C11orf95‐RELA fusion present in a primary intracranial extra‐axial ependymoma: Report of a case with literature review

Ependymomas are gliomas that recapitulate the ependymal cells microscopically and ultrastructurally. They commonly occur along the ventricular surfaces and central canal of the brain and spinal cord. Intracranial extra‐axial ependymoma (IEAE) is a rare entity and is commonly misdiagnosed clinically and radiologically as a meningioma. The histogenesis of such IEAEs is obscure. A novel recurrent oncogenic fusion involving the C11orf95 and RELA genes was recently described in supratentorial ependymomas. A 9‐year‐old girl presented with a dural based parafalcine mass that, in addition to exhibiting classical immunohistochemical features of an ependymoma, also demonstrated C11orf95‐RELA fusion, characteristic of supratentorial ependymomas. We suggest that IEAEs share their histogenesis with their intra‐axial counterparts, arising either from dural extension of subcortical, subependymal rests or directly from ectopic dural rests.     

Cortical ependymoma or monomorphous angiocentric glioma?

Ependymoma is the third most common childhood intracranial tumor after medulloblastoma and pilocytic astrocytoma. Most ependymomas occur in the posterior fossa and spinal cord but only five cases confined to the cerebral cortex have been reported. The current case is a 5‐year‐old boy with a somewhat ill‐defined cortical tumor diagnosed as pilocytic astrocytoma on biopsy, and treated with radiotherapy. Nine years later, resection of the essentially unaltered tumor was performed for treatment of intractable seizures. Histologically, the tumor had some areas with the typical appearance of ependymoma as well other areas which contained piloid cells. There was also evidence of focal infiltrative growth. These findings bore resemblance to a recently described entity monomorphous angiocentric glioma/angiocentric neuroepithelial tumor, which combines features of ependymoma with pilocytic and diffuse astrocytomas. Both cortical ependymomas and angiocentric monomorphous glioma/angiocentric neuroepithelial tumor appear to be low‐grade tumors although their rarity makes accurate prognosis problematic. The current case has features of both entities, suggesting they may be closely related.     

Follow-up and quality of survival of 67 consecutive children with CNS tumors

We report the finding at follow-up in 67 consecutive children with central nervous system tumors treated over a 5-year-period at a single institution. The diagnoses were supratentorial astrocytoma (n = 12), cerebellar astrocytoma (n = 10), ependymoma (n = 9), medulloblastoma (n = 9), brain stem glioma (n = 6), optic pathway glioma (n = 5), and others (n = 16). The survival rates were 83% for supratentorial astrocytomas at a median of 46.5 months, 90% for cerebellar astrocytomas and 55% for ependymomas at 40 months, respectively, 55% for medulloblastomas at 22 months, 33% for brain stem gliomas at 23 months, and 80% for optic pathway gliomas at 49 months. With regard to neurological sequelae, 13 patients were treated for epilepsy, 13 patients had mild to moderate neurological deficits, and 4 patients were severely disabled. Seventeen of 37 tested patients performed below average on formal neuropsychometric testing, one-fourth attended special education courses, and at least one-fourth suffered from behavioral and adjustment problems.     

Association of lower cranial nerve schwannoma with spinal ependymoma in ? NF2.

A 15 year old male, who had earlier been operated for intraspinal intramedullary ependymoma, subsequently developed a right cerebello pontine (CP) angle mass. A diagnosis of right CP angle ependymoma was considered, in view of established histology of previously operated spinal lesion. Histopathological examination of the well defined extra-axial mass, which was attached with ninth cranial nerve, however revealed a schwannoma. A diagnosis of Neurofibromatosis-2 (NF2) is strongly suspected, because of well established fact, that the spinal ependymomas may have association with lower cranial nerve schwannomas in NF2. Cranial and spinal MRI screening for early diagnosis of associated, asymptomatic lesions, in suspected cases of NF2, particularly in children, is recommended.     

Hemispheric cerebral gliomas in children with NF1: arguments for a long-term follow-up

BACKGROUND: Neurofibromatosis type 1, or peripheral neurofibromatosis, is the most form of common phakomatosis. In some instances, it can be associated with tumors of the central nervous system. CASE REPORT: We describe four cases of hemispheric cerebral glioma in children with NF1. Two of these tumors were pilocytic astrocytomas and two, ependymomas. We reviewed the literature on hemispheric cerebral gliomas in NF1 patients in an attempt to find characteristic features of and some explanations for these lesions. CONCLUSION: We conclude that surgical resection of these tumors should be proposed whenever possible, with due consideration for their progressive nature and the uncertainties about malignancy. We advocate yearly clinical and neuroradiological follow-up over a long period in NF1 children, since they may develop additional CNS tumors during their lifetime.     

