Strong OLIG2 expression in supratentorial ependymoma, ZFTA fusion-positive: A potential diagnostic pitfall.

Ependymomas (EPN) are central nervous system neoplasms that exhibit an ependymal phenotype. In particular, supratentorial EPN (ST-EPN) must be differentiated from more aggressive entities such as glioblastoma, IDH-wildtype. This task is frequently addressed with the use of immunohistochemistry coupled with clinical presentation and morphological features. Here we describe the case of a young adult presenting with migraine-like symptoms and a temporoinsular-based expansile mass that was first diagnosed as a GBM, mostly based on strong and diffuse oligodendrocyte transcription factor 2 (OLIG2) expression. Molecular characterization revealed a ZFTA::RELA fusion, supporting the diagnosis of ST-EPN, ZFTA fusion-positive. OLIG2 expression is rarely reported in tumors other than GBM and oligodendrocyte-lineage committed neoplasms. The patient was treated with radiotherapy and temozolomide after surgery and was alive and well at follow-up. This report illustrates the need to assess immunostains within a broader clinical, morphological and molecular context to avoid premature exclusion of important differential diagnoses.

[Verification of the diagnosis of supratentorial ependymomas by real-time PCR]. / Verifikatsiya diagnoza supratentorial'nykh ependimom metodom PTsR v rezhime real'nogo vremeni.

BACKGROUND: Differential diagnosis of supratentorial ependymomas is of particular difficulty in neurooncology due to nonspecific clinical and radiographic findings, a rare seen «classic¼ morphological picture, and a nonspecific immunophenotype. Thanks to molecular genetic methods, in particular real-time PCR, it has become possible to verify supratentorial ependymomas and identify their molecular group, on which further prognosis depends. OBJECTIVE: To develop a set of molecular genetic tests based on real-time PCR to verify supratentorial ependymomas. MATERIAL AND METHODS: 56 tissue samples were collected from patients with supratentorial ependymomas, WHO Grade II, and anaplastic ependymomas, WHO Grade III. We developed primers and fluorescent TaqMan probes for real-time PCR analysis to detect the ZFTA::RELA, ZFTA::MAML2, ZFTA::NCOA2, ZFTA::MAML3, YAP1::MAMLD1, and YAP1::FAM118B gene fusions. For immunohistochemical analysis, monoclonal rabbit anti-NF-kb p65 antibodies (HUABIO, China) were used, the study was carried out on AutostainerLink 48 immunostainer (DAKO, Denmark). RESULTS: Real-time PCR was able to verify the diagnosis for 69.9% (n=39) of samples and classify them into molecular groups of ZFTA- or YAP1-positive supratentorial ependymomas. Immunohistochemically it was possible to verify 58% (n=29) ependymomas. CONCLUSION: Diagnosis by real-time PCR is a relatively fast, accessible and easily interpreted method that allows verification of the molecular group in 70% of cases of supratentorial ependymomas without the use of additional methods.

Factors associated with preoperative and early and late postoperative seizures in patients with supratentorial meningiomas.

OBJECTIVE: Risk factors for epilepsy in meningioma patients are not yet clearly defined, however, seizure freedom is a significant factor for quality of life after surgery. METHODS: We performed a retrospective study of the 333 adult patients who received surgery for supratentorial meningioma at our center. Various clinical, radiological, and surgical variables were included in the multivariate regression, and the outcomes measured were the occurrence of seizure(s) preoperatively, during the hospitalization, and during the follow-up period. RESULTS: A total of 89 (26.7%) patients experienced preoperative seizures, of whom 62.9% were seizure free after the surgery. Of 244 patients without epilepsy before surgery, 11.9% had at least one seizure postoperatively. In total, 63 of our patients (18.9%) experienced seizures after the surgery, of whom 20 had refractory epilepsy. Multivariate analysis identified the following predictors of preoperative seizures: the absence of headache (OR: 0.23, CI: 2.55-8.50), the presence of significant peritumoral edema (OR: 4.35, CI: 2.57-7.35), and younger age (OR: 0.97 per year increase, CI: 0.95-0.99). Factors associated with early postoperative seizures were: younger age (OR: 0.96 per year increase, CI: 0.93-0.99) and the presence of preoperative seizures (OR: 2.73, CI: 1.13-6.57), while the presence of preoperative seizures (OR: 4.73, CI: 2.05-10.92), tumor progression (OR: 5.38, CI: 2.25-12.89), and neurological worsening (OR: 5.21 CI: 1.72-15.81) were significant for late postoperative seizures. SIGNIFICANCE: Our results from a single-center meningioma cohort confirm, in general, data from some previous studies regarding patients' characteristics for both preoperative and overall postoperative epilepsy. Besides previously described risk factors, younger age was important for preoperative and early postoperative seizures. Epilepsy is common in patients with recurrence of meningioma, but the variables of significance for refractory seizures in these patients require further examination.

