Histopathological observations on vestibular schwannomas after Gamma Knife radiosurgery: the Marseille experience.

BACKGROUND AND PURPOSE: Radiosurgery has become a successful treatment modality in the management of vestibular schwannomas (VS) during the past four decades. Although the number of treated cases has been increasing continuously we know relatively little about the pathological effect of high dose irradiation on VS following radiosurgery. The purpose of this study was to analyze histopathological changes in VS after Leksell Gamma Knife (LGK) radiosurgery. METHODS: Out of a series of 1350 VS cases treated with LGK surgery 22 patients underwent craniotomy for tumor removal in 6-92 Months interval after radiosurgery. Surgical pathology material was available in 17 cases. Routine histological and immunohistochemical investigations were performed on the tIssue samples. Histopathological findings were compared with clinical and radiological follow-up data. RESULTS: Coagulation necrosis in the central part of the schwannomas surrounded with a transitional zone containing loosened tIssue structure of shrunken tumor cells covered with an outer capsule of vigorous neoplastic cells was the basic histopathological lesion. Granulation tIssue proliferation with inflammatory cell infiltration, different extent of hemorrhages and scar tIssue development was usually present. Endothelial destruction or wall damage of vascular channels was a common finding. Analyzing the follow-up data it turned out that 7 patients out of the 22 were operated on because of radiological progression only without clinical deterioration and 4 of them was removed during the latency period after radiosurgery. CONCLUSION: Results of the present histopathological study suggest that radiosurgery works with double effect on VS: it seems to destroy directly tumor cells (with necrosis or inducing apoptosis), and causes vascular damages as well. The loss of central contrast enhancement on CT and MR images following radiosurgery might be consequence of necrosis and vascular impairment. From clinical-pathological point of view we think that patients should not undergo craniotomy just because of radiological progression of the tumor without clinical deterioration, mainly in the latency period. This requires consultation and common decision-making between the radiosurgical and the microsurgical team.

[Radiosurgery of the brain at the beginning of the 21st century: gamma knife with C-table]. / Sugár agysebészet a XXI. Század hajnalán: a gamma-kés C-modell automata pozícionáló robot rendszerrel.

The goal of stereotactic radiosurgery by definition is "the delivery of a single, high dose of radiation allowing the precise and complete destruction of chosen target structures containing healthy and/or pathological cells, without significant concomitant or late radiation damage to adjacent tissues". This effect is obtained by the precise focusing of multiple low energy radiation beams crossing at the target. Three different techniques can be used for radiosurgery: linear accelerator (LINAC) based radiosurgery, Bragg-peak (proton) therapy and Gamma Knife radiosurgery. Leksell Gamma Knife (LGK) is a dedicated neurosurgical device for brain surgery to destroy predetermined intracranial targets through the intact skull. It operates via the radiobiological effect of stereotactically directed, highly focused ionizing gamma-beams of 201 cobalt-60 sources. The LGK offers the best precision of target during irradiation. The mechanical accuracy is about 0.3 mm, which makes it particularly suitable for highly sophisticated neurosurgical interventions. Radiosurgery was originally developed to treat functional neurological disorders, but soon after its introduction cerebral arteriovenous malformations, and brain tumors became the main targets for the technique. Since the first LGK installation at the Sophiahemmet Hospital, Stockholm, Sweden in 1967, over 150,000 patients have already been treated in more than 150 units worldwide. The accumulated clinical experience with the LGK has established this method as the "golden standard" of radiosurgery. In December 1999, a new development, the LGK Model-C was installed at the Centre Gamma Knife, Université Libre de Bruxelles, Hôpital Académique Erasme, Brussels, Belgium. This was followed by completion of two similar units in Krefeld, Germany, and at the Presbyterian University Hospital, Pittsburgh, Pennsylvania, U.S.A. The major innovation in the design of the LGK Model-C is the robotic Automatic Positioning System, which allows computer-controlled automatic and sequential positioning of multiple shots during treatment. Thus all steps of the procedure are performed through an unbroken digital chain, from stereotactic image acquisition to the control of the irradiation sequence. This represents a significant achievement which increases the accuracy and practicality of the treatment. The technical details of the method are described, and the main treatment indications are reviewed.

Surgical experience with frontolateral keyhole craniotomy through a superciliary skin incision.

