Loss of H3K27 trimethylation is frequent in IDH1-R132H but not in non-canonical IDH1/2 mutated and 1p/19q codeleted oligodendroglioma: a Japanese cohort study.

Oligodendrogliomas are defined by mutation in isocitrate dehydrogenase (NADP(+)) (IDH)1/2 genes and chromosome 1p/19q codeletion. World Health Organisation diagnosis endorses testing for 1p/19q codeletion to distinguish IDH mutant (Mut) oligodendrogliomas from astrocytomas because these gliomas require different treatments and they have different outcomes. Several methods have been used to identify 1p/19q status; however, these techniques are not routinely available and require substantial infrastructure investment. Two recent studies reported reduced immunostaining for trimethylation at lysine 27 on histone H3 (H3K27me3) in IDH Mut 1p/19q codeleted oligodendroglioma. However, the specificity of H3K27me3 immunostaining in this setting is controversial. Therefore, we developed an easy-to-implement immunohistochemical surrogate for IDH Mut glioma subclassification and evaluated a validated adult glioma cohort. We screened 145 adult glioma cases, consisting of 45 IDH Mut and 1p/19q codeleted oligodendrogliomas, 30 IDH Mut astrocytomas, 16 IDH wild-type (Wt) astrocytomas, and 54 IDH Wt glioblastomas (GBMs). We compared immunostaining with DNA sequencing and fluorescent in situ hybridization analysis and assessed differences in H3K27me3 staining between oligodendroglial and astrocytic lineages and between IDH1-R132H and non-canonical (non-R132H) IDH1/2 Mut oligodendroglioma. A loss of H3K27me3 was observed in 36/40 (90%) of IDH1-R132H Mut oligodendroglioma. In contrast, loss of H3K27me3 was never seen in IDH1-R132L or IDH2-mutated 1p/19q codeleted oligodendrogliomas. IDH Mut astrocytoma, IDH Wt astrocytoma and GBM showed preserved nuclear staining in 87%, 94%, and 91% of cases, respectively. A high recursive partitioning model predicted probability score (0.9835) indicated that the loss of H3K27me3 is frequent to IDH1-R132H Mut oligodendroglioma. Our results demonstrate H3K27me3 immunohistochemical evaluation to be a cost-effective and reliable method for defining 1p/19q codeletion along with IDH1-R132H and ATRX immunostaining, even in the absence of 1p/19q testing.

All-cause and tumor-specific mortality trends in geriatric oligodendroglioma (OG) patients: A surveillance, epidemiology, and end results (SEER) analysis.

Recent efforts have been made to identify mortality risk factors in Oligodendroglioma (OG) patients, however, efforts have fallen short within the geriatric population. The purpose of this study was to identify mortality trends and risk factors within a geriatric cohort of patients with OGs. 762 cases (1973-2012, age at diagnosis 65+ years) within the Surveillance, Epidemiology, and End Results (SEER) database were included. Variables were age at diagnosis, decade of diagnosis, sex, race and whether or not surgery was performed. All-cause mortality was identified prior to stratification, while tumor-specific mortality was identified after stratification of data by the SEER cause of death "Dead (attributable to this cancer dx)". Before stratification, decade 4 and patients aged 65-74 years at diagnosis had the lowest mortality, while 85+ years had the highest. Furthermore, women had lower mortality than men and surgery performed resulted in lower mortality in the univariate, but not the multivariate analysis. Following stratification, however, multivariate analysis showed less mortality with surgery performed, but differences between decades and sex were no longer detected. Similarly, patients aged 65-74 years at diagnosis continued to have the lowest mortality, while 85+ years continued to have the highest. Although all-cause mortality decreased over time, tumor-specific mortality remained unchanged since 1973 for geriatric patients with OGs. This highlights the need for further research into new therapeutic strategies for this rapidly growing population.

