The Role of Fibroblast Activation Protein in Glioblastoma and Gliosarcoma: A Comparison of Tissue, 68Ga-FAPI-46 PET Data, and Survival Data.

Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68Ga-FAP inhibitor (FAPI)-46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0-3, with higher values indicating stronger expression). Additionally, 68Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue (P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUVmean and SUVpeak of 68Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUVmean and SUVpeak in 68Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis.

Transformation of IDH-wildtype glioblastoma to gliosarcoma with features of osteosarcoma.

Gliosarcoma (GS) is a rare variant of IDH-wildtype glioblastoma. It is classified as grade 4 in the latest WHO CNS classification of both glial and mesenchymal components. Gliosarcoma may arise de novo or secondary from glioblastoma. It occurs in up to 2% of patients diagnosed with glioblastoma. We present a case report of a 51-year-old patient who was initially diagnosed with glioblastoma multiforme, which transformed into secondary gliosarcoma with an osteosarcoma component 16 months after the initial diagnosis. We believe that increasing reporting of secondary gliosarcoma (sGS) will be helpful in understanding, diagnosing and providing more effective treatment for this cancer.

Molecular signature of stem-like glioma cells (SLGCs) from human glioblastoma and gliosarcoma.

Glioblastoma multiforme (GBM) and the GBM variant gliosarcoma (GS) are among the tumors with the highest morbidity and mortality, providing only palliation. Stem-like glioma cells (SLGCs) are involved in tumor initiation, progression, therapy resistance, and relapse. The identification of general features of SLGCs could contribute to the development of more efficient therapies. Commercially available protein arrays were used to determine the cell surface signature of eight SLGC lines from GBMs, one SLGC line obtained from a xenotransplanted GBM-derived SLGC line, and three SLGC lines from GSs. By means of non-negative matrix factorization expression metaprofiles were calculated. Using the cophenetic correlation coefficient (CCC) five metaprofiles (MPs) were identified, which are characterized by specific combinations of 7-12 factors. Furthermore, the expression of several factors, that are associated with GBM prognosis, GBM subtypes, SLGC differentiation stages, or neural identity was evaluated. The investigation encompassed 24 distinct SLGC lines, four of which were derived from xenotransplanted SLGCs, and included the SLGC lines characterized by the metaprofiles. It turned out that all SLGC lines expressed the epidermal growth factor EGFR and EGFR ligands, often in the presence of additional receptor tyrosine kinases. Moreover, all SLGC lines displayed a neural signature and the IDH1 wildtype, but differed in their p53 and PTEN status. Pearson Correlation analysis identified a positive association between the pluripotency factor Sox2 and the expression of FABP7, Musashi, CD133, GFAP, but not with MGMT or Hif1α. Spherical growth, however, was positively correlated with high levels of Hif1α, CDK4, PTEN, and PDGFRß, whereas correlations with stemness factors or MGMT (MGMT expression and promoter methylation) were low or missing. Factors highly expressed by all SLGC lines, irrespective of their degree of stemness and growth behavior, are Cathepsin-D, CD99, EMMPRIN/CD147, Intß1, the Galectins 3 and 3b, and N-Cadherin.

Competing Risk Model to Determine the Prognostic Factors for Patients with Gliosarcoma.

BACKGROUND: Gliosarcoma (GSM) is a highly aggressive variant of brain cancer with an extremely unfavorable prognosis. Prognosis is not feasible by traditional methods because of a lack of staging criteria, and the present study aims to screen more detailed demographic factors to predict the prognostic factors of the tumors. METHODS: For this study, we extracted data of patients diagnosed with GSM from the SEER (Surveillance Epidemiology and End Results) database between 2000 and 2019. To account for the influence of competing risks, we used a Cumulative Incidence Function. Subsequently, univariate analysis was conducted to evaluate the individual variables under investigation. Specifically for patients with GSM, we generated cumulative risk curves for specific mortality outcomes and events related to competing risks. In addition, we used both univariate and multivariate Cox analysis to account for non-GSM-related deaths that may confound our research. RESULTS: The competing risk model showed that age, marital status, tumor size, and adjuvant therapy were prognostic factors in GSM-related death. The analysis results showed that older age (60-70 years, ≥71 years) and larger tumor size (≥5.3 cm) significantly increased the risk of GSM-related death. Conversely, surgical intervention, chemotherapy, and being single were identified as protective factors against GSM-related death. CONCLUSIONS: Our study using a competing risk model provided valuable insights into the prognostic factors associated with GSM-related death. Further research and clinical interventions targeted at minimizing these risk factors and promoting the use of protective measures may contribute to improved outcomes and reduced mortality for patients with GSM.

