Subependymoma Research Articles

Pathological Classification of the Intramedullary Spinal Cord Tumors According to 2021 World Health Organization Classification of Central Nervous System Tumors, a Single-Institute Experience.

According to the new 2021 World Health Organization (WHO) classification of tumors of the central nervous system (CNS) the classification of the primary intramedullary spinal cord tumors (IM-SCT) follows that of CNS tumors. However, since the genetics and methylation profile of ependymal tumors depend on the location of the tumor, the ‘spinal (SP)’ should be added for the ependymoma (EPN) and subependymoma (SubEPN). For an evidence-based review, the authors reviewed SCTs in the archives of the Seoul National University Hospital over the past decade. The frequent pathologies of primary IM-SCT were SP-EPN (45.1%), hemangioblastoma (20.0%), astrocytic tumors (17.4%, including pilocytic astrocytoma [4.6%] and diffuse midline glioma, H3 K27-altered [4.0%]), myxopapillary EPN (11.0%), and SP-subEPN (3.0%) in decreasing order. IDH-mutant astrocytomas, oligodendrogliomas, glioneuronal tumors, embryonal tumors, and germ cell tumors can occur but are extremely rare in the spinal cord. Genetic studies should support for the primary IM-SCT classification. In the 2021 WHO classifications, extramedullary SCT did not change significantly but contained several new genetically defined types of mesenchymal tumors. This article focused on primary IM-SCT for tumor frequency, age, sex difference, pathological features, and genetic abnormalities, based on a single-institute experience.

DNA methylation-based classification of ependymomas in adulthood: implications for diagnosis and treatment

Ependymal tumors are glial tumors that commonly manifest in children and young adults. Their classification has remained entirely morphological until recently, and surgery and radiotherapy are the main treatment options, especially in adults. Here we sought to correlate DNA methylation profiles with clinical and pathological characteristics in the prospective cohort of the German Glioma Network. Tumors from 122 adult patients with myxopapillary ependymoma, ependymoma, anaplastic ependymoma, subependymoma, or RELA fusion-positive ependymoma classified according to the World Health Organization (WHO) 2016 were subjected to DNA methylation profiling using the Illumina HumanMethylation450 BeadChip platform. Molecular data were correlated with histologic features and clinical characteristics. At a median follow-up of 86.7 months, only 22 patients experienced progression (18.0%) and 13 patients (10.7%) died. Each tumor could be assigned to one of the previously defined molecular ependymoma subgroups. All histologic subependymomas corresponded to subependymoma (SE) DNA methylation subgroups, but the reverse was not true: 19 histologic ependymomas (WHO grade II) were allocated to molecular SE groups. Similarly, all histological myxopapillary ependymomas were assigned to the molecularly defined spinal myxopapillary ependymoma (SP-MPE) class, but this molecular subgroup additionally included 15 WHO grade II ependymomas by histology. Overall, WHO grade II ependymomas distributed into 7 molecular subgroups. Most adult patients with ependymoma show a favorable prognosis. Molecular classification may provide diagnostic and prognostic information beyond histology and facilitate patient stratification in future clinical trials. The prognostic significance of a subependymoma or myxopapillary ependymoma DNA methylation phenotype without corresponding histology requires further study. 1. Ependymoma diagnosed in adult patients most often shows a good prognosis. 2. Molecular classification can support diagnostic and prognostic information beyond histology.

Molecular dissection of ependymomas.

Molecular dissection of ependymomas.

