Chul-Kee Park

Atypical and anaplastic meningiomas: prognostic implications of clinicopathological features

Objectives: To evaluate patient outcome and investigate the prognostic factors of high-grade meningiomas by adopting the 2000 World Health Organization (WHO) classification system. Methods: Between 1986 and 2004, 74 patients were diagnosed with high-grade meningioma: 33 with atypical and 41 with anaplastic meningioma. The mean follow-up was 58.5 months. We reclassified all surgical specimens, according to the 2000 WHO classification system, using two expert neuropathologists. Results: Forty of 74 meningiomas were reclassified as atypical meningioma and 24 as anaplastic meningioma. Overall and recurrence-free survivals were significantly longer in patients with atypical than in those with anaplastic meningioma: 142.5 versus 39.8 months and 138.5 versus 32.2 months, respectively (p<0.001). In patients with atypical meningiomas, brain invasion and adjuvant radiotherapy were not associated with survival; however, in the brain invasion subgroup, adjuvant radiotherapy improved patients’ survival. In patients with anaplastic meningioma, the prognostic factors were brain invasion, adjuvant radiotherapy, malignant progression, p53 overexpression and extent of resection. The p53 overexpression was the only factor associated with malignant progression (p = 0.009). Conclusions: The 2000 WHO classification has identified the truly aggressive meningiomas better than did the previous criteria. A precise meningioma grading system may help to avoid over-treatment of patients with an atypical meningioma as, once the tumour has “declared itself” by recurrence and histological features, it becomes a tumour that is poorly amenable to current therapies.

Differentiating radiation necrosis from tumor recurrence in high-grade gliomas: assessing the efficacy of 18F-FDG PET, 11C-methionine PET and perfusion MRI.

PURPOSE The authors analyzed the characteristics of perfusion magnetic resonance imaging (MRI), (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and (11)C-methionine (MET) PET to compare the efficacies of these modalities in making the distinction between radiation necrosis and tumor recurrence of high-grade glioma. PATIENTS AND METHODS Ten patients were evaluated with dynamic susceptibility contrast perfusion MRI, (11)C-MET PET and (18)F-FDG PET to visualize gadolinium-enhanced lesions during the post-radiation follow-up period. In the perfusion MRI, four regions of interest (ROIs) were identified and average values were calculated. A reference ROI of the same size was defined in the contralateral white matter to obtain the relative cerebral blood volume (rCBV). After coregistering the PET images with the MRI, we measured the maximum uptake values of the lesion and of the contralateral cerebral white matter as reference area to calculate the L(max)/R(max) ratio. RESULTS The rCBV was higher in the recurrence group than in the necrosis group (p=0.010). There was no difference between groups in terms of the L(max)/R(max) ratio as derived from the (18)F-FDG and (11)C-MET PET. CONCLUSION A quantitative rCBV as calculated from a perfusion MRI scan might be superior to the L(max)/R(max) ratio as derived from (18)F-FDG and (11)C-MET PET in order to distinguish a recurrence of high-grade glioma from radiation necrosis.

Sox2 Expression in Brain Tumors : A Reflection of the Neuroglial Differentiation Pathway

Sox2 is a key transcription factor that maintains the proliferation of neuroglial stem cells and inhibits neuronal fate commitment. Moreover, it was recently found that brain tumors contain stem cells that resemble normal neuroglial stem cells in many respects. This study was undertaken to describe Sox2 expression in various brain tumors, and to determine whether Sox2 expression is a universal feature of brain tumors, or whether its expression is limited to a specific lineage of brain tumors. Sox2 immunohistochemistry was performed on 194 brain tumor tissues of various kinds. Fetal and adult normal brain tissues obtained by autopsy and brain tissues of epilepsy patients with cortical dysplasia were used as controls. Semiquantitative reverse transcription polymerase chain reaction was used to confirm the immunohistochemical results. Double immunofluorescence was performed to characterize the lineage of Sox2-positive cells. Sox2 was found to be expressed in various glial tumors, including those with astroglial, oligodendroglial, and ependymal lineages, and in the glial components of mixed neuroglial tumors, regardless of pathologic grade. In brain tumors of embryonal origin, supratentorial primitive neuroectodermal tumors showed robust Sox2 expression, whereas medulloblastomas and pineoblastomas did not. The majority of Sox2-positive tumor cells coexpressed glial fibrillary acidic protein, and most Sox2-negative cells in medulloblastomas and pineoblastomas showed neuronal differentiation. This study suggest that Sox2 may be a tumor marker of glial lineages rather than a universal brain tumor stem cell marker, because its expression pattern was found to correspond to differentiation pathways. On the other hand, the aberrant coexpressions of Sox2 and of a neuronal marker were widely observed in glioblastomas, which reflects a disorganized differentiation pattern that characterizes highly malignant tumors.

Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Radiation Therapy and Concomitant Temozolomide: Comparison Study of Standard and High-b-Value Diffusion-weighted Imaging

PURPOSE To explore the role of histogram analysis of apparent diffusion coefficient (ADC) maps obtained at standard- and high-b-value (1000 and 3000 sec/mm(2), respectively) diffusion-weighted (DW) imaging in the differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide. MATERIALS AND METHODS This retrospective study was approved by the institutional review board of Seoul National University Hospital, and informed consent requirement was waived. Thirty patients with histopathologically proved glioblastoma who had undergone concurrent chemotherapy and radiation therapy (CCRT) with temozolomide underwent diffusion-weighted MR imaging with b values of 1000 and 3000 sec/mm(2), and corresponding ADC maps were calculated from entire newly developed or enlarged enhancing lesions after completion of CCRT. Histogram parameters of each ADC map between true progression (n = 15) and pseudoprogression (n = 15) groups were compared by using the unpaired Student t test. Receiver operating characteristic analysis was used to determine the best cutoff values for predictors in the differentiation of true progression from pseudoprogression. Results were validated in an independent test set of nine patients by using the best cutoff value to predict differentiation of true progression from pseudoprogression. The accuracy of the selected best cutoff value in the independent test set was then calculated. RESULTS In terms of cumulative histograms, the fifth percentile of both ADC at b value of 1000 sec/mm(2) (ADC1000) and the ADC at b value of 3000 sec/mm(2) (ADC3000) were significantly lower in the true progression group than in the pseudoprogression group (P = .049 and P < .001, respectively). In contrast, neither the mean ADC1000 nor the mean ADC3000 was significantly different between the two groups. The diagnostic values of the parameters derived from ADC1000 and ADC3000 were compared, and a significant difference (0.224, P = .016) was found between the area under the receiver operating characteristic curve of the fifth percentile for ADC1000 and that for ADC3000. The accuracies were 66.7% (six of nine patients) and 88.9% (eight of nine patients) based on the fifth percentile of both ADC1000 and ADC3000 in the independent test set, respectively. CONCLUSION The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter in the differentiation of true progression from pseudoprogression of the newly developed or enlarged enhancing lesions after CCRT with temozolomide for glioblastoma treatment. Online supplemental material is available for this article.

Spatiotemporal Evolution of the Primary Glioblastoma Genome

Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen.

Surgically treated tuberculum sellae and diaphragm sellae meningiomas: the importance of short-term visual outcome.

OBJECTIVE:The visual outcome in patients with tuberculum and diaphragm sellae meningiomas treated with microsurgery was evaluated. Prognostic and diagnostic values of short- and long-term postoperative visual outcome and etiology for postoperative visual deterioration are discussed with special attention. METHODS:Clinical data for 30 surgically treated patients with tuberculum and diaphragm sellae meningiomas were reviewed retrospectively. The mean duration of the follow-up period was 75.9 months (range, 12–151 mo). Mean tumor diameter and volume was 25.9 mm (range, 16.3–63.3 mm) and 12.4 cm3 (range, 2.3–125.6 cm3). A visual impairment score was used to assess the short-term (≤2 wk after surgery) and the long-term (>6 mo after surgery) postoperative visual outcome. Various predictive factors for visual outcome were tested statistically. RESULTS:Complete resection was achieved in 23 out of 30 (76.7%) patients. Average preoperative, short- and long-term visual impairment scores were 48.2, 43.4, and 40.9, respectively. Favorable visual outcome was achieved in 80% of patients in the short term and 70% in the long term. Short-term postoperative aggravation of visual function was an ominous sign of further aggravation or at least of little hope for recovery, whereas there was a tendency to improve in the long term if short-term postoperative visual function showed favorable outcome. Recurrence or regrowth of tumor fully was responsible for late deterioration of visual function. No significant prognostic factor for visual outcome could be found. CONCLUSION:Short-term postoperative visual outcome was a strong indicator of permanent visual outcome after surgery for tuberculum sellae and diaphragm sellae meningiomas.

Gamma knife radiosurgery for skull base meningiomas: long-term radiologic and clinical outcome.

