Local versus diffuse recurrences of meningiomas: factors correlated to the extent of the recurrence

OBJECTIVE: The aim of this study is to evaluate the factors correlated with the different patterns (local, peripheral and diffuse) of meningioma recurrence. MATERIAL AND METHODS: 55 patients with benign (WHO I) meningiomas which recurred after seemingly complete removal were reviewed; 40 (Group I) had local or peripheral recurrences (< 3 cm from the initial dural attachment) and 15 (Group II) had distant and diffuse recurrences. Patient age and sex, tumor location, interval of recurrence, tumor shape, type of brain-tumor interface, histological subtype, mitotic index (MI) and progesterone receptor (PR) expression of the initial tumor, histological WHO Grade of the recurrent tumor and patient outcome were analyzed and correlated with the pattern of recurrence. RESULTS: Flat-shaped meningiomas with large dural attachment showed a significantly higher rate of diffuse recurrences than round tumors, whereas the brain-tumor interface and the tumor location were not relevant (excepting the lack of convexity meningiomas in the group of diffuse tumors). There were no significant differences of histology, MI and PR expression of the initial tumor and histological grade of the recurrent tumor between the two groups. CONCLUSIONS: The different patterns of meningioma recurrences (local, peripheral, diffuse) are not correlated with the tumor location and histology and do not represent a different biological tumor progression. We agree that most unexpected extensive recurrences result from a more extensive microscopic dural involvement.     

Histological subtypes and prognostic problems in meningiomas

The incidence of the various histological subtypes of meningiomas was examined in 1238 patients with surgically treated meningiomas, about 80% arising within the cranial cavity. The histological classification used was that of Courville (1950) and Rubinstein (1972), but "angioblastic" meningiomas were segregated into 3 groups: highly vascularized meningiomas, hemangioblastomas, and hemangiopericytomas. Endotheliomatous and transitional forms constituted 85% of the total (71.5% of intracranial tumors), fibroblastic forms 6.6 and 7.5%, respectively, and highly vascularized (endotheliomatous or transitional) meningiomas 5.2% of the intracranial tumors, while true "angioblastic" meningiomas (hemangioblastomas and hemangiopericytomas) amounted to 2.8% of the total (3.1% of the intracranial tumors). 1.2% were "atypical" (so-called malignant) meningiomas; true meningeal sarcomas were excluded. The incidence of recurrence in patients surviving at least 5 years after apparently complete removal of the tumor was 13% for all sites, and 14.2% for intracranial tumors, but almost twice as high after partial removal. There were no significant differences in the recurrence rate and intervals between first and second operation according to the various histological subtypes of meningiomas, except for hemangiopericytomas which recurred with significantly higher frequency and, together with atypical meningiomas, at much shorter intervals than the others. The prognostic significance of some histological criteria in "non-angiomatous" meningiomas was examined in 211 patients surviving at least 5 years after apparently complete removal of the tumor. Among the recurrences, there was a significantly higher degree of cellularity and increased mitotic rate and, probably, of cortical invasion, while nuclear pleomorphism, increased vascularity, and focal necroses showed no definite differences. The presence of mitotic figures alone appeared to be of no prognostic value. While most recurrent meningiomas did not change their basic morphological type significantly, about 12.5% of the recurrences appeared to have a different rate of growth as suggested by increased cellularity and mitotic rates. In 2 cases an isomorphic (benign) meningioma became a true spindle cell sarcoma.     

Intracranial Meningiomas, WHO Grade Il : Prognostic Implications of Clinicopathologic Features

Objective

Intracranial meningiomas are primarily benign tumors with a good prognosis. Although WHO grade II meningiomas are rare (2-10%), WHO grade II meningiomas have higher recurrence and mortality rates than benign. We evaluated the patient recurrence rate and investigated the prognostic factors of WHO grade II meningiomas.

Methods

Between 1993 and 2005, 55 patients were diagnosed with WHO grade II meningiomas in our hospital. WHO grade II meningiomas (n=55) were compared with other WHO grades meningiomas (I, n=373; and III, n=20). The patients had a median age of 48.4 years (range, 14-17 years), a male-to-female ratio of 26 : 29, and a mean follow-up time of 45 months (range, 3-175 months).

