Consensus guidelines for the management of primary supra-tentorial intraventricular tumour for low- and middle-income countries.

Almost any primary or metastatic brain tumour can manifest in intraventricular (IV) locations. These tumours may either originate within the ventricular system or extend into the IV space through growth. Such neoplasms represent a broad spectrum, with supratentorial IV tumours forming a heterogeneous group. This group includes primary ependymal tumours, central neurocytomas, choroid plexus tumours, and notably, meningiomas, as well as a variety of non-neoplastic, benign, glial, and metastatic lesions that can secondarily invade the IV compartment. Often presenting with nonspecific symptoms, these tumours can lead to delayed medical attention. The diversity in potential diagnoses, combined with their deep and complex locations, poses significant management challenges. This paper aims to delineate optimal management strategies, underscoring the importance of multidisciplinary care, especially in settings with limited resources, to effectively navigate the complexities associated with treating intraventricular brain tumours.

How I do it? Resection of left ventricular central neurocytoma via trans-sulcal approach.

BACKGROUND: The management of lateral ventricle tumors requires a balance between maximizing safe resection and preserving neurological function. METHOD: The authors present a successful case of a left lateral ventricular central neurocytoma resection. The trans-superior frontal sulcus approach was employed, providing a safe corridor while minimizing damage to the surrounding neuroanatomy. The use of an endoscope further facilitated the procedure, enabling the confirmation of complete tumor removal and the preservation of deep venous drainage and periventricular structures. CONCLUSION: This case highlights the utility of the trans-sulcal approach and the benefits of endoscopic assistance in the management of lateral ventricle tumors.

Radiotherapy for central neurocytoma: A multicentric retrospective study in France.

PURPOSE: Neurocytomas represent 0.25 to 0.5% of primary brain tumours and are mainly found in young adults. These tumours have neuronal differentiation. The cornerstone treatment is neurosurgery. The efficacy of other therapies, including radiotherapy, is still unclear. The objective of this study was to evaluate the management of central neurocytomas and the role of radiotherapy. MATERIALS AND METHODS: All adult patients (age 18 years or older) newly diagnosed with a histologically confirmed neurocytoma between 2006 and 2015 in France were included. RESULTS: One hundred and sixteen patients were diagnosed with a central neurocytoma during the study period. All patients underwent surgical resection, and six received adjuvant radiotherapy. Eleven patients received radiotherapy due to progression. After a median follow-up of 68.7 months, local failure occurred in 29 patients. The 5-year local control rate was 73.4%. According to univariate analysis, marker of proliferation Ki67 index greater than 2% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.40-1.57; P=0.027) and subtotal resection (HR: 8.48; CI: 8.01-8.99; P<0.001) were associated with an increase in local failure. Gross total resection was associated with a higher risk of sequelae epilepsy (HR: 3.62; CI: 3.42-3.83; P<0.01) and memory disorders (HR: 1.35; CI: 1.07-1.20; P<0.01). Ten patients (8.6%) died during the follow-up. The 10-year overall survival rate was 89.0%. No prognostic factors for overall survival were found. CONCLUSION: The analysis showed that patients who underwent subtotal surgical resection, particularly when the tumour had a Ki67 index greater than 2%, had an increased risk of local recurrence. These patients could benefit from adjuvant radiotherapy.

Long-term outcomes of central neurocytoma - an institutional experience.