EP-03 * MOLECULAR CLASSIFICATION OF EPENDYMAL TUMORS ACROSS ALL CNS COMPARTMENTS, HISTOPATHOLOGICAL GRADES AND AGE GROUPS

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. DNA methylation patterns in tumors have been shown to represent a very stable molecular memory of the respective cell of origin throughout disease course, making them particularly suitable for tumor classification purposes. To attempt a uniform molecular classification for ependymal tumors across all age groups, histopathological grades and all anatomical CNS compartments – spine (SP), posterior fossa (PF), supratentorial region (ST) - we generated genome-wide DNA methylation profiles for 500 ependymal tumors using the Illumina 450k methylation array. Unsupervised hierarchical clustering of the DNA methylation data identified nine distinct molecular subgroups of ependymal tumors, three within each CNS compartment. One of the subgroups within each compartment was enriched with grade I subependymomas (SE) which were labeled as SP-SE, PF-SE and ST-SE. Within the spinal compartment the other molecular subgroups showed a relatively good concordance with the histopathological subtypes myxopapillary ependymoma (SP-MPE) and ependymoma (SP-EPN). The remaining molecular subgroups within the posterior fossa were previously described as posterior fossa Group A and B ependymomas and are now labeled as PF-EPN-A and PF-EPN-B. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA(ST-EPN-RELA) and YAP1 (ST-EPN-YAP1), respectively. Notably, the vast majority of high-risk patients (mostly children), for whom novel therapeutic concepts are desperately needed, were restricted to just two of the nine molecular subgroups identified, namely PF-EPN-A and ST-EPN-RELA. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next WHO classification of CNS tumors.

Abstract 3094: Epigenetic classification of ependymal brain tumors across age groups

Abstract Since it has become evident that histopathological grading of ependymoma according to the WHO classification of CNS tumors is not capable of accurately classifying patients into meaningful strata, a broadly accepted molecular classification scheme with prognostic significance is desperately needed. In recent years, ependymomas were classified into molecular subgroups based on transcriptomic alterations. In tumors localized within the posterior fossa, two distinct biological entities of ependymoma were delineated by several studies (designated posterior fossa A and posterior fossa B), which show striking differences in genetic characteristics and clinical outcome. A similar consensus for supratentorial and spinal ependymoma is lacking. We studied genome-wide DNA methylation (Illumina HumanMethylation450 (450k) array) in 180 primary ependymal tumors (80 with corresponding gene expression profiling data generated by Affymetrix 133plus2.0 arrays), including ependymomas (posterior fossa, supratentorial, spinal), subependymomas (SE), myxopapillary ependymoma (MPE), pineal parenchymal tumors of intermediate differentiation (PPTID), and papillary tumors of the pineal region (PTPR). We performed hierarchical clustering to identify robust molecular subgroups. Independent gene expression profiling datasets from previously published ependymoma studies (Johnson et al.; Wani et al.; Witt et al.) were used as validation cohorts. DNA methylation data showed that ependymal brain tumors can be classified into eight molecular subgroups. Notably, MPE, SE, PPTID and PTPR tumors formed robust distinct clusters, as did posterior fossa Group A and Group B ependymomas. Supratentorial ependymomas can be classified into two principle molecular subgroups, one of which displays a dismal prognosis, and comprises predominantly children and infants, and is associated with highly recurrent gene fusion. Notably, a significant number of ependymomas previously classified by histology as WHO Grade II/III look like SE by methylation, and also have extremely good survival. In summary, using genome-wide DNA methylation and transcriptome analysis we could decipher robust molecular subgroups of ependymal brain tumors including supratentorial ependymoma. Diagnoses of tumors with challenging histopathological features can now be supported by this technology. Hence, this approach offers the possibility to replace the unambiguous histological grading system that is currently in use with a robust molecular classification that readily distinguishes biologically, genetically, and clinically meaningful subgroups of ependymal brain tumors. Citation Format: Hendrik Witt, Martin Sill, Khalida Wani, Steve Mack, David Capper, Stephanie Heim, Pascal Johann, Sally Lambert, Marina Rhyzova, Volker Hovestadt, Theophilos Tzaridis, Kristian Pajtler, Sebastian Bender, Till Milde, Paul A. Northcott, Andreas E. Kulozik, Olaf Witt, Peter Lichter, V Peter Collins, Andreas von Deimling, Marcel Kool, Michael D. Taylor, Martin Hasselblatt, David TW Jones, Andrey Korshunov, Ken Aldape, Stefan Pfister. Epigenetic classification of ependymal brain tumors across age groups. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3094. doi:10.1158/1538-7445.AM2014-3094