Results

In WHO grade II meningiomas, only the extent of resection was a significant prognostic factor. Post-operative radiotherapy had no significant influence on tumor recurrence (p=0.053). The relative risk of recurrence was significantly higher in WHO grade II meningiomas with incomplete resection (10/27, RR=37%) than in WHO grade II meningiomas with complete resection (4/28, RR=14%) regardless of post-operative radiotherapy. In the incomplete resection group, Simpson grade III or IV had a significantly high risk of recurrence regardless of post-operative RT (n=3, RR=100%) However, if the degree of resection was Simpson grade II, the recurrence rate was similar to the complete resection group even though post-operative RT was not performed.

Conclusion

Complete resection was the most powerful independent predictive factor of the recurrence rate in WHO grade II meningiomas. Post-operative adjuvant RT was not a significant factor in this study.     

Diagnostic validity of the Ki-67 labeling index using the MIB-1 monoclonal antibody in the grading of meningiomas

BACKGROUND: About 10% of meningiomas behave aggressively and are graded atypical or malignant with important therapeutic and prognostic implications. Routine histological parameters are inconsistent in the assessment of their aggressive behavior. AIMS: The aim of this study was to find a threshold level of the MIB-1 labeling index (MIB-1 LI) with the highest diagnostic validity in predicting histological atypia in a meningioma. SETTING AND DESIGN: This was a retrospective study of all atypical and malignant meningiomas diagnosed at our center between January 1995 and June 2000 and which were identified from the General Pathology Registry. MATERIAL AND METHODS: These meningiomas were assessed histologically with respect to the individual criteria of atypia. They were categorized according to the WHO 2000 classification as benign, atypical and anaplastic meningiomas, WHO Grades I, II and III respectively and by immunohistochemical analysis using the MIB-1 monoclonal antibody. STATISTICAL ANALYSIS: The diagnostically useful cut-off level for the prediction of atypia was estimated by calculating the sensitivity and specificity of the MIB-1 LI at various levels and a receiver operated characteristic (ROC) analysis was performed. The correlation between the individual histological parameters was studied and the MIB-1 LI was obtained using Fisher's exact test. RESULTS: Of the 40 meningiomas studied 21 were benign, 16 atypical and 3 anaplastic. Atypical tumors had a higher MIB-1 LI than benign tumors, with diagnostic validity highest at a threshold of 7%, with a sensitivity of 0.86 and a specificity of 0.93, giving a likelihood ratio of 17. The MIB-1 LI correlated well with mitotic activity and the other individual criteria in the WHO 2000 definition of atypia in a meningioma. MIB-1 LI did not, however, correlate well with brain invasion. CONCLUSION: The MIB-1 LI has the highest validity in the diagnosis of atypia in meningiomas at a threshold level of 7%. The MIB-1 LI used in conjunction with histological features can help in making a recommendation regarding potentially aggressive behavior in meningiomas.     

Radiation-induced tumours of meninges. Report on eight cases and review of the literature

Background and purposeDespite their rarity, post-radiation meningeal tumours seem to be a growing problem due to the increasing application of radiation therapy. The aim of the study was to ascertain the specific features of these tumours.Material and methodsAmong 433 intracranial meningeal tumours treated from 2000 to 2008, eight cases (2%) have been presumed to be associated with high-dose therapeutic radiation for previous neoplasm of the head (7) or neck (1). On average, tumours were diagnosed 24 years after irradiation. All patients had a solitary meningeal tumour, but two of them also developed other neoplasms in the irradiated area.ResultsAll tumours were microsurgically removed. The postoperative course was uncomplicated in two cases only. In the remaining 6 (75%), complications included liquorrhoea (2), brain oedema (1), venous thrombosis (1), bleeding into the tumour bed (1) and focal deficit due to manipulation (3). Most tumours (5) were WHO grade I meningiomas. These benign meningiomas exhibited some peculiar histological features, including focal increase of cellularity, focal enhancement of proliferation index, pleomorphism of nuclei, occasional mitotic figures and, in one case, evidence of brain invasion. One meningioma was assigned to WHO grade II, one to WHO grade III and one appeared to be meningeal fibrosarcoma. The event-free survival and overall survival rate at 4.4 years of follow-up were 63% and 75%, respectively.ConclusionsRadiation-induced tumours of the meninges show certain characteristic histopathological features, which may promote invasiveness of the tumour and higher risk of malignancy.     

