Cases Of WHO Grade Research Articles

NIMG-73. RADIOGRAPHIC CHANGES AFTER RADIATION THERAPY IN SUBTOTALLY RESECTED ATYPICAL MENINGIOMAS

Abstract BACKGROUND Adjuvant radiotherapy (RT) has been shown to improve outcomes after subtotal resection (STR) of atypical meningioma, but little is known about how tumors evolve on magnetic resonance imaging (MRI) and whether this correlates with RT response. METHODS We retrospectively identified histologically confirmed cases of WHO Grade II atypical meningioma at a large academic institution from 2004-2020 who underwent subtotal resection and received radiation. Clinicodemographic, surgical, RT, and histopathologic data were collected, as well as clinical outcomes, with a median follow-up time of 69 months (IQR 61). Patients were stratified by external beam RT (EBRT) and stereotactic radiosurgery (SRS). Radiographic data included tumor location, cerebral edema, susceptibility changes, leptomeningeal enhancement, calcification, necrosis, and time to recurrence. Progression was defined by radiology report. RESULTS Of 31 patients with STR for newly diagnosed atypical meningioma, 65% (20 of 31) received RT and 11 of 20 (55%) received EBRT while nine received SRS. Of the convexity/parasagittal meningiomas (N=10), 40% demonstrated venous sinus invasion. 65% (N=13) of cases were treated upfront; the other seven progressed at a median 9.4 months before undergoing RT. Post-RT, 74% decreased in size (N=5) or stabilized (N=9); imaging was not available for one case. Recurrence after RT was observed in five cases. 11 cases developed restricted diffusion at median onset of 24.9 months; 7 developed adjacent leptomeningeal enhancement at median onset of 14.7 months, of which 86% (6 of 7) received SRS. Other patterns included adjacent nodular (N=3) and linear (N=2) enhancement, and adjacent confluent T2 signal (N=4); these could potentially represent radiation-related changes. Only one case developed calcification after 70 months. CONCLUSIONS Atypical meningiomas exhibit variable patterns of evolution after RT which may predict treatment outcomes. Multivariate analysis is planned to correlate radiographic changes with pathology characteristics, RT modality, and time to recurrence.

Long-Term Follow-Up, Treatment Strategies, Functional Outcome, and Health-Related Quality of Life after Surgery for WHO Grade 2 and 3 Intracranial Meningiomas.

Simple SummaryMeningiomas are the most common group of primary intracranial tumors. While the majority are classified as WHO grade 1, WHO grade 2 and 3 meningiomas have poorer outcomes, even after gross total resection, and often require supplementary treatment. Long-term follow-up data regarding the progression-free survival (PFS) and overall survival (OS) for grade 2 and 3 tumors are scarce, and data evaluating the routine use of supplementary radiotherapy and radiosurgery have been inconclusive. Furthermore, few studies have reported data on the health-related quality of life (HRQoL), anxiety, and depression for these patients. In this population-based cohort study, we reviewed 51 cases of WHO grade 2 and 3 meningiomas. We found that the median OS was 13 years for grade 2 and 1.4 years for grade 3 meningiomas. Meningioma was the cause of death in 93% of the patients who passed away. The surviving patients showed HRQoL measures comparable to that of the general population, with the exception of significantly more anxiety and depression. All patients who worked preoperatively returned to work after their treatment.Progression-free survival (PFS) and overall survival (OS) for WHO grade 2 and 3 intracranial meningiomas are poorly described, and long-term results and data evaluating the routine use of supplementary fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) has been inconclusive. The aim of this study was to determine the long-term PFS and OS at a center that does not employ routine adjuvant RT. For this purpose, a retrospective population-based cohort study was conducted of all WHO grade 2 and 3 meningiomas surgically treated between 2005 and 2013. The cohort was uniformly defined according to the WHO 2007 criteria to allow comparisons to previously published reports. Patient records were reviewed, and patients were then prospectively contacted for structured quality-of-life assessments. In total, 51 consecutive patients were included, of whom 43 were WHO grade 2 and 8 were grade 3. A Simpson grade 1–2 resection was achieved in 62%. The median PFS was 31 months for grade 2 tumors, and 3.4 months for grade 3. The median OS was 13 years for grade 2, and 1.4 years for grade 3. The MIB-1-index was significantly associated with an increased risk for recurrence (p = 0.018, OR 1.12). The median PFS was significantly shorter for high-risk tumors compared to the low-risk group (10 vs. 46 months; p = 0.018). The surviving meningioma patients showed HRQoL measures comparable to that of the general population, with the exception of significantly more anxiety and depression. All patients who worked before surgery returned to work after their treatment. In conclusion, we confirm dismal prognoses in patients with grade 2 and 3 meningiomas, with tumor-related deaths resulting in severely reduced OS. However, the cohort was heterogenous, and a large subgroup of both grade 2 and 3 meningiomas was alive at 10 years follow-up, suggesting that a cure is possible. In addition, fractionated radiotherapy and chemotherapy had little benefit when introduced for recurrent and progressive diseases.