Atypical Hemorrhagic Presentation of a Fourth Ventricle Subependymoma: Case Report

To present a case of a fourth ventricle subependymoma (SE) with a spontaneous acute subarachnoid intra-cisternal bleeding. A 33-year-old man was admitted with 5 days history of oppressive occipital headache and neck pain without additional neurological focus. Unenhanced computed tomography (CT) scan demonstrated an isointense mass located in the fourth ventricle with a spontaneously hyperdense acute extratumoral hemorrhage in the cisterna magna. Contrast-enhanced magnetic resonance imaging (MRI) revealed a well-delimitated non-enhanced tumor, hypointense on T1-weighted and hyperintense on T2-weighted images, involving the floor of the fourth ventricle and extending caudally into the cervical spinal canal via foramen magnum. Intraoperative, a large blood clot was removed and a macroscopically hypovascularlesion was completely excised from the right lateral recess and the floor of the fourth ventricle. Intra and postoperative immuno-histopathological examination revealed a SE. The patient has a normal postoperative course and was discharged in the fifth postoperative day. A 10-month postoperative MRI study confirmed a complete tumor resection. Symptomatic SEs should be surgically treated emphasizing the urgency in the presence of hemorrhage. The interest of this case is to demonstrate that infratentorial SEs although extremely rare, might present with acute subarachnoid bleeding.

Diagnosis and treatment of subependymoma in spinal cord

Objective To summarize the clinial characteristics and treatment of subependymoma in spinal cord.Methods A total of 10 cases of subependymoma in spinal cord from 2002 to 2011in the department of neurosurgery Shanghai Huashan hospital were enrolled.Results In all the 10 cases,total removal was performed in 7 patients,subtotal in 2 and partial in 1.Postoperative symptom was improved in 6 patients and decreased in 4 patients.A follow - up was performed from 1to 8 years,no recurrence occurred in the patients with tumor totally or subtotally removed.Conclusions Subependymoma in spinal cord is a rare kind of tumor in the central nerve system.The characteristic in MRI may help us to make the correct diagnosis before operation.The best treatment for subependymoma is surgical resection,patients with tumor totally removed may have good outcome. Key words: Intramedullary tumor; Subependymoma; Surgical procedures,operative

Diagnosis and microsurgical treatment of intracranial subependymoma:report of 33 cases

Objective To explore the clinical characteristics and treatment of intracranial subependymoma.Method 33 patients with intracranial subependymoma treated with microneurosurgical management at Beijing Tiantan Hospital from 1998 to 2008 were analyzed retrospectively.Results In this serials,19 patients were in male and 14 patients in female.Tumors located in the lateral ventricles in 18cases,located in the fourth ventricle in 13 cases,intra -brain tissue in 2 cases.On MRI scans,the tumors showed iso/hypointensity on T1 - weighted and hyperintensity on T2 - weighted images.On enhanced scans,the tumors showed no enhancement or only slightly enhancement.Tumors located in the lateral ventricles,were totally removed in 13 cases and subtotal in 5 cases; tumors located in the fourth ventricle,were totally removed in 3 cases,subtotally in 7 cases and partial in 3 cases;tumors were subtotally removed in 2 cases in intra- brain tissue type.Conclusions MRI may contribute to diagnose the intracranial subependymoma and surgical management.Radical resection usually contributes to a good outcome. Key words: Glioma,subependymal ; Diagnosis ; Microsurgery ;

Spontaneous acute hemorrhage within a subependymoma of the lateral ventricle: successful emergent surgical removal through a frontal transcortical approach