OBJECTIVE: The purpose of this study was to evaluate the results of 173 frontolateral keyhole minicraniotomies performed on 155 patients with aneurysms of the anterior or posterior cerebral circulation and for supratentorial tumors. METHODS: The frontolateral keyhole craniotomy is a modification of the generally used pterional approach. Of the 155 patients studied, 102 harbored saccular arterial aneurysms in the vessels of the anterior or posterior cerebral circulation, and 53 had various tumors in the frontal base, suprasellar, or parasellar region. The operations were carried out through an approximately 2.5- x 3-cm frontolateral miniaturized craniotomy after a skin incision just above the eyebrow. RESULTS: Despite the small size of the craniotomy, the exploration allows enough room for intracranial manipulation with maximal protection of the brain and other intracranial structures. The presented series of patients did not have any craniotomy-related complications. CONCLUSION: In our experience, the frontolateral keyhole craniotomy, together with the advent of the modern neuroanesthesia, cerebrospinal fluid drainage, and microsurgical techniques, is a safe approach for an experienced neurosurgeon to use in the treatment of supratentorial aneurysms or tumors of the anterior fossa and sellar regions.

Gamma surgery for intracranial metastases from renal cell carcinoma.

OBJECT: The goal of this study was to evaluate the effectiveness and limitations of gamma surgery (GS) in the treatment of renal cell carcinoma that has metastasized to the brain. METHODS: The authors performed a retrospective analysis of a consecutive series of 21 patients with 37 metastatic brain deposits from renal cell carcinoma who were treated with GS at the University of Virginia from 1990 to 1999. Clinical data were available in all patients. No patient died of progression of intracranial disease or deteriorated neurologically following GS. Eight patients clinically improved. Follow-up imaging studies were available for 23 tumors in 12 patients. Nine patients did not undergo follow-up imaging. One patient lived 17 months and succumbed to systemic disease: no brain imaging was performed in this case. Another patient refused further imaging and lived 7 months. Seven patients lived up to 4 months after the procedure; however, their physicians did not require these patients to undergo follow-up imaging examinations because of their general conditions-all had systemic progression of disease. Of the 23 tumors that were observed posttreatment, one remained unchanged in volume, 16 decreased in volume, and six disappeared. No tumor progressed at any time, and there were no radiation-induced changes on follow-up imaging an average of 21 months after GS (range 3-63 months). CONCLUSIONS: Gamma surgery provides an alternative to surgical resection of metastatic brain deposits from renal cell carcinoma. Neurological side effects were seen in only one case; freedom from progression of disease was achieved in all cases.

[The gamma-knife in stereotaxic surgery. A new era in brain surgery]. / A gamma-kés stereotaxiás sugársebészetröl. Uj korszak az agysebészetben.

The gamma knife is a dedicated neurosurgical equipment for brain surgery to treat predetermined intracranial normal or pathological targets through the intact skull without damaging the surrounding normal brain tissue. The operating method is called radiosurgery and it works with the biological effect of stereotactically directed, highly focused ionizing beams of 201 independent cobalt-60 sources. The treatment is a single day procedure with obvious advantages over the invasive conventional craniotomy-related surgery. It has the benefits of increased biological efficacy of the irradiation along with decreased hospital stay and side effects. The device and radiosurgery was originally developed to treat functional neurological diseases, but very soon arteriovenous malformations and tumours became the main objects for the method, and a new dimension opened in the treatment of brain pathologies with difficult access. The first gamma knife was installed in Stockholm, Sweden in 1968. Since then 85 units have been set up, and more than 70,000 patients were treated with the device worldwide. The simple management technique and high mechanical and beam accuracy made the gamma knife a reliable and effective tool for its intended purpose over 30 years now. This review summarizes the history of the device, the basic radiation physics and biology related to stereotactic radiosurgery, the description of the unit and the possibilities and limits of the treatment modality.

The potential role of myofibroblasts in the obliteration of arteriovenous malformations after radiosurgery.

OBJECTIVES: To examine the structural changes in arteriovenous malformations (AVMs) after stereotactic radiosurgery and to identify the cytoskeletal antigen phenotype of the proliferating cells to gain information about the possible mechanism of obliteration. METHODS: We conducted immunohistochemical and electromicroscopic investigations of surgical material that was removed from seven patients. The patients were harboring cerebral AVMs that had been previously treated with gamma knife irradiation, and they experienced subsequent bleeding 10 to 52 months after treatment. RESULTS: Light microscopy revealed spindle-shaped cell proliferation in the connective tissue stroma and in the subendothelial region of the vessels. The ultrastructural and immunohistochemical characteristics of these spindle cells were identical to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Whereas in nonirradiated specimens of AVMs, similar cells expressed vimentin and desmin positivity, in irradiated cases, alpha-smooth muscle actin activity was also observed. CONCLUSION: In view of the contractile activity of myofibroblasts, the proliferation generated by irradiation and the transformation of the resting cells into an activated form could be relevant to the shrinking process and eventual occlusion of AVMs after radiosurgery.