An autopsy case of primary gliosarcoma with multiple extracranial metastases: pathology after administration of bevacizumab and genetic profile.

Gliosarcoma (GS), a morphological variant of glioblastoma, pathologically shows a biphasic pattern with gliomatous and sarcomatous components. It has been reported that GS has much higher metastatic capacity than glioblastoma. A few reports on the pathology of the extracranial metastasis of GS have shown that metastatic lesions had a sarcomatous component alone or a mixture of gliomatous and sarcomatous ones. Therefore, it is considered that GS tends to disseminate hematogenously due to its mesenchymal sarcomatous component. Herein, we report an autopsy case of GS with multiple extracranial metastases treated by craniotomy, radiotherapy, and bevacizumab. In this case, metastatic lesions at autopsy contained a gliomatous component alone, but no sarcomatous component. In addition, the sarcomatous component disappeared from the intracranial lesion at autopsy after the administration of bevacizumab. In this report, we discuss the clinical course and pathological findings at the initial state, recurrence, and autopsy, including the results of whole-genome analysis.

Gliosarcomas: magnetic resonance imaging findings / Gliossarcomas: achados de ressonância magnética

Abstract Background: Central nervous system (CNS) gliosarcoma (GSM) is a rare primary neoplasm characterized by the presence of glial and sarcomatous components. Objective: In this report, we describe the clinical and neuroimaging aspects of three cases of GSM and correlate these aspects with pathological findings. We also provide a brief review of relevant literature. Methods: Three patients were evaluated with magnetic resonance imaging (MRI), and biopsies confirmed the diagnosis of primary GSM, without previous radiotherapy. Results: The analysis of conventional sequences (T1, T1 after contrast injection, T2, Fluid attenuation inversion recovery, SWI and DWI/ADC map) and advanced (proton 1H MR spectroscopy and perfusion) revealed an irregular, necrotic aspect of the lesion, peritumoral edema/infiltration and isointensity of the solid component on a T2-weighted image. These features were associated with irregular and peripheral contrast enhancement, lipid and lactate peaks, increased choline and creatine levels in proton spectroscopy, increased relative cerebral blood volume (rCBV) in perfusion, multifocality and drop metastasis in one of the cases. Conclusion: These findings are discussed in relation to the general characteristics of GSM reported in the literature.

Resumo Introdução: O gliossarcoma (GSM) do sistema nervoso central (SNC) é uma neoplasia primária rara, caracterizada pela presença de componentes gliais e sarcomatosos. Objetivo: Nosso objetivo é descrever os aspectos clínicos e de neuroimagem de três casos com este diagnóstico e correlacioná-los com os achados patológicos. Também foi realizada uma breve revisão da literatura relevante. Métodos: Três pacientes foram avaliados por ressonância magnética (RM), e biópsias confirmaram o diagnóstico de GSM primário, sem radioterapia prévia. Resultados: Foram analisadas as sequências convencionais (T1, T1 após injeção de contraste, T2, FLAIR-fluid attenuation inversion recovery, SWI, DWI/mapa ADC) e as sequências avançadas (espectroscopia de prótons 1H e perfusão), observando-se aspecto necrótico e irregular da lesão, edema/infiltração peritumoral, isointensidade do componente sólido em T2, associada a realce irregular e periférico pelo meio de contraste, pico de lípides e de lactato e aumento dos níveis de colina e creatina na espectroscopia de prótons, aumento do volume sanguíneo cerebral relativo (rCBV) na perfusão, multifocalidade e "drop" mestástase em um dos casos. Conclusão: O presente estudo descreve características do GSM, discutindo as informações na literatura científica, ilustrando algumas particularidades desses tumores.