Introduccion. Los subependimomas son neoplasias benignas que se desarrollan en estrecha relacion con el sistema ventricular y que excepcionalmente asocian fenomenos hemorragicos. Describimos el caso de un subependimoma localizado en el ventriculo lateral que presento una hemorragia intratumoral aguda de forma espontanea, como se evidencio en los estudios neurorradiologicos y patologicos realizados, incluyendo un analisis exhaustivo de los casos similares descritos en la literatura cientifica. Caso clinico. Se trata de un varon de 71 anos que recibia tratamiento anticoagulante, y que presento un cuadro brusco y progresivo de disminucion del nivel de conciencia. Los estudios de neuroimagen evidenciaron la presencia de una masa localizada en el ventriculo lateral izquierdo, con signos de hemorragia reciente en su seno, que producia hidrocefalia biventricular aguda. La lesion fue resecada en su totalidad de forma urgente mediante un abordaje frontal transcortical. El estudio patologico de la lesion demostro que se trataba de un subependimoma con focos hemorragicos. En el periodo postoperatorio, el paciente presento un deficit de memoria global, tanto anterograda como retrograda. Conclusiones. Los episodios de hemorragia espontanea aguda constituyen un fenomeno excepcional en el caso de los tumores de histologia benigna como los subependimomas, y pueden transformar un curso clinico asintomatico en una emergencia quirurgica debido al desarrollo de hidrocefalia aguda. La extirpacion completa de la lesion de forma urgente representa la opcion de manejo quirurgico mas apropiada, ya que permite un reestablecimiento inmediato de la circulacion de liquido cefalorraquideo y previene la aparicion de resangrado.

Intracranial subependymoma: clinical features and surgical management of 22 cases

To study the clinical features, neuro-radiology and treatment of intracranial subependymomas. A total of 22 subependymomas were reviewed with regards to clinical presentation, neuro-imaging features, treatment, histopathological features and long-term follow-up. There were 13 males and 9 females with an age range of 5 to 54 years old. Fourteen tumors were located in lateral ventricles, 1 located on frontal-parietal lobe, 1 on mesencephalon, 2 on pons, 2 in fourth ventricle and 1 on cerebellum. One tumor was located in temporal lobe, mesencephalon, thalamus and pons. All tumors were surgically removed, including 18 totally removed (including 14 supra-tentorial and 4 infra-tentorial tumors) and 4 partially removed (including 1 supra- and infra-tentorial and 3 infra-tentorial tumors). During the follow-up, there was 1 recurrent case. Intracranial subependymoma is a rare benign tumor. And microsurgery represents the most effective therapy. Total resection can be expected for supra-tentorial tumors, but partial resection is often performed for infra-tentorial tumors. The prognosis is excellent and there is a rare tumor recurrence.

Genome‐Wide Analysis of Subependymomas Shows Underlying Chromosomal Copy Number Changes Involving Chromosomes 6, 7, 8 and 14 in a Proportion of Cases

Subependymomas (SE) are slow‐growing brain tumors that tend to occur within the ventricles of middle‐aged and elderly adults. The World Health Organization classifies these tumors within the ependymoma group. Previous limited analysis of this tumor type had not revealed significant underlying cytogenetic abnormalities.We have used microarray comparative genomic hybridization to study a series of SE (n = 12). A whole‐genome array at 0.97‐Mb resolution showed copy number abnormalities in five of 12 cases (42%). Two cases (17%) showed regions of loss on chromosome 6. More detailed analysis of all cases using a chromosome 6 tile‐path array confirmed the presence of overlapping regions of loss in only these two cases. One of these cases also showed trisomy chromosome 7. Monosomy of chromosome 8 was seen in a further two cases (17%), and a partial loss on chromosome 14 was observed in one additional case.This is the first array‐based, genome‐wide study of SE. The observation that five of 12 cases examined (42%) at 0.97‐Mb resolution showed chromosomal copy number abnormalities is a novel finding in this tumor type.