Extraventricular site indicates higher grade but better prognosis in adult supratentorial ependymomas: a 14-year single-center retrospective cohort.

Supratentorial extraventricular ependymoma (STEE) and supratentorial intraventricular ependymoma (STIE) are two subsets of supratentorial ependymoma (SE). These two subsets have similar gene features and only differ in original sites: STEE occurs in the brain parenchyma, and STIE is located in ventricles and surrounded by cerebral spinal fluid. The present study aims to depict the diversities of these two subsets and elucidate the potential effects of the anatomic site on the tumor with the same type, grade, and molecular features. Sixty-six consecutive adult SE patients from 2008 to 2021 were enrolled in our study. Clinical data, pathological features, and long-term outcomes were analyzed retrospectively. Results demonstrated that adult STEE presented with a higher proportion of WHO grade 3 (P = .028) and higher Ki-67 index (≥10%) (P = .019) compared to adult STIE. Survival analysis demonstrated that patients of grade 3 STEE exhibited a significantly longer overall survival (OS) than patients of grade 3 STIE (median OS, 24.4 months vs. 13.0 months; P = .004). Grade 2 (hazard ratio (HR) = 0.217; P < .001) and gross total resection (GTR) (HR = 0.156; P < .001) were identified as favorable prognostic factors for all adult SE. The STEE was also associated with a lesser hazard of death for patients of grade 3 on multivariate analysis (HR = 0.263; P = .047). These findings suggested that the extraventricular site was an indicator for higher grade and better prognosis in adult supratentorial ependymoma.

Supratentorial extra-axial RELA fusion-positive ependymoma misdiagnosed as meningioma by intraoperative histological and cytological examinations: a case report.

BACKGROUND: Dura-attached supratentorial extra-axial ependymoma is a very rare type of tumor, with only nine reported cases. Preoperative diagnosis of dura-attached supratentorial extra-axial ependymoma is difficult and often radiologically misdiagnosed as a meningioma. We report a case of dura-attached supratentorial extra-axial ependymoma that was misdiagnosed using intraoperative histological and cytological examinations. CASE PRESENTATION: A 26-year-old Japanese man with headache and nausea was referred to our medical facility. Magnetic resonance imaging revealed a cystic mass of 70 × 53 × 57 mm in the left temporoparietal lobe. A peritumoral band with hyperintensity on T2-weighted imaging was observed at the periphery of the lesion, suggesting an extra-axial lesion with no apparent connection to the ventricle. A dural tail sign was also noted on the gadolinium-enhanced T1-weighted image. Preoperative clinical diagnosis was meningioma. Proliferated tumor cells in sheets with intermingled branching vessels were observed in the frozen tissue. Perivascular rosettes were inconspicuous, and the tumor cells had rhabdoid cytoplasm. The tumor was intraoperatively diagnosed as a meningioma, suspected to be a rhabdoid meningioma. Perivascular rosettes were evident in the formalin-fixed paraffin-embedded tissues, suggesting ependymoma. The tumor cells had eosinophilic cytoplasm without a rhabdoid appearance. Anaplastic features, such as high tumor cellularity, increased mitotic activity, microvascular proliferation, and necrosis, were observed. Ependymal differentiation was confirmed on the basis of ultrastructural analysis. Molecular analysis detected C11orf95-RELA fusion gene. The final diagnosis was RELA fusion-positive ependymoma, World Health Organization grade III. CONCLUSION: Owing to its unusual location, dura-attached supratentorial extra-axial ependymomas are frequently misdiagnosed as meningiomas. Neuropathologists should take great precaution in intraoperatively diagnosing this rare subtype of ependymoma to avoid misdiagnosis of the lesion as other common dura-attached tumors.

