A single-center, retrospective analysis of relapse and progression patterns of primary central nervous system lymphoma: can whole brain radiotherapy be replaced? / 南方医科大学学报

OBJECTIVE@#To analyze recurrence and progression patterns of primary central nervous system lymphoma (PCNSL) in patients without whole brain radiotherapy (WBRT) and assess the value of WBRT in PCNSL treatment.@*METHODS@#This retrospective single-center study included 27 patients with PCNSL, who experienced recurrence/progression after achieving complete remission (CR), partial remission, or stable disease following initial treatments with chemotherapy but without WBRT. The patients were followed up regularly after the treatment for treatment efficacy assessment. By comparing the anatomical location of the lesions on magnetic resonance images (MRI) at the initial diagnosis and at recurrence/progression, we analyzed the patterns of relapse/progression in patients with different treatment responses and different initial status of the lesions.@*RESULTS@#MRI data showed that in 16 (59.26%) of the 27 patients, recurrence/progression occurred in out-field area (outside the simulated clinical target volume [CTV]) but within the simulated WBRT target area in 16 (59.26%) patients, and within the CTV (in-field) in 11 (40.74%) patients. None of the patients had extracranial recurrence of the tumor. Of the 11 patients who achieved CR after the initial treatments, 9 (81.82%) had PCNSL recurrences in the out-field area but within WBRT target area; of the 13 patients with a single lesion at the initial treatment, 11 (84.62%) experienced PCNSL recurrence in the out-field area but within WBRT target area.@*CONCLUSIONS@#Systemic therapy combined with WBRT still remains the standard treatment for PCNSL patients, especially those who achieve CR after treatment or have a single initial lesion. Future prospective studies with larger sample sizes are needed to further explore the role of low-dose WBRT in PCNSL treatment.

Primary central nervous system T-cell lymphoma in children and adolescents: a clinicopathological analysis of five cases / 中华病理学杂志

Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.

Análise Epidemiológica, Clínica e Patológica de Crianças com Neoplasias do Sistema Nervoso Central Tratadas com Radioterapia no Instituto Nacional de Câncer / Epidemiological, Clinical, and Pathological Analysis of Children with Central Nervous System Neoplasms Treated with Radiotherapy at the National Cancer Institute / Análisis Epidemiológico, Clínico y Patológico de Niños con Neoplasias del Sistema Nervioso Central Tratados con Radioterapia en el Instituto Nacional de Cáncer

Introdução: As neoplasias de sistema nervoso central representam 21% do câncer infantojuvenil, sendo a principal causa de morte nessa população em países desenvolvidos. Avanços na neuroimagem têm melhorado seu diagnóstico, e a combinação de terapias tem permitido a cura, com maior preservação neurológica. A cirurgia é o principal tratamento, frequentemente combinada com radioterapia e quimioterapia. Objetivo: Descrever achados socioeconômicos, sinais e sintomas, e aspectos histológicos dos tumores cerebrais pediátricos, tratados com radioterapia. Método: Estudo transversal e descritivo, utilizando prontuários de 257 crianças e adolescentes portadores de neoplasias de sistema nervoso central, tratados com radioterapia no Instituto Nacional de Câncer, no Rio de Janeiro, de 2012 a 2020. As variáveis foram divididas em sociodemográficas, clínicas e patológicas. Resultados: Crianças brancas do sexo masculino foram as mais prevalentes, com mediana de idade de 7,5 anos no diagnóstico e de 8,0 anos na radioterapia. A maioria possuía casa própria com infraestrutura básica e renda familiar de até um salário-mínimo. Os sintomas mais comuns foram cefaleia, vômitos e alterações na marcha, variando de acordo com a localização do tumor e a idade da criança. A radioterapia foi utilizada em 64% dos pacientes, principalmente para meduloblastoma, tumores de tronco cerebral e ependimoma anaplásico. Conclusão: Estudos específicos sobre crianças e adolescentes com neoplasias cerebrais tratados com radioterapia são raros na literatura. Quando comparados com a população em geral, apresentam perfis sociodemográficos e clínicos semelhantes, com diferenças notáveis apenas na frequência dos tipos tumorais

Introduction: Central nervous system neoplasms account for 21% of pediatric cancer cases and are the leading cause of death in this population in developed countries. Advances in neuroimaging have improved diagnosis, and combination therapies have ensured the cure with greater neurological preservation. Surgery is the primary treatment, often combined with radiation therapy and chemotherapy. Objective: To describe socioeconomic findings, signs and symptoms, and histological aspects of pediatric brain tumors treated with radiation therapy. Method: A cross-sectional and descriptive study was conducted with 257 children and adolescents utilizing medical records with central nervous system neoplasms treated with radiotherapy at the National Cancer Institute, Rio de Janeiro, from 2012 to 2020. The variables were divided into sociodemographic, clinical, and pathological categories. Results: White male children were the most prevalent, with a median age at diagnosis of 7.5 years and at radiotherapy, of 8.0 years. The majority had their own home with basic infrastructure and family income of up to one minimum wage. The most common symptoms were headache, vomiting, and gait disorders, varying according to tumor location and child's age. Radiation therapy was used in 64% of patients, mainly for medulloblastoma, brainstem tumors, and anaplastic ependymoma. Conclusion: Specific studies on children and adolescents with brain neoplasms treated with radiotherapy are rare in the literature. When compared with the general population, they present similar sociodemographic and clinical profiles, with remarkable differences only in the frequency of tumor types

Introducción: Las neoplasias del sistema nervioso central representan el 21% del cáncer infantil y juvenil, siendo la principal causa de muerte en esta población en países desarrollados. Los avances en neuroimagen han mejorado su diagnóstico y la combinación de terapias viene permitiendo la cura, con una mayor preservación neurológica. La cirugía es el tratamiento principal, a menudo combinada con radioterapia y quimioterapia. Objetivo: Describir los hallazgos socioeconómicos, los signos y síntomas, y los aspectos histológicos de los tumores cerebrales pediátricos tratados con radioterapia. Método: Estudio transversal y descriptivo utilizando las historias clínicas de 257 niños y adolescentes con neoplasias del sistema nervioso central, que fueron tratados con radioterapia en el Instituto Nacional del Cáncer en Río de Janeiro entre 2012 y 2020. Las variables se dividieron en sociodemográficas, clínicas y patológicas. Resultado: Los niños blancos y de sexo masculino fueron los más prevalentes, con una mediana de edad de 7,5 años en el momento del diagnóstico y de 8,0 años en el momento de la radioterapia. La mayoría poseía una vivienda propia con infraestructura básica y un ingreso familiar de hasta un salario mínimo. Los síntomas más comunes fueron dolor de cabeza, vómitos y alteraciones en la marcha, que variaban según la ubicación del tumor y la edad del niño. Se utilizó radioterapia en el 64% de los pacientes, principalmente para meduloblastoma, tumores del tronco cerebral y ependimoma anaplásico. Conclusión: Los estudios específicos sobre niños y adolescentes con neoplasias cerebrales tratados con radioterapia son raros en la literatura. Cuando se comparan con la población en general, presentan perfiles sociodemográficos y clínicos similares, con diferencias notables solo en la frecuencia de los tipos tumorales

Avaliação da linguagem em cirurgia de craniotomia com paciente acordado: relato de caso / Language assessment in awake craniotomy: case report

RESUMO O objetivo deste relato foi descrever o caso de um paciente submetido à craniotomia, acordado, para a ressecção neurocirúrgica de um glioma e a avaliação linguística pré-operatória, intraoperatória e pós-operatória. Paciente do gênero masculino, 27 anos, escolaridade nível superior incompleto, apresentando vômitos, confusão mental e crise convulsiva tônico-clônica. Após a avaliação do paciente pela equipe e devidas orientações pré-operatórias, a proposta de excisão da lesão em estado de vigília foi esclarecida e aceita. Ao iniciar o procedimento, os campos foram ajustados para manter as vias aéreas e os olhos acessíveis para mapeamento com estimulação elétrica e avaliação da linguagem no período intraoperatório. Devido à localização do tumor próximo à área motora da fala, foram propostas tarefas para a avaliação da linguagem em quatro momentos: pré-operatório, intraoperatório, pós-operatório imediato e pós-operatório mediato. As habilidades linguísticas testadas nas quatro avaliações foram: compreensão e expressão da linguagem oral, transposição linguística, linguagem associativa, nomeação, discriminação visual, fluência e organização da sintaxe. Com o objetivo de controlar e eliminar o efeito de aprendizagem da testagem, foram solicitadas as mesmas tarefas, porém, com diferentes conteúdos para a testagem das habilidades nas quatro fases. A cirurgia com o paciente acordado permitiu a ressecção completa e segura do tumor, sem prejuízo motor ou linguístico. O engajamento da equipe, a interação interdisciplinar e o planejamento cirúrgico detalhado constituem um pilar para o bom resultado de um procedimento tão complexo e delicado.

ABSTRACT The purpose of this report is to describe the case of a patient who underwent awake craniotomy for neurosurgical resection of a glioma and pre, intra and postoperative linguistic assessment. Male patient, 27 years old, incomplete higher education presenting vomiting, mental confusion and tonic-clonic seizures. After the evaluation of the patient by the team and due preoperative guidance, the proposal of excision of the lesion while awake was clarified and accepted. At the start of the procedure, the fields were adjusted to keep the airway and eyes accessible for mapping with electrical stimulation and intraoperative language assessment. Due to the location of the tumor close to the speech motor area, tasks were proposed for the assessment of language in four moments: preoperative, intraoperative, immediate postoperative and mediate postoperative. The language skills tested in the four assessments were: comprehension and expression of oral language, linguistic transposition, associative language, naming, visual discrimination, fluency and syntax organization. In order to control and eliminate the learning effect of testing, the same tasks were requested, but with different contents for testing skills in the four phases. Surgery with the patient awake allowed the complete and safe resection of the tumor, without motor or linguistic damage to the patient. Team engagement, interdisciplinary interaction and detailed surgical planning constitute the pillar for the good result of such a complex and delicate procedure

Caracterização epidemiológica das neoplasias do sistema nervoso central em pacientes da região Norte do Brasil / Epidemiological characterization of central nervous system tumors in patients from Northern Brazil

Introdução: A incidência de neoplasias que acometem o Sistema Nervoso Central (SNC) tem aumentado gradativamente no mundo. No Brasil, as neoplasias encefálicas primárias são classificadas como a sétima causa de morte entre as neoplasias malignas. O objetivo do presente estudo foi caracterizar o perfil epidemiológico dos pacientes acometidos por neoplasias do SNC em um estado do Norte do Brasil.Métodos: Estudo retrospectivo, onde 196 prontuários, entre 2012 e 2016, de dois hospitais na região Norte do Brasil foram analisados.Resultados: O glioblastoma multiforme foi predominante (30,6%) entre as neoplasias primárias, seguido pelo astrocitoma (12,2%). As neoplasias secundárias, identificadas como metástases encefálicas, corresponderam a 29,9% da amostra, principalmente derivadas de neoplasias do pulmão e mama. A gravidade histológica das lesões neoplásicas foi mais frequente nos homens (p= 0,01). Foi observado que as neoplasias ocorreram com maior frequência a partir da 4º década de vida, exceto nos casos de astrocitoma e meduloblastoma, que foram detectadas principalmente em crianças e adultos jovens.Conclusão: A caracterização dos casos de neoplasias do SNC é de importante para a compreensão da situação atual deste problema de saúde pública na região norte do Brasil.

