Evaluation of the melting temperature of TaqMan probes as a genotyping method for IDH1, IDH2, and H3F3A in pediatric astrocytomas / Evaluación del método de temperatura de disociación de sondas TaqMan para la genotipificación de IDH1, IDH2 y H3F3A en astrocitomas pediátricos

Abstract Background: Astrocytomas are cancer tumors of the central nervous system and represent the most common type of solid tumors during human childhood. In 2016, the World Health Organization established a molecular classification system to regroup tumor entities to achieve a more accurate diagnosis and a better clinical decision-making and selection of treatment in patients with these types of tumors. Methods: We evaluated a genotyping assay for rapid and cost-effective mutation detection in astrocytomas using TaqMan probes in an asymmetric polymerase chain reaction (PCR) assay. Results: Four diffuse astrocytomas (Grade II), three anaplastic astrocytomas (Grade III), and four glioblastomas (Grade IV) were sequenced, and all of them displayed the wild-type (WT) sequence. We tried to set up this melting analysis for the genotyping of pediatric astrocytomas by identifying the specific melting temperatures of the TaqMan probes due to the presence of the WT sequences in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and H3.3 histone A genes (H3F3A). We used an IDH1-TaqMan probe to identify the WT status of IDH1 in two different WT deoxyribonucleic acid (DNA) templates (pilocytic and diffuse astrocytoma) and obtained four melting temperature values ranged from 65.6 to 92.2°C. Furthermore, only four out of 29 reactions displayed amplification of the DNA template. Sanger sequencing was faster and more reliable to detect the gene status in all the sequenced samples. Conclusions: We conclude that conventional Sanger sequencing remains the gold standard for the genotyping of pediatric astrocytomas.

Resumen Introducción: Los astrocitomas son un tipo de cáncer que afecta al sistema nervioso central y representan el tumor sólido más común durante la infancia. En el año 2016, la Organización Mundial de la Salud estableció un sistema de clasificación molecular para reagrupar tumores con identidades genéticas similares y lograr un diagnóstico más preciso, lo que lleva a tomar las decisiones clínicas idóneas al elegir el tratamiento de pacientes con este tipo de tumores. Métodos: Se evaluó un protocolo que involucra el uso de sondas TaqMan en un ensayo de reacción en cadena de la polimerasa asimétrica para la detección de mutaciones en astrocitomas. Se secuenciaron cuatro astrocitomas difusos (Grado II), tres astrocitomas anaplásicos (Grado III) y cuatro glioblastomas (Grado IV). Se intentó establecer las condiciones del análisis para la genotipificación de los astrocitomas pediátricos mediante la identificación de las temperaturas de disociación específicas de las sondas TaqMan producidas por la prescencia de las secuancias WT en los genes isocitrato deshidrogenasa 1 y 2 (IDH1, IDH2) y H3.3 histona A (H3F3A). Resultados: Los astrocitomas mostraron la secuencia wild type (WT) (silvestre) de los genes. Se utilizó una sonda TaqMan IDH1 para identificar el estado de este gen en dos templados WT de DNA (astrocitoma pilocítico y difuso) y se obtuvieron cuatro valores de temperatura de disociación (65.6-92.2 °C). Solo cuatro de las 29 reacciones mostraron amplificación de DNA. La secuenciación de Sanger fue más rápida y confiable para detectar el estado de los genes en todas las muestras. Conclusiones: La secuenciación de Sanger sigue siendo la técnica más práctica para la genotipificación de astrocitomas pediátricos.

Uso de nimotuzumab en paciente con astrocitoma anaplásico / Nimotuzumab in the treatment of a patient with anaplastic astrocytoma

Introducción: Nimotuzumab es una inmunoglobina de isotipo IgG1, obtenido por tecnología de ADN recombinante. La expectativa de vida de niños con tumores cerebrales recurrentes, refractarios a tratamientos a la cirugía, la radioterapia y la quimioterapia es de un mes aproximadamente. Con este tratamiento la supervivencia alcanza 44,5 meses. Objetivos: Presentar el caso clínico de un paciente con diagnóstico de Astrocitoma anaplásico que recibió tratamiento oncoespecífico concurrente con Nimotuzumab. Presentación de caso: Se realizó la descripción del diagnóstico, tratamiento y evolución de un paciente de 31 años de edad que fue diagnosticado con una neoplasia del sistema nervioso central. (Astrocitoma anaplásico). Recibió la combinación terapéutica de cirugía, radioterapia y anticuerpos monoclonales, lográndose una sobrevida de 39 meses. Conclusiones: La adición del anticuerpo monoclonal al tratamiento estándar de los tumores cerebrales aumentó la sobrevida del paciente, convirtiéndose en una alternativa terapéutica segura, ventajosa y factible como parte del tratamiento convencional en las condiciones asistenciales(AU)