Gliosarcoma: presentación de un caso y hallazgos por tomografía y resonancia magnética convencional y tractografía / Gliosarcoma: Case Report and Findings by Tomography and Conventional and DTI Magnetic Resonance Imaging

El gliosarcoma es un tumor raro del sistema nervioso central y de alto grado de malignidad. La OMS lo clasifica como variante del glioblastoma (grado IV) y es de mal pronóstico. Histológicamente se caracteriza por tener componentes gliales y mesenquimatosos. El cuadro clínico varía dependiendo de su localización y tamaño, los signos y síntomas más frecuentes son convulsiones, cefalea y déficit neurológico focal. El acercamiento diagnóstico inicial es la tomografía computarizada que aporta datos de sospecha; sin embargo, la resonancia magnética constituye el pilar diagnóstico, con importantes elementos de diagnóstico que se vuelven más significativos con el uso de secuencias funcionales como la tractografía. Se presenta un caso clínico con revisión de la literatura y los hallazgos más significativos en los estudios de imagen.

Gliosarcoma is a rare and highly malignant central nervous system tumor. It is classified by the WHO as a variant of glioblastoma (grade IV) and has a poor prognosis. Histologically it is characterized by having both glial and mesenchymal components. Clinically, it varies depending on the location and size of the tumor, the most frequent symptoms being seizures, headaches and focal neurological deficit. The initial diagnostic approach is computed tomography, which provides suspicionus data; however, magnetic resonance is the diagnostic pillar, providing important data that becomes more significant with the use of functional sequences such as tractography. A clinical case is presented with a literature review and the most significant findings in the imaging studies.

Gliosarcoma in a young patient with neurofibromatosis type 1. case report

ABSTRACT Introduction: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that has variable phenotypic expressivity, with manifestations ranging from cutaneous lesions to functional compromise. It manifests clinically during childhood and adolescence. The NF-1 gene encodes a protein, neurofibromin gene, which acts as a tumor suppressor under normal conditions by regulating another protein that stimulates cell growth and proliferation. In case of alteration, different tumor processes may occur, such as the one seen in a small number of cases. Case presentation: 20-year-old male patient with NF1, who presented café-au-lait spots and developed a glioblastoma, which happens infrequently. Discussion: Immunohistochemistry methods that contribute greatly to prognosis are included to achieve the confirmed diagnosis since the median overall survival of glioblastoma patients is higher in patients with NF1 than in those without said pathological entity. Conclusion: The early diagnosis of the lesions favors a timely management of NF1. These patients require a comprehensive and interdisciplinary management to achieve full rehabilitation.

RESUMEN Introducción. La neurofibromatosis tipo 1 (NF1) es una condición autosómica dominante que presenta una expresividad fenotípica variable, con manifestaciones que van desde lesiones cutáneas hasta compromiso funcional. Se manifiesta clínicamente durante la infancia y la adolescencia; su gen codifica una proteína, la neurofibromina, que actúa como un supresor tumoral en condiciones normales regulando, a su vez, otra proteína que estimula el crecimiento y proliferación celular. En caso de alteración se podrían presentar diferentes procesos tumorales como el que se evidencia en un reducido número de casos. Presentación de caso. Paciente masculino de 20 años con NF1, quien presentaba lesiones cutáneas como manchas color café con leche y desarrolló un glioblastoma, lo cual sucede de manera infrecuente. Discusión. Para obtener el diagnóstico confirmado se incluyen métodos de inmunohistoquímica que contribuyen en gran medida al pronóstico puesto que la mediana de supervivencia global de los pacientes de glioblastoma es mayor en pacientes con NF1 que aquellos sin dicha entidad patológica. Conclusión. El diagnóstico temprano de las lesiones favorece un manejo a tiempo de la NF1. Estos pacientes requieren un manejo integral e interdisciplinar para favorecer su rehabilitación total.

Gliosarcoma cerebeloso asociado aneurofibromatosis tipo I: presentación de caso / Cerebellar gliosarcoma associated with neurofibromatosis type I: case presentation

El Gliosarcoma es un raro Glioblastoma que contiene tantos elementos gliales comparable con un Glioblastoma como componentes mesenquimal. Aproximadamente entre 2-8% de todos los Glioblastomas están asociados con elementos sarcomatosos. Clínica y genéticamente muy parecido a los Glioblastomas, excepto por la ausencia de amplificación del EGFR. El gliosarcoma es un tumor de alto grado de malignidad y pobre pronóstico, con alta tasa de recurrencia. Presentamos el caso de un paciente masculino de 54 años de edad con diagnóstico de gliosarcoma cerebeloso, asociado a Neurofibromatosis tipo I. La NF I es el síndrome hereditario más común que predispone a la neoplasia, es una enfermedad polifacética asociado no sólo a tumores benignos.

