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Werner Paulus and Jörg C. Tonn

✓ Basement membrane invasion precedes meningeal dissemination and systemic metastasis of glioma cells. In order to investigate the invasive ability of glioblastomas and the functional role of extracellular matrix receptors, the authors performed in vitro invasion assays where the number of cells was determined from freshly resected tumors (primary cultures and fifth passages) and from cell lines (U-138 MG, U-373 MG, and GaMg) that had migrated through a filter coated with a reconstituted basement membrane (Matrigel). The involvement of integrin adhesion molecules was examined by preincubation of glioma cells with blocking antibodies to specific integrin chains. Cells from all of the glioblastomas had migrated through the Matrigel after 4 to 24 hours; the number of invasive cells was highest in the cell lines. Invasion of U-138 MG cells was reduced with antibodies to α7, αv, β1, and β3 integrin chains and markedly increased by anti-α5, while invasion of U-373 MG cells was reduced by antibodies to α3, αv, β1, and β3 and increased by anti-α6. It is concluded that: 1) glioma cells are able to penetrate Matrigel, indicating that the basement membrane is not a resistant barrier for infiltrating cells; and 2) basement membrane invasion is mediated by integrins in a complex manner. Some integrins promote while others inhibit basement membrane invasion. Furthermore, the integrins involved may differ between various glioma cells.

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Joo-Hun David Eum, Astrid Jeibmann, Werner Wiesmann, Werner Paulus and Heinrich Ebel

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.

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Rudolf Fahlbusch, Jürgen Honegger, Werner Paulus, Walter Huk and Michael Buchfelder

Object. The goal of this study was to assess the outcome of surgical management in 168 consecutive patients harboring craniopharyngiomas treated between January 1983 and April 1997.

Methods. In 148 patients undergoing initial (primary) surgery, the pterional approach was most frequently used (39.2%), followed by the transsphenoidal approach (23.6%). For large retrochiasmatic craniopharyngiomas, the bifrontal interhemispheric approach was used increasingly over the pterional approach and led to improved surgical results. Total tumor removal was accomplished in 45.7% of transcranial and 85.7% of transsphenoidal procedures. The main reasons for incomplete removal were attachment to and/or infiltration of the hypothalamus, major calcifications, and attachment to vascular structures. The success rate in total tumor removal was inferior in the cases of tumor recurrence. The operative mortality rate in transcranial surgery was 1.1% in primary cases and 10.5% in cases of tumor recurrence. No patient died in the group that underwent transsphenoidal surgery. The rate of recurrence-free survival after total removal was 86.9% at 5 years and 81.3% at 10 years. In contrast, the 5-year recurrence-free survival rate was only 48.8% after subtotal removal and 41.5% after partial removal. Following primary surgery, the actuarial survival rate was 92.7% at 10 years, with the best results after complete tumor removal. At last follow up, 117 (79%) of 148 patients who underwent primary surgery were independent and without impairment.

Conclusions. Total tumor removal while avoiding hazardous intraoperative manipulation provides favorable early results and a high rate of long-term control in craniopharyngiomas.

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Rudolf Fahlbusch, Jürgen Honegger, Werner Paulus, Walter Huk and Michael Buchfelder

The surgical management of 168 consecutive patients harboring craniopharyngiomas treated between January 1983 and April 1997 is described. In 148 patients undergoing initial (primary) surgery, the pterional approach was most frequently used (39.2%) followed by the transsphenoidal approach (23.6%). For large retrochiasmatic craniopharyngiomas, the bifrontal interhemispheric approach was used increasingly over the pterional approach and led to improved surgical results. Total tumor removal was accomplished in 45.7% of transcranial and 85.7% of transsphenoidal procedures. The main reasons for incomplete removal were attachment and/or infiltration of the hypothalamus, major calcifications, and attachment to vascular structures. The success rate in total tumor removal was inferior in the cases of tumor recurrence. The operative mortality rate in transcranial surgery was 1.1% in primary cases and 10.5% in cases of tumor recurrence. No patient died in the group undergoing transsphenoidal surgery. The rate of recurrence-free survival after total removal was 86.9% at 5 years and 81.3% at 10 years. In contrast, the 5-year recurrence-free survival rate was only 48.8% after subtotal removal and 41.5% after partial removal. Following primary surgery, the actuarial survival rate was 92.7% at 10 years, with the best results after complete tumor removal. At last follow up, 117 (79%) of 148 patients who underwent primary surgery were independent and without impairment.

Total tumor removal while avoiding hazardous intraoperative manipulation provides favorable early results and a high rate of long-term control in craniopharyngiomas.

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Werner Paulus, Johann Romstöck, Manfred Weidenbecher, WalterJ. Huk and Rudolf Fahlbusch

✓ Middle ear adenocarcinoma is a very rare, locally invasive neoplasm assumed to arise from the middle ear mucosa. Although endolymphatic sac tumor (aggressive papillary middle ear tumor) and jugulotympanic paraganglioma may show brain invasion, intracranial extension of histologically confirmed middle ear adenocarcinoma has not been previously reported. The authors describe a 53-year-old man who suffered from otalgia and tinnitus for more than 10 years and from neurological deficits for 1 year due to a large temporal bone tumor that invaded the temporal lobe. A combined neurosurgical and otolaryngological resection was performed. Pathological analysis revealed a low-grade adenocarcinoma of a mixed epithelial—neuroendocrine phenotype, which showed a close histological similarity to, and topographical relationship with, middle ear epithelium. The authors conclude that middle ear adenocarcinoma belongs to the spectrum of extracranial tumors that have possible local extension to the brain.

