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Neuro-oncology Apr 2016With advances in the understanding of histopathology on outcome, accurate meningioma grading becomes critical and drives treatment selection. The 2000 and 2007 WHO...
BACKGROUND
With advances in the understanding of histopathology on outcome, accurate meningioma grading becomes critical and drives treatment selection. The 2000 and 2007 WHO schema greatly increased the proportion of grade II meningiomas. Although associations with progression-free survival (PFS) and overall survival (OS) have been independently validated, interobserver concordance has not been formally assessed.
METHODS
Once mature, NRG Oncology RTOG-0539 will report PFS and OS in variably treated low-, intermediate-, and high-risk cohorts. We address concordance of histopathologic assessment between enrolling institutions and central review, performed by a single pathologist (AP), who is also involved in developing current WHO criteria.
RESULTS
The trial included 170 evaluable patients, 2 of whom had 2 eligible pathology reviews from different surgeries, resulting in 172 cases for analysis. Upon central review, 76 cases were categorized as WHO grade I, 71 as grade II, and 25 as grade III. Concordance for tumor grade was 87.2%. Among patients with WHO grades I, II, and III meningioma, respective concordance rates were 93.0%, 87.8%, and 93.6% (P values < .0001). Moderate to substantial agreement was encountered for individual grading criteria and were highest for brain invasion, ≥20 mitoses/10 high-powered field [HPF], and spontaneous necrosis, and lowest for small cells, sheeting, and ≥4 mitoses/10 HPF. In comparison, published concordance for gliomas in clinical trials have ranged from 8%-74%.
CONCLUSION
Our data suggest that current meningioma classification and grading are at least as objective and reproducible as for gliomas. Nevertheless, reproducibility remains suboptimal. Further improvements may be anticipated with education and clarification of subjective criteria, although development of biomarkers may be the most promising strategy.
Topics: Cohort Studies; Humans; Meningeal Neoplasms; Meningioma; Neoplasm Grading; Observer Variation; Prognosis
PubMed: 26493095
DOI: 10.1093/neuonc/nov247 -
Journal of Cancer Research and... 2014This study evaluates the magnetic resonance imaging (MRI) manifestation of intradural extramedullary (IDEM) tumors to improve the imaging diagnostic level.
OBJECTIVE
This study evaluates the magnetic resonance imaging (MRI) manifestation of intradural extramedullary (IDEM) tumors to improve the imaging diagnostic level.
MATERIALS AND METHODS
From January 2005 to December 2012, a retrospective analysis of the MRI examination was performed on 108 patients with IDEM tumors confirmed by surgical pathology postoperatively in our hospital. According to the pathological classification; the gender, age, location, size, foraminal state extension, signal intensity (compared with the spinal cord), and enhancement were recorded and statistically analyzed.
RESULTS
A total of 108 cases (111 lesions) were reported; 69 (70 lesions), 31 (31 lesions), three (five lesions), four (four lesions), and one (one lesion) of which were schwannoma, meningioma, neurofibroma, teratoma, and metastatic tumor, respectively. MRI manifestations of different IDEM tumors have certain specificities.
CONCLUSION
MRI is the preferred examination method for to diagnose IDEM tumors and provide a reliable imaging basis for clinical treatment and prognosis judgment.
Topics: Adolescent; Adult; Aged; Artifacts; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Metastasis; Neurilemmoma; Neurofibroma; Prognosis; Retrospective Studies; Spinal Cord; Spinal Cord Neoplasms; Teratoma; Young Adult
PubMed: 25579530
DOI: 10.4103/0973-1482.137993 -
Virchows Archiv : An International... Apr 2021Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared... (Comparative Study)
Comparative Study
Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared the inter- and intra-observer concordance for atypical meningioma, using glass slides and WSI. Two neuropathologists and two residents assessed the histopathological features of 35 meningiomas-originally diagnosed as atypical-in a representative glass slide and corresponding WSI. For each histological parameter and final diagnosis, we calculated the inter- and intra-observer concordance in the two viewing modes and the predictive accuracy on recurrence. The concordance rates for atypical meningioma on glass slides and on WSI were 54% and 60% among four observers and 63% and 74% between two neuropathologists. The inter-observer agreement was higher using WSI than with glass slides for all parameters, with the exception of high mitotic index. For all histological features, we found median intra-observer concordance of ≥ 79% and similar predictive accuracy for recurrence between the two viewing modes. The higher concordance for atypical meningioma using WSI than with glass slides and the similar predictive accuracy for recurrence in the two modalities suggest that atypical meningioma may be safely diagnosed using WSI.
