Purines and purinergic receptors in primary tumors of the central nervous system.

Purine nucleotides and nucleosides play critical roles in various pathological conditions, including tumor cell growth. Adenosine triphosphate (ATP) activates pro-tumor receptors, while adenosine (ADO) is a potent immunosuppressant and modulator of cell growth. This study aims to analyze the purinergic actions of ATP and its metabolites, associated enzymes, and P1 or P2 class receptors in primary central nervous system tumors. Additionally, we sought to correlate the levels of nucleosides and the density of P1, P2X, and P2Y receptors in cells with tumor progression. The results indicate that purinergic signaling depends on the receptor concentration and signaling molecules specific to each cell type, tissue, and tumor histology. The purinergic system may function as either a tumor-promoting agent or an antitumor factor, depending on the microenvironmental conditions and the concentrations of receptors and their respective activators. Notably, ATP emerges as the most significant extracellular signal, capable of being converted into other cellular stimulators pertinent to neoplasms, such as adenosine diphosphate, adenosine monophosphate, adenosine, and inosine. Consequently, a cascade of responses to these stimuli promotes tumor development, cell division, and metastasis. Purine nucleotides in central nervous system tumors are pivotal in cellular responses in glioblastoma multiforme, vestibular schwannoma, medulloblastoma, adenomas, gliomas, meningiomas, and pineal tumors. These findings hold the potential for developing novel therapeutic strategies and aiding in therapeutic management.

Tumores del sistema nervioso central. Clasificación de la Organización Mundial de la Salud 2021. Hacia un cambio de paradigma / Tumors of the central nervous system. Classification of the World Health Organization 2021. Towards a paradigm shift

El estudio de los tumores del sistema nervioso central (SNC) resulta ser un tema de gran consideración y su conocimiento reviste una alta importancia en la práctica médica. Las clasificaciones de las neoplasias del SNC comenzaron a mediados del siglo XIX hasta que en 1979 la Organización Mundial de la Salud (OMS) publicó la primera edición de una sistemática útil con el objetivo de establecer un lenguaje común para todas las especialidades médicas. Al día de hoy, 5 ediciones actualizaron la taxonomía neoplásica. La quinta edición del año 2021 consolida el cambio de paradigma dado por los avances moleculares, si bien todavía la transición se encuentra en proceso entre la caracterización morfológica y la biológica molecular. En este artículo, se analizan las nuevas modificaciones incorporadas en las diferentes familias tumorales más frecuentes en pediatría haciendo hincapié en aquella información de utilidad para el médico pediatra en su práctica diaria y la consulta multidisciplinaria.

The study of central nervous system (CNS) tumors is a subject of great interest and such knowledge is of great importance in medical practice. The classifications of CNS neoplasms began in the mid-19 th century, until the World Health Organization (WHO) published, in 1979, the first edition of a useful systematic review for the purpose of establishing a common language for all medical specialties. To date, 5 updated editions of neoplastic taxonomy have been published.The fifth edition, from 2021, consolidates the paradigm shift brought about by molecular advances, although the transition between morphological and molecular biological characterization is still in progress. In this article, the new modifications introduced in the different most frequent families of tumors in pediatrics are analyzed, emphasizing useful information for pediatricians in their daily practice and multidisciplinary consultations.

Tumors of the central nervous system. Classification of the World Health Organization 2021. Towards a paradigm shift. / Tumores del sistema nervioso central. Clasificación de la Organización Mundial de la Salud 2021. Hacia un cambio de paradigma.

The study of central nervous system (CNS) tumors is a subject of great interest and such knowledge is of great importance in medical practice. The classifications of CNS neoplasms began in the mid-19th century, until the World Health Organization (WHO) published, in 1979, the first edition of a useful systematic review for the purpose of establishing a common language for all medical specialties. To date, 5 updated editions of neoplastic taxonomy have been published. The fifth edition, from 2021, consolidates the paradigm shift brought about by molecular advances, although the transition between morphological and molecular biological characterization is still in progress. In this article, the new modifications introduced in the different most frequent families of tumors in pediatrics are analyzed, emphasizing useful information for pediatricians in their daily practice and multidisciplinary consultations.

El estudio de los tumores del sistema nervioso central (SNC) resulta ser un tema de gran consideración y su conocimiento reviste una alta importancia en la práctica médica. Las clasificaciones de las neoplasias del SNC comenzaron a mediados del siglo XIX hasta que en 1979 la Organización Mundial de la Salud (OMS) publicó la primera edición de una sistemática útil con el objetivo de establecer un lenguaje común para todas las especialidades médicas. Al día de hoy, 5 ediciones actualizaron la taxonomía neoplásica. La quinta edición del año 2021 consolida el cambio de paradigma dado por los avances moleculares, si bien todavía la transición se encuentra en proceso entre la caracterización morfológica y la biológica molecular. En este artículo, se analizan las nuevas modificaciones incorporadas en las diferentes familias tumorales más frecuentes en pediatría haciendo hincapié en aquella información de utilidad para el médico pediatra en su práctica diaria y la consulta multidisciplinaria.

Tumor fibroso solitario cerebral: A propósito de un caso / Solitary fibrous tumor of the brain: A case report

RESUMEN Introducción: Los tumores fibrosos solitarios (TFS) son neoplasias raras de origen mesenquimal que, aunque generalmente se desarrollan en la pleura visceral, ocasionalmente se presentan en la cavidad intracraneal. Además, se caracterizan por altas tasas de metástasis y recurrencia. Caso clínico: Se presenta el caso de un paciente masculino de 59 años con cuadro de 3 meses de cefalea y bradipsiquia. La tomografía reveló una tumoración neoformativa que infiltra cavidad nasal, celdillas etmoidales, y fosa craneal anterior, comprometiendo lóbulo frontal izquierdo. El paciente fue sometido a dos craniectomías exploratorias donde se realizaron los diagnósticos sugestivos de neoplasia glial de alto grado y TFS. Para la precisión diagnóstica se realizó inmunohistoquímica que fue compatible con tumor fibroso solitario. Se analiza el caso centrándose particularmente en los aspectos histopatológicos, localización inusual de este tumor y sus manifestaciones clínicas variables.