Gliosarcoma are rare glioblastomas that contain an anaplastic glial component comparable to a glioblastoma, as well as,a mesenchymal component, that have a biphasic pattern. Approximately 2-8% of all glioblastomas are associated with a sarcomatous element. Clinically and genetically close to glioblastomas, except for the absence of EGFR amplification. The Gliosarcoma is a high-grade tumor of malignity and poor prognosis, with high rate of recurrence. We present the case of a masculine patient of 54 elderly years, with diagnosis of Gliosarcoma Cerebellar associate to Neurofibromatosis type I. The NF I is the hereditary syndrome more common that predisposes to the tumor, it is a versatile disease that not only becomes a partner of benign tumors.

Metaplasia óssea no gliossarcoma: um achado histológico pouco usual. Relato de caso / Osseous metaplasia in gliosarcoma: an unusual histologic finding. Case report

Gliosarcoma (GS) is a malignant neoplasm of the central nervous system that has coexisting glial and mesenchymal components. GSs are rarely related to osseous metaplasia. The authors report a case of GS in a male patient presenting apathy and catatonia. Computed tomography/magnetic resonance imaging showed an expansive process affecting the left frontal lobe. At microscopy, a malignant glioma constituted by highly atypical glial cells intermingled with spindle-shaped cells was identified. The lesion showed areas of necrosis with pseudopalisading formation, focus of osseous metaplasia, and positive immunoexpression of S100, CD99 and vimentin in both elements. Only the sarcomatous component exhibited negative immunoexpression of glial fibrillary acidic protein (GFAP). The diagnosis of GS was then established...

Gliossarcoma (GS) é uma neoplasia maligna do sistema nervoso central que apresenta coexistência de componentes glial e mesenquimal. Raramente, os GS estão associados à metaplasia óssea. Os autores descrevem um caso de GS em paciente masculino apresentando apatia e catatonia. A tomografia computadorizada e a ressonância magnética mostraram um processo expansivo comprometendo o lobo frontal esquerdo. À microscopia, foi identificado um glioma maligno constituído por células gliais extremamente atípicas entremeadas com células fusiformes. A lesão mostrava áreas de necrose com formação de pseudopaliçada, focos de metaplasia óssea e expressão imuno-histoquímica positiva para S100, CD99 e vimentina em ambos os componentes. Somente o componente sarcomatoso exibiu imunoexpressão negativa para proteína glial fibrilar ácida (GFAP). O diagnóstico de GS foi, então, estabelecido...

Utilidad de 11C-metionina PET/CT en neurooncología / Utility of 11C-methionine PET/CT in neuro-oncology

La tomografía por emisión de positrones con metionina carbono 11 (11C-metionina PET/TC) se utiliza en la evaluación de los tumores primarios del sistema nervioso central. Describimos nuestra experiencia sobre los primeros 4 pacientes con tumores de la serie glial estudiados con 11C-metionina PET/TC. Este es un estudio descriptivo, observacional y prospectivo. Se presentan 4 pacientes entre 38-50 años de edad con diagnóstico de gliomas (clasificación de la OMS). A todos se les realizó RM y 11C-metionina PET/TC para evaluar actividad tumoral y diferenciar progresión tumoral de pseudoprogresión. Caso 1, gliomatosis cerebri grado II posradioterapia. Caso 2, glioblastoma grado IV postratamiento RT + temozolomida. Caso 3, oligodendroglioma grado II posradioterapia en 1993. Caso 4, oligoastrocitoma anaplásico grado III postratamiento RT + temozolomida. El patrón de captación de la 11C-metionina comparativamente con la RM, demostró progresión tumoral en los casos 1, 3 y 4; en el caso 2 mostró captación aunque el diagnóstico final fue pseudoprogresión. A diferencia del PET con 18fluordeoxiglucosa, la captación de 11C-metionina en el tejido cerebral normal y en la pseudoprogresión es baja, y los gliomas se visualizan como áreas metabólicamente activas. En los casos presentados, el 11C-metionina PET/TC proveyó información valiosa sobre el comportamiento y extensión de la lesión, aunque en uno de los casos presentados no diferenció progresión tumoral de pseudoprogresión. El 11C-metionina PET/TC sería una herramienta útil en el estudio y seguimiento de los pacientes con gliomas.

