Satoshi Nakasu

bcl-2 Protein expression in tumors of the central nervous system

Abstractbcl-2 protein (BCL-2) expression was immunohistochemically studied in 140 varied central nervous system tumors. The protein was most frequently expressed in neuronomas and ependymomas, and in normal ependymal cells and Schwann cells. Most pituitary adenomas could be classified into one of two subgroups, diffusely positive or diffusely negative tumors, while BCL-2 localized heterogeneously in normal pituitary glands. Although the protein was not detected in normal astrocytes, it was positive in reactive hypertrophic astrocytes observed in various pathological conditions. Similarly, astrocytic tumor cells often expressed BCL-2. Since lowgrade astrocytomas more often exhibited the protein than malignant gliomas, the degree of BCL-2 expression appeared to be related to the degree of malignancy of the gliomas. On the other hand, 7 out of 17 recurrent gliomas and medulloblastomas showed an increase in the frequency of protein expression compared with specimens from initial treatments. One recurrent astrocytic tumor which demonstrated anaplastic change showed a decrease in the frequency of BCL-2-positive cells. It is concluded that the frequency of BCL-2 expression in CNS tumors is increased when the non-neoplastic counterparts of the tumors exhibit the protein. Although it has been reported that overexpression of BCL-2 protects cells from damage by radiation and/or chemotherapy, we could not find any significant relationship between the degree of BCL-2 expression and the length of survival of patients with glioblastomas or medulloblastomas.

Significance of MIB-1 staining indices in meningiomas: comparison of two counting methods.

The authors evaluated the predictability of MIB-1 immunohistochemistry for growth and recurrences of meningiomas using two different counting methods: 1) in the area of the highest MIB-1 labeling (HL method) and (2) in randomly selected fields (RS method). The MIB-1 staining indices (SIs) determined by the HL method were approximately twice as high as those by the RS method, and the correlation coefficient between them was high (R = 0.86) in 139 meningiomas when transformed logarithmically. The differences in SIs in histologic grades were significant with either method. Tumor doubling time (Td) was calculated in 22 meningiomas from serial radiologic examinations. The RS method yielded a slightly higher correlation coefficient between log Td and log SI than the HL method. When the authors examined the predictability of recurrence in 112 totally removed meningiomas, the RS method distinguished the recurrent group more definitively. Several benign meningiomas with low SIs by the RS method exhibited focal accumulation of MIB-1-positive cells. Although they were assigned high MIB-1 values by the HL method, these meningiomas did not recur, and therefore obscured the prognostic importance of the MIB-1 value with the HL method. Focal accumulation of MIB-1-positive cells in meningiomas is not likely to correlate with their biologic aggressiveness.

Meningioma: proliferating potential and clinicoradiological features.

We examined the proliferative potentials of meningiomas in 120 patients using the MIB-1 antibody against the Ki-67 antigen and compared them with the clinicoradiological features. The Ki-67 staining index (SI) did not relate to the age and sex of the patients or the location of the tumors. Asymptomatic meningiomas showed significantly lower SIs (mean +/- standard deviation [SD], 0.87 +/- 0.56%) than symptomatic meningiomas (mean +/- SD, 1.63 +/- 2.17%). We found no relation between SIs and clinical symptoms and signs in the symptomatic meningiomas. A weak correlation was found between the size of tumors and Ki-67 SIs (r = 0.21; P = 0.024). There were significant differences in SIs between calcified (mean +/- SD, 0.77 +/- 0.41%) and noncalcified tumor (mean +/- SD, 1.75 +/- 2.25%). Diffusely calcified tumors (mean +/- SD, 0.57 +/- 0.34%) showed lower SIs than focally calcified tumors (mean +/- SD, 0.92 +/- 0.41%). Lobulated tumors showed higher SIs (mean +/- SD, 2.85 +/- 3.68%) than round tumors (mean +/- SD, 1.06 +/- 0.67%). Tumors with perifocal edema or unclear borders had higher SIs than did those without such features. Signal intensities on T1-weighted magnetic resonance images had no relation to SIs, whereas low-intensity tumors on T2-weighted images, most of which presented diffuse calcification on computed tomographic scans, showed lower SIs. This study indicates that several clinicoradiological features relate to the proliferative potential of meningiomas and that they may contribute to the management of patients.

Immunohistochemical study for O6-methylguanine-DNA methyltransferase in the non-neoplastic and neoplastic components of gliomas.