Introduction: The incidence of central nervous system (CNS) cancer has gradually increased worldwide. In Brazil, primary brain tumors are the seventh leading cause of death among malignant tumors. The objective of the present study was to characterize the epidemiological profile of patients with CNS cancer from a state in northern Brazil.Methods: This retrospective study analyzed 196 medical records between 2012 and 2016 from two hospitals in northern Brazil.Results: Glioblastoma multiforme was predominant (30.6%) among primary tumors, followed by astrocytoma (12.2%). Secondary cancer, defined as brain metastases, accounted for 29.9% of the sample and was mostly associated with lung and breast cancer. The histological severity of neoplastic lesions was more frequent in men (p = 0.01). Cancer occurred more frequently after the fourth decade of life, except in cases of astrocytoma and medulloblastoma, which mostly affected children and young adults.Conclusion: The characterization of CNS tumors is important for understanding the current situation of this public health problem in northern Brazil.

Distribuição da Mortalidade Infantojuvenil por Tumores do Sistema Nervoso Central no Estado do Ceará / Distribution of Children and Adolescent Mortality by Central Nervous System Tumors in the State of Ceará / Distribución de la Mortalidad Infantil y Juvenil por Tumores del Sistema Nervioso Central en el Estado de Ceará

Introdução: Os tumores do sistema nervoso central (SNC) são um dos tipos mais comuns de tumores sólidos que acometem crianças. Apresentam heterogeneidade por compreender mais de 100 tipos histológicos definidos com base na origem da célula e outras características histopatológicas. Objetivo: Analisar a distribuição espacial da mortalidade por tumores do SNC em crianças e adolescentes no Estado do Ceará, no período de 2008-2018. Método: Estudo ecológico realizado com dados de fontes secundárias de 2008-2018 disponíveis no Sistema de Informação sobre Mortalidade (SIM). Foram calculadas as taxas brutas, o Índice de Moran Global e Local e o risco relativo para todos os óbitos. Resultados: Dos 378 óbitos, 197 eram do sexo masculino (52%), 116 apresentavam a faixa etária entre 5-9 anos (30,7%), 193 eram pardos (51%) e 354 morreram no hospital (93,6%). Os municípios que apresentaram as maiores taxas (49,94 e 99,88 óbitos/1 milhão de habitantes) foram Aracati, Barreira, Catunda, Coreaú e Fortaleza. Pelo Índice de Moran, observou-se a formação de um cluster com padrão alto-alto e significância estatística de distribuição na Mesorregião do Metropolitana de Fortaleza. O município de Pacujá apresentou o maior risco relativo (7,32) seguido do município de Catunda (6,94). Conclusão: As Regiões Norte e Noroeste do Ceará possuem taxas mais elevadas e risco maior para mortalidade por tumores do SNC

Introduction: Central nervous system (CNS) tumors are one of the most common types of solid tumors that affect children. Due to their heterogeneity, they comprise more than 100 defined histological types of cell origin-based and other histopathological characteristics. Objective: To analyze the spatial distribution of mortality by CNS tumors in children and adolescents in the State of Ceará in the period 2008-2018. Method: Ecological study, with secondary data of the period selected available in the Mortality Information System (SIM). Crude rates, Moran Global and Local index, and relative risk for all deaths were calculated. Results: Of the 378 deaths, 197 were males (52%) mostly, 116 aged between 5-9 years (30.7%), 193 brown (51%) and 354 died in the hospital (93.6%). The municipalities with the highest rates (49.94 and 99.88 deaths/1 million inhabitants) were Aracati, Barreira, Catunda, Coreaú and Fortaleza. The Moran Index showed the formation of a cluster with a high-high standard and statistical significance of distribution in the Metropolitana Fortaleza Mesoregion. The municipality of Pacujá had the highest relative risk (7.32) followed by the municipality of Catunda (6.94). Conclusion: The North and Northwest Regions of Ceará presented the higher mortality and risk rates by CNS tumors

Introducción: Los tumores del sistema nervioso central (SNC) son uno de los tipos más comunes de tumores sólidos que afectan a los niños. Presentan heterogeneidad al comprender más de 100 tipos histológicos definidos y basados en el origen celular y otras características histopatológicas. Objetivo: Analizar la distribución espacial de la mortalidad por tumores del SNC en niños y adolescentes en el Estado de Ceará en el período 2008-2018. Método: Estudio ecológico realizado con datos de fuentes secundarias de 2008-2018 disponibles en el Sistema de Información de Mortalidad (SIM). Se calcularon las tasas brutas, el Índice de Moran Global y Local y el riesgo relativo de todas las muertes. Resultados: De los 378 fallecidos, 197 eran varones (52%), 116 presentaban el grupo de edad entre 5-9 años (30,7%), 193 eran morenos (51%) y 354 murieron en el hospital (93,6%). Los municipios con mayores tasas (49,94 y 99,88 defunciones/1 millón de habitantes) fueron Aracati, Barreira, Catunda, Coreaú y Fortaleza. El Índice de Moran observó la formación de un cluster con un patrón alto-alto y significación estadística de distribución en la Mesoregión de Fortaleza Metropolitana. El municipio de Pacujá presentó el mayor riesgo relativo (7,32) seguido del municipio de Catunda (6,94). Conclusión: Las regiones del Norte y Noroeste de Ceará tienen tasas más elevadas y un mayor riesgo de mortalidad por tumores del SNC

The value of CXorf67 and H3K27me3 for diagnosing germ cell tumors in central nervous system / 中华病理学杂志

Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r2=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.