Introduction: Nimotuzumab is an IgG1 isotype immunoglobin, obtained by recombinant DNA technology. Life expectancy is approximately one month in children with recurrent brain tumors, refractory to treatments to surgery, radiotherapy and chemotherapy. Survival reaches 44.5 months when using Nimotuzumab. Objectives: To report the clinical case of a patient diagnosed with anaplastic astrocytoma who received concurrent oncospecific treatment with Nimotuzumab. Case report: This paper describes the diagnosis, treatment and evolution of a 31-year-old male patient with neoplasm of the central nervous system (Anaplastic astrocytoma). He received the therapeutic combination of surgery, radiotherapy and monoclonal antibodies, achieving a survival of 39 months. Conclusions: The adding the monoclonal antibody to the standard treatment of brain tumors increased patient survival, making it a safe, advantageous and feasible therapeutic alternative as part of conventional treatment in healthcare conditions(AU)

Astrocitoma medular de alto grado no infiltrante / Astrocitoma medular não infiltrativo. Apresentação do caso / Non-infiltrating medullary astrocytoma. Case presentation

Se presentó el caso de una paciente femenina de 20 años de edad que acudió al servicio de Neurocirugía por presentar dolor en la región lumbar. Al interrogatorio la paciente refirió tener constipación, retención urinaria y dolor lumbar. En los exámenes complementarios lo más significativo fue la resonancia magnética nuclear que mostró una imagen hiperdensa a nivel de D12-L5. Se realizó laminectomía de D12-L5, durotomía y extracción tumoral, fijación transpedicular con tornillos ubicados en T12-L1-L3-L4 con barras de titanio, se obtuvo un diagnóstico de astrocitoma grado II-III. Al analizar los diferentes aspectos del caso en cuestión, los investigadores concluyen que con la conducta terapéutica tomada con este caso se sientan las bases para un correcto manejo de posteriores pacientes(AU)

The case of a 20-year-old female patient who went to the Neurosurgery department for presenting pain in the lumbar region was presented. At the interrogation, the patient reported having constipation, urinary retention and low back pain. In the complementary tests, the most significant was nuclear magnetic resonance, which showed a hyperdense image at the level of D12-L5. Laminectomy of D12-L5, durotomy and tumor extraction, transpedicular fixation with screws located in T12-L1-L3-L4 with titanium bars was performed, a diagnosis of grade II-III astrocytoma was obtained. When analyzing the different aspects of the case in question, the researchers conclude that with the therapeutic behavior taken with this case, the basis is laid for the correct management of subsequent patients(AU)

Foi apresentado o caso de uma paciente de 20 anos que foi ao departamento de Neurocirurgia por apresentar dor na região lombar. No interrogatório, o paciente relatou constipação, retenção urinária e lombalgia. Nos testes complementares, o mais significativo foi a ressonância magnética nuclear, que mostrou uma imagem hiperdensa ao nível de D12-L5. Foi realizada laminectomia de D12-L5, durotomia e extração de tumores, fixação transpedicular com parafusos localizados em T12-L1-L3-L4 com barras de titânio e foi obtido o diagnóstico de astrocitoma grau II-III. Ao analisar os diferentes aspectos do caso em questão, os pesquisadores concluem que, com o comportamento terapêutico adotado neste caso, é lançada a base para o manejo correto dos pacientes subsequentes)AU=

Síndrome diencefálico en un niño con desnutrición crónica e hiperactividad / Diencephalic syndrome in a child with chronic malnutrition and hyperactivity

El síndrome diencefálico es una causa infrecuente de desnutrición. Se produce por la disfunción del hipotálamo y está asociado a tumores del encéfalo. Los pacientes presentan una grave y progresiva pérdida de peso, aunque el apetito y la ingesta calórica son, por lo general, adecuados. Característicamente, los síntomas neurológicos son tardíos, lo que retrasa la sospecha diagnóstica. Se presenta a un paciente de 2 años y 6 meses de edad con desnutrición crónica grado II, derivado con diagnóstico presuntivo de enfermedad celíaca con mala adherencia y fracaso del tratamiento. Durante la internación, se arribó al diagnóstico de síndrome diencefálico secundario a un astrocitoma pilocítico grado I.