ABSTRACT Introduction: Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that, although typically develop in the visceral pleura, occasionally occur in the intracranial cavity. Furthermore, they are characterized by high rates of metastasis and recurrence. Case Report: We present the case of a 59-year-old male patient with a 3-month history of headache and bradyphrenia. Computed tomography revealed a neoformative tumor infiltrating the nasal cavity, ethmoid sinuses, and anterior cranial fossa, involving the left frontal lobe. The patient underwent two exploratory craniectomies, during which diagnoses suggestive of high-grade glial neoplasia and SFT were made. For precise diagnosis, immunohistochemistry was performed, which was consistent with solitary fibrous tumor. The case is analyzed, focusing particularly on histopathological aspects, the unusual location of this tumor, and its variable clinical manifestations.

Exposição a agrotóxicos e o risco de tumores do Sistema Nervoso Central em crianças: revisão sistemática com metanálise / Pesticide exposure and risk of Central Nervous System tumors in children: a systematic review with meta-analysis

Resumo Os tumores do Sistema Nervoso Central (SNC) representam mais da metade das neoplasias infantis malignas que acometem crianças. Objetivou-se analisar o risco de exposição a agrotóxicos relacionado com o desenvolvimento de tumores do SNC em crianças. Realizou-se uma revisão sistemática da literatura nas bases de dados PubMed/MEDILINE, Embase, Web of Science, Scopus e CINAHL. Foram incluídos estudos de coorte e caso-controle sobre o desenvolvimento de tumores do SNC (todos os tipos histológicos do grupo III Classificação de Câncer Infantil) decorrentes da exposição a agrotóxicos em crianças de 0-14 anos. Na metanálise utilizou-se o modelo de efeito aleatório e o método estatístico de Mantel-Haenszel. A Razão de Chances (RC) ou Odds Ratio (OR) foi a medida de associação aplicada. A revisão foi registrada no International Prospective Register of Systematic Reviews (PROSPERO) sob o número CRD42021209354. A busca identificou 1.158 estudos, dos quais 14 compuseram a revisão. Verificou-se evidência de associação entre o desenvolvimento de astrocitomas e a exposição a todas as classes de pesticidas (OR 1,50; IC95% 1,15-1,96; p=0,03). A síntese dos resultados apontou para uma relação da exposição aos agrotóxicos com o desfecho de alguns tipos histológicos de tumores do SNC na infância.

Abstract Central Nervous System (CNS) tumors represent more than half of all childhood malignant neoplasms. The aim of this study was to determine the relationship between environmental exposure to pesticides and the development of CNS tumors in children. We conducted a systematic review of the literature in the PubMed/MEDILINE, Embase, Web of Science, Scopus, and CINAHL databases. The inclusion criteria were cohort and case-control studies investigating the association between exposure to pesticides and CNS tumors (all histological types included in group III of the WHO Classification of Childhood Cancer) in children aged 0-14 years. The meta-analysis was performed using a random effects model and the Mantel-Haenszel method. Strength of association was measured using odds ratios (OR). The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under identification number CRD42021209354. The search identified 1,158 studies, 14 of which were included in the review. There was evidence of an association between the development of astrocytomas and exposure to all classes of pesticides (OR 1.50; 95%CI 1.15-1.96; p=0.03). The synthesis of the evidence pointed to a relationship between exposure to pesticides and some histological types of CNS tumors in childhood.

The 2021 World Health Organization classification of gliomas: an imaging approach.

The purpose of this pictorial essay is to describe the recommendations of the 2021 World Health Organization classification for adult-type and pediatric-type gliomas and to discuss the main modifications in relation to the previous (2016) classification, exemplified by imaging, histological, and molecular findings in nine patients followed at our institutions. In recent years, molecular biomarkers have gained importance in the diagnosis and classification of gliomas, mainly because they have been shown to correlate with the biological behavior and prognosis of such tumors. It is important for neuroradiologists to familiarize themselves with this new classification of central nervous system tumors, so that they can use this knowledge in evaluating and reporting the imaging examinations of patients with glioma.

O propósito deste ensaio iconográfico é descrever e discutir as novas recomendações da Organização Mundial da Saúde de 2021, referente aos gliomas dos tipos adulto e infantil, e suas principais diferenças com a classificação anterior (2016), exemplificadas com imagens de nove casos de pacientes atendidos nas nossas instituições. Recentemente, há uma crescente significância dos marcadores moleculares no diagnóstico e classificação dos gliomas e tumores do sistema nervoso central, principalmente pela correlação com o comportamento biológico e o prognóstico. É importante que os neurorradiologistas estejam familiarizados com a nova classificação dos tumores do sistema nervoso central para a prática clínica, na avaliação e emissão de laudos e opiniões nas imagens dos pacientes com gliomas.

The 2021 World Health Organization classification of gliomas: an imaging approach / Nova classificação das neoplasias gliais segundo a Organização Mundial da Saúde 2021, com enfoque radiológico

Abstract The purpose of this pictorial essay is to describe the recommendations of the 2021 World Health Organization classification for adult-type and pediatric-type gliomas and to discuss the main modifications in relation to the previous (2016) classification, exemplified by imaging, histological, and molecular findings in nine patients followed at our institutions. In recent years, molecular biomarkers have gained importance in the diagnosis and classification of gliomas, mainly because they have been shown to correlate with the biological behavior and prognosis of such tumors. It is important for neuroradiologists to familiarize themselves with this new classification of central nervous system tumors, so that they can use this knowledge in evaluating and reporting the imaging examinations of patients with glioma.

