Anaplastic Ependymoma Research Articles

Simultaneous cerebrospinal fluid and hematologic metastases in a high-grade ependymoma

Background:Ependymomas are relatively uncommon tumors that constitute about 7% of all primary intracranial neoplasms. Among these, high-grade ependymomas are locally aggressive and recur most commonly at the primary site following resection. Ependymomas are also known to be the one glial neoplasm that tends to frequently metastasize inside and outside the central nervous system (CNS) that complicates workup and management. Metastasis due to surgical manipulation is common and neurosurgeons should be well-versed in the most effective methods to remove these tumors in order to avoid such metastases.Case Description:Here, we report a case of a 28-year-old female who initially presented with a parenchymal World Health Organization (WHO) grade III anaplastic ependymoma of the occipital lobe without metastasis. After multiple resections, the patient showed no evidence of disease recurrence for 2 years. During follow-up, new metastasis to the frontal lobe as well as to the lung were discovered 2 years after the initial surgery, without recurrence at the tumor's primary site.Conclusions:While uncommon, this case demonstrates the possibility for ependymomas to metastasize via cerebrospinal fluid to other locations within the CNS and hematologically to extraneural locations without recurring locally.

Supratentorial extraventricular ependymomas: A retrospective study focused on long-term outcomes and prognostic factors

ObjectiveSupratentorial extraventricular ependymomas are relatively rare. Long-term outcomes and prognostic factor for this rare tumor have not been well established. The purpose of this study was to demonstrateprogression-freesurvival(PFS),overallsurvival(OS), and prognostic factors of such tumor. Patients and methodsFifty-five patients with supratentorial extraventricular ependymomas from our hospital were included in this study. Epidemiological characteristics, clinical features, treatment,long-term outcomes, and prognostic factors for PFS and OS were reviewed retrospectively. ResultsThe patients consisted of 30 males and 25 females with mean age of 30.0 ± 23.6 years (range, 1–74 years). Twenty-nine tumors were located in the right hemisphere, and 26 in the left side. The 2 most common tumor locations were the frontal (n = 19; 35%) and parietal lobe (n = 11; 20%). All patients underwent surgical resection. Gross-total resection (GTR) was achieved in 42 cases (76%) and subtotal resection (STR) was performed in 13 patients (24%). According to the WHO classification system, 38 tumors (69%) were Grade III (anaplastic ependymoma), and 17 (31%) were Grade II (ependymoma). Three-,5-, and 10 year PFS rates were 60%, 49%, and 36%, respectively. Three-,5-, and 10 year OS rates were 79%, 64%, and 49%, respectively. EOR and tumor grade were identified as prognostic factors for PFS and OS on univariate analysis, multivariate analysis, and Kaplan-Meierlog-rank testing. Subtotal resection (STR) predicted a worse PFS (HR = 4.808; 95%, 1.942–11.905; P = .001) and OS (HR = 5.650; 95%, 2.114–15.152; P = .001). WHO Grade III tumors also had worse PFS (HR = 3.922; 95%, 1.429–18.182; P = .012) and OS (HR = 6.329; 95%, 1.328–30.303; P = 0.021). For patients with tumor recurrence, reoperation was significant prognostic factors for OS (HR = 2.091; 95%, 0.939–4.654; p = .000). Age, sex, tumor side, and postoperativeradiotherapy were not prognostic factors for PFS and OS. ConclusionsMost supratentorial extraventricular ependymomas are WHO grade III tumors. STRandWHO Grade III pathology predicted worse PFS and OS. Gross-total resection remains the optimal treatment for patients with supratentorial extraventricular ependymoma. Reoperation should be considered first in cases of recurrence. The role of postoperative radiotherapy as an adjuvant treatment for supratentorial extraventricular ependymoma needs further investigation.

EANO guidelines for the diagnosis and treatment of ependymal tumors.