Expression of prostaglandin H synthase-2 in human brain tumors

Numerous studies have demonstrated that prostaglandin H synthase-2 (PHS-2) is involved in gastrointestinal carcinogenesis, and that nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit PHS, can reduce the risk of colon cancer. In brain tumors, elevated prostaglandin production and its correlation to anaplastic grade of gliomas have been demonstrated. To determine whether the increased prostaglandin production is due to enhanced expression of PHS-2 and whether the up-regulation of PHS-2 has any correlation to histopathological findings in brain tumors, we evaluated the profile of PHS expression in several human glioma cell lines and surgical specimens from patients with various types of brain tumors. In glioma cell lines, five out of six cell lines showed constitutive expression of PHS-2, whereas PHS-1 was weakly expressed in all of them. All surgical specimens, except an ependymoma, which expressed both isozymes equally, expressed PHS-2 mRNA predominantly. Immunohistochemistry of various types of brain tumors, including six glioblastomas, nine astrocytomas, six meningiomas, five medulloblastomas, four craniopharyngiomas, three ependymomas, three neurinomas, two oligodendrogliomas, two malignant lymphomas, two dysembryoplastic neuroepitherial tumors and one metastatic brain tumor showed PHS-2 staining in most cases. In gliomas, astrocytomas (grade 2 and 3) were strongly stained, but the staining intensity of glioblastomas was relatively weak. Meningiomas and a metastatic brain tumor were also strongly stained. Our data thus suggest that most brain tumors express PHS-2, which may also play a role in tumorigenesis in the brain.     

Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas

Pattern and extent of epithelial membrane antigen (EMA) immunoreactivity in ependymomas as compared to other glial tumors have only been investigated in small series. To determine sensitivity and specificity of EMA staining, 54 ependymomas were evaluated in comparison to 54 glioblastomas, 43 fibrillary astrocytomas and 21 oligodendrogliomas. Distinct punctate intracytoplasmic EMA immunoreactivity was observed in 48/54 ependymomas (89%), whereas ring-like EMA staining was observed in 17/54 ependymomas (31%). Apart from the absence in most myxopapillary ependymomas, neither staining pattern was related to tumor grade or localization. Dot-like EMA immunoreactivity was less frequently observed in glioblastomas [32/54 (59%), P<0.05 vs ependymomas], fibrillary astrocytomas [10/43 (23%), P<0.001 vs ependymomas] and oligodendrogliomas [2/21 (10%), P<0.001 vs ependymomas], whereas ring-like EMA staining was absent. Sensitivity and specificity of punctate EMA staining for the diagnosis of ependymoma as compared to other glial tumors were determined: A finding of 5 EMA dots/high-power field was associated with a sensitivity of 72% and a specificity of 81%. The presence of ring-like EMA positive structures was less sensitive (32%), but highly specific (100%). To conclude, distinct punctate and ring-like EMA staining might serve as sensitive and specific markers of ependymal differentiation in glial tumors and, thus, may aid the diagnosis of ependymoma.     

Pediatric ganglioglioma with an H3 K27M mutation arising from the cervical spinal cord

The 2016 edition of the World Health Organization Classification of Tumors of the Central Nervous System introduced “diffuse midline glioma H3 K27M mutant” as a new diagnostic entity. These tumors predominately affect pediatric patients and arise from midline structures such as the brainstem, thalamus and spinal cord. Here, we report a rare patient with spinal ganglioglioma carrying an H3 K27M mutation. A 10‐year‐old boy presented with an intramedullary tumor in the cervical spinal cord. The lesion was partially removed and histologically diagnosed as ganglioglioma. After the remnant tumor grew within 3 months after surgery, the patient underwent radiotherapy. Genetic analyses revealed an H3F3A K27M mutation but no other genetic alterations such as IDH and BRAF mutations. This case may point to pathological heterogeneity in gliomas with H3 K27M mutations.     