Remarkable Clinical Improvement Following Microsurgical Resection of Left Lingual Gyrus Cerebral Cavernous Malformation: A Case Report

Moyamoya disease is a chronic and unusual cerebrovascular disorder characterized by progressive stenosis and occlusion of the distal portions of internal carotid arteries and its main branches within the circle of Willis. Posterior circulation (vertebral and basilar arteries) may also be affected; however, this presentation is uncommon. As well as stenosis of the terminal portion of intracranial arteries, it is seen the development of a network of collateral vessels abnormally dilated at the base of the brain with an aspect of a "puff of smoke," whose term in Japanese is described as "moyamoya." The present study aims to report two consecutive cases of patients who presented to our service with different clinical manifestations. Further investigation with digital subtraction angiography showed a moyamoya pattern.

Central nervous system international prognostic index impacts overall survival in diffuse large b-cell lymphoma treated with r-chop in a third level cancer center from Mexico: a survey of 642 patients

Background: Central nervous system international prognosis index (CNS-IPI) is validated in European and the USA cancer databases. However, no validation has been done in Mexican population. Objective: The objective of the study was to assess the impact of the CNS-IPI on central nervous system (CNS) relapse and survival in Mexican patients with diffuse large B-cell lymphoma (DLBCL). Methods: In this retrospective analysis, clinical, biochemical, and histological variables and the CNS-IPI were analyzed. Results: Six hundred and forty-two patients with DBLCL were included in the study. The mean ± SD age was 56.8 ± 14.9 years. Most had an ECOG of 0-1: 75% (n = 484) had absence of B-symptoms and advanced disease (clinical stage: III-IV, n = 433, 67.4%). According to the CNS-IPI, almost one-half were in the low-risk category. According to the CNS-IPI, CNS relapse rate was 1.36% (95% CI: 83.2-92.8), 3.1% (95% CI: 132.4-162.8), and 7.4% (95% CI 61-91) for patients in the low-, intermediate-, and high-risk categories, respectively. The median overall survival in the high-risk group (CNS-IPI) was 22 months, and it has not been achieved after 80 months of follow-up for the other groups. Conclusions: CNS-IPI was associated with survival; therefore, we propose its use as a prognostic tool for prospective validation.

Marcadores moleculares y biomarcadores de imagen: importancia en el avance terapéutico de los tumores cerebrales intraaxiales / Molecular markers and image biomarkers. Importance in the therapeutic advance of intraaxial brain tumors

RESUMEN: La clasificación de los Tumores Primarios del Sistema Nervioso Central (SNC) tiene su origen en la descripción morfológica, cuyo análisis histopatológico ha permitido identificar la línea celular involucrada en estos tumores y obtener el reconocimiento de ciertas características de estas lesiones y su evolución clínica. El estudio molecular ha venido a complementar el diagnóstico inicial permitiendo reconocer entidades que no son distinguibles de otra manera y que han variado los conceptos y definiciones de varias entidades patológicas que modifican el horizonte visible de estas enfermedades. El papel de las imágenes de Resonancia Magnética (RM) en el manejo de los tumores intraaxiales se puede dividir ampliamente en el diagnóstico y la clasificación de los tumores, la planificación del tratamiento y el tratamiento posterior. El presente artículo resume la evidencia epidemiológica relacionada en la clasificación de los tumores primarios del SNC con marcadores moleculares y biomarcadores de imágenes de RM, apuntando a la importancia del uso de la investigación clínica con el manejo terapéutico.

SUMMARY: The classification of primary tumors of the Central Nervous System (CNS) has its origin in the morphological description whose histopathological analysis has allowed to identify the cell line involved in these tumors and obtain the recognition of certain characteristics of these lesions and their clinical evolution. The molecular study has come to complement the initial diagnosis allowing to recognize entities that are not distinguishable in another way and that have varied the concepts and definitions of various pathological entities modifying the visible horizon of these diseases. The role of Magnetic Resonance (MR) images in the management of intraaxial tumors can be broadly divided into the diagnosis and classification of tumors, treatment planning and subsequent treatment. The present article summarizes the epidemiologic evidence related to the classification of primary tumors of the CNS with molecular markers and MR imaging biomarkers.