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Martin Hasselblatt, Abolghassem Sepehrnia, Marcus von Falkenhausen and Werner Paulus

✓✓ Intracranial occurrence of follicular dendritic cell (FDC) sarcoma, a rare tumor derived from dendritic cells of the lymphoid follicle, has not yet been described. Therefore, the case of a 53-year-old man presenting with an intracranial mass invading the clivus is reported. The diagnosis of FDC sarcoma was confirmed by immunohistochemical staining for dendritic cell markers, that is, CD21, CD23, and CD35. Due to some similarities with meningioma, intracranial FDC sarcoma might be an underdiagnosed disease.

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Benjamin Brokinkel, Johanna Sicking, Dorothee Cäcilia Spille, Katharina Hess, Werner Paulus and Walter Stummer

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Martin Hasselblatt, David Maintz, Thomas Goll, Uwe Wildförster, Christoph Schul and Werner Paulus

Object

The value of routine histopathological examination of intervertebral disc tissue has been questioned, but sufficient numbers of studies have yet to be conducted to provide a definitive sense of its importance. The aim of this study was to investigate the nature and frequency of unexpected histopathological findings in intervertebral disc surgery.

Methods

The authors conducted a retrospective examination of consecutive surgical specimens obtained in patients with benign indication for discectomy at four neurosurgical centers.

Surgical specimens obtained during 2102 operations (2177 intervertebral discs) in 2017 patients were evaluated. In addition to one case of cavernous malformation, two specimens (obtained in 0.1% of patients) revealed unexpected pathological diagnoses of malignancy (metastasized prostate carcinoma and diffuse large B-cell lymphoma).

Conclusions

The results of this retrospective study suggest that routine histopathological examination of specimens obtained during intervertebral disc procedures is both justified and cost effective.

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Werner Paulus, Inge Baur, Daniel M. Oberer, Xandra O. Breakefield and Steven A. Reeves

✓ Because accurate regulation of toxin gene expression is critical for safe and effective gene therapy applications, the authors have examined the regulation of diphtheria toxin A (DTA) fragment expression in human glioma cell lines using two transcriptional control systems derived from Escherichia coli: the tetracycline (Tet) system and the lactose (Lac) system. The Tet system includes a tetracycline-controlled transactivator (tTA), a tTA-responsive minimum human cytomegalovirus (hCMV) promoter controlling the expression of the DTA gene, and tetracycline as an allosteric inhibitor. The Lac system includes the lac repressor (lacR), a lacR-regulated Rous sarcoma virus—long terminal repeat (RSV-LTR) promoter controlling the expression of the DTA gene, and isopropyl-thio-β-d-galactoside (IPTG) as an allosteric inducer. Expression plasmids encoding either tTA or lacR were transfected into U-87MG and U-343MG glioma cells along with the responsive DTA plasmid. Cell killing was monitored by the ability of the toxin to abolish protein synthesis and was quantitated using a luciferase reporter gene. In the Tet system, tumor cell killing could be regulated by tetracycline up to 120-fold. In contrast, only a twofold IPTG-dependent regulation was obtained using the Lac system because of an incomplete repression of DTA expression in the uninduced state. Replacement of the RSV-LTR promoter with the heavy metal—inducible mouse metallothionein-1 promoter in the lacR-responsive unit, as well as the generation of a clonal glioma cell line expressing lacR, did not significantly enhance regulation of DTA in the Lac system. In conclusion, this study demonstrates that the Tet system is of potential use in gene therapy applications in which regulated expression of a therapeutic gene is an important issue.

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Astrid Jeibmann, Brigitte Wrede, Ove Peters, Johannes E. Wolff, Werner Paulus and Martin Hasselblatt

Object

Malignant progression of choroid plexus papillomas has been occasionally reported, but this issue has not yet been systematically addressed.

Methods

Frequency and extent of malignant progression were examined in a retrospective series of 124 primary choroid plexus papillomas using uniform histological criteria.

Results

After gross-total resection and a mean follow-up period of 59 months, 12 recurrences necessitating neuro-surgical intervention had occurred in the 103 cases of choroid plexus papilloma (World Health Organization [WHO] Grade I) and 21 cases of atypical choroid plexus papilloma (WHO Grade II). The proportion of recurring tumors was higher in cases of atypical choroid plexus papilloma than in cases of choroid plexus papilloma (six [29%] of 21 compared with six [6%] of 103, respectively; p < 0.05). In the majority (10 of 12) of the recurrences, there was a close correspondence between the primary tumor and the recurrence with respect to features identified on routine histological examination as well as Ki 67 (MIB-1) proliferation indices (median value 4% for both primary and recurrent tumors; range 0–15% for primary compared with 0–12% for recurrent tumors). However, two patients experienced a transition from a choroid plexus papilloma (WHO Grade I) and an atypical choroid plexus papilloma (WHO Grade II) to choroid plexus carcinomas (WHO Grade III).

Conclusions

Recurrent tumor growth after gross-total resection is rare in choroid plexus papillomas, but malignant progression to choroid plexus carcinoma does occur in a small percentage of tumors.