PURPOSE To analyze the long-term outcomes in patients with skull base meningiomas (SBMNGs) treated with Gamma Knife radiosurgery (GKRS). METHODS AND MATERIALS Of the 98 consecutive patients with SBMNGs treated with GKRS between 1998 and 2002, 63 were followed up for more than 48 months. The mean (+/-SD) age of the patients was 50 +/- 12 years, the mean tumor volume was 6.5 cm(3) (range, 0.5-18.4 cm(3)), the mean marginal dose was 12.6 Gy (range, 7.0-20.0 Gy), and the mean follow-up duration was 77 +/- 18 months. The mean number of shots was 13.7 +/- 3.8. The tumor volume was decreased at the last follow-up in 28 patients (44.4%) and increased in 6 (9.6%). The actuarial tumor control rate was 90.2% at 5 years. No notable prognostic factor related to tumor control was identified. Ten patients (15.9%) with a cranial neuropathy showed unfavorable outcomes. The rate of improvement in patients with a cranial neuropathy was 45.1%. Age >70 years was likely correlated with an unfavorable outcome in patients with cranial neuropathy (odds ratio = 0.027; p = 0.025; 95% confidence interval 0.001-0.632). Cavernous sinus location was significantly associated with improvement of a cranial neuropathy (odds ratio = 7.314; p = 0.007; 95% confidence interval 1.707-31.34). CONCLUSIONS Gamma Knife radiosurgery is an effective modality for the treatment of SBMNGs and provides favorable outcomes in patients with cranial neuropathy, even in the long-term follow-up period. However, radiosurgery for patients with no or only mild symptoms should be performed cautiously because neither complication rate is low enough to be negligible, especially in elderly patients. A cranial neuropathy by MNGs involving the cavernous sinus seems to have a higher chance of improvement after radiosurgery than other SBMNGs.

Meningioma manifesting intracerebral haemorrhage: a possible mechanism of haemorrhage.

Summary¶ We present a possible mechanism of intracerebral peritumoural haemorrhage in meningioma based on the clinical data of three of our cases. A meningioma manifesting intracerebral haemorrhage is uncommon and some sporadic case reports have been presented, but without any proven mechanisms. We are presenting three cases of convexity meningioma manifesting spontaneous intracerebral haemorrhage with apoplectiform onset. All three patients had no evidence of bleeding tendency or other predisposing factors for haemorrhage. Preoperative radiological studies showed a solid mass attached to the dura with intracerebral peritumoural haematoma. Total removal of the tumour and haematoma could be achieved in every case. Histological investigation revealed extensive tumour infarction in two cases and fibrosis related to pre-existing ischaemia in the other case. The diagnoses were atypical meningioma in two cases and transitional type in one case. We suggest that extensive tumour infarction might be a cause of spontaneous intracerebral peritumoural haemorrhage in our series of patients.

Diffusion-weighted MR imaging for the differentiation of true progression from pseudoprogression following concomitant radiotherapy with temozolomide in patients with newly diagnosed high-grade gliomas.

RATIONALE AND OBJECTIVES The assessment of the therapeutic response of high-grade gliomas treated with concomitant chemoradiotherapy (CCRT) using temozolomide is difficult because of the frequent occurrence of early imaging changes that are indistinguishable from tumor progression, termed pseudoprogression. The purpose of this study was to determine whether diffusion-weighted imaging could be used to differentiate true progression and pseudoprogression. MATERIALS AND METHODS Magnetic resonance images and diffusion-weighted images obtained within 2 months of CCRT completion in patients with high-grade gliomas were retrospectively reviewed. A total of 22 patients with increases in measurable enhancing regions were identified and classified into true progression and pseudoprogression groups on the basis of contrast-enhanced magnetic resonance images obtained 12 weeks after CCRT. Qualitative and quantitative analysis of diffusion-weighted images and apparent diffusion coefficient maps, respectively, was performed to discriminate true progression and pseudoprogression. Statistical analyses were performed using Fishers exact test, unpaired t tests, and receiver-operating characteristic analysis. RESULTS The true progression group showed a higher incidence of homogeneous or multifocal high signal intensity on diffusion-weighted images (seven of 10 patients [70%]), whereas rim high or no high signal intensity (10 of 12 [83%]) was observed in the pseudoprogression group (P = .027). True progression was defined by newly appearing or enlarged enhancing lesions with mean apparent diffusion coefficient values of 1200 × 10(-6) mm(2)/s inside the radiation field after CCRT; the sensitivity, specificity, and accuracy were 80% (eight of 10), 83.3% (10 of 12), and 81.2% (18 of 22), respectively. CONCLUSIONS The assessment of diffusion-weighted images for patients with increases of measurable enhancing regions 2 months after CCRT completion is useful for differentiating true progression from pseudoprogression.

True Progression versus Pseudoprogression in the Treatment of Glioblastomas: A Comparison Study of Normalized Cerebral Blood Volume and Apparent Diffusion Coefficient by Histogram Analysis

Objective The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Materials and Methods Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm2). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Students t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. Results The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10-6 mm2/sec for observer 1 and 907 × 10-6 mm2/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). Conclusion The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas.