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According to current World Health Organization (WHO) criteria, counting mitotic figures (MF), which is equal to the mitotic index (MI), on paraffin sections stained with hematoxylin and eosin (HE) is one of the recognized classification methods for meningiomas. However, it is not always easy to find the area of highest mitotic activity, and there are different perspectives among pathologists with regard to differentiating MF from non-MF, i.e., which are apoptotic figures and which are crushed or distorted cells. Moreover, there is an issue of overgrading in meningiomas with preoperative feeder embolization. Recently, anti-phosphohistone-H3 (PHH3) antibody has been reported as a mitosis-specific marker for meningioma grading. In this study, we attempted PHH3 immunostaining for our meningioma cases and verified not only the sensitivity of PHH3 immunostaining but also that of its usefulness in grading meningiomas. Forty-five initial histologically confirmed meningiomas (37 benign, 7 atypical, and 1 anaplastic) were reviewed according to current WHO criteria based on counting MF on HE-stained slides. PHH3-immunostained MF were counted in the same way, and the MIB-1 labeling index (LI) was calculated for each sample. PHH3-labeled MF were easily identified and permitted rapid recognition of the areas of highest mitotic activity. As a result, significant increase of PHH3 mitotic index (PHH3-MI) in comparison with HE mitotic index (HE-MI) and strong correlations with HE-MI to PHH3-MI as well as PHH3-MI to MIB-1 LI were demonstrated. Furthermore, no significant differences of PHH3-MI between cases with and without feeder embolization were demonstrated. As such, PHH3 may be a sensitive and useful marker for meningioma grading as based on the MF.

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The object of the present study was to determine the histopathological guidelines for accurate diagnosis of cases of acute focal demyelinating disease that simulates brain tumors. The surgical pathology of three such cases is assessed. Histopathological keys to the diagnosis of such cases are as follows. First, a pattern of sheets of atypical gemistocytic astrocytes in the white matter that show well-formed processes and that are adequately distanced from each other argues against a diagnosis of neoplasm. Second, uniform distribution of foamy macrophages aligned along axons, with occasional focal collections surrounding blood vessels and in the absence of any associated coagulative necrosis argues against the presence of a tumor. Third, perivascular chronic inflammatory infiltration, especially a mixture of lymphocytes and macrophages, favors the diagnosis of demyelination plaque. In such cases the lymphocytes will be predominantly T cells. Fourth, pleomorphic astrocytic proliferation with a lack of vascular endothelial proliferation should raise the suspicion that the lesion may not be a brain tumor. These diagnostic keys should be followed when diagnosing cases that are suspected to be demyelination processes rather than brain tumors. The presence of demyelination plaque should then be confirmed by imaging modalities such as staining with myelin-and axon-specific stains.

Autocrine fibroblast growth factor (FGF) signaling mediates an uncontrollable growth of human gliomas. We investigated the intracellular signaling of FGF on cell survival activity. U251MG human glioma cells were infected with adenovirus vectors expressing dominant negative type I FGF receptor (DNFR), constitutive active Ras (RasL61), or dominant negative Ras (RasN17). DNFR reduced glioma cell accumulation with apoptosis and this reduction was alleviated with exogenous epidermal growth factor (EGF), which can activate Ras independent of FGFR but not with bFGF. RasL61 prevented but RasN17-enhanced DNFR-induced apoptosis. Reportedly, cell survival signaling through Akt was constitutively active in U251MG cells and this effect may be dependent on autocrine signaling and dysfunction of PTEN, a tumor suppressor gene limiting phosphatidylinositol 3-kinase (PI3K) activity. DNFR dose-dependently inhibited Akt activity and this inhibition was recovered by RasL61, whereas RasN17 inhibited Akt activity. Wortmannin (a PI3K inhibitor) inhibited Akt activity and mildly promoted apoptosis. RasL61 prevented the down-regulation of Akt activity and apoptosis induced by wortmannin, but RasN17 plus wortmannin strongly inhibited Akt activity and promoted marked apoptosis. Our data suggested that the cell survival activity of human gliomas is largely dependent on cross-talk between Ras and the PI3K-Akt pathway, and this cross-talk could be a potential target for molecular-based therapeutics.

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Hematoma expansion is an important consideration in patients with traumatic brain injury (TBI). No precise methods are available, however, for predicting the expansion of TBI-related hematoma. We aimed to establish a more sensitive predictor for contusional hematoma expansion based on the presence of leakage signs on computed tomography angiography (CTA). Thirty-three patients with pure contusion were included in the analysis (age: 64.1 ± 20.6 years; 24 men and 7 women). We compared Hounsfield unit (HU) values within set regions of interest (diameter, 10 mm) between serial CTA phase and delayed-phase CT images (5 min after CTA phase). Positive leakage signs were defined as >10% increases in HU value. Hematoma expansion was determined using plain CT at 24 h in patients who did not undergo emergent surgery. Glasgow Coma Scale (GCS) scores measured at admission and 24 h after admission were also compared. Leakage signs predicted hematoma expansion with high specificity (100%) and sensitivity (92.8%). Patients with positive leakage signs had significant decreases in GCS scores 24 h after the scan (GCS change: positive group, -0.92 ± 0.59; negative group, 1.14 ± 0.82). Positive leakage signs were clearly associated with surgical hematoma removal. Five patients without hematoma who had positive leakage signs at admission exhibited significant expansion of hematomas 24 h later. Our results indicate that leakage signs had high sensitivity in the prediction of contusional hematoma expansion and were significantly associated with delayed neurological deterioration and the necessity of surgical removal.

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