[Comparative characteristics of genetic aberrations in glioblastomas in children and adults].

Glioblastomas in children and adults are a heterogeneous group of tumors that can be divided into at least three different subgroups: pediatric glioblastomas, IDH1-mutant glioblastomas in adults (the most favorable prognostic subtype), and IDH1-wild type glioblastomas in adults. According to the frequency of detected cytogenetic aberrations (amplification of the MYC/MYCN, EGFR and PDGRFA oncogenes, homozygous deletion of the CDKN2A gene, and deletion of the PTEN gene), pediatric glioblastomas bear analogy to the subgroup of IDH1-mutant glioblastomas in adults.

[Stereotactic radiotherapy and radiosurgery in treatment of patients with deep-seated pilocytic astrocytomas].

Pilocytic astrocytoma (PA) is a low-grade glial tumor (WHO grade I) with predominant occurrence in pediatric patients. According to many authors, stereotactic radiosurgery (SRS) and radiotherapy (SRT) promote long-term remission or retardation of tumor progression in patients with in inoperable lesions after incomplete resection or recurrence. Therefore it is essential to determine the role of SRS and SRT in complex management of patients with deep-seated PA. Since April 2005 till May 2010 101 patient with intracranial PA