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| ORIGINAL ARTICLE |
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| Year : 2013 | Volume
: 61
| Issue : 1 | Page : 40-44 |
Three risk factors for WHO grade II and III meningiomas: A study of 1737 cases from a single center
Peizhi Zhou, Weichao Ma, Senlin Yin, Youping Li, Shu Jiang
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| Date of Submission | 04-Sep-2012 |
| Date of Decision | 17-Sep-2012 |
| Date of Acceptance | 23-Jan-2013 |
| Date of Web Publication | 4-Mar-2013 |
Correspondence Address:
Shu Jiang
Department of Neurosurgery, West China Hospital, Sichuan University, NO. 37. Guoxue Alley, Chengdu, Sichuan Province, 610041
China
 Source of Support: This work was supported by the National Natural
Science Foundation of China (Grant No. 81072077) and Foundation
of Science and Technology Department of Sichuan Provience (Grant
NO.2010SZ0160), Conflict of Interest: None  | Check |
DOI: 10.4103/0028-3886.107928
Background: Meningiomas account for 35.5% of central nervous system (CNS) tumors, of which 21-37.8% are atypical or anaplastic/malignant. High-grade meningiomas have higher rates of recurrence and worse outcome than grade I/II meningiomas. Thus, it is of importance to assess the tumor biology before treatment initiation. Materials and Methods: This study reviewed 1737 patients with histologically confirmed meningioma at a single institution. Meningiomas were classified according to World Health Organization (WHO) 2007 grading and the location of the tumor was confirmed from the operation records and preoperative imaging. Univariate and multivariate logistic regression were used to analyze the potential risk factors for high-grade pathology. Results: Young men and pediatric patients were less likely to have meningioma, but they had high-grade meningioma. Tumors originated from non-skull base and lateral intracranial are more likely to be grade II/III meningioma. Conclusions: Lateral and non-skull base location, male sex, and the younger patients increase the risk for grade II and III pathology. These factors should be considered while deciding treatment choice, surgical resection, and prognosis as well.
Keywords: Benign, location, meningioma, malignant, risk factor
How to cite this article:
Zhou P, Ma W, Yin S, Li Y, Jiang S. Three risk factors for WHO grade II and III meningiomas: A study of 1737 cases from a single center. Neurol India 2013;61:40-4 |
How to cite this URL:
Zhou P, Ma W, Yin S, Li Y, Jiang S. Three risk factors for WHO grade II and III meningiomas: A study of 1737 cases from a single center. Neurol India [serial online] 2013 [cited 2023 Jun 3];61:40-4. Available from: https://www.neurologyindia.com/text.asp?2013/61/1/40/107928 |
| » Introduction | |  |
Meningiomas are the most common intracranial tumor and account for 35.5% of central nervous system (CNS) tumors. [1] About 21-27.8% of meningiomas are World Health Organization (WHO) grade II and III. [2],[3],[4],[5] High-grade tumors have higher risk of recurrence and requires special attention of neurosurgeons. [5],[6],[7] Surgical resection is the standard treatment; however, with wide use of gamma knife surgery (GKS), patients with small lesions and no neurological defects are no longer candidates for surgery. [8],[9],[10] Extensive resection in patients with invasive lesions and lesions in complex anatomical location may be associated with significant postoperative deficits. In patients with small lesions, GKS is chosen as the initial treatment modality, and if they turn out be high-grade tumors, further management becomes difficult. Determining the tumor grade preoperatively may help neurosurgeons plan appropriate surgical planning.
In order to identify high-grade tumors before treatment initiation, many studies have attempted to define the possible predictors suggestive of high-grade meningiomas. [11],[12],[13],[14],[15],[16],[17] Most of these studies suggested meningiomas, other than skull-based meningiomas, have higher risk of being atypical or malignant/anaplastic. The conclusions as regard to other risk factors like age and gender were inconsistent. One of the major limitations of these studies was inadequate patient sample size. The other limiting factor is the lack of uniform classification criteria. This study included a large patient sample from a single center, and WHO guidelines proposed in 2007 were adopted while classifying the meningiomas. [18]
| » Materials and Methods | | |
This study was a retrospective review of case records of all patients who underwent neurosurgical intervention for intracranial meningiomas between 2005 and 2010 in the West China Hospital. The data collected included age, gender, radiological findings, location of the meningioma, and histopathological findings. All tumor specimens were reviewed and classified according to the WHO 2007 guidelines. [18] Patients with other intracranial tumor or spinal meningiomas were excluded. For patients with repeated operation, only the first operation was included in the data analysis.
