar region have been reported to date and all have had classic histologic features. Herein, we describe the clinicopathologic features of a sellar, low-grade ependymoma with unusual histology, but classic ultrastructural features, occurring in an elderly patient and thus expanding the spectrum of reported cases. The literature is reviewed and concepts of histogenesis are explored, particularly an origin in "ependymal pituicytes." The concept that sellar ependymoma is pituicyte-derived is explored.

Intramedullary amputation neuromas associated with spinal ependymomas.

We report 5 spinal intramedullary masses containing combined ependymoma and traumatic neuroma. The ependymomas, grade II "cellular" types, were intermixed with or separate from wavy, vaguely fascicular tissue that contained multiple axons immunoreactive for neurofilament protein. The neuromas presumably arose from small perivascular nerve twigs that have been implicated in the pathogenesis of intramedullary neuromas in non-neoplastic spinal diseases. Pathologists should be aware of this distinctive intramedullary tissue that is not to be confused with a neoplasm.

Nogo-a expression in glial CNS tumors: a tool to differentiate between oligodendrogliomas and other gliomas?

Gliomas are the most frequent primary brain tumors. In a minority of cases, the differentiation between astrocytomas and oligodendrogliomas based on morphologic characteristics alone can be difficult; though it is important, as patients with oligodendrogliomas follow a more favorable clinical course. Here we report on the immunohistochemical expression pattern of the oligodendrocytic marker Nogo-A in 113 central nervous system tumors including 28 oligodendrogliomas [15, World Health Organization (WHO) grade II; 13, grade WHO III], 50 astrocytomas [10, grade WHO II; 11, grade WHO III; 29 glioblastoma multiforme (GBM)], 11 ependymomas WHO grade II, 7 central neurocytomas, 2 dysembryoplastic neuroepithelial tumors (DNTs), 5 clear cell meningiomas, and 10 metastases to the brain. The oligodendrocytic marker Nogo-A was found to be strongly expressed in 71% of oligodendrogliomas, but in 0% of ependymomas WHO grade II, astrocytomas WHO grade II or III, DNTs, central neurocytomas, or clear cell meningiomas. In GBM, a subgroup of tumors (24%) showed strong expression of Nogo-A coincidently with Ki67 positivity but glial fibrillary acidic protein-negativity. However, neither in oligodendrogliomas nor GBM was a correlation between the loss of 1p19q and the extent of Nogo-A expression observed. Our findings indicate that Nogo-A is strongly expressed in the majority of oligodendrogliomas and might be a helpful marker to distinguish oligodendrogliomas from astrocytomas WHO grades II and III as well as ependymomas. They also support the hypothesis that GBM may be a heterogeneous group of tumors derived from different progenitor cells.

Ki67 index in intracranial ependymoma: a promising histopathological candidate biomarker.

AIMS: The Ki67 tumour cell proliferation index is an independent prognostic factor in ependymoma patients. Essential prerequisites for validation of the Ki67 index as a histopathological biomarker are the reproducibility of this factor and its prognostic influence by different observers (proof of objective clinical and analytical performance). To this end, the aim was to analyse systematically inter- and intraobserver agreement and reproducibility of the prognostic impact of the Ki67 index in intracranial ependymoma. METHODS AND RESULTS: The study cohort contained 78 cases of intracranial ependymoma. In all cases, the Ki67 index was assessed by four experienced observers (EOs) and by four inexperienced observers (IOs) using the manual hot-spot method. There was considerable agreement on Ki67 index assessment. There was higher observer agreement among EOs compared with IOs. For each observer, survival analysis showed significant association of low Ki67 index with favourable patient outcome. CONCLUSIONS: Our data show that the Ki67 index in intracranial ependymoma is a reproducible and robust prognostic factor and can be considered a promising histopathological candidate biomarker. Attainment of biomarker status requires further translational studies in the context of prospective therapeutic trials.

Various components of the insulin-like growth factor system in tumor tissue, cerebrospinal fluid and peripheral blood of pediatric medulloblastoma and ependymoma patients.

