[Supratentorial neuroepithelial tumor with PLAGL1 gene fusion - a new type of morphologically variable pediatric brain neoplasm defined by a distinct DNA methylation class. A case report and literature review]. / Supratentorial'naya neiroepitelial'naya opukhol' so sliyaniem gena PLAGL1 u detei ­ novyi tip opukholi mozga s raznoobraznoi morfologicheskoi kartinoi i otlichitel'nym metilyatsionnym profilem(sluchai iz praktiki i obzor literatury).

BACKGROUND: Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types. OBJECTIVE: To describe the MRI and histological pattern of neuroepithelial tumor with PLAGL1 gene fusion. MATERIAL AND METHODS: We present a 6-year-old patient with small right frontal intraaxial tumor causing drug resistant epilepsy. Despite indolent preoperative clinical course and MRI features suggesting glioneuronal tumor, histological evaluation revealed characteristics of high-grade glioma, ependymoma and neuroblastoma. RESULTS: Methylation analysis of tumor DNA confirmed a new type of a recently discovered neoplasm - neuroepithelial tumor with PLAGL1 fusion (NET PLAGL1). PCR confirmed fusion of PLAGL1 and EWSR1 genes. No seizures were observed throughout the follow-up period. There was no tumor relapse a year after surgery. CONCLUSION: Methylation analysis in neurooncology is essential for unclear tumor morphology or divergence between histological and clinical data. In our case, this technique confirmed benign nature of tumor, and we preferred follow-up without unnecessary adjuvant treatment.

Polymorphous low-grade neuroepithelial tumour of young (PLNTY): the new kid on the block.

INTRODUCTION: Polymorphous low grade neuroepithelial tumor of the young (PLNTY) is a newly described epileptogenic tumor first reported by Jason. T. Huse et al. in 2016. Only a very few cases have been reported so far and has been recently incorporated in the World Health Organization (WHO) Central Nervous System Classification of tumours, 5th edition, 2021. Here we report a rare case of PLNTY which closely resembles DNET (Dysembryoplastic neuroepithelial tumor) with plenty of interesting findings which would otherwise go unnoticed resulting in a nonspecific or misclassified diagnosis. CASE REPORT: A 12 year old boy presented to the Neurosurgery OPD with seizures for the past five years and was given multiple antiepileptics for the same. Magnetic resonance imaging (MRI) showed a well-defined lobulated cortical mass with T1 hypo intensity and T2 hyperintensity in the left temporal lobe measuring 2.1 × 2 × 1.3 cm suggesting a DNET. Left temporal craniotomy and excision of the lesion was done. Frozen section showed features of a low grade glial neoplasm. Routine sections demonstrated polymorphous findings including oligodendroglia like features, neuronal nuclear pleomorphism, spindled astroglial elements, perivascular rosettes, calcification, and vascular mineralization. By immunohistochemistry (IHC), the tumor cells were diffusely positive for GFAP and CD34.Ki67 labelling index was low. A final diagnosis of PLNTY was made based on the above findings. The child has been epilepsy free since the past one-month post-surgery and is on follow up. DISCUSSION/CONCLUSION: PLNTY is a newly discovered distinct pediatric low grade glial neoplasm which was earlier grouped into nonspecific forms of DNET. It is characterized morphologically and molecularly by the presence of oligodendroglial component, CD34 expression, BRAFV600E mutation and alterations in the MAP kinase pathway. They are known to behave in a low-grade fashion amenable to control by excision with occasional cases of recurrence reported. It is important to recognize and report similar tumors to determine the long-term risk of recurrence and create a more complete understanding on their radiology and molecular genetics.

Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series.

BACKGROUND: Dysembryoplastic neuroepithelial tumors are rare benign supratentotrial epilepsy-associated glioneuronal tumors of children and young adults. Patients have a long history of seizures. Proper surgical resection achieves long term seizure control. We describe the clinicopathological features of dysembryoplastic neuroepithelial tumor cases reported in our practice and review the published literature. METHODS: All cases of Pakistani ethnicity were diagnosed between 2015 and 2021 were included. Slides were reviewed and clinicopathological features were recorded. Follow-up was obtained. Extensive literature review was conducted. RESULTS: Fourteen cases were reported. There were 12 males and 2 females. Age range was 9-45 years (mean 19 years). Majority were located in the temporal and frontal lobes. Duration of seizures prior to resection ranged from 2 months to 9 years with mean and median duration of 3.2 and 3 years, respectively. Histologically, all cases demonstrated a multinodular pattern, specific glioneuronal component, and floating neurons. Simple and complex forms comprised seven cases each. No significant nuclear atypia, mitotic activity, or necrosis was seen. Ki-67 proliferative index was very low. Cortical dysplasia was noted in adjacent glial tissue in four cases. Follow-up ranged from 20 to 94 months. Seizures continued following resection in all but one case but were reduced in frequency and intensity. In one case, seizures stopped completely following surgery. CONCLUSION: Clinicopathological features were similar to those in published literature. However, a marked male predominance was noted in our series. Seizures continued following resection in all but one case but were reduced in frequency and intensity. This series will help raise awareness among clinicians and pathologists in our part of the world about this seizure-associated tumor of children and young adults.