Treatment of cystic craniopharyngiomas with yttrium-90 colloid solution.

The authors analyzed long-term follow-up data to assess the value of intracavitary irradiation with stereotactically implanted beta-emitting radioisotope (90)Y-silicate colloid for the treatment of craniopharyngiomas. Fifty-seven craniopharyngiomas in 42 patients were selected for retrospective analysis. The yttrium-90 was implanted intracavitally, using computerized tomography-guided and three-dimensional stereotactic treatment planning. The cumulative dose aimed at the inner surface of the cyst wall was 300 Gy. An average of 75% shrinkage of the initial cyst volume was observed. In 18 cases the reduction was more than 91%, and the cyst disappeared totally in 11 cases. A 50% decrease in cyst volume was usually apparent between the 2nd and 4th months. A 70% decrease in cyst volume was seen by the 5th and 6th months and an 80% reduction by the 7th and 8th months. Cysts that were unchanged remained so throughout the observation period. The time course of volume reduction could be expressed mathematically by the formula of 0.73 X e(-0.62 X T) + 0.27, where "e" is the basic number of natural logarithm and "T" is the time expressed in months. Mean survival duration after intracavitary irradiation was 9.4 years. The shrinkage of the cyst was a consequence of fibrosis of the wall, as seen on histopathological examination. The neuroophthalmological prognosis was favorable only when the optic disc was normal or nearly normal at the time of the treatment. In the presence of preexisting optic atrophy, visual deterioration proved to be irreversible. The long-term results support the view that intracavitary (90)Y-irradiation is a noninvasive and very effective method of treatment for craniopharyngioma cysts. Because of the 1.1 mm half-life decay of beta irradiation, it cannot influence the solid part of the tumor; therefore, the best result can be expected in solitary cysts.

Could craniopharyngiomas produce pituitary hormones?

The authors have studied the endocrinological characteristics of 13 craniopharyngioma biopsy specimens in paraffin embedded histological sections with immunohistochemical methods for pituitary hormones (GH, PRL, ACTH, TSH, FSH and LH). Scattered cell groups with mild to moderate positivity for at least one hormone were found in all but one case. This finding supplies further evidence to the hypothesis which suggests the Rathke's pouch origin of craniopharyngiomas. Beside the hypothalamic-hypophyseal lesion it might explain the endocrinological disturbances accompanying the patients suffering from these tumours.

Pathological characteristics of surgically removed craniopharyngiomas: analysis of 131 cases.

Pathological specimens of 131 surgically removed craniopharyngiomas were obtained from the registry of the National Institute of Neurosurgery, Budapest between 1977 and 1991. The cases were reviewed statistically with reference to their gross and microscopic features and clinical characteristics. Macroscopically, 34% of the tumours were cystic, 23% solid and 43% mixed. Histologically, 38% of the cases belonged to the adamantinous group, 26% were squamous epithelial type, 15% were combined, that is expressing the characteristics of both. In 21% of the cases the surgically removed samples did not contain enough material for correct histopathologic classification. There was no recurrence in the group with the squamous epithelial type tumours, while 59% of the adamantinous, and 36% of the combined craniopharyngiomas recurred. The 5-year survival proportion was 73% at the squamous epithelial, 60% in the adamantinous, and 55% at the combined histological types.

Third ventricle germinoma after total removal of intrasellar teratoma. Case report.

A unique case is presented of a third ventricle germinoma developing 3 years after total removal of an intrasellar teratoma. The third ventricle germinoma was not considered to be a recurrence or dissemination of the mature intrasellar teratoma but to have been transformed from multicenter germ cells present in the midline of the brain with different temporal development. The relevant literature is reviewed and the problems of management of patients with germ-cell tumors are discussed.

Characterization of human gliomas by a monoclonal antibody both on tissue culture and paraffin-embedded sections.

A monoclonal antibody designated OITIC3-11 was produced against GFAP positive human glioblastoma multiforme tumour cells. The specificity of the monoclonal antibody was tested on different types of human brain tumours and on normal adult brain both on tissue cultures and paraffin-embedded sections. The OITIC3-11 monoclonal antibody reacted with 16 of 18 malignant and 1 of 6 benign gliomas but did not react with meningioma, pituitary adenoma, metastatic brain tumours and normal adult brain tissue.

Abscess formation in Rathke's cleft cyst.

Two patients are discussed who presented at our Institute with endocrine dysfunction and sellar enlargement. CT scans revealed intra and suprasellar expanding lesions with ring enhancement. The postoperative histological examination showed remnants of Rathke's cleft cyst together with signs of inflammation. CT and MRI pictures, and possible mechanisms of abscess formation in this region are discussed.

