Treatment implications of posterior fossa ependymoma subgroups

Posterior fossa ependymoma comprises two distinct molecular entities,ependymoma_posterior fossa A(EPN_PFA)and ependymoma_posterior fossa B(EPN_PFB),with differentiable gene expression profiles.As yet,the response of the two entities to treatment is unclear.To determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment,we studied a cohort of 820 patients with molecularly profiled,clinically annotated posterior fossa ependymomas.We found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA,which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era:a retrospective multicohort analysis" in the Journal ofClinical Oncology.Patients with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy,whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.

Invasive myxopapillary ependymoma of the lumbar spine: A case report

BACKGROUND Myxopapillary ependymomas are rare spinal tumours.Although histologically benign,they have a tendency for local recurrence.CASE SUMMARY We describe a patient suffering from extra-and intradural myxopapillary ependymoma with perisacral spreading.He was treated with subtotal resection and postoperative radiation therapy.After treatment,he experienced slight sphincter disorders and lumboischialgic pain with no motor or sensory disturbances.Eight months later,a tumour regression was documented.The patient is still followed-up regularly.CONCLUSION Lumbar myxopapillary ependymomas may present with lumbar or radicular pain,similar to more trivial lesions.Magnetic resonance imaging(MRI)is the primary modality for diagnosis.The treatment aim is to minimize both tumour and therapy-related morbidity and to involve different treatment modalities.

Expression and sub-cellular localization of leucine-rich repeats and immunoglobulin-like domains are related to antioxidant enzymes in human ependymoma and oligodendroglioma

The current study investigated correlations between the expression of leucine-rich repeats and immunoglobulin-like domain 1 （LRIG1） and antioxidant enzymes and related proteins, including manganese superoxide dismutase, glutamate cysteine ligase catalytic or regulatory subunit, thioredoxin and thioredoxin reductase, in both human ependymoma and oligodendroglioma. Results revealed that the cytoplasmic expression of LRIG1 was associated with expression of glutamate cysteine ligase catalytic subunit in the human ependymoma, while the nuclear expression of LRIG1 was associated with expression of thioredoxin reductase. In human oligodendroglioma, the cytoplasmic expression of LRIG1 was associated with expression of the glutamate cysteine ligase catalytic subunit. Both the nuclear and perinuclear expressions of LRIG1 were associated with expression of glutamate cysteine ligase regulatory subunit. These results indicated that several antioxidant enzymes and related proteins contributed to LRIG1 expression, and that these may participate in the antioxidation of the cells.

Cognitive and Psychological Outcomes in Younger vs. Older Children with Subtentorial/Supratentorial Ependymoma after Radiation Therapy

Purpose: to investigate cognitive and psychological problems in children treated for intracranial ependymoma, the evolution of these disorders over time and the role of age at radiotherapy and tumor site, in their onset and persistence. Methods and Materials: 23 patients received a complete evaluation;some of them underwent follow-ups. The clinical data collected included sex, age (at diagnosis, assessment and tumor treatment, thus dividing patients into two cohorts: younger or older than 5 years), site (supratentorial vs. subtentorial), the presence of hydrocephalus, neurological examination, tumor treatment. All the patients received an age-appropriate cognitive and psychological evaluation. Results: The mean cognitive level was within the norm, with lower scores on the Performance Intelligence Quotient (PIQ). The psychological assessment revealed Internalizing problems and impaired independence. Children older than 5 years had a lower Intelligence Quotient (IQ) than the younger children, both at the initial evaluation and at follow-ups. Initially, the supratentorial group appeared to be less impaired than the subtentorial group but then exhibited a progressive decline in the IQ. In the subtentorial group, the children with an IQ within the normal range remained stable at the follow-up, while the children with below-norm scores at the initial evaluation showed deterioration over time. Conclusions: Tumor site seems to affect the cognitive outcome to a greater extent than age at radiotherapy.