Clinicopathological Features of Meningiomas in Tibet

Objective To analyze the clinicopathological features and immunohistochemical expression of meningiomas in the Tibetan population in Tibet,and improve the understanding of meningiomas. Methods The clinical and pathological data of all the meningiomas diagnosed by pathology in Tibet Autonomous Region People's Hospital from April 2013 to March 2021 were analyzed retrospectively.All the cases underwent immunohistochemical staining of trimethylation of lysine 27 on histone H3 (H3K27me3),mucin 4 (MUC4),somatostatin receptor 2 (SSTR2),progesterone receptor,epithelial membrane antigen,glial fibrillary acidic protein,vimentin,S-100,P53,and Ki-67.The histopathological features and the staining results were observed under a light microscope. Results A total of 116 cases of meningiomas were included in this study,with the male-to-female ratio of 1.0∶2.6 and the age of 4-73 years.The main clinical symptom was headache.The imaging examination showed that 114 cases had single lesions and 2 cases had multiple lesions.The tumors were located in the cranium (108 cases) and spinal canal (8 cases).The maximum diameter of the tumors ranged from 0.3 cm to 10.0 cm,with a mean of (5.7±2.2) cm.In terms of microscopic grading and histological types,the 116 cases included 111 cases of WHO grade Ⅰ (including 53 cases of fibrous type,20 cases of meningothelial type,24 cases of transitional type,10 cases of psammomatous type,etc.),4 cases of WHO grade Ⅱ (3 cases of atypical type and 1 case of clear cell type),and 1 case of WHO grade Ⅲ (papillary type).The immunohistochemical staining showed H3K27me3 expression absent in 9 cases (9/116,7.8%),MUC4 positive in 64 cases (64/116,55.2%),SSTR2 positive in 101 cases (101/116,87.1%).Eighty cases had follow-up results,among which 71 cases had no recurrence,while 9 cases recurred. Conclusions Meningioma is the most common tumor in the central nervous system in the pathological file of Tibet.It mainly attacks the middle-aged female patients,occupying the parasagittal sinus,falx,and convex surface of the brain.Fibrous meningioma of WHO grade Ⅰ is common,while the meningiomas of WHO grades Ⅱ and Ⅲ are rare.The expression degree of MUC4 is higher in meningothelial and transitional meningiomas but lower in fibrous meningiomas.There may be no correlation between the absence of H3K27me3 expression and prognosis.

Skeletal Metastases in a Treated Case of WHO Grade IV Glioma without Relapse of Primary Tumor: A Rare Entity

Glioblastoma is the most common primary malignant brain tumors of the adult with a very dismal prognosis, representing 12-15% of all intracranial tumors in adult. The mean age of survival after diagnosis is approximately 14.6 months despite treatment. However, extracranial metastases are rare in the case of glioblastoma. We report a case of a 37-year-old female who had right frontal lobe glioblastoma and was operated on in December 2019 and received radiotherapy. There was complete remission of the tumor. After 1 year, she developed a low backache and pain in her right hip. Investigations revealed new-onset lesions in the bones. HPE proved the lesions to be metastatic glioblastoma.

Les glioblastomes de l'enfant au service de neurochirurgie de Fann à Dakar

INTRODUCTION : Le glioblastome (GBM) est une tumeur généralement de l’adulte. Cependant, il est rare en pédiatrie. Leur pronostic est uniformément péjoratif et les directives de prise en charge restent encore non codifiées. Nous avons réalisé une étude rétrospective afin d’en rechercher les particularités cliniques et pathologiques ainsi que les éventuels facteurs pronostiques. PATIENTS ET METHODES : Il s’agit d’une étude rétrospective portant sur 8 enfants porteurs de GBM confirmé à l’histologie, colligés au service de neurochirurgie du Centre Hospitalier National Universitaire de Fann, du 1er janvier 2016 au 31 décembre 2018. RESULTATS : La fréquence annuelle était de 2,6 cas. On notait une prédominance masculine avec un sex-ratio de 1,6. Le délai de consultation moyen était de 3 mois et demi. Le motif de consultation principal était le syndrome d’hypertension intracrânienne (HTIC) retrouvé chez 62,5% des cas. La région la plus concernée était le lobe pariétal (n=4). Le délai moyen de prise en charge chirurgicale était de 2,3 mois. La chirurgie d’exérèse a permis une résection macroscopiquement complète dans la moitié des cas. L’étude histologique avait retrouvé huit cas de glioblastome classé grade IV de l’OMS. Un seul patient avait bénéficié d’une radio-chimiothérapie adjuvante. Le taux de mortalité à 6 mois était de 85,7% avec une médiane de survie de 6,5 mois. CONCLUSION : Les glioblastomes demeurent une rareté chez l’enfant. Le traitement multimodal associant chirurgie d’exérèse, chimio- et radiothérapie reste le garant pour un meilleur pronostic.

