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Aims: Histological invasion into the adjacent brain parenchyma is frequently investigated in meningioma because it is an important morphological criterion for grade II meningioma according to the 2016 WHO classification. However, few studies have focused on dural invasion of meningiomas. Herein, we propose a novel histopathological classification based on dural invasion of meningiomas., Methods: Forty-nine cases with WHO grade I meningiomas who underwent Simpson grade I removal were collected. After the meningeal layer (ML) and periosteal layer (PL) of dura mater were visualised by Masson's trichrome stain, we evaluated the depth (to the ML and PL) and the patterns (1, expanding; 2, infiltrating) of dural invasion of meningiomas using serial paraffin sections. Invasion-associated markers, including Ki-67, matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13, aquaporin 1 and Na-K-2Cl cotransporter, were quantitatively analysed by immunohistochemistry., Results: Thirty-five cases (71.4%) showed the dural invasion. In 27 of these 35 cases (77.1%), dural invasion was localised in ML. Type 1 (expanding type) and type 2 (infiltrating type) invasions were observed in 23 and 12 cases, respectively. The recurrence rate in cases with type 2 invasion was significantly higher than that in cases with type 1 invasion. The percentage of MMP-1-positive tumour cells was also significantly higher in cases with dural invasion than those without, suggesting involvement of MMP-1 in dural invasion., Conclusions: We quantitatively evaluated the depth and patterns of dural invasion in meningiomas. The patterns of dural invasion were associated with meningioma recurrence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Meningiomas are common brain tumours that are usually defined by benign clinical course. However, some meningiomas undergo a malignant transformation and recur within a short time period regardless of their World Health Organization (WHO) grade. The current study aimed to identify potential markers that can discriminate between benign and malignant meningioma courses., Methods: We profiled the metabolites from 43 patients with low- and high-grade meningiomas. Tumour specimens were analyzed by nuclear magnetic resonance analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm., Results: We observed two distinct clusters marked by alterations in glycine/serine and choline/tryptophan metabolism. Glycine/serine cluster showed significantly lower WHO grades and proliferation rates. Also progression-free survival was significantly longer in the glycine/serine cluster., Conclusion: Our findings suggest that alterations in glycine/serine metabolism are associated with lower proliferation and more recurrent tumours. Altered choline/tryptophan metabolism was associated with increases proliferation, and recurrence. Our results suggest that tumour malignancy can be reflected by metabolic alterations, which may support histological classifications to predict the clinical outcome of patients with meningiomas.

Meningiomas are the commonest types of tumours in the central nervous system (CNS). It is a benign type of tumour divided into three WHO grades (I, II and III) associated with tumour growth rate and likelihood of recurrence, where surgical outcomes and patient treatments are dependent on the meningioma grade and histological subtype. The development of alternative approaches based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy could aid meningioma grade determination and its biospectrochemical profiling in an automated fashion. Herein, ATR-FTIR in combination with chemometric techniques is employed to distinguish grade I, grade II and grade I meningiomas that re-occurred. Ninety-nine patients were investigated in this study where their formalin-fixed paraffin-embedded (FFPE) brain tissue samples were analysed by ATR-FTIR spectroscopy. Subsequent classification was performed via principal component analysis plus linear discriminant analysis (PCA-LDA) and partial least squares plus discriminant analysis (PLS-DA). PLS-DA gave the best results where grade I and grade II meningiomas were discriminated with 79% accuracy, 80% sensitivity and 73% specificity, while grade I versus grade I recurrence and grade II versus grade I recurrence were discriminated with 94% accuracy (94% sensitivity and specificity) and 97% accuracy (97% sensitivity and 100% specificity), respectively. Several wavenumbers were identified as possible biomarkers towards tumour differentiation. The majority of these were associated with lipids, protein, DNA/RNA and carbohydrate alterations. These findings demonstrate the potential of ATR-FTIR spectroscopy towards meningioma grade discrimination as a fast, low-cost, non-destructive and sensitive tool for clinical settings. Graphical abstract Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was used to discriminate meningioma WHO grade I, grade II and grade I recurrence tumours.

Introduction: PELICAN ("Partager Efficacement en Laboratoire les Informations des Comptes rendus ANatomopathologiques") is a software, which generates standardized reports, and allows to automatically create a database. It has been used in central nervous system tumor pathology at the University Hospital of Nancy since 2014. The purpose of this article was to illustrate the use of this application for meningiomas, with a first statistical evaluation., Materials and Methods: The export of data included all cases of meningiomas recorded in the PELICAN application until July 2018. The PELICAN application is a Microsoft Excel file containing a software, written in Visual Basic for Applications, and used by the pathologist to create the report. The main clinical data were collected from the Hérault Register census form. Follow-up was systematically reported for atypical meningiomas., Results: Two hundred and ninety-five meningiomas were analyzed, including 250 grade I meningiomas, 42 grade II meningiomas, and 3 grade III meningiomas. Grade II meningiomas were characterized by a significantly higher proportion of men (P=0.002) and dural infiltration (P<0.001), a significant increase in the Ki-67 index (P<0.0001), and a significant decrease in progesterone receptor expression (P<0.001). In atypical meningiomas, a Ki-67 index of more than 20 % was significantly correlated with a shorter progression-free survival (P=0.032)., Conclusion: The PELICAN software is an easy-to-use tool that allows to generate standardized reports and feed a database, opening very interesting perspectives from an epidemiological and scientific point of view., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Aims: Although ultrastructural studies showed that minute pulmonary meningothelial-like nodules (MPMNs) cells closely resembled meningothelial cells, their immunophenotype has not been well characterised, partly due to their rarity., Methods: Somatostatin receptor 2a (SSTR2a) and other markers of meningioma, including epithelial membrane antigen (EMA), progesterone receptor (PR) and S100, were analysed retrospectively in 19 MPMN cases from two institutions in China., Results: The median age of patients with MPMNs was 62.5 years (32-73 years), with a male-to-female ratio of 1:8.5. Most (15/19) patients with MPMNs had coexisting diseases, including adenocarcinomas (12 cases), bronchiectasis (1 case) and tuberculosis (2 cases). Just over half of the cases (10/19) were multifocal lesions (2-5 lesions). An additional 53 cases with 123 lesions from the literature were reviewed with reported immunophenotype information. In total, 162 lesions were included in the analysis. The size of nodules was 1-4 mm. All MPMN lesions (39/39) in the 19 cases showed strong and diffuse cytoplasmic expression of SSTR2a. The expression rate of SSTR2a was higher than that of conventional markers of meningioma, including EMA (86/138), PR (32/68) and S100 (1/125)., Conclusions: Our observations expand the spectrum of recognised SSTR2a-positive lesions and once again demonstrated that MPMNs show immunohistochemical characteristics similar to meningothelial cells., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The TRPV1-4 members of TRPV cation channel subfamily are mainly regarded as polymodal receptors that may be activated by diverse changes in cellular microenvironment and endogenous and exogenous agents. Abnormal expression of these channels has been reported in various tumors but not in meningiomas. Meningioma cells are thought to originate from arachnoid cap cells due to cytological and functional similarities between the two types of cells. To investigate the expression profile of TRPV1-4 channels in meningiomas and compare with TRPV1-4 channel expression in leptomeninges, we used immunohistochemistry in formalin-fixed, paraffin-embedded semi-serial tissue sections from 175 meningiomas with different grades and histological subtypes, and normal brain or meningioma specimens that contained leptomeninges. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined. Leptomeninges were TRPV1-4 immunonegative. A significant percentage of tumors exhibited TRPV1-4 channel expression which was independent of the proliferation index of the tumors but was significantly associated with histopathological subtypes. The TRPV1 and TRPV3 immunoexpression was decreased whereas TRPV4 immunoexpression was significantly greater in high-grade (WHO, grade II and III) as compared with low-grade (WHO, grade I) meningiomas. Additionally, TRPV4 emerged as an independent predictor for the degree of malignancy using the binary logistic regression model [dependent variable: grade I versus higher grades (II and III)]. Kaplan-Meier analysis for 102 patients showed no significant association of TRPV1-4 expression with overall survival. The above data support that TRPV1-4 channels are implicated in meningioma pathogenesis, and TRPV4 has predictive significance in the disease.