Resumo O propósito deste ensaio iconográfico é descrever e discutir as novas recomendações da Organização Mundial da Saúde de 2021, referente aos gliomas dos tipos adulto e infantil, e suas principais diferenças com a classificação anterior (2016), exemplificadas com imagens de nove casos de pacientes atendidos nas nossas instituições. Recentemente, há uma crescente significância dos marcadores moleculares no diagnóstico e classificação dos gliomas e tumores do sistema nervoso central, principalmente pela correlação com o comportamento biológico e o prognóstico. É importante que os neurorradiologistas estejam familiarizados com a nova classificação dos tumores do sistema nervoso central para a prática clínica, na avaliação e emissão de laudos e opiniões nas imagens dos pacientes com gliomas.

Mutaciones en los genes PDGFRA, KIT y KDR en pacientes con glioblastoma se relacionan con un peor desenlace / Mutations in the PDGFRA, KIT, and KDR genes in patients with glioblastoma are associated with a worse outcome

Resumen Introducción: existen varios Receptores Tirosina Quinasa que están involucrados en el desarrollo, crecimiento y progresión de las células tumorales, por ejemplo, en los glioblastomas se ha encontrado que por un posible desequilibrio de ligamiento los genes PDGFRA, KIT y KDR, ubicados en el brazo largo del cromosoma 4 (4q11-q12), podrían estar relacionados con la progresión de esta neoplasia. Objetivo: reportar dos casos clínicos de pacientes con diagnóstico de glioblastoma y mutaciones en los genes PDGFRA, KIT, KDR, y su relación con un peor desenlace. Casos clínicos: en este artículo se presenta el caso de dos pacientes con glioblastomas que presentan mutaciones en los genes anteriormente mencionados resultado de la secuenciación de un panel genético que evalúa 324 genes y 37 fusiones génicas y la progresión clínica acelerada durante el transcurso de la enfermedad. Conclusión: los cambios producidos en los glioblastomas por las mutaciones en los receptores tirosina quinasa a nivel biológico podrían describir una mayor capacidad proliferativa del tumor, lo que en el ámbito clínico se ha evidenciado como un peor pronóstico para el paciente, de ahí nace la necesidad de tener paneles genéticos que ayuden a identificar el perfil tumoral, e incentivar más estudios clínicos relacionados a fármacos que tengan como objetivo dichos receptores.

Abstract Introduction: there are several Tyrosine Kinase Receptors that are involved in the development, growth and progression of tumor cells, for example, in glioblastomas it has been found that due to a possible linkage imbalance the PDGFRA, KIT and KDR genes, located in the arm length of chromosome 4 (4q11-q12), which could be related to the progression of this neoplasm. Objective: to report two clinical cases of patients diagnosed with glioblastoma and mutations in the PDGFRA, KIT, and KDR genes, and their relationship with a worse outcome. Clinical cases: this article presents the case of two patients with mutations in the genes, the result of a genetic panel that evaluated 324 genes and 37 gene fusions and accelerated clinical progression during the course of the disease. Conclusion: the changes produced in glioblastomas by mutations in receptor tyrosine kinases at the biological level describe a greater proliferative capacity of the tumor, which in the clinical setting has been evidenced as a worse prognosis for the patient, hence the need for have genetic panels that help identify the tumor profile and encourage more clinical studies related to drugs that target those receptors.

Primary central nervous system tumors survival in children in ten Colombian cities: a VIGICANCER report.

Purpose: Primary central nervous system (CNS) tumors are the second most common cancer in children and adolescents, leading to premature death and disability. Population-based survival estimates aid decision-making in cancer control, however data on survival for primary CNS tumors in Latin America is lacking. We describe survival rates for children with primary CNS tumors treated in ten Colombian cities. Methods: We analyzed data from children and adolescents newly diagnosed with cancer between 2012 and 2021, participating in the Childhood Cancer Clinical Outcomes Surveillance System (VIGICANCER) in ten cities in Colombia. VIGICANCER collects information on clinical outcomes from twenty-seven pediatric oncology units and conducts active follow-up every three months. VIGICANCER does not register craniopharyngiomas; we excluded intracranial germ cell tumors for this report. We used the Kaplan-Meier method to estimate the overall survival probability, stratified by sociodemographic variables, topography, WHO grading, receipt of radiation therapy, and type of surgical resection. We analyzed the prognostic capacity of variables using multivariate proportional Cox's regression, stratified by city and year of diagnosis. Results: During the study period, VIGICANCER included 989 primary CNS tumors in 879 children and 110 adolescents. The cohort median age was 9 years; 53% of patients were males, and 8% were Afro-descendants. Most common tumors were supratentorial astrocytomas (47%), astrocytic tumors (35%), medulloblastomas (20%), ependymomas (11%), and mixed and unspecified gliomas (10%). Five-year overall survival of the entire cohort was 54% (95% CI, 51-58); for supratentorial gliomas, WHO grade I was 77%, II was 62%, III-IV was 27%, respectively, and for medulloblastoma was 61%. The adjusted hazard rate ratio for patients with WHO grade III and IV, for those with subtotal resection, for brainstem location, and for those not receiving radiation therapy was 7.4 (95% CI, 4.7-11.8), 6.4 (95% CI, 4.2-9.8), 2.8 (95% 2.1-3.8), 2.0 (95% CI, 1.3-2.8) and 2.3 (95% CI, 1.7-3.0), respectively. Conclusion: We found that half of Colombia's children and adolescents with primary CNS tumors survive five years, compared to 70% to 80% in high-income countries. In addition to tumor biology and location, gross total resection was crucial for improved survival in this cohort. Systematic monitoring of survival and its determinants provides empirical data for guiding cancer control policies.