INTRODUCTION: Central Neurocytoma (CN) is a rare, WHO grade 2 brain tumor that predominantly affects young adults. Gross total resection (GTR) is often curative for CNs, but the optimal treatment paradigm including incorporation of RT, following subtotal resection (STR) and for scarcer pediatric cases has yet to be established. METHODS: Patients between 2001 and 2021 with a pathologic diagnosis of CN were reviewed. Demographic, treatment, and tumor characteristics were recorded. Recurrence free survival (RFS) and overall survival (OS) were calculated according to the Kaplan Meier-method. Post-RT tumor volumetric regression analysis was performed. RESULTS: Seventeen adults (≥ 18 years old) and 5 children (< 18 years old) met the criteria for data analysis (n = 22). With a median follow-up of 6.9 years, there was no tumor-related mortality. Patients who received STR and/or had atypical tumors (using a cut-off of Ki-67 > 4%) experienced decreased RFS compared to those who received GTR and/or were without atypical tumors. RFS at 5 years for typical CNs was 67% compared to 22% for atypical CNs. Every pediatric tumor was atypical and 3/5 recurred within 5 years. Salvage RT following tumor recurrence led to no further recurrences within the timeframe of continued follow-up; volumetric analysis for 3 recurrent tumors revealed an approximately 80% reduction in tumor size. CONCLUSION: We provide encouraging evidence that CNs treated with GTR or with RT after tumor recurrence demonstrate good long-term tumor control.

Adult Central Neurocytomas: Clinical Features and Long-Term Treatment Outcomes in Different Age Groups.

BACKGROUND: Central neurocytomas (CNs) usually occur in young adults, and the clinical characteristics and surgical outcomes of patients in different age groups may be different. METHODS: This study was undertaken to compare the clinical and long-term treatment outcomes of patients with CNs in younger and older adult age groups. RESULTS: Eighty consecutive adults with CNs were included, with a mean presentation age of 28.4±7.6 years (range: 19-66 years). Thirty (37.5%) patients were <27 years old, and they tended to manifest with multiple symptoms (P = 0.002), increased intracranial pressure (ICP) symptoms (P = 0.036), an acute clinical course (P = 0.037), worse preoperative neurologic function (P = 0.023), and a larger lesion size and volume (P = 0.004 and 0.007, respectively) than their older age counterparts (≧27 years). An older onset age (P = 0.005) or age ≧27 years (P = 0.014) and worsened Karnofsky Performance Status (KPS) scale (P = 0.040) immediately after microsurgery were associated with unimproved long-term outcomes. CONCLUSIONS: CNs in younger adult patients behave differently from those in the older age group. Surgery can halt neurologic deterioration and ensure satisfactory outcomes.

Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression.

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Whole-exome sequencing reveals genetic variants that may play a role in neurocytomas.

OBJECTIVES: Neurocytomas (NCs) are rare intracranial tumors that can often be surgically resected. However, disease course is unpredictable in many patients and medical therapies are lacking. We have used whole exome sequencing to explore the molecular etiology for neurocytoma and assist in target identification to develop novel therapeutic interventions. METHODS: We used whole exome sequencing (WES) to compare the molecular landscape of 21 primary & recurrent NCs to five normal cerebellar control samples. WES data was analyzed using the Qiagen Clinical Insight program, variants of interest (VOI) were interrogated using ConSurf, ScoreCons, & Ingenuity Pathway Analysis Software to predict their potential functional effects, and Copy number variations (CNVs) in the genes of interest were analyzed by Genewiz (Azenta Life Sciences). RESULTS: Of 40 VOI involving thirty-six genes, 7 were pathogenic, 17 likely-pathogenic, and 16 of uncertain-significance. Of seven pathogenic NC associated variants, Glucosylceramidase beta 1 [GBA1 c.703T > C (p.S235P)] was mutated in 5/21 (24%), Coagulation factor VIII [F8 c.3637dupA (p.I1213fs*28)] in 4/21 (19%), Phenylalanine hydroxylase [PAH c.975C > A (p.Y325*)] in 3/21 (14%), and Fanconi anemia complementation group C [FANCC c.1162G > T (p.G388*)], Chromodomain helicase DNA binding protein 7 [CHD7 c.2839C > T (p.R947*)], Myosin VIIA [MYO7A c.940G > T (p.E314*)] and Dynein axonemal heavy chain 11 [DNAH11 c.3544C > T (p.R1182*)] in 2/21 (9.5%) NCs respectively. CNVs were noted in 85% of these latter 7 genes. Interestingly, a Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 [CTDSP2 c.472G > A (p.E158K)] of uncertain significance was also found in > 70% of NC cases. INTERPRETATION: The variants of interest we identified in the NCs regulate a variety of neurological processes including cilia motility, cell metabolism, immune responses, and DNA damage repair and provide novel insights into the molecular pathogenesis of these extremely rare tumors.