Immunohistochemical study of central neurocytoma, subependymoma, and subependymal giant cell astrocytoma

For investigation of histogenesis of central neurocytomas (CNs), subependymoma (SEs), subependymal giant cell astrocytomas (SEGAs), we studied expression of various neuronal and glial biomarkers by immunohistochemical (IHC) study and reverse transcriptase-polymerase chain reaction (RT-PCR). The materials for IHC were paraffin section of seven CNs, three SEs, and eight SEGAs and those for RT-PCR were frozen tissues of seven CNs, three SEs, and five SEGAs. Control group was five ependymomas (EPs) and four pilocytic astrocytomas (PAs). The neuronal biomarkers included nestin, chromogranin A (chrA), synaptophysin (SNP), neuronal cell adhesion molecule (NCAM), neuron specific enolase (NSE), neuronal nuclear antigen (NeuN), neurofilament (NF) and the glial marker was GFAP. CNs expressed all neuronal markers except NF (0%), SNP (100%), NCAM (100%), NSE (100%), NeuN (100%), nestin (29%) and chrA (43%), but GFAP expression was found only in one case (14%). SEGA coexpressed several neuronal markers and a glial marker; NeuN (100%), NSE (88%), NCAM (63%), nestin (100%), SNP (weakly and focally, 100%), and GFAP (100%), however, other neuronal markers including chrA, SNP and NF were all negative. SE expressed nonspecific neuronal markers (NCAM (100%) and NSE (100%)) which showed weak intensity and a GFAP (100%), but not nestin. Among control cases of EPs and PAs, no one case expressed neuronal markers except nonspecific neuronal marker of NCAM, but robustly expressed GFAP. RT-PCR product of nestin was expressed in 29% of CNs (2/7cases), 60% of SEGAs (3/5 cases), 100% of SEs (3/3 cases), 80% of EPs (4/5 cases), and 25% of PAs (1/4 cases). Conclusively, coexpression of neuronal and glial markers and expression of nestin in CNs, SEGAs and SEs suggested the origin of these tumor cells might be the stem cells being able to differentiate into both neuronal and glial phenotypes. But CNs might be originated from rather neuronally committed stem cells and SEs from rather glially committed stem cells.

Supratentorial Ependymomas of the First Two Decades of Life. Long-Term Follow-up of 20 Cases (Including Two Subependymomas)

In order to better elucidate the lesser known aspects of the biological behavior and prognosis of supratentorial ependymomas in children and young adults, we studied a series of 20 patients, ages 1 to 20 years. The tumor site was extraventricular in 14 cases and intraventricular in 6 (including one third ventricle tumor). Histologically, according to World Health Organization criteria, there were 12 ependymomas (E), 2 subependymomas (SE), and 6 malignant ependymomas (ME). Of the 18 patients surviving surgery, 12 (66.6%) are alive and disease free 63 to 252 months (mean, 146 mo) after the operation; 9 harbored an E, 2 had an SE and 1 had an ME. Four patients are now out of risk of recurrence according to Collin's law. Six of the long-term survivors (50%), four E and two SE, did not receive postoperative radiotherapy. However, two patients with E, initially treated by surgery alone, had a recurrence and one subsequently died. Two ME patients showed signs of spinal metastases after subsequent operation for recurrence and shortly before death. Considering the partially good results as well as failures after surgery alone in our and in other series and the risks of irradiating the child's brain, we tried to elucidate in what cases radiotherapy could be reasonably withheld, or alternatively, when prophylactic craniospinal irradiation should be prescribed. The main conclusions of our study are the following: 1) Radical surgery alone is a reasonable option as the initial treatment for lateral ventricle tumors and for solid extraventricular tumors located far from eloquent brain areas, provided the histology is benign, especially if of the SE type.(ABSTRACT TRUNCATED AT 250 WORDS)