Clinical assessment was performed by one neurosurgeon and then re-checked by another neurosurgeon. The anatomical location was confirmed by radiological records and operation notes. Tumors originating from lateral cerebral convexity, cerebellar convexity, and lateral ventricle were considered lateral, non-skull base tumors; other tumor locations including falx, tentorium, sagittal sinus, fourth ventricle, and pineal region were considered median line of non-skull base tumors; skull-base tumors with lateral locations like sphenoid wing, parasellar, petroclival, jugular petrous, lateral anterior, and middle skull-base, and foramen were considered lateral skull-base tumors; olfactory groove, tuberculum, sella, clinoid, and foramen magnum were considered median line of skull-base tumors.
Statistical analysis
The risk factors were selected for analysis based on prior hypothesis and our clinical findings. Univariate analysis was used to identify covariates that might affect the frequency of grade II/III meningiomas. Risk factors with a significance of P ≤ 0.2 in univariate analysis were included in a stepwise binary logistic regression. We fit the binary logistic regression model (backward stepwise method) to analyze the risk factors. The specific setting of the variables was shown in [Table 1]. The goodness of fit of the regression model was confirmed by a non-significant P value on the Hosmer-Lemeshow test (χ2 =6.859, P =0.552). According to the result of the goodness of fit, we finally set age group as dummy variables instead of continuous variable (P =0.037). Odds ratios on multivariate analysis reflected the odds of having high-grade meningioma. All statistical tests were performed using SPSS 16.0. Probability values of 0.05 or less were considered statistically significant. | Table 1: Anatomical location and histological grade according to the world health organization 2007 classification
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| » Results | | |
A total of 1737 patients had undergone surgical resection for histologically verified meningioma [Table 2]. The mean age was 50.3 ± 13.2 years (0.5-81 years). Data on anatomical location and histological grade are presented in [Table 1].
The results of univariate and multivariate logistic regression analysis are presented in [Table 3] and [Table 4]. Analysis by age showed young patients having increased risk of grade II/III meningiomas. Compared to older (>60 years) patients, grade II/III meningiomas had higher incidence in the age group ≤20 years (OR, 2.36; 95% CI, 1.1-5.2; P =0.033), 21-40 years age group (OR, 1.39; 95% CI, 1.0-1.9; P =0.045), but there was no significant difference in the age group between 41 and 60 years (OR, 0.97; 95% CI, 0.7-1.3; P > 0.05). About half of the pediatric patients had II/III meningiomas (5/11, 45.5%) and 23.1% of patients > 65 years of age had higher-grade meningiomas. Univariate analysis demonstrated increased risk for males for grade II/III meningiomas (34.4% vs. 19.7%, P < 0.001) and the risk was increased two-fold (OR, 2.10; 95% CI, 1.7-2.6; P < 0.001) on the multivariate analysis. | Table 3: Univariate analysis of potential risk factors for grade II/IIImeningiomas
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 | Table 4: Multivariate analysis of risk factors for grade II/III meningiomas
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Tumor location was classified into four groups according to their origins into median line of skull-base, lateral skull-base, median line of non-skull base, and lateral non-skull base. Tumors with median line of skull-base had the lowest rate of grade II/III meningiomas (26/202, 12.9%). Compared with tumors located at the median line of skull-base with other locations had increased incidence of high-grade meningiomas. Tumors with lateral non-skull base location had the highest incidence (OR, 2.89; 95% CI, 1.9-4.5; P < 0.001) of grade II/III meningiomas, followed by the location of median line of non-skull base (OR, 2.80; 95% CI, 1.4-5.4; P =0.002) and lateral skull base (OR, 1.72; 95% CI, 1.0-2.8; P =0.032).
| » Discussion | | |
Determining factors that can accurately predict grade of meningioma before pathological diagnosis would help neurosurgeons to appropriately balance the risk of surgery and the extent of surgical resection. The strength of our study is large patient sample size from a single centre. We stratified the sample according to the age and anatomical locations. The analysis indicates that male gender, younger age, non-skull base location are significant risk factors for grade II/III pathology.
Our results demonstrated that males conferred about two-fold risk of having grade II/III meningiomas and females had a higher overall incidence of meningiomas. [16],[19],[20] The possible reasons for this male gender association with high-grade meningiomas are still unclear. Various studies suggested that hormone levels, hormone receptor status, and chromosome abnormalities may affect the tendency for high-grade tumors. [21],[22],[23],[24],[25] Some studies have also shown an inverse relationship between progesterone receptor expression level and tumor histological grade and tumor recurrence. [22],[22],[23],[24],[25] The hormone-related molecules may be used as markers to identify low-grade and high-grade meningiomas.
