Long-term epilepsy associated-tumors (LEATs): what is new?

Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma MIB or MYBL1 altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.

Tumores associados a epilepsia de longa duração constituem uma série de neoplasias asatrocitárias ou glioneuronais que comumente incidem em crianças, adolescentes e jovens adultos e que são histologicamente benignos (OMS grau 1), de localização neocortical e predominantemente situados nos lobos temporais. Clinicamente, a epilepsia crônica refratária é, de modo geral, o único sintoma. Gangliogliomas (GG) e tumores neuroepiteliais disembrioplásticos (DNT) são as entidades mais representativas associadas a astrocitomas pilocíticos (AP) e gliomas angiocêntricos (GA). Estudos moleculares recentes permitiram a definição de novas entidades clínico-patológicas reconhecidas pela classificação de tumores cerebrais da OMS 2021. Algumas delas, como o astrocitoma difuso MIB ou MIBL1 alterados, o tumor neuroepitelial polimorfo do jovem (PLNTY) e o tumor neuronal multilocular e vacuolizado (MVNT) são atualmente considerados tumores associados a epilepsia de longa duração. A relação entre este grupo de tumores e epilepsia é ainda debatida e há um consenso geral sobre o benefício prognóstico de intervenção cirúrgica precoce.

Uncommon Glioneuronal Tumors: A Radiologic and Pathologic Synopsis.

Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors). Most of these tumors occur in young patients and are related to epilepsy. While ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile tumor are common glioneuronal tumors, anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent. Advances in immunohistochemical and molecular diagnostics have improved the characterization of these tumors and favored the description of variants and new subtypes, some not yet classified by the World Health Organization. Not infrequently, the histologic findings of biopsies of glioneuronal tumors simulate low-grade glial neoplasms; however, some imaging findings favor the correct diagnosis, making neuroimaging essential for proper management. Therefore, the aim of this review was to present key imaging, histopathology, immunohistochemistry, and molecular findings of glioneuronal tumors and their variants.

Central nervous system high-grade neuroepithelial tumor with BCOR alteration: a short report

Central nervous system high-grade neuroepithelial tumors with BCOR alteration are rare. Currently, there are only 24 cases reported in the literature. These tumors are characterized by a change involving the BCOR gene and have a poor prognosis. Studies are needed to improve the current therapy and outcomes of these neoplasms. This case report describes the clinical history of a patient with this disease and aims to contribute to the current knowledge about this new entity.

Treatment response of CNS high-grade neuroepithelial tumors with MN1 alteration.

Central nervous system high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) is a rare recently described entity. Fourteen CNS HGNET-MN1 patients were identified using genome-wide methylation arrays/RT-PCR across seven institutions. All patients had surgery (gross total resection: 10; subtotal resection: four) as initial management followed by observation alone in three patients, followed by radiotherapy in eight patients (focal: five; craniospinal: two; CyberKnife: one) and systemic chemotherapy in three patients. Seven patients relapsed; five local and two metastatic, despite adjuvant radiotherapy, of which three died. Treatment of CNS HGNET-MN1 remains a major treatment challenge despite aggressive surgical resections and upfront radiotherapy, warranting new approaches to this rare malignancy.

[Primary Tumors of the Central Nervous System. Clinical Experience at a Third Level Center].

Background: Central nervous system (CNS) tumors are a group of neoplasms that originate from various cells in the CNS. The increasing incidence and prevalence of this type of tumor in developing countries are striking; however, there are few current studies in Latin America including Mexico estimating the impact of these pathological entities on the general population. Objective: The objective of the study was to study the characteristics of primary CNS tumors over a period of 52 years. Methods: A review of records from patients with a histopathological diagnosis of CNS neoplasm over a period of 52 years was conducted at a tertiary-care academic medical center. Patients were grouped by sex, age, and the tumor's anatomical location. Results: A sample of 9615 patients with tumor lesions was obtained; 51% were female, 49% were male, and their mean age was 42 years. The tumors with the highest prevalence were neuroepithelial tumors (38.6%), followed by meningeal tumors (22.8%). Neuroepithelial tumors accounted for 64% in the group of patients under 40 years of age and 56% among those above 40 years of age. The most frequently involved location was supratentorial, in 78.9% of cases. Conclusions: Although retrospective in nature and based on a small sample, this study reports the epidemiology and characteristics of primary brain tumors in the Mexican population.

