Adult gangliocytoma arising within the lateral ventricle: A case report and review of the literature

Background: Gangliocytomas are rare neuronal tumors with an incidence of <1% of all central nervous system (CNS) neoplasms. They occur mostly in the pediatric age group, localizing within the cerebral cortex, most often the temporal lobe. Case Description: We report a case of an intracranial gangliocytoma arising within the lateral ventricle in a 66-year-old female. Magnetic resonance imaging of the brain showed a diffusely enhancing lobulated mass situated within the frontal horn of the right lateral ventricle with extension into the foramen of Monro and obstructive hydrocephalus. The patient underwent an interhemispheric transcallosal approach with gross total resection and relief of her hydrocephalus. Pathological examination showed clusters of highly pleomorphic neuron-like cells without evidence of neoplastic glial cells. Histopathological and immunohistochemistry findings were consistent with the diagnosis of gangliocytoma (World Health Organization Grade 1). Conclusion: Gangliocytomas are rare low-grade CNS neoplasms that can present in an older population within unusual locations and should be included within the differential whenever a suspicious lesion is encountered.

Non-dysraphic Subpial Intramedullary Lipoma of Cervicothoracic Spine

Intramedullary spinal cord tumors are rare and comprise less than one percentage of all central nervous system (CNS) neoplasms. When encountered, most are found in the lumbosacral region with coinciding spinal dysraphism. Here, we discuss a case of isolated non-dysraphic intramedullary lipoma of cervicothoracic spine in an adolescent who was surgically managed with posterior decompression and subtotal resection via laminoplasty. A 21-year-old male adolescent, without a history of spinal dysraphism, presented with a progressive sensory ataxia. This manifestation was attributed to magnetic resonance documented intramedullary lipoma, extending from C7 to T2 spinal level. Patient underwent subtotal surgical resection of the lesion; and histopathology report was confirmed as spinal lipoma. Surgical management of this rare pathology has a wide variety of options depending on clinical presentation. In our case, a subtotal resection and laminoplasty was achieved with no further worsening of neurologic symptoms.

Frequência dos tipos histológicos de tumores no sistema nervoso central em um hospital universitário: levantamento de casos ao longo de quatro anos / Frequency of central nervous tumors histological types in an university hospital: data from a four-year period

Introdução: A realização de um padrão epidemiológico das neoplasias do sistema nervoso central (SNC) é prejudicada pela sua heterogeneidade de apresentações, causando uma falta de dados a respeito da incidência de seus diversos tipos. É necessário, dessa forma, realizar estudos com a adoção de critérios de classificação. Objetivo: Desenvolver um banco de dados das neoplasias do SNC, incluindo além dos cânceres primários do SNC, os tumores benignos primários do SNC e as metástases. Método: Foram acessados 1010 casos de biópsias no sistema eletrônico de arquivos do Serviço de Anatomia Patológica, sendo incluídos 381 diagnósticos no estudo, em concordância com os critérios de inclusão e exclusão (neoplasias benignas e malignas do SNC). Resultado: A análise dos diagnósticos histológicos demonstrou um total de 212 pacientes do gênero feminino (55,64%) e 169 do gênero masculino (44,36%). Do total de neoplasias, 307 foram primárias do SNC (80,58%) e 74metástases (19,42%). A distribuição etária variou de 1 a 85 anos, com uma média de idade de 48,953 e a mediana de 52 anos. Os gliomas foram o grupo histológico mais frequente, correspondendo a 30,45% (116 casos), sendo “gliomas difusos” o subtipo histológico mais frequente (73%). Conclusão: O presente estudo documenta a frequência dos tipos histológicos das neoplasias do SNC no Serviço de Anatomia Patológica em um Hospital Universitário entre os anos de 2015 e 2018.Palavras chave: Neoplasias, Neuropatologia, Patologia cirúrgica, Neoplasias do sistema central nervoso, Neoplasias encefálicas AbstractIntroduction: The achievement of an epidemiological pattern of central nervous system tumors (CNS) is hampered by their heterogeneity of presentations, causing a lack of dataregarding the incidence of their various types. Therefore, it is necessary to carry out studies with the adoption of classification criteria. Objective: Develop a database of CNStumors including primary cancers, primary benign tumors and metastases. Methods: A total of 1010 cases of biopsies were accessed in the Department of Pathological Anatomy’selectronic archive system, 381 of which were included in the study, in accordance with the inclusion and exclusion criteria (benign and malignant CNS neoplasms). Results: The histological diagnoses analysis revealed a total of 212 female patients (55.64%) and 169 male patients (44.36%). Overall, 307 were primary CNS neoplasms (80.58%) and 74 CNS metastases (19.42%). The age distribution span ranged from 1 to 85 years of age, with a mean age of 48.953 and a median of 52 years of age. Gliomas were the most frequenthistological group, corresponding to 30.45% (116 cases), with “diffuse gliomas” being the most frequent histological subtype (73%). Conclusion: The present study documentsthe frequency of histological types of CNS neoplasms in the Pathological Anatomy Service of a University Hospital between 2015 and 2018.Keywords: Neoplasms, Neuropathology, Surgical pathology, Central nervous system neoplasms, Brain tumors

Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors

Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.

First-in-human dose escalation and food effect study of oral ONC206 in adults with recurrent primary CNS neoplasms.

TPS2072 Background: The majority of recurrent CNS tumors lack effective systemic therapy options following surgical resection and adjuvant radiotherapy. ONC201, the founding member of the imipridone class of small molecules, has induced durable tumor regressions in patients with diffuse midline glioma, H3 K27M-mutant (DMG H3K27M). ONC206, the second imipridone to enter clinical development, is a DRD2 antagonist and ClpP agonist that exhibits differentiated receptor pharmacology and gene expression profiles in tumors relative to ONC201. The compound is orally bioavailable, penetrates the blood-brain barrier, and exhibits anti-cancer efficacy without toxicity in several preclinical cancer models with pronounced efficacy in myc-overexpressing CNS tumors. Methods: A first-in-human, open label, dose escalation, and food effect Phase I study of oral ONC206 (NCT04541082) is currently enrolling. Patients must be 18 years or older and diagnosed with a recurrent, primary CNS neoplasm. Eligible diseases include recurrent glioblastoma, WHO Grade 2 and 3 infiltrating glial neoplasms, DMG H3K27M, ependymoma, medulloblastoma, malignant meningiomas, and other rare primary CNS neoplasms. Dose escalation, initially with weekly dosing, will follow a standard 3+3 design. After the MTD is established, a food effect cohort will enroll with a balanced, single-dose, two-arm, two-period, crossover design. The primary endpoint is to determine DLT during the first 28-day cycle. Secondary endpoints will include objective response rate by RANO criteria, overall and progression-free survival, and disease control rate. Exploratory biomarker analyses based on preclinical correlations with efficacy will include DRD2, DRD2 dimer, ClpP, DRD5, c-myc, and n-myc expression. Clinical trial information: NCT04541082.

Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial ependymoma

Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of largely ependymoma-like tumors. Immunohistochemically, tumors were GFAP-positive and OLIG2- and SOX10-negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. Consistent with other fusion-positive ependymal groups, all tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Analysis of time to progression or recurrence revealed survival times comparable to those of patients with ZFTA:RELA-fused ependymoma. In summary, our findings suggest the existence of a novel group of supratentorial ependymomas that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.