Ependymal tumors are rare CNS tumors and may occur at any age, but their proportion among primary brain tumors is highest in children and young adults. Thus, the level of evidence of diagnostic and therapeutic interventions is higher in the pediatric compared with the adult patient population.The diagnosis and disease staging is performed by craniospinal MRI. Tumor classification is achieved by histological and molecular diagnostic assessment of tissue specimens according to the World Health Organization (WHO) classification 2016. Surgery is the crucial initial treatment in both children and adults. In pediatric patients with intracranial ependymomas of WHO grades II or III, surgery is followed by local radiotherapy regardless of residual tumor volume. In adults, radiotherapy is employed in patients with anaplastic ependymoma WHO grade III, and in case of incomplete resection of WHO grade II ependymoma. Chemotherapy alone is reserved for young children <12 months and for adults with recurrent disease when further surgery and irradiation are no longer feasible. A gross total resection is the mainstay of treatment in spinal ependymomas, and radiotherapy is reserved for incompletely resected tumors. Nine subgroups of ependymal tumors across different anatomical compartments (supratentorial, posterior fossa, spinal) and patient ages have been identified with distinct genetic and epigenetic alterations, and with distinct outcomes. These findings may lead to more precise diagnostic and prognostic assessments, molecular subgroup-adapted therapies, and eventually new recommendations pending validation in prospective studies.

Aggressive Supratentorial Ependymoma, RELA Fusion-Positive with Extracranial Metastasis: A Case Report.

Ependymoma is the third most common pediatric primary brain tumor. Ependymomas are categorized according to their locations and genetic abnormalities, and these two parameters are important prognostic factors for patient outcome. For supratentorial (ST) ependymomas, RELA fusion-positive ependymomas show a more aggressive behavior than YAP1 fusion-positive ependymomas. Extracranial metastases of intra-axial neuroepithelial tumors are extremely rare. In this paper, we report a case of aggressive anaplastic ependymoma arising in the right frontoparietal lobe, which had genetically 1q25 gain, CDKN2A homozygous deletion, and L1CAM overexpression. The patient was a 10-year-old boy who underwent four times of tumor removal and seven times of gamma knife surgery. Metastatic loci were scalp and temporalis muscle overlying primary operation site, lung, liver, buttock, bone, and mediastinal lymph nodes. He had the malignancy for 10 years and died. This tumor is a representative case of RELA fusion-positive ST ependymoma, showing aggressive behavior.

PATH-47. CLINICAL SENSITIVITY AND SPECIFICITY OF ILLUMINA METHYLATION ARRAY FOR CLASSIFYING ADULT GLIOMAS INTO WHO GROUPS

WHO criteria now classify adult glioma into groups using combination of tumor grade and two tumor markers: 1p/19q codeletion and IDH1/2 mutation. TERT promoter mutation has also been shown to further classify tumors into clinically-meaningful groups. The Cancer Genome Atlas (TCGA) recently identified six methylation subtypes of glioma. Thus, as part of a clinical transformation process, we evaluated sensitivity and specificity of the Illumina methylation array to classify adult gliomas into appropriate WHO groups. We molecularly profiled 86 specimens from our institution via Illumina EPIC methylation array: 76 adult gliomas, seven other brain tumors (anaplastic ependymoma, glial neoplasm, pilocytic astrocytoma) and three gliosis samples. The 76 adult gliomas also have Affymetrix OncoScan array, IDH1/2 and TERT promoter mutation sequencing data. Using only methylation data, the EPIC array correctly classified 70 (92%) of 76 gliomas into appropriate WHO groups. When EPIC array copy number data were used to verify codeletion status, 71 (93%) were correctly classified. Similarly, using only Illumina methylation data, 560 (90%) of 622 TCGA gliomas were correctly classified into WHO groups. When methylation array copy number data were used to verify codeletion status 611 (98%) were correctly classified. While the OncoScan and EPIC methylation array had 100% concordant codeletion status, there were discrepancies for other genomic regions; especially in gliomas that carry IDH1/2, ATRX and TP53 mutations. All seven (100%) of the other brain tumors were classified as LGm6. With respect to TERT mutation, of 44 TCGA IDH wildtype, TERT wild-type and non-codeleted gliomas, 64% were classified as LGm6; thus, supporting the importance of TERT for further classifying gliomas. Overall, when methylation and 1p/19q copy number data are used, the Illumina methylation array correctly classified most adult gliomas into appropriate WHO groups. However, caution should be used when evaluating genome-wide copy number alterations solely using the methylation array.

Ectopic Solitary Cortical Anaplastic Ependymoma in a Child: A Rare Entity with Short Illustrative Review

AbstractEpendymomas are usually infratentorial and intraventricular. They originate from the ependymal cell lining of the ventricles. Cortical extraventricular supratentorial ependymomas are rare and fewer than 15 cases are reported worldwide. In pediatric age group, seven cases are reported. We report a rare case of 4-year-old boy with right frontoparietal anaplastic ependymoma who underwent gross total excision of lesion.

Ependymomas arising outside of the central nervous system: A case series and literature review

BackgroundExtracranial and extraspinal ependymomas are extremely rare tumors mostly published in the literature as case reports. MethodsMD Anderson Cancer Center institutional database was screened for patients with extra CNS ependymomas over a 25 year period. ResultsEight patients with extra CNS ependymoma were identified. Five cases originated in the sacrum or subcutaneous sacral area, and the other 3 cases originating in the breast, lung and adnexa of the uterus. By histology, most cases were myxopapillary ependymomas (5 cases), 2 cases were grade II ependymoma and 1 case was an anaplastic ependymoma. Metastases occurred in 6 cases and 3 patients died due to progressive disease. Most cases required surgery, radiation and chemotherapy. ConclusionExtra CNS ependymomas are very rare tumors that tend to metastasize, even though most cases are histologically classified as low grade ependymomas.

Surgery for spinal intramedullary tumors: technique, outcome and factors affecting resectability.

Intramedullary spinal cord tumors (IMSCTs) are relatively infrequent lesions with ependymomas and astrocytomas representing the most common types. Microsurgical resection is established as the treatment of choice for these challenging lesions. We reviewed the surgical outcome of 29 cases operated for IMSCTs by the same surgeon between 2009 and 2015. The median follow-up period was 31months, and all patients were followed up at least for 1year. Among these 29 cases, 5 patients were previously operated for partial resection elsewhere. Age ranged from 9 to 62years with a median of 39years. All patients were symptomatic before surgery. The most common pathology was ependymoma (16 cases), and the most common tumor location was the cervical spine (18 cases). Gross total resection was achieved in 20 out of 29 cases (68.9%). Tumors were totally excised in all cases of ependymoma except in two patients; one was previously operated and irradiated and the second had an extensive anaplastic ependymoma. Sixteen cases experienced immediate post-operative worsening which was temporary in all but one case. At 1-year follow up, 23 patients (79.3%) maintained their pre-operative McCormick grade, 5 patients (17.2%) had a better grade, and 1 patient (3.5%) deteriorated. Surgery still represents the mainstay in the management of IMSCT. Gross total resection can be achieved safely in many cases especially in the presence of an identifiable plane of cleavage between the tumor and the normal spinal cord.

Clinical and molecular subgroups of ependymoma in adulthood: An analysis of the German Glioma Network.

2038 Background: Ependymoma is a subtype of glioma that is rare in adults. Its classification has remained entirely morphological until recently, and surgery and radiotherapy remain the mainstays of treatment. Here we characterized DNA methylation profiles and their clinical correlates in the prospectively assembled cohort of the German Glioma Network. Methods: The GGN cohort was screened for patients diagnosed with myxopapillary ependymoma, subependymoma, classic ependymoma and anaplastic ependymoma for whom clinical data and remaining tumor tissue were available. Tumors were subjected to DNA methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip platform. Molecular data were correlated with morphological tumor and clinical patient characteristics. Results: One hundred and twenty-two ependymoma patients with available tumor tissue were identified. Each adult tumor could be assigned to one of the previously defined methylation classes of ependymoma. Molecular entities of ependymal brain tumors display distinct copy-number variations. PF-EPN-B and ST-EPN-RELA tumors tend to have a worse prognosis than other ependymal subtypes in adults. Conclusions: Molecular classification of adult ependymal methylation subclasses should be implemented in routine diagnostics. Patients with PF-EPN-B and ST-EPN-RELA subtypes might benefit from early treatment beyond surgery.