Central nervous system tumours profile at a referral center in the Brazilian Amazon region, 1997-2014.

Tumours of the Central Nervous System (CNS) are an important cause of mortality from cancer. Epidemiological data on neoplams affecting the CNS are scarce in Brazil, especially in the Amazon region. The study aims at describing the histopathological profile of CNS tumours cases at a high-complexity referral cancer center. This study has described a 17-year-series profile of CNS tumours, registered at a high-complexity referral cancer center in Pará state, from January 1997 until July 2014 in the Brazilian Amazon Region. Data was gathered from histopathology reports kept in the hospital's cancer registry and 949 cases of CNS tumours were analyzed. The most common histopathology were neuroepithelial tumours (approx. 40%) and meningioma was the most frequent especific tumor histologic subtype (22.2%). Neuroepithelial tumours were more frequent in patients with ages ranging from less than a year to 19 years, whereas metastatic tumours were prevalent in patients over 40 years of age. It was not found temporal trends during the studied period. The knowledge of these tumours profile is valuable for the understanding of cancer epidemiology in the region, since its prevalence is currently underreported and more awareness on the disease is needed.

Hipertensão intracraniana relacionada a um raro padrão de neoplasia: gliomatose cerebral / Intracranial hypertension related to a rare pattern of neoplasm: gliomatosis cerebri

Gliomatose cerebral (GC) é um raro padrão de crescimento dos gliomas cerebrais, que infiltra difusamente os hemisférios cerebrais e estruturas adjacentes. As características radiológicas e histopatológicas são fundamentais para estabelecer ante mortem o diagnóstico. Em geral, a GC corresponde a uma neoplasia com diferenciação astrocítica e de grau histológico III / alto grau, a qual apresenta um curso clínico variável. No presente relato, os autores apresentam um caso de GC determinando hipertensão intracraniana, descrevem os principais achados histopatológicos e o diagnóstico diferencial desta neoplasia pouco frequente (AU)

Gliomatosis cerebri (GC) is a rare growth pattern of brain gliomas, which diffusely infiltrates the cerebral hemispheres and adjacent structures. Radiological and histopathological characteristics are key to establish ante-mortem diagnosis. In general, GC corresponds to a neoplasm with astrocytic differentiation and histological grade III/high degree, which presents a variable clinical course. In this report, the authors present a case of GC determining intracranial hypertension and describe the main histopathological findings and the differential diagnosis of this uncommon neoplasm (AU)

Dysembryoplastic neuroepithelial tumor originally diagnosed as astrocytoma and oligodendroglioma.

UNLABELLED: Dysembryoplastic neuroepithelial tumor (DNT), described in 1988 and introduced in the WHO classification in 1993, affects predominantly children or young adults causing intractable complex partial seizures. Since it is benign and treated with surgical resection, its recognition is important. It has similarities with low-grade gliomas and gangliogliomas, which may recur and become malignant. OBJECTIVES: To investigate whether DNT was previously diagnosed as astrocytoma, oligodendroglioma, or ganglioglioma and to determine its frequency in a series of low-grade glial/glio-neuronal tumors. METHODS: Clinical, radiological, and histological aspects of 58 tumors operated from 1978 to 2008, classified as astrocytomas (32, including 8 pilocytic), oligodendrogliomas (12), gangliogliomas (7), and DNT (7), were reviewed. RESULTS: Four new DNT, one operated before 1993, previously classified as astrocytoma (3) and oligodendroglioma (1), were identified. One DNT diagnosed in 2002 was classified once more as angiocentric glioma. Therefore, 10 DNT (17.2%) were identified. CONCLUSIONS: Clinical-radiological and histopathological correlations have contributed to diagnose the DNT.

Dysembryoplastic neuroepithelial tumor originally diagnosed as astrocytoma and oligodendroglioma / Tumor neuroepitelial disembrioplásico diagnosticado originalmente como astrocitoma ou oligodendroglioma

Dysembryoplastic neuroepithelial tumor (DNT), described in 1988 and introduced in the WHO classification in 1993, affects predominantly children or young adults causing intractable complex partial seizures. Since it is benign and treated with surgical resection, its recognition is important. It has similarities with low-grade gliomas and gangliogliomas, which may recur and become malignant. OBJECTIVES: To investigate whether DNT was previously diagnosed as astrocytoma, oligodendroglioma, or ganglioglioma and to determine its frequency in a series of low-grade glial/glio-neuronal tumors. METHODS: Clinical, radiological, and histological aspects of 58 tumors operated from 1978 to 2008, classified as astrocytomas (32, including 8 pilocytic), oligodendrogliomas (12), gangliogliomas (7), and DNT (7), were reviewed. RESULTS: Four new DNT, one operated before 1993, previously classified as astrocytoma (3) and oligodendroglioma (1), were identified. One DNT diagnosed in 2002 was classified once more as angiocentric glioma. Therefore, 10 DNT (17.2%) were identified. CONCLUSIONS: Clinical-radiological and histopathological correlations have contributed to diagnose the DNT.