Anaplastic myxopapillary ependymoma:A case report and review of literature

BACKGROUND Myxopapillary ependymoma(MPE)is a pathological grade I tumor that arises in the filum terminale.MPE with anaplastic features is extremely rare,and only 5 cases have shown malignancy at the time of recurrence.CASE SUMMARY The patient(a 46-year-old woman)had undergone a MPE operation 30 years ago.After subtotal resection of the tumor located in L4-S1,it had a solid component that extended to the adjacent subcutaneous region.Histologically,the tumor consisted of a typical MPE with anaplastic features.The anaplastic areas of the tumor showed hypercellularity,a rapid mitotic rate,vascular proliferation,and connective tissue proliferation.Pleomorphic cells and atypical mitotic figures were occasionally observed.The MIB-1 index in this area was 12.3%.The immunohistochemical study showed immunoreactivity for vimentin,glial fibrillary acidic protein and S100.The morphological pattern and immunohistochemical profile were consistent with anaplastic MPE.The patient tolerated surgery well without new neurological deficits.She underwent local irradiation for the residual tumor and rehabilitation.CONCLUSION Although extremely rare,anaplastic MPE occurs in both pediatric and adult patients,similar to other ependymomas.At a minimum,close monitoring is recommended,given concerns about aggressive biological potential.In the future,further study is needed to determine the WHO classification criteria and genetic indicators of tumor progression.The possibility of malignant transformation of MPE should be taken into account,and patients with MPE should be treated with care and follow-up.

Supra-Tentorial Cortical Ependymoma in an Adult: Case Report and Review of the Literature

Supratentorial cortical ependymoma is a rare primary brain tumor in adults. Only 50 cases are reported in the literature including pediatric and adult patients. We report a 30-year-old male with sensory-type seizures who was found to have a right posterior frontal cortical lesion with large cystic component. The lesion was resected completely and histopathology and immunohistochemistry examinations confirmed anaplastic ependymoma WHO grade III. The patient received radiotherapy treatment post-surgery, and he was tumor free one year after treatment.

Extracranial Metastasis of an Anaplastic Ependymoma, RELA Fusion-Positive: A Rare Occurrence

Primary intracranial ependymomas originate from ependymal cells. They may migrate mainly in the spinal cord but rarely metastasize outside the central nervous system. Metastases outside the central nervous system are rare. Metastatic diffusion from the central nervous system is low due to the unique interaction of the brain and the tumor with the blood-brain barrier. Nevertheless, three main hypotheses have been mentioned in the literature, the tumor growth, the surgical manipulation (which may be considered to be the case in our patient), and the aggressiveness of the tumor according to the Ki67 index. We report the case of a 16-year-old female, who underwent complete surgical removal of a left occipital 2007 WHO grade II ependymoma. 3 years later, the patient presented multiple cervical and occipital indurated masses. MRI showed a left hemispheric meningeal infiltration, with multiple nodules located on the neck, occiput and mastoid. Histopathological study of a left temporal surgical biopsy and resection of an occipital subcutaneous nodule turned to be metastases of an anaplastic ependymoma. The ependymoma considered as a benign tumor could very quickly turn into malignancy by its metastatic potential. Early diagnosis and longer follow-up of patients would be recommended for a rapid management.

Intradural Extra Medullary Cervical Anaplastic Ependymoma. Case Report and Review of the Literature

Introduction: Intra-dural and extramedullary ependymomas are rare lesions. We report a clinical case confirmed by the histology supported by the neurosurgery department of Martinique University Hospital. Clinical, paraclinical and therapeutic data will be compared to a literature review. Observation: A 38-year-old patient was admitted for tetraparesthesia evolving since 3 months, associated with a left hemiparesis. The clinical examination revealed deterioration of the general condition and a tetrapyramidal syndrome. MRI of the cervical spine revealed extensive cervical extra-medullary intradural lesion of C3 to C5. The treatment had been an excisional surgery that had been subtotal in two stages, supplemented by craniospinal radiotherapy because the pathological examination had found a grade III anaplasic ependymoma. Conclusion: Because of their rarity, the treatment of these forms of ependymoma is not yet well codified.

Myxopapillary Ependymoma of the III Ventricle: Example of a Histological Variant of Ependymoma with Exceptional Localization

We present morphological findings observed from the study of a myxopapillary ependymoma located in the III ventricle. This tumor, which is a rare occurrence at this level, was observed in a 73-year-old woman with no relevant medical history who presented with obstructive hydrocephalus due to compression and blockage of the foramen of Monro. The good delineation of the lesion allowed its surgical excision, and histological examination of the material obtained after excisional biopsy revealed a glial neoplasm with a low degree of cytological malignancy that was strongly positive for glial fibrillary acidic protein (GFAP) as well as a myxopapillary architecture analogous to that observed in ependymomas of the filum terminale. Subsequent radiological examination allowed us to rule out a metastatic nature of the tumor, confirming its primary origin. We briefly discuss the case and review the main characteristics of this neoplasia, which is quite rare at the site identified in our patient.