Relación entre el coeficiente de difusión aparente y la celularidad de gliomas en centro de tercer nivel de Panamá / Relationship between the apparent diffusion coefficient and cellularity of gliomas in tertiary care center of Panamá

Introducción: Los gliomas son tumores malignos altamente celulares del sistema ner­ vioso central. Su grado histológico preoperatorio es de utilidad en el manejo quirúrgico, por lo que la resonancia magnética con secuencias avanzadas intenta brindar mayor información tumoral. Objetivo: Relacionar el coeficiente aparente de difusión (CAD) y celularidad de los gliomas de pacientes entre enero 2015 a diciembre 2017. Metodo­ logía: Retrospectivamente se obtuvieron de archivos clínicos la edad, sexo, tipo, grado histológico y sitio anatómico. Se calculó el CAD en 5mm 2 en los estudios de resonancia magnética preoperatorias y se utilizó las laminillas para conteo de celularidad en 5mm 2 digitalmente. Se utilizó análisis estadísticos descriptivos y coeficiente de correlación entre CDA con celularidad. Se utilizaron valores de p < 0.05 para significancia estadís­ tica. Resultados: 46 casos fueron incluidos, 56.5% fueron hombres. El rango de 41­64 años fueron los más afectados. El glioblastoma fue el tipo histológico más frecuente (47.8%), así como los gliomas de alto grado (73.9%). El 95.7% fueron supratentoriales. La celularidad promedio fue de 3970 ± 2900 vs 2436 ± 948 núcleos/5mm 2 (p = 0.13), con valores promedio de CDA mínimo de 0.813 x 10­3 ± 0.229 mm 2 /s vs 1.052 x 10­3 ± 0.196 mm 2 /s (p = 0.002), para los gliomas de alto y bajo grado respectivamente. La co­ rrelación entre CDA y celularidad fue débil (R = ­ 0.13, p = 0.37). Conclusión: Existe co­ rrelación débil inversamente proporcional entre el CDA y la celularidad con distinción de gliomas de bajo y alto grado con valores de CDA mínimos

Introduction: Gliomas are highly cellular malignant tumors of the central nervous sys­ tem. Its preoperative histological grade is useful in surgical management, so magnetic resonance imaging with advanced sequences tries to provide more tumor information. Objective: Correlate apparent diffusion coefficient (ADC) and cellularity of gliomas of patients between January 2015 to December 2017. Methodology: Data of age, sex, ty­ pe, histologic grade and anatomic site were retrospectively obtained from clinical archi­ ves. The preoperative magnetic resonance ADC was calculated in a 5 mm 2 region of interest and the microscope slides were used for the cellularity digitally count in 5 mm 2 . Descriptive statistical analysis and correlation coefficient between ADC and cellularity were used. Values of p <0.05 were used for statistical significance. Results: 46 cases were included, 56.5% were men. The 41­64 years ranges were the most affected. Glio­ blastoma was the most frequent histological type (47.8%), as well as high grade glio­ mas (73.9%). 95.7% were supratentorial. The average cellularity was 3970 ± 2900 vs 2436 ± 948 nuclei/ 5mm 2 (p = 0.13), with average minimum ADC values of 0.813 x 10­3 ± 0.229 mm 2 /s vs 1052 x 10­3 ± 0.196 mm 2 /s (p = 0.002), for high­ and low­grade glio­ mas, respectively. The correlation between ADC and cellularity was weak (R = ­ 0.13, p = 0.37). Conclusions: There is a weak inversely proportional correlation between ADC and cellularity. With distinction of low­ and high­grade gliomas with minimum ADC values

Oligodendroglioma confers higher risk of radiation necrosis.

BACKGROUND: Radiation therapy (RT) remains a mainstay for the treatment of lower grade gliomas. Radiation neurotoxicity is a serious complication, carrying high morbidity in the absence of tumor progression. The incidence remains poorly categorized and known risk factors identified are related to the radiation modality. We hypothesized that patients with oligodendroglioma have a higher risk of radiation necrosis (RN) as compared to patients with astrocytoma. METHODS: We conducted a retrospective review of adults with lower grade diffuse gliomas over a 10-year span. The primary outcome was RN, either pathologically confirmed or clinically diagnosed. Cases without pathological confirmation must have been symptomatic, requiring administration of bevacizumab or high-dose steroids. Cox proportional hazard ratios were used for multivariate analyses. RESULTS: In 319 patients, we identified RN in 41 patients (12.9%): 28 patients (21.3%) with oligodendroglioma and 13 (6.9%) with astrocytoma (HR 3.42, p < 0.001). Patients with oligodendroglioma who received > 54 Gy had a higher incidence (31.2%) than those receiving ≤ 54 Gy (14.3%, HR 6.9, p = 0.002). There was no similar correlation among patients with astrocytoma. There was no difference in incidence based on use of concomitant temozolomide. Radiation necrosis appeared within 24 months from radiation in 80.5% of patients. CONCLUSION: Our study suggests that patients with oligodendroglioma are at higher risk of developing RN. The incidence increases with increasing radiation dose in patients with oligodendroglioma but not with astrocytoma. RN usually appears within 24 months from RT. Patients with oligodendroglioma receiving > 54 Gy are at highest risk.