Extra-Axial supratentorial anaplastic ependymoma: Unusual location of an aggressive tumor, A case report.

Introduction: Ependymomas are more common in the pediatric population, in whom they are commonly infratentorial. Extra axial location of a supratentorial ependymoma is extremely rare. Diagnosis: Radiologically these tumors are often misdiagnosed as meningioma or other extra axial lesions owing to their unusual location and lack of any pathognomonic features. Hence, histopathological examination becomes imperative for proper evaluation and an adequate diagnosis. Case: Herein we report a case of a supratentorial extra axial anaplastic ependymoma misdiagnosed as a metastatic tumor on radiological examination and mimicking meningioma intra operatively, located in the frontal and temporal region in a 20 year old man.

A rare case of pediatric primary central nervous system differentiating neuroblastoma: an unusual and rare intracranial primitive neuroectodermal tumor (a case report).

Neuroblastoma represents the most common solid extracranial tumor in children under 5, accounting for 8% to 10% of all childhood cancers. Primary central nervous system (CNS) neuroblastomas are a very rare location and only few cases are available in the literature. It was first described in 1973 by Hart and Earl as supratentorial primitive neuroectodermal tumors. Clinical presentation is highly variable and depends on the initial location of the tumor. Regarding imaging, primary brain neuroblastoma shows no pathognomonic appearance on brain computed tomography (CT) whether or not enhanced or magnetic resonance imaging (MRI). There were no standard guidelines available for the adjuvant treatment in case of primary CNS neuroblastoma. Surgery remains the main and the first tool toward these lesions. Radiotherapy associated or not to chemotherapy is offered based on patient´s age. Here, the authors report a new pediatric case of primitive central nervous system neuroblastoma revealed by an intracranial hypertension syndrome and confirmed by both histopathological and immunohistochemistry study after a gross total surgical excision. The postoperative course was uneventful and the child had good recovery.

The clinical and prognostic values of optic nerve sheath diameter and optic nerve sheath diameter/eyeball transverse diameter ratio in comatose patients with supratentorial lesions.

BACKGROUND: The optic nerve sheath diameter (ONSD) and ONSD/eyeball transverse diameter (ETD) ratio have been proven to be correlated with intracranial pressure. This study aimed to evaluate the prognostic roles of ONSD and the ONSD/ETD ratio in comatose patients with supratentorial lesions and to determine the relationship of these two indices with the prognosis of such patients. METHODS: A total of 54 comatose patients with supratentorial lesions and 50 healthy controls were retrospectively included in this study. ONSD and ETD were measured by unenhanced computed tomography (CT). The differences in ONSD and the ONSD/ETD ratio between the two groups were compared. The prognosis of comatose patients was scored using the Glasgow Outcome Scale (GOS) at the 3-month follow-up, and these patients were classified into good (GOS score ≥ 3) and poor (GOS score < 3) prognosis groups. The differences in ONSD and the ONSD/ETD ratio were compared between comatose patients with good prognoses and those with poor prognoses. RESULTS: The ONSD and ONSD/ETD ratios in the comatose patients were 6.30 ± 0.60 mm and 0.27 ± 0.03, respectively, and both were significantly greater than those in the healthy controls (5.10 ± 0.47 mm, t = 11.426, P < 0.0001; 0.22 ± 0.02, t = 11.468, P < 0.0001; respectively). ONSD in patients with poor prognosis was significantly greater than that in patients with good prognosis (6.40 ± 0.56 vs. 6.03 ± 0.61 mm, t = 2.197, P = 0.032). The ONSD/ETD ratio in patients with poor prognosis was significantly greater than that in patients with good prognosis (0.28 ± 0.02 vs. 0.26 ± 0.03, t = 2.622, P = 0.011). The area under the receiver operating characteristic (ROC) curve, used to predict the prognosis of comatose patients, was 0.650 (95% confidence interval (CI): 0.486-0.815, P = 0.078) for ONSD and 0.711 (95% CI: 0.548-0.874, P = 0.014) for the ONSD/ETD ratio. CONCLUSIONS: The ONSD and ONSD/ETD ratios were elevated in comatose patients. The ONSD/ETD ratio might be more valuable than ONSD in predicting the prognoses of comatose patients with supratentorial lesions.