Glioneuronal and Neuronal Tumors of the Central Nervous System.

Glioneuronal and neuronal tumors (GNTs) are rare neoplasms composed of neural and glial elements frequently located in the temporal lobe. Epilepsy is the main symptom and diagnosis mostly occurs before adulthood. The great majority of GNTs are WHO grade I tumors, but anaplastic transformations and forms exist. Their common association with focal cortical dysplasia is well recognized and should be taken into consideration during neurophysiological presurgical and surgical planning since the aim of surgery should be the removal of the tumor and of the entire epileptogenic zone according to anatomo-electrophysiological findings. Surgery still remains the cornerstone of symptomatic GNT, while radiotherapy, chemotherapy, and new target therapies are generally reserved for anaplastic, unresectable, or evolving tumors. Furthermore, since many GNTs show overlapping clinical and neuroradiological features, the definition of specific histopathological, genetic, and molecular characteristics is crucial. Epileptological, oncological, neurosurgical, and pathological issues of these tumors make a multidisciplinary management mandatory.

Staged Gamma Knife radiosurgery for a rosette-forming glioneuronal tumor of the fourth ventricle: a case report.

BACKGROUND: Rosette-forming glioneuronal tumor (RGNT) is a rare slow-growing neoplasm with mixed glial and neurocytic components. Surgical resection is the mainstay of treatment, whereas the role of adjuvant radiation therapies for residual or recurrent tumors has been poorly investigated. CASE PRESENTATION: We describe the case of a patient with a recurrent fourth ventricular RGNT who was treated with two-staged Gamma Knife radiosurgery (GKRS). GKRS was effective in controlling tumor growth and safe up to seven years from treatment. CONCLUSIONS: This case suggests that GKRS may be a safe and effective treatment for patients with recurrent or residual RGNT.

Radiological and surgical aspects of polymorphous low-grade neuroepithelial tumor of the young (PLNTY).

BACKGROUND: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a low-grade epilepsy-associated tumor recently introduced in WHO 2021 classification. Since it has been recognized as an independent nosological entity, PLNTY has been mainly studied from a genetic and molecular perspective, not recognizing unique characteristic clinical and radiological features. METHODS: A systematic literature research has been conducted aiming to identify all relevant studies about the radiological, clinical and surgical features of PLNTY. We described a representative case of a 45-year-old man treated with awake-surgery with confirmed diagnosis of PLNTY, reporting the radiological and surgical characteristics through imaging and intra-operative video. We performed a statistical meta-analysis attempting to assess the presence of relationships between surgical and radiologic tumor characteristics and clinical outcome and type of surgery. RESULTS: A total of 16 studies were included in the systematic review. The final cohort was composed of 51 patients. Extent of resection (EOR) and outcome are not significantly associated with the different genetic profiling (p = 1), the presence of cystic intralesional component, calcification (p = 0.85), contrast-enhancing and lesion boundaries (p = 0.82). No significant correlation there is between EOR and remission or better control of epilepsy-related symptoms (p = 0.38). The contrast enhancement in the tumor is significantly associated with recurrence or poor control of epileptic symptoms (p = 0.07). CONCLUSIONS: In PLNTYs, contrast enhancement seems to impact prognosis, recurrence, and seizure control much more than radiological features, genetic features and type of resection of the tumor.

Transcallosal and endoscopic hybrid approach to a rare entity of pediatric intraventricular tumors-cribriform neuroepithelial tumor: a case report and literature review.

