Consenso chileno para el diagnóstico y tratamiento de gliomas del adulto / Diagnosis and treatment of glioma in adult: Chilean consensus

Resumen Los tumores cerebrales se caracterizan por su gran morbilidad y mortalidad. La gran mayoría corresponde a tumores secundarios (metástasis). Dentro de los tumores primarios del sistema nervioso central, los gliomas corresponden al 30% de éstos. En EEUU, entre el 2007-2011, se estima una incidencia aproximada de 21,4 casos por 100.000 habitantes. Los recientes avances en la comprensión molecular de la biología de estos tumores han permitido mejorar sustancialmente su clasificación, posibilitando realizar un mejor correlato con los desenlaces clínicos y el pronóstico. En esta línea, hoy en día es posible estratificar a los pacientes por riesgo y entregar tratamientos capaces de prolongar la sobrevida global entre 5-7 años, para los gliomas grado II y III. El presente consenso, elaborado por un panel multidisciplinario de expertos de diversas sociedades científicas chilenas y, por tanto, de todas las especialidades involucradas en el manejo médico-quirúrgico de las personas portadoras de gliomas cerebrales. A la luz de este nuevo conocimiento desarrollado al alero de la oncología molecular, esta propuesta ofrece un insumo de utilidad clínica real, que, articulado a una revisión actualizada en relación con el tratamiento y seguimiento de estos pacientes, permite entender la relevancia de estos biomarcadores en el manejo de precisión de la enfermedad. Cabe señalar que, este manuscrito emerge de la misma fuerza de trabajo, que elaboró el Protocolo Clínico de Gliomas del Adulto 2019, publicado por el Ministerio de Salud, y que ha diferencia de esta, que ofrece los detalles clínicos-operativos, como flujogramas y dosis, nuestra revisión intenta relevar los avances imagenológicos y moleculares y como estos impactan en el manejo actual de la enfermedad.

Brain tumors are characterized by high morbidity and mortality. The vast majority correspond to secondary tumors (metastasis). On the other hand, within the primary tumors of the central nervous system, gliomas correspond to 30% of these. In the US, between 2007-2011, an approximate incidence of 21.4 cases per 100,000 inhabitants was estimated. Recent advances in the molecular understanding of the biology of these tumors have made it possible to substantially improve their classification, allowing a better correlation with clinical outcomes and prognosis. Along these lines, today, it is possible to stratify patients by risk and deliver treatments capable of prolonging global survival between 5-7 years, for grade II and III gliomas. The present consensus, prepared by a multidisciplinary panel of experts from various Chilean scientific societies and, therefore, from all the specialties involved in the medical and surgical therapy. Enlightened from the molecular oncology, this proposal offers an input of clinical utility, which, together with an updated review in relation to the treatment and follow-up of these patients, allows us to understand the relevance of these biomarkers in precision disease management. It should be noted that this manuscript emerges from the same work force, which prepared the Clinical Protocol for Adult Gliomas 2019, published by the Ministry of Health, and that differs from it, which offers clinical-operative details, such as flowcharts and dose, our review attempts to reveal imaging and molecular advances and how they impact the current management of the disease.

Pleomorphic Xanthoastrocytoma with Oligodendroglioma-Like Areas with Negative 1p19q Co-Deletion

The most common mixed glioma encountered in routine surgical practice is oligoastrocytoma (OA); however, its is currently considered a vanishing entity. The 2016 classification of the World Health Organization (WHO) discourages the diagnosis of tumors as mixed glioma. The recommendations are that diffuse gliomas, including those withmixed or ambiguous histological features, should be subjected tomolecular testing. Dual-genotype OAs are not yet a distinct entity or variant in the classification. We report a case ofmixed glioma: a pleomorphic xanthoastrocytoma (PXA)mixed with an oligodendroglioma. The immunohistochemistry (IHC) pattern of isocitrate dehydrogenase 1 (IDH1) negativity with retained nuclear expression of the alpha-thalassemia x-linked intellectual disability syndrome (ATRX) protein, and 1p19q co-deletion negativity in both the components enabled its identification as a mixed glioma rather than a collision tumor. To the best of our knowledge, the case herein presented is the fourth case of PXA with oligodendroglioma. Out of the other three reported cases, only one was of a collision tumor with a dual genotype, and the other two showed similar molecular signatures in both components. The present article discusses the histological, immunohistochemical and molecular features of the aforementioned case.