Pediatric Basal Ganglia Region Tumors: Clinical and Radiologic Features Correlated with Histopathologic Findings.

To summarize the clinical and radiologic features of pediatric basal ganglia region tumors (PBGRT) in correlation with their histopathologic findings to reduce inappropriate surgery and identify tumors that can benefit from maximal safe resection. The records of 35 children with PBGRT treated in our hospital from December 2011 to December 2015 were analyzed retrospectively. The clinical and radiologic features of these tumors were summarized and correlated with their histopathologic diagnosis. Our series included 15 astrocytomas and 11 germ cell tumors (GCTs). Basal ganglia astrocytomas were characterized by various clinical presentations and an ill-circumscribed mass with the involvement of surrounding structures on neuroimaging and mostly occurred in the first decade of life (n= 10; 66.7%). Basal ganglia GCT mostly occurred in the second decade of life (n= 8; 72.7%) with hemiparesis as the most common symptom (n= 9; 81.8%). The tumors were located predominantly in the caput of caudate nucleus (n= 8; 72.7%) with hemiatrophy as the typical sign (n= 8; 72.7%). Occasionally, other tumors also could occur in this region, including primitive neuroectodermal tumor (n= 1), atypical teratoid/rhabdoid tumor (n=1), anaplastic ependymoma (n=1), lymphoma (n=1), extraventricular neurocytoma (n= 1), gangliogliomas (n= 2), oligodendroglioma (n= 1), and dysembryoplastic neuroepithelial tumor (n= 1). Astrocytoma and GCT are the most common PBGRTs. Low-grade astrocytomas could benefit from maximal surgical resection, whereas GCTs merit neoadjuvant chemoradiation therapy followed by second-look surgery. We advocate routine testing of tumor markers and analysis of their clinical and radiologic features to optimize the therapeutic strategy.

Diffusion tensor MR fiber tractography in assessment of inflammatory processes and neoplasms of the cervical cord

Our goal of this research is to assess the value of MR fiber tractography in assessment of inflammatory process and neoplasms of the cervical cord. PatientsWe included 40 patients diagnosed as inflammatory diseases and neoplasm of the cervical cord in our research. 17 patients with pathologically proved cervical cord neoplasms, including three patients with anaplastic astrocytoma, five patients with cellular ependymoma, two patients with anaplastic ependymoma, two patients with fibrillary astrocytoma, one glioblastoma multiforme (GBM), one with cervicomedullary glioma, two with metastasis and one hemangioblastoma. The remaining 23 patients were finally diagnosed as inflammatory processes of the cervical cord, through clinical examination, laboratory results and serial follow up. The latter category include ten patients with myelitis, eight with multiple sclerosis, three patients with post irradiation myelitis and two patients with neuromyelitis optica. MethodsMRI sequences including T2W (sagittal and axial), pre and post contrast T1 (Sagittal and axial) and diffusion tensor MR fiber tractography. ResultsAll the 17 patients with neoplasm of the cervical cord show more or less displacement of the cervical tract fibers, ten without fibers disruption and seven with fibers disruption. In all patients with inflammatory processes (23 patients) of the cervical cord no fibers displacement identified, but different grades of fibers disruption or sparse fibers. ConclusionMR fibers tractography is a very promising tool in assessment of inflammatory processes and neoplasms of the cervical cord.

The Molecular Feature of HOX Gene Family in the Intramedullary Spinal Tumors.