[Targeted therapies with BRAF inhibitors for pediatric low- and high-grade gliomas with BRAFv600e mutation. Prof. Dr. Juan P. Garrahan Hospital experience]. / Terapias dirigidas con inhibidores del BRAF en gliomas pediátricos de alto y bajo grado con la mutación BRAFV600E. Experiencia del Hospital Prof. Dr. Juan P. Garrahan.

The BRAFV600E point mutation plays a key role in the tumorigenesis of many gliomas. Inhibiting its product is part of the innovative therapies emerging in recent years. Knowing the role of these treatments is essential. The aim of this experience was to describe the clinical-radiological response of pediatric BRAFV600E mutated gliomas treated with BRAF inhibitors. To this end, a descriptive and retrospective study was performed in patients under 16 years of age with BRAFV600E gliomas, who received vemurafenib or dabrafenib at Hospital Garrahan. Thirteen patients treated in the last 7 years were included: 9 were low-grade and 4 high-grade gliomas. The median age at diagnosis was 8.6 years (0.89-14.04) and at start of targeted therapy was 11.62 years (3.64-15.42). All patients had previously a surgical procedure, and 12/13 had received another therapy prior BRAF inhibition: 11 chemotherapy (in one case, up to 4 different protocols) and 4 radiotherapy. Under targeted therapy, tumour response was obtained in 10 patients (size reduction equal to or greater than 25%), and best response was observed in the first 6 months of treatment in 7 children. Four patients progressed under treatment (all high-grade gliomas) and 2 progressed shortly after stopping the inhibitor (both low-grade gliomas). Five patients had grade 3-4 toxicity, with subsequent full recovery. A good and sustained clinical-radiological response, with acceptable tolerance, is described in patients with BRAFV600E mutated low-grade gliomas treated with BRAFV600E inhibitors. In contrast, the response in patients with high-grade gliomas was intermediate and of short duration, with early tumour progression.

La mutación puntual V600E del gen BRAF juega un papel fundamental en la tumorigénesis de muchos gliomas. La inhibición de su producto forma parte de terapias innovadoras emergentes en los últimos años. Conocer el rol de estos tratamientos resulta imprescindible. El objetivo del trabajo fue describir la respuesta clínico-radiológica en niños con gliomas BRAFV600E mutado tratados con inhibidores BRAF. Para ello se realizó un estudio descriptivo y retrospectivo en pacientes menores de 16 años con gliomas BRAFV600E mutado que recibieron vemurafenib o dabrafenib en el Hospital Garrahan. Trece pacientes tratados en los últimos 7 años fueron incluidos: 9 gliomas de bajo grado y 4 de alto grado. La mediana de edad al diagnóstico fue 8.6 años (0.89-14.04) y del comienzo del inhibidor 11.62 años (3.64-15.42). Inicialmente, todos habían realizado tratamiento quirúrgico, y 12/13 recibieron previamente otra terapia: 11 quimioterapia (eventualmente hasta 4 líneas distintas) y 4 radioterapia. Con la terapia dirigida, 10 pacientes tuvieron una disminución tumoral mayor o igual al 25%, quedando evidenciada en 7 niños la mejor respuesta dentro de los 6 meses del inicio. Hubo 4 progresados intratratamiento (todos alto grado), y 2 progresados prontamente luego de suspender el inhibidor (ambos bajo grado). Cinco presentaron efectos adversos grado 3-4, con recuperación ad-integrum. Se describe una buena y sostenida respuesta clínico-radiológica, con tolerancia aceptable, en pacientes con gliomas de bajo grado BRAFV600E mutado tratados con inhibidores BRAFV600E. En contraste, la respuesta en pacientes con gliomas de alto grado fue intermedia y de poca duración, con progresión tumoral precoz.

Terapias dirigidas con inhibidores del braf en gliomas pediátricos de alto y bajo grado con la mutación brafv600e. Experiencia del hospital Prof. Dr. Juan P. Garrahan / Targeted therapies with BRAF inhibitors for pediatric low- and high-grade gliomas with BRAF v600e mutation. Prof. Dr. Juan P. Garrahan Hospital experience

Resumen La mutación puntual V600E del gen BRAF juega un papel fundamental en la tumorigénesis de muchos gliomas. La inhibición de su producto forma parte de terapias innovadoras emergentes en los últimos años. Conocer el rol de estos tratamientos resulta imprescindible. El objetivo del trabajo fue describir la respuesta clínico-radiológica en niños con gliomas BRAF V600E mutado tratados con inhibidores BRAF. Para ello se realizó un estudio descriptivo y retrospectivo en pacientes menores de 16 años con gliomas BRAF V600E mu tado que recibieron vemurafenib o dabrafenib en el Hospital Garrahan. Trece pacientes tratados en los últimos 7 años fueron incluidos: 9 gliomas de bajo grado y 4 de alto grado. La mediana de edad al diagnóstico fue 8.6 años (0.89-14.04) y del comienzo del inhibidor 11.62 años (3.64-15.42). Inicialmente, todos habían realizado tratamiento quirúrgico, y 12/13 recibieron previamente otra terapia: 11 quimioterapia (eventualmente hasta 4 líneas distintas) y 4 radioterapia. Con la terapia dirigida, 10 pacientes tuvieron una disminución tumoral mayor o igual al 25%, quedando evidenciada en 7 niños la mejor respuesta dentro de los 6 meses del inicio. Hubo 4 progresados intratratamiento (todos alto grado), y 2 progresados prontamente luego de suspender el inhibidor (ambos bajo grado). Cinco presentaron efectos adversos grado 3-4, con recuperación ad-integrum. Se describe una buena y sostenida respuesta clínico-radiológica, con tolerancia aceptable, en pacientes con gliomas de bajo grado BRAF V600E mutado tratados con inhibidores BRAF V600E . En contraste, la respuesta en pacientes con gliomas de alto grado fue intermedia y de poca duración, con progresión tumoral precoz.

