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Peter Clarenbach, Paul Kleihues, Eberhard Metzel and Johannes Dichgans

✓ At the age of 22 years, identical twin brothers simultaneously developed symptoms of intracranial pressure. Radiological investigation revealed cerebellar midline tumors with occlusive hydrocephalus of the third and lateral ventricles. At operation, subependymomas with identical histological features were found in the fourth ventricle in both twins. This is the first report of subependymomas in identical twins. The clinical data suggest that this tumor type is of maldevelopmental origin.

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Alex M. Landolt, Taichiro Shibata and Paul Kleihues

✓ The immunohistological detection of a proliferation-associated nuclear antigen by the monoclonal antibody Ki-67 allows the determination of the growth fraction in human cell populations. In this study, biopsy specimens of 31 pituitary adenomas representing all major endocrine types were examined. All adenomas contained proliferating cells and the percentage of nuclei that were immunoreactive to Ki-67 ranged from 0.1% to 3.7%. Low values (0.1% to 1.0%) were present in 11 endocrine-inactive adenomas and higher values (1.1% to 1.5%) were found in six acromegalic patients. The percentages of Ki-67-positive cells in 12 prolactinomas and two adenomas from patients with Cushing's disease covered the entire range (0.1% to 3.7%). Preoperative bromocriptine treatment of prolactinomas did not influence Ki-67 expression. Invasive adenomas, as determined by preoperative computerized tomography, surgical observation, and histological examination of the sella dura demonstrated significantly higher Ki-67 values (average 1.15%) than noninvasive adenomas (average 0.60%). Determination of the incidence of proliferating cells by Ki-67 immunoreactivity represents a new tool for intraoperative quantitative assessment of tumor growth characteristics and may aid in the planning of adjuvant therapy and estimation of prognosis.

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Peter C. Burger, E. Ralph Heinz, Taichiro Shibata and Paul Kleihues

✓ To provide baseline information for the “local” therapy of the glioblastoma multiforme (GBM), whole-brain histological sections of 15 untreated GBM's were studied to determine the distribution of neoplastic cells. These findings were then compared with the computerized tomography (CT) scans in 11 cases in order to determine the extent to which the peripheral portion of the neoplasm can be estimated by the presence of a low-density area without contrast enhancement. The results of the histological study confirmed the marked heterogeneity of GBM's and disclosed a great variability in the geometry, extent, and character of the peripheral “infiltrating” margin. In spite of the widely held concept that glioblastomas are localized within 2 cm of the contrast-enhanced rim, there were three cases in this two-dimensional study in which this distance was exceeded, and it seems likely that three-dimensional reconstructions would have detected additional cases in which neoplastic cells extended beyond this arbitrary limit. Only three of the 15 GBM's were restricted to the distribution of one internal carotid or one vertebral artery. To the extent that the neoplasms in the present series are representative, this suggests that glioblastomas will be difficult to treat successfully by intra-arterial therapy using existing therapeutic agents. Correlations of histological sections with the CT scans revealed that the vast majority of the neoplastic tissue was contained within the contrast-enhancing and “peritumoral” areas of low density, but that in five cases fingers of neoplasm extended for short distances beyond the outer margin of the latter region. This indicates that the distribution of cells of a GBM cannot be inferred from CT images since the “peritumoral” area of low density can over- or underestimate the extent of the lesion.

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Tim E. Adamson, Otmar D. Wiestler, Paul Kleihues and M. Gazi Yaşargil

✓ Surgical specimens of 104 craniopharyngiomas from 93 patients were reviewed and characterized histopathologically. They were found to have either a classic adamantinous or a squamous papillary structure. The clinical features of each group were then assessed. The frequently solid (50%), always uncalcified squamous papillary tumor type was found in one-third of the adult patients (≥ 20 years) but did not occur in children. It was associated with a good functional postoperative outcome (84.6%). There have been no cases of tumor recurrence in the squamous papillary group. However, in the group with the adamantinous type of craniopharyngioma, the recurrence rate was 13% in adult patients and 9% in children. When compared to the adult adamantinous cases, the incidence of visual deficits was lower in the squamous papillary group (75% vs. 84%) but the incidence of endocrine abnormalities was higher (75% vs. 52%). Thus, the preoperative, operative, and postoperative features of the two types of craniopharyngioma were found to be distinctly different in adults and children.

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Christoph Burkhard, Pier-Luigi Di Patre, Danielle Schüler, Georges Schüler, M. Gazi Yaşargil, Yasuhiro Yonekawa, Urs M. Lütolf, Paul Kleihues and Hiroko Ohgaki

Object. The incidence of pilocytic astrocytomas and the rate of patient survival were analyzed in a population-based study in the canton of Zürich, Switzerland.

Methods. Between 1980 and 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 55 (5.5%) were pilocytic astrocytomas. The incidence rate, adjusted to the World Standard Population, was 4.8 per 1 million per year. The mean age at clinical diagnosis was 19.6 ± 12.7 years, and the male/female ratio was 1.12. The most frequent tumor sites were the cerebellum (40%), followed by supratentorial locations (35%), the optic pathway and hypothalamus (11%), and the brainstem (9%). The mean follow-up period was 12 years. Observed survival rates were 100% at 5 years and 95.8% at 10 years after diagnosis (relative survival rate at 10 years: 96.8%). Seven patients (13%) received postoperative radiotherapy, but this did not significantly affect survival. In all patients the tumors were histologically classified as WHO Grade I, except in two patients who had anaplastic pilocytic astrocytoma (Grade III), one of whom died after 7 years, whereas the other was still alive after 10 years.

Conclusions. This population-based study shows that, because of the benign biological behavior of pilocytic astrocytomas and advances in microneurosurgery, the survival rates for patients with these tumors are excellent, regardless of postoperative radiotherapy.

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S. Clifford Schold Jr., Thomas P. Brent, Eric von Hofe, Henry S. Friedman, Sankar Mitra, Darell D. Bigner, James A. Swenberg and Paul Kleihues

✓ The level of O6-alkylguanine-deoxyribonucleic acid (DNA) alkyltransferase (AT) was determined in 15 human brain-tumor xenografts in athymic mice. This enzyme is a primary intracellular repair mechanism for lesions produced at the O6 position of guanine by a wide range of alkylating agents, including nitrosoureas and procarbazine. Its activity ranged from undetectable in five tumor lines to 2338 fmol/mg protein in N-1941, a human glioblastoma xenograft. The sensitivity of 10 of these xenografts to procarbazine was determined and it was found that four of the five tumor lines with AT levels of more than 100 fmol/mg protein had growth delays after procarbazine treatment of less than 20 days, whereas all five lines with undetectable AT levels had growth delays of over 30 days. The primary cytotoxic DNA adduct produced by procarbazine (namely, O6-methylguanine) was found to be significantly higher in two sensitive lines with low AT levels than in a highly resistant line with a high AT level. These data suggest that the AT levels of individual brain tumors can be used as predictive indicators of their susceptibility to drugs that exert their antineoplastic effect primarily by O6-alkylation of guanine in nuclear DNA.