Biomarcadores radiológicos en RM para una aproximación al diagnóstico molecular en gliomas IDH-mutados (grado II y III) / MR Imaging Biomarkers for a Diagnostic Approach of IDH-mutated Gliomas (Grades II/III)

Resumen Objetivo: Analizar características por resonancia magnética (RM) de gliomas IDH-mutados (grado II y III) en base a parámetros cualitativos, a fin de valorar el rendimiento del signo del mismatch T2-FLAIR y otras características morfológicas de los tumores, en predecir el estado del 1p/19q y su reproducibilidad interobservador. Métodos Estudio retrospectivo, descriptivo y analítico sobre una cohorte de 53 gliomas IDH-mutados (grado II y III) y molecularmente definidos respecto al 1p/19q, seleccionados a partir de la base de datos de la institución, durante el periodo 2014- 2019. Dos neuroradiólogos evaluaron características imagenológicas de forma independiente y enmascarada al diagnóstico: mismatch T2-FLAIR, localización tumoral, bordes, señal, infiltración cortical e inhomogeneidad en T2. Los casos discordantes fueron evaluados por un tercer neuroradiólogo de mayor experiencia. Resultados: Treinta de 53 (56,6%) gliomas fueron no codelecionados, y 23/53 (43,4%) codelecionados. El signo del mismatch T2-FLAIR fue positivo en 16/53 (30,18%) pacientes, 15/16 (93,75%) no codelecionados y 1/16 (6,25%) codelecionado (Exacto de Fisher p = <,0001). Los dos evaluadores demostraron una concordancia interobservador casi perfecta para ese signo, κ =,907 (95% CI, 0,781 a 1,0). La especificidad y el valor predictivo positivo del signo para predecir la ausencia de la codeleción fue de un 95,7% y un 93,8% respectivamente. Discusión: La reciente actualización en la clasificación de los gliomas los clasifica acorde a su perfil molecular. En los últimos años, varios investigadores han estudiado características morfológicas por RM de los tumores con la intención de predecir las características moleculares de los mismos. Conclusión: En nuestra población, el signo del mismatch T2-FLAIR es el único biomarcador radiológico que muestra asociación estadísticamente significativa en predecir la ausencia de codeleción en los gliomas IDH-mutados (grado II y III), con una alta especificidad y un alto valor predictivo positivo.

Abstract Objective: To analyze magnetic resonance (MR) characteristics of IDH-mutated gliomas (grades II/III) utilizing qualitative parameters with the goal of assessing the performance of the T2-FLAIR mismatch sign and other morphological characteristics of tumors in predicting the 1p/19q co-deletion status as well as inter-observer reproducibility. Methods: Retrospective and descriptive study analyzing a cohort of 53 IDH-mutated lower-grade (grades II/III) gliomas with known 1p/19q co-deletion status. Patients meeting selection criteria for this study were taken from our institutional data from 2014-2019. Two neuroradiologists assessed the following imaging characteristics independently, and blinded from the diagnosis: T2-FLAIR mismatch, tumor location, borders, signal characteristics, cortical infiltration and T2* inhomogeneity. In the event of discordant interpretations, a third senior neuroradiologist also evaluated the case. Results: 23 of the 53 (43.4%) gliomas demonstrated 1p/19q co-deletion and 30 of 53 (56.6%) did not. T2-FLAIR mismatch was positive in 16 of 53 cases (30.2%) with 15 of 16 (93.8%) demonstrating no co-deletion and 1/16 (6.25%) with co-deletion (Fisher's exact p = < .0001). The two readers showed an almost perfect interreader agreement for this sign κ = 0.907 (95% CI, 0.781 to 1.0). Specificity and positive predictive value of the sign to predict the absence of co-deletion was 95.7% and 93.8% respectively. Discussion: The recent update in classification of lower-grade gliomas segregates gliomas according to molecular profile. In the recent past, many researchers have studied MR morphologic characteristics of these tumors with the intention of predicting molecular features of said tumors Conclusion: In our patient population, T2-FLAIR mismatch sign is the only radiologic biomarker that shows statistically significant association with the absence of 1p/19q co-deletion in lower-grade gliomas, with high specificity and positive predictive value.