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p<0.05); however, there were no differences in age, Cho/Cr, or NAA/Cr. According to conditional inference tree analysis, the optimal cut-off point for the Cho/NAA ration between high-grade and low-grade meningioma was 2.409 (sensitivity = 61.54%; specificity = 86.36%). This analysis of pre-operative 1H-MRS metabolite ratio demonstrated that the Cho/NAA ratio may provide a simple and practical predictive value for high-grade intracranial meningiomas, and may aid neurosurgeons in efforts to design an appropriate surgical plan and treatment strategy before surgery., Competing Interests: The authors have declared that no competing interests exist.

Purpose Minute pulmonary meningothelial-like nodules are incidentally discovered in lung specimens. We analyzed the clinicopathologic features of 14 cases identified in surgically resected lungs. Methods Among patients who underwent lung resection in our hospital from October 2007 to March 2016, 14 were found to have minute pulmonary meningothelial-like nodules. The clinical parameters, radiologic findings, and pathologic features of these patients were retrospectively reviewed using the medical records. Results The patients included 4 men and 10 women, with a mean age of 69 years (range 53-82 years). The coexisting main disease was adenocarcinoma in 8 patients, squamous cell carcinoma in 1, atypical adenomatous hyperplasia in 1, and metastatic pulmonary tumor in 3. In one patient, the minute pulmonary meningothelial-like nodules presented as multiple lung nodules on chest computed tomography. The median size of the nodules was 1.4 mm (range 0.3-6.0 mm). Similar to meningioma, one case had immunoreactivity to progesterone receptor and epithelial membrane antigen, although the minute pulmonary meningothelial-like nodules were not associated with a meningioma. Conclusions The relationship between minute pulmonary meningothelial-like nodules and meningioma should be investigated. If minute pulmonary meningothelial-like nodules are found on preoperative computed tomography, thoracoscopic lung biopsy is helpful for differential diagnosis.

Ectopic meningothelial proliferations are rare and can occur in a multitude of extracranial/spinal anatomic locations. Perineurioma is another uncommon entity that shares similar histological characteristics to those found in meningothelial proliferations. These include bland spindle cells with thin, bipolar nuclei; eosinophilic cytoplasm; and indistinct cell borders, arranged in short fascicles with whorl formation. Given their uncommon occurrence and shared histological and immunohistochemical features, their distinction can present a diagnostic challenge. Immunohistochemical studies can provide guidance when attempting to distinguish between these 2 lesions. Here, we present an unusual case of a patient with Cowden syndrome who was discovered to have a meningothelial proliferation within an axillary lymph node. To the best of our knowledge, this is the first case in which a meningothelial proliferation has been identified in a lymph node. Furthermore, the occurrence in a patient with Cowden syndrome is intriguing and raises the possibility of a pathogenetic link., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Leptomeningeal dissemination of low-grade Schwann cell neoplasms is an exceptionally rare occurrence and has not been well documented in the literature. We encountered 2 cases of leptomeningeal dissemination of low-grade Schwann cell neoplasms. Patient 1 was a 63-year-old woman with neurofibromatosis type 1 and a progressive low-grade malignant peripheral nerve sheath tumor developing from a diffuse/plexiform orbital neurofibroma that arose in childhood. The neoplasm demonstrated local and leptomeningeal dissemination intracranially leading to the patient's death. There was partial loss of H3K27 tri-methylation, p16 and collagen IV. Patient 2 was a 60-year-old man without neurofibromatosis type 1 who presented with cranial nerve symptoms and a disseminated neoplasm with a Schwann cell phenotype. The neoplasm stabilized after irradiation and chemotherapy, but the patient died of medical complications. Autopsy findings documented disseminated leptomeningeal disease in the intracranial and spinal compartment. H3K27M tri-methylation was preserved. The clinicopathologic and autopsy findings are studied and presented, and the literature is reviewed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Hot-spot based examination of immunohistochemically stained histological specimens is one of the most important procedures in pathomorphological practice. The development of image acquisition equipment and computational units allows for the automation of this process. Moreover, a lot of possible technical problems occur in everyday histological material, which increases the complexity of the problem. Thus, a full context-based analysis of histological specimens is also needed in the quantification of immunohistochemically stained specimens. One of the most important reactions is the Ki-67 proliferation marker in meningiomas, the most frequent intracranial tumour. The aim of our study is to propose a context-based analysis of Ki-67 stained specimens of meningiomas for automatic selection of hot-spots., Methods: The proposed solution is based on textural analysis, mathematical morphology, feature ranking and classification, as well as on the proposed hot-spot gradual extinction algorithm to allow for the proper detection of a set of hot-spot fields. The designed whole slide image processing scheme eliminates such artifacts as hemorrhages, folds or stained vessels from the region of interest. To validate automatic results, a set of 104 meningioma specimens were selected and twenty hot-spots inside them were identified independently by two experts. The Spearman rho correlation coefficient was used to compare the results which were also analyzed with the help of a Bland-Altman plot., Results: The results show that most of the cases (84) were automatically examined properly with two fields of view with a technical problem at the very most. Next, 13 had three such fields, and only seven specimens did not meet the requirement for the automatic examination. Generally, the Automatic System identifies hot-spot areas, especially their maximum points, better. Analysis of the results confirms the very high concordance between an automatic Ki-67 examination and the expert's results, with a Spearman rho higher than 0.95., Conclusion: The proposed hot-spot selection algorithm with an extended context-based analysis of whole slide images and hot-spot gradual extinction algorithm provides an efficient tool for simulation of a manual examination. The presented results have confirmed that the automatic examination of Ki-67 in meningiomas could be introduced in the near future.

