✓ 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.
Tim E. Adamson, Otmar D. Wiestler, Paul Kleihues and M. Gazi Yaşargil
A 10-year study with special reference to von Hippel-Lindau syndrome
Hartmut P. H. Neumann, Hans R. Eggert, Klaus Weigel, Hartmut Friedburg, Otmar D. Wiestler and Peter Schollmeyer
✓ The findings of a 10-year study (1976 to 1986) conducted in southwest Germany on hemangioblastomas (HBL's) of the central nervous system (CNS) are presented. During that period, 47 HBL's were diagnosed and surgically removed in 44 patients, with a good postoperative survival rate and prognosis. The majority (83%) of these tumors were located in the cerebellum. By thorough clinical examination of the patients and careful evaluation of their family background, it was found that 23% of the HBL patients were afflicted with von Hippel-Lindau syndrome. In addition to the CNS tumors, 14 neoplastic or similar lesions were detected in other tissues. These included angiomatosis of the retinae, pheochromocytomas, pancreatic cysts, renal cysts, and renal carcinoma. The diagnosis of von Hippel-Lindau syndrome was thus established in seven families. The authors suggest the need for a screening program for patients with HBL of the CNS which is designed to confirm or exclude ocular or visceral lesions associated with von Hippel-Lindau syndrome.
M. Gazi Yaşargil, Klaus von Ammon, Andreas von Deimling, Anton Valavanis, Werner Wichmann and Otmar D. Wiestler
✓ The central neurocytoma has recently been added to the differential diagnosis of intraventricular tumors. Histopathologically, this tumor is characterized by a uniform neoplastic cell population with features of neuronal differentiation. Central neurocytomas occur in young adults, develop in the area of the foramen of Monro, and are usually associated with the septum pellucidum. Initial reports appeared to indicate that these tumors are benign lesions with a favorable postoperative prognosis. The authors present clinical and neuropathological findings in a series of eight patients with central neurocytoma. An anterior transcallosal microneurosurgical approach yielded good outcomes. Postoperative radiation therapy was restricted to two patients with a malignant variant of central neurocytoma and one patient with a recurrent tumor. Observations of anaplastic variants of this neoplasm in two cases and local tumor recurrences in three indicate that the biological behavior and postoperative prognosis of central neurocytoma may not always be as favorable as previously assumed.
Josef Zentner, Helmut K. Wolf, Christof Helmstaedter, Thomas Grunwald, Ales F. Aliashkevich, Otmar D. Wiestler, Christian E. Elger and Johannes Schramm
Object. The goal of this study was to define the incidence and clinical significance of amygdala sclerosis (AS) in patients with temporal lobe epilepsy (TLE).
Methods. Surgical specimens of the lateral amygdaloid nucleus and the hippocampus excised from 71 patients who were treated for medically intractable TLE were quantitatively evaluated using a computer-assisted image-analysis system and compared with 10 normal autopsy specimens. Densities of neurons and reactive astrocytes in the patients with TLE were correlated with clinical, neuropsychological, and depth-electroencephalography data. The neuron counts of the lateral amygdaloid nucleus did not correlate with various presumed etiological factors of TLE including hereditary seizures, birth complications, febrile convulsions, traumatic brain injury, infections, seizure semiology, and epileptological outcome. However, patient age at surgery was significantly higher (mean difference 10 years) when AS was present, as compared with patients without AS (p < 0.01). Seizure origin, as determined by using amygdalohippocampal depth electrodes, did not correlate with the presence or absence of AS. Neuropsychologically, there was a significant correlation between the neuronal densities of the lateral amygdaloid nucleus and both preoperative visual recognition and postoperative deterioration of short-term verbal memory performance (p < 0.05).
Conclusions. Except for the relatively long history of epilepsy, the presence of AS is not associated with specific clinical or electrocorticographic features of mesial TLE. However, patients without AS are particularly at risk for deterioration of short-term verbal memory following amygdalohippocampectomy.
Armin P. Stangl, Ruth Wellenreuther, Doris Lenartz, Jürgen A. Kraus, Anil G. Menon, Johannes Schramm, Otmar D. Wiestler and Andreas von Deimling
✓ A significant number of patients with meningiomas develop multiple tumors without anatomical bridges. To understand the mechanism by which multiple meningiomas arise, the authors analyzed DNA from 39 multiple meningiomas in 12 patients to locate alterations in the neurofibromatosis type 2 (NF2) gene. This gene has been shown to be inactivated in meningiomas. No patient in our series had a family history of meningiomas or NF2. All tumors were investigated by single-strand conformation polymorphism analysis of the entire coding region of the NF2 gene and by direct DNA sequencing of altered fragments. The DNA from meningiomas in 10 patients carried NF2 gene mutations. In six of the 10 patients with NF2 mutations, all tumors in the respective individual exhibited the identical DNA alteration in the NF2 gene, thus indicating clonal origin. All four patients with more than two lesions had clonal meningiomas and four patients with two meningiomas each carried different mutations in their tumors. Analysis of constitutional DNA revealed a wild-type NF2 sequence in all 12 patients, thus excluding a forme fruste of NF2 in these cases. Our data demonstrate that the majority of multiple meningiomas with NF2 gene mutations are of somatic and clonal origin. Spread of tumor cells via the cerebrospinal fluid is the most likely mechanism to account for the development of these multiple meningiomas.
Andreas von Deimling, David N. Louis, Klaus von Ammon, Iver Petersen, Tomas Hoell, Richard Y. Chung, Robert L. Martuza, David A. Schoenfeld, M. Gazi Yaşargil, Otmar D. Wiestler and Bernd R. Seizinger
✓ Although the loss of tumor suppressor genes and the activation of oncogenes have been established as two of the fundamental mechanisms of tumorigenesis in human cancer, little is known about the possible interactions between these two mechanisms. Loss of genetic material on chromosome 10 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequently reported genetic abnormalities in glioblastoma multiforme. In order to examine a possible correlation between these two genetic aberrations, the authors studied 106 gliomas (58 glioblastomas, 14 anaplastic astrocytomas, five astrocytomas, nine pilocytic astrocytomas, seven mixed gliomas, six oligodendrogliomas, two ependymomas, one subependymoma, one subependymal giant-cell astrocytoma, and three gangliogliomas) with Southern blot analysis for loss of heterozygosity on both arms of chromosome 10 and for amplification of the EGFR gene. Both the loss of genetic material on chromosome 10 and EGFR gene amplification were restricted to the glioblastomas. Of the 58 glioblastoma patients, 72% showed loss of chromosome 10 and 38% showed EGFR gene amplification. The remaining 28% had neither loss of chromosome 10 nor EGFR gene amplification. Without exception, the glioblastomas that exhibited EGFR gene amplification had also lost genetic material on chromosome 10 (p < 0.001). This invariable association suggests a relationship between the two genetic events. Moreover, the presence of 15 cases of glioblastoma with loss of chromosome 10 but without EGFR gene amplification may further imply that the loss of a tumor suppressor gene (or genes) on chromosome 10 precedes EGFR gene amplification in glioblastoma tumorigenesis.