Calidad de vida en niños supervivientes de tumor de sistema nervioso central / Quality of life in child survivors of central nervous system tumor

INTRODUCCIÓN: Los cuidados de calidad de los supervivientes incluyen vigilancia de la recurrencia y de segundos tumores, intervención en el control de síntomas y de necesidades psicosociales y coordinación del cuidado. OBJETIVO: Conocer la calidad de vida en los niños sobrevivientes de cáncer que son vistos en la consulta externa del servicio de Oncología Pediátrica. MATERIAL Y MÉTODO: Estudio descriptivo transversal, realizado en la consulta externa del Servicio de Oncología Pediátrica del Centro Médico Nacional 20 de noviembre ISSSTE, con 16 pacientes supervivientes de Tumor de Sistema Nervioso Central aplicando Inventario de calidad de vida. (PedsQL MT) Resultados: La dimensión menos afectada fue la social con una media de 73.44 seguida de la física tuvo una media de 71.87, con emocional media de 67.19 y la escolar fue la que menos afectada estuvo con media de 68.75. CONCLUSIÓN: Es fundamental que el médico detecte problemas tardíos derivados del tratamiento y de la enfermedad, prevenir complicaciones y secuelas graves, otorgar ayuda al niño y a su familia para integrarse a la sociedad necesarias para enfrentar a la sociedad e integrarse a ella sin dificultades, logrando así una mejor calidad de vida.

INTRODUCTION: Quality care survivors include surveillance of recurrence and second tumors, intervention in the control of symptoms, psychosocial needs and coordination of care. OBJECTIVE: To determine the quality of life in childhood cancer survivors who are seen in outpatient pediatric oncology service. MATERIALS AND METHODS: A cross sectional study was performed in the outpatient clinic of pediatric oncology of National Medical Center "20 de Noviembre" ISSSTE, with 16 surviving patients of central nervous system tumor applying quality of life inventory. (PedsQL TM) RESULTS: The least affected was the social dimension with an average of 73.44 followed by physics which had an average of 71.87, emotional with a mean of 67.19 and school was the least affected with an average of 68.75. CONCLUSIONS: It is essential that the physician detected late problems from treatment and disease, prevent complications and serious sequelae, grant helps the child and family to join the society and integrate it seamlessly, making a better quality of life.

Reactivos de inmunohistoquímica para diagnóstico diferencial oncológico de neoplasias del sistema nervioso central / Immunohistochemical reagents for differential cancer diagnosis of central nervous system neoplasms