Topics: Humans; Meningeal Neoplasms; Meningioma; Neoplasm Grading; Observer Variation; Reproducibility of Results
PubMed: 33305338
DOI: 10.1007/s00428-020-02988-1 -
Cytometry. Part B, Clinical Cytometry 2015Meningiomas have classically been considered to include benign and atypical/anaplastic tumors. Despite the availability of clinical and pathologic parameters for...
BACKGROUND
Meningiomas have classically been considered to include benign and atypical/anaplastic tumors. Despite the availability of clinical and pathologic parameters for prognostic prediction prognosis, the behavior of each meningioma may be difficult to predict. Here, we used DNA flow-cytometric studies to predict biological tumor behaviors of intracranial meningiomas.
METHODS
The specimens were obtained from fresh tumoral tissues of 43 microsurgically resected meningiomas as approved by the institutional review board. The presence of G2/M-phase and S+G2/M-phase fractions were analyzed and correlated with the proliferation index of Ki-67 and the World Health Organization grading. The check point of G2/M-phase fraction, cyclin B, and pCdk1 (Y15), were analyzed by Western blotting.
RESULTS
Our results showed that there were significant differences in Ki-67, G2/M-phase, S+G2/M-phase fractions, and cyclin B between benign and atypical/anaplastic meningiomas. The optimal cutoff point of G2/M-phase and S+G2/M-phase fractions were 5.12 and 7.52%, respectively, and this can be used to discriminate those cases with benign or atypical/anaplastic meningiomas. Besides, both the G2/M-phase and S+G2/M-phase fractions were correlated well with Ki-67 and the histopathological features such as focal necrosis, infiltration of dura mater and mitotic activity. In addition, the occurrence of tumor recurrence and patient age were correlated to the G2/M-phase and S+G2/M-phase fractions, respectively. The G2/M-phase and S+G2/M-phase fractions, however, did not correlate well with histologic invasion to adjacent bone, sinus, or brain tissues.
CONCLUSIONS
The use of flow cytometry facilitates additional information for G2/M-phase and S+G2/M-phase fractions represent tumoral grading and risk of recurrence in patients with meningiomas.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Blotting, Western; CDC2 Protein Kinase; Cell Proliferation; Cyclin B; Cyclin-Dependent Kinases; DNA, Neoplasm; Female; Flow Cytometry; G2 Phase Cell Cycle Checkpoints; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Predictive Value of Tests; Prospective Studies; Risk Factors; Treatment Outcome
PubMed: 25408130
DOI: 10.1002/cyto.b.21202 -
International Journal of Clinical and... 2013Papillary meningioma is a rare subtype of malignant meningiomas, which is classified by the World Health Organization as Grade III. Because of lack of large sample size...
Papillary meningioma is a rare subtype of malignant meningiomas, which is classified by the World Health Organization as Grade III. Because of lack of large sample size case studies, many of the specific characteristics of papillary meningioma are unclear. This study investigated by retrospective analysis the clinical, radiological and histopathological findings of 17 papillary meningioma patients who underwent surgical resection or biopsy, to assess the characteristics of papillary meningioma. Eight female and nine male patients were included, with a mean age of 40 (range: 6 to 55) years. Tumors were mostly located in the cerebral convexity and showed irregular margins, absence of a peritumoral rim, heterogeneous enhancement and severe peritumoral brain edema on preoperative images. Brain invasion was often confirmed during the operations, with abundant to exceedingly abundant blood supply. Intratumoral necrosis and mitosis was frequently observed on routinely stained sections. The average MIB-1 labeling index was 6.9%. Seven cases experienced tumor recurrence or progression, while seven patients died 6 to 29 months after operation. Radiation therapy was given in 52.9% of all cases. Univariate analysis showed that only the existence of intratumoral necrosis and incomplete resection correlated with tumor recurrence. The 3-year progression free survival was 66.7% after gross total resection and 63.6% for other cases. The 3-year mortality rate was 50% after gross total resection and 63.6% for other cases. Papillary meningioma has specific clinical and histopathological characteristics. Tumor recurrence (or progression) and mortality are common. Gross total tumor resection resulted in less recurrence and mortality.
Topics: Adolescent; Adult; Child; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Recurrence, Local; Neurosurgical Procedures; Prognosis; Radiotherapy; Retrospective Studies; Young Adult
PubMed: 23638219
DOI: No ID Found -
International Journal of Clinical and... 2014Brain-invasive meningiomas have an adverse prognosis, so it is important to detect and correctly evaluate brain invasion by light microscopy. Furthermore, the underlying...