脑膜瘤级别及其临床特点

目的 探讨脑膜瘤分级、发病规律、治疗及愈后.方法 回顾性分析经手术及病理证实的脑膜瘤791例,按照2007年WHO脑膜瘤分级标准将其分为Ⅰ、Ⅱ、Ⅲ级并进行对照分析.结果 WHO Ⅰ级脑膜瘤占同期手术治疗脑膜瘤的93.0％,WHOⅡ级占4.6％,WHOⅢ占2.4％.WHO Ⅰ、Ⅱ、Ⅲ级脑膜瘤男女之比分别为1∶2.46、1∶1.77及1∶1.11(P＞0.05).WHO Ⅰ级脑膜瘤的高发年龄为40～60岁,Ⅱ级为30～70岁,Ⅲ级为20 ～30岁、50 ～ 70岁.WHOⅡ、Ⅲ级脑膜瘤发生率与肿瘤的部位有关,凸面及矢状窦旁发生率较高,而鞍上及前颅窝发生率较低(P＜0.05).WHO Ⅰ、Ⅱ、Ⅲ级脑膜瘤手术切除级别差异无统计学意义(P＞0.05),WHO Ⅰ、Ⅱ、Ⅲ级脑膜瘤复发率分别为4.8％、38.7％及68.8％,差异有统计学意义(P＜0.05).结论 绝大多数脑膜瘤为WHO Ⅰ级,Ⅱ、Ⅲ级脑膜瘤发生率较低,Ⅱ级脑膜瘤男女之比高于Ⅰ级脑膜瘤,而Ⅲ级脑膜瘤男女之比更高.凸面及矢状窦旁WHOⅡ、Ⅲ级脑膜瘤发生率较高,而鞍上及前颅窝发生率较低.脑膜瘤切除级别与WHO脑膜瘤分级无关,术后复发与WHO分级相关.     

Ki‐67 proliferative index predicts clinical outcome in patients with atypical or anaplastic meningioma

Meningiomas represent the second most common central nervous system neoplasms in adults and account for 26% of all primary brain tumors. Although most are benign, between 5% and 15% of meningiomas are atypical (grade II) whereas 1–2% are anaplastic meningiomas (grade III). Although histological grade is the most relevant prognostic factor, there are some unusual cases in which establishing a diagnosis of high‐grade meningioma following 2000 World Health Organization (WHO) histological criteria is extremely difficult. Therefore, the aim of the present study was to evaluate the predictive value of Ki‐67 labeling index and its contribution to current WHO classification in predicting tumor recurrence and overall survival in patients with high‐grade meningiomas. A total of 28 patients (with 16 atypical meningiomas and 12 anaplastic meningiomas) were evaluated for demographic, clinical, radiological and therapeutic variables, and for Ki‐67 immunohistochemistry. Median Ki‐67 labeling index in the whole series was 7.0 (0.5–31.5) with no differences with respect to the histological grade (P = 0.87). In the univariate analysis, Ki‐67 labeling index and postoperative Karnofsky performance status were identified as significant prognostic factors of tumor recurrence and overall survival. The multivariate analysis demonstrated that Ki‐67 labeling index is the only independent predictor of both tumor recurrence and overall survival. More importantly, this predictive value was maintained in both patients with atypical and patients with anaplastic meningioma.     

Invasive meningioma is associated with a low expression of E-cadherin and beta-catenin

Invasive meningioma shows benign histological features (WHO grade 1) and the brain expansion at the tumor-brain interface, and recurs more frequently than common meningiomas. To determine the mechanism of brain expansion, we studied the relationship between invasive meningioma and cell adhesion molecules. Immunostaining for E-cadherin (E-CH), N-cadherin (N-CH), beta-catenin, and Ki-67 was performed in 103 meningiomas that consisted of 61 meningothelial meningiomas, 25 fibrous meningiomas, 12 invasive meningiomas and 5 anaplastic meningiomas. All tumors were negative for N-CH. All the 61 meningothelial meningiomas, 10 of 12 invasive meningiomas, and 3 of 5 anaplastic meningiomas were positive for both E-CH and beta-catenin, while these were both negative in all of the fibrous meningiomas. In invasive meningiomas, the expansive part of the tumor showed a lower rate (4/12 tumors) of E-CH and beta-catenin positivity, while the central part showed a higher rate (10/12 tumors). The Ki-67 labeling index was higher in invasive and anaplastic meningiomas than in meningothelial meningiomas. These results suggest that a reduction in cell adhesion molecules and increased proliferative activity may be related, which may lead to a better understanding of the mechanism of meningioma expansion in the future.     