Expression of cyclo‐oxygenase‐2 in ependymal tumors

Up‐regulation of cyclo‐oxygenase‐2 (COX‐2), a cytokine‐induced enzyme that metabolizes arachidonic acid into prostaglandins, has been described in some brain tumors, including astrocytomas. Little is known about its expression in ependymal neoplasms. The objective of the present study was to assess COX‐2 immunostaining of ependymal tumors. Retrospective COX‐2 immunohistochemical analysis was conducted on 117 ependymal tumors. Statistical analysis was performed using Student t‐test. The study group (56 men and 44 women, mean age, 30.8 years) was comprised of 48 low‐grade ependymomas (WHO grade II), 12 anaplastic ependymomas (WHO grade III), 27 myxopapillary ependymomas (WHO grade I) and 13 subependymomas (WHO grade I). At last known follow‐up (range, 12–226 months; mean, 74 months), 52 patients were alive with no evidence of tumor, 16 patients were alive with residual tumor, nine patients died with tumor, one patient died with no tumor and three died with tumor status unknown. Nineteen patients had less than 12 months of follow‐up. Thirty‐six (36%) patients had tumors, which demonstrated positive COX‐2 staining, including 16/27 (59%) myxopapillary ependymomas, 3/13 (23%) subependymomas, 14/48 (29%) ependymomas and 3/12 (25%) anaplastic ependymomas. Statistically significant COX‐2 positive immunostaining was observed in myxopapillary ependymomas versus WHO grade II (P = 0.03) and grade III (P = 0.02) tumors. Increased COX‐2 expression in myxopapillary ependymoma as compared to the WHO grade II and II ependymoma was observed. The reason for this apparent increased immunoexpression in these low‐grade tumors is uncertain. COX‐2 inhibitors may play a role in treatment of the subset of ependymal tumors that demonstrate increased expression. COX‐2 staining did not reliably predict tumor behavior.     

Low grade diffuse gliomas: Shared cellular composition and morphometric differences

Low grade diffuse gliomas arising in the brain are challenging to treat because of their ability to infiltrate adjacent tissue. We attempted to clarify the cellular composition and histopathological features of low grade gliomas by utilizing morphometric and immunohistochemical analyses. Seventy‐eight cases of low grade gliomas were examined including 21 diffuse astrocytomas (DA), 36 oligodendrogliomas (OL), and 21 oligoastrocytomas (OA), based on the WHO classification system. Moreover, OL were subdivided into three types based on the morphological characteristics advocated by Daumas‐Duport et al.: OL type I, OL type II, and OL type III. The cellularity, nuclear form factor, and conditional entropy corresponding to the nuclear pleomorphism were measured in each sample by the image analysis software “Gunmetry.” Twenty‐two cases were immunohistochemically analyzed for the expression of several antigens. Morphometric data indicated that the cellularity of OL type II was significantly higher than that of DA, and that the conditional entropy of OL type III was significantly lower than that of DA. Although the results of the immunohistochemical studies were almost consistent with previous reports, there were significant differences in the expression of GFAP, nestin and p53 between DA and OL. Double immunostaining revealed that expression of Olig2 and GFAP, and Olig2 and nestin was mutually exclusive in most glioma cells. Moreover, the coexpression of nestin and GFAP occurred in DA and OA, but not in OL. We conclude that each glioma include cells expressing GFAP, cells expressing nestin, and cells expressing Olig2 in a characteristic proportion for each tumor type. We suggest that diffuse gliomas share cellular compositions in different ratios and that they can be distinguished by morphometrical analysis.     

Immunocytochemical studies in canine neuroectodermal brain tumors

Summary Seventy-four canine neuroectodermal tumors were examined immunocytochemically for the presence of glial fibrillary acidic protein (GFAP). Eleven oligodendrogliomas were examined for the presence of myelim basic protein (MBP) and myelin-associated glycoprotein (MAG). Twenty-three tumors, including ten astrocytomas, one ependymoma, two glioblastomas, one case of gliomatosis, and nine poorly differentiated gliomas were positive for GFAP. Two astrocytomas, eleven oligodendrogliomas, eight ependymomas, four choroid plexus papillomas, two medulloblastomas, one glioblastoma, nine poorly differentiated gliomas, six cases of gliomatosis, and three unclassified tumors were GFAP-negative. In six tumors (including four that were classified as astrocytoma) GFAP staining was equivocal. All oligodendrogliomas were MBP-negative but three expressed MAG. It was concluded that many canine gliomas are not only morphologically but also mmunocytochemically similar to human gliomas, but that a larger proportion of canine neuroctodermal growths are undifferentiated tumors.Supported by the Swiss National Science Foundation (grant no, 3.809.81)     

Immediate and remote results of surgical treatment of intramedullary astrocytoma and ependymoma of the spinal cord

In the Department of Neurosurgery, Medical Academy in Lód? 219 patients were operated on the years 1948-1982 for intraspinal tumours, 39 of which were situated within the spinal cord. Excluding 9 cases of tumours situated in the lumbar or lumbosacral areas in the remaining 30 cases 11 astrocytomas, 11 ependymomas, 3 malignant gliomas, and 1 case each of teratoma, sarcoma, carcinoma, neurinoma and ganglioblastoma were found. Only the groups of astrocytomas and ependymomas were analyzed with respect to the clinical state of the patients and early and late results considering them as sufficiently large.     