Supratentorial ependymoma with YAP1:FAM118B fusion: A case report.

We report a case of a 26-year-old Chinese man who had experienced three grand mal seizures in the past two months. Magnetic resonance imaging revealed a relatively well-circumscribed lesion in the left frontal lobe. A craniotomy with total excision of the tumor was performed. Histopathological investigations confirmed a grade 2 ependymoma according to the World Health Organization classification. Genetic analysis revealed a tumor harboring FAM118B fusion to YAP1, and no other genetic alterations or methylation of the O6 -methylguanine-DNA methyltransferase gene promoter were detected. This is the second case report of ependymoma with YAP1:FAM118B fusion.

Robot-Assisted Stereotactic Biopsies in 377 Consecutive Adult Patients with Supratentorial Diffuse Gliomas: Diagnostic Yield, Safety, and Postoperative Outcomes.

BACKGROUND: Multiple biopsy samples are warranted for the histomolecular diagnosis of diffuse gliomas in the current molecular era, which possibly increases morbidity. OBJECTIVE: We assessed diagnostic yield, safety, and risk factors of postoperative morbidity after robot-assisted serial stereotactic biopsy sampling along 1 biopsy trajectory for diffuse gliomas. METHODS: Observational retrospective analysis of consecutive magnetic resonance imaging-based robot-assisted stereotactic biopsies performed at a single institution to assess the diagnosis of nonresectable newly diagnosed supratentorial diffuse gliomas in adults (2006-2016). RESULTS: In 377 patients, 4.2 ± 1.9 biopsy samples were obtained at 2.6 ± 1.2 biopsy sites. The histopathologic diagnosis was obtained in 98.7% of cases. Preoperative neurologic deficit (P = 0.030), biopsy site hemorrhage ≥20 mm (P = 0.004), and increased mass effect on postoperative imaging (P = 0.014) were predictors of a new postoperative neurologic deficit (7.7%). Postoperative neurologic deficit (P < 0.001) and increased mass effect on postoperative imaging (P = 0.014) were predictors of a Karnofsky Performance Status decrease ≥20 points postoperatively (4.0%). Increased intracranial pressure preoperatively (P = 0.048) and volume of the contrast-enhanced area ≥13 cm3 (P = 0.048) were predictors of an increased mass effect on postoperative imaging (4.4%). Preoperative Karnofsky Performance Status <70 (P = 0.045) and increased mass effect on postoperative imaging (P < 0.001) were predictors of mortality 1 month postoperatively (2.9%). Preoperative neurologic deficit (P = 0.005), preoperative Karnofsky Performance Status <70 (P < 0.001), subventricular zone contact (P = 0.004), contrast enhancement (P = 0.018), and steroid use (P = 0.003), were predictors of the inability to discharge to home postoperatively (37.0%). CONCLUSIONS: Robot-assisted stereotactic biopsy sampling results in high diagnostic accuracy with low complication rates. Multiple biopsy sites and samples do not increase postoperative complications.

Pediatric atypical choroid plexus papilloma: Clinical features and diagnosis.