Introduction: The 2007 World Health Organization (WHO) classification of tumors of the central nervous system distinguishes meningeal hemangiopericytomas (HPC) from solitary fibrous tumors (TFS). In the WHO classification of tumors of soft tissue and bone, those neoplasms are no longer separate entities since the discovery in 2013 of a common oncogenic event, i.e. the NAB2-STAT6 gene fusion. A shared histopronostic grading system, called "Marseille grading system", was recently proposed, based on hypercellularity, mitotic count and necrosis. We evaluated the immunophenotype and histoprognosis in a retrospective cohort of intracranial HPC and TFS., Methods: Fifteen initial tumors and 2 recurrences were evaluated by immunohistochemistry for STAT6, CD34, EMA, progesterone receptors and Ki67. The pronostic value of the WHO and the Marseille grading systems was tested on 12 patients with clinical follow-up., Results: Initial tumors were 11 HPC and 4 SFT. STAT6 and CD34 were expressed in 16/17 tumors, EMA and progesterone receptors in 2 and 5 cases, respectively. The Ki67 labelling index was 6.25% in HPC and 3% in SFT. Half of the tumors recurred between 2 years and 9 years after initial diagnosis (mean time 5 years). No statistical difference in the risk of recurrence was associated with either grade (WHO or Marseille), in this small cohort., Conclusion: The diagnosis of HPC and TFS is facilitated by the almost constant immuno-expression of STAT6, and this justifies their common classification. The high rate of recurrence implies a very long-term follow-up because the current grading systems do not accurately predict the individual risk., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Meningeal solitary fibrous tumors-hemangiopericytomas (SFT-HPC) and meningiomas can be difficult to distinguish on histologic examination. STAT6 immunohistochemistry (IHC) is a reliable diagnostic marker of SFT-HPCs. Recently, GRIA2 has also been reported to be a diagnostic marker of SFT-HPC, although no extensive data are available for meningeal SFT-HPCs yet. The aim of this study was to test their diagnostic performance in a large cohort of SFT-HPCs and meningiomas. IHC analyses for GRIA2 and STAT6 were performed on tissue microarrays containing 76 SFT-HPCs and 181 meningiomas. Results were compared with previous data with ALDH1 and CD34. Two different anti-STAT6 antibodies were tested: SC-20 polyclonal and YE361 monoclonal antibody. Ninety-six percent of meningeal SFT-HPCs but no meningioma displayed nuclear STAT6 positivity. With SC-20 antibody, concomitant cytoplasmic staining for STAT6 was observed in >50% of all cases, including meningiomas. However, using YE361 antibody, cytoplasmic staining was absent, and nuclear signal intensity was stronger leading to better interpretation of STAT6 IHC. GRIA2 was positive in 84% of SFT-HPCs and in 16% of meningiomas. STAT6 had excellent sensitivity (96%) and specificity (100%), ALDH1 and GRIA2 had same sensitivity (84%), but ALDH1 and CD34 had better specificity than GRIA2 (97% and 96% vs. 84%, respectively). For the differential diagnosis of SFT-HPCs versus meningiomas, the best diagnostic approach is to perform STAT6, followed by ALDH1 and CD34 in the case of uncommon STAT6-negative cases. Because of meningioma positivity, GRIA2 seems less useful in this indication.

Objective: To investigate the diagnostic role of STAT6 immunohistochemistry in solitary fibrous tumors (SFT)/meningeal hemangiopericytomas (HPC)., Method: Evaluated the expression of STAT6, vimentin, CD34, EMA, PR, S-100, CD56, GFAP and Ki-67 in a cohort of 37 SFT/meningeal HPC, 30 meningiomas and 30 schwannomas by immunohistochemistry staining., Results: All SFT/meningeal HPC demonstrated nuclear positivity for STAT6, and the proportion of positive tumor cells ranged from 60% to 95%, with no significant difference cases.Vimentin was strongly positive in all cases. CD34, EMA and PR positivity was found in 32 cases, 1 case and 4 cases, respectively.S-100 protein, CD56 and GFAP were negative; Ki-67 labeling index was 1%-8%. However, the meningiomas and schwannomas were negative for STAT6., Conclusions: STAT6 is a relatively specific biomarker for SFT/meningeal HPC, and may be used in the diagnosis and differential diagnosis of SFT/meningeal HPC, especially for the atypical cases, and allows the precise pathologic diagnosis of SFT/meningeal HPC.

Purpose: Primary intracranial melanocytomas are rare neoplasms, especially in the sellar region. Intracranial melanocytoma is usually a dural-based tumor, fed by dural arterial branches in a manner similar to meningioma. Primary sellar melanocytoma may be misdiagnosed as hemorrhagic pituitary macroadenoma, spindle cell oncocytoma, and intrasellar meningioma. These tumors differ in some radiological respects, but are difficult to differentiate preoperatively., Methods: Only five cases of primary sellar/suprasellar melanocytic tumors, excluding melanomas have been reported thus far. In this paper, we report an instructive new case of a 31-year-old woman presenting with a 2-year history of amenorrhea and an intrasellar mass with suprasellar extension, suggestive of hemorrhagic pituitary adenoma., Results: Transsphenoidal surgical excision was difficult due to extensive bleeding from the lesion, and at the time, the tumor could not be diagnosed histopathologically. Six years later, we operated again because of tumor regrowth. Angiography revealed a hypervascular tumor, which was fed from the dorsal sellar floor. We had difficulty resecting the tumor, but achieved total removal. Our case had typical radiographic characteristics of melanocytoma, revealed by both magnetic resonance imaging and angiography. However, it was difficult to reach a final diagnosis. Further histopathological examination, including immunohistochemical and ultrastructural studies, was helpful for diagnosis of melanocytoma., Conclusions: Primary sellar melanocytic tumors are derived from melanocytes in the meningeal lining of the sellar floor or in the diaphragm sellae, based on both embryological assumptions and the clinical findings of our case. We discuss the problems of differential diagnosis and management of primary sellar melanocytic tumors.

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., (© 2014 International Clinical Cytometry Society.)

We describe an unusual case of a recurrent dural neoplasm, previously diagnosed as meningioma. Histopathologically, the tumor is characterized by aggregates of divergently differentiated clear cells embedded in an abundant lymphoplasmacyte-rich stroma, mimicking a lymphoplasmacyte-rich meningioma. This study focuses on the histologic and immunohistochemical characterization of a unique dural-based tumor and provides useful guidelines for differentiating meningioma from other uncommon dural-based neoplasms. We propose that this recurrent dural neoplasm is a distinctive entity and, therefore, enlarges the spectrum of dural-based neoplasms that enter the differential diagnosis with meningiomas. Awareness of this tumor entity could prove useful for appropriate patient management., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Meningiomas are one of the most common tumors that arise within the central nervous system; they represent up to 30% of all primary intracranial tumors. Extradural meningiomas are rare (<2% of all meningiomas), and most arise within the calvarium. Intraosseous calvarial meningiomas are usually easy to diagnose histologically if they are of the meningothelial type; however, they may cause diagnostic challenges when they manifest as unusual morphologic variants, such as the microcystic type. To address this issue we present a series of 9 cases of calvarial microcystic meningiomas arising in 7 female and 2 male patients; all patients were adults. The tumors had heterogenous findings on imaging studies and ranged in size from 1.1 to 4.3 cm in greatest dimension. The neoplasms were composed predominantly of stellate and spindle cells with long, thin interconnecting cytoplasmic processes arranged in a complex network. The resulting cellular architecture was "sieve-like" in appearance because of the formation of numerous small "cyst-like" spaces interposed between the cytoplasmic processes of the tumor cells. All of the neoplasms expressed the characteristic immunophenotype of meningiomas (EMA, PR positive). Most tumors were resected, and none of these have recurred during a follow-up period of 1 to 83 months (average 17 mo). The morphology of the tumors and their anatomic location generated problems in diagnosis, especially in 6 patients with a history of malignancy and for whom metastatic disease was suspected clinically. Intraosseous microcystic meningioma is uncommon, and this series, the largest reported to date, describes their clinicopathologic findings, biological behavior, and features that facilitate their accurate diagnosis.