Detección de la mutación de la enzima isocitrato deshidrogenasa en gliomas difusos grados II, III y IV / Detection of isocitrate dehydrogenase enzyme mutation in grades II, III and IV diffuse gliomas

Introducción. Los gliomas son las neoplasias malignas primarias más frecuentes del sistema nervioso central, asociadas con una mortalidad y morbilidad elevadas. Las mutaciones en los genes IDH1 e IDH2 de la enzima isocitrato deshidrogenasa (IDH) son clave en la tumorogénesis, y son consideradas un factor pronóstico importante en estas neoplasias. En este estudio se buscó determinar la presencia de mutaciones de los genes IDH1 e IDH2 en pacientes con diagnóstico de glioma difuso en diferentes grados, y su correlación con la sobrevida. Metodología. Se realizó un estudio descriptivo, prospectivo y retrospectivo. La población de estudio fueron pacientes entre los 18 y 45 años con diagnóstico de glioma difuso grado II, III y IV, atendidos en el Hospital San Vicente Fundación de Medellín, entre 2012 y 2017, en quienes se realizó un análisis de mutaciones en los genes IDH1 e IDH2 por secuenciación Sanger y tinción de inmunohistoquímica. Resultados. Se incluyeron 14 pacientes con edad promedio de 37 años, 57% de sexo masculino. Glioblastoma fue la neoplasia más frecuente, diagnosticada en el 42,9% de casos. Por inmunohistoquímica, 10 de los 14 (71,4%) pacientes presentaron mutación de la enzima IDH1, en tanto que 1 de los 11 (9%) pacientes en quienes se logró la secuenciación del gen IDH2, mostró mutación. En general, el 78,6% presentó mutaciones de la enzima IDH, con promedio de sobrevida de 48 meses. Conclusión. Estos hallazgos sugieren que los gliomas son un grupo heterogéneo de tumores, con gran variabilidad genética que impacta en su pronóstico y comportamiento

Introduction. Gliomas are the most common primary malignancies of the central nervous system, associated with high mortality and morbidity. Mutations in the isocitrate dehydrogenase (IDH) enzyme IDH1 and IDH2 genes, are key in tumorigenesis, and are considered an important prognostic factor in these neoplasms. This study aimed to determine the presence of IDH1 and IDH2 gene mutations in patients diagnosed with diffuse glioma in different degrees, and their correlation with survival. Methodology. A descriptive, prospective and retrospective study was conducted. The study population consisted of patients between the ages of 18 and 45 with a diagnosis of grade II, III and IV diffuse glioma, treated at the Hospital San Vicente Fundación in Medellín, between 2012 and 2017, in whom an analysis of IDH1 and IDH2 gene mutations was performed by Sanger sequencing and immunohistochemical staining. Results. Fourteen patients with a mean age of 37 years were included, 57% were male. Glioblastoma was the most frequent neoplasm, diagnosed in 42.9% of the cases. By immunohistochemistry, 10 of the 14 (71.4%) patients had a mutation of the IDH1 enzyme, while 1 of the 11 (9%) patients in whom IDH2 gene sequencing was achieved showed a mutation. In general, 78.6% had IDH enzyme mutations, with an average survival of 48 months. Conclusion. These findings suggest that gliomas are a heterogeneous group of tumors, withgreat genetic variability that impacts their prognosis and behavior

Oligodendroglioma anaplásico quístico: reporte de caso / Anaplastic cystic oligodendroglioma: case report

Resumen: Los oligodendrogliomas anaplásicos son gliomas infiltrantes grado III de la organización mundial de la salud (OMS). Son tumores poco frecuentes y representan el 5-10% de todas las neoplasias intracraneales primarias. Su incidencia es de 0.3 por 100.000 habitantes por año en Estados Unidos. Con frecuencia se presentan en adultos entre los 40-60 años de edad. Los síntomas principales pueden ser déficit motor, déficit cognitivos y síntomas de aumento de la presión intracraneal. Su comportamiento en resonancia magnética muestra un aspecto heterogéneo con necrosis, degeneración quística y hemorragia intratumoral. Las presentaciones quísticas extensas son poco frecuentes. Reportamos el caso de un oligodendroglioma anaplásico de aspecto predominantemente quístico en una mujer joven.