Positron emission tomography (PET) with 11C-methionine (11C-methionine PET/CT) is a new technique used to evaluate primary central nervous system (CNS) tumors. We describe our experience regarding the first 4 patients with glial tumors and 11C-methionine PET/CT. This is a descriptive, observational and prospective study of 4 patients between 38-50 years of age, with different gliomas (WHO classification). MRI and 11C-methionine PET/CT were performed in all cases. Case 1, gliomatosis cerebri grade II post-radiotherapy. Case 2, oligodendroglioma grade II diagnosed and treated with radiotherapy in 1993. Case 3, glioblastoma grade IV post-radiotherapy + temozolomide. Case 4, anaplastic oligoastrocytoma grade III post-radiotherapy + temozolomide. The pattern of 11C-methionine uptake compared with MRI showed tumor progression in cases 1, 3 and 4, and in case 2 showed uptake although the final diagnosis was pseudoprogression. Unlike 18fluordeoxiglucose PET/TC, 11C-methionine uptake in normal brain tissue and pseudoprogression is low, and gliomas are displayed as metabolically active areas. The 11C-methionine PET/CT provided valuable information on the tumoral behavior and extension, although in one case presented did not differentiate tumor progression from pseudoprogression. 11C-methionine PET/CT could be a useful tool in the study and follow-up to patients with gliomas.

Gliosarcoma: presentación de caso / Gliosarcoma: case report

En este artículo se presenta el caso de un paciente con gliosarcoma, un tumor glial poco frecuente con gran componente vascular. Las características vasculares de estos tumores dificultan su diagnóstico imaginológico inicial, debido a la alta frecuencia de zonas de hemorragia dentro de la lesión. La resonancia magnética permite una mejor caracterización de estas lesiones, asociadas con un pobre pronóstico clínico.

Gliossarcoma: um desafio clínico e terapêutico / Gliosarcoma: a clinical and therapeuctic challenge

O Gliossarcoma (GSa) é uma neoplasia primária rara do sistema nervoso central, caracterizada por padrão histológico bifásico que inclui os componentes glial e sarcomatoso. Os autores relatam o caso de um paciente masculino, de 49 anos de idade, que apresentou cefaleia como manifestação clínica predominante. O diagnostico foi suspeitado devido à arquitetura microscópica e confirmado pelo estudo imuno-histoquímico. Na terapêutica, foi submetido à craniotomia com microcirurgia para ressecção do tumor e tratamento radioterápico complementar. Dados epidemiológicos, histogênese e achados frequentes em exames de imagem são discutidos, assim como o tratamento e prognóstico.

The gliosarcoma (GSA) is a rare primary neoplasm of the central nervous system characterized by a biphasic histological pattern that includes the glial and sarcomatous components. Here the authors report the case of a 49-year-old male patient who presented headache as predominant clinical manifestation. The diagnosis was suspected on account of microscopic architecture and confirmed by immunohistochemical study. The patient underwent craniotomy with microsurgery for tumor resection and additional radiotherapy. Epidemiological data, histogenesis and common findings on imaging are discussed, as well as treatment and prognosis.

Gliosarcoma cerebeloso: presentación de un caso / Cerebellar gliosarcoma: case report

El gliosarcoma es un tumor intraaxial poco frecuente, más aún en la edad pediátrica, que se caracteriza por un patrón bifásico en el cual alternan áreas de diferenciación glial y mesenquimal. Constituye del 2 por ciento al 8 por ciento de todos los glioblastomas multiformes. Las manifestaciones clínicas dependen de la localización y la extensión del tumor. El diagnóstico se apoya en estudios de imagen, sin embargo el diagnóstico defInitivo está dado por el estudio anátomo-patológico. El gliosarcoma es un tumor de alto grado y pobre pronóstico, con alta tasa de recurrencia. A continuación presentamos el el caso de un paciente masculino de 6 años de edad con diagnóstico de gliosarcoma cerebeloso.

Gliosarcoma multicéntrico / Multicentric gliosarcoma

Objetivo. Presentar un caso de esta infrecuente patología; realizar una revisión bibliográfica y analizar su etiología, características clínicas y tratamiento. Descripción. Paciente femenina de 60 años de edad, que consultó por presentar hemiparesia braquiocrural derecha y afasia de expresión de 30 días de evolución. La TAC y RMN evidenciaron lesiones localizadas a nivel parieto-occipital izquierda, parainsular y occipital derecha. El screening oncológico fue negativo. Intervención. Se realizó craniotomía y exéresis subtotal de la lesión parieto-occipital izquierda. La anatomía patológica informó gliosarcoma. Completó tratamiento con radioterapia holocraneana y quimioterapia con temozolamida. La paciente falleció a los diez meses del diagnóstico.