INTRODUCCIÓN: El Departamento de Equipo Funcional de Patología Quirúrgica y Necropsia del Instituto Nacional de Enfermedades Neoplásicas, en relación a nuevos reactivos de inmunohistoquímica para diagnóstico oncológico de tumores del sistema nervioso central, ha solicitado la opinión técnica de la UFETS. 2. Existen neoplasias del sistema nervioso central que presentan una pobre respuesta al tratamiento estandarizado y un peor pronóstico, por lo cual ameritan un diagnóstico eficaz y temprano. Los marcadores para inmunohistoquímica H3 K27M, H3 K27m3, GAB-1, YAP-1, H3.3G34R y MAP-2 permitirían un diagnóstico más eficaz e incluso influiría en su tratamiento y seguimiento. Estrategia de búsqueda de información: a) Pregunta Clínica: Sección A: SNC: En la población con tumores de SNC, ¿Cuál es la utilidad de los marcadores de H3 K27m3, GAB-1, YAP-1, H3.3G34R y MAP-2 como diagnóstico oncológico en tumores del SNC? b) Recolecciòn de los Manuscritos a Revisar: Tipos de estudios: La estrategia de búsqueda sistemática de información científica para el desarrollo del presente informe se realizó siguiendo las recomendaciones de la Pirámide jerárquica de la evidencia propuesta por Haynes y se consideró los siguientes estudios: Sumarios y guías de práctica clínica. Revisiones sistemáticas y/o meta-análisis. Ensayos Controlados Aleatorizados (ECA) Estudios Observacionales (cohortes, caso y control, descriptivos) No hubo limitaciones acerca de la fecha de publicación o el idioma para ningún estudio. DISCUSION: Tomando los criterios para un marco de valor de la Health Technology Assessment International (2018)13 para la toma de decisiones y formulación de la recomendación, se encontró una serie de estudios de los cuales no se encontraron revisiones sistemáticas ni estudios diagnósticos. La calidad de evidencia evaluada con metodología GRADE fue baja en todos los estudios evaluados, considerando el diseño de estudio observacional, y por el pequeño tamaño de las muestras estudiadas. Esta valoración indica que los resultados obtenidos en el mundo real por la aplicación de estas tecnologías pueden ser significativamente diferentes a los resultados diagnósticos de los estudios presentados. Los estudios que evaluaron el H3K27M y H3K27me3 evaluaron la utilidad diagnóstica de los anticuerpos para detección de estas mutaciones. El diagnóstico de glioma de línea media con mutación K27M permite reconocer una entidad de peor pronóstico y sólo se logra con la aplicación de estos marcadores. Si bien existe una cantidad limitada de evidencia, los estudios llevados por Tina Huang y col. evaluaron el rendimiento diagnóstico de estos marcadores comparándolos con estudios de mutación en muestras de tejido con diagnóstico de glioma (n=69) y tejido sano (n=4) en población pediátrica. Otro estudio por Sriram Venneti y col. tomaron como población 290 muestras de cáncer con mutación H3F3A K27M conocida. Los estudios reportan una sensibilidad 100% y una especificidad 100% para el marcador H3K27M y Sriram Venneti reportó una sensibilidad 100% y especificidad 98% para H3K27me3. Ambos marcadores cuentan con una utilidad diagnóstica importante su aplicación permitiría diagnosticar precozmente una enfermedad con mal pronóstico en edad pediátrica y adulta. El GAB-1 y el YAP-1 intervienen en el proceso de desarrollo del cáncer a nivel de sistema nervioso central. La detección de ambas mutaciones por inmnohistoquimica permite la clasificación molecular del meduloblastoma en SHH, WNT y no-SHH/WNT. El determinar el subtipo molecular es importante ya que cada uno cuenta con un pronóstico diferente y su reconocimiento permitiría realizar un mejor diagnóstico y hasta influir en el tipo de tratamiento que recibiría. David W. Ellison y su equipo reconocer al meduloblastoma como una enfermedad heterogenea y a través de inmunohistoquímica determinan los subtipos de meduloblastoma en una cohorte de 235 muestras en pacientes de un rango de edad 0.4 ­ 52 años. Los subtipos moleculares SHH, WNT, y no SHH/WNT correspondían al 31%, 14%, y 55% de los casos. Hye Sook Min y col. evaluaron la detección de mutaciones a través de anticuerpos para inmunohistoquímica en cada subtipo molecular de meduloblastoma. El GAB-1 fue hallado en el 100% de los subtipos SHH y en sólo el 25% del subtipo WNT. El YAP-1 se encontró en el 50% de los subtipos WNT, el 80%de SHH y sólo el 2% en los subtipos no-SHH/WNT. Ambos marcadores son relevantes para poder clasificar adecuadamente cada subtipo molecular de meduloblastoma. Las mutaciones H3.3G34R y MAP-2 están asociadas con la progresión de enfermedad oncológica. Farhana Haque y col. evaluaron la eficacia de la inmunotinción para la detección de H3.3G34R en una cohorte de 22 muestras de tumores incluidos en parafina con mutación H3.3 G34R conocida. 17 eran tumores supratentoriales de alto grado, 2 gangliomas anaplasicos, 2 oligoastrocitomas grado III y 1 glioma de alto grado. La IHC detectó con éxito la proteína mutante correspondiente en todos los casos (11/11 G34R). Los resultados demostraron una concordancia adecuada entre estudio diagnóstico con inmunohistoquímica y estudio mutacional correspondiente. Se reportó una sensibilidad del 100% y especificidad del 98% para diagnóstico. Con respecto al estudio de inmunohistoquímica del MAP-2, Ingmar Blümcke y su grupo de estudio demostraron que el análisis por inmunohistoquímica presentó una sensibilidad del 98% y una alta especificidad para la detección de esta mutación, la cual está asociada con la progresión de tumores astrocíticos de alto grado en el sistema nervioso central. En este momento el INEN no cuenta con marcadores que puedan diagnosticar los gliomas de línea media con mutación K27M, una entidad de pobre repuesta al tratamiento y peor pronóstico y que por ende ameritaría un diagnóstico precoz. De la misma forma, la clasificación molecular de los meduloblastomas es algo importante. Cada subtipo molecular cuenta con un pronóstico diferente lo cual podría impactar en el tratamiento y la forma de seguimiento de los pacientes. Tampoco se cuenta con una forma de detección de la mutación 3.3 G34R y el MAP-2 cuenta con una alta eficacia diagnóstica para el diagnóstico de astrocitomas de alto grado. Ninguno de estos procedimientos diagnósticos está siendo realizado en este momento por lo cual la aplicación de estos marcadores supone un impacto positivo al considerar la población de pacientes diagnosticados que contarían con un tratamiento adecuado. Todos estos marcadores se integrarían al arsenal diagnóstico, sin reemplazar otro marcador que ya se esté aplicando en el INEN. El impacto económico de esta prueba para el INEN es incierto y es necesario realizar un análisis de impacto presupuestario para estimar cuantitativamente el gasto sanitario del uso de esta prueba en la población con linfomas. CONCLUSIONES: Algunas patologías oncológicas del sistema nervioso centran tienen una mala respuesta al tratamiento convencional, lo cual les da un peor pronóstico y un curso más agressivo. Los marcadores H3 K27M y H3 K27m3 presentan una alta sensibilidad y especificidad para el diagnóstico de gliomas de la línea media con mutación K27M. Esta entidad cuenta con una peor respuesta a tratamiento y peor pronóstico. Su detección temprana podría permitir un mejor tratamiento y optimizar las pautas de seguimiento. Los marcadores H3.3G34R y MAP-2 reconocen mutaciones que intervienen con el desarrollo del cáncer. Ambos cuentan con una alta sensibilidad y especificidad para el diagnóstico de tumores astrocíticos de alto grado. Los marcadores GAB-1 y YAP-1 se utilizan para determinar los subtipos moleculares de meduloblastoma, teniendo el GAB-1 una sensibilidad alta para el tipo SHH. Cada subtipo molecular de meduloblastoma cuenta con un pronóstico diferente lo cual podría influenciar en la forma de tratamiento que recibirían. Los marcadores de inmunohistoquímica permitirían un eficaz y temprano diagnóstico, lo cual influiría positivamente en el pronóstico de los pacientes con estas patologías, las cuales hasta la fecha no han sido diagnosticadas adecuadamente.

Primary diffuse large B-cell lymphoma of the CNS, with a "Lymphomatosis cerebri" pattern

We describe an unusual case of lymphomatosis cerebri in a middle-aged lady presenting with rapid-onset dementia. The lymphomatous infiltrate, instead of forming mass lesions, percolated throughout the brain parenchyma, which is often missed on a stereotactic biopsy and hence warrants caution and awareness about this entity. The nonspecific symptoms at presentation and a variable picture at imaging make this entity diagnostically challenging.

Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL).@*METHODS@#Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People's Hospital from February 2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX (3.5 g/m@*RESULTS@#There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed.@*CONCLUSION@#The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite short-term effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.