Abstract: Anaplastic oligodendrogliomas are grade III infiltrating gliomas of the World Health Organization (WHO). They are rare tumors and represent 5-10% of all primary intracranial neoplasms. Its incidence is 0.3 per 100.000 inhabitants per year in the United States. They often occur in adults between 40-60 years of age. The main symptoms may be motor deficit, cognitive deficits and symptoms of increased intracranial pressure. Its behavior in MRI shows a heterogeneous appearance with necrosis, cystic degeneration and intratumoral hemorrhagic. Extensive cystic presentations are rare. We report the case of an anaplastic oligodendroglioma of predominantly cystic appearance in a young woman.

FISHing for 1p19q codel in oligodendroglioma

@#Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.

Oligodendroglioma with Sarcomatous Transformation: Case Report and Literature Review

Oligodendrogliomas are infiltrative tumors of the central nervous systemconsidered to be morphologically stable and to offer a better prognosis. Here, we describe the case of a 36- year-old man with an initial diagnosis of oligodendroglioma, World Health Organization (WHO) grade II, who presented transformation to a sarcomatous form, while maintaining the oligodendroglial component as well as the genetic characteristics of the initial tumor without having undergone any complementary treatments previously. Despite the favorable genetic characteristics, the tumor presented poor response to complementary treatments, and rapid progression, including spinal metastasis.

Diagnóstico molecular de pérdida de heterocigosidad para 1p/19q en tumores oligodendrogliales por PCR multiplex en el Instituto Nacional de Enfermedades Neoplásicas, Lima- Perú / Molecular diagnosis of heterozygosity loss for 1p/19q in oligodendroglial tumors by multiplex PCR at the National Institute of Neoplastic Diseases, Lima-Peru

La pérdida de heterocigosidad 1p/19q tiene valor pronóstico clínico y está fuertemente asociada con características histológicas clásicas de oligodendroglioma. Objetivos: El presente artículo, propone un método molecular para determinar la pérdida de heterocigosidad (LOH por sus siglas en inglés) para 1p/19q y permitir la clasificación de tumores oligodendrogliales. Material y Métodos: Se utilizaron muestras en fresco del Banco de Tejidos Tumorales del Instituto Nacional de Enfermedades Neioplásicas (INEN) y biopsias de tejido embebido en parafina de tumores oligodendrogliales, con diagnóstico patológico de oligodendroglioma y oligoastrocitoma. Los métodos propuestos son PCR Multiplex y amplificación de fragmentos por electroforesis capilar de los productos de PCR, y fueron aplicados a un total de 39 casos que presentaban grado histológico II y III. Resultados: Los resultados obtenidos permiten una adecuada clasificación molecular de los tumores oligodendrogliales.

A heterozygosity loss of 1p/19q has clinical prognostic value and is strongly associated with classical histologic features of oligodendroglioma. Objectives: The present article proposes a molecular method to determine the loss of heterozygosity (LOH) for 1p/19q and to allow the classification of oligodendroglial tumors. Material and Methods: Fresh samples from the National Institute of Neoplastic Diseases’ Tumor BioBank and paraffin-embedded tissue biopsies of oligodendroglial tumors with pathological diagnosis of oligodendroglioma and oligoastrocytoma were used. The proposed methods are Multiplex PCR and amplification of fragments by capillary electrophoresis of PCR products, and were applied to a total of 39 cases which presented histological grade II and III. Results: The results obtained allow an adequate molecular classification of oligodendroglial tumors.

Superior Sagittal Sinus Invasion by Malignant Glioma: Case Report and Literature Review

Anaplastic oligodendrogliomas (AOs) correspond to 23% of all oligodendrogliomas. They correspond to a tumor with malignant histological characteristics, focal or diffuse, associated with a worse prognosis. In the present case report, we describe the case of a 30-year-old female submitted to resection of a right parietal lesion whose histology showed to be an AO. She underwent complementary treatment with chemotherapy and radiotherapy according to the Roger Stupp protocol. Four years after the initial diagnosis, there was tumor recurrence within the superior sagittal sinus, with no evidence of recurrence elsewhere. In the literature, we have found no similar published case reinforcing the rarity of this condition.