Early results of irradiation of intracranial meningiomas using CyberKnife

Meningiomas are frequently diagnosed intracranial lesions which cannot be resected radically in the majority of cases. Traditional radiotherapeutical techniques allow control of tumor growth in such situations. CyberKnife system may be used for radiosurgery and in sight hypofractionation. During 27 months 231 patient with intracranial meningiomas of different localization was treated in department for radiation therapy of Burdenko Neurosurgical Institute using CyberKnife system (Accuray Inc., USA). Mean age was 53 years. 55% of patients underwent previous surgical treatment, and diagnosis of meningioma was histologically verified. In 231 patient 374 targets were irradiated. Mean volume of irradiation reached 15.8 cm3 (range - 0.73-108.5 cm3). In 89% of cases hypofractionated therapy was used, in 10.1% we performed radiosurgery. Catamnestic data were available in 80 patients. Mean follow-up period was 11.6 months (6-27 months). Control of tumor growth was established in 100% of cases with WHO grade I tumors, in 66.7% of WHO grade II tumors and 60% in WHO grade III tumors. Deterioration after radiation treatment was observed in 16% of cases of 75 with control of tumor growth. In 8 cases worsening was due to radiation-induced reactions verified by MRI studies. Radiosurgical and hypofractionated treatment of meningiomas using CyberKnife is actual and highly-effective technique. Further investigations are needed to determine optimal standards of hypofractionated radiotherapy of meningiomas.     

Allelic losses in neurofibromatosis 2-associated meningiomas

More than 50% of patients with neurofibromatosis 2 (NF2) develop meningiomas. Recently, a higher proliferative activity, more mitotic figures, and greater nuclear pleomorphism have been described for NF2-associated meningiomas compared with sporadic ones. To analyze whether such histological differences could reflect underlying genetic differences, we examined 30 meningiomas from 22 NF2 patients for allelic losses on those chromosome arms that are frequently affected by deletions in sporadic meningiomas. In addition, we assessed the proliferative activity of the tumors and studied NF2 germline mutations. Twenty-three meningiomas corresponded to WHO grade I (10 fibrous, 6 psammomatous, 4 transitional, 3 meningothelial) and 7 to WHO grade II. The average MIB-1 index was 1.60 +/- 0.85 (WHO grade I: 1.41 +/- 0.80, WHO grade II: 2.13 +/- 0.82). When compared with several published studies of sporadic meningiomas, the MIB-1 index in NF2-associated meningiomas was not higher. Loss of heterozygosity (LOH) flanking or within the NF2 locus at 22q12 was detected in 100% of the tumors. LOH on 1p was the second most frequent abnormality (40%), followed by losses on 10q (27%), 6q and 14q (24%), 18q (23%), and 9p (17%). LOH on 19q and 17p, which is not commonly seen in sporadic meningiomas, was also only rarely detected in NF2-associated meningiomas. NF2 gene mutations were detected in 8 of 15 patients analyzed and were located in exons 2, 5, 6, 7, and 8. We conclude that sporadic and NF2-associated meningiomas share a common spectrum and frequency of allelic deletions as well as, in contrast to previous observations, a similar proliferative activity.     

Immunohistochemical expression of progesterone and estrogen receptors in meningiomas

In this study we present results of investigations of progesterone and estrogen receptors in most frequent, WHO grade I histological types of meningiomas (meningothelial, fibrous, and transitional) and in atypical--WHO grade II variant of these tumors. Samples from 64 tumors were examined. The cohort consisted of 46 WHO grade I (21 transitional, 13 fibrous and 12 meningothelial histologic variants) and of 18 atypical meningiomas. Apart from immunohistochemical examination of progesterone and estrogen receptors, MIB 1 labeling index was estimated. Positive immunoreaction for progesterone receptors was found in 100% meningothelial, 95% transitional, 46% fibrous and 78% atypical variant of meningiomas. Intensity of immunoreaction was stronger in grade I than in grade II tumors. Immunoexpression of estrogen receptors was found in 48% of the investigated meningiomas. No correlation was stated between WHO grade I and grade II tumors, and between meningothelial, transitional and fibrous variants of the neoplasms.     

Immunocytochemical analysis of glucose transporter protein‐1 (GLUT‐1) in typical,brain invasive,atypical and anaplastic meningioma

Glucose transporter‐1 (GLUT‐1) is one of the major isoforms of the family of glucose transporter proteins that facilitates the import of glucose in human cells to fuel anaerobic metabolism. The present study was meant to determine the extent of the anaerobic/hypoxic state of the intratumoral microenvironment by staining for GLUT‐1 in intracranial non‐embolized typical (WHO grade I; n = 40), brain invasive and atypical (each WHO grade II; n = 38) and anaplastic meningiomas (WHO grade III, n = 6). In addition, GLUT‐1 staining levels were compared with the various histological criteria used for diagnosing WHO grade II and III meningiomas, namely, brain invasion, increased mitotic activity and atypical cytoarchitectural change, defined by the presence of at least three out of hypercellularity, sheet‐like growth, prominent nucleoli, small cell change and “spontaneous” necrosis. The level of tumor hypoxia was assessed by converting the extent and intensity of the stainings by multiplication in an immunoreactive score (IRS) and statistically evaluated. The results were as follows. (1) While GLUT‐1 expression was found to be mainly weak in WHO grade I meningiomas (IRS = 1–4) and to be consistently strong in WHO grade III meningiomas (IRS = 6–12), in WHO grade II meningiomas GLUT‐1 expression was variable (IRS = 1–9). (2) Histologically typical, but brain invasive meningiomas (WHO grade II) showed no or similarly low levels of GLUT‐1 expression as observed in WHO grade I meningiomas (IRS = 0–4). (3) GLUT‐1 expression was observed in the form of a patchy, multifocal staining reaction in 76% of stained WHO grade I‐III meningiomas, while diffuse staining (in 11%) and combined multifocal and areas of diffuse staining (in 13%) were only detected in WHO grades II and III meningiomas, except for uniform staining in angiomatous WHO grade I meningioma. (4) “Spontaneous” necrosis and small cell change typically occurred away from the intratumoral capillary network embedded within the pattern of GLUT‐1 staining. Taken together, GLUT‐1 staining cannot be applied as a substitute for histologic grading in order to predict tumor behavior. However, assessment of tumor hypoxia in association with “spontaneous” necrosis and foci of small cell change may substantially contribute to the neuropathologic diagnosis of WHO grades II and III meningioma.     

Multiple recurrences require long-term follow-up in patients diagnosed with spindle cell oncocytoma of the sella turcica

Spindle cell oncocytoma (SCO) of the sella turcica is characterized as a WHO grade I non-endocrine neoplasm of the sella turcica. Histologically, these tumors contain spindled and variably oncocytic cellular processes. Although SCOs lack immunoreactivity for neuroendocrine markers and pituitary hormones, they are clinically indistinguishable from non-functioning pituitary adenomas. In contrast to the initially described benign clinical course, several reports have subsequently illustrated cases with multiple recurrences with or without histological features of anaplasia in the form of nuclear pleomorphism, frequent mitoses, high Ki-67 index, and/or necrosis. With a follow-up of 14 years, we report a case of SCO with multiple recurrences along with an exhaustive clinico-pathological review of all 41 cases of SCO reported in the literature, of which recurrence has been described in 11 cases. Collectively, this report highlights the importance of long-term follow-up and the possible need for adjuvant radiotherapy in patients diagnosed with a sellar SCO and provides a comprehensive review of this rare nonadenomatous sellar tumor.     