OBJECTIVE: Atypical choroid plexus papilloma (aCPP) is a newly introduced subtype of choroid plexus tumors (CPTs) defined by the World Health Organization (WHO) in 2007 and is characterized by intermediate characteristics between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). Currently, the available data describing the clinical features of aCPP in children are limited. METHODS: We performed a retrospective review of 24 pediatric patients with CPTs in our institute and focused on the clinical, radiological and histopathological features of 9 patients with aCPP. RESULTS: The median age of aCPP patients was 12 (3-144) months, which was younger than the age of CPP patients (36 (5-132) months, P < 0.05). Of the 9 aCPPs, there were 4 cases of giant masses in the cerebral hemisphere, which was significantly higher than that in CPPs (44.4 % vs 0.0 %, P < 0.05). According to MRI analysis, cysts and necrosis (66.7 % vs 16.7 %, P < 0.05), peritumoral edema (55.6 % vs 8.3 %, P < 0.05) and blurred borders (55.6 % vs 8.3 %, P < 0.05) were more common in aCPPs than in CPPs. T1WI isointense signals were mainly observed in aCPPs and CPPs (aCPP66.7 % vs CPP58.3 %, P >0.05), while T2WI slightly low signals were more common in CPPs (CPP41.7 % vs aCPP0%, P < 0.05); moreover, the tumor volume of aCPPs was significantly larger than that of CPPs (aCPP78.3 cm3 vs 8.4 cm3, P < 0.05). For the DWI sequence scans, isointense signals were more common in aCPPs (aCPP77.8 %>CPP25.0 %, P < 0.05), while slightly low signals were more common in CPPs (CPP58.3 %>aCPP0%, P < 0.05). Both aCPPs and CPPs mainly showed homogeneously strong enhancement (aCPP66.7 % vs CPP91.7 %, P > 0.05). Interestingly, 1 aCPP showed annular enhancement. For the pathological and immunohistochemical studies, the Ki67 proliferation index was significantly higher in aCPPs than in CPPs (13 % vs 6%, P < 0.05), and the S-100(+)/Vim(+)/Syn(+) positive rate was higher in aCPPs (58.3 % vs 11.1 %, P < 0.05). CONCLUSIONS: aCPP shows some distinctive clinical features compared with CPP, such as younger age, larger tumor size, more frequent necrosis and peritumoral edema, blurred borders, slightly low signals on T2WI and isointense signals on DWI, and a higher S-100(+)/Vim(+)/Syn(+) positive rate, which may provide more valuable evidence for differential diagnosis and clinical decisions surrounding aCPP.

RELA fusion-positive ependymoma accompanied by extensive desmoplasia: a case report.

We report a case of 33-year-old Japanese male who presented with a headache and visual disturbances. Magnetic resonance imaging revealed a large tumor in the left frontal lobe, measuring 7 cm in diameter, which was diagnosed as supratentorial anaplastic ependymoma accompanied by extensive desmoplasia. The patient underwent a gross total resection. Histologically, the tumor cells had oval or short, spindle-shaped nuclei, and proliferating cells in perivascular pseudorosettes with anucleate zones and mitotic figures. Desmoplasia with abundant collagen fibers among the tumor cells was detected at numerous sites, and perinuclear dot- or ring-like immunoreactivity for epithelial membrane antigen was identified. Five years and six months after the initial procedure, a small recurrent tumor was identified at the removal site. The patient underwent a second total resection. The histology of the resected tumor showed decreased collagen production and more apparent anaplastic features as compared to those of the initial tumor. In addition to the histological findings, molecular examinations revealed ependymoma, RELA fusion positive. Although not commonly observed, this case suggests that desmoplasia could be associated with ependymomas, including RELA fusion-positive variant. Moreover, our findings indicate that high-grade ependymoma requires careful, long-term follow-up even if gross total resection is performed.

Resection of Invasive Sphenoorbital and Cavernous Sinus Meningioma via Frontotemporal Craniotomy.