Recurrencia de oligodendroglioma luego de cirugía, quimioterapia y radioterapia / Recurrence of oligodendroglioma after surgery, chemotherapy and radiotherapy

Introducción: Los gliomas conforman la mayoría de los tumores primarios que surgen del parénquima cerebral. Reporte de caso: varón de 39 años, con antecedente de hace 08 años de oligodendroglioma grado II sometido a cirugía para exéresis completa, más quimioterapia y radioterapia; que se presentó con 6 semanas de enfermedad caracterizada por crisis convulsivas tónico clónicas generalizadas, adormecimiento y disminución de fuerza de hemicuerpo derecho. El examen clínico revelo hemiparesia derecha a predominio braquial 2/5, Glasgow 15 puntos. En la resonancia cerebral se encontró extenso realce nodular de 4.8 cm localizado en región fronto-parietal izquierda, con abundante edema vasogénico ejerciendo efecto de masa. Se realiza segunda cirugía encontrando en anatomía patología un glioma de IV grado OMS. Conclusión: Los oligodendrogliomas son tumores de crecimiento lento, cuyo tratamiento es conjunto, cirugía, quimioterapia y radioterapia. La recurrencia generalmente se da con un grado más elevado, disminuye la esperanza de vida del paciente.

MRI manifestations of cystic oligodendrocytoma / 中国医学影像技术

Objective To investigate MRI features of cystic oligodendrocytoma.Methods MRI features of 10 patients with oligodendroglial tumors proved with operation and pathology were analyzed retrospectively.Results Among 10 patients,lesionslocated on the supratentorium in 8 patients,while on the cerebellar vermis in 2 patients.Solitary lesion was found in 9 cases,and multiple lesions were found in 1 case.Complete cystic lesions were observed in 4 cases,large cystic lesions with solid nodules were found in 3 cases,and multi-cystic lesions were found in 3 cases.Smooth cyst wall of lesions were found in 7 cases,locally depressed and rough wall were found in 3 cases.Calcifications were found in 3 cases.Mild peritumoral edema was found in 9 cases,moderate to severe edema was found in 1 case.The lesions significantly enhanced in 3 cases,ring enhanced in 3 cases,and locally enhanced in 1 case.Conclusion COD is difficult to diagnose,but has certain MRI characteristics.COD should be considered when supratentorial complete cystic lesion or large cystic lesion with septum and/or solid nodule was found with MRI.

Imaging features of oligodendroglioma in cerebellar hemispheres / 实用放射学杂志

Objective To improve the diagnosis of oligodendroglioma(OD)in cerebellar hemispheres and discuss MRI features. Methods Clinical and imaging data of 7 cases with OD in cerebellar hemispheres were analyzed retrospectively,which were confirmed by surgery and pathology.Results In 7 patients,4 patients were OD,and 3 patients were anaplastic oligodendroglioma(AOD).MRI showed hypointense on T1WI and vividly hyperintense or mixed hyperintense on T2WI.The time intensity curve(TIC)manifested rise slowly;DWI(b=1 000 s/mm2) showed homogeneously hypointense or iso-hypointense.The ratios of OD and AOD were 1.753±0.784,1.660±0.551 respectively;Magnetic resonance spectroscopy(MRS)of oligodendrogliomas revealed a increased choline(Cho)and reduced N-acetylaspartate(NAA)without lactate(Lac)peak.Conclusion MRI manifestation of OD in cerebellar hemispheres has certain characteristics:the boundary of lesion is unclear, irregular in shape,easy to cystic and necrotic,with or without peripheral edema of the tumor,delayed enhancement,higher in Cho peak,lower in NAA peak and lacking in Lac peak.

Reclassification of Mixed Oligoastrocytic Tumors Using a Genetically Integrated Diagnostic Approach

BACKGROUND: Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients. METHODS: Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups. RESULTS: We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old). CONCLUSIONS: Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.