Extent of resection and survival for oligodendroglioma: a U.S. population-based study.

BACKGROUND: National guidelines recommend maximal safe resection of low-grade and high-grade oligodendrogliomas. However, there is no level 1 evidence to support these guidelines, and recent retrospective studies on the topic have yielded mixed results. OBJECTIVE: To assess the association between extent of resection (EOR) and survival for oligodendrogliomas in the general U.S. METHODS: Cases diagnosed between 2004 and 2013 were selected from the Surveillance, Epidemiology, and End-Results (SEER) Program and retrospectively analyzed for treatment, prognostic factors, and survival times. Cases that did not undergo tumor de-bulking surgery (e.g. no surgery or biopsy alone) were compared to subtotal resection (resection) and gross-total resection (GTR). The primary end-points were overall survival (OS) and cause-specific survival (CSS). An external validation cohort with 1p/19q-codeleted tumors was creating using the TCGA and GSE16011 datasets. RESULTS: 3135 Cases were included in the final analysis. The 75% survival time (75ST) and 5-year survival rates were 47 months and 70.8%, respectively. Subtotal resection (STR, 75ST = 50 months) and GTR (75ST = 61 months) were associated with improved survival times compared to cases that did not undergo surgical debulking (75ST = 20 months, P < 0.001 for both), with reduced hazard ratios (HRs) after controlling for other factors (HR 0.81 [0.68-0.97] and HR 0.65 [0.54-0.79], respectively). GTR was associated with improved OS in both low-grade and anaplastic oligodendroglioma subgroups (HR 0.74 [0.58-0.95], HR 0.60 [0.44-0.82], respectively) while STR fell short of significance in the subgroup analysis. All findings were corroborated by multivariable analysis of CSS and externally validated in a cohort of patients with 1p19q-codeleted tumors. CONCLUSION: Greater EOR is associated with improved survival in oligodendrogliomas. Our findings in this U.S. population-based cohort support national guidelines.

Leptomeningeal metastases in glioma: The Memorial Sloan Kettering Cancer Center experience.

OBJECTIVE: To perform a retrospective analysis examining the incidence and prognosis of glioma patients with leptomeningeal disease (LMD) at Memorial Sloan Kettering Cancer Center over a 15-year period and correlate these findings with clinicopathologic characteristics. METHODS: We conducted a retrospective review of glioma patients with LMD at Memorial Sloan Kettering Cancer Center diagnosed from 2001 to 2016. Patients were identified through a keyword search of their electronic medical record and by ICD-9 codes. RESULTS: One hundred three patients were identified with disseminated LMD and 85 patients with subependymal spread of disease, 4.7% of all patients with glioma. These cohorts were analyzed separately for time to development of disseminated LMD/subependymal LMD, median overall survival, and survival from LMD diagnosis. Patients were pooled for subsequent analyses (n = 188) because of comparable clinical behavior. LMD was present at glioma diagnosis in 10% of patients. In the remaining 90% of patients diagnosed at recurrence, time to LMD diagnosis, survival after LMD diagnosis, and overall survival varied by original histology. Patients with oligodendroglioma had a median survival of 10.8 (range 1.8-67.7) months, astrocytoma 6.5 (0.1-28.5) months, and glioblastoma 3.8 (0.1-32.6) months after LMD diagnosis. In addition, we found that treatment of LMD was associated with superior performance status and increased survival. CONCLUSION: Patients with LMD diagnosed at relapse may not have decreased overall survival as compared to historical controls with parenchymal relapse and may benefit from treatment.

Primary central nervous system neoplasms in African hedgehogs.