New Advances in the Treatment of Primary Central Nervous System Lymphoma--Review / 中国实验血液学杂志

Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma outside the lymph nodes. At present, high-dose chemotherapy based on methotrexate is the standard induction therapy for newly diagnosed PCNSL, but the effective therapy of relapse/refractory and elderly PCNSL is still unclear. With the progress of clinical trials, new drugs and combined treatment method appear constantly, such as rituximab and ibrutinib, the remission rate of refractory and relapsed patients increased, while lenalidomide showed a good activity in the maintenance treatment of elderly patients. This review summarized briefly the recent advances of research on immunocheckpoint inhibitors, immunoregulatory agents, bruton tyrosine kinase (BTK) and PI3K/AKT/mTOR pathway inhibitors.

Tumor de sistema nervoso central e o paciente pediátrico: alterações fonoaudiológicas / Central nervous system tumor and the pediatric patient: speech-language alterations / Tumor del sistema nervioso central y el paciente pediátrico: trastornosdelhabla y ellenguaje

Introdução: Os tumores do sistema nervoso central (SNC) constituem a segunda neoplasia mais frequente na criança. Os distúrbios tratados pela equipe de fonoaudiologia mais observados em pacientes com tumores são: disfagia, disfonia, alterações de linguagem, transtorno da articulação temporomandibular, disacusia, disartria e paralisia facial. A detecção precoce de alterações fonoaudiológicas em pacientes com tumores pediátricos, na fase do diagnóstico ou início do tratamento, é essencial para um manejo terapêutico mais adequado. Objetivo: descrever as alterações fonoaudiológicas de pacientes pediátricos com diagnóstico de tumor de sistema nervoso central em atendimento durante internação hospitalar. Método: Estudo retrospectivo, com coleta realizada através da pesquisa de dados extraídos de prontuário eletrônico, com dados dos pacientes internados de março de 2016 a agosto de 2018. Para avaliar a associação entre as variáveis categóricas, o teste Qui-quadrado de Pearson foi aplicado. O nível de significância adotado foi de 5% (p<0,05). Resultados: Verificou-se maior relevância nos dados relacionados aos distúrbios de deglutição e motricidade orofacial. Observou-se significância estatística na variável local da lesão - em fossa posterior -, com presença de alterações fonoaudiológicas. Conclusão: A amostra de pacientes oncológicos pediátricos demonstrou alterações fonoaudiológicas, principalmente nas áreas de disfagia e de motricidade orofacial.

Introduction: Central nervous system (CNS) tumors are the second most frequent neoplasm in children. The disorders treated by the speech therapy team most observed in patients with tumors are: dysphagia, dysphonia, language disorders, temporomandibular joint disorder, dysacusis, dysarthria and facial paralysis. Early detection of speech-language pathology changes in patients with pediatric tumors, at the stage of diagnosis or initiation of treatment, is essential for a more appropriate therapeutic management. Objective: to describe speech disorders in pediatric patients diagnosed with a tumor of the central nervous system in care during hospitalization. Method: Retrospective study, with collection performed through the research of data extracted from electronic medical records, with data of patients hospitalized from March 2016 to August 2018. To evaluate the association between categorical variables, Pearson's Chi-square test was applied. The level of significance adopted was 5% (p <0.05). Results: There was greater relevance in the data related to swallowing disorders and orofacial motricity. Statistical significance was observed in the local variable of the lesion - in the posterior fossa -, with the presence of speech-language disorders. Conclusion: The sample of pediatric cancer patients demonstrated speechlanguage disorders, especially in the areas of dysphagia and orofacial motricity.

Introducción: Los tumores del sistema nervioso central (SNC) son la segunda neoplasia maligna más frecuente em niños. Los trastornos tratados por el equipo de terapia del habla más observados en pacientes con tumores son: disfagia, disfonía, transtornos del lenguaje, trastorno de la articulación temporomandibular, disacusis, disartria y parálisis facial. La detección temprana de los câmbios em la patologia del habla y el linguaje en pacientes con tumores pediátricos, em la etapa de diagnóstico o inicio del tratamiento, es esencial para un manejo terapéutico más adecuado. Objetivo: describir los transtornos del habla y el lenguaje de los pacientes pediátricos diagnosticados con tumor del sistema nervioso central em la atención durante la hospitalización. Método: Estudio retrospectivo, com recopilación realizada a través de la investigación de datos extraídos de registros médicos electrónicos, com datos de pacientes hospitalizados de marzo de 2016 a agosto de 2018. Para evaluar la asociación entre variables categóricas, se aplico la prueba de Chi-cuadrado de Pearson. El nivel de significancia adoptado fue del 5% (p<0,05). Resultados: Hubo mayor relevância em los datos relacionados com los trastornos de la deglución y la motricidad orofacial. Se observo importancia estadística em la variable local de la lesión, em la fosa posterior, com la presencia de alteraciones de la patologia del habla y el lenguaje. Conclusión: La muestra de pacientes com cáncer pediátrico demostró la presencia de transtornos del habla y el lenguaje, especialmente em las áreas de disfagia y motricidad orofacial.