Background: The meningeal hemangiopericytoma (MHPC) is a vascular tumor arising from pericytes. Most intracranial MHPCs resemble meningiomas (MNGs) in their clinical presentation and histological features and may therefore be misdiagnosed, despite important differences in prognosis., Materials and Methods: We report 8 cases of MHPC and 5 cases of MNG collected from 2007 to 2011 from the Neuro-Surgery and Histopathology departments. All 13 samples were re reviewed by two independent pathologists and investigated by immunohistochemistry (IHC) using mesenchymal, epithelial and neuro-glial markers. Additionally, we screened all tumors for a large panel of chromosomal alterations using multiplex ligation probe amplification (MLPA). Presence of the NAB2-STAT6 fusion gene was inferred by immunohistochemical staining for STAT6., Results: Compared with MNG, MHPCs showed strong VIM (100% of cases), CD99 (62%), bcl-2 (87%), and p16 (75%) staining but only focal positivity with EMA (33%) and NSE (37%). The p21 antibody was positive in 62% of MHPC and less than 1% in all MNGs. MLPA data did not distinguish HPC from MNG, with PTEN loss and ERBB2 gain found in both. By contrast, STAT6 nuclear staining was observed in 3 MHPC cases and was absent from MNG., Conclusions: MNG and MHPC comprise a spectrum of tumors that cannot be easily differentiated based on histopathology. The presence of STAT6 nuclear positivity may however be a useful diagnostic marker.

Background: Intracranial chondrosarcoma is rare, and most cases occur in the skull base. Intradural chondrosarcoma is even rarer., Case: Here, we describe a case of dural chondrosarcoma with a radiation history for nasopharyngeal carcinoma and a radical prostatectomy for prostatic cancer 15 and 8 years earlier, respectively. A 67-year-old man presented with a 3-week memory disturbance and dysarthria. Computed tomography and magnetic resonance images of the brain revealed a dural-based mass in the left temporal area. Under the impression of a glioblastoma, a resection and an intraoperative squash cytology were done. A necrotic dirty background as well as bluish-to-pinkish myxoid stroma were characteristic; the nuclei of highly pleomorphic tumor cells were hyperchromatic to vesicular with an occasional ground-glass appearance. The cytoplasm was of an eosinophilic hyalinized condensed morphology with an occasional granular appearance. Histologically, the lobulated mass was composed of hypercellular lobules of well-differentiated chondrocytes intermixed with anaplastic pleomorphic cells and diagnosed as a conventional grade III chondrosarcoma. These cells were immunoreactive for D2-40, S-100 protein and vimentin. Brain invasion was also found., Conclusion: Albeit rare, dural-based chondrosarcomas should be considered in the differential diagnosis for meningeal tumors, especially in the case of previous radiation therapy., (© 2015 S. Karger AG, Basel.)

Patients with esophageal squamous cell carcinoma generally present at an advanced stage at the time of diagnosis. The most common sites of visceral metastasis are the lung, liver and bone, but brain and bone marrow involvement is exceedingly rare. Herein, we report a 62-year-old man with a 4-wk history of progressive low back pain with radiation to bilateral lower legs, dysphagia and body weight loss. Esophageal squamous cell carcinoma with regional lymph node, liver and bone metastases was diagnosed. He underwent concurrent chemoradiotherapy and got a partial response. Four months later, he complained of headache, diplopia and severe hearing impairment in the left ear. There was no evidence for bacterial, fungal, tuberculous infection or neoplastic infiltration. Magnetic resonance imaging of the brain demonstrated thickening and enhancement of bilateral pachymeninges and multiple enhancing masses in bilateral skull. Dural metastasis was diagnosed and he received whole brain irradiation. In addition, laboratory examination revealed severe thrombocytopenia and leucopenia, and bone marrow study confirmed the diagnosis of metastatic squamous cell carcinoma. This is the first described case of esophageal squamous cell carcinoma with dural and bone marrow metastases. We also discuss the pathogenesis of unusual metastatic diseases and differential diagnosis of pachymeningeal thickening.

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.

We report on a 51-year-old woman who presented with a cervical spinal cord tumor clinically suspected to be a metastasis. Histological examination revealed an anaplastic meningioma containing epithelial nests arranged in a gland-like pattern suggestive of adenocarcinoma. This component strongly expressed cytokeratins whereas the meningothelial component was vimentin--epithelial membrane antigen--and progesterone receptor-immunoreactive, suggesting either anaplastic meningioma with adenocarcinoma-like metaplasia, or adenocarcinoma metastasis in a meningioma, but the search for a primitive neoplasia including thoracic-abdominal-pelvic computed tomography and mammography was negative. Anaplastic meningiomas with adenocarcinoma-like metaplasia are uncommon lesions, 4 cases having been reported in the literature so far. Their immunohistochemical and chromosomal characteristics are similar to those observed in secretory meningiomas. When available, fluorescence in situ hybridization detects the same chromosomal alterations in the two components, confirming a common clonal origin. This observation demonstrates the necessity to perform the correct diagnosis of malignant meningioma with adenocarcinomatous metaplasia, whose prognosis and treatment radically differ from those of metastatic adenocarcinoma located in a meningioma., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Meningiomas are generally benign tumors, but rarely metastasize outside of the central nervous system. A 25-year-old female was admitted to our institute because of an abnormal shadow on her chest x-ray. A computed tomography (CT) scan showed a 3-cm, well- circumscribed mass in the right lower lobe of the lung. We performed thoracotomy and resected three pulmonary tumors at the right lung and diaphragm. Histological examination revealed a benign meningothelial meningioma. Six months later, she complained of heaviness of her head and a head CT scan revealed an intracranial mass. A craniotomy was performed and a brain tumor was found to be histologically identical to the lung tumors. During the 21 years since the first operation, we performed three times of pulmonary and pleural metastasectomies and two times of resection of intracranial local recurrences. All of those tumors were meningothelial meningioma without malignant change. The patient is alive without metastasis after the last resection of metastatic tumors.

The authors describe a male patient who developed a large intracranial meningioma during the hormone therapy for pre-existing prostate cancer. A 70-year-old man received a brain check-up, and no intracranial abnormality was detected. Five months later, prostate cancer was diagnosed, and he underwent prostatectomy. Leuprorelin acetate, a luteinizing hormone-releasing hormone (LH-RH) agonist, was subsequently administered to the patient once a month for 3 years. After that he presented with a large parasagittal mass, which was excised. The tumor was histologically diagnosed as meningothelial meningioma, and LH-RH receptors were verified immunohistochemically in the cytoplasm of the tumor cells. Leuprorelin acetate may accelerate the rapid growth of meningioma in this patient.

Isolated spinal leptomeningeal metastases (LMM) without brain metastases are infrequent, accounting for about 1% of all solid tumors. In LMM, cerebrospinal fluid (CSF) analyses are mostly abnormal. Demonstrations of intrathecal tumor markers are highly suggestive, but only a positive cytology is diagnostic. The initial CSF cytology can give a false negative result in up to 40-50% of patients with pathologically proven LMM on autopsy. We report a case of intrahepatic cholangiocarcinoma with spinal LMM confirmed using cytokeratin7 and pancytokeratin (AE1/AE3) immunocytochemical studies on paucicellular cerebrospinal fluid cytospin preparation. Given the paucicellularity of the smears and difficult morphologic categorization, immunocytochemistry is vital for confirmatory diagnosis and can help reduce false negative results. To the best of our knowledge this is the first case report of cytologically confirmed LMM from an intrahepatic cholangiocarcinoma while the patient was undergoing treatment., (Copyright © 2013 Wiley Periodicals, Inc.)

The occurrence of metastasis of a systemic neoplasm to an intracranial tumor is a rare phenomenon. Meningiomas have been reported as the most common intracranial tumor to harbor a systemic metastasis, with breast and lung carcinomas being the most common sites of origination. Here, we report a case of an adenocarcinoma metastasis of an adenosquamous lung carcinoma found within a meningioma, resulting in the patient's first clinical manifestations. We also review the literature for other cases of adenocarcinoma metastatic to a meningioma and suggest mechanisms that make meningiomas likely to harbor systemic metastases including increased vascularity, slow growth rate, increased hyaline content and expression of cell-cell adhesion molecules.

Angiomatous meningiomas are rare meningioma subtypes, which are characterized by abundant, well-formed vessels. We encountered two cases of newly diagnosed angiomatous meningiomas exhibiting tumor cells with brown pigments, which were histochemically proven to be iron. In an attempt to understand its pathological significance, we assessed this unusual finding in representatives for each grade of meningiomas and immunoexpression of transferrin receptor (CD71) and the oxidative DNA damage marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG). Iron deposition in the tumor cells was observed in 8/15 (53%) angiomatous meningioma cases, 2/6 (33%) microcystic meningiomas and 2/20 (10%) meningothelial meningiomas, which included clustered microvessels, but not in fibrous, atypical or anaplastic meningiomas (P = 0.001). Cytoplasmic CD71 expression was largely negative in angiomatous meningioma cases, but positive in meningothelial and high-grade meningiomas, suggesting that the transferrin-dependent iron transporter was involved in iron uptake in meningiomas. Nuclear expression of 8-OHdG was observed in ≥ 50% of the tumor cells in all 15 cases of angiomatous meningioma and was associated with the presence of regressive histopathological findings, such as hyalinized vessels and cystic changes. In addition, the fraction of iron-containing tumor cells was correlated to those expressing 8-OHdG (P = 0.005). Our finding indicates that cytoplasmic iron deposition in tumor cells is characteristic of highly vascularized benign meningiomas and related to increased oxidative DNA damage markers., (© 2013 Japanese Society of Neuropathology.)

Purpose: In a series of 78 consecutive patients we analyzed the influence of peritumoral edema (PTE) and angiogenesis (vascular endothelial growth factor/ VEGF expression) on the prognosis of morbidity and postoperative complications after intracranial meningioma surgery., Methods: A retrospective analysis was performed of clinical, neuroradiological and histological data of 78 microsurgically treated patients with intracranial supratentorial meningioma, with follow-up period of at least one year., Results: The severity of PTE showed significant correlation with VEGF expression, and all patients with large PTE (>40 mm) had strong VEGF expression (>50%). Treatment outcome was significantly better in patients with low VEGF expression (p<0.05). All of the monitored postoperative complications were more frequent in the group with PTE.The duration of intensive care treatment in the group with PTE (mean 6.85 days) was significantly longer than in the group without PTE (mean 3.68 days) (p=0.003). In the group without PTE, the outcome was significantly better than in patients with PTE (p<0.01)., Conclusion: PTE in intracranial meningiomas has significant influence on the prognosis in surgically treated patients in terms of increased risk of morbidity and postoperative complications. VEGF expression is strongly correlated with PTE formation, which also affects the outcome in the management of patients with intracranial meningioma.

The main goal of brain tumor surgery is to maximize tumor resection while preserving brain function. However, existing imaging and surgical techniques do not offer the molecular information needed to delineate tumor boundaries. We have developed a system to rapidly analyze and classify brain tumors based on lipid information acquired by desorption electrospray ionization mass spectrometry (DESI-MS). In this study, a classifier was built to discriminate gliomas and meningiomas based on 36 glioma and 19 meningioma samples. The classifier was tested and results were validated for intraoperative use by analyzing and diagnosing tissue sections from 32 surgical specimens obtained from five research subjects who underwent brain tumor resection. The samples analyzed included oligodendroglioma, astrocytoma, and meningioma tumors of different histological grades and tumor cell concentrations. The molecular diagnosis derived from mass-spectrometry imaging corresponded to histopathology diagnosis with very few exceptions. Our work demonstrates that DESI-MS technology has the potential to identify the histology type of brain tumors. It provides information on glioma grade and, most importantly, may help define tumor margins by measuring the tumor cell concentration in a specimen. Results for stereotactically registered samples were correlated to preoperative MRI through neuronavigation, and visualized over segmented 3D MRI tumor volume reconstruction. Our findings demonstrate the potential of ambient mass spectrometry to guide brain tumor surgery by providing rapid diagnosis, and tumor margin assessment in near-real time.

A number of meningeal neoplastic lesions may radiologically and clinically simulate meningioma. In the present paper, we review meningeal non-meningothelial tumors which may also mimic different histotypes of meningioma at the histological examination. Awareness that these lesions exist may facilitate their recognition and correct diagnosis, which is of fundamental importance for prognosis and an appropriate therapeutic approach. Histological and immunohistochemical clues for the differential diagnosis are discussed., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Object: Radiation-associated meningiomas (RAMs) arise after treatment with radiation to the cranium and are recognized as clinically separate from sporadic meningiomas. Compared with their sporadic counterparts, RAMs are often aggressive or malignant, likely to be multiple, and have a high recurrence rate. However, limited information exists about the clinical, pathological, and cytogenetic features of RAMs in pediatric patients. The authors report the findings in 9 children with meningiomas following therapeutic radiation to the cranium. In addition, they performed a critical review of the English language literature on pediatric RAMs., Methods: Medical files were searched for patients who demonstrated meningiomas after a history of radiation to the brain. Only those patients in whom a meningioma occurred before the age of 18 years were included in this study. Clinical and demographic data along with the MIB-1 labeling index and cytogenetic studies were evaluated., Results: The patients consisted of 5 males and 4 females with a median age of 5 years (range 2-10 years) at radiation therapy. The latency period was a median of 10 years after radiation therapy (range 6-13 years). The MIB-1 labeling index was a median of 6.6% (range 4%-10%). Five patients (55.6%) displayed multiple meningiomas at the first presentation. Histological types included clear cell meningioma in 1 patient, fibroblastic meningioma in 2, chordoid meningioma in 2, meningothelial meningioma in 7 (atypical in 2 cases), xanthomatous meningioma in 1, and chordoid meningioma in 1. Cytogenetic studies showed that the loss of 22q12.2 was the most common abnormality (3 patients), followed by complex cytogenetic abnormalities (2 patients) and rearrangements between chromosomes 1 and 12 (1 patient) and a 1p deletion (1 patient)., Conclusions: In contrast to RAMs occurring in adults, those in pediatric patients show an increased incidence of multiplicity on first presentation and unusual histological variants, some of which are described here for the first time. There was no difference in the MIB-1 labeling index in children with RAMs as compared with that in children with non-RAMs.

Hemangioblastoma (HBL) accounts for up to 2.5% of all intracranial tumors. It may occur as a sporadic entity or as a part of Von Hippel-Lindau syndrome. Patients with Von Hippel-Lindau syndrome are also at an increased risk of developing clear cell renal cell carcinoma (CCRCC). The distinction of HBL from CCRCC metastatic to the central nervous system (CNS) or from other histologic mimics can be challenging at times when based solely on hematoxylin and eosin-stained sections. In the present study we evaluated the potential use of the immunohistochemical evaluation of brachyury protein in the differential diagnosis of these lesions. Archival tissues from 22 HBLs, 16 primary CCRCCs, 8 CCRCCs metastatic to the CNS, and 4 angiomatous and 4 clear cell meningiomas were retrieved from our surgical pathology files and submitted to the immunohistochemical procedures against brachyury. Cases showing nuclear and/or cytoplasmic staining were considered to be positive for brachyury. Positive cytoplasmic staining was evidenced in the stromal cells of 20 of the 22 HBLs. In most cases, >50% of the neoplastic cells were labeled, with strong or moderate intensity of staining. No nuclear or cytoplasmic staining for brachyury was observed in any of the primary renal or metastatic CCRCCs, nor in either of the meningioma types. Thus, brachyury cytoplasmic staining was demonstrated to be highly specific for HBL (specificity, 100%) and represented a sensible (sensitivity, 91%) method, with high positive (100%) and negative (89%) predictive values and high diagnostic accuracy (95%) in the differential diagnosis between HBL and CCRCC metastatic to the CNS or meningioma. On the basis of our findings we propose the use of brachyury as an additional helpful immunohistochemical marker to resolve the differential diagnosis of HBL toward histologic mimics.

Background: Bone involvement is a common finding in many types of lymphoma. Cranial vault involvement is extremely rare, and the majority of patients are found at staging to have concurrent disease in lymph nodes. Thirty-eight cases of primary lymphoma of the cranial vault have been reported to date., Methods: This article presents a rare case of primary cranial vault lymphoma and conducts a systematic review of the current literature. A total of 36 articles comprising 38 cases were included for analysis. The relevant demographic, clinical, and imaging characteristics, as well as the treatment and outcomes of this unique disease presentation were studied., Results: The average patient age was 60 years. There was no significant difference in patient gender. The predominant patient complaint was a subcutaneous scalp mass. Of the patients, 11.7% were immunocompromised. CT scans showed signs of osteolysis in 74% of lesions and hyperostosis in 5%, and the cranial vault was observed as normal in 18% of cases. MRI was performed in 23 cases. There was a wide range of histological subtypes, with a slight predominance of diffuse large B-cell lymphoma. Treatment consisted of surgery alone, surgery followed by radiotherapy, and surgery followed by radiotherapy and chemotherapy. The follow-up periods ranged from 5 months to 6 years, with a median value of 7 months. Sixteen patients were followed up to 12 months; 13 of them were alive at 1 year from diagnosis., Conclusion: Primary cranial vault lymphoma is an extremely rare finding. It should be considered in the differential diagnosis of scalp masses. Although the analysis of outcome of the reported cases is difficult because of the small number of occurrences of this entity and the variability of follow-up, a combination of surgery, radiotherapy, and chemotherapy seems to offer better outcomes.

The phenomenon of tumor-to-tumor metastasis has been reported in the literature for over a century. However, it remains fairly uncommon, with fewer than 100 cases being described during that time. Virtually any benign or malignant tumor can be a recipient, but meningiomas have been implicated as the most common intracranial neoplasm to harbor metastasis. The donor neoplasm is most frequently lung or breast carcinoma, while rare cases of metastasis from other primary tumors have been reported. We report here three examples of such rare metastases. This case series reports the first documented instance involving rectal adenocarcinoma. In addition, we report two cases of metastatic prostate adenocarcinoma to a meningioma; to date of which only three cases have been published. The terms "tumor-to-tumor metastasis" and "collision tumor" are addressed, as are details of the pathology. The limitations of standard radiological imaging techniques, such as standard CT and MR, which cannot reliably identify the presence of metastasis within a meningioma are compared with physiology-based neuroimaging methods, such as perfusion MR and MR spectroscopy, which may be more useful in noninvasively differentiating tumor histology.

Object: With the wider use of CT and MRI, many meningiomas are discovered as incidental findings during diagnostic work-up for unrelated symptoms. The majority shows no or minimal growth. The purpose of this study was to distinguish pathological features of incidentally-found growing meningiomas by comparing incidentally-found with symptomatic meningiomas., Methods: One hundred and thirty two consecutive non-recurrent surgically-treated meningiomas treated between 2005 and 2007 were divided into three categories: 19 incidentally-found growing meningiomas (IG), 50 incidentally-found meningiomas (I), and 63 symptomatic (S) meningiomas. The average follow-up period for the IG meningiomas was 3.7 years. Six out of 19 patients of the IG meningiomas became symptomatic during observation., Results: There is a significant difference of the incidence of WHO grades I, II, and III between all three groups (p=0.035). The incidence of WHO grades II and III in groups IG, I, and S were 26%, 2%, and 10%, respectively. We compare MIB-1 staining index between three groups: an average was 3.8% in IG, 1.3% in I, and 2.4% in S meningiomas., Conclusions: Incidentally-found meningiomas need careful follow-up. One fourth of the meningiomas that showed signs of growing belonged to the atypical or malignant grade.