Value of MRI Radiomics Based on Enhanced T1WI Images in Prediction of Meningiomas Grade

Different grades of meningiomas require different treatment strategies and have a different prognosis; thus, the noninvasive classification of meningiomas before surgery is of great importance. The purpose of this study was to explore the application value of magnetic resonance imaging (MRI) radiomics based on enhanced-T1-weighted (T1WI) images in the prediction of meningiomas grade. A total of 98 patients with meningiomas who were confirmed by surgical pathology and underwent preoperative routine MRI between January 2017 and December 2019 were analyzed. There were 82 cases of low-grade meningiomas (WHO grade I) and 16 cases of high-grade meningiomas (7 cases of WHO grade II and 9 cases of WHO grade III). These patients were randomly divided into a training group and test group according to 7:3 ratio. The lesions were manually delineated using ITK-SNAP software, and radiomics analysis were performed using the Analysis Kit (AK) software. A total of 396 tumor texture features were extracted. Subsequently, the LASSO algorithm was used to reduce the feature dimensions. Next, a prediction model was constructed using the Logistic Regression method and receiver operator characteristic was used to evaluate the prediction performance of the model. A radiomics prediction model was constructed based on the selected nine characteristic parameters, which performed well in predicting the meningiomas grade. The accuracy rates in the training group and the test group were respectively 94.3% and 92.9%, the sensitivities were respectively 94.8%, and 91.7%, the specificities were respectively 91.7% and 100%, and the area under the curve values were respectively 0.958 and 0.948. The MRI radiomics method based on enhanced-T1WI images has a good predictive effect on the classification of meningiomas and can provide a basis for planning clinical treatment protocols.

Whole-tumor histogram analysis of apparent diffusion coefficient maps in grading diagnosis of ependymoma

ObjectiveTo study the value of whole-tumor histogram analysis which is based on apparent diffusion coefficient maps in grading diagnosis of ependymoma.Methods71 patients with ependymal tumors were retrospectively analyzed, including 13 cases of WHO grade I, 28 cases of WHO grade II, and 30 cases of WHO grade III. Mazda software was used to draw the region of interest (ROI) in the apparent diffusion coefficient maps of three groups on every layer of tumor level. The whole-tumor gray histogram analysis was carried to obtained nine characteristic parameters, including mean, variance, kurtosis, skewness, Perc.01%, Perc.10%, Perc.50%, Perc.90%, and Perc.99%. When the parameters satisfy the test of normal distribution and homogeneity of variance, single factor analysis of variance (ANOVA) was carried to compare the three groups and LSD t test was performed to compare the two groups. Besides, the ROC curve was used to analyze the diagnostic efficacy of the parameters.ResultsVariance, Perc.01%, and Perc.10% had significant differences among the three groups (all P < 0.05). The remaining six parameters had no significant difference among the three groups (all P > 0.05). And, between WHO I and WHO II, the sensitivity and specificity of the Perc.10% were 85.7% and 100.0%, the AUC was 0.872, and the cut-off was 126.5. Between WHO I and WHO III, the sensitivity and specificity of the Perc.10% were 85.7% and 87.7%, the AUC was 0.835, and the optimum critical value was 131.33. Besides, the sensitivity, specificity, and AUC of variance between WHO II and WHO III are 68.4%, 76.9%, 0.794, and 2645.7, respectively. They had higher identification efficiency.ConclusionWhole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps could provide ancillary diagnostic value in grading diagnosis of ependymoma. Perc.10% had a high diagnostic efficiency.