O tumor neuroepitelial disembrioplásico (DNT), descrito em 1988 e incorporado na classificação da OMS em 1993, acomete predominantemente crianças ou adultos jovens, causando crises convulsivas parciais complexas farmacorresistentes. Como é benigno e tratável com ressecção cirúrgica, seu reconhecimento é importante. Tem semelhanças com gliomas de baixo grau e gangliogliomas, que podem recidivar e malignizar. OBJETIVOS: Investigar se o DNT foi originalmente diagnosticado como astrocitoma, oligodendroglioma ou ganglioglioma e determinar sua frequência numa série de neoplasias gliais/glioneuronais de baixo grau. MÉTODOS: Foram revistos aspectos clínicos, radiológicos e histológicos de 58 neoplasias operadas entre 1978 e 2008, classificadas como astrocitomas (32, sendo 8 pilocíticas), oligodendrogliomas (12), gangliogliomas (7) e DNT (7). RESULTADOS: Foram identificados quatro novos DNT, um operado antes de 1993, originalmente diagnosticado como astrocitoma (3) e oligodendroglioma (1). Um DNT diagnosticado em 2002 foi reclassificado como glioma angiocêntrico. Portanto, 10 DNT (17,2%) foram identificados. CONCLUSÕES: Correlações clínico-radiológicas e histopatológicas contribuíram para o diagnóstico do DNT.

[Standardizing a central nervous system tumor DNA biobank]. / Estandarización de un biobanco de ADN de tumores del sistema nervioso central.

BACKGROUND: Brain tumors are one of the leading cancers worldwide; in the National Institute of Neurology and Neurosurgery (INNN) these tumors are the leading cause of morbitity and mortality. OBJECTIVE: Standardize biopsies, colletion, processing and storage biologic material of molecular studies. METHODS: with a previously signed surgical consent, a tumor and blood biopsy was done to 134 patients. Their DNA was extracted and a database was filled considering technical, ethical and legal aspects. In order to have optimal biologic material the procedure was standardized between the surgical and research laboratory teams. RESULTS: The biopsy, transportation, processing and storage were standardized. 134 patients were included (67 male and 67 female) with an average age of 46.28 years (range 15-81). The most frequently biopsied tumor was the meningioma (42%). The integrity of the obtained material was determined by agarose gel electrophoretic analysis. CONCLUSION: the INNN biobank has a standardized system that biopsies, processes and stores optimum quality biologic material that will be the basis of future molecular studies.

Factores clínico patológicos relacionados con el tratamiento de tumores neuroepiteliales, estudio descriptivo de pacientes del Hospital IESS Cuenca / The clinical pathological factors related to treatment, from neuroepithelial tumors, descriptive study to patients in IESS Hospital city Cuenca

OBJETIVO: explorar los factores clínico–patológicos asociados con el procedimiento de resección quirúrgica de neoplasia neuroepitelial, en pacientes del hospital del IESS Cuenca. MATERIALES Y MÉTODOS: es un estudio descriptivo con referente muestral propositivo no probabilístico, en el que se incluyeron 37 casos consecutivos con tratamiento neuroquirúrgico en adultos con edades entre 20 y 69 años, sobre ésta base se estudiaron los factores:, tiempo con sintomatología hasta el diagnostico, aparición de déficit, presencia de edema cerebral, tipo anatomo–patológico, topografía y elocuencia, finalidad de la intervención y los resultados del procedimiento. RESULTADOS: El tamaño medio del tumor fue de 4,22cm, la proporción entre procedimientos fue amplio 59,5 , limitado 40,5. Hasta el 70,3 de los pacientes intervenidos se caracterizó por lesiones con afectación de aéreas elocuentes. En el 56, 8 se determino la presencia de edema cerebral, se distinguió que el 37,8 sufrieron lesiones que desplazan el parénquima, ésta condición se relacionó con procedimientos de exéresis parcial.