Meningiomas are uncommon in the pediatric age group and the prognosis is poor probably related to the aggressive behavior and high recurrence rate. [26],[27],[28],[29],[30],[31],[32],[33] Most of the earlier literature suggested that the pediatric and adolescent meningiomas are more likely to be high-grade meningiomas. Because of large sample size, we were able to stratify the patients into various age groups. In this study, children had the highest rate of grade II/III meningiomas and young men aged ≤40 years had increased incidence of grade II/III meningiomas (44.8% for aged ≤20 years, 28.9% for aged 21-40 years). The possible reason for this occurrence of age-related grade of meningioma may be embryologic abnormality like genetic mutations. These results suggest that, in young patients, surgical therapy should be considered as the first choice even for tumors <3 cm so that high-grade meningiomas are included. Young patients may benefit more from primary surgical intervention and higher grade resection grade. [29] On the other hand, for the aged patients with small tumor or residual tumor, which is hard to remove, GKS could be applied to control the tumor or avoid the increased surgical morbidity, especially for grade I meningioma. [34],[35]
There have been reports regarding the association between grade of meningioma and anatomical location [11],[12],[13],[14],[15],[16] , the observations were that non-skull base meningiomas have a two- to four-folds increased risk of being grade II/III meningiomas. Our study also confirms these observations. Based on the detailed anatomical stratification, we found that meningiomas with lateral non-skull base location have the highest risk of high-grade pathology, followed by tumors with median line of non-skull base location. Our results further support previous conclusions. Besides, we found that meningiomas with median line of skull-base location have the lowest risk of grade II/III pathology. These observations suggest that surgical resection should be the treatment for the tumors with non-skull base location, especially lateral non-skull base meningiomas. Because of the close proximity to important neurovascular structures; complete surgical resection of the skull-base meningiomas may be associated with significant morbidity. As most meningiomas located at the median line of skull-base are benign (87.1%), high Simpson resection grade is associated with higher rates of surgical morbidity and neurological damage, staged operation can be chosen because of the slow growth of the tumor. [36] GKS could also play an important role in the management of the residual tumor. [37],[38],[39],[40],[41],[42] Although some studies claimed that prior surgery is a risk factor for high-grade meningioma, [16] we believe that it is the high-grade meningioma that leads to reoperation.
In addition, the radiological features and histopathological findings are also important predictions for high-grade meningioma and tumor recurrence. Some authors thought that tumor-brain interface and heterogeneous enhancement on magnetic resonance imaging (MRI) were independent predictive factors for high-grade meningioma and capsular enhancement; tumor margin were also useful in distinguishing high-grade tumors from benign tumors. [17] The pathological findings including high mitotic index, brain invasion, high MIB-1 index, spontaneous necrosis, and macronucleoli may also prompt high-grade meningioma and high risk of recurrence. Most of those factors were related to the proliferation of tumor cells and growing speed. Many molecular markers have been used to evaluate the recurrence-free survival, especially the MIB-1 index, hypoxia-inducible factor-1α, and vascular endothelial growth factor. Those markers could be beneficial for planning tailored optimal follow-up strategies and the associated signal system may be used as the target of targeted therapy. [43],[44]
In conclusion, we found that anatomical location, gender, and age are all independent preoperative risk factors for grade II/III meningioma. Notably, the limitations of our study should be acknowledged. First, this is a retrospective study and only important factors inherent to this study design are analyzed. Second, our department mainly serves patients with large and complex tumors because of its role as the tertiary referral center of southwest China. It is highly possible that our sample may not demographically represent the entire meningioma population.
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[Table 1], [Table 2], [Table 3], [Table 4]
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| P. H. Domingues,P. Sousa,A. Otero,J. M. Goncalves,L. Ruiz,C. de Oliveira,M. C. Lopes,A. Orfao,M. D. Tabernero | | Neuro-Oncology. 2014; 16(5): 735 | | [Pubmed] | [DOI] | | | 18 |
Long-term survival analysis of atypical meningiomas: survival rates, prognostic factors, operative and radiotherapy treatment |
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| Salah Hammouche,Simon Clark,Alex Hie Lin Wong,Paul Eldridge,Jibril Osman Farah | | Acta Neurochirurgica. 2014; 156(8): 1475 | | [Pubmed] | [DOI] | |
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