The expression of HOXB13 and HOXA9 proteins was detected. The purpose of this study was to investigate the molecular signature of spinal ependymoma (EPN) and astrocytoma, 2 most common types of intramedullary spinal tumor. Intramedullary spinal tumor is unusual. It leads to high neurological morbidity and mortality without treatment. Till now, its molecular feature has been elucidated up to a little extent. A total of 37 cases of spinal EPN, including 12 myxopapillary EPNs (MEPNs), 18 classic EPNs, and 7 anaplastic EPNs, and another 12 cases of astrocytoma were selected for this study. Immunohistochemical analysis of a large cohort of patients providing clinical tumor samples was performed to compare the expression of HOXB13 and HOXA9 not only between spinal EPN and astrocytoma but also among all 3 World Health Organization grades of spinal EPN. The results showed that HOXB13 and HOXA9 were selectively expressed in spinal EPN instead of astrocytoma. Furthermore, we found the strongest positive response of HOXB13 in MEPN whereas that of HOXA9 was ubiquitously detected in all subgroups of EPN. Both specificity and sensitivity of HOXB13 in MEPN indicated that HOXB13 might be a diagnostic marker to distinguish MEPN from other 2 types of EPN and a promising therapeutic target for MEPN. The strong immunoreactivity of HOXA9 in spinal EPN suggested an indispensable role in the progression of spinal EPN, and further research on its molecular function will provide new clues for the development of treatment options. N /A.

Cerebellopontine Angle Anaplastic Ependymoma: A Case Report and Literature Review

Anaplastic ependymomas are World Health Organization (WHO) Grade III neoplasms with extremely rare cases. We describe a case of cerebellopotine angle (CPA) anaplastic ependymoma in a 42-year-old woman. To the best of our knowledge, this is the first reported case of an anaplastic ependymoma at CPA space in the literature. To fill this gap, we here describe this unusual case to provide more insight into this tumor.

"Drop" Metastases from an Operated Case of Intracranial Anaplastic Ependymoma Identified on Fluoro-2-deoxyglucose Positron Emission Tomography/Computed Tomography.

The seeding of tumor through cerebrospinal fluid (CSF) from primary intracranial tumors is very rare, often goes undetected, and is usually identified only on autopsy. CSF cytology along with magnetic resonance imaging constitutes the standard approach of diagnosing this grave condition. Use of fluoro-2-deoxyglucose positron emission tomography/computed tomography (PET/CT) in indentifying spinal metastases from primary intracranial malignancies is very limited and has been reported in patients with metastatic glioblastoma multiforme and medulloblastomas. We present a rare case of metastatic anaplastic ependymoma to show the potentially clinically utility of PET/CT in diagnosing leptomeningeal or the so-called “drop” metastases.

Ependymomas: Prognostic Factors and Outcome Analysis in a Retrospective Series of 33 Patients.

BackgroundThe purpose of this study was to evaluate the prognostic factors and outcomes in patients with ependymoma to management plans.MethodsBetween 1997 and 2013, 33 patients with 25 ependymomas (WHO grade II) and eight anaplastic ependymomas (WHO grade III) were pathologically diagnosed. Six were pediatric patients (mean age, 6.15 years; range, 1.3–11 years), while 27 were adults (mean age, 47.5 years; range, 19–70 years). Of those, there were 12 adult patients with totally resected ependymomas without anaplastic pathology and adjuvant treatment. Prognostic factors were assessed in ependymoma patients. Prognostic factors were studied using Kaplan-Meier estimates in subgroups.ResultsFor six pediatric patients, the progression-free survival (PFS) was 43.7±13.5 months, and the overall survival (OS) was 58.1±13.7 months. For 27 adult patients, the PFS was 125.6±14.3 months, and the OS was 151.2±12.5 months. Age demonstrated a statistically significant effect on PFS (p=0.03) and OS (p=0.03). In adult ependymomas, the extent of tumor removal significantly affected PFS (p=0.03) and trended towards an effect on OS (p=0.06). Out of 12 patients with totally resected ependymomas without anaplastic pathology and adjuvant treatment, one patient showed tumor recurrence during follow-up (mean, 93.5 months; range, 27.9–162.7 months).ConclusionAdult patients with ependymomas were found to have better survival rates compared to pediatric patients. We suggest that totally resected adult ependymomas without anaplastic pathology could be observed without any adjuvant treatment, regardless of the tumor location.