Secretory component of cystic craniopharyngiomas: a mucino-histochemical and electron-microscopic study.

Ten cases with cystic craniopharyngioma were investigated. Histologically, eight of them belonged to the adamantinomatous group and two were squamous epithelial type. Histochemical investigation revealed mucin secretion in microcysts, and electron microscopy demonstrated zymogen granules in the epithelial cells. When the protein content of the cyst fluid was analyzed by polyacrylamide-gel electrophoresis, the electrophoretic pattern and immunological properties were found to be similar to the normal human serum control. The results of the morphological study suggest that cystic craniopharyngiomas have a secretory component in addition to the classical histological structures.

[Persistent trigeminal artery associated with pituitary adenoma]. / Hypophysis adenomával társult persistáló intrasellaris arteria trigemini primitiva.

The authors report of a case with a pituitary macroadenoma which was associated with a persistent trigeminal artery. The tumour was removed by transsphenoidal microsurgical approach to the sella turcica. To recognise the developmental anomaly is very important to avoid complications during operation.

Pathological changes in cystic craniopharyngiomas following intracavital 90yttrium treatment.

Radiosurgery, using 90Y injected directly into the cavity of cystic craniopharyngiomas produces remarkable reduction of tumour size and diminishes cyst fluid production. The authors have studied the histology of biopsy and autopsy material obtained from seven patients presented with cystic craniopharyngiomas. Histological examination was carried out before and after 90Y silicate implantation. As an effect of 90Y irradiation, histology of samples taken from the cyst wall revealed that the lining epithelial cell layer became destroyed and the cyst wall shrunk. Large amount of collagen fibres with focal hyaline degeneration was present. Proliferation of intimal cells and subendothelial connective tissue narrowing small vessel lumina also occurred. Considering that fibrotic tissue is more susceptible to shrink, the fibrosis induced by irradiation together with destruction of the squamous epithelium and vascular changes, might explain the reduction of the cyst volume and diminished fluid secretion after 90Y treatment.

Pathological confirmation of foetal cystic fibrosis following prenatal diagnosis.

Here we report on the results of histopathological analysis of several organs of 5 foetuses and 2 newborn infants with cystic fibrosis. They were examined with HE, PAS, AB, HID and "Stains-all" techniques on paraffin sections. We concluded that there were significant differences in the epithelial mucin composition of several organs of the effected foetuses compared to 6 controls as early as the 17th week of gestation. An increase in the amount of neutral and acidic mucins was observed in the acini of the pancreas, bronchi and the mucosa of the gastrointestinal tract accompanied with a well defined decrease of sialic acid rich components of pharyngeal submucosal glands.

Transplantation of cultured embryonic spinal cord grafts into the hemisected spinal cord of adult rabbits.

Spinal cord fragments from 20-day-old rabbit embryos cultivated for 1 week were transplanted into the hemisected and intact spinal cord of adult rabbits. The morphological changes at the site of intervention were investigated by light and electron microscopy 3, 12, and 29 weeks following implantation. In 80% of the animals the procedure was successful. The implants grew in volume, the cells matured, and many new neural processes with myelinization and synapse formation appeared. The histological findings indicate the survival, maturation, and integration of transplanted cultured embryonic spinal cord tissue in the lesioned adult spinal cord.

[Intracystic instillation of yttrium 90 silicate colloid in cystic craniopharyngioma]. / Cystás craniopharyngeomák intracavitalis ittrium-90 szilikát kolloid kezelése.

The authors evaluate the intracavital treatment with 90 Yttrium silicate colloid given in 31 occasion in 26 patients of cystic craniopharyngioma. The method has been applied since 1975 in the National Institute of Neurosurgery Budapest, using practically the same method as described by Backlund et al. (1972). Although the intracavital treatment was only one among several applied forms of treatment (resection, aspiration, shunting etc.) the effectiveness of the internal irradiation is obvious. The main effect is shrinkage of the cyst. At the 26 patients there was an average of more than 70% volume decrease of the cysts. In 5 cases the cysts totally disappeared and only on two occasions the volume has remained unchanged. Neuroophtalmological data: Preoperatively visual field defects or an impairment of visual activity have been observed in 24 out of the 26 patients studied. After the 90-Yttrium treatment the ophtalmological state of the patients improved 4, worsened in 2 cases. There was no change in 18 cases. The neuroophtalmological prognosis was good only when a relatively intact optic disc was seen; when the disc was atrophic the visual deterioration proved to be irreversible. Pathologically, the fibrotic tissue is responsible for the shrinkage of the cyst.