A current review of spinal meningiomas: epidemiology, clinical presentation and management.

PURPOSE: To provide an up-to-date review of the epidemiology, histopathology, molecular biology, and etiology of spinal meningiomas, as well as discuss the clinical presentation, clinical evaluation, and most recent treatment recommendations for these lesions. METHODS: PubMed and Google Scholar search was performed for studies related to meningiomas of the spine. The terms "meningioma," "spinal meningioma," "spine meningioma," "meningioma of the spine," "benign spinal tumors," and "benign spine tumors," were used to identify relevant studies. All studies, including primary data papers, meta-analyses, systematic reviews, general reviews, case reports, and clinical trials were considered for review. RESULTS: Eighty-four studies were identified in the review. There were 22 studies discussing adverse postoperative outcomes, 21 studies discussing tumor genetics, 19 studies discussing epidemiology and current literature, 9 studies discussing radiation modalities and impact on subsequent tumor development, 5 studies on characteristic imaging findings, 5 studies discussing hormone use/receptor status on tumor development, 2 discussing operative techniques and 1 discussing tumor identification. CONCLUSION: Investigations into spinal meningiomas generally lag behind that of intracranial meningiomas. Recent advancements in the molecular profiling of spinal meningiomas has expanded our understanding of these tumors, increasing our appreciation for their heterogeneity. Continued investigation into the defining characteristics of different spinal meningiomas will aid in treatment planning and prognostication.

Pharmacokinetic analysis of [68Ga]Ga-DOTA-TOC PET in meningiomas for assessment of in vivo somatostatin receptor subtype 2.

PURPOSE: DOTA-D-Phe1-Tyr3-octreotide with gallium-68 ([68Ga]Ga-DOTA-TOC) is one of the PET tracers that forms the basis for peptide receptor radionuclide therapy based on somatostatin receptor subtype 2 (SSTR2) expression in meningiomas. Yet, the quantitative relationship between [68Ga]Ga-DOTA-TOC accumulation and SSTR2 is unknown. We conducted a correlative analysis of a range of [68Ga]Ga-DOTA-TOC PET metric(s) as imaging surrogate(s) of the receptor binding in meningiomas by correlating the PET results with SSTR2 expression from surgical specimens. We additionally investigated possible influences of secondary biological factors such as vascularization, inflammation and proliferation. METHODS: Fifteen patients with MRI-presumed or recurrent meningiomas underwent a 60-min dynamic [68Ga]Ga-DOTA-TOC PET/CT before surgery. The PET data comprised maximum and mean standardized uptake values (SUVmax, SUVmean) with and without normalization to reference regions, and quantitative measurements derived from kinetic modelling using a reversible two-tissue compartment model with the fractional blood volume (VB). Expressions of SSTR2 and proliferation (Ki-67, phosphohistone-H3, proliferating cell nuclear antigen) were determined by immunohistochemistry and/or quantitative polymerase chain reaction (qPCR), while biomarkers of vascularization (vascular endothelial growth factor A (VEGFA), endothelial marker CD34) and inflammation (cytokine interleukin-18, microglia/macrophage-specific marker CD68) by qPCR. RESULTS: Histopathology revealed 12 World Health Organization (WHO) grade I and three WHO grade II meningiomas showing no link to SSTR2. The majority of [68Ga]Ga-DOTA-TOC PET metrics showed significant associations with SSTR2 protein, while all PET metrics were positively correlated with SSTR2 mRNA with the best results for mean tumour-to-blood ratio (TBRmean) (r = 0.757, P = 0.001) and SUVmean (r = 0.714, P = 0.003). Significant positive correlations were also found between [68Ga]Ga-DOTA-TOC PET metrics, and VEGFA and VB. SSTR2 mRNA was moderately correlated with VEGFA (r = 0.539, P = 0.038). Neither [68Ga]Ga-DOTA-TOC PET metrics nor SSTR2 were correlated with proliferation or inflammation. CONCLUSION: [68Ga]Ga-DOTA-TOC accumulation in meningiomas is associated with SSTR2 binding and vascularization with TBRmean being the best PET metric for assessing SSTR2.

Quantitative assessment and clinical relevance of VEGFRs-positive tumor cells in refractory brain tumors.

Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)1 and 2 signaling is a potent activator of tumor angiogenesis. Although the expressions of VEGFR1 and VEGFR2 were initially thought to be limited to the endothelial cells, it is now known that both the receptors are expressed in tumor cells. This is the first study wherein VEGFRs-positive tumor cells are quantitatively evaluated for brain tumors with upregulated VEGF/VEGFR signaling. The percentage of VEGFRs-positive tumor cells was quantitatively evaluated in various brain tumors (10 glioblastomas, 22 neurofibromatosis type 2 [NF2]-related schwannomas, 21 sporadic schwannomas, 27 chordomas, 36 meningiomas, 29 hemangioblastomas, 11 hemangiopericytoma, and 13 ependymomas) using immunohistochemistry. VEGF-A expression was also analyzed using quantitative real-time polymerase chain reaction. Double immunofluorescence staining using anti-PDGFR-ß and anti-CD34 antibody, microvessel density, and vessel diameter were analyzed to evaluate the vascular characteristics. Chordomas demonstrated an extremely higher percentage of VEGFR1 and VEGFR2-positive tumor cells than other tumors. In contrast, meningiomas and hemangiopericytomas showed few VEGFRs-positive tumor cells. The percentage of positive tumor cells in chordomas, hemangioblastomas, and NF2 schwannomas was associated with clinical courses, such as shorter progression free survival, and growth speed. Glioblastomas and NF2 schwannomas showed larger tumor vessels without pericyte coverage. The present study is the first to quantitatively analyze VEGFR1- and VEGFR2- positive tumor cells in various types of refractory brain tumors. This novel parameter significantly correlated with the progressive clinical courses.

Assessment of expression of epidermal growth factor receptor and p53 in meningiomas.

BACKGROUND: Meningiomas represent about 30% of primary adult central nervous system tumors. Though slow growing, they recur, causing significant morbidity and mortality. OBJECTIVE: The objective of the following study is to grade meningiomas according to World Health Organization (WHO) 2007 criteria and to correlate the grade with degree of expression of epidermal growth factor receptor (EGFR) and p53. MATERIALS AND METHODS: Meningiomas diagnosed in the year 2010 in the Department of Pathology of our institute, were included in the study. Clinical and radiological findings were noted from medical records. The histopathology slides were reviewed and the tumors were graded according to WHO 2007 criteria. Tissue microarrays (TMA) were prepared and immunohistochemical analysis with epithelial membrane antigen, Vimentin, Ki67, EGFR and p53 was performed on the TMA slides. RESULTS: A total of 79 meningiomas diagnosed during the study period included 30 male and 49 female patients with an age range of 10-75 years. There was a female preponderance with M:F ratio of 1:1.63. EGFR was found to be higher in grade I (82.93%) compared with grade II (35.71%) and grade III tumors (20%) with an overall positivity of 60.81%. Mean p53 indices were higher in grade III (50%) compared with grade II (39.29%) and grade I tumors (38.46%) with an overall positivity of 39.44%. Ki67 labeling index (LI) was significantly high in grade III (16.4%) compared with grade II (6.46%) and grade I tumors (3.13%). CONCLUSION: EGFR expression and Ki67 LI correlated with grade of meningioma P < 0.0001 and P < 0.0001 respectively which were statistically significant whereas p53 expression did not correlate (P - 0.90).

Comparison of occupational exposure assessment methods in a case-control study of lead, genetic susceptibility and risk of adult brain tumours.

OBJECTIVES: There is great interest in evaluating gene-environment interactions with chemical exposures, but exposure assessment poses a unique challenge in case-control studies. Expert assessment of detailed work history data is usually considered the best approach, but it is a laborious and time-consuming process. We set out to determine if a less intensive method of exposure assessment (a job exposure matrix (JEM)) would produce similar results to a previous analysis that found evidence of effect modification of the association between expert-assessed lead exposure and risk of brain tumours by a single nucleotide polymorphism in the ALAD gene (rs1800435). METHODS: We used data from a study of 355 patients with glioma, 151 patients with meningioma and 505 controls. Logistic regression models were used to examine associations between brain tumour risk and lead exposure and effect modification by genotype. We evaluated Cohen's κ, sensitivity and specificity for the JEM compared to the expert-assessed exposure metrics. RESULTS: Although effect estimates were imprecise and driven by a small number of cases, we found evidence of effect modification between lead exposure and ALAD genotype when using expert- but not JEM-derived lead exposure estimates. κ Values indicated only modest agreement (<0.5) for the exposure metrics, with the JEM indicating high specificity (∼0.9) but poor sensitivity (∼0.5). Disagreement between the two methods was generally due to having additional information in the detailed work history. CONCLUSION: These results provide preliminary evidence suggesting that high quality exposure data are likely to improve the ability to detect genetic effect modification.