The 2016 Edition of the WHO Classification of Primary Brain Tumors: Applicable to Assess Individual Risk of Recurrence in Atypical Meningioma? A Single-Center Experience.

BACKGROUND AND STUDY AIMS/OBJECT: Despite the relevance of molecular criteria for brain tumor diagnosis and prognosis, meningioma grading is still solely based on histologic features. Atypical meningiomas (AMs; WHO grade II) display a great histologic heterogeneity and individual courses of disease can differ significantly. This study aimed to identify clinically aggressive AMs that are prone to early recurrence after gross total resection (GTR) by assessing a specific histologic score. PATIENTS AND METHODS: A retrospective analysis of 28 consecutive patients (17 females and 11 males; mean age of 62 years [range: 35-88 years]) treated in our institution between January 2006 and December 2015 was performed. Basic demographic and clinical characteristics were assessed. A scoring scale was designed to address the histologic diversity by summing up the individual histologic features in every tumor sample. According to that, points were awarded as follows: major AM defining criterion (3 points) and minor criterion (1 point). RESULTS: The subclassification based on our specific histologic score revealed no significant difference in frequency of one (46.4%) or two (42.9%) AM defining features; three criteria were less frequently seen (10.7%). Mean follow-up was 61.89 ± 9.03 months. Local recurrence occurred in 35.7% after a mean time of 37.4 ± 22.6 months after primary surgery. Age > 60 years was significantly associated with a shorter progression-free survival (PFS). There was a trend toward shorter PFS with increasing scores, tantamount with the presence of several AM defining histologic criteria in one sample. No tumor relapse was seen when diagnosis was based only on minor criteria. CONCLUSION: AMs display a histologic diversity. There is a trend toward shorter PFS with increasing numbers of AM defining histologic features. The inclusion of this score in the decision algorithm regarding further treatment for patients >60 years after GTR might be helpful and should be evaluated in further studies.

Activation of multiple angiogenic signaling pathways in hemangiopericytoma.

Hemangiopericytoma (HPC) is a highly vascularized mesenchymal tumor. Local recurrence and distant metastasis are common features of HPC. Considering the remarkable hyper-vasculature phenotype of HPC, we assumed that dysregulated angiogenic signaling pathways were involved in HPC. The key components of angiogenic signaling pathways including VEGF-VEGF-R2, EphrinB2-EphB4 and DLL4-Notch were examined by real-time RT-PCR, Western blotting and immunostaining in 17 surgical specimens of HPC patients and in 6 controls. A significant upregulation of VEGF and VEGF-R2 associated with elevated levels of p-Akt and proliferating cell nuclear antigen (PCNA) was detected in HPC. Moreover, a dramatic increase in the mRNA and protein expression of EphB4 and its downstream factor p-Erk1/2 was found in HPC. A massive activation of core-components of DLL4-Notch signaling was detected in HPC. Double-immunofluorescent staining confirmed the expression of these upregulated key factors in the endothelial cells of tumor vessels. The present study identified the activation of multiple and crucial angiogenic signaling pathways, which could function individually and/or synergistically to stimulate angiogenesis in HPC and eventually contribute to tumor growth and progression. Our findings emphasize the importance to target multiple angiogenic signaling pathways when an anti-angiogenic therapy is considered for this highly vascularized tumor.

High noon back pain- severe pseudoradicular pain as a lead symptom of superficial siderosis: a case report.

A superficial siderosis of the central nervous system following a traumatic cervical nerve root avulsion usually leads to gait difficulties and hearing loss, whereas back pain is described only rarely. Here we report on the first case with circadian occurrence of severe back pain as the only symptom of a superficial siderosis. We present a case with the most severe pseudoradicular lumbosacral pain occurring daily at noon for the past 5 weeks. The 48-year-old male white patient did not complain of pain in the morning. A traumatic root avulsion 26 years earlier led to a brachial plexus palsy and Horner's syndrome in this patient. Superficial hemosiderosis in cranial MRI and examination of the cerebrospinal fluid revealing massive red blood cells as well as xanthochromia and elevated protein levels (742 mg/l) led to the diagnosis of a superficial siderosis. A pseudomeningocele caused by a cervical nerve root avulsion is described as a rare reason for superficial siderosis. Surgery on a pseudomeningocele, diagnosed by MRI, led to an immediate disappearance of complaints in our case. Regular neurological investigation and possibly repeated lumbar puncture to exclude superficial siderosis should be considered in cases with severe back pain and a history of traumatic root avulsion. Modern susceptibility weighted MR imaging (SWI) techniques, sensible to the detection of superficial hemosiderosis, might be helpful in the making of a diagnosis.

Expression of aquaporin 5 and the AQP5 polymorphism A(-1364)C in association with peritumoral brain edema in meningioma patients.

Aquaporins (AQP) are a growing family of water-channel proteins, numbering 13 to date. Recent studies have reported AQP1 and AQP4 to be involved in the development and resorption of brain edemas of different origin. Other AQPs have also been detected in brain tissue, but their impact on brain edema remains to be shown. To evaluate a possible role of AQP5 in brain edema, we investigated the association of AQP5 expression and the functional AQP5 promoter polymorphism A(-1364)C with occurrence and intensity of peritumoral edema in meningioma patients. Peritumoral edema was classified in three degrees based on preoperative imaging in 89 meningioma patients treated at the University Hospital Essen between 2003 and 2006. AQP5 expression was assessed immunohistochemically in tumor tissue obtained during neurosurgical tumor resection. Genotypes of the A(-1364)C polymorphism were determined using the "slowdown" polymerase chain reaction. Higher levels of AQP5 expression were significantly correlated with the AQP5-1364 AA genotype (P = 0.02). AQP5 expression was positively correlated with edema (P = 0.04). AQP5 genotypes were not significantly associated with the occurrence, but with the intensity of peritumoral brain edema (P = 0.04). In our cohort, 40 % of patients with grade I, 66.7 % with grade II, and 76.5 % with grade III edema possessed at least one A allele. Development and intensity of peritumoral edema in meningiomas are associated with AQP5 expression. The intensity of edema correlates with the AQP5 A(-1364)C genotype. This suggests AQP5 as an interesting new candidate involved in peritumoral brain edema in meningioma patients.