In this retrospective study, we describe the clinicopathologic and immunohistochemical findings in a series of primary central nervous system (CNS) neoplasms in African hedgehogs ( Atelerix albiventris). Twelve CNS neoplasms were found among 762 African hedgehog submissions (1.6%) to a private diagnostic laboratory in an 18-y period. The median age of affected hedgehogs was 3.5 y. No sex predilection was found. Hindlimb paresis, weakness, and ataxia were the most commonly reported clinical signs. Gangliogliomas ( n = 6) and astrocytomas ( n = 5) were the most commonly observed neoplasms; one oligodendroglioma was found. Gangliogliomas were found in the cerebellar white matter (2 of 6), brainstem (4 of 6), cervical spinal cord (1 of 6), and frontal lobe (1 of 6); one metastasized to the tongue. Gangliogliomas were immunoreactive for neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), S100, and CD34. All astrocytomas were gemistocytic, located in the cerebrum, and none of these neoplasms metastasized. Astrocytomas were positive for GFAP, S100, and CD34, but negative for NFP. The oligodendroglioma was located in the cerebrum, and was positive for S100, but negative for GFAP and NFP.

Oligodendroglioma resection: a Surveillance, Epidemiology, and End Results (SEER) analysis.

OBJECTIVE The available evidence suggests that the clinical benefits of extended resection are limited for chemosensitive tumors, such as primary CNS lymphoma. Oligodendroglioma is generally believed to be more sensitive to chemotherapy than astrocytoma of comparable grades. In this study the authors compare the survival benefit of gross-total resection (GTR) in patients with oligodendroglioma relative to patients with astrocytoma. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) Program (1999-2010) database, the authors identified 2378 patients with WHO Grade II oligodendroglioma (O2 group) and 1028 patients with WHO Grade III oligodendroglioma (O3 group). Resection was defined as GTR, subtotal resection, biopsy only, or no resection. Kaplan-Meier and multivariate Cox regression survival analyses were used to assess survival with respect to extent of resection. RESULTS Cox multivariate analysis revealed that the hazard of dying from O2 and O3 was comparable between patients who underwent biopsy only and GTR (O2: hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.73-1.53; O3: HR 1.18, 95% CI 0.80-1.72). A comprehensive search of the published literature identified 8 articles without compelling evidence that GTR is associated with improved overall survival in patients with oligodendroglioma. CONCLUSIONS This SEER-based analysis and review of the literature suggest that GTR is not associated with improved survival in patients with oligodendroglioma. This finding contrasts with the documented association between GTR and overall survival in anaplastic astrocytoma and glioblastoma. The authors suggest that this difference may reflect the sensitivity of oligodendroglioma to chemotherapy as compared with astrocytomas.

Survival trends of oligodendroglial tumor patients and associated clinical practice patterns: a SEER-based analysis.

There is limited information on the management strategies and survival trends for oligodendroglioma patients. Here we used the Surveillance, Epidemiology and End Results (SEER, 1999-2012) database to analyze the historical trends of oligodendroglioma patient survival and correlate these trends to evolving clinical practice of radiation therapy (RT) use and surgical practice of gross total resection (GTR). We identified 2689 World Health Organization (WHO) grade II oligodendroglioma (abbreviated as O2) and 1191 WHO grade III oligodendroglioma (abbreviated as O3). Time-trend analyses were performed for overall survival, radiation treatment (RT) use, and extent of surgical resection (EOR). In multivariable Cox models that accounted for age, race, sex, tumor size, tumor location, EOR, and RT status, the hazard of dying from O3 has significantly decreased over the study period (p  <  0.01), while the hazard of dying from O2 has remained largely unchanged. A search of the published literature revealed articles reporting results largely supportive of these observations. The pattern of surgical practice and RT for O3 patients remained unchanged throughout the study period, suggesting that the survival improvement may be related to evolving patterns of medical management. Results from the SEER database indicate significant gains have been made in survival for O3 patients between 1999 and 2012. Such gains were not observed for O2 patients during this study period.

Incidence and survival trends in oligodendrogliomas and anaplastic oligodendrogliomas in the United States from 2000 to 2013: a CBTRUS Report.