MNGI-10. ATYPICAL MENINGIOMA: EARLY OUTCOMES WITH OR WITHOUT POSTOPERATIVE RADIATION

Abstract BACKGROUND Adjuvant radiotherapy (RT) in atypical meningioma, especially for gross-totally resected tumors, remains controversial. METHODS We retrospectively identified histologically-confirmed cases of WHO Grade II atypical meningioma at a large academic institution from 2004–2018. Clinicodemographic, surgical, radiation therapy (RT), and histopathologic data were collected, as well as imaging and clinical outcomes, with a median follow-up time of 26 months (IQR 32). Patients were stratified by resection status and whether or not upfront RT was administered. Additionally, subanalyses were performed to compare external beam RT (EBRT) and stereotactic radiosurgery (SRS). Progression was defined by radiology report. RESULTS Of 122 patients, 45 were excluded for lacking adequate records of previous treatment, less than 3 months follow-up, or lacking MR imaging. Of 77 patients analyzed, 57% (44/77) were female; median 59-years-old. 48% (24/50) of gross-total-resections (GTR) received upfront RT – only a single case progressed, at 39 months. Of 26 GTR patients without upfront RT, 8/26 (31%) progressed at median 19.5 months – of these, 2 were lost to follow-up, 5 received salvage RT, and 1 had surgery alone. Adjuvant RT was associated with superior progression free survival (PFS) in GTR (Cox proportional hazard ratio 0.15, likelihood-ratio p=0.025; median PFS not reached). Of 15 subtotal resections (STR) receiving upfront RT, 11 received EBRT and 4 received SRS – 6 progressed (median 37 months), all after EBRT. Upfront SRS demonstrated superior PFS over EBRT following STR (p=0.036). Across the cohort there was one confirmed death, a GTR patient (without RT) who suffered an ischemic stroke at 11 months. CONCLUSION This large single-center retrospective analysis indicates adjuvant RT improves PFS in GTR atypical meningiomas, in concordance with prior studies. It is limited by short median follow-up, possibly related to long-term stability in treated patients. In STR tumors, SRS may contribute to improved PFS compared to EBRT.

P09.02 Surgical treatment for intracranial meningiomas in elderly patients growing during follow-up study

Abstract BACKGROUND In Japan in which life expectancy exceeds 85 years old, there are many elderly people who have sufficient healthy life even over 75 years of age and maintain social activities. With the increase in life expectancy and widespread use of magnetic resonance imaging (MRI), it is estimated that the number of asymptomatic meningioma diagnosed in elderly patients will increase. They are often followed up for the elderly, but they often become symptomatic as the tumor grows. Considering the inherent complications of the elderly and the patient’s life expectancy, it is often difficult to decide whether to operate. Here, we report the results of surgical treatment for intracranial meningiomas in elderly patients growing during follow-up study. MATERIAL AND METHODS Between January 2010 and December 2018, we treated 322 meningioma patients, including 18 patients older than 75 years old who had grown during follow-up. We performed a retrospective analysis of the 18 patients and measured Tumor doubling time (TDT) using CT scan or MRI image. We mainly examined the relationship between TDT and WHO classification, MIB-1 index, edema and calcification, intensity on MRI T2 weighted-imaging. RESULTS 5 were male and 13 were female. There were 6 cases of skull base meningioma and 13 cases in which the tumor showed high intensity on the MRI T2 weighted-imaging. 4 cases showed intratumoral hemorrhage. 8 cases had edema. 11 cases were symptomatic meningiomas and 7 cases were asymptomatic meningiomas. There were 7 cases of WHO grade I meningioma and 11 cases of WHO grade II or III meningiomas. TDT was an average of 1.82 year (0.37–3.74). 9 patients have taken anticoagulant or antiplatelet medication. CONCLUSION In following up elderly meningioma patients, MRI should be performed at periodic intervals if the tumor showed high intensity on the MRI T2 weighted-imaging or had edema. In case of surgical treatment, we should pay attention to taking anticoagulant or antiplatelet medication, and treatment strategy is needed to avoid complications with sufficiently preoperative examination.

Quantitative evaluation of intravoxel incoherent motion diffusion-weighted imaging and three-dimensional arterial spin labeling in Ki-67 labeling index and grading of brain gliomas

Objective: To investigate the value of multiple parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional arterial spin labeling (3D-ASL) in Ki-67 labeling index (Ki-67 LI) and grading of human brain gliomas. Methods: From December 2015 to May 2018, 45 patients of gliomas confirmed by surgical pathology in Li Huili Hospital, Ningbo Medical Center were divided into low-grade group (20 cases of WHO grade Ⅱ) and high-grade group (12 cases of WHO grade Ⅲ, 13 cases of WHO grade Ⅳ), and the Ki-67 LI of glioma was obtained by immunohistochemistry. All patients, 24 males and 21 females, aged 25-83 years, mean(53±12)years, underwent conventional magnetic resonance imaging (MRI), IVIM-DWI and 3D-ASL before operation, then measured the true water diffusion coefficient (D), microcirculation perfusion coefficient (D(*)), perfusion fraction (f) and cerebral blood flow (CBF) in the tumor solid area and the contralateral normal white matter area. Those parameters and the Ki-67 LI were compared between the low-and high-grade groups with Mann-Whitney U test. Spearman's correlation was used to analyze the correlation between the quantitative parameters and Ki-67 LI. The ROC curve was used to assess the diagnostic efficacy of parameters in the grading assessment of brain gliomas. Results: The D(0.791×10(-3)mm(2)/s) and f (0.261) of the high-grade group were lower than those of the low-grade group, whereas D(*) (4.153×10(-3) mm(2)/s), CBF(102.027 ml·min(-1)·100 g(-1)) and Ki-67 LI (0.25) were higher (P<0.05). There was a moderate negative correlation between D, f and Ki-67 LI(r=-0.513,-0.457, all P<0.05). There was no significant correlation between D(*) and Ki-67 LI (P=0.571). The area under the curve (AUC) for identifying high-and low-grade gliomas by D, D(*), f and CBF values was 0.965, 0.745, 0.842, and 0.830 respectively (all P<0.05). Conclusion: D and f can be used for quantitative prediction of Ki-67 LI. IVIM-DWI and 3D-ASL are helpful in the grading assessment of gliomas, and the diagnostic efficiency of D is the highest.