Atypical Virchow-Robin SpacesMimicking Cystic Primary Brain Tumor ­ Clinical Report and Literature Review

The Virchow-Robin spaces (VRSs), which are often incidentally observed in modern structural neuroimaging examinations, are small cystic cavities that usually surround the small arteries and arterioles at the level of basal ganglia, the anterior perforated substance and the thalamic-mesencephalic junction. Typically, they have similar physicochemical characteristics to cerebral spinal fluid (CSF) and there is no contrast enhancement on brain CT andMRI images. Its real meaning is unknown, although some contemporary studies have suggested that it might be related to certain traumatic brain injury or several other central nervous system (CNS) disorders, as degenerative diseases. Occasionally, some wide and atypical VRS may be mistaken for primary cystic brain tumors, especially in the context of large and symptomatic lesions, multiple clustered cysts, cortical lesions and if there is adjacent reactive gliosis. The present paper reports four patients who were affected by atypical VRS mimicking brain tumors that required imaging follow-up or even a biopsy to confirm the diagnosis or to indicate the correct approach. Although it is not so unusual, one of them occurred concomitantly and adjacent to a diffuse glioma (co-deleted 1p19q, WHO-GII).

Temozolamide as an adjuvant in glioblastoma. How long? The experience of a cancer center in Colombia / Temozolamide como adyuvancia en glioblastoma. ¿Por cuánto tiempo?. Experiencia en un centro oncológico de Colombia

Abstract Introduction: glioblastoma multiforme is considered to be highly lethal, for which the optimal duration of adjuvant temozolamide chemotherapy has not been determined. Objective: to evaluate survival according to the length of adjuvant chemotherapy based on the standard Stupp platform protocol. Materials and methods: a retrospective cohort analysis of 299 high-grade central nervous system tumors seen at Oncólogos del Occidente, focused solely on glioblastoma multiforme, according to clinical, treatment and outcome variables. Results: one hundred ninety-three patients with glioblastoma; 84 (44%) received standard Stupp platform treatment; mean age 54 years; 55% males; mean tumor size 28,793 mm2; 48% right hemisphere; 21% crossed the midline; 33% had seizures and 42% neurological deficit; 55% Karnofsky less than 70% and 66% RPA IV classification; 77% received radiation with 60.00 Gy or more; 19% had complications; 79% partial resection and 12% total resection; 77% relapsed; at closure, 57% were alive, global survival of 26% and mean of 26 months, with a difference of 31 months for adjuvance of <or> 6 months and 30 months for adjuvance of <or> 12 months, without reaching a median in the 18 and 24 month groups, all of them favoring the group with the longest time. Conclusion: a clear increase in survival is shown with adjuvant temozolamide for periods longer than six months, as well as a tendency towards better results with increased duration of adjuvance.

Resumen Introducción: el glioblastoma multiforme se considera altamente letal, donde la duración óptima de quimioterapia adyuvante con base en temozolamide no ha sido definida. Objetivo: evaluar la sobrevida según la duración de quimioterapia adyuvante basada en el esquema estándar de plataforma Stupp. Material y métodos: análisis de cohorte retrospectiva de 299 tumores del sistema nervioso central de alto grado, valorados en Oncólogos del Occidente enfocado sólo a glioblastoma multiforme según variables clínicas, terapéuticas y de resultados. Resultados: ciento noventa y tres pacientes con glioblastoma, 84 (44%) recibieron manejo estándar tipo plataforma Stupp; edad media 54 años; hombres 55%; tamaño tumoral medio 28.79 mm2; hemisferio derecho 48%; 21% cruzaban línea media; 33% presentaron convulsiones y 42% déficit neurológico; 55% Karnofsky menor a 70% y 66% clasificación RPA IV; 77% recibieron radioterapia con 60.00 Gys o mayor; 19% presentaron complicaciones; resección parcial 79% y 12% total; 77% recayeron; al cierre 57% se encontraban vivos, sobrevida global de 26% y media de 26 meses con diferencia de 31 meses para adyuvancia en <o> a 6 meses y 30 meses en adyuvancia <o> a 12 meses sin alcanzar mediana en los grupos <o> de 18 y 24 meses favoreciendo en todos al grupo de mayor tiempo. Conclusión: se demuestra aumento claro en la sobrevida con el empleo de temozolamide adyuvante por periodos mayores a seis meses y una tendencia a mejores resultados mientras mayor sea el tiempo de adyuvancia.

Intra-Axial Metastatic Angiosarcoma of the Central Nervous System Associated with Anemia, Pulmonary Tuberculosis and Short Survival

Introduction Angiosarcoma (AG) is a malignant mesenchymal neoplasm that predominantly affects the soft tissues and, to variable degrees, expresses themorphological and functional characteristics of the endothelium. The incidence of sarcomas of the central nervous system(CNS) is low (0.5% to 2.7%), and AGs involving the brain are even rarer. Case Description A 45-year-old male patient presented with complaints of headache, nausea, and vomiting. An examination showed bilateral papilledema and a right lung pleurotomy. The patient's previous history included drug addiction, pulmonary tuberculosis, lung abscess, pleural empyema, and pulmonary artery embolization for severe hemoptysis. Computed tomography/magnetic resonance imaging scans revealed a large intra-axial lesion extending into the right parietal and temporal lobes, with hemorrhagic zones. The patient underwent surgical resection of the lesion. Microscopy showed a poorly-differentiated, high-grade malignant tumor composed of plump/epithelioid cells forming small vascular spaces and solid nests, compatible with AG.In the postoperative period, the patient developed recurrent hemoptysis. A biopsy of the tissues adjacent to the pleurotomy determined the diagnosis of pulmonary AG. At 30 days after the resection, the patient died from hemoptysis, hemothorax, lung atelectasis, and intracranial hypertension related to the recurrence of the brain tumor. Conclusion Angiosarcoma is a rare neoplasia related to short survival due to the high proliferative index, which must be considered in patients presenting hemorrhagic tumors. No specific genetic abnormalities have been described for this neoplasia.