Abstract The BRAF V600E point mutation plays a key role in the tumorigenesis of many gliomas. Inhibiting its product is part of the innovative therapies emerging in recent years. Knowing the role of these treatments is essential. The aim of this experience was to describe the clinical-radiological response of pediatric BRAF V600E mutated gliomas treated with BRAF inhibitors. To this end, a descriptive and retrospective study was performed in patients under 16 years of age with BRAF V600E gliomas, who received vemurafenib or dabrafenib at Hospital Garrahan. Thirteen patients treated in the last 7 years were included: 9 were low-grade and 4 high-grade gliomas. The median age at diagnosis was 8.6 years (0.89-14.04) and at start of targeted therapy was 11.62 years (3.64-15.42). All patients had previously a surgical procedure, and 12/13 had received another therapy prior BRAF inhibition: 11 chemotherapy (in one case, up to 4 different protocols) and 4 radiotherapy. Under targeted therapy, tumour response was obtained in 10 patients (size reduction equal to or greater than 25%), and best response was observed in the first 6 months of treatment in 7 children. Four patients progressed under treatment (all high-grade gliomas) and 2 progressed shortly after stopping the inhibitor (both low-grade gliomas). Five patients had grade 3-4 toxicity, with subsequent full recovery. A good and sustained clinical-radiological response, with acceptable tolerance, is described in patients with BRAF V600E mutated low-grade gliomas treated with BRAF V600E inhibitors. In contrast, the response in patients with high-grade gliomas was intermediate and of short duration, with early tumour progression.

New genetic prognostic biomarkers in primary central nervous system lymphoma (PCNSL).

BACKGROUND: PCNSL is a rare extranodal NHL with poor prognosis. Tumorigenesis has been associated with hyperactivation of BCR downstream and NFkB pathways. We studied the prognosis of the relative expression profile of target genes of NFkB pathway (MYC, BCL2), the essential transcriptional regulator in hematopoiesis LMO2, the checkpoint regulation pathway MGMT, the transcription factor POU2F1, the immune checkpoint gene PDCD1, and the proto-oncogene and transcriptional repressor gene BCL6 and its proteins in PCNSL. METHODS: This study is a retrospective cohort study; 35 immunocompetent PCNSL-DLBCL patients had their gene expression (RT-qPCR) normalized to internal control gene GUSB. RESULTS: Median patient age was 62 years, median OS was 42.6 months (95% CI: 26.6-58.6), PFS was 41 months (95% CI: 19.7-62.4), and DFS was 59.2 months (95% CI 31.9-86.6). A moderate correlation was found between the gene/protein expressions of MYC (kappa = 0.596, p = .022) and of BCL2 (kappa = 0.426, p = .042). Relative gene expression of MYC ≥ 0.201 (HR 6.117; p = .003) was associated with worse 5-year OS. Relative gene expression of MYC ≥ 0.201 (HR 3.96; p = .016) and MGMT ≥ 0.335 (HR 3.749; p = .056) was associated with worse PFS. Age > 60 years and IELSG score moderate/high were also associated with worse prognosis. CONCLUSIONS: Overexpression of MYC and overexpression of MGMT were prognostic markers associated with unfavorable clinical outcomes in PCNSL.

Clinical, demographic, anatomopathological, and molecular findings in patients with medulloblastoma treated in a single health facility / Achados clínicos, demográficos, anatomopatológicos e moleculares de portadores de meduloblastoma tratados em uma única instituição

ABSTRACT Objective: To describe the clinical, demographic, anatomopathological, molecular, and survival characteristics of patients with medulloblastoma. Methods: Retrospective study based on patient information obtained from the review of medical records. Overall and event-free survival were analyzed using the Kaplan-Meier estimator, and the curves were compared by the log-rank test. Results: Among the patients investigated, 70 were male (66%), and age at diagnosis ranged from 2 months to 22 years. The most frequent signs and symptoms were headache (80.8%) and vomiting (75.8%). Regarding treatment, most patients (63.2%) underwent complete surgical resection, with a predominance of classic histology (63.2%). The 5-year overall survival rate was 67.9%, and the 10-year rate was 64.2%. Patients with molecular profile characteristic of the wingless (WNT) subgroup had a better prognosis, with 5-year overall survival of 75%. Conclusions: The clinical, demographic, anatomopathological, and molecular characteristics of patients with medulloblastoma described in the present study were mostly similar to those reported in the literature. Patients submitted to complete tumor resection had better clinical outcomes than those who underwent incomplete resection/biopsy. Patients classified as high-risk showed worse overall and event-free survival than those in the standard-risk group, and the presence of metastasis at diagnosis was associated with recurrence.

RESUMO Objetivo: Descrever as características clínicas, demográficas, anatomopatológicas, moleculares e de sobrevida de pacientes portadores de meduloblastoma. Métodos: Estudo retrospectivo, no qual as informações dos pacientes foram obtidas pela revisão dos prontuários médicos. Análises de sobrevida global e de sobrevida livre de eventos foram realizadas por meio da construção de curvas de Kaplan-Meier e a comparação entre as curvas foi feita pelo teste log-rank. Resultados: Entre os pacientes analisados, 70 pertenciam ao sexo masculino (66%) e a idade ao diagnóstico variou de dois meses a 22 anos. Os sinais e sintomas de maior frequência foram cefaleia (80,8%) e vômitos (75,8%). Em relação ao tratamento, a maioria (63,2%) dos pacientes foi submetida à ressecção cirúrgica total e apresentava como histologia predominante a forma clássica (63,2%). A taxa de sobrevida global em cinco anos foi de 67,9% e, em 10 anos, de 64,2%. Os pacientes com perfil molecular característico do subgrupo wingless (WNT) apresentaram melhor prognóstico, com sobrevida global em cinco anos de 75%. Conclusões: As características clínicas, demográficas, anatomopatológicas e moleculares dos pacientes com meduloblastoma descritas no presente estudo foram majoritariamente semelhantes às descritas na literatura. Pacientes submetidos à ressecção completa do tumor tiveram melhor evolução clínica do que aqueles com ressecção incompleta/biópsia. Pacientes estratificados como de alto risco apresentaram pior sobrevida global e livre de eventos do que o grupo standard e a presença de metástases ao diagnóstico se mostrou associada à ocorrência de recidiva da doença.