The insulin-like growth factor (IGF) system plays an important role in neuronal development and may contribute to the development of brain tumors. In this study, we studied mRNA expression levels of IGFs, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor receptors (IGFRs) in 27 pediatric medulloblastomas, 13 pediatric ependymomas and 5 control cerebella. Compared to normal cerebellum, mRNA levels of IGFBP-2 and IGFBP-3 were significantly increased in medulloblastomas and ependymomas. IGFBP-2 expression was indicative of poor prognosis in medulloblastomas, whereas IGFBP-3 mRNA levels were especially high in anaplastic ependymomas. IGFBP-5 and IGF-II mRNA levels were significantly increased in ependymomas compared to control cerebellum. Protein expression levels of IGFs and IGFBPs were analyzed in the cerebrospinal fluid (CSF) of 16 medulloblastoma, 4 ependymoma and 23 control patients by radioimmuno assay to determine whether they could be used as markers for residual disease after surgery. No aberrant CSF protein expression levels were found for ependymoma patients. In medulloblastoma patients, the IGFBP-3 protein levels were significantly higher than in ependymoma patients and controls. Moreover, enhanced levels of proteolytic fragments of IGFBP-3 were found in the CSF of medulloblastoma patients, being in concordance with a significantly increased IGFBP-3 proteolytic activity in the CSF of these patients. In conclusion, our data suggest that the IGF system is of importance in pediatric medulloblastomas and ependymomas. Larger studies should be conducted to validate the predictive values of the levels of intact IGFBP-3 and proteolytic fragments in CSF in the follow-up of medulloblastomas.

Ependymal tumors with sarcomatous change ("ependymosarcoma"): a clinicopathologic and molecular cytogenetic study.

Gliosarcomas are uncommon primary tumors of the central nervous system defined as exhibiting both glial and sarcomatous components. Sarcomatous change occurring in ependymal tumors is rare. We identified 11 such examples. There were 6 female and 5 male patients (median age, 18 y; range, 2 to 63). The tumors were located in the parieto-occipital (n=2), temporal (n=1), parietal (n=1), frontal (n=1), and occipital lobes (n=1), as well as the lateral ventricles (n=2), insula (n=1), cerebellopontine angle (n=1), and fourth ventricle/cerebellopontine angle (n=1). At presentation, the sarcomatous component was noted in 6 (of 10) cases and the ependymal element was grade III in 7 and grade II in 3 tumors, respectively. The sarcomatous component consisted of a reticulin rich, glial fibrillary acidic protein-negative fibrosarcoma (n=5) or pleomorphic spindle cell sarcoma (n=3), and 2 examples with heterologous elements: osseous and cartilaginous (n=1) and osseous only (n=1). The single case involving the fourth ventricle/left cerebellopontine angle consisted of subependymoma and fibrosarcoma components in roughly equal proportions at presentation. Fluorescence in situ hybridization studies performed with probes targeting the NF2 gene and other members of the protein 4.1 gene family demonstrated similar alterations in the ependymal and sarcomatous components in the cases tested, including polysomies/polyploidy (n=3), gains of 1q (n=3), deletions of 22q (n=2) and 6q (n=1), and monosomy 18 (n=1). There was no evidence of MDM2 or CCND1 amplification in any of the cases tested. On follow-up, 5 patients expired 4 months to 18 years after initial resection and 4 to 11 months after development of the sarcomatous component (mean, 7.6 mo); 1 patient is alive at 5 years with recurrent disease, and 1 is alive without recurrence 12 years after initial gross total resection followed by radiation therapy. Although rare, ependymal neoplasms must be included among the gliomas prone to undergo sarcomatous change and we propose the term "ependymosarcoma" for these tumors.

Clear-cell ependymoma of the cerebellum: a case report.

A case of clear-cell ependymoma occurring in the cerebellum of a 3-year-old girl is reported. Light-microscopically, the tumor consisted mainly of clear cells with a perinuclear halo and showed some vague perivascular pseudorosettes, not true rosettes. In addition, the histological features of anaplasia, characterized by increased mitosis and focal pseudopalisading necrosis, were also observed. Immunohistochemically, the tumor cells were focally positive for glial fibrillary acidic protein and weakly positive for epithelial membrane antigen. Ultrastructurally, the intermediate junctions and rudimentary cilia confirmed the ependymal differentiation. Fifteen cases of infratentorial clear-cell ependymoma have been reported to date, and this case is the second childhood tumor among them, to the best of the authors' knowledge.