Diencephalic syndrome is an infrequent cause of malnutrition. It is produced by a malfunctioning hypothalamus, and it is related to encephalic tumors. Patients present a serious and progressive weight loss although the appetite and calorie intake are, usually, adequate. Neurological symptoms typically have a late appearance, delaying diagnostic suspicion. We present a patient aged 2 years and a half with grade II chronic malnutrition, referred with presumptive diagnosis of celiac disease, with poor adherence and treatment failure. During hospitalization, diagnosis of diencephalic syndrome secondary to grade I pilocytic astrocytoma was reached.

Astrocitoma pilocítico en niños: Reporte de un caso / Pilocytic astrocytoma in children. Case Report

Se reporta el caso de un niño de 10 años que se presentó con dos semanas de enfermedad caracterizada por cefalea, vómitos, marcha tambaleante y somnolencia. El examen clínico reveló bradilalia, ataxia, hiperreflexia, nistagmo horizontal y vertical, parálisis del VI nervio craneal izquierdo y signos de frontalización. En la tomografía y resonancia cerebrales se encontró hidrocefalia obstructiva por un tumor de la fosa posterior. La anatomía patológica reveló Astrocitoma Pilocítico grado I (WHO)...

We report a 10 years old boy with 2 weeks of symptoms characterized by headache, vomiting, staggering gait and drowsiness. The initial clinical examination showed bradilalia, ataxia, hyperreflexia, horizontal and vertical nystagmus, VI left cranial nerve paresis and signs of frontalization. The brain CT and MRI showed a posterior fossa tumor causing hydrocephaly. The histhopatology revealed grade I pilocytic astrocytoma (WHO)...

Correlação entre ressonância magnética, expressão do Ki-67 e p53, e prognóstico em astrocitomas / Correlation between Magnetic Ressonance Image, Expression of Ki-67 and p53, and Prognosis in Astrocytomas

Objetivos Avaliar a correlação entre a expressão do Ki-67 e do p53 em astrocitomas graus II a IV, as características da RM e seu prognóstico. Métodos e Resultados Este é um estudo longitudinal retrospectivo do tipo coorte histórico que avaliou 45 pacientes. O prognóstico foi avaliado mediante revisão dos prontuários. A avaliação imuno-histoquímica foi realizada no Serviço de Patologia do HB. A avaliação das imagens de RMfoi feita no Serviço de Radiologia. A sobrevidamédia dos pacientes foi de 581,4 dias no grau IV; 1.704,8 dias no grau III; e 1.044,8 dias no grau II. Para cada grau, os seguintes percentuais de células positivas de Ki-67 e p53 tiveram respectivamente: 97,8 e 80% de positividade no grau IV; 72,7 e 73,4% de positividade no grau III; e 70 e 80% de positividade no grau II. Observou-se diferença estatística na expressão de Ki-67 entre os graus III e IV (P » 0,014). A RM mostrou especificidade de 64% e sensibilidade de 100% para a presença de necrose tumoral. Conclusão Concluímos que a análise da positividade do Ki-67 e do p53 não permite sua correlação com a sobrevida dos pacientes, apesar de ambos terem sua frequência distribuída de maneira semelhante. A RM tem especificidade moderada em relação ao exame patológico.rada em relação ao exame patológico.

Objectives To evaluate the correlation between the expression of Ki -67 and p53 in astrocytomas grades II to IV, the characteristics of MRI and its prognosis. Methods This was a retrospective longitudinal cohort study of its kind that evaluated 45 patients. Prognosis was assessed by review of medical records. The immunohistochemical evaluation was performed at the Pathology Service of HB. The evaluation of MRI images was taken in the Radiology Department. The median survival of patients was 581.4 days in grade IV; 1704.8 days in grade III; 1044.8 days in grade II. For each grade, the following percentages of cells positive for Ki -67 and p53 , respectively : 97.8% and 80% had a positive grade IV ; 72.7% and 73.4% positivity in grade III ; 70% and 80% in stage II positivity . There was statistical difference in Ki -67 between grades III and IV (P » 0.014).MRI showed 64% specificity and 100% sensitivity for the presence of tumor necrosis Conclusion We conclude that the analysis of the positivity of Ki -67 and p53 expression does not allow correlation with patient survival, although both their frequency distributed similarly. MRI hasmoderate specificity in relation to pathological examination.