Epidemiología descriptiva y cambios en la frecuencia de tumores astrocíticos en el Instituto Nacional de Neurología y Neurocirugía de México / Descriptive epidemiology and frequency variations of astrocytic tumors in the National Institute of Neurology and Neurosurgery of Mexico

Resumen: Objetivo: Determinar distribución, localización y cambios de la frecuencia de tumores astrocíticos (TA) en un instituto mexicano de neurología. Material y métodos: Se revisaron los registros institucionales de TA de cinco décadas. Se compararon las relaciones TA/egresos quirúrgicos (EQ) y TA/total de tumores del sistema nervioso central (TSNC) de 1995 a 2014. Resultados: Se analizaron 2 287 TA (1 356 en hombres y 931 en mujeres). El glioma más común fue el glioblastoma multiforme (GBM), que estuvo presente en adultos jóvenes con una frecuencia mayor a la reportada en otros estudios. La relación TA/EQ y TA/TNSC fue similar entre 1995 y 2014. Conclusiones: En general, la frecuencia de TA atendidos en el Instituto es similar a la reportada internacionalmente. No obstante, los casos de TA en el subgrupo de adultos jóvenes con GBM son más frecuentes (40%) que las incidencias reportadas en otros estudios (menores al 5%). No se encontró variación significativa en la frecuencia de TA durante las últimas dos décadas.

Abstract: Objective: To determine distribution, localization and frequency variations of astrocytic tumors (AT) in a Mexican Institute of neurology. Materials and methods: Institutional registries of AT from five decades were analyzed. AT/Surgical discharges (SD) and AT/Central Nervous System Tumors (CNST) from 1995 to 2014 were compared. Results: Two thousand two hundred and eighty-seven AT (1 356 men and 931 women) were analyzed. The most common glioma was glioblastoma multiforme (GBM), found in young adults with a higher frequency to that reported in other studies. Relation of AT/SD, as well as, relation of AT/CNST was similar between 1995 and 2014. Conclusions: In general, the frequency of AT attended at the Institute is similar to that found worldwide, being only higher the number of GBM in younger adults. There was not significant variation in the frequency of AT during the time studied.

Neurocytoma mimicking macroadenoma.

BACKGROUND: Intraventricular and extraventricular central neurocytomas (CN) are equally frequent among 20-40-year-old men and women. However, sellar and suprasellar extraventricular CN are extremely rare, with only 12 reported cases. CASE DESCRIPTION: The authors report the case of a Brazilian 27-year-old man who presented with progressive vision loss during the last 4 years and serious bilateral keratoconus. We also review the epidemiological, clinical, radiological, pathological, and treatment features of the 12 reported cases. The patient developed left amaurosis and right temporal hemianopsia after undergoing bilateral corneal transplantation, which was detected during campimetry testing, and subsequently underwent magnetic resonance imaging, which revealed a huge hypophyseal tumor. Endocrinological evaluation revealed complete loss of pituitary function. The patient was referred to our department and underwent a two-step surgery (using transsphenoidal approach and cranio-orbital zygomatic approach) based on the diagnosis of an extraventricular central nervous system neurocytoma. Tumor removal was successful, and the patient was discharged at 3 weeks after admission to our department. CONCLUSION: Although extraventricular neurocytomas of the brain are rare, careful preoperative consideration of its anatomy, pathophysiological features, and radiological features can enhance the treatment outcomes.

Challenges and opportunities in primary CNS lymphoma: A systematic review.

BACKGROUND: Historically, high-dose methotrexate (HD-MTX) plus consolidation chemotherapy and/or whole brain radiotherapy (WBRT) has been the gold standard on Primary Central Nervous System Lymphoma (PCNSL) management. We sought to examine and summarize the data, on clinical trial (CT) setting, investigating multi-modality treatment to PCNSL. METHODS: We performed a systematic review of electronic databases (Medline, EMBASE, Cochrane Database and clinicaltrials.gov) and a manual search to identify original PCNSL phase 2 and phase 3 CT from the last 10years. After a 4stage Prisma based selection process, 32 published (3 Randomized CT and 29 phases 2 CT) studies ultimately were selected for review. Four ongoing clinical trials found on clinicaltrial.gov were reviewed. Two investigators reviewed titles, abstracts, and articles independently. Two investigators abstracted data sequentially and evaluated each study independently. FINDINGS: Treatment of PCNSL requires a multidisciplinary approach. HD-MTX represents the most accepted standard of care induction therapy for newly diagnosed PCNSL. When HD-MTX is given with WBRT for consolidation delayed neurotoxicity can be an important complication, particularly in elderly patients. Studies have suggested that WBRT may be deferred until relapse without compromising survival and deferring WBRT may be the best approach in elderly patients. Results from dose-reduced WBRT and consolidative HD-Ara-C are encouraging. High-dose chemotherapy in combination with autologous stem cell transplantation (HDC-ASCT) as chemotherapy alone has emerged as an important consolidative treatment for selected population. The optimal salvage therapy is still to be defined. CONCLUSION: WBRT for consolidation is a well-studied modality; however emerging options to selected population such as HDC-ASCT, dose-reduced WBRT or chemotherapy alone are associated with similar survival outcome and less neurotoxicity in selected series. Ongoing and future clinical trials will better define the best approach on this rare disease.