PP39. 5-AMINOLEVULINIC ACID AIDED RESECTION OF PAEDIATRIC BRAIN TUMOURS: THE UK’S FIRST CASE SERIES

BACKGROUND: 5-aminolevulinic acid (5-ALA, Gliolan) use is well documented and established in the resection of adult high-grade gliomas. There is growing interest in its safety and usefulness in the paediatric populations. The main challenge in the latter is the diverse range of histopathological tumour types that can occur. We present the UK’s first case series of 5-ALA use in the paediatric population. METHODS: Parental consent was obtained for the 6 patients (age 1.6–15 years, median 6.5 years) to be given a dose of 20mg/kg of 5-ALA 3 hours pre-operatively. Intra-operatively the tumours were viewed under violet-blue light and the presence of fluorescence was recorded. Fluorescence status was compared with histopathological classification and grade. RESULTS: The case series included: a pilocytic astrocytoma (grade I), a pilomyxoid astrocytoma (II), a glioneuronal tumour (II), a ganglioglioma (II-III), an anaplastic ependymoma (III) and an anaplastic medulloblastoma (IV). Only the grade III ependymoma showed strong fluorescence with 5-ALA. The pilocytic astrocytoma (I) and pilomxyoid astrocytoma (II) showed moderate fluorescence and the ganglioglioma (II-III) showed weak fluorescence. No fluorescence was observed in the glioneuronal tumour (II) or the medulloblastoma (IV). No significant adverse drug reactions were recorded. CONCLUSION: This case series adds to the growing body of evidence demonstrating the safety of 5-ALA in the paediatric population. Our case series highlights the need for larger trials into the usefulness of 5-ALA in the different paediatric brain tumour types. KEYWORDS: 5-aminolevulinic, 5-ALA, Gliolan, Fluoresence, Paediatric, Child, Brain tumour

EPID-08. TREATMENT OUTCOME FOR EPENDYMAL TUMORS IN THE UNITED STATES

Ependymal tumors are rare CNS neuroectodermal neoplasm with a significant impact on patient mortality and quality of life. This study is to compare the effect of surgery and adjuvant radiation therapy (RT) on survival outcomes for ependymal tumors in the United States. 2091 patients aged >=18 with ependymal tumors were identified from the Surveillance, Epidemiology, and End Results registry (2000-2009). Surgical treatment was categorized into gross total resection (GTR) and no GTR. Log-rank test and multivariate Cox proportional hazard modeling were used to examine treatment effect on overall survival (OS). On univariate analysis, GTR was associated with improved OS for ependymoma (89% vs. 81%, p<0.01) and similar trend was observed for myxopapillary ependymoma (97% vs. 94%, p=0.13), subependymoma (93% vs. 89%, p=0.37), anaplastic ependymoma (50% vs. 26%, p=0.10). In multivariate analysis adjusting for age, sex, race, marital status, and year of diagnosis, GTR was associated with significantly improved OS for ependymoma (HR 0.711, 95% CI 0.527-0.953, p=0.02) but only a trend toward OS for anaplastic ependymoma (HR 0.703, 95% CI 0.426-1.145, p=0.16). Using multivariate analysis, adjuvant RT was found to associate with worse OS for ependymoma (HR 2.049, 95% CI 1.207-3.387, p=0.01), and no association was observed for the other histological groups. Among all prognostic factors, advanced age was determined to most significantly affect OS for all 4 histological groups: for age group 60-74 (compared to age group 18-44), myxopapillary ependymoma (HR 17.661, 95% CI 4.326-82.000, p<0.01), subependymoma (HR 4.932, 95% CI 1.522-19.044, p=0.01), ependymoma (HR 5.943, 95% CI 3.967-8.996, p<0.01), anaplastic ependymoma (HR 3.076, 95% CI 1.389-6.520, p=0.01). Ependymoma was the most common histological subtype among all ependymal tumors in the United States. Age at diagnosis was found to significantly contribute to patient long term survival. Surgery in the format of GTR provided survival benefit particularly in ependymoma.