Objetive. We report a rare case of Multicentric Gliosarcoma, we review the literature and analyze its causes, clinical features and treatment.Description. Sixty-year-old female patient who has presented right hemiparesis and motor aphasia for a month. CT and MRI showed lesions at the left parieto-occipital lobes, right occipital and parainsular lobes. Oncologic screening was negative.Intervention. A craniotomy and subtotal excision of parietooccipital lesion was performed. Histological examination revealed gliosarcoma. She received radiotherapy and chemotherapy,however she died ten months after the diagnosis. Conclusion. Multicentric gliosarcoma is very unfrequent. Thereare only two cases reported in the literature. Even so, it must besuspected in multiple cerebral lesions.

Tumores infrecuentes del SNC: gliosarcoma. Reporte de un caso / Uncommon Tumors of Central Nervous System: Gliosarcoma. A case Report

El gliosarcoma es un tumor intraaxial, poco frecuente, que se compone de elementos gliales y sarcomatosos, y constituye del 2% al 8% de todos los glioblastomas multiformes (GBM). Se presenta el caso de una mujer de 41 años que consulta por una historia de dos meses de evolución de cefalea y pérdida progresiva de la visión. Las imágenes de TAC y RM demostraron la presencia de una masa temporoparietal derecha. La paciente fue llevada a cirugía, y el reporte histopatológico fue consistente con gliosarcoma. El gliosarcoma es un tumor raro, de alto grado y pobre pronóstico, con alta tasa de recurrencia. A continuación presentamos el caso y una breve revisión de las características clínicas e imagenológicas de esta neoplasia infrecuente.

Correlação entre componente oligodendroglial, anormalidades cromossômicas e prognóstico nos glioblastomas / Correlation between oligodendroglial component, genetic abnormalities and prognosis in glioblastomas

Glioblastoma é a neoplasia glial mais comum e de maior agressividade nos adultos. Apesar do tratamento multimodal, o prognóstico é pobre e a média de sobrevida de menos de 1 ano. O padrão histológico é bastante variado e uma pequena fração destes tumores pode apresentar um componente oligodendroglial. O significado clínico da distinção entre tais tumores e glioblastomas convencionais ainda permanece desconhecido, mas já foi sugerido que a presença do componente oligodendroglial pode estar associada a uma maior sobrevida. Os estudos moleculares de glioblastomas com componente oligodendroglial têm mostrado alterações genéticas heterogêneas, com freqüências variadas na literatura de perda de heterozigosidade em 1p e 19q, alterações relacionadas com sobrevida prolongada e resposta à quimioterapia em tumores oligodendrogliais e que levaram a um interesse na investigação destas alterações em outros gliomas. A literatura apresenta dados controversos e ainda não foi possível estabelecer uma associação definitiva entre a maior sobrevida observada em alguns pacientes e o perfil genético/molecular. O objetivo deste estudo foi pesquisar as alterações cromossômicas associadas ao fenótipo oligodendroglial em uma série de 88 glioblastomas, 24 deles com componente oligodendroglial, utilizando duas técnicas complementares (FISH e análise quantitativa de microssatélites) para investigação de perdas alélicas, correlacionando os resultados com o prognóstico. Os resultados mostraram que deleções nos cromossomos 1p e 19q são infreqüentes nos glioblastomas com componente oligodendroglial. Apesar do fenótipo híbrido, o padrão de alterações genéticas nos cromossomos 1p/19q foi semelhante aquele observado nos glioblastomas convencionais e não mostrou impacto na sobrevida. O presente estudo também confirmou a relação da idade e do tratamento adjuvante com o prognóstico nos pacientes com glioblastomas.