Sphenoorbital meningiomas require extensive bone removal around the superior and lateral orbital walls, superior orbital fissure, and anterior middle fossa floor. Incomplete resection can lead to recurrence or growth into the cavernous sinus (CS). A 46-year-old woman with a history of childhood leukemia treated with chemotherapy and whole-body radiotherapy had presented to an outside institution in 2004 with headache and vision changes and undergone subtotal resection for right sphenoorbital meningioma. Residual tumor growth caused progressive optic neuropathy, and she underwent multiple orbital decompressions and fractionated radiotherapy. In 2017, she underwent another craniotomy for repeat resection. Additional tumor growth causing neuropathic facial pain syndrome and progressive ophthalmoplegia was treated with orbital enucleation. On referral to our institution, magnetic resonance imaging demonstrated right sphenoorbital and CS meningioma extending into the sella and nearly to the medial border of the contralateral CS. Given her complete ophthalmoplegia and recent orbital enucleation, she underwent revision right frontotemporal craniotomy for radical resection of invasive meningioma, including right internal carotid artery occlusion and CS resection (Video 1). The skull-base defect was repaired with autologous fascia and a free muscle flap. Postoperative transient aphasia and left hemiparesis resolved over several days. At the 1-month follow-up examination, she was neurologically intact, with moderate improvement of facial pain syndrome (preoperative pain score, 9 of 10; postoperative pain score, 6 of 10). Magnetic resonance imaging demonstrated gross total resection. Pathological tissue analysis was consistent with grade 1 meningioma with an increased MIB-1 proliferative index, although, clinically, the tumor behaved more malignantly. The patient provided consent.

Small Cell Variant of Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma of the Dura Mimicking Tentorial Meningioma.

BACKGROUND: Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)-positive ALCL have been reported so far, with no reported cases of a small cell variant. CASE DESCRIPTION: A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE). CONCLUSIONS: In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment.

Utility of copy number variants in the classification of intracranial ependymoma.

Ependymomas are neuroepithelial tumors that differentiate along the ependymal cell lineage, a lining of the ventricles of the brain and the central canal of the spinal cord. They are rare in adults, but account for around 9% of brain tumors in children, where they usually have an aggressive course. Efficient stratification could lead to improved care but remains a challenge even in the genomic era. Recent studies proposed a multivariate classification system based on tumor location, age, and broad genomic findings like global patterns of methylation and copy number variants (CNVs). This system shows improved prognostic utility, but is relatively impractical in the routine clinical setting because it necessitates multiple diagnostic tests. We analyzed 13 intracranial grade II and III ependymoma specimens on a DNA microarray to identify discrete CNVs that could support the existing classification. The loss of chr22 and the gain of 5p15.31 were common throughout our cohort (6 and 11 cases, respectively). Other CNVs correlated well with the previously proposed classification system. For example, gains of chr20 were unique to PF-EPN-B tumors of the posterior fossa and may differentiate them from PF-EPN-A. Given the ease of detecting CNVs using multiple, clinically validated methods, these CNVs should be further studied to confirm their diagnostic and prognostic utility, for incorporation into clinical testing algorithms.

Histopathological features of malignant craniopharyngioma: Case report and literature review.

Malignant transformation in craniopharyngiomas is a very uncommon event and scarcely mentioned in the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS). So far, there are only 34 reported cases. AIMS: We report an additional case in a 63-year-old woman who was diagnosed with craniopharyngioma 47 years ago. We reviewed the literature in order to define the histological features of malignant craniopharyngioma and its overlap with odontogenic tumors. RESULTS: Our case presented morphology of mixed odontogenic ghost cell/ameloblastic carcinoma. Analyzing all reported cases, 18 of them presented malignization as squamous cell carcinoma (SCC), 1 as odontogenic ghost cell carcinoma, 2 as ameloblastic carcinoma, and 10 cases were mentioned just as malignant craniopharyngiomas. CONCLUSION: We concluded that SCC represented only half of the malignant cases, while the morphology of ~ 11% of them was comparable with ameloblastic or odontogenic ghost cell carcinomas and 28% lacked a specific histological diagnosis. Most cases were fatal, which makes it necessary to include the entity of malignant craniopharyngioma in the WHO Classification of Tumors of the CNS as a high-grade tumor defining its histological variability.