Gamma Knife radiosurgery for central neurocytoma: a quantitative systematic review and metanalysis.

Central neurocytomas (CN) are rare tumors within the central nervous system. Originating from the septum pellucidum and subependymal cells, they are typically found in the third and lateral ventricles. For this reason, they may lead to hydrocephalus and increased intracranial pressure. CNs are generally benign lesions that exhibit locally aggressive behavior and a high recurrence rate. Complete surgical resection is the preferred treatment; however, due to their anatomical location, this is often not feasible. Based on these findings, Gamma Knife radiosurgery (GKRS) has been introduced for managing both residual and recurrent tumors and as an initial therapy in selected cases. This study aimed to systematically review the available knowledge regarding GKRS for CN. A systematic investigation of the scientific literature was undertaken through an exhaustive search across prominent databases, including PubMed, Web of Science, and Google Scholar, by employing precise MeSH terms such as "Central neurocytoma," "Radiosurgery," "Gamma Knife," and "Stereotactic Radiosurgery." A comprehensive quantitative systematic review and meta-analysis were meticulously conducted, focusing on cases of CN treated with GKRS for a thorough evaluation of outcomes and efficacy. Seventeen articles, including 289 patients, met the inclusion criteria. Random effects meta-analysis estimates for disease control and local tumor control were 90% (95% CI 87-93%; I2 = 0%, p < 0.74) and 94% (95% CI 92-97%; I2 = 0%, p < 0.98), respectively. When considering only studies with at least 5 years of follow-up, progression-free survival was 89% (95% CI 85-94%; I2 = 0.03%, p < 0.74). The mean clinical control rate was 96%. This systematic review and meta-analysis confirmed the safety and efficacy of GKRS in managing CN.

Two novel tumours with NTRK2 fusion in the methylation class of extraventricular neurocytomas, including one intraventricular.

We report here about two novel tumours classified as extraventricular neurocytomas (EVN) using DNA-methylation profiling, associated with NTRK2 fusions instead of the usual FGFR1 alterations so far attributed to this tumoural entity. We present the second detailed case of an intraventricular presentation in the MC EVN. Our findings broaden the spectrum of MC EVN and have implications in terms of diagnosis, therapy and terminology.

Intraventricular central neurocytoma molecularly defined as extraventricular neurocytoma: a case representing the discrepancy between clinicopathological and molecular classifications.

Central neurocytoma (CN) is classically defined by its intraventricular location, neuronal/neurocytic differentiation, and histological resemblance to oligodendroglioma. Extraventricular neurocytoma (EVN) shares similar histological features with CN, while it distributes any site without contact with the ventricular system. CN and EVN have distinct methylation landscapes, and EVN has a signature fusion gene, FGFR1-TACC1. These characteristics distinguish between CN and EVN. A 30-year-old female underwent craniotomy and resection of a left intraventricular tumor at our institution. The histopathology demonstrated the classical findings of CN. Adjuvant irradiation with 60 Gy followed. No recurrence has been recorded for 25 years postoperatively. RNA sequencing revealed FGFR1-TACC1 fusion and methylation profile was discrepant with CN but compatible with EVN. We experienced a case of anatomically and histologically proven CN in the lateral ventricle. However, the FGFR1-TACC1 fusion gene and methylation profiling suggested the molecular diagnosis of EVN. The representative case was an "intraventricular" neurocytoma displaying molecular features of an "extraventricular" neurocytoma. Clinicopathological and molecular definitions have collided in our case and raised questions about the current definition of CN and EVN.

Tumors of Choroid Plexus and Other Ventricular Tumors.