p53 protein alterations in adult astrocytic tumors and oligodendrogliomas

BACKGROUND: p53 is a tumor suppressor gene implicated in the genesis of a variety of malignancies including brain tumors. Overexpression of the p53 protein is often used as a surrogate indicator of alterations in the p53 gene. AIMS: In this study, data is presented on p53 protein expression in adult cases (>15 years of age) of astrocytic (n=152) and oligodendroglial (n=28) tumors of all grades. Of the astrocytic tumors, 86% were supratentorial in location while remaining 14% were located infratentorially - 8 in the the cerebellum and 13 in the brainstem. All the oligodendrogliomas were supratentorial. MATERIALS AND METHODS: p53 protein expression was evaluated on formalin-fixed paraffin-embedded sections using streptavidin biotin immunoperoxidase technique after high temperature antigen retrieval. RESULTS: Overall 52% of supratentorial astrocytic tumors showed p53 immunopositivity with no correlation to the histological grade. Thus, 58.8% of diffuse astrocytomas (WHO Grade II), 53.8% of anaplastic astrocytomas (WHO Grade III) and 50% of glioblastomas (WHO Grade IV) were p53 protein positive. In contrast, all the infratentorial tumors were p53 negative except for one brainstem glioblastoma. Similarly, pilocytic astrocytomas were uniformly p53 negative irrespective of the location. Among oligodendroglial tumors, the overall frequency of p53 immunopositivity was lower (only 28%), though a trend of positive correlation with the tumor grade was noted - 25% in Grade II and 31.5% in grade III (anaplastic oligodendroglioma). Interestingly, p53 labeling index (p53 LI) did not correlate with the histopathological grade in both astrocytic and oligodendroglial tumors. CONCLUSIONS: Thus, this study gives an insight into the genetic and hence biological heterogeneity of gliomas, not only between astrocytic tumors vs. oligodendrogliomas but also within astrocytic tumors with regard to their grade and location. With p53 gene therapy trials in progress, this will possibly have future therapeutic implications.     

Deletion mapping of the short arm of chromosome 1 identifies a common region of deletion distal to D1S496 in human meningiomas

We have studied a series of 63 meningiomas, including 47 benign meningiomas (World Health Organization, WHO, grade I), 13 atypical meningiomas (WHO grade II) and 3 anaplastic meningiomas (WHO grade III), using microsatellite and restriction fragment length polymorphism analysis for loss of heterozygosity (LOH) at 21 polymorphic loci on chromosome 1 (19 loci on 1p and 2 loci on 1q). LOH on 1p was found in 9 of 13 atypical meningiomas (70%) and in 3 of 3 (100%) anaplastic meningiomas, but only in 6 of 47 (13%) benign meningiomas. In 13 tumors allelic loss was observed at all informative loci on 1p. Terminal deletions with retention of heterozygosity at one or more proximal 1p loci were found in 5 tumors. The region commonly deleted in all tumors was located distally to the D1S496 locus, i.e., at cytogenetic bands 1p34 – 1pter, and included the chromosomal segment which is frequently deleted in neuroblastoma, malignant melanoma, and different types of carcinoma. Received: 11 February 1997 / Revised: 9 May 1997 / Accepted: 12 May 1997     

Recurrent meningiomas--the immunohistochemical analysis of angiogenesis and cellular proliferation. Preliminary study

Meningiomas exhibit a tendency to the local regrowth after their surgical resection, and some of those recurrent tumors show histological malignancy progression. The present study was performed on 10 cases of recurrent meningiomas chosen out of total 122 meningiomas diagnosed in our Department of Pathomorphology in the period 1993-1998. The tissue material from both operations was examined. One patient was operated three times. In three cases at the second operation there was progression from benign to atypical meningioma. The other tumors did not change their histological grade (four benign, one atypical and two anaplastic). The tumor tissue section were stained immunohistochemically with monoclonal antibodies raised against epithelial membrane antigen (EMA), Ki-67 and von Willebrand factor (vWf). The percentage of EMA-positive cells and Ki-67 immunoreactive cells (proliferation cell index--PCI) were counted. The vascular density (number of blood vessels/mm2) was assessed in the preparations stained with anti-vWf, as the measure of the intensity of angiogenesis. The values of the examined parameters were greatly differentiated within both the initial and the recurrent tumor groups. The values of vascular density ranged 12-96 vessels/mm2, the percentage of EMA-positive cells was 0.75%, PCI was from 0.3 to 9.3%. The values of the examined parameters did not differ significantly between initial and recurrent meningiomas groups. It is however worth to point out that PCI in the most recurrent tumors were higher than in their primary counterparts.     