Although the expression O6-methylguanine-DNA methyltransferase (MGMT) is an important hallmark for decision of nitrosourea chemotherapy for glioma patients, no immunohistochemical method for analysis of MGMT has been standardized yet. Gliomas usually contain non-neoplastic cells even deep in the tumor. It is not known which of these components expresses MGMT. To clarify this point, we investigated MGMT expression in the non-neoplastic cells in autopsy and surgical specimens by immuno-histochemistry. High grade gliomas were also studied to find a cut-off point for treatment decision. MGMT immunohistochemistry in the normal brain or brain with non-neoplastic disease revealed nuclear staining in some endothelial cells, inflammatory cells, ependymal cells, astrocytes and oligodendroglias. Some cells were double stained with CD68 (macrophages or microglias). The neurons were consistently MGMT-negative. High grade gliomas always contained an MGMT-positive non-neoplastic component. Although the endothelial cells were easily distinguished from the neoplastic cells, other cells were often mistaken for tumor cells. The population of MGMT-positive non-neoplastic cells was usually less than 10%. We set a cut off-point at 10% between the positive and negative groups because the statistical difference in the overall survival was most distinct at this value. In 51 high grade glioma patients, who received both radiotherapy and chemotherapy with nimustine (ACNU), the median overall survival of the MGMT-negative group (23months) was significantly longer than that of the MGMT-positive group (14months) (P<0.009). Multivariate analysis revealed that the negative MGMT expression was a significant prognostic variable next to the degree of surgical removal for the overall survival. In the MGMT-positive group, addition of platinum-based chemotherapy did not improve the survival.

Recurrence and regrowth of benign meningiomas

The World Health Organization (WHO) grading system for meningioma is helpful for predicting aggressive subtypes. However, even benign meningiomas sometimes show relatively rapid growth and may recur after total removal. We attempted to find histopathological features that would be valuable for predicting recurrence or regrowth of WHO grade I meningiomas. We investigated 135 benign meningiomas, of which 120 were totally removed (Simpson’s grade I–III). The median follow-up period was 9.7 years (1–21 years). The recurrence rate in the patients with total removal was 7.5% at 10 years and 9.3% at 20 years. The univariate analysis revealed that MIB-1 index (≥2%), existence of mitosis, absence of calcification, and paucity of fibrosis significantly correlated with recurrence. On the other hand, the histological features of sheet-like growth, prominent nucleoli, and necrosis did not correlate with recurrence, because they were relatively rare in grade I tumors. Multivariate analysis revealed that high MIB-1 index and absence of calcification significantly correlated with recurrence. The patients with recurrent or residual tumors did not always receive adjuvant treatment. Including subtotally treated tumors, the retreatment rate was 9.8% at 10 years and 25.6% at 20 years. MIB-1 index and Simpson’s grade significantly correlated with retreatment in both univariate and multivariate analyses.

Solitary intracranial chondroma of the convexity dura: case report

We present a rare case of chondroma originated from the dura mater of the cerebral convexity in a 16-year-old girl. Radiologic findings are reported with emphasis on computed tomography and magnetic resonance imaging scans, and histogenesis is briefly discussed.

Maturational changes in diffusion anisotropy in the rat corpus callosum: Comparison with quantitative histological evaluation

To determine the main histological components that affect fractional anisotropy (FA) in postnatal development of the rat corpus callosum and compare FA values with histological changes evaluated quantitatively.

Computed tomography of intracranial epidermoid tumours with special reference to atypical features.

SummaryIntracranial intradural epidermoid tumours have been known to show characteristic CT features consisting of non-enhancing lucent lesions with sharply defined margins that are often irregular and scalloped. Since the epidermoid tumours are benign, potentially curable lesions, it should be also noted that they may occasionally show atypical CT features such as dense lesion, definite marginal enhancement following contrast medium injection, or tumour associated with large, heavy calcifications. Four such atypical cases are reported, and the literature is reviewed.

Third ventricular chordoid glioma: case report and review of the literature

BACKGROUND Chordoid glioma of the third ventricle is a rare type of brain tumor that was recently characterized as a novel tumor entity. We present a case and review of the literature. CASE REPORT A 49-year-old woman presented with progressive headache, memory impairment and urinary incontinence. MRI showed a large well-circumscribed tumor in the third ventricle. The tumor was partially removed via a trans-lamina terminalis approach. The histologic findings indicated chordoid glioma. Residual tumor was treated by stereotactic radiosurgery and showed no regrowth at 2-year follow-up. CONCLUSIONS The ideal therapy is total removal of the tumor. However, according to the literature, total removal of the tumor carries a high risk because of its location, and conventional radiation therapy has little effect on the residual tumor. On the other hand, stereotactic radiosurgery appears more promising, and to date, no regrowth has been reported after gamma-knife therapy.

Pituitary adenoma with multiple ciliated cysts: Transitional cell tumor?

The case of a prolactin-secreting pituitary tumor with multiple cyst formation is described. Ultrastructurally, the cyst-lining cells were ciliated and closely resembled those of Rathkes cleft cyst but contained secretory granules, and no basal lamina formation was seen between the adenoma cells and the lining cells. Immunohistochemical study revealed that the adenoma cells consisted of both prolactin-secreting cells and growth hormone-secreting cells. The lining cells were immunoreactive with the antiserum to cytokeratin. No S-100 protein-positive cells were seen. The origin of this tumor is discussed.