PURPOSE: Cribriform neuroepithelial tumor (CRINET) is a provisional category of intraventricular tumors, sharing similarities with AT/RTs, and there is a lack of data about its pathology, prognosis, and surgical approaches in the literature. We have been challenged to describe the surgical approach to a rare case of CRINET and describe the intraoperative features since none has been described before. Surgical resection and chemotherapy hold a great importance of favorable prognosis. METHODS: Twenty-month-old male with intraventricular tumor underwent transcallosal intraventricular tumor resection and endoscopic intraventricular second look stages. The tumor was initially considered choroid plexus carcinoma and histopathological results pointed CRINET. The patient also received Ommaya reservoir for intrathecal chemotherapy employment. The patient's preoperative and postoperative MRI scans and tumor's pathological features are described with a brief history of the disease in the literature. RESULTS: Lack of SMARCB1 gene immunoreactivity and presence of cribriform non-rhabdoid trabecular neuroepithelial cells led to the CRINET diagnosis. The surgical technique helped us to approach directly into the third ventricle and perform total resection and intraventricular lavage. The patient recovered without any perioperative complications and is consulted pediatric oncology for further treatment planning. CONCLUSION: With our limited knowledge on the matter, our presentation may provide an inside to the course and progress of the CRINET as a very rare tumor and may help to set a basis for future investigations focused on its clinical and pathological features. Long courses of follow-up periods are required for establishing treatment modules and assessing the responses to surgical resection techniques and chemotherapy protocols.

Radiology-Pathology and Surgical Correlation in Astroblastoma.

Astroblastoma is a rare astrocytic glial neoplasm that affects mainly young girls, peaking between 10 and 30 years of age, with low- and high-grade manifestations. Imaging characteristics are well-described, but histopathologic and, more recently, molecular analysis is fundamental to establish the diagnosis, now based on MN1 alterations. We describe a case with typical imaging and histologic features of an MN1-altered astroblastoma.

Early ependymal tumor with MN1-BEND2 fusion: a mostly cerebral tumor of female children with a good prognosis that is distinct from classical astroblastoma.

PURPOSE: Review of the clinicopathologic and genetic features of early ependymal tumor with MN1-BEND2 fusion (EET MN1-BEND2), classical astroblastomas, and recently described related pediatric CNS tumors. I also briefly review general mechanisms of gene expression silencing by DNA methylation and chromatin remodeling, and genomic DNA methylation profiling as a powerful new tool for CNS tumor classification. METHODS: Literature review and illustration of tumor histopathologic features and prenatal gene expression timelines. RESULTS: Astroblastoma, originally descried by Bailey and Cushing in 1926, has been an enigmatic tumor. Whether they are of ependymal or astrocytic derivation was argued for decades. Recent genetic evidence supports existence of both ependymal and astrocytic astroblastoma-like tumors. Studies have shown that tumors exhibiting astroblastoma-like histology can be classified into discrete entities based on their genomic DNA methylation profiles, gene expression, and in some cases, the presence of unique gene fusions. One such tumor, EET MN1-BEND2 occurs mostly in female children, and has an overall very good prognosis with surgical management. It contains a gene fusion comprised of portions of the MN1 gene at chromosomal location 22q12.1 and the BEND2 gene at Xp22.13. Other emerging pediatric CNS tumor entities demonstrating ependymal or astroblastoma-like histological features also harbor gene fusions involving chromosome X, 11q22 and 22q12 breakpoint regions. CONCLUSIONS: Genomic DNA profiling has facilitated discovery of several new CNS tumor entities, however, traditional methods, such as immunohistochemistry, DNA or RNA sequencing, and cytogenetic studies, including fluorescence in situ hybridization, remain necessary for their accurate biological classification and diagnosis.

Imaging in a new pediatric brain tumor-a supratentorial neuroepithelial tumor with PLAGL1 fusion.

Molecular diagnostics have dramatically influenced the classification of tumor groups in the 2021 WHO CNS tumor classification. Studies focusing on molecular diagnostics continue to identify new tumors. Soon after the summary of the new classification was published, "Supratentorial Neuroepithelial Tumor with PLAGL1 Fusion" was described as a distinct entity. Although this new entity is defined pathologically, its imaging features are undefined. This case report discusses the imaging findings and possible differential diagnosis of the new tumor.

Tectal region papillary neuroglial tumour: a case report.

Papillary glioneuronal tumor (PGNT) is a rare central nervous system neoplasm. Of reported cases, the vast majority are located in the frontal and temporal lobes. We present the case of a 39-year-old male who presented with a one day history of gait disturbance following chemotherapy treatment for metastatic rectal adenocarcinoma. Following MRI of the head showed a tectal mass. Following an occipital interhemispheric craniotomy for tumor resection, final pathology was diagnostic of a papillary neuroglial tumor, WHO grade I. To the best or out knowledge this is the only report of it arising from the tectal plate.

Seizure-outcome after surgery of low-grade epilepsy associated neuro-epithelial tumors.