Background and Purpose: A unique molecular and/or cellular marker for meningiomas, the most common intracranial tumours, has not been identified yet., Material and Methods: We investigated the co-localization fraction of CD133/Ki-67 in meningioma tissue array slide composed of 80 meningioma tissue samples of various histological variants. CD133 - a cell membrane stem cell marker - was previously proved to be associated with the initiation and progression of intracerebral gliomas and medulloblastomas., Results: Immunohistochemical co-localization of CD133/Ki-67 was significantly higher in fibroblastic variant than in meningothelial and transitional subtypes. However, since there were only 3 atypical and 1 malignant meningioma spots in the tumour tissue array slide, it is difficult to draw a firm conclusion regarding the actual co-localization percentage and persistence of CD133/Ki-67 in atypical and malignant meningiomas., Conclusions: Far higher co-staining percentage of CD133/ Ki-67 in fibroblastic meningioma samples compared to meningothelial subtype, a histological meningioma variant, architectonically resembling the non-neoplastic meningeal cells, gave us the impression that CD133 may play a role in the formation and progression of fibroblastic meningioma variants. The persistency and the validity of this finding need to be verified by further histopathological and molecular research in order to clarify the possible role of CD133 in meningiogenesis.

The authors expose the clinical, radiological and histological presentation of three cases of solitary fibrous tumors of the meninges, initially thought to be meningiomas. Actually, these three cases show typical anatomoclinical features. The authors also mention the differential diagnosis, and recall the essential contribution of immunohistochemistry., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Tumor invasion or infiltration of adjacent tissues is the source of clinical challenges in diagnosis as well as prevention and treatment. Among brain tumors, infiltration of the adjacent tissues with diverse pleiotropic mechanisms is frequently encountered in benign meningiomas. We assessed whether a multiparametric analysis of meningiomas based on data from both clinical observations and molecular analyses could provide a consistent and accurate appraisal of invasive and infiltrative phenotypes and help determine the diagnosis of these tumors. Tissue analyses of 37 meningiomas combined enzyme-linked immunosorbent assay (ELISA) and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) assays of two different protein biomarkers (thrombospondin 1 and a phosphorylated form of vimentin) as well as gene expression analyses with oligonucleotide micro-arrays. Up to four different clinical and molecular parameters were then examined for tumor classification. From this study, we were able to cluster 36 out of the 37 tumors into two different subsets corresponding to infiltrative/invasive and non-infiltrative tumors. In addition, meningiomas that invade brain and those that infiltrate the neighboring skull bone exhibited no distinguishable molecular features. Our multi-parameter analysis that combines clinical data, transcriptomic and molecular assays clearly reveals the heterogeneity of meningiomas and distinguishes the intrinsically infiltrative/invasive tumors from the non-infiltrative meningiomas.

Background: Meningiomas are slow-growing tumors. Grading of meningiomas based on histological features has certain limitations in predicting the exact biological behavior, necessitating ancillary techniques., Objective: To study the Ki67 labeling index (Ki67 LI) in various histological subtypes and grades of meningioma and correlate it with various parameters for recurrence., Material and Methods: All intracranial and intraspinal meningiomas diagnosed between 2005 and 2008 were graded according to WHO 2007 criteria. Immunohistochemistry was performed using Ki67 (Dako, USA 1:50) in 300 cases. Statistical analysis was performed. Results : There was female predominance. The age ranged from 2-75 years including 11 children below the age of 18 years. There were 211 Grade I, 78 Grade II and 11 Grade III meningiomas. The mean Ki67 LI increased from Grade I to II and from Grade II to III and these were statistically significant. The Ki67 LI was high for the subtypes of clear cell, chordoid, papillary and rhabdoid but there was no statistical significance between the subtypes. The difference in Ki67 LI between recurrent versus non-recurrent and brain-invasive versus non-invasive meningiomas was statistically significant., Conclusion: High Ki67 LI indicates higher grade of meningioma. The difference in KI67 LI between recurrent and non-recurrent meningiomas was statistically significant.

Malignant ectomesenchymoma is a rare tumor arising from mature ganglion cells with immature myogenous elements, with only 4 pediatric intracranial cases having been previously reported. The authors report a rare case of intracranial malignant ectomesenchymoma originating from the falx cerebri in a 10-year-old boy. The patient presented with a 2-week history of headache, nausea, and blurry vision, with mild lateral gaze diplopia. A CT scan revealed a solitary 7.2 × 3.8-cm dural-based mass that extended along the falx. No metastatic disease was identified, and the lesion was grossly resected without complication. Pathological investigation identified single and small groups of cells in a myxoid background, with polygonal or spindle-shaped cells containing eccentric nuclei and prominent nucleoli. Immunohistochemical staining of some cells was positive for smooth-muscle actin, CD99, and vimentin, whereas other cells (often process forming) were positive for S100 protein, synaptophysin, and neurofilament protein. Staining was negative for CD138, CD45, α-fetoprotein, CK AE1/3, glial fibrillary acidic protein, CK7, CK20, CD31, CD34, myoD, and desmin. Normal immunopositivity was seen for INI-1. The Ki 67 immunostaining had < 25% reactivity. The patient was treated with a sarcoma-based chemotherapy regimen and radiation to the craniospinal axis, and was found to be without recurrence or metastatic disease at 20 months.

Meningiomas are common intracranial tumors, but relatively little is known about the genetic events responsible for their clinical diversity. Although recent genomic studies have provided clues, the genes identified often differ among publications. We used microarray expression profiling to identify genes that are differentially expressed, with at least a 4-fold change, between grade I and grade III meningiomas. We filtered this initial set of potential biomarkers through a second cohort of meningiomas and then verified the remaining genes by quantitative polymerase chain reaction followed by examination using a third microarray expression cohort. Using this approach, we identified 9 overexpressed (TPX2, RRM2, TOP2A, PI3, BIRC5, CDC2, NUSAP1, DLG7, SOX11) and 2 underexpressed (TIMP3, KCNMA1) genes in grade III versus grade I meningiomas. As a further validation step, we analyzed these genes in a fourth cohort and found that patients with grade II meningiomas with high topoisomerase 2-α protein expressions (>5% labeling index) had shorter times to death than patients with low expressions. We believe that this multistep multi-cohort approach provides a robust method for reducing false-positives while generating a list of reproducible candidate genes that are associated with clinically aggressive meningiomas and are suitable for analysis for their potential prognostic value.

Aims: Clear cell meningioma (CCM) is a rare variant of meningioma, which is important to distinguish because of its aggressive behaviour. Sixty-eight cases have been previously described in the literature. In this retrospective study, we report seven cases of CCM operated in our institution between 1994 and 2008., Methods: Seven CCM cases were retrieved from the files of our pathology department. Clinical and radiological data were reviewed. A standard histological study was realized and immunohistochemistry was performed with epithelial membrane antigen (EMA), cytokeratin KL1, progesterone receptors, Ki-67 (MIB-1), S100 protein., Results: Patients' age ranged from 2 to 70 years (median age: 36 years), with a female predominance (5/7 patients). Three patients belonged to the same family, probably affected by neurofibromatosis type 2. CCM occurred in various locations: medullary region (two), sphenoid wing (two), ponto-cerebellar angle (two), tentorium (one). The tumour could be fully resected in three cases. Follow-up ranged from 3 months to 15 years: recurrence occurred in four patients, three of whom eventually died from the disease., Discussion: In our series, the frequency of CCM (0,6% of all meningiomas operated on in our institution) and its histological aspects are almost identical to those observed of the literature. We discuss the predictive value of proliferation index (MIB-1) and the role of patient status and quality of surgical resection in the evolution., Conclusion: Our study supports the fact that MCC course is less favourable than meningioma WHO grade I, even in the absence of anaplastic area, high mitotic activity, or necrosis. In this series, MIB-1 index was of no interest identifying patients with or without recurrence., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Primary diffuse meningeal melanomatosis can clinically mimic a wide variety of other conditions, including lymphoma, leukemia, neurosarcoidosis, metastatic carcinoma, acute disseminated encephalomyelitis, subacute meningitis, viral encephalitis, and idiopathic hypertrophic cranial pachymeningitis. We report on a young patient with primary diffuse meningeal melanomatosis who presented with papilledema, flaccid paraparesis, and cognitive impairment. The importance of imaging of the whole central nervous system, cerebrospinal fluid analysis, and pathohistological examination is emphasized in making the appropriate diagnosis.