Clinical analysis of 14 cases of supratentorial parenchymal ependymomas

Objective To study the clinical feature,image,treatment and prognosis of supratentorial parenchymalependymomas.Methods14cases of patients sufferedfrom supratentorial parenchymal ependymomas were treated.There were10ependymomas and4malignantependymomas.Tumor located in frontal lobe in4cases,

Prognostic analysis of intramedullary ependymomas in medulla oblongata and cervical cord

Objective To analyze factors affecting operative prognosis of intramedullary ependymomas in medulla oblongata and cervical cord. Methods Thirty patients harboring intramedullary ependymomas in medulla oblongata and cervical cord were operated. The preoperative and postoperative status was taken by follow-up and

Molecular genetics of ependymoma

Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained elusive.Until recently,ependymoma research was hindered by the small number of tumors available for study,low resolution of cytogenetic techniques,and lack of cell lines and animal models.Ependymoma heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this disease.Despite these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic(copy number) and transcriptome profiling platforms.Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin.This review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field.

Ventricular system-unrelated cerebellar ependymoma:A case report

BACKGROUND An ependymoma is a glial tumor that usually occurs in or near the ventricle,close to the ependyma.It rarely occurs exclusively in the brain parenchyma without being associated with the ventricle.CASE SUMMARY Here,we report a rare case of a cerebellar ependymoma completely located in the brain parenchyma.A previously healthy 32-year-old female with a 1-month history of dizziness was admitted to our hospital.During hospitalization,magnetic resonance imaging of the brain revealed a space-occupying lesion measuring 57 mm×41 mm×51 mm in the right cerebellar hemisphere and inferior cerebellar vermis.The patient underwent surgical resection for the right cerebellar mass.Postoperative pathological examination revealed an ependymoma.At 1 year follow-up,the patient was doing well and showed no recurrence.CONCLUSION We conducted a literature review and summarized three theories regarding ependymomas located exclusively in the brain parenchyma,which are key to the diagnosis of intraparenchymal cerebellar ependymomas.Surgery and postoperative radiotherapy are the primary treatment options for ependymomas.

Hydrocephalus Secondary to Intraventricular Myxopapillary Ependymoma: Case Report

Ependymomas are a somewhat diverse category of glial tumors that often develop from the lining of the brain’s ventricles, or the spinal cord’s central canal. They make up 5% of all neuroepithelial tumors, 10% of paediatric brain tumors, and up to 33% of brain tumors in children under the age of three. Hydrocephalus is one of the complications, and it can be identified as progressive macrocephaly or increasing head circumference crossing percentiles, nausea, vomiting, poor appetite, irritability, and regression of developmental milestones.

Aszonapyrone A Isolated from Neosartorya spinosa IFM 47025 Inhibits the NF-κB Signaling Pathway Activated by Expression of the Ependymoma-Causing Fusion Protein ZFTA-RELA

Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.

盆腹腔原发性室管膜瘤临床病理观察及文献复习

目的 总结盆腹腔原发性室管膜瘤的临床病理特征、诊断要点及治疗和预后情况。方法 总结经北京协和医院会诊确诊的1例及文献报道的共30例盆腹腔原发室管膜瘤病例。结果 本例患者女性,34岁,B超显示左侧髂窝边界清楚的弱回声团块,于外院行肿瘤细胞减灭术,术中见左髂窝实性肿物,包膜完整,质地中等。镜下见肿瘤组织排列成筛管状、实性、乳头状及腺样,可见菊形团,核分裂象罕见。免疫组化肿瘤细胞EMA、D2-40呈核旁点状阳性,GFAP、ER、PR、PAX-8、S-100和WT-1不同程度阳性。结论 盆腹腔原发室管膜瘤十分罕见,多见于年轻女性,误诊率高,ER、PR、WT-1和PAX-8免疫组化有较高的表达率。治疗以手术及术后化疗为主,肿瘤易复发,但死亡率低。

后颅窝室管膜瘤临床病理分析

目的探讨后颅窝室管膜瘤临床病理特征。方法收集2022年10月-2023年10新疆医科大学第一附属医院病理科存档的后颅窝室管膜瘤共6例。调阅组织切片,分析免疫组化法检测相应指标表达情况,并收集随访信息,查阅相关文献总结其临床病理学表现。结果6例后颅窝室管膜瘤中PFA组4例,PFB组2例。临床表现为头疼,呕吐,继发性脑积水等。PFA组患者均为儿童,年龄10个月-11岁,其中女性3例,男性1例;肿瘤3例位于四脑室,1例位于脑干。2例PFB组患者均为成年女性,年龄分别为32岁和45岁,肿瘤均位于四脑室。肿瘤组织学形态呈片状生长模式,出现血管周围假性菊形团,真性室管膜菊形团,组织学分级CNS WHO 2级1例,3级5例。6例后颅窝室管膜瘤免疫组化染色结果显示肿瘤细胞GFAP、S-100均弥漫性强阳性表达,EMA、D2-40表现为核旁点状及腔缘阳性,P53大部分为野生型,oligo-2、Neu-N均阴性。PFA组出现特征性H3 K27Me3细胞核表达缺失,Ki-67增殖指数20%-60%。PFB组H3 K27Me3细胞核未缺失,Ki-67增殖指数4%-15%。结论后颅窝室管膜瘤PFA组好发于儿童且预后较差,通过H3 K27me3免疫组化染色初筛并分组,对于明确诊断及指导临床辅助治疗具有重要临床意义。