Glioblastoma is the most frequent and aggressive astrocytic tumor in adults. Despite the multimodal therapy, the prognosis remains poor and the mean survival is of less than a year. The histology of glioblastomas can be quite variable and a small fraction of the tumors may present an oligodendroglial component. The clinical significance of the distinction between these tumors and conventional glioblastomas remains uncertain, but the presence of an oligodendroglial component has been associated with longer survival. Molecular genetic studies of glioblastomas with oligodendroglial component have shown heterogeneous genetic alterations, with a variable frequency of LOH on chromosomes 1p and 19q. The presence of 1p/19q deletions has been related to prolonged survival and response to chemotherapy in oligodendrogliomas and led to a growing interest in search for the same genetic alterations in other gliomas. At present, literature data is not sufficient to establish a definite correlation between the longer survivals observed in some patients and the molecular genetic profile. The aim of this study was to identify chromosomal alterations related to oligodendrogliomas (1p/19q loss) in a series of 88 glioblastomas, 24 of them with an oligodendroglial component, through quantitative microsatellite analysis using real time PCR and fluorescent in situ hybridization, correlating genetic data with prognosis. Deletions on 1p and/or 19q were infrequent in glioblastomas with oligodendroglial component. Despite the hybrid phenotype observed, the pattern of genetic changes on chromosomes 1p and 19q wasn't different from that usually observed in conventional glioblastomas and showed no correlation with survival. Our study also confirmed the already known impact of young age and adjuvant treatment on prognosis (AU)

Resposta in vitro de células gliossarcoma 9L após terapia fotodinâmica utilizando imagem de bioluminescência / In vitro gliosarcoma 9L cells response after photodynamic therapy using bioluminescence imaging

Objetivos: O presente estudo tem o objetivo de demonstrar os resultados iniciais da utilização da técnica deimagem de bioluminescência como método de monitoramento do tratamento de células de gliossarcoma de rato 9L após Terapia Fotodinâmica (TFD) utilizando o ácido aminolevulínico (ALA) como agente fotossensibilizante. Métodos: Para o presente estudo, células 9L foram transfectadas com um plasmídeo contendo o gene da luciferase, permitindo que essa linhagem celular produzisse a proteína luciferase, um dos substratos necessários para a reação de bioluminescência. No presente estudo, a TFD foi realizada utilizando diferentes doses de luz e de ácido aminolevulínico. Para validar a técnica de imagem de bioluminescência como método para o monitoramento da resposta de células tumorais e para a verificação da correlação entre o sinal luminoso e o grau de morte celular após TFD, foi utilizado o ensaio de viabilidade celular com Sulforodamina B (SRB). Resultados: Os resultados destetrabalho mostram alta correlação entre o número de células e o sinal de bioluminescência (R2 = 0,996). Os ensaios de viabilidade celular utilizando a técnica SRB, mostraram excelente correlação entre o número relativo de células sobreviventes após TFD e o sinal de bioluminescência, mostrando que a técnica de imagem de bioluminescência pode ser utilizada para o monitoramento da resposta tumoral após o tratamento de células tumorais com TFD. Os resultados do tratamento das células com terapia fotodinâmica mostram que a taxa de indução de morte celular varia de acordo com a dose de luz e fotossensibilizante empregada durante o tratamento. Nesse sentido, doses maiores de TFD resultaram em níveis mais elevados de indução de morte celular, com efeitos mais prolongados observados através do sinal bioluminescente decorridos 48 horas após a TFD. Conclusão: Este estudo demonstra que a técnica de imagem de bioluminescência pode ser utilizada para o estudo dos efeitos da terapia fotodinâmica em células tumorais. Trabalhos em animais estão em andamento no presente momento para validar a técnica de imagem de bioluminescência após TFD in vivo.

Gliosarcoma: report of four cases with immunohistochemical findings

Gliossarcoma (GSa) é uma neoplasia primária rara do sistema nervoso central, caracterizada por padrão histológico bifásico incluindo componentes tanto glial como sarcomatoso. São discutidos os aspectos clínicos, morfológicos e imunohistoquímicos de quatro casos de GSa e seus mecanismos patogêneticos. A relação masculino/feminino foi 3:1. A média de idade foi 39 anos, variando de 19 a 48. Cefaléia foi a manifestação predominante. Todos os pacientes foram submetidos a craniotomia com microcirurgia e ressecção total do tumor. O diagnostico foi suspeitado devido à arquitetura microscópica e foi confirmada por presença de fibras de reticulina através de técnicas de histoquímica. A análise imuno-histoquímica foi positiva para p53 tanto em células gliais como em células sarcomatosas nos quatro casos. EGFR foi localmente positivo em células gliais em apenas um caso. Esses achados apoiam uma origem monoclonal do GSa relacionada com alteração no Tp53, gene supressor de tumor. No entanto, outras vias alternativas na gênese desses tumores não podem ser afastadas.