The peculiar radiological and pathological findings of four pediatric cases admitted to the University Hospital of Padua between 1990 and 2007 are described. In all cases, the contrast-enhanced head and spine magnetic resonance images revealed thickened and abnormally enhancing subarachnoid spaces particularly at the level of basal cisterns and interhemispheric fissure. Furthermore, small cystic lesions scattered throughout the brain and mainly in the cerebellum were also visible. All patients were missing a well-defined intraparenchymal mass, although during the follow-up a small intramedullary lesion appeared within the cervical spine in two and subsequently in the frontal horn of the left lateral ventricle in one of those. All patients presented an indolent long-term follow-up. Histologically, the tumors were composed by a monotonous population of cells arranged in straight lines or in small lobules. The cells were characterized by round to oval nuclei with finely granular dispersed chromatin, inconspicuous nucleoli with oligodendrocyte-like features. The morphological and immunohistochemical findings suggested in all cases a "glioneuronal commitment" of the tumors. Because of the unique similar clinical and neuroradiological characteristics, we propose this small series of tumors as a new possible distinct pathological and clinical entity.

The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as from the area in which the meningioma had its dural attachment. Immunohistochemical characterization and distribution of neurotrophins, with their receptors, were analyzed. The concrete role played by these neurotrophic factors in general regulation, vascular permeability, algic responsivity and release of locally active substances in the human dura mater is still controversial. Our study revealed a general structural alteration of dural tissue due to the invasivity of meningiomatous lesions, together with an improved expression of brain derived neurotrophic factor (BDNF) in highly proliferating neoplastic cells and an evident production of nerve growth factor (NGF) in inflammatory cells, suggesting that BDNF has a role in supporting the proliferation rate of neoplastic cells, while NGF is involved in the activation of a chronic inflammatory response in neoplastic areas.

Chordoid meningioma, World Health Organization grade II, is an uncommon variant of meningioma with a propensity for aggressive behavior and increased likelihood of recurrence. As such, recognition of this entity is important in cases that show similar morphologic overlap with other chondroid/myxoid neoplasms that can arise within or near the central nervous system. A formal comparison of the immunohistochemical features of chordoid meningioma versus tumors with significant histologic overlap has not been previously reported. In this study, immunohistochemical staining was performed with antibodies against D2-40, S100, pankeratin, epithelial membrane antigen (EMA), brachyury, and glial fibrillary acidic protein (GFAP) in 4 cases of chordoid glioma, 6 skeletal myxoid chondrosarcomas, 10 chordoid meningiomas, 16 extraskeletal myxoid chondrosarcoma, 18 chordomas, 22 low-grade chondrosarcomas, and 27 enchondromas. Staining extent and intensity were evaluated semiquantitatively and mean values for each parameter were calculated. Immunostaining with D2-40 showed positivity in 100% of skeletal myxoid chondrosarcomas, 96% of enchondromas, 95% of low-grade chondrosarcomas, 80% of chordoid meningiomas, and 75% of chordoid gliomas. Staining with S100 demonstrated diffuse, strong positivity in all (100%) chordoid gliomas, skeletal myxoid chondrosarcomas, low-grade chondrosarcomas, and enchondromas, 94% of chordomas, and 81% of extraskeletal myxoid chondrosarcomas, with focal, moderate staining in 40% of chordoid meningiomas. Pankeratin highlighted 100% of chordoid gliomas and chordomas, 38% of extraskeletal myxoid chondrosarcomas, and 20% of chordoid meningiomas. EMA staining was positive in 100% of chordoid gliomas, 94% of chordomas, 90% of chordoid meningiomas, and 25% of extraskeletal myxoid chondrosarcomas. Brachyury was positive only in the chordomas (100%), whereas GFAP was positive only in the chordoid gliomas (100%). EMA was the most effective antibody for differentiating chordoid meningioma from skeletal myxoid chondrosarcoma, low-grade chondrosarcoma, and enchondroma, whereas D2-40 was the most effective antibody for differentiating chordoid meningioma from extraskeletal myxoid chondrosarcoma and chordoma. Our findings demonstrate that in conjunction with clinical and radiographic findings, immunohistochemical evaluation with a panel of D2-40, EMA, brachyury, and GFAP is most useful in distinguishing chordoid meningioma from chordoid glioma, skeletal myxoid chondrosarcoma, extraskeletal myxoid chondrosarcoma, chordoma, low-grade chondrosarcoma, and enchondroma. A lack of strong, diffuse S100 reactivity may also be useful in excluding chordoid meningioma. Among the neoplasms evaluated, brachyury and GFAP proved to be both sensitive and specific markers for chordoma and chordoid glioma, respectively. Of note, this study is the first to characterize the D2-40 immunoprofile in extraskeletal myxoid chondrosarcoma, results that could be of utility in differential diagnostic assessment.

Meningiomas are histologically heterogeneous tumors with at least 15 different subtypes. They can be subdivided into well-differentiated, atypical, and anaplastic or malignant categories. The secretory meningioma is a well-differentiated variant, is relatively rare. Orbital involvement of secretory meningiomas is rarity. We report two cases of secretory meningiomas of orbit and review of current literature.

Ganglioglioma is a tumor occurring in children and young adults and characterized by a superficial cortical location and biphasic histologic differentiation encompassing neuronal and glial elements. Ganglioglioma may arise anywhere throughout the neuraxis, including the optic nerve, brain stem, pineal gland, cerebellum, cerebrum, and spinal cord; however, the majority of glioneuronal neoplasms involve the temporal lobe. Gangliogliomas may show focal leptomeningeal involvement, but predominant leptomeningeal involvement by gangliogliomas is extremely rare; only 2 cases of ganglioglioma extensively involving the leptomeninges have been reported. In this report, we present an unusual case of a ganglioglioma predominantly present within the leptomeninges of a 15-year-old boy with a history of seizures. Furthermore, the cerebral cortex beneath the tumor showed dysplastic changes. We report a very unusual case of ganglioglioma involving predominantly the cerebral leptomeninges and associated with adjacent cerebral cortical dysplasia. Histologic characteristics and diagnostic pitfalls are discussed.