Astrocitoma pilocítico da região selar/suprasselar determinando manifestações endócrinas / Pilocytic astrocytoma of sellar/suprasellar region determining endocrine manifestations

Pilocytic astrocytoma (PA) is a grade I glial neoplasm arising mainly in the cerebellum of children. Herein, the authors report a case of PA in a 21 year-old male patient, who presented headache, vomiting and delayed pubertal development. Serum level of cortisol and testosterone corresponded to 32.8 ug/dl and 0.19 ng/ml, respectively. The computed tomography/magnetic resonance (CT/RM) imaging showed an expansive process compromising suprasellar/hypothalamic region and determining hydrocephalus. The patient underwent resection of the process. Histological evaluation revealed a glial neoplasm constituted by loose glial tissue, small microcysts, areas of dense piloid tissue and Rosenthal fibers. The neoplastic cells were immunoreactive for glial fibrillary acidic protein (GFAP) and negative for chromogranin and synaptophysin. The diagnosis of PA was then established.

O astrocitoma pilocítico (AP) é uma neoplasia glial grau I encontrada principalmente no cerebelo de crianças. Os autores relatam um caso de AP em paciente masculino, 21 anos de idade, que apresenta cefaleia, vômitos e retardo do desenvolvimento puberal. Os níveis séricos de cortisol e testesterona corresponderam a 32,8 ug/dl e 0,19 ng/ml. A tomografia computadorizada/ressonância magnética (TC/RM) identificaram um processo expansivo que comprometia a região suprasselar/hipotalâmica e determinava hidrocefalia.O paciente foi submetido à ressecção do processo. À microscopia, foi identificada uma neoplasia glial constituída por tecido glial frouxo, pequenos microcistos, áreas de tecido piloide denso e fibras de Rosenthal. As células neoplásicas foram imunopositivas para glial fibrillary acidic protein (GFAP) e negativas para cromogranina e sinaptofisina. O diagnóstico de AP foi, então, estabelecido.

An Infant with Prenatally Diagnosed Congenital Anaplastic Astrocytoma Who Remains Disease-Free after Proton Therapy

The authors present a rare of prenatally diagnosed congenital anaplastic astrocytoma. A 9-month-old boy had three recurrences despite two surgical resections and various chemotherapeutic regimens. He underwent the 3rd gross tumor removal at 11 months of age, followed by proton therapy, and now he remains disease-free for 3 yr without a significant neurocognitive dysfunction. This is the 1st case of a pediatric tumor treated by proton therapy in Korea, and proton therapy may be a treatment of choice for a congenital anaplastic astrocytoma in infants and young children, considering limitation of radiation therapy.

Application of 31P MR Spectroscopy to the Brain Tumors

OBJECTIVE: To evaluate the clinical feasibility and obtain useful parameters of 31P magnetic resonance spectroscopy (MRS) study for making the differential diagnosis of brain tumors. MATERIALS AND METHODS: Twenty-eight patients with brain tumorous lesions (22 cases of brain tumor and 6 cases of abscess) and 11 normal volunteers were included. The patients were classified into the astrocytoma group, lymphoma group, metastasis group and the abscess group. We obtained the intracellular pH and the metabolite ratios of phosphomonoesters/phosophodiesters (PME/PDE), PME/inorganic phosphate (Pi), PDE/Pi, PME/adenosine triphosphate (ATP), PDE/ATP, PME/phosphocreatine (PCr), PDE/PCr, PCr/ATP, PCr/Pi, and ATP/Pi, and evaluated the statistical significances. RESULTS: The brain tumors had a tendency of alkalization (pH = 7.28 +/- 0.27, p = 0.090), especially the pH of the lymphoma was significantly increased (pH = 7.45 +/- 0.32, p = 0.013). The brain tumor group showed increased PME/PDE ratio compared with that in the normal control group (p = 0.012). The ratios of PME/PDE, PDE/Pi, PME/PCr and PDE/PCr showed statistically significant differences between each brain lesion groups (p < 0.05). The astrocytoma showed an increased PME/PDE and PME/PCr ratio. The ratios of PDE/Pi, PME/PCr, and PDE/PCr in lymphoma group were lower than those in the control group and astrocytoma group. The metastasis group showed an increased PME/PDE ratio, compared with that in the normal control group. CONCLUSION: We have obtained the clinically applicable 31P MRS, and the pH, PME/PDE, PDE/Pi, PME/PCr, and PDE/PCr ratios are helpful for differentiating among the different types of brain tumors.