Diagnostic and prognostic roles of loss of CIC protein expression in oligodendroglial tumors / 中华病理学杂志

Objective@#To investigate the usefulness of loss of CIC expression as the prescreening detection of 1p/19q co-deletion in the diagnosis of oligodendroglial tumors and its prognostic implication.@*Methods@#The retrospective study included 113 oligodendroglial tumors diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University. Expression of CIC protein was detected by immunohistochemistry, and the 1p/19q co-deletion by fluorescence in situ hybridization in all the tumors; and the correlation of the loss of protein and 1p/19q co-deletion with prognosis was assessed.@*Results@#The rate of negative CIC protein expression was 59.3% (67/113) in 113 oligodendroglial tumors. CIC protein expression was differentially lost in various gliomas, 85.7% (42/49) in pure oligodendrogliomas and 39.1% (25/64) in mixed oligodendroglial tumors (P<0.01). The loss of CIC protein expression showed a sensitivity of 76.1% (54/71), specificity 71.1% (27/38), false positive rate of 16.9% (11/65), and a false negative rate of 38.6% (17/44). In 63 cases integrated diagnosis as oligodendroglial tumors with mutant IDH and 1p/19q co-deletion, the loss of CIC protein expression was 81.0% (51/63); the sensitivity and specificity were increased to 81.0% (51/63) and 76.9% (20/26), and the false positive rate and false negative rate decreased to 10.5% (6/57) and 37.5% (12/32), respectively. By using Kaplan-Meier analysis, the CIC negative group showed a trend towards better outcome than the CIC positive group, but there was no statistical difference (overall survival: P=0.218; progression free survival: P=0.249).@*Conclusions@#Detection of the lost CIC protein expression can predict the chromosome 1p/19q co-deletion. In oligodendroglial tumors with IDH mutant and 1p/19q co-deletion, there is no relation between prognosis and CIC protein expression.

Clinical and MR features of oligodendroglioma / 实用放射学杂志

Objective To study the MR features and differential diagnosis of oligodendroglioma.Methods Clinical and MR data of 34 pathology-diagnosed oligodendroglioma cases were analyzed retrospectively, which included tumor location,signal,size,enhanced and MRS features.Results 22 cases were diagnosed as WHOⅡoligodendroglioma and 12 cases WHOⅢ anaplastic oligodendroglioma.22 tumors located in the frontal lobes,4 tumors in the temporal lobes, 7 tumors in both frontal and temporal lobes,1 tumor located at the optic chiasma.25 tumors located in the superficial areas of the brain.For anaplastic oligodendrogliomas,tumor necrosis and cystic degenerations were showed in 11 cases,and hemorrhage or calcification in 6 cases.For oligodendroglioma,tumor necrosis and cystic degenerations were showed in 6 cases,hemorrhage in 2 cases,calcification in 8 cases.The average tumor diameter was 35 mm for oligodendroglioma and 58 mm for anaplastic oligodendroglioma.For anaplastic oligodendroglioma,obvious irregular or ring enhancements were showed in 11 cases.For oligodendroglioma, mild enhancement was showed in 6 cases,no enhancement in 6 cases and mild or moderate irregular ring-type enhancements in 4 cases.MRS was performed in 6 anaplastic oligodendrogliomas the Cho/Cr ratio was over 4 in 5 cases.MRS was performed in 12 oligodendrogliomas the Cho/Cr ratio was between 2.3 to 3.3 in 10 cases and below 2 in 2 cases.Conclusion The main MR feature of anaplastic oligodendroglioma is that tumor is located in the frontal lobe and superficial area of the brainwith irregular or ring-type enhancement,and the Cho/Cr ratio over 4.

Expression of FABP5 and its clinic pathological significance in oligodendroglioma / 临床与实验病理学杂志

Purpose To investigate the expression of FABP5 in oligodendroglioma and its clinic pathological significance.Methods Immunostaining of FABP5 and Ki-67 were performed in 87 oligodendrogliomas and 23 paracancerous brain tissues.The relationships between FABP5 expression and Ki-67 expression or clinic pathological parameters were statistically analyzed.Patients were followed up after operation.Results (1) The expression of FABP5 was significantly higher in oligodendroglioma [63.2％ (55/87)] than that in normal control [34.8％ (8/23)].(2)The expression of FABP5 was positively correlated with the histological grade (P =0.018,rs =0.254) and the Ki-67 expression (P =0.003,rs =0.318) in oligodendroglioma.(3) Univariate analysis showed that the expression of FABP5 protein,Ki-67 protein,age and chemotherapy were significant prognostic factors for oligodendroglioma patients.Conclusion FABP5 may play an important role in the pathogenesis and progression of oligodendroglioma,and could be used as a novel biological indicator of disease progress as well as prognosis for oligodendroglioma patients.