BACKGROUND: Most patients with glioneuronal tumors present with seizures. Although several studies have shown that greater extent of resection improves overall patient survival, few studies have focused on postoperative seizure outcome after resection of these tumors. The aim of this study was to characterize seizure control rates in patients undergoing glioneuronal tumor resection and evaluate the association between poor seizure outcome and tumor recurrence or progression. METHODS: The study population included patients who had undergone resection of glioneuronal tumors between 2014 and 2019 at our institution. Seizure outcome was assessed using Engel grading. Preoperative seizure characteristics, tumor characteristics, surgical factors, and postoperative seizure outcomes were reviewed. RESULTS: Twenty-six patients (N.=16, temporal lobe; N.=6, frontal lobe; N.=4, parietal lobe) with mean seizures duration of 56.9-months, were assessed. Histopathologically, N.=15 dysembryoplastic neurepithelial tumor, N.=7 ganglioglioma and N.=4 Diffuse lepto-meningeal neuroepithelial tumor. There were 2 cases of complex DNET and one case of DLMNT had associated cortical dysplasia. At mean follow-up of 49.7 months, N.=20 Engel 1, N.=4 Engel 2 and N.=2 had Engel 3 outcome. N.=20 underwent gross total excision (N.=18 Engel 1 and N.=2 Engel 2) and N.=6 sub-total excision. Among the 4 patients who needed re-surgery, two were in Engel 2 and another two were in Engel 3. CONCLUSIONS: Good seizure-outcome is likely associated with extent of resection. Younger age of patient, less than one-year of seizure duration and absence of generalization of seizure are good prognostic indicators. The best seizure-control can be achieved by early surgical intervention.

The long-term surgical outcomes of low-grade epilepsy-associated neuroepithelial tumors.

OBJECTIVE: This study aimed to evaluate the surgical outcomes and relevant prognostic factors in patients with low-grade epilepsy-associated neuroepithelial tumors (LEAT) and, especially, to develop a scoring system to predict postoperative seizure outcomes. METHODS: The clinical data of patients who underwent epilepsy surgery for LEAT were retrospectively studied. The surgical outcomes of seizure and neurological statuses in patients were evaluated using Engel classification and modified Rankin Scale (mRS) scoring, respectively. A scoring system of seizure outcomes was constructed based on the weight of the ß-coefficient estimate of each predictor in the final multivariate predicting model of seizure outcomes. RESULTS: Of the 287 patients (106 female) enrolled, the median age was 19 years at surgery and 10 years at seizure onset, with a median duration of epilepsy of 60 months. Among 258 patients who were followed up for at least 12 months, 215 (83.3%) patients had a favorable seizure outcome (Engel class I) after surgery, and 43 (16.7%) patients had an unfavorable seizure outcome; longer duration of epilepsy, discordant magnetoencephalography (MEG) findings, and acute postoperative seizures were significantly included in the scoring system to predict unfavorable seizure outcomes, and in the scoring system, accumulated scoring of 0-19 scores was recorded, which were finally grouped into three risk levels: low risk (risk < 30%), medium risk (30% ≤ risk < 70%), and high risk (risk ≥ 70%). In addition, favorable neurological outcomes (mRS score 0-1) were recorded in 187 (72.5%) patients, while unfavorable neurological outcomes were recorded in 71 (27.5%) patients, which were significantly related to poor seizure control, older age at surgery, and longer duration of epilepsy and hospitalization time. SIGNIFICANCE: The long-term surgical outcomes of LEAT after surgery were satisfactory. A scoring system for predicting unfavorable seizure outcomes with different risk levels was developed, which could partly guide clinical treatments of LEAT.

The cognitive functions and seizure outcomes of patients with low-grade epilepsy-associated neuroepithelial tumors.

PURPOSE: The aim of the study was to evaluate the cognitive functions and seizure outcomes of patients with low-grade epilepsy-associated neuroepithelial tumors (LEATs). METHODS: We retrospectively reviewed the clinical data of patients who underwent preoperative neuropsychological evaluations and subsequent epilepsy surgery for LEATs. The neuropsychological results of full-scaled intelligence quotient (FSIQ) and full-scaled memory quotient (FSMQ) were analyzed, as well as the postoperative seizure outcomes. RESULTS: Of the 138 patients included in the study, 59 patients (40.4%) were female and 47 (36.6%) patients were children. Preoperatively, 138 patients received FSIQ assessments and 30 patients (21.7%) had an intellectual deficit (FSIQ < 80 scores); 124 patients received FSMQ assessments and 32 patients (25.8%) had a memory deficit (FSMQ < 80 scores). Younger age at seizure onset (OR 0.93; P = 0.035) and discordant ictal electroencephalography (EEG) findings (OR 5.26; P = 0.001) were found to predict intellectual deficits, while abnormal hippocampus (OR 2.36; P = 0.051) as well as discordant ictal EEG findings (OR 4.03; P = 0.007) tended to cause memory deficits. During postoperative follow-up, 123 patients (90.7%) were followed up at least 12 months, and among them, 105 patients (85.4%) got seizure-free (Engel class I), while 18 patients (14.6%) were not (Engel class II-IV); longer duration of epilepsy (OR 1.01; P < 0.001) and discordant interictal EEG findings (OR 5.91; P = 0.005) were found to be related to poor seizure outcomes in patients with LEATs. CONCLUSION: Cognitive deficits commonly occur in patients with LEATs, especially in patients with early or childhood seizures. Early surgical intervention, however, could prevent most of patients from repeated seizure onsets and thus cognitive impairments.