Brain-invasive meningiomas have an adverse prognosis, so it is important to detect and correctly evaluate brain invasion by light microscopy. Furthermore, the underlying biological mechanisms responsible for brain-invasive growth are incompletely understood. The primary aim of this study was to identify immunohistochemical markers that could improve identification and evaluation of brain invasion in meningiomas. A second aim was to investigate the process of brain invasion using immunohistochemical markers of proliferation, extracellular matrix modulation, and cell adhesion. From a series of 196 human meningiomas, 67 cases were selected for analysis because of the presence of brain tissue in tumor specimens. Fourteen of these 67 meningiomas were brain-invasive. Invasiveness was determined primarily by evaluation of hematoxylin-erytrosin-saffron- (HES-) stained specimens, although glial fibrillary acidic protein (GFAP), anti-collagen IV, and cluster of differentiation 44 (CD44) markers provided additional information. It was important to examine microscopic sections from various levels of the paraffin-embedded tissue block to adequately assess invasiveness. Sections stained using antibodies against Ki-67/MIB-1, phospohistone-H3 (PHH3), matrix metalloproteinase-9 (MMP-9), cathepsin D, plasminogen activator inhibitor-1 (PAI-1), and E-cadherin antigens were used to characterize brain-invasive meningiomas and to investigate the process of brain invasion. Only increased expression of the extracellular matrix modulator MMP-9 correlated with brain-invasive growth (p=0.025). Examination of HES-stained sections identified brain invasion. Use of relevant immunohistochemical markers did not contribute substantially to this evaluation. Evaluation of stepwise sections should be considered when brain-invasive growth is suspected. MMP-9 may be an important mediator of brain-invasive growth.
Topics: Biomarkers, Tumor; Biopsy; Cell Adhesion; Cell Proliferation; Female; Humans; Immunohistochemistry; Male; Matrix Metalloproteinase 9; Meningeal Neoplasms; Meningioma; Neoplasm Invasiveness; Predictive Value of Tests; Treatment Outcome
PubMed: 25400818
DOI: No ID Found -
International Journal of Molecular... Jan 2021There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas. There is currently no...
There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas. There is currently no consensus on the optimum management of WHO grade II meningiomas. In this study, we identified the calcium binding extracellular matrix glycoprotein, Fibulin-2, via mass-spectrometry-based proteomics, assessed its expression in grade I and II meningiomas and explored its potential as a grade II biomarker. A total of 87 grade I and 91 grade II different meningioma cells, tissue and plasma samples were used for the various experimental techniques employed to assess Fibulin-2 expression. The tumours were reviewed and classified according to the 2016 edition of the Classification of the Tumours of the central nervous system (CNS). Mass spectrometry proteomic analysis identified Fibulin-2 as a differentially expressed protein between grade I and II meningioma cell cultures. Fibulin-2 levels were further evaluated in meningioma cells using Western blotting and Real-time Quantitative Polymerase Chain Reaction (RT-qPCR); in meningioma tissues via immunohistochemistry and RT-qPCR; and in plasma via Enzyme-Linked Immunosorbent Assay (ELISA). Proteomic analyses ( < 0.05), Western blotting ( < 0.05) and RT-qPCR ( < 0.01) confirmed significantly higher Fibulin-2 (FBLN2) expression levels in grade II meningiomas compared to grade I. Fibulin-2 blood plasma levels were also significantly higher in grade II meningioma patients compared to grade I patients. This study suggests that elevated Fibulin-2 might be a novel grade II meningioma biomarker, when differentiating them from the grade I tumours. The trend of Fibulin-2 expression observed in plasma may serve as a useful non-invasive biomarker.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Grading; Prognosis; Proteomics
PubMed: 33429944
DOI: 10.3390/ijms22020560 -
Scientific Reports Jul 2020Atypical or malignant transformation (AT/MT) has been described in WHO grade I meningiomas. Our aim was to identify predictive factors of AT/MT at recurrence. A total of...