Astrocitoma pilomixoide de fossa posterior em criança: relato de caso / Pilomyxoid astrocytoma of the posterior fossa in children: case report

Descrever um caso de astrocitoma pilomixoide, um tumor do sistema nervoso central raro, descrito e classificado recentemente diante de sintomatologia e achados pouco específicos. Análise e descrição de um caso de astrocitoma pilomixoide submetido a tratamento cirúrgico no Instituto José Frota, Fortaleza, Ceará. Paciente evolui com regressão importante dos sintomas, sem indícios de recidiva tumoral. O diagnóstico e a classificação correta dos tumores cerebrais são de extrema importância clínica, pois modificam de forma impactante o prognóstico, assim como a abordagem terapêutica.

To describe a pilomyxoid astrocytoma case, a tumor of the central nervous system rare recently described and classified in the face of a specific symptomatology and little found. Analysis and description of a case of pilomyxoid astrocytoma underwent surgical treatment at the José Frota Institute in Fortaleza, Ceará. Patient developed a significant decrease of symptoms without evidence of tumor relapse. The diagnosis and the correct classification of cerebral tumors are of extreme clinical importance, because it changes so as impacting the prognosis as well as therapeutic approach.

Practical value of MIB-1 index in predicting behavior of astrocytomas.

Background : The MIB-1 labeling index (LI) has proved to be useful in assigning grading and prognosis to astrocytomas. The purpose of our study was to analyze the utility of MIB-1 LI in differentiating astrocytomas of varying grades and the possible relationships of MIB-1 LI with clinical parameters like age and sex. We also wanted to study the prognostic role of MIB-1 index in predicting behavior of astrocytomas. Materials and Methods : Our study included 145 patients with astrocytic tumors of varying grades. Immunolabeling for all patients was done using MIB-1 antibody. Survival data could be obtained for 64 patients. A Mann-Whitney U test was used to test the difference in MIB-1 LI between different histological grades. The univariate analysis was done by the Kaplan-Meier method, and the multivariate analysis for survival was performed using the Cox proportional hazard model. Results : Significant differences were noted in mean MIB-1 LI of high-grade and low-grade diffuse astrocytomas. MIB-1 LI did not vary significantly with age and sex. Univariate analysis showed favorable prognostic factors for low histopathological grade, young patient age and low MIB-1 LI; however, multivariate analysis showed that only histopathological grade had independent prognostic significance. Conclusions : Our study proves that MIB-1 LI is not dependent on factors like age and sex and is solely dependent on histological grade. Though the average level of MIB-1 LI varies considerably in the different grades of astrocytomas, considerable overlap can be observed between them. MIB-1 LI is a very useful adjunct to the histopathological diagnosis and can be of great help in situations where the clinical and radiological findings do not correlate with histological diagnosis.

A Spinal Cord Astrocytoma and Its Concurrent Osteoblastic Metastases at the Time of the Initial Diagnosis: a Case Report and Literature Review

Bone metastasis from a spinal cord astrocytoma has been reported only twice in the English medical literature. It is generally known that bone metastasis is found after the initial diagnosis with/without intervening surgery rather than being found at the time of the diagnosis of astrocytoma. The purpose of this article is to report for the first time a case of concurrent bone metastasis from a spinal cord astrocytoma at the time of diagnosing the spinal cord astrocytoma.

Retinoblastoma and retinal astrocytoma: unusual double tumor in one eye

Retinoblastoma is the most common intraocular neoplasm in children. Glial tumor of the retina and optic nerve head are considered to be congenital and are therefore classified as hamartomas. Concurrent occurrence of these tumors in one eye is uncommon and by reviewing the studies, a few cases have been reported. We report a 9 years old boy with eye enucleation and concurrent occurrence of retinoblastoma and astrocytoma in one eye as two separate and different masses. Although retinoblastoma and astrocytoma are two distinct tumors and their concurrent occurrence in one eye is rare, concurrent occurrence of these tumors may suggest differentiation of these two tumors from a neuroectodermal primary cell

Intramedullary tumors in children: analysis of 24 operated cases / Tumores intramedulares em crianças: análise de 24 casos operados

Intramedullary tumors are rare. The authors reviewed 24 cases operated between 1996 and 2006. The study assessed the clinical characteristics and surgical results based upon the neurological function. METHOD: Medical records of patients with intramedullary astrocytoma and ependymoma were reviewed. The minimal follow up time was 6 months and, at the end of this period, a comparative analysis of the neurological function was performed based using the McCormick scale score. RESULTS: Most patients had astrocytoma (75 percent). Male gender was more prevalent (58.3 percent). The most common type of tumor was graded as I or II, and in three cases these were malignant. The total resection of the tumor was achieved in 20.8 percent of the cases. The statistical analysis did not show a statistically significant difference between preoperative and postoperative grades at McCormick scale. CONCLUSION: The authors concluded that microsurgery to intramedullary tumors did not significantly alter the neurological function after six months.

Os tumores intramedulares são doenças raras. Os autores analisaram 24 casos operados entre 1996 e 2006. O estudo analisou as características clínicas e o resultado da cirurgia quanto à função neurológica. MÉTODO: Foram analisados pacientes com astrocitomas e ependimomas intramedulares. O tempo mínimo de acompanhamento foi de 6 meses e ao final deste período foi realizada a avaliação comparativa da variação do estado neurológico baseado na escala de McCormick. RESULTADOS: A maioria dos pacientes era de astrocitoma (75 por cento). O gênero masculino foi mais prevalente (58,3 por cento). A maioria dos tumores era de grau I ou II, 3 casos eram malignos. A ressecção total do tumor ocorreu em 20,8 por cento dos casos. A avaliação estatística demonstrou que não houve diferença significativa entre o estado neurológico na escala de McCormick pré-operatória e pós-operatória. CONCLUSÕES: Os autores concluem que a microcirurgia para ressecção dos tumores intramedulares não ocasionou variação funcional significativa nos pacientes após seis meses da cirurgia.

H magnetic resonance spectroscopy assessment of the temozolomide response in peaditric pilocytic astrocytomas

Pilocytic Astrocytomas (PA) treatment and prognosis is variable depending on location. ¹H Magnetic Resonance Spectroscopy (MRS) is used to characterize tumor metabolism providing additional information to the Magnetic Resonance Imaging (MRI) evaluation assessing the therapy response. This study was designed to evaluate brain metabolic changes that result from Temozolomide (TMZ) administration on pediatric PA using MRS. Twenty children with PA were studied. We performed MRI and MRS pretreatment and after 12 months of therapy on a 3.0 Tesla scanner in order to monitor the chemotherapy response to 5-day treatment with oral TMZ (200 mg/mt² x day) given every 28 days for 12 cycles. Multivoxel Proton Spectroscopic Imaging was performed using a Point Resolved Spectroscopy sequence (PRESS). Analysis of Variance (ANOVA) was applied to the results in order to evaluate the possible statistical differences. Pairwise comparisons with Bonferroni correction test were assessed in order to verify the differences among ratio means. It was observed a significant decrease in Cho/Cr ratio (p<0.05) and a significant increase in NAA/Cr ratio (p<0.05) while TMZ therapy was taking place. These results are linked with tumor size reduction (r = 0.95, p< 0.05) detected by MRI. Results show MRS can detect early tumor reaction to therapy prior to MRI. Therefore, MRS could provide a useful tool to monitor the answer of pediatric PA to TMZ. The link between metabolic markers changes due to TMZ treatment assessed by MRS and the tumor volume reduction may also provide a fertile ground to developa TMZ-based therapy for pediatric PA and to predict its efficacy to improve PA’s response to treatment.

Multicentric astrocytoma presenting with supra- and infratentorial involvement: a case report

This report describes the case of a 56 year-old man with a history of diplopia. His brain imaging showed multiple lesions with a metastatic appearance, however all investigations to determine the primary source of malignancy were negative. The patient underwent a brain biopsy, which was positive for anaplastic astrocytoma, a rare tumor that should be considered in the differential diagnosis of secondary brain tumors