Linfoma primario del sistema nervioso central: el aporte de las técnicas convencionales de diagnóstico por imágenes / Primary CNS lymphoma: The contribution of conventional diagnostic imaging techniques

El linfoma primario del sistema nervioso central (LPSNC) tiene una presentación predecible en las imágenes convencionales, tanto en pacientes inmunocompetentes como inmunodeprimidos. Analizamos las características imagenológicas que nos permiten reconocer ambos casos y realizamos una revisión de las formas clínicas más relevantes del LPSNC, así como su aspecto en las imágenes obtenidas con técnicas convencionales del Diagnóstico por Imágenes, basándonos en un análisis retrospectivo de nuestros archivos institucionales y la literatura actual. La revisión abarca todas las presentaciones relevantes de esta enfermedad poco frecuente para permitir un diagnóstico temprano, crucial para el adecuado tratamiento.

Primary central nervous system lymphoma (PCNSL) has a predictable imaging appearance on conventional imaging in immunocompetent and immunocompromised patients. The imaging features that enable both types of patients are discussed. The extensive imaging review presented here of the most relevant PCNSL clinical presentations and their imaging appearances using conventional imaging techniques is based on a retrospective analysis of our institutional files and on the current literature. The review covers all of the relevant appearances of this uncommon disease to enable early diagnosis, which is crucial for proper patient management.

Historical distribution of central nervous system tumors in the Mexican National Institute of Neurology and Neurosurgery / Distribución histórica de neoplasias del sistema nervioso central en el Instituto Nacional de Neurología y Neurocirugía de México

Abstract Objective: To determine the frequency of central nervous system (CNS) tumors in the first fifty years of the National Institute of Neurology and Neurosurgery of Mexico Manuel Velasco Suárez (Instituto Nacional de Neurología y Neurocirugía de México, INNN) from 1965 to 2014. Materials and methods: A total of 16 116 institutional records of CNS tumors were analyzed. The frequency and distribution of CNS tumors were evaluated by tumor type, patient age and patient gender. The annual relationship between CNS tumors and surgical discharges (SD) over the last 20 years was estimated. Results: The frequencies of most CNS tumors were consistent with those found worldwide, and the most common tumors were neuroepithelial tumors (33%), particularly astrocytic tumors (67%); meningeal tumors (26%); and pituitary tumors (20%). The incidence of pituitary tumors in these data was twice as high as that reported in other regions of the world, and the relationship between CNS tumors and SD was consistent over time (0.22-0.39). Conclusion: This study summarizes the largest sample of CNS tumor cases analyzed in Mexico and provides an important reference of the frequency of this tumor type in the country. This work will serve as a basis for conducting studies evaluating factors associated with the presence of CNS tumors and for identifying adequate public health interventions.

Resumen Objetivo: Determinar la frecuencia de neoplasias del sistema nervioso central (NSNC) en los primeros 50 años del Instituto Nacional de Neurología y Neurocirugía de México (INNN). Material y métodos: Se analizaron 16 116 registros institucionales de las NSNC, atendidas en el INNN de 1965 a 2014; se estimó su frecuencia y distribución por tipo de neoplasia, edad y género, y se determinó la relación anual de NSNC y egresos quirúrgicos (EQ) en un período de 20 años. Resultados: Las frecuencias de la mayoría de NSNC fueron consistentes con las encontradas a nivel mundial. Las más frecuentes fueron las neuroepiteliales (33%), entre las cuales destacaron las astrocíticas (67%); meníngeas (26%), e hipofisiarias (20%). El número de neoplasias hipofisiarias en esta serie fue dos veces mayor al reportado en otras regiones del mundo y la relación NSNC/EQ fue similar a través del tiempo (0.22-0.39). Conclusión: Ésta es la mayor serie de casos de NSNC analizados en México y proporciona un referente importante sobre la frecuencia de este tipo de neoplasias en el país. Este trabajo servirá de base para llevar a cabo estudios de los factores asociados a la presencia de NSNC e identificar intervenciones de salud pública adecuadas.

Tumores del sistema nervioso central en población pediátrica entre 0 y 14 años / Tumores do sistema nervoso central em pacientes pediátricos entre 0 e 14 / Central nervous system tumors in pediatric population from 0 to 14 years

Introducción: Los tumores pediátricos primarios del sistema nervioso central (SNC), ocupan el segundo lugar en frecuencia, superados solamente por las neoplasias hematológicas. Objetivo: Realizar una revisión y análisis de la literatura médica existente sobre tumores del SNC en población entre los 0 y 14 años centrado en la epidemiologia, factores etiológicos, manifestaciones clínicas y diagnóstico. Metodología: Se realizó una búsqueda en las bases de datos PubMed, MedlinePlus, BIREME y red interna de trabajos de grados y tesis de la Universidad Industrial de Santander. Además, se realizó revisión de las páginas de los entes gubernamentales encargados del registro epidemiológico sobre cáncer nacional e internacional. Resultados: Los tumores de SNC en la población pediátrica son la segunda causa de muerte infantil solo superado por la leucemia; tienen una clínica y factores etiológicos bien establecidos. La epidemiología no difiere en el mundo. Los síntomas más frecuentes son vómito, cefalea, ataxia, síntomas visuales y alteraciones motoras. Los factores etiológicos más representativos son virus, síndromes genéticos, infecciones maternas y perinatales, exposición a radiación electromagnética e ionizante; algunos son muy discutidos como la presencia de trauma al momento del nacimiento. Además, existen documentados factores protectores tales como consumo de antioxidantes, frutas y verduras, e historia reportada de alergias. Conclusiones: El adecuado entrenamiento a los médicos de atención primaria en la identificación de los signos y síntomas para la sospecha y diagnóstico de los estadios iniciales de estos tumores pueden disminuir los índices de mortalidad.

