Angiogenic potential of the cerebrospinal fluid (CSF) of patients with high-grade gliomas measured with the chick embryo chorioallantoic membrane assay (CAM)

High-grade gliomas are highly vascularized tumors. Neo-angiogenesis plays a key role in tumor growth and resistance to therapy. A cerebrospinal fluid (CSF) sample could be a useful way to obtain pro-angiogenic predictive or prognostic markers at different stages of the disease. As a first step we looked for pro-angiogenic activity in the CSF of patients with high-grade gliomas. We performed the chicken embryo chorio-allantoic membrane (CAM) assay to study the angiogenic potential of the cerebrospinal fluid (CSF), obtained either by lumbar puncture (LP) or craniotomy from six patients with high-grade brain tumors (three glioblastoma (WHO grade IV), one anaplastic oligodendroglioma (WHO grade III), two anaplastic ganglioglioma (WHO grade III)), and four healthy controls. Significantly increased neo-angiogenesis was observed on the surface of the growing CAM in the 6 patients with high-grade gliomas compared to controls (3.69 ± 1.23 versus 2.16 ± 0.97 capillaries per area (mean ± SD), p<0.005). There was no statistical difference related to the hystological grade of the tumor (WHO grade III or IV), previous treatment (radio-chemotherapy plus temozolomide, temozolomide alone or no treatment), or the site of CSF sample (surgery or lumbar puncture). Our results suggest a pro-angiogenic potential in the CSF of patients with high-grade gliomas.

Actividad angiogénica comparada de líquido cefalorraquídeo de pacientes con tumores primarios del sistema nervioso central / Compared angiogenic activity of cerebrospinal fluid of patients with primary central nervous system tumors

Introducción: Los tumores cerebrales continúan siendo una patología de mal pronóstico, lo que se refleja en la baja expectativa de vida de quienes los padecen. La angiogénesis es un proceso cardinal en el crecimiento tumoral y en la producción de metástasis. No obstante el conocimiento de los mecanismos subyacentes a la oncogénesis, las terapias continúan obteniendo resultados modestos. Está demostrado que el parénquima tumoral secreta factores que estimulan la cascada angiogénica. Sin embargo, no existen trabajos que evalúen el efecto angiogénico del líquido cefalorraquídeo (LCR). La hipótesis propuesta en este trabajo es que el LCR de los pacientes con tumores primarios del sistema nervioso central (SNC), posee en sí mismo propiedades angiogénicas. Material y Método: Estudio experimental preclínico. Se utilizó, en ciento ochenta huevos de gallina White Leghorn, el modelo de membrana alantocoriónica (MAC) de pollo. Estos huevos fueron incubados y sobre la membrana se implantaron filtros de metilcelulosa con líquidos cefalorraquídeos de pacientes con diferentes tumores cerebrales. Al grupo control se le adicionó suero fisiológico. Tras diez días de incubación se realizaron cortes histológicos de las muestras y se procedió al conteo de vasos sanguíneos en un microscopio con rejilla graduada. Resultados: Se demostró con significancia estadística (p<0,05) que existe efecto angiogénico en el LCR de pacientes con tumores primarios del SNC. Discusión: A partir de los resultados obtenidos, podemos proyectar futuros trabajos hacia nuevas terapias enfocadas en la angiogénesis diferencial. Los factores angiogénicos presentes en el LCR podrían constituir un nuevo blanco terapéutico contra los tumores cerebrales.

Introduction: Nowadays, brain tumors remains being a poor-prognosis pathology, which is reflected in the low life expectancy of the patients. The angiogenesis, is a fundamental process in the tumoral growing and the metastatic feasibility. In spite of knowing of the underlying mechanism of the oncogenesis, therapies still get poor results. It is demonstrated that tumoralparenchyma secretes factors that enhance the angiogenic cascade. However, any work has ever evaluated the angiogenic effect in the cerebrospinal fluid (CSF) itself. We hypothesize that CSF belonging of patients with primary central nervous system (CNS) brain tumors, presents angiogenic properties on their own. Material and Method: Preclinical experimental trial. In 180 eggs of White Legorn chicken it was used the chorioallantoic membrane (CAMA) assay. This eggs were incubated for tendays and over the membrane were implanted methylcellulose filters containing cerebrospinal fluid coming from patients affected by different brain tumors. The control group was instilledwith saline solution. It was performed different histological sections of the samples and then proceeded to the counting of the vessels in a microscope with a squared grille inside it. Results:We demonstrated with statistical significance (p<0.05) that CSF from primary brain tumor’s affected patients presents angiogenic effect. Discussion: Owing the presented results, we can plan future investigations targeting new therapies focused on the differential angiogenesis. The angiogenic factors in the CSF could represent a new therapeutic target against brain tumors.