A comparative study of ectonucleotidase and P2 receptor mRNA profiles in C6 cell line cultures and C6 ex vivo glioma model.

Glioblastoma multiforme is the most common type of primary brain tumour and has the worst clinical outcome. Nucleotides represent an important class of extracellular molecules involved in cell proliferation, differentiation and apoptosis. Alterations in purinergic signalling have been implicated in pathological processes, such as cancer, and glioma cell lines are widely employed as a model to study the biology of brain tumours. Increasing evidence, however, suggests that glioma cell lines may not present all the phenotypic and genetic characteristics of the primary tumours. We have compared the biological characteristics of C6 rat glioma cells in culture and the same cells after their implantation in the rat brain and growth in culture (denominated as the C6 ex vivo culture model). Parameters evaluated included cell morphology, differentiation, angiogenic markers, purinergic receptors and ecto-nucleotidase mRNA profile/enzymatic activity. Analysis of the C6 glioma cell line and C6 ex vivo glioma cultures revealed distinct cell morphologies, although cell differentiation and angiogenic marker expressions were similar. Both glioma models co-expressed multiple P2X and P2Y receptor subtypes with some differences. In addition, the C6 glioma cell line and C6 ex vivo glioma cultures exhibited similar extracellular ATP metabolism and cell proliferation behaviour when exposed to cytotoxic ATP concentrations. Thus, the disruption of purinergic signalling is a feature shown not only by glioma cell lineages, but also by primary glioma cultures. Our results therefore suggest the participation of the purinergic system in glioma malignancy.

Differential expression of E-cadherin gene in human neuroepithelial tumors.

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.

Differential expression of E-cadherin gene in human neuroepithelial tumors

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.

Glioneuroma asociado a anoftalmía / Glioneuroma associated to anophthalmia

Se presenta un caso de glioneuroma de órbita izquierda asociado a anoftalmía bilateral y quiste meníngeo, en un recién nacido con múltiples anomalías congénitas y con historia familiar de retraso mental y disontogenias. El glioneuroma es una neoplasia benigna constituida por células gliales, neuronas y un neurópilo de fondo. Se demostró el componente astroglial y clasmatodendrítico por medio de técnicas histoinmunoquímicas

Tumor disembrioplástico neuroepitelial: experiencia en 18 casos / Dysembryoplastic neuroepithelial tumor: experience in 18 cases

El tumor disembrioplástico neuroepitelial es una lesión muy infrecuente del sistema nervioso central, la cual fue descrita por primera vez en 1988 por Daumas-Duport e incluida en la última clasificación de tumores cerebrales de la Organización Mundial de la Salud. Nosotros comunicamos 18 casos consecutivos de DNT, en los que analizamos sus características clínicas y discutimos su diagnóstico diferencial con otras lesiones histológicamente similares asociados a epilepsia fármaco-resistente crónica. La edad media al momento de la operación y al inicio de la epilepsia fueron 27,9 años y 16,9 años respectivamente. Todos los pacientes presentaron epilepsia parcial compleja y sólo un paciente tuvo un leve déficit motor. La localización fue siempre supratentorial, 16 casos temporales y 2 frontales. La resonancia magnética (RM) mostró de regla una lesión quística, usualmente poliquística. Cinco pacientes tuvieron una cirugía previa en otra institución, 3 reacciones subtotales y 2 biopsias. Ningún paciente tuvo el diagnóstico de DNT previo a la segunda cirugía. Las operaciones fueron resecciones del DNT incluyendo el tejido epileptógeno. Un paciente con un DNT frontal localizado en ganglios basales tuvo la resección sub-total. El período de seguimiento varió entre 0.5 y 7 años (media 3,7 años). En nuestro grupo de 14 pacientes, 10 están libres de crisis y 3 presentan una reducción mayor a un 75 por ciento de sus crisis. Ningún paciente ha mostrado evidencia de recurrencia en el seguimiento con RM. La larga historia de epilepsia en nuestra serie indica que el DNT es una lesión que ha permanecido largo tiempo en el encéfalo, con lento o nulo crecimiento. El resultado post-operatorio sugiere que el DNT tiene un execlente pronóstico. Sin embargo, es aún necesario un mayor período de seguimiento, para establecer su real pronóstico en la era de la RM