World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia

When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment.

Molecular biology techniques for loss of heterozygosity detection: the glioma example / Técnicas de biologia molecular para avaliação da perda de heterozigosidade: o exemplo em glioma

ABSTRACT In recent years, many oncology institutions have implemented the use of molecular approaches to assess and manage cancer patients. One commonly observed type of genetic alteration in cancer is the loss of heterozygosity (LOH). In the clinical setting, this molecular genetic marker is an important tool for disease prognosis, diagnosis and treatment. For example, the loss of 1p/19q is a classical molecular marker for oligodendroglioma assessment. In addition, this marker is associated with a favorable prognosis and chemosensitivity in oligodendroglial tumors. Interpretation of the clinical significance of molecular markers requires that health professionals and biomedical scientists understand the basic theoretical fundamentals of molecular diagnostic techniques. Although there are different methodologies to assess LOH, including high-performance techniques, this review aims to describe the polymerase chain reaction (PCR)-based LOH assays and fluorescence in situ hybridization (FISH), which are the molecular techniques most used for evaluation of 1p/19q status in pathology laboratories.

RESUMO Nos últimos anos, instituições de oncologia têm implementado o uso de abordagens moleculares para avaliar e conduzir pacientes com câncer. O tipo mais comum de alteração encontrada no câncer é a perda de heterozigosidade (LOH). Na clínica, esse marcador molecular pode ter importância para o prognóstico, o diagnóstico e/ou na decisão do tratamento. Por exemplo, a perda de 1p/19q é um marcador molecular clássico para a avaliação do oligodendroglioma. Além disso, esse marcador está associado ao prognóstico favorável e à quimiossensibilidade em tumores oligodendrogliais. A interpretação do significado clínico dos marcadores moleculares exige que os profissionais da área da saúde entendam os fundamentos básicos teóricos das técnicas de diagnóstico molecular. Embora existam diferentes metodologias para avaliar a LOH, inclusive técnicas de alta performance, esta revisão tem o objetivo de descrever o ensaio de LOH com base na reação da cadeia da polimerase (PCR) e a hibridização in situ fluorescente (FISH), que são as técnicas moleculares mais usadas para avaliação do status 1p/19q em laboratórios de patologia.

Primary Spinal Cord Oligodendroglioma with Postoperative Adjuvant Radiotherapy: A Case Report

Primary spinal cord oligodendrogliomas are rare tumors comprising two percent of all spinal cord tumors. Although a treatment guideline has yet to be established, maximal surgical resection is primary in the treatment of spinal cord oligodendrogliomas. Adjuvant radiotherapy has remained controversial, and it is unclear whether chemotherapy adds any benefit. In this case report, the authors present a 24-year-old male who had a seven-year history of left leg weakness and a radiating pain in both legs. Magnetic resonance image (MRI) showed an intramedullary mass at the T4-T8 level. He underwent subtotal removal of the tumor and pathologic diagnosis revealed a WHO grade II oligodendroglioma. The patient was treated with radiotherapy postoperatively and followed up with MRI annually. Clinical and radiological status of the patient had been stationary for four years after the surgery. The five-year follow-up MRI showed an increase in the size and extent of the residual tumor. Despite radiological progression, considering that symptoms and the performance status of the patient had remained unchanged, further treatment has not been performed. Given the clinical outcome of this patient, close observation after subtotal removal with adjuvant radiotherapy is one of the acceptable treatment options for WHO grade II spinal cord oligodendrogliomas.

Temozolomide Salvage Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligo-Astrocytoma

OBJECTIVE: To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA). METHODS: A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed. RESULTS: TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (> or =grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01). CONCLUSION: For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.