基于生物信息学建立室管膜瘤TGF-β通路相关基因预后风险模型及其应用

目的:基于生物信息学方法建立室管膜瘤中TGF-β信号通路相关基因的预后预测模型。方法:利用无监督聚类算法区分室管膜瘤的不同分子亚型;利用基因集变异分析(gene set variation analysis,GSVA)计算不同室管膜瘤分子亚型中TGF-β信号通路相关评分;利用乘积极限法(Kaplan-Meier analysis,KM)计算不同室管膜瘤分子亚型中患者的生存率;利用线性模型算法(linear models for microarray data,limma)分析不同室管膜瘤分子亚型间的差异基因;利用最小绝对收缩和选择算子算法(least absolute shrinkage and selection operator,LASSO)和COX比例风险模型(COX proportional-hazards model)构建室管膜瘤中TGF-β信号通路相关基因的预后预测模型;利用受试者工作特征曲线(receiver operating characteristic curve,ROC)评估预后预测模型的性能;利用皮尔逊相关性分析考察关键基因的相关性;利用qRT-PCR技术和免疫印迹技术考察室管膜瘤组织中关键基因的表达水平。结果:无监督聚类算法显示,室管膜瘤中存在两种不同的分子亚型;GSVA和KM分析显示,不同亚型的室管膜瘤中TGF-β信号通路评分和预后存在显著差异;基因差异表达分析结果显示,不同亚型的室管膜瘤中TGF-β通路相关基因表达存在显著差异;LASSO显示,BMP4、FBN1、CDC20、TGFB1是预后预测模型的关键基因;ROC分析结果显示,TGF-β信号通路相关基因模型具有较高的预测性能;皮尔逊相关性分析结果显示,BMP4、FBN1、CDC20、TGFB1与TGF-β信号通路下游基因具有显著的表达相关性;qRT-PCR和免疫印迹技术结果显示,BMP4、FBN1、CDC20、TGFB1在室管膜瘤组织中的表达显著上调。结论:基于TGF-β通路相关基因BMP4、FBN1、CDC20、TGFB1构建的预后预测模型能够有效预测患者的生存情况。

完全囊变脊髓室管膜瘤1例报告并文献复习

目的 探讨完全囊变脊髓室管膜瘤的临床特点、影像学特征以及治疗方法。方法 回顾性分析南昌大学第二附属医院神经外科2021年4月收治的1例完全囊变脊髓室管膜瘤临床资料,并对相关文献进行复习。结果 术中见肿瘤呈粉红色,柔软,有一定包膜,肿瘤几乎完全囊性,囊液暗红色,囊壁为肿瘤组织,厚度约2~3 mm。术后病理诊断为脊髓室管膜瘤(WHOⅡ级)。随访6个月,未见肿瘤复发。结论 脊髓室管膜瘤常伴有肿瘤囊变,完全囊变的情况罕见,囊壁多为肿瘤细胞;磁共振平扫肿瘤表现为T_(1)低信号,T_(2)高信号,增强扫描肿瘤呈环形强化;临床表现多为相应阶段的神经功能损害;对于完全囊变的肿瘤,尽可能保留囊壁的完整性将肿瘤全切是其治疗的关键,避免肿瘤细胞随囊液播散转移。

纵隔原发性室管膜瘤误诊分析

目的分析纵隔原发性室管膜瘤的误诊原因。方法回顾性分析2023年7月收治的1例纵隔原发性室管膜瘤的临床资料及影像学表现。结果患者体检发现后纵隔无痛性肿物,实验室检查未见明显异常;胸部CT示后纵隔囊性肿物,考虑神经源性可能性大;纵隔囊肿穿刺活检后病理涂片倾向于胸腺来源囊肿,患者住院后行右侧胸腔镜下纵隔囊肿切除术,术后病理诊断为纵隔原发性室管膜瘤。随访未见复发和并发症。结论纵隔原发性室管膜瘤发病极为罕见,易误诊为胸腺或神经来源囊肿,临床及影像科医师遇到此部位病变应考虑到该病可能,确诊需结合病理学免疫组化检查。