Introduction. The primary pediatric tumors of the central nervous system (CNS) rank second in frequency, only surpassed by hematological malignancies. Objective. Conduct a review and analysis of existing literature on CNS tumors in population between 0 and 14 focused on the epidemiology, etiological factors, clinical manifestations, and diagnosis. Methodology: The search for articles was conducted using the databases PubMed, MedLinePlus, BIREME and intranet degrees and thesis work of the Universidad Industrial de Santander. Further review of the pages from government agencies in charge of epidemiological registry of cancer was made. Results: CNS tumors in pediatric population are the second leading cause of infant death second only to leukemia, have a clinic and etiological factors well established. The epidemiology don´t differs in the world. The most common symptoms are vomiting, headache, ataxia, visual symptoms and motor disturbances. The most representative etiologic factors are viruses, genetic syndromes, maternal and perinatal infections, exposure to electromagnetic and ionizing radiation, some others are discussed as the presence of trauma at birth. There are also documented protective factors such as consumption of antioxidant, fruits and vegetables, and reported history of allergies. Conclusions: The adequate training of primary care physicians in the identification of signs and symptoms for suspicion and diagnosis of the initial stages of these tumors can reduce mortality rates.

Introdução: Os tumores pediátricos primários do sistema nervoso central (CNS), classificação em segundo lugar na frequência, superado apenas pelo malignidades hematológicas. Objetivo: Revisar e análise da literatura existente sobre os tumores do SNC na população entre 0 e 14 anos, com foco em epidemiologia, fatores etiológicos, as características clínicas e diagnóstico. Metodologia: A pesquisa foi realizada no PubMed, MedlinePlus, NLM e graus de rede internos e tese de trabalho dos dados Universidade Industrial de Santander. Além disso, páginas de revisão de agências governamentais encarregadas de registro epidemiológico sobre câncer nacional e internacional foi realizada. Resultados: tumores do SNC na população pediátrica são a segunda principal causa de morte infantil perdendo apenas para a leucemia, têm fatores clínicos e etiológicos bem estabelecidos. Epidemiologia difere no mundo. Os sintomas mais comuns são vômitos, dor de cabeça, ataxia, sintomas visuais e distúrbios motores. Os fatores etiológicos mais representativos são os vírus, síndromes genéticas, infecções maternas e perinatais, a exposição às radiações electromagnéticas e ionizantes; alguns são muito discutidos como a presença de trauma no nascimento. Além disso, existe são documentados fatores de proteção, tais como o consumo de antioxidantes, frutas e legumes, e história de alergia relatados. Conclusões: O treinamento adequado para médicos de cuidados primários na identificação dos sinais e sintomas de suspeita e diagnóstico dos estágios iniciais desses tumores pode diminuir as taxas de mortalidade.

Tooth abnormalities in pediatric patients submitted to antineoplastic treatment for central nervous system neoplasms / Anormalidades dentárias em pacientes pediátricos submetidos a tratamento antineoplásico para neoplasias do sistema nervoso central

Objective: The aim of this study was to evaluate the frequency of tooth abnormalities in pediatric patients treated for central nervous system neoplasms. Material and methods: This crosssectional study assessed thirty-one patients, median age 14.2 years (range 5 - 25), who were off therapy for at least one year, comparatively with a control group of thirty-one healthy patients matched for age with the study group. Tooth abnormalities were evaluated by panoramic radiographs. Results: There was no statistical significant evidence that patients of the study group (age range 5 - 25 years) have more frequency of tooth abnormalities comparatively with controls. However, in children who were diagnosed before five years of age, microdontia was the most common abnormality with statistically significant difference (P = 0.037). Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, also with statistical significance (P = 0.046). Conclusions: There was no difference in the frequency of tooth abnormalities in pediatric patients treated for central nervous system neoplasms, comparatively with the control group. However, the findings of this study highlight the importance of giving parents and patients orientation about maintenance of good oral hygiene and proper treatment.

Objetivo: O objetivo deste estudo foi avaliar a frequência de anormalidades dentárias em pacientes pediátricos tratados para neoplasias do sistema nervoso central. Material e Métodos: Este estudo transversal avaliou trinta e um pacientes, com média de idade de 14,2 anos (entre 5 – 25 anos), que estavam fora de terapia há pelo menos um ano, comparativamente com um grupo controle composto por 31 pacientes saudáveis pareados por idade com o grupo de estudo. As anormalidades dentárias foram avaliadas por meio de radiografias panorâmicas. Resultados: Não houve evidência estatisticamente significante de que pacientes do grupo de estudo (entre 5 – 25 anos) apresentam maior frequência de anormalidades dentárias quando comparados aos pacientes do grupo controle. No entanto, em crianças diagnosticadas antes dos cinco anos de idade, microdontia foi a anormalidade mais comumente encontrada, com diferença estatisticamente significante (P=0.037). Encurtamento radicular grau III foi observado em pacientes com mais de 10 anos de idade ao exame radiográfico, também com significância estatística (P=0.046). Conclusão: Não houve diferença na frequência de anormalidades dentárias em pacientes pediátricos submetidos a tratamento antineoplásico para neoplasias do sistema nervoso central, comparativamente ao grupo controle. No entanto, os achados deste estudo ressaltam a importância de reconhecer os efeitos dentários tardios do tratamento antineoplásico em crianças com câncer e deste modo orientar pacientes e responsáveis sobre cuidados de higiene bucal e sobre opções de tratamento apropriado.