Tumors arising inside the ventricular system are rare but represent a difficult diagnostic and therapeutic challenge. They usually are diagnosed when reaching a big volume and tend to affect young children. There is a wide broad of differential diagnoses with significant variability in anatomical aspects and tumor type. Differential diagnosis in tumor type includes choroid plexus tumors (papillomas and carcinomas), ependymomas, subependymomas, subependymal giant cell astrocytomas (SEGAs), central neurocytomas, meningiomas, and metastases. Choroid plexus tumors, ependymomas of the posterior fossa, and SEGAs are more likely to appear in childhood, whereas subependymomas, central neurocytomas, intraventricular meningiomas, and metastases are more frequent in adults. This chapter is predominantly focused on choroid plexus tumors and radiological and histological differential diagnosis. Treatment is discussed in the light of the modern acquisition in genetics and epigenetics of brain tumors.

Central Neurocytoma with Extensive Intratumoral Hemorrhage: A Case Report.

BACKGROUND Central neurocytoma (CN) is a rare neuronal tumor of neuroepithelial origin. It has been assigned to World Health Organization classification grade 2. These tumors are usually benign and located in the anterior half of the lateral ventricle, though they can also be found in the third and fourth ventricles. Left untreated, a CN can cause blockage of cerebrospinal fluid, thus leading to hydrocephalus. CNs are exceedingly uncommon, making up just 0.1-0.5% of primary intracranial tumors. The tumors typically develop in people aged 20 to 40. There are no official guidelines on how to treat CN, so treatment options are often individualized on the basis of specific case findings. CASE REPORT A 39-year-old man with an uncomplicated medical history presented with dizziness, increasingly worse headaches, presyncope, and a loss of appetite. Radiological data and postoperative histopathological and histochemical analysis led to the diagnosis of CN with extensive intratumoral hemorrhage. Surgical resection of the tumor was proposed to the patient, to which he agreed. CONCLUSIONS CN is a benign tumor, but it can cause serious or life-threatening complications. Gross total resection of the tumor is recommended if possible, and if deemed beneficial to the patient's clinical condition. This case reports the symptoms of a patient with CN, who underwent gross total resection and showed no sign of any residual tumor tissue on postoperative MRI. By reporting these types of cases, we can take necessary steps ahead of widespread agreement on optimal treatment of patients with neurocytomas.

Pediatric atypical extraventricular neurocytoma: Clinical features and survival outcomes.

BACKGROUND: Extraventricular neurocytoma (EVN) in children is an extremely rare encountered tumor. Little information is available about the treatment and prognosis of this rare disease in children. This study was undertaken to elucidate the clinical-radiological characteristics and treatment outcomes of pediatric patients with atypical EVN. METHODS: A retrospective review of patients' demographic features, treatment modalities, and outcomes in our institution from January 2011 to December 2019 was conducted. RESULTS: Seven consecutive children harboring atypical EVN in our center were included, with a male predominance (n = 5, 71.4%) and a mean age of 11.8 ± 4.9 years (range: 2-18 years). The lesions mainly involved the frontal (n = 4, 57.1%) and temporal lobes (n = 4, 57.1%). Gross total resection (GTR) was achieved in 6 patients (85.7%), and subtotal resection (STR) was achieved in the remaining patient (14.3%). All lesions demonstrated a high Ki-67 index (≧5%) and atypical features pathologically. Five patients (71.4%) received radiotherapy and/or chemotherapy after surgery. During follow-up, 5 patients (71.4%) experienced lesion progression, and 2 (14.3%) of them died. The median progression-free survival was 48 months. CONCLUSIONS: The prognosis of pediatric patients with atypical EVN was dismal after aggressive treatment. Most tumors progressed, and this progression was positively correlated with the Ki-67 index. Surgical excision is the main treatment modality for atypical EVN, and radiation/chemotherapy should also be introduced after surgery.

Epigenetic Alteration of H3K27me3 as a Possible Oncogenic Mechanism of Central Neurocytoma.