Elevated cerebrospinal fluid beta-2 microglobulin as a tumor marker in a patient with myeloma of the central nervous system

Myeloma involvement of the nervous system is rare. Extensive literature review revealed only a few cases reported from different parts of the world. The presence of CNS symptoms and detection of plasma cells in the CSF is the usual basis of diagnosis. In addition, immunoelectrophoresis and immunofixation for detection of monoclonal protein confirm the diagnosis in some cases, while some authors used flow cytometry and cytogenetic studies on CSF. Reports of multiple myeloma also include unfavorable cytogenetic abnormalities of chromosome 13. We report a case with relapsed CNS multiple myeloma with the detection of elevated beta-2 microglobulin [beta2M] as a tumor marker in the CSF

Líquido cefalorraquiano no diagnóstico de metástase cérebro-meníngea de melanoma maligno derivado de nevo melanocítico gigante congênito: relato de caso / Cerebrospinal fluid in the diagnosis of the cerebro-meningeal metastasis from malignant melanoma arising from giant congenital melanocytic nevus: case report

Relatamos o caso de um paciente, de 28 anos, portador de nevo melanocítico gigante congênito(NMGC), com transformaçao em melanoma e metátase no sistema nervoso central (SNC). Descreveremos resumidamente as características patológicas de ambas as lesoes (NMGC e melanoma), a frequência de malignizaçao no NMGC, os órgaos mais frequentemente acometidos pelas metástases do melanoma - dando ênfase ao acometimento do SNC - além dos fatores que podem levar à malignizaçao do NMGC, os exames usados para o diagnóstico das metástases no SNC - ressaltando a importância do líquido cefalorraquiano - e algumas modalidades terapêutica para o melanoma com acometimento do SNC.

Cerebrospinal fluid cytomorphologic findings in 41 intracranial tumors

O objectivo fundamental desta revisäo retrospectiva dos dados clínicos e do estudo do líquido céfalo-raquidiano (LCR) de 41 doentes com tumores intracranianos diagnosticados entre 1975 e 1989 é análisar a importância do achado de células neoplásicas no LCR, principalmente quando o recurso à tomografia computadorizada e ressônancia magnética cerebrais era raro. Outro objectivo diz respeito ao estudo das alteraçöes proteicas do LCR nos tumores cerebrais. A análise do LCR compreendeu a contagem celular, a observaçäo dos quadros citomorfológicos obtidos após sedimentaçäo, o doseamento das proteínas totais e a determinaçäo dos perfis electroforéticos. Encontraram-se células tumorais em 12 doentes (29 por cento): meduloblastomas - 6, meningites carcinomatosas - 3, glioblatoma multiforme - 1, ependimoma - 1, metástases cerebrais -1; em 2 casos este achado foi inesperado. Na maior parte dos casos a localizaçäo do tumor perto do sistema ventricular favoreceu a esfoliaçäo celular. Embora a pleocitose fosse rara e näo se correlacionasse com a presença de células neoplásicas, verificamos que na maioria dos casos, incluindo todos aqueles com etiologia "positiva", os quadro citomorfológicos eram patológicos. Os nossos resultados mostram que a pesquisa de células tumorais no LCR continua a ser util e o seu achado particularmente relevante quando inesperado

Linfoma primario cerebral post trasplante renal: comunicación de un caso y revisión de la literatura / Primary brain lymphoma post renal transplantation: report of a case and literature review

We report a 30 years old male, presenting eight years after a kidney transplant with intracraneal hypertension and two hyperdense masses detected in a brain CAT scan, whose histopathological study revealed a giant cell immnunoblastic lymphoma. The patient was successfully treated with chemo and radiotherapy and after 18 months of follow up there is no evidence of tumoral relapse. Immunocompromised patients specially transplant recipients, had a several fold higher incidence of malignant tumors, specially primary lymphomas of the central nervous system. These are generally of B type, are associated to Epstein Barr virus and have a high mortality. Cancer must be considered in the differential diagnosis of masses of uncertain origin in transplant recipients

Presentación primaria de reticulohistiocitosis maligna meníngea: caso clínico / Primary presentation of malignant meningeal reticulohistiocytosis: clinical case

Se presenta en detalle el caso clínico de un paciente con una meningitis reticulohistiocitaria maligna primaria, entidad no descrita previamente y tratada exitosamente con metotrexato y citosina arabinósido, administrados intratecalmente. Se destacan las múltiples posibilidades de diagnóstico diferencial y se pone énfasis en la importancia diagnóstica del estudio citomorfológico e inmunocitoquímico del líquido cefalorraquídeo

Eosinofilorraquia em tumor maligno: apresentaçäo em caso / CSF eosinophils in malignant tumor: a case report

A presença de grnaulócitos cosinófilos associados a tumores malignos que acometem o sistema nervoso tem sido raramente comunicada. O propósito deste registro é apresentar o caso de um paciente com 47 anos de idade com tumor cerebral maligno (astrocitoma grau III), cujo estudo citológico do LCR revelou quadro inflamatório com presença de elevada percentagem de granulócitos cosinófilos