术中超声在脊髓髓内室管膜瘤和星形细胞瘤外科治疗中的应用

目的探讨术中超声在脊髓髓内室管膜瘤和星形细胞瘤显微外科手术中的应用价值。方法回顾性分析2010年1月至2018年5月华中科技大学同济医学院附属同济医院神经外科收治的78例脊髓髓内室管膜瘤和34例脊髓髓内星形细胞瘤患者的临床资料。根据术中是否使用超声辅助,分别将室管膜瘤和星形细胞瘤患者分为超声组(前者44例,后者18例)和对照组(前者34例,后者16例)。对所有患者行门诊或电话随访,通过影像学复查和改良McCormick量表(MMS)分级评估肿瘤复发和脊髓功能恢复情况。分别比较室管膜瘤和星形细胞瘤两组患者的疗效,并评价术中超声对肿瘤完全切除率的评估准确率。结果两组室管膜瘤和星形细胞瘤患者的性别、年龄、首诊症状、MMS分级及肿瘤累及脊髓节段的差异均无统计学意义(均P>0.05),基线资料均基本一致。室管膜瘤的超声组和对照组患者肿瘤完全切除率[分别为97.7%(43/44)、91.2%(31/34)]、术后并发症发生率[分别为8.8%(3/44)、11.8%(4/34)]及术后3个月脊髓功能恢复良好率[分别为36.4%(16/44)、32.4%(11/34)]的差异均无统计学意义(均P>0.05)。超声组和对照组的星形细胞瘤患者术后并发症发生比例(分别为:0/18、2/16)和术后3个月脊髓功能恢复良好比例(分别为:3/18、2/16)的差异均无统计学意义(均P>0.05);但与对照组比较,超声组的肿瘤完全切除比例高[分别为16/18、9/16,P<0.05]、无进展生存期(PFS)长[中位PFS分别为84.0(67.5~100.5)个月、75.0(52.0~98.0)个月,P<0.05]。以增强MRI为标准,术中超声判断室管膜瘤和星形细胞瘤全切除的准确比率分别为97.7%(42/43)、14/16。结论术中超声有助于实时、准确地判断脊髓髓内室管膜瘤和星形细胞瘤的肿瘤切除程度,且对星形细胞瘤的应用价值较大。     

Spinal neurofibromatosis in a family with classical neurofibromatosis type 1 and a novel NF1 gene mutation

Familial spinal neurofibromatosis (FSNF) is a rare form of neurofibromatosis type 1 (NF1) characterized by multiple, histologically proven neurofibromas of the spinal roots leaving no intact segments and associated neurofibromas of major peripheral nerves. It is sometimes associated with other NF1 stigmata. Most patients have NF1 gene mutations. We describe a patient who fulfilled the diagnostic criteria for spinal neurofibromatosis and belonged to a family in which other affected members exhibited classical NF1 stigmata. A novel missense (c.7109 T > A; p.Val2370Asp) mutation in exon 39 of the NF1 gene was present in the affected family members. The family displayed extreme phenotypic variability in the spectrum of NF1. To our knowledge, this is the first patient with spinal neurofibromatosis in the context of classical NF1 with an NF1 gene mutation. The term FSNF is inaccurate as this condition simply reflects the typical autosomal dominant pattern of NF1 inheritance with phenotypoc variability and does not encompass patients with sporadic disease or those in the context of a classical NF1 phenotype as reported in the present family. The term could be replaced by “spinal neurofibromatosis”.     

Survival of children with brain tumors: SEER Program, 1973-1980

Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (1973-1980). Twenty-five percent were low-grade supratentorial astrocytomas, medulloblastomas were 23%, cerebellar astrocytomas 12%, high-grade supratentorial astrocytomas 11%, brainstem gliomas 9%, and ependymomas 8%. The worst survivals were in children less than 2 years of age, and the best were in those aged 10 to 14 years. Five-year survivals of children with cerebellar astrocytomas were 91%, low-grade supratentorial astrocytomas 71%, high-grade supratentorial astrocytomas 35%, medulloblastomas 39%, ependymomas 28%, and brainstem gliomas 18%.