Central neurocytoma (CN) is a low-grade neuronal tumor that mainly arises from the lateral ventricle (LV). This tumor remains poorly understood in the sense that no driver gene aberrations have been identified thus far. We investigated immunomarkers in fetal and adult brains and 45 supratentorial periventricular tumors to characterize the biomarkers, cell of origin, and tumorigenesis of CN. All CNs occurred in the LV. A minority involved the third ventricle, but none involved the fourth ventricle. As expected, next-generation sequencing performed using a brain-tumor-targeted gene panel in 7 CNs and whole exome sequencing in 5 CNs showed no driver mutations. Immunohistochemically, CNs were robustly positive for FGFR3 (100%), SSTR2 (92%), TTF-1 (Nkx2.1) (88%), GLUT-1 (84%), and L1CAM (76%), in addition to the well-known markers of CN, synaptophysin (100%) and NeuN (96%). TTF-1 was also positive in subependymal giant cell astrocytomas (100%, 5/5) and the pituicyte tumor family, including pituicytoma and spindle cell oncocytoma (100%, 5/5). Interestingly, 1 case of LV subependymoma (20%, 1/5) was positive for TTF-1, but all LV ependymomas were negative (0/5 positive). Because TTF-1-positive cells were detected in the medial ganglionic eminence around the foramen of Monro of the fetal brain and in the subventricular zone of the LV of the adult brain, CN may arise from subventricular TTF-1-positive cells undergoing neuronal differentiation. H3K27me3 loss was observed in all CNs and one case (20%) of LV subependymoma, suggesting that chromatin remodeling complexes or epigenetic alterations may be involved in the tumorigenesis of all CNs and some ST-subependymomas. Further studies are required to determine the exact tumorigenic mechanism of CN.

Central neurocytomas: research trends, most cited papers, and scientometrics analysis to date.

Central neurocytoma is the most common primary intraventricular tumor in adults being classified by the World Health Organization (WHO) as a benign grade II tumor with a good prognosis. Given the recent advances with regard to this tumor, a bibliometric analysis was due to study the future direction of research for neurocytomas. A comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies to date relevant to neurocytoma. A discrete set of validated bibliometric parameters were extracted and analyzed on R v4.1.3. A total of 1002 documents were included in our analysis covering a period between 1910 and 2021 (111 years). Around 98.5% of the documents were multi-author publications with a collaboration index (CI) of 4.21. Acta Neuropathologica, The American Journal of Surgical Pathology, and Cancer were the journals to include the highest number of top ten cited articles (2 out of 10 most cited articles, 20%). Switzerland (4 out of 10, 40%) accounted for the country to have the highest number of top 10 most cited articles with the USA (5588 out of 16,395 citations, 34.1%) having the greatest number of citations. Lastly, our analysis reported an annual growth rate of 6.9% for the number of papers produced by year. This is the first bibliometric analysis to study the top 10 most cited articles with regard to neurocytomas. A shift from histopathologic and clinical symptoms towards the treatment and management of the tumor was observed in our analysis.

Central neurocytomas in children: Clinicopathologic features and long-term surgical outcomes.

PURPOSE: Pediatric central neurocytomas (PCNs) is an extremely rare entity, and very few reports have exclusively focused on the clinicopathologic features and surgical outcomes of PCNs. METHODS: This study was undertaken to elucidate the clinical and pathological characteristics and long-term surgical outcomes of PCNs. RESULTS: Fourteen consecutive patients with pathologically verified PCNs were identified, including 9 girls and 5 boys, with a mean age of 15.2 ± 3.9 years (range 3-18 years). Children tended to present with symptoms of increased intracranial pressure (ICP) (p = 0.003), an acute clinical course (p = 0.044), and a shorter duration of symptoms (p = 0.019) than their adult counterparts. Surgery was performed under the guidance of a neuronavigation system and intraoperative ultrasound; gross total resection (GTR) was achieved in 12 patients (85.7%), and subtotal resection (STR) was achieved in two patients (14.3%). One child received adjuvant radiotherapy (RT) owing to the atypical features of the lesion. During a mean follow-up of 90.2 ± 37.0 months (range 42-156 months), one patient (7.1%) with atypical features experienced lesion relapse 2 years after surgery and received RT, and the symptoms of all children were relieved. CONCLUSION: Surgery can benefit children with CNs and ensure relatively long-term progression-free survival. RT can be administered to patients with residual or relapsed lesions.