Brain invasion in meningiomas: does surgical sampling impact specimen characteristics and histology?

Brain invasion (BI) is a new criterion for atypia in meningiomas and therefore potentially impacts adjuvant treatment. However, it remains unclear whether surgical practice and specimen characteristics influence histopathological analyses and the accuracy of detecting BI. Tumor location, specimen characteristics, and rates of BI were compared in meningioma samples obtained from 2938 surgeries in different neurosurgical departments but diagnosed in a single neuropathological institute. Non-skull base tumor location was associated with CNS tissue on the microscopic slides (OR 1.45; p < .001), increasing specimen weight (OR 1.01; p < .001), and remaining tissue not subjected to neuropathological analyses (OR 2.18; p < .001) but not with BI (OR 1.29; p = .199). Specimen weight, rates of residual tissue not subjected to histopathological analyses, of BI and of brain tissue, on the microscopic slides differed among the neurosurgical centers (p < .001, each). Frequency of BI was increased in one department (OR 2.07; p = .002) and tended to be lower in another (OR .61; p = .088). The same centers displayed the highest and lowest rates of brain tissue in the specimen, respectively (p < .001). Moreover, the correlation of BI with the neurosurgical center was not confirmed when only analyzing specimen with evidence of brain tissue in microscopic analyses (p = .223). Detection of BI was not correlated with the intraoperative use of CUSA in subgroup analyses. Rates of brain invasion in neuropathological analyses are not associated with tumor location but differ among some neurosurgical centers. Evidence raises that surgical nuances impact specimen characteristics and therefore the accuracy of the detection of BI.

Histopathological analysis of intracerebral hemorrhage: implications for clinical management.

BACKGROUND: The clinical impact of routine neuropathologic examination of samples from patients with intracerebral hemorrhage (ICH) is unclear. METHODS: Therefore, we evaluated a consecutive series of 378 surgical specimens from patients with ICH concerning demographic data, localization of hemorrhage, preoperative clinical diagnosis and neuropathological diagnosis. RESULTS: Histological examination revealed the putative origin of ICH in 143 cases (37.8%). Vascular pathologies were detected in 127 patients (33.6%), while tumors were identified in 9 patients (2.4%), infarction in 6 patients (1.6%) and abscess in 1 patient (0.3%). Preoperatively, tumor was considered in 65 patients (17.2%), while vascular malformations were supposed in 94 patients (24.9%), infarction in 18 cases (4.8%) and abscess in 3 cases (0.8%). In 198 patients (52.4%) no specific assumption was made. CONCLUSIONS: Comparing preoperative assumptions and histological diagnoses, tumor, vascular malformations and infarctions were clinically overestimated, while arteriolosclerosis and amyloid angiopathy were underestimated. In conclusion, we found that histological findings potentially affecting clinical management and prognosis were obtained in 37.8% of cases. Our data suggest that histopathological examination of intracerebral hemorrhage provides important information for patient management and should be routinely performed.

Multiple myeloma manifesting as an intraventricular brain tumor.

Primary intracerebral manifestation of multiple myeloma is rare and usually arises from the meninges or brain parenchyma. The authors present a case of multiple myeloma primarily manifesting within the lateral ventricle. A 67-year-old man was admitted with headache accompanied by slowly progressing right hemiparesis. Magnetic resonance imaging showed a large homogeneous contrast-enhancing intraventricular midline mass and hydrocephalus. The tumor was completely resected, and histopathological examination revealed plasmacytoma. After postoperative radio- and chemotherapy, vertebral osteolysis was detected as a secondary manifestation of multiple myeloma.

Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis.

The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults.

The effect of mitomycin C in reducing epidural fibrosis after lumbar laminectomy in rats.

OBJECT: Extensive epidural fibrosis after lumbar spine surgery might be an important underlying cause of failed-back syndrome. Based on previously obtained data, the effect of mitomycin C (MMC) in a concentration of 0.1 mg/ml on spinal epidural fibrosis in a rat laminectomy model was investigated in a large series. METHODS: Eighty adult Wistar rats underwent lumbar laminectomy. In 40 rats, MMC in a concentration of 0.1 mg/ml was locally applied to the laminectomy sites. No similar treatment was performed in the other 40 rats. At intervals from one to 12 weeks after laminectomy, both macroscopic and histological evaluations were performed. For radiological investigation, 10 rats underwent magnetic resonance (MR) imaging at 6 weeks postoperatively. Furthermore, the concentration of MMC in cerebrospinal fluid (CSF) and serum was determined 12 hours postoperatively in seven rats. Due to ease of absorption, high levels of MMC were rapidly detectable in serum, whereas the values obtained from the CSF were markedly lower. In the majority of MMC-treated laminectomy sites, epidural scarring was significantly reduced and dural adhesions were absent, in comparison with control sites (p < 0.001), as confirmed by MR images. Accordingly, the macroscopic dissection of epidural fibrous tissue to reexpose the dura mater was performed more easily and without severe bleeding in these rats. The healing of skin and the lumbar fascia was not affected, and dural leakage was not observed. All control sites showed dense epidural fibrosis with marked dural adherence. CONCLUSIONS: In this experimental model, it was shown that locally applied MMC in a concentration of 0.1 mg/ml effectively reduces epidural fibrosis and dural adherence without side effects in rats that underwent lumbar laminectomy.

Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats.

OBJECT: Extensive epidural fibrosis after lumbar surgery may be the underlying cause in most cases of failed-back surgery syndrome. Various materials have been used to prevent epidural fibrosis, but only moderate success has been shown. Mitomycin C, an alkylosing antibiotic substance isolated from Streptomyces caespitosus, potentially supresses fibroblast proliferation after surgery. In this study, the authors investigated the effect of mitomycin C by local application on spinal epidural fibrosis in a rat laminectomy model. METHODS: Five Wistar rats underwent laminectomy at cervical, thoracic, and lumbar levels. Based on data obtained from ophthalmological studies, mitomycin C was applied to the laminectomy sites in various concentrations (0.01, 0.05, and 0.1 mg/ml). One laminectomy site in each rat was left untreated and thus served as a control. Evoked potentials were measured pre- and postoperatively, and all rats underwent clinical evaluation. Mobility status and evidence of neurological deficit were recorded. Twelve weeks later, the rats were killed, and the spinal column, including surrounding muscle tissue, was removed en bloc, decalcified, and fixed in formaldehyde. Epidural fibrosis was evaluated histologically. In all mitomycin C-treated laminectomy sites, epidural scarring was significantly reduced compared with control sites. Remarkably, dural adhesions were absent in laminectomy defects treated with mitomycin C concentrations of 0.05 and 0.1 mg/ml. Moderate to marked epidural fibrosis with adhesion to the dura mater was noted at sites receiving 0.01 mg/ml of mitomycin C. All control sites showed dense epidural fibrosis with marked dura adherence. CONCLUSIONS: In this experimental model, mitomycin C applied locally at a concentration of 0.1 mg/ml effectively reduced epidural fibrosis, completely avoided dural adherence, and induced no side effects.

Various surgical treatments of chronic subdural hematoma and outcome in 172 patients: is membranectomy necessary?

BACKGROUND: The initial surgical management of chronic subdural hematoma (CSDH) is still controversial, and a standard therapy does not exist. Because of the advanced age and multiple medical problems of the patients, surgical therapy is frequently associated with complications. METHODS: A retrospective study was performed on 172 patients with CSDH, comparing the efficacy of three different primary surgical methods: drainage of hematoma through two different burr-holes without membranectomy (Group A, n = 38); enlarged craniectomy with a size of about 30 mm craniotomy with partial membranectomy and drainage (Group B, n = 121); and extended craniotomy with partial membranectomy and drainage (Group C, n = 13). RESULTS: Independent of surgical method, the general outcome of the patients was good. The rate of reoperation in the group of burr-hole drainage was 16%, slightly lower than in partial membranectomy with enlarged craniectomy or extended craniotomy with 18% and 23%, respectively. In patients with coagulopathy, the rate of reoperation was 41% (16/43), significantly higher than the rate in noncoagulopathic patients 12% (15/129). CONCLUSIONS: In this study, an extended surgical approach with partial membranectomy has no advantages regarding the rate of reoperation and the outcome. As initial treatment, burr-hole drainage with irrigation of the hematoma cavity and closed-system drainage is recommended. Extended craniotomy with membranectomy is now reserved for instances of acute rebleeding with solid hematoma.

Expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 in primary and recurrent WHO grade III meningiomas.

AIMS: WHO grade III meningiomas are malignant neoplasms for which new and more targeted treatment strategies are urgently needed. Although clinical trials investigating anti-angiogenic vascular endothelial growth factor (VEGF) targeted therapies are currently recruiting, knowledge about the expression of VEGF and VEGF receptors remains to be determined. METHODS: We investigated the expression of VEGF and its receptors VEGFR1 and VEGFR2 in 32 WHO grade III meningioma samples by immunohistochemistry. Furthermore, we performed in-situ hybridisation for VEGF. RESULTS: We found low VEGF expression in tumor and endothelial cells. Highest VEGF expression levels were seen in peri-necrotic tumor cells potentially suffering from hypoxia. VEGFR1 and 2 were virtually absent on tumor cells, although endothelial cells displayed significantly higher levels reaching stronger expression for VEGFR2 than VEGFR1. CONCLUSIONS: Our findings showing constant expression levels of VEGFR2 in endothelial cells serve as a first indication that the use of small tyrosine kinase inhibitors such as Sunitinib directly targeting the VEGF-receptors might be worth testing, also in the clinical context in cases of therapy-refractory meningiomas. Further investigations are needed to study the response to drugs targeting the VEGF pathway in relation to the expression profile of VEGF and its receptors in high grade meningiomas.