Atypical or malignant transformation (AT/MT) has been described in WHO grade I meningiomas. Our aim was to identify predictive factors of AT/MT at recurrence. A total of N = 15 WHO grade increases were observed in N = 13 patients (0.96% of the study population, risk of transformation of 0.12% per patient-year follow-up). Patients with and without progression at recurrence were similar regarding age, gender distribution, skull-base location, bone infiltration, and Simpson grades. Recurrence-free survival was lower in patients with transformation (5 ± 4.06 years versus 7.3 ± 5.4 years; p = 0.03). Among patient age, gender, skull base location, extent of resection or post-operative RT, no predictor of AT/MT was identified, despite a follow-up of 10,524 patient-years. The annual risk of transformation of WHO grade I meningiomas was 0.12% per patient-year follow-up. Despite the important number of patients included and their extended follow-up, we did not identify any risk factor for transformation. A total of 1,352 patients with surgically managed WHO grade I meningioma from a mixed retro-and prospective database with mean follow-up of 9.2 years ± 5.7 years (0.3-20.9 years) were reviewed. Recurring tumors at the site of initial surgery were considered as recurrence.
Topics: Adult; Aftercare; Aged; Disease Progression; Disease-Free Survival; Female; Humans; Male; Meningeal Neoplasms; Meninges; Meningioma; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neurosurgical Procedures; Radiotherapy, Adjuvant; Retrospective Studies; Risk Factors
PubMed: 32641701
DOI: 10.1038/s41598-020-68177-x -
Chinese Clinical Oncology Jun 2021Atypical meningioma is a variant of meningioma with a high risk of recurrence. Gross total resection is the standard of treatment, while no consensus on optimal adjuvant...
BACKGROUND
Atypical meningioma is a variant of meningioma with a high risk of recurrence. Gross total resection is the standard of treatment, while no consensus on optimal adjuvant management has been found.
METHODS
Between 2008 and 2018, a retrospective search identified 216 grade II meningiomas treated in six centers. Clinical, histological, and therapeutic data were analyzed to determine the prognostic factors of recurrence and survival.
RESULTS
In total, 216 patients underwent surgical resection. Among these, 122 patients (56%) underwent gross total resection, and 21% of the patients received adjuvant radiotherapy. Univariate analysis reported subtotal resection, high Ki-67, negative progesterone receptor (PR) and histological grade evolution as unfavorable prognosis factors. According to multivariate analysis, the Ki-67 proliferative index (cut-off value of 17.5%) was the only prognostic factor of recurrence (HR 1.1; 95% CI, 1.0-1.2, P=0.048). Gross total resection improved progression-free survival (PFS) (P=0.03) but without impact on overall survival (OS) (P=0.2). Median PFS and OS times were longer for patients receiving adjuvant radiotherapy than those who did not receive adjuvant radiotherapy. PFS (P=0.3) and OS (P=0.7) were associated with adjuvant RT by trend only. After a median follow-up time of 6.7 years, 99 (46%) patients relapsed. Median progression-free and OS rates were 4.5 (95% CI, 3.5-5.5) and 14.7 years (11.4-NA), respectively.
CONCLUSIONS
In this study, Ki-67 proliferative index was significantly associated with recurrence. Gross total resection significantly improved PFS without impacting OS. Adjuvant radiotherapy delayed recurrence and improved OS, but a longer follow-up time is needed to distinguish a statistically significant difference. Large prospective studies are needed to determine postoperative treatment guidelines.
Topics: Humans; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Prognosis; Radiotherapy, Adjuvant; Retrospective Studies
PubMed: 33752411
DOI: 10.21037/cco-20-226 -
Oncology (Williston Park, N.Y.) Jan 1995Although generally benign tumors, meningiomas can cause serious neurological injury and, at times, vexatious management difficulties. Currently, the accepted management... (Review)
Review
Although generally benign tumors, meningiomas can cause serious neurological injury and, at times, vexatious management difficulties. Currently, the accepted management of these tumors is attempted total surgical excision when technically possible and associated with an acceptable risk. However, even with innovations in instrumentation and refinements in surgical technique, the goal of total resection may not be achievable. For these patients, and for those with recurrent tumors, options for treatment include reoperation, radiation therapy, and chemotherapy. Recent developments in surgical technique and instrumentation, radiosurgery, and brachytherapy have increased the treatment options, while clinical trials with tamoxifen and mifepristone (RU486) are adding information on the effectiveness of these drugs as chemotherapeutic agents. While the search continues for a uniformly successful management plan, physicians must be aware of the available options and try to help the patient decide which treatment is appropriate, based on current medical knowledge.
Topics: Adult; Female; Humans; Magnetic Resonance Imaging; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Neoplasm Staging; Neurosurgery; Radiosurgery
PubMed: 7718443
DOI: No ID Found