Clinical features and treatment analysis of intracranial extraventricular ependymomas

Objective To study the clinical features, imaging demonstration and treatment outcomes of intracranial extraventricular ependymomas. Methods A total of 17 patients with intracranial extraventricular ependymoma underwent surgical treatment at Department of Neurosurgery, Renmin Hospital of Wuhan University from March of 2010 to June of 2016 and were enrolled into this retrospective study. Pre-operative MR scan showed single lesion located at supratentorial region in all cases. Those lesions were located in occipital lobe (5 cases), occipitoparietal lobe (2 cases), temporal lobe (3 cases), frontal lobe (4 cases) and parietal lobe (3 cases). Among those, 7 were solid and 10 were cystic lesions. Surgical excision was performed for all lesions. Post-operative follow-up was performed for every patient through telephone and outpatient review. Results Of those cases, total resection was achieved in 15 cases, including 10 cases of WHO grade Ⅱ and 5 case of WHO grade Ⅲ, and partial resection in 2 (WHO grade Ⅲ). Intraoperative pathological diagnosis suggested that 10 cases were ependymoma (WHO gradeⅡ) and 7 cases were anaplastic ependymoma (WHO grade Ⅲ). All patients′ clinical symptoms were relieved following surgery. Four cases (grade Ⅲ), including 2 cases undergoing partial resection, received post-operative radiotherapy. The follow-up time of those patient were from 14 to 74 months, with a median of 33.2 months. During the follow-up, no case showed any signs of spinal cord metastasis. Recurrence was reported in 7 cases and 4 of them (grade Ⅲ) received post-operative radiotherapy. Among those, 1 case underwent the second tumor total resection and postoperative radiotherapy, 1 case died 3 months after the second tumor total resection, 2 cases of tumor partial resection rejected the second operation and died after 4 and 6 months, respectively, and the other 3 recurrent cases included 2 (grade Ⅱ) and 1 (grade Ⅲ) undergoing the second tumor total resection without postoperative radiotherapy and 1 (grade Ⅲ) that died of postoperative hemorrhage. Conclusions As intracranial extraventricular ependymoma has non-specific clinical and imaging features, accurate pre-operative diagnosis is difficult. Total tumor resection is the primary method of treatment, if it is possible. The choice of resection type and pathological grading could be predictive factors in postoperative evaluation. Key words: Ependymoma; Neurosurgical procedures; Treatment outcome; Intracranial extraventricular

World Health Organization grade III meningiomas. A retrospective study for outcome and prognostic factors assessment

Background. Anaplastic meningiomas are uncommon primary intracranial tumours associated with high level of recurrence and low life expectancy. Through three institutions experience, we analysed the clinical characteristics of patients with malignant meningiomas to determine their outcome and identify prognostic factors that may influence recurrence and survival. Material and methods. A retrospective search identified 62 cases of WHO grade III meningiomas, of whom 9 (14.5%) were not considered in the survival analysis as no follow-up data were available. Thirty patients (48.4%) had a previous history of non-malignant meningioma surgery. The patients underwent a total of 139 surgical resections and 42 courses of radiotherapy of which 27 were given after the WHO grade III meningioma diagnosis. Results. Eighteen patients (29.5%) were re-operated for a relapse of their anaplastic meningioma. Median time between the first and the second surgery was 1.3 years. Median overall survival time was 3.5 years. Overall survival probabilities at 1, 2 and 5 years were 74.6%, 95% confidence interval (CI) [63.8, 87.1], 58.7%, 95% CI [46.4, 74.3] and 37.7%, 95% CI [25, 56.8], respectively. Extent of resection was associated with the survival. Discussion. This retrospective series highlights the poor prognosis associated with the diagnosis of malignant meningioma. Complete or subtotal resection may prolong the patients’ survival. We could not confirm the usefulness of postoperative radiotherapy.