MPTH-35. CLINICOPATHOLOGICAL STUDY OF LONG SURVIVORS OF GLIOBLASTOMA (GBM) – MULTI-INSTITUTIONAL RETROSPECTIVE SURVEY

Only a small subsets of patients with glioblastoma (GBM) survives more than 5 years. To analyze clinico-pathological features of “long survivor” will leads to better management of GBM. With the retrospective survey of records in 9 institutes, 22 patients were identified who survived 5 year or longer after initial surgery. Clinical course, neuroimages and unstained slides from FFPE specimen were obtained. Among 22 cases registered, diagnosis of GBM was confirmed in16 patients with central pathological review, Six patients were diagnosed as non-GBM (anaplastic astrocytoma 1, anaplastic oligodendroglioma 1, anaplastic ependymoma 1, pilocytic astrocytoma 1, PNET 1) and excluded from further analysis. There were 7 men and 9 women with the age range of 14 - 77 (median 44.5 year old). KPS before surgery were 60 - 100 (median 80), The extent of surgery were total in 10, subtotal in 4 and partial removal in 2. All patients received concomitant radiation chemotherapy (60-64Gy, median 64). The chemotherapeutic regiments were nitrosourea based in 8 and temozolomide in 8. The patients were followed for 65 to 214 months (median 96 months). With histopathological analysis including immunohistochemistry, 2 patients were diagnosed to have IDH-1mutation. Another 2 patients had giant cell features. Lymphocyte infiltration was observed strongly in 3 patients and moderately in 6 patients. Range of MIb-1 index was diverse; 4 – 41% (Mean 15.6, Median 13.5). In conclusion long survivors of GBM were younger in age, in good KPS and received extensive surgical resection. Histological examination showed favorable features and immunological reaction might play some role in certain patients.

RARE-03. EPENDYMOMAS ARISING OUTSIDE OF THE CENTRAL NERVOUS SYSTEM: A CASE SERIES

Extracranial and extraspinal ependymomas are extremely rare tumors mostly published in the literature as case reports. Our institutional database was screened for patients with extra CNS ependymomas over a 25 year period. Eight patients with extra CNS ependymoma were identified. Five cases originated in the sacrum or subcutaneous sacral area, and the other 3 cases originating in the breast, lung and adnexa of the uterus. By histology, most cases were myxopapilary ependymomas (5 cases), 2 cases were grade 2 ependymoma and 1 case was an anaplastic ependymoma. Metastases occurred in 6 cases and 3 patients died due to progressive disease. Most cases required surgery, radiation and chemotherapy. Extra CNS ependymomas are very rare tumors that tend to metastasize, even though most cases are histologically classified as low grade ependymomas, suggesting that the tumor biology does not correlate with conventional histologic findings. Future plans include molecular phenotyping to determine if these rare cancers are molecular similar to the recent findings from infratentorial, supratentorial ependymomas or the metabolic profile of classic spinal myxopapillary ependymoma.

Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma.

Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers are needed to improve patient outcome. To date, the most promising candidate marker is chromosome 1q gain, which has been associated in independent studies with adverse outcome. Furthermore, gene expression and methylation profiles revealed distinct molecular subgroups in the supratentorial and posterior fossa (PF) compartment and Laminin alpha-2 (LAMA2) and Neural Epidermal Growth Factor Like-2 (NELL2) were suggested as surrogate markers for the two PF subgroups PF-EPN-A and PF-EPN-B. PF-EPN-A tumors were also characterized by tenascin-C (TNC) expression and tenascin-C has been suggested as candidate gene on 9q, involved in tumor progression. Therefore, we have analyzed the status of chromosome 1q, TNC, LAMA2, and NELL2 expression in a series of pediatric PF ependymomas in terms of their frequency, associations among themselves, and clinical parameters, as well as their prognostic impact. We confirm the negative prognostic impact of 1q gain and TNC expression and could classify PF ependymomas by these two markers into three molecular subgroups. Tumors with combined 1q gain and TNC expression had the poorest, tumors without 1q gain and TNC expression had a favorable and TNC positive 1q non-gained cases had an intermediate outcome. We found also differences in age and tumor grade in the three subgroups and thus, provide evidence that PF pediatric ependymomas can be divided by chromosome 1q status and TNC expression in three molecular subgroups with distinct clinico-pathological features. These analyses require only few amounts of tumor tissue, are broadly available in the routine clinical neuropathological setting and thus, could be used in further therapy trials to optimize treatment of ependymoma patients.