Dysembryoplastic neuroepithelial tumors of childhood: Ege University experience.

BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are rare, low-grade tumors of the central nervous system (CNS) of childhood. It is an important cause of intractable epilepsy, and it is surgically curable. We aimed to review our institutional experience with DNET in children. METHODS: Medical records of children aged less than 18 years of age diagnosed with DNET between 2009 and 2020 at Ege University Hospital were reviewed. Clinical features of the patients including age, gender, initial symptoms, duration of symptoms, medical treatments, age at the time of surgery, tumor location, degree of surgical resection, and outcome of the patients were documented. RESULTS: We reviewed the records of 17 patients with DNETs. Twelve of them were male (70%), 5 of them female (30%). The median age was 11 years (19 months-17 years). The major symptom was a seizure in all of the patients. Thirteen patients presented with complex partial seizures, whereas 2 had a simple partial seizure, and 2 generalized tonic-clonic seizures. Seven patients had drug resistant epilepsy and had received at least two anti-epileptic drugs before surgery. The median duration of symptoms was 6.6 months (0-48 months). In surgery, total surgical resection was performed in 15 patients, and 2 patients underwent partial resection. From these 15 patients, seven patients underwent lesionectomy of the tumor while the other eight patients had extended lesionectomy. The mean follow-up time was 107 months (54-144 months), the seizure control was achieved in 14 patients (82.4%) after surgery, but 3 patients experienced tumor recurrence in the follow-up. CONCLUSION: In DNETs, the complete total resection of the lesion is generally associated with seizure-free outcomes. In the patients with partial resection and lesionectomy, MRI follow-up is recommended for recurrence.

Clinicoradiological and histopathological characteristics and treatment outcomes of cerebral astroblastoma in children: a single-institution experience.

OBJECTIVE: Astroblastoma (AB) is a rare glial tumor. The optimal treatment and prognosis of this tumor remain unclear. The authors retrospectively analyzed the clinical characteristics, neuroimaging findings, histopathological results, and treatment outcomes of 7 patients with AB. METHODS: The study comprised 7 patients with pathologically proven AB who were surgically treated at Samsung Medical Center from November 1994 to January 2019. Clinicoradiological, histopathological, and surgical records were reviewed. RESULTS: The patients included 5 girls (71.4%) and 2 boys (28.6%), with a median age of 13 years. All patients showed contrast enhancement on preoperative MRI: 5 ABs (71.4%) showed a concomitant solid and cystic appearance, and 2 (28.6%) demonstrated a solid appearance. ABs in 6 patients (85.7%) showed a well-circumscribed, characteristic "bubbly" appearance on T2-weighted MRI. Gross-total resection (GTR) was achieved in all cases (100%). Six patients (85.7%) were diagnosed with high-grade AB and 1 (14.3%) with low-grade AB. Six (85.7%) of the 7 patients received adjuvant treatment after resection, including 5 (83.3%) with AB who received chemotherapy and radiotherapy and 1 (16.7%) who received proton therapy alone. The median clinical follow-up duration was 96 months (range 48-189 months). Two patients experienced recurrence, and all patients in this series were alive at the last follow-up. CONCLUSIONS: In this study, the clinicoradiological and histopathological features of AB were described. Based on the authors' limited experience with 7 cases, resection with the goal of GTR is currently the mainstream treatment for AB, and adjuvant radiation treatment should be considered after surgery.

Spinal astroblastoma: a rare tumour in an unusual location.

Astroblastomas are central nervous system tumours with unknown cell of origin and clinical behaviour. These tumours occur most commonly in cerebral hemispheres with spinal astroblastomas being very rare. We report a case of spinal astroblastoma which harboured MN1 alteration.