Atypical (anaplastic) meningioma: relationship between histologic features and recurrence--a clinicopathologic study

Two-hundred-and-eighty meningiomas of the surgical pathological files of the Taipei Veterans General Hospital from the period 1976-1986 were reviewed by the authors without prior knowledge of clinical circumstances or outcome. Thirty-four cases were regarded as atypical or anaplastic based on high cellularity, pleomorphism and the presence of mitotic figures with 6 cases showing only the above features and the remaining 28 displaying in addition one or more of the following "ominous" variables: papillary formation, necrosis and invasion of the underlying brain. With a median follow-up of three years after surgery the recurrence rate was 44% (15 cases) for this group of tumors whereas the remaining 246 histologically benign meningiomas had a 6% recurrence rate during the same period. This difference was statistically significant (p less than 0.0001). Once the atypical or anaplastic character of a meningioma was established, no difference in the recurrence rate was found related to the number of mitoses and whether the additional ominous variables were present, alone or in conjunction with others. Immunostaining for vimentin, S100, fibronectin and EMA showed variable results in the 34 atypical meningiomas but without significant difference between those that recurred within 3 years and the ones that did not.     

Intraparenchymal cystic chordoid meningioma: A case report and review of the literature

Meningiomas usually present as benign tumors corresponding to WHO grade I. The development of the intraparenchymal chordoid variant of meningiomas with cyst formation in the CNS is extremely rare. We report a case of cystic chordoid meningioma in a middle‐aged man occurring in the brain parenchyma of the left temporal region. The tumor exhibited a marked peritumoral cyst, with contrast enhancement on MRI in accordance with type 2 of Zee's classification of cystic meningioma. Histologically, the tumor displays a typical chordoid structure with trabeculae or cords of eosinophilic vaculoated cells in the abundant mucoid matrix. Tumor cells are diffusely positive for epithelial membrane antigen (EMA), vimentin and focally positive for D2‐40, but lack immunoreactivity for cytokeratin (CK) and GFAP. MIB‐1 labeling is low, focally accounting for 2% of the tumor. A diagnosis of primary intraparenchymal cystic chordoid meningioma (WHO grade II) was made. There was no evidence of tumor recurrence during the postoperative 6‐month follow‐up period. To our knowledge, there is no report describing the radiological and histological characteristics of cystic chordoid meningioma entirely presenting in the brain parenchyma. In addition, the biological behavior and histological differential diagnoses of this tumor are discussed.     

Comparative genomic hybridization analysis of genomic alterations in benign,atypical and anaplastic meningiomas

BACKGROUND: Meningiomas are common tumors of the central nervous system. Although most are benign tumors, approximately 10% show a histologic progression to a higher malignancy grade similar to atypical (GII) and anaplastic (GIII) meningiomas. Monosomy 22q12 is the most frequent genetic alteration detected in these tumors, but failure of detection of 22q mutations in about 40% of tumors which are indistinguishable from meningiomas with 22q deletions with respect to clinical and histopathologic features, makes it apparent that an alternative mechanism is responsible for the initiation of meningioma. Moreover, little is known about genetic alterations during malignant progression of meningioma. PURPOSE: In order to determine the genetic pathways underlying the development of meningioma, 15 benign (WHO grade I), 7 atypical (WHO grade II) and 3 anaplastic (WHO grade III), sporadic meningiomas were screened by Comparative Genomic Hybridization (CGH). RESULTS: Statistical analysis revealed a significant correlation between the number of chromosomal imbalances and the tumor grade; the numbers of total alterations detected per tumor were 2.20 (2.24 for GI, 10.00 (1.17 for GII and 14.66 (1.15 for GIII. The most frequent abnormality seen in benign tumors was loss on 22q (47%). The second alteration was 1p deletion (33%) and this abnormality was also the common aberration in three tumors without CGH detected 22q deletion. In GII, aberrations most commonly identified were losses on 1p (6/7 cases), 22q (5/7 cases), 10q (4/7 cases), 14q and 18q (3/7 cases) as well as gains on 15q and 17q (3/7 cases). In GIII, genomic loss on 1p was the most commonly observed abnormality (3/3). Losses on 9p, 10q, 14q, 15q, 18q and 22q as well as gains on 12q, 15q and 18p were the other genomic alterations detected by CGH. Combined 1p/14q deletions were encountered in 2/15 benign, 3/7 atypical and 2/3 anaplastic meningiomas. By CGH, DNA sequences on 17q21-qter were seen to be amplified in 1/7 GII and 2/3 GIII, whereas highly amplified DNA sequences on 12q13-qter, 20q and 22q11-q12 were seen in one GII, two GII/one GIII, and one GIII, respectively. CONCLUSION: It was concluded that chromosomal deletion from 1p could play a major role in the initiation and progression of meningiomas and that 1p/14q deletions could be a primary focus of further detailed assessment of tumour genesis.