Chordoid Meningioma: Differentiating a Rare World Health Organization Grade II Tumor from Other Meningioma Histologic Subtypes Using MRI.

Meningiomas are very commonly diagnosed intracranial primary neoplasms, of which the chordoid subtype is seldom encountered. Our aim was to retrospectively review preoperative MR imaging of intracranial chordoid meningiomas, a rare WHO grade II variant, in an effort to determine if there exist distinguishing MR imaging characteristics that can aid in differentiating this atypical variety from other meningioma subtypes. Ten cases of WHO grade II chordoid meningioma were diagnosed at our institution over an 11-year span, 8 of which had preoperative MR imaging available for review and were included in our analysis. Chordoid meningioma MR imaging characteristics, including ADC values and normalized ADC ratios, were compared with those of 80 consecutive cases of WHO grade I meningioma, 21 consecutive cases of nonchordoid WHO grade II meningioma, and 1 case of WHO grade III meningioma. Preoperative MR imaging revealed no significant differences in size, location, signal characteristics, or contrast enhancement between chordoid meningiomas and other meningiomas. There were, however, clear differences in the ADC values and normalized ADC ratios, with a mean absolute ADC value of 1.62 ± 0.33 × 10(-3) mm(2)/s and a mean normalized ADC ratio of 2.22 ± 0.47 × 10(-3) mm(2)/s in chordoid meningiomas compared with mean ADC and normalized ADC values, respectively, of 0.88 ± 0.13 × 10(-3) mm(2)/s and 1.17 ± 0.16 × 10(-3) mm(2)/s in benign WHO grade I meningiomas, 0.84 ± 0.11 × 10(-3) mm(2)/s and 1.11 ± 0.15 × 10(-3) mm(2)/s in nonchordoid WHO grade II meningiomas, and 0.57 × 10(-3) mm(2)/s and 0.75 × 10(-3) mm(2)/s in the 1 WHO grade III meningioma. Chordoid meningiomas have statistically significant elevations of ADC and normalized ADC values when compared with all other WHO grade I, II, and III subtypes, which enables reliable preoperative prediction of this atypical histopathologic diagnosis.

Congenital oligodendroglioma: clinicopathologic and molecular assessment with review of the literature.

Oligodendroglioma is an infiltrating glial neoplasm frequently seen in adults. Pediatric oligodendrogliomas are rare, with very few cases presenting in infancy and only rare congenital examples. In contrast to adult oligodendrogliomas, pediatric cases typically lack 1p/19q codeletion. Herein we report a case of WHO grade II oligodendroglioma diagnosed in a 7-month-old male infant. The patient initially presented at 3 months of age with symptoms suspicious for seizure. Initial workup including electroencephalography (EEG), electrocardiogram (EKG), and computed tomography (CT) of the head was negative. His symptoms persisted, and subsequent magnetic resonance imaging (MRI) performed at age of 7 months revealed a 2 cm contrast-enhancing left temporal lobe mass. The mass was excised and the microscopic appearance was that of a classic low grade oligodendroglioma composed of cells with uniformly round nuclei, perinuclear halos, delicate branching capillaries, and an absence of high grade features. Mutant specific (R132H) isocitrate dehydrogenase-1 (IDH1) immunohistochemistry was negative, and the tumor lacked detectable 1p or 19q deletions by fluorescent in situ hybridization (FISH). The onset of neurological symptoms in early infancy followed by the positive MRI findings suggests that this case represents a rare example of congenital oligodendroglioma.

Prognostic value of blood flow estimated by arterial spin labeling and dynamic susceptibility contrast-enhanced MR imaging in high-grade gliomas.

Several studies evaluated the predictive value of dynamic susceptibility contrast enhanced (DSC) imaging and arterial spin labeling (ASL) with regard to histological grade. Yet still less is known about their significance in terms of patients prognosis. Our purpose was to evaluate the agreement between them and the prognostic value of ASL- and DSC-CBF measurements for time-to-recurrence (TTR). Sixty nine cases of WHO Grade 3-4 gliomas underwent both DSC- and ASL-MRI. Normalized ASL and DSC-based cerebral blood flow (CBF) maps as well as DSC-derived cerebral blood volume maps (CBV) were analyzed. Wilcoxon test and Bland-Altman plot analysis were applied in order to compare DSC-rCBF and ASL-rCBF. Spearman's rank correlation coefficients were determined for all perfusion parameters. Receiver operating characteristic (ROC) curve and survival curve analyses were performed. The median values of ASL-rCBF, DSC-rCBF, and DSC-rCBV were 5.3, 6.9, and 8.0, respectively. There was neither significant correlation nor difference between ASL-rCBF and DSC-rCBF. Slight proportional bias was demonstrated in the Bland-Altman plot analysis of ASL-rCBF and DSC-rCBF values. Unlikely to DSC-rCBV, DSC- and ASL-based rCBF parameters demonstrated moderate sensitivity and specifitity for tumor recurrence but no statistical significance regarding their prognostic values for TTR in the Kaplan-Meier analysis. There were neither correlation nor interchangeability between the DSC-rCBF and ASL-rCBF estimations, which demonstrated comparable, though not significant prognostic value for the prediction of TTR. rCBV measurements seem to provide the best sensitivity and specificity to predict tumor recurrence and survival time in these patients.

Malignant clinical features of anaplastic gliomas without IDH mutation.

Diagnosis of WHO grade III anaplastic gliomas does not always correspond to its clinical outcome because of the isocitrate dehydrogenase (IDH) gene status. Anaplastic gliomas without IDH mutation result in a poor prognosis, similar to grade IV glioblastomas. However, the malignant features of anaplastic gliomas without IDH mutation are not well understood. The aim of this study was to examine anaplastic gliomas, in particular those without IDH mutation, with regard to their malignant features, recurrence patterns, and association with glioma stem cells. We retrospectively analyzed 86 cases of WHO grade III anaplastic gliomas. Data regarding patient characteristics, recurrence pattern, and prognosis were obtained from medical records. We examined molecular alterations such as IDH mutation, 1p19q loss, TP53 mutation, MGMT promoter methylation, Ki67 labeling index, and CD133, SOX2, and NESTIN expression. Of the 86 patients with anaplastic gliomas, 58 carried IDH mutation, and 40 experienced recurrence. The first recurrence was local in 25 patients and distant in 15. Patients without IDH mutation exhibited significantly higher CD133 and SOX2 expression (P = .025 and .020, respectively) and more frequent distant recurrence than those with IDH mutation (P = .022). Patients with anaplastic gliomas without IDH mutation experienced distant recurrence and exhibited glioma stem cell markers, indicating that this subset may share some malignant characteristics with glioblastomas.

Clinical and pathologic analysis of astrocytic tumors with loss of heterozygosity on chromosome 10q

To study the correlation between loss of heterozygosity (LOH) on chromosome 10q and pathologic features, pathogenesis, prognosis of astrocytic tumors. LOH on 10q was studied by interphase fluorescence in-situ hybridization (FISH) in 85 cases of astrocytic tumor, including 35 cases of WHO grade II tumors and 50 cases of WHO grade IV tumors. LOH on 10q was detected in 6 cases (17.1%) of diffuse astrocytoma (WHO grade II) and 34 cases (68.0%) of glioblastoma (WHO grade IV). 10q polysomy was detected in 7 cases (20.0%) of diffuse astrocytoma and 11 cases (22.0%) of glioblastoma. The rates of LOH on 10q in young age group and elderly group were 36.4% (12/33) and 82.4% (28/34), respectively. The difference was of statistical significance (P < 0.05). The rates of LOH on 10q in the diffuse astrocytoma and glioblastoma were 21.4% (6/28) and 87.2% (34/39), respectively. The difference was also statistically significant (P < 0.05). Univariate survival analysis showed that patient age, pathologic grade and 10q on LOH correlated with duration of survival (P < 0.05). There are correlation between 10q LOH, patient age and pathologic grade of astrocytic tumors. LOH on 10q is also related to the pathogenesis of astrocytic tumors and is helpful in predicting prognosis.

Effects of expressions of VEGF, VEGF ⁃ C, VEGFR ⁃ 3 on interstitial angiogenesis and tumor cell proliferation in human gliomas

Objective To explore the changes of vascular endothelial growth factor (VEGF), vascular endothelial growth factor⁃C (VEGF⁃C) and vascular endothelial growth factor receptor⁃3 (VEGFR⁃3) expression and their impacts on tumor cell proliferation and interstitial angiogenesis in gliomas. Methods The specimens of 20 cases of WHO grade Ⅰ -Ⅱ, 20 cases of grade Ⅲ and 20 cases of grade Ⅳ gliomas were collected from Department of Neurosurgery in Tianjin Medical University General Hospital during the period from 2000 to 2009. The expressions of VEGF, VEGF⁃C, VEGFR⁃3 and Ki⁃67 as well as the density of CD31 positive vessels were detected in 60 gliomas with different grades of malignancy by means of tissue microarray and immunohistochemistry. Results In the tumor cells and vascular endothelial cells of 60 patients with gliomas, the positive rate of VEGF, VEGF ⁃ C and VEGFR ⁃ 3 was 88.33% (53/60) and 100% (60/60), 100% (60/60) and 16.67% (10/60), and 100% (60/60) and 21.67% (13/60) of tumor cells, respectively. No significant differences were seen among groups in different grades (P > 0.05, for all). In grade Ⅰ-Ⅱ, gradeⅢ and gradeⅣ gliomas, the density of VEGF positive tumor cells was (17.65 ± 9.00), (37.30 ± 18.54) and (83.40 ± 22.98) positive cell number/0.05 mm2, the density of VEGF⁃C positive tumor cells was (38.00 ± 17.82), (79.30 ± 5.23) and (102.00 ± 13.07) positive cell number/0.05 mm2, the density of VEGFR⁃3 positive vessels was (3.65 ± 2.01), (10.50 ± 3.98) and (14.60 ± 7.29) positive vessel number/4 HF, the density of Ki⁃67 positive tumor cells was (9.30 ± 3.48), (31.15 ± 9.44) and (60.15 ± 13.60) positive cell number/0.05 mm2, and CD31 positive microvessels was (6.75 ± 2.24), (10.35 ± 2.98) and (14.30 ± 3.51) positive vessel number/4 HF, respectively. The differences of each parameter mentioned above were all significant among the groups in different grades (P < 0.05 or P < 0.01), and they were positively correlated with each other (r = 0.663-0.910, P < 0.01). Conclusion Over⁃expression of VEGF and VEGF⁃C was seen in glioma cells, and VEGFR⁃3 was also over⁃expressed in interstitial vascular endothelial cells. Their expression levels increased along with the grade of malignancy. The paracrine loops composed by them can induce interstitial angiogenesis and tumor cell proliferation, and thereby play a crucial role in the occurrence and progression of gliomas. DOI：10.3969/j.issn.1672-6731.2010.04.017

Front-Line Treatment of Low-Grade Non-Follicular Non-Hodgkin Lymphoma (Final Report of Gisl LL02 Trial).

Indolent Non-follicular non-Hodgkin Lymphoma (NFo-NHL) is a group of relatively frequent lymphoproliferative diseases, nevertheless extended clinical and prognostic studies are still lacking. In 2002 the Gruppo Italiano Studio Linfomi (GISL) initiated a LL02 prospective multicenter phase II trial, with the aim to evaluate the efficacy and safety of FC combination in the first-line therapy of NFo-NHL patients younger than 70 years. Between July 2002 and September 2006, 58 adult patients (35 males and 23 females, median age 64 yrs, range 40–75) affected by NFo-NHL in active disease phase, were consecutively enrolled in 12 GISL Hematological Centres. Patients were treated with a dose of 25 mg/mq Fludarabine plus 250 mg/mq Cyclophosphamide administred intravenously daily for 3 days; each cycle was repeated every 28 days for 6 courses. During the treatment patients received oral thrimethoprim-sulphametoxazole prophylaxis. After the intermediate evaluation, 48/58 patients (82.8%) had an objective response (ORR) with a 20.7% of complete remission (CR) plus 62.1% of partial remission (PR); at the final evaluation the ORR percentage was 84.5% with a 41.4% of CR (24 pts) and 43.1% of PR (25 pts); three patients were in progressive disease (5.2%) and one in stable disease (1.7%). The median overall survival (OS) was not reached with an 88% and 84% at 12 and 24 months; the progression free survival (PFS) was 89% and 77% and the event free survival (EFS) was 81% and 66% at 12 and 24 months respectively.About the toxicity profile, the major toxicity was hematological with a 18% cases of WHO grade III or IV anemia, 40% leucopenia, 33% neutropenia and 10% piastrinopenia. The 12% of patients had an infective episode wich a 7.7% of WHO grade III–IV.In conclusion the FC chemotherapy is a useful chance for advanced untreated non follicular low-grade NHL, with an optimal ORR, CR and PFS. The crucial point of FC remains OS, that not seems to be significantly improved in comparison with fludarabine alone or with standard therapy, even though the better quality of responses; Rituximab plus FC association is growing in literature as the probably key to find a real improvement also in this aspect.

Low grade ganglioglioma rapidly progressing to a WHO grade IV tumor showing malignant transformation in both astroglial and neuronal cell components

Gangliogliomas are rare CNS neoplasms mostly occuring in young adults and are usually assigned to WHO grade I. The few cases of WHO grade IV gangliogliomas were either primarily malignant glio-neuronal tumors or underwent malignant progression from other WHO grades after radiotherapy. Herein, we present the case of a now 47-year-old female patient presenting with a benign ganglioglioma and showing a tumor recurrence 2 years later with an anaplastic ganglioglioma, assigned to WHO grade IV, with malignant transformation in both glial and neuronal components. The presented case is the first reported low-grade ganglioglioma rapidly progressing to a WHO grade IV glio-neuronal tumor not being associated with radiotherapy and showing malignant transformation in both astroglial and neuronal tumor cell components.