Epidemiology of tumors of the spinal cord and spine in Ukraine in 2000-2019

Objective. To determine the dynamics and state of neurosurgical care for tumors of the spinal cord and spine (TSCS) in Ukraine. Materials and methods. The work is based on the analysis of hospitalizations and surgical treatment of patients with TSCS in neurosurgical departments of Ukraine in 2000-2019. Results. In 2019, 1,325 patients with TSCS were hospitalized in neurosurgical departments of Ukraine, which is 2,3 times more than in 2000 (567), per 1 million population - almost 3 times (34,7 vs. 11, 6 ). Over 20 years, the number of operated patients increased 2,8 times (from 385 to 1079), per 1 million population - 3,6 times (from 7,9 to 28,3), there was an increase in surgical activity by 20% (from 67,9 to 81,4%), a decrease in the general and postoperative mortality - twice (from 2,6 to 1,2% and from 2,6 to 1,3% respectively). Patients with TSCS account for 1,5% of all patients hospitalized in neurosurgical departments of Ukraine, 12,8% of all CNS neoplasms and 5,2% of all spinal pathology. Vertebral tumors account for 42,64% of all TSCS and extramedullary tumors have an incidence rate similar to vertebral tumors (42,64%), intramedullary tumors account for 14,72%. In 2019, 74.4% more patients with extramedullary tumors were hospitalized than in 2000 (565 and 324 respectively), and 84.5% more were operated on (463 and 251 respectively). The rate of increase is even higher per 1 million population. In 2019, there were 14.8 hospitalizations per 1 million population for extramedullary tumors, which is 2.2 times greater than in 2000 (6,6 hospitalizations), and 12,1 operations, which is 2,4 times greater than in 2000 (5,1 operations). In 2019, patients with intramedullary tumors were hospitalized 2,2 times more than in 2000. (195 and 89 respectively), were operated 2,5 times more (151 and 61 respectively). The rate of increase is even 4higher per 1 million population. In 2019, there were 5,1 hospitalizations for intramedullary tumors per 1 million population, which is 2,8 times greater than in 2000 (1,8 hospitalizations), and 4,0 operations, which is 3,2 times greater than in 2000 (1,2 operations). In 2019, patients with vertebral tumors were hospitalized 3.7 times more than in 2000 (565 and 154 respectively), were operated 6,4 times more (465 and 73 respectively). The rate of increase is even higher per 1 million population. In 2019, there were 14,8 hospitalizations per 1 million population for vertebral tumors, which is 4,7 greater than in 2000 (3,1 hospitalizations), and 12,2 surgeries, which is 8,2 greater than in 2000 (1,5 operations). Сonclusions. The introduction of modern neuroimaging methods and advanced treatment methods into clinical practice has contributed to an increase in the number of hospitalizations and surgical interventions in TSCS.

Bivalent Genes Targeting of Glioma Heterogeneity and Plasticity

Gliomas account for most primary Central Nervous System (CNS) neoplasms, characterized by high aggressiveness and low survival rates. Despite the immense research efforts, there is a small improvement in glioma survival rates, mostly attributed to their heterogeneity and complex pathophysiology. Recent data indicate the delicate interplay of genetic and epigenetic mechanisms in regulating gene expression and cell differentiation, pointing towards the pivotal role of bivalent genes. Bivalency refers to a property of chromatin to acquire more than one histone marks during the cell cycle and rapidly transition gene expression from an active to a suppressed transcriptional state. Although first identified in embryonal stem cells, bivalent genes have now been associated with tumorigenesis and cancer progression. Emerging evidence indicates the implication of bivalent gene regulation in glioma heterogeneity and plasticity, mainly involving Homeobox genes, Wingless-Type MMTV Integration Site Family Members, Hedgehog protein, and Solute Carrier Family members. These genes control a wide variety of cellular functions, including cellular differentiation during early organism development, regulation of cell growth, invasion, migration, angiogenesis, therapy resistance, and apoptosis. In this review, we discuss the implication of bivalent genes in glioma pathogenesis and their potential therapeutic targeting options.

Mortality Rate of CNS neoplasms in childhood in Brazil

Background: The variety of tumors of the Central Nervous System (CNS) during childhood is related to heterogenous clinical manifestations and to an important mortality rate (MR). In Brazil, CNS tumors represent the second most incident cancer during childhood and the main cause of death of children between ages 0-9. Objectives: To describe the number of hospitalizations and the MR of CNS neoplasms by childhood age group in Brazil. Design and Methods: This is a descriptive ecological study based on secondary data, obtained from DATASUS. Data were collected regarding the number of hospitalizations and MR by childhood age group due to neoplasm of the CNS in Brazil between the years 2009-2019. Results: A total of 38192 hospitalizations happened, resulting in 5.91% of MR. The highest value of brain’s neoplasms MR was found in children up to 1 year old (9,34%), but when it comes to number of hospitalizations, the group between ages 5-9 had the highest number, both in neoplasms of the brain (9364) and of other parts of the CNS (1767). Conclusions: The present study pointed out that the childhood age group with the lowest number of hospitalizations (less than 1 year) presented simultaneously the highest MR of CNS tumors.

Central Nervous System Tumors

This chapter provides an overview of behavioral presentations of central nervous system (CNS) neoplasms in adults. Epidemiology of CNS tumors is briefly reviewed. Complications including cognitive dysfunction and emotional disturbances including mood disorders, anxiety, and psychosis are described. The behavioral adverse effects of treatments for CNS cancer, including radiation therapy and steroids, are discussed. The chapter reviews the differential diagnosis of behavioral presentations in this setting as well as an approach to workup and treatment, including neuropsychological testing, psychotherapy, and pharmacotherapy. The potential effects of CNS cancer on caregivers and staff, and possible assistance for them, are covered.