Measuring tumor-specific trends in incidence is necessary to elucidate tumor-type contribution to overall cancer burden in the US population. Recently, there have been conflicting reports concerning the incidence of oligodendrogliomas (OD) and anaplastic oligodendrogliomas (AOD). Therefore, our goal was to examine trends in OD and AOD incidence and survival by age, gender and race. Data was analyzed from the Central Brain Tumor Registry of the United States (CBTRUS) from 2000 to 2013. Age-adjusted incidence rates per 100,000 person-years with 95% confidence intervals (CI) and annual percent changes (APCs) with 95% CI were calculated for OD and AOD by age, sex and race. Survival rates were calculated for age, sex and race using a subset of the CBTRUS data. OD and AOD incidence peaked at 36-40 and 56-60 years, respectively. AOD:OD ratio increased up to age 75. Overall, OD and AOD incidence decreased [OD: APC -3.2 (2000-2013), AOD: -6.5 (2000-2007)]. OD incidence was highest in Whites but decreased significantly (2000-2013: APC -3.1) while incidence in Black populations did not significantly decrease (2000-2013: APC -1.6). Survival rates decreased with advancing age for OD, while persons aged 0-24 had the lowest survival for AOD. The current study reports a decrease in overall OD and AOD incidence from 2000 to 2013. Furthermore, AOD makes up an increasing proportion of oligodendroglial tumors up to age 75. Lower AOD survival in 0-24 years old may indicate molecular differences in pediatric cases. Thus, surveillance of tumor-specific trends by age, race and sex can reveal clinically relevant variations.

Radiotherapy, Especially at Young Age, Increases the Risk for De Novo Brain Tumors in Patients Treated for Pituitary/Sellar Lesions.

CONTEXT: De novo brain tumors developing after treatment of pituitary/sellar lesions have been reported, but it is unknown whether this is linked to any of the treatment modalities. OBJECTIVE: To study the occurrence of malignant brain tumors and meningiomas in a large cohort of patients treated for pituitary/sellar lesions, with special emphasis on the role of radiotherapy (RT). PATIENTS AND METHODS: Patients (n = 8917) who were hypopituitary due to pituitary adenomas, craniopharyngiomas, and other sellar tumors followed in KIMS (Pfizer International Metabolic Database) from 1994 to 2012 were included. Treatment consisted of surgery and/or medical therapy in 4927 patients, RT alone, or with surgery in 3236 patients; data were missing in 754. Incidence rate ratios (RRs) were analyzed through Poisson regression methods with internal comparisons. RESULTS: During 53,786 patient-years, 17 cases of malignant brain tumors (13 exposed to RT) and 27 meningiomas (22 exposed to RT) were reported. RR for RT vs no RT was 3.34 [95% confidence interval (CI), 1.06 to 10.6] for malignant brain tumors, and 4.06 (95% CI, 1.51 to 10.9) for meningiomas. The risk of developing a malignant brain tumor increased by 2.4-fold (P = 0.005) and meningioma by 1.6-fold with every 10 years of younger age at RT (P = 0.05). Incidence rates were similar in patients treated with conventional RT compared with stereotactic RT. CONCLUSION: RT of pituitary tumors is associated with increased risk of developing malignant brain tumors and meningiomas, especially when given at younger ages. In balancing risks and benefits of RT, our findings emphasize that special consideration should be given to the age of the patient.

Histological spectrum of oligodendroglial tumors: Only a subset shows 1p/19q codeletion.

BACKGROUND: Canonical oligodendroglial tumors (ODGs) are characterized genetically by chromosomes 1p/19q codeletion. AIMS: This study was essentially aimed at the detection of frequency of 1p/19q codeletion in the different histological spectrum of ODG tumors in a large cohort of Indian patients. MATERIALS AND METHODS: All the ODG tumors evaluated for 1p/19q by fluorescence in-situ hybridization (FISH) during 2009-2015 were correlated with histology, immunohistochemical expression for p53 protein and clinical features. RESULTS: A total of 676 cases included both pediatric (n = 18) and adult (n = 658) patients. Histologically, 346 pure ODGs [oligodendroglioma (OD) and anaplastic oligodendroglioma (AOD)] and 330 mixed ODGs [oligoastrocytomas (OA), anaplastic oligoastrocytomas (AOA) and glioblastoma with oligodendroglioma component (GBM-O)] were included. 1p/19q co-deletion was noted in 69% (60/87), 55.9% (145/259), 18.2% (18/99), 10.5% (18/172), and in 5.1% (3/59) cases of OD, AOD, OA, AOA, and GBM-O, respectively. In the pediatric age-group, 1p/19q codeletion was seen in 25% (2/8) of pure ODGs and in 10% (1/10) of mixed ODGs. In adults, it was observed in 60% (203/338) cases of pure ODGs and in 11.9% (38/320) cases of mixed ODGs. In adults, pure ODG histology (P = 0.00), frontal location (P = 0.004), calcification [in pure ODGs] (P = 0.03), and lack of p53 protein overexpression (P = 0.00) showed significant statistical correlation with 1p/19q codeletion. CONCLUSIONS: This study is unique in being one of the largest on ODGs for 1p/19q co-deletion including both pediatric and adult age groups of Indian patients. The results showed co-deletion in 60% of adult ODGs and 25% of pediatric pure ODGs. This reemphasizes the occurrence of 1p/19q codeletion, even though rare, in the pediatric age group.

Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort.

The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1-84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma IDH mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma IDH mutant (IDH (mut)) (11.0 %), anaplastic astrocytoma IDH wild type (IDH (wt)) (5.3 %), glioblastoma IDH (mut) (17.1 %), and glioblastoma IDH (wt) (33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (p < 0.001). We did not find prognosis differences between grades III and IV for IDH (mut) 1p/19q intact and IDH (wt) gliomas in univariate and multivariate analyses. Among anaplastic astrocytoma IDH (wt), cases with chromosome arm 7p gain and 10q loss (55 %) had shorter PFS than the others (p = 0.027). In conclusion, the new WHO histomolecular classification of diffuse gliomas presented with high prognostic value. Grading was not discriminant between grade III and IV high-grade gliomas.

Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients.

The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p < 0.001), had Karnofsky Performance Status >70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income ≥$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease.

Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome.

BACKGROUND AND PURPOSE: Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome. METHODS: The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life-time risk for brain tumors in Lynch syndrome, and the mismatch repair (MMR) status in all tumors available was evaluated. RESULTS: Primary brain tumors developed in 41/288 families at a median age of 41.5 (range 2-73) years. Biallelic MMR gene mutations were linked to brain tumor development in childhood. The risk of brain tumors was significantly higher (2.5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6. Glioblastomas predominated (56%), followed by astrocytomas (22%) and oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of which showed MMR defects. None of these tumors showed immunohistochemical staining suggestive of the IDH1 R132H mutation. CONCLUSION: In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects.

Clinicopathological findings and five year survival rates for patients with central nervous system tumors in Yazd, Iran.

BACKGROUND: The incidence rate of brain tumors has increased more than 40% in the past 20 years, especially in adults. We aimed to study the clinical and pathological findings of central nervous system (CNS) tumor patients and to evaluate their 5 year survival rates. MATERIALS AND METHODS: The archives of all patients with CNS tumors in 6 health care centers in Yazd, Iran, from 2006 to 2013, were studied. Patients data were extracted using a checklist which included age, sex, date of reference and diagnosis, date of death, clinical signs, radiography findings, pathology report, size and location of tumor, patient treatment and grade of tumor. RESULTS: A total of 306 patient records were studied in the 8 year period. The most prevalent type of tumor was astrocytoma (n=113, 36.9%). The frequency of almost all tumor types was statistically higher in male patients (p=0.025). In most cases surgery with radiotherapy was the treatment of choice (49.3%). The most frequent symptom reported was headache (in 60.8% of patients) followed by convulsions (15.7%). Most of the tumors were located in the right hemisphere (46.1%) and the frontal and parietal lobe (26% and 12%, respectively). Radiography findings displayed edema with a nonhomogeneous lesion in majority of the patients (87%). The survival fraction of the patients with malignant tumors decreased over time (0.807 in the first year and 0.358 at the end of the 5th year). CONCLUSIONS: Astrocytoma was the more common CNS tumor with male predominance. Overall survival rates of malignant tumors decreased over time and this was in relation with tumor grade.

[Occurrence and molecular pathology of low grade gliomas]. / Alacsony grádusú glialis daganatok elofordulása és molekuláris patológiája.

BACKGROUND: The WHO grade I. and II. low-grade gliomas represent nearly the 15% of all primary brain tumors. These tumours contain clinically, histologically and molecularly distinct tumor types. According to their histologic characteristic, grade II glial tumours are the diffuse astrocytoma, oligodendroglioma and oligoastrocytoma subgroups; ependymal tumors are not included in this study. METHODS: In our publication, we analysed the histologically diagnosed glioma cases between 2007 and 2011 at our institution. RESULTS: Low-grade gliomas were diagnosed in 127 cases (62 male / 65 female), and the mean ages were 39 years (+/- 20.3). More than half of the cancers were localized in the frontal lobe, and the second most frequent area was the temporal lobe. Finally, we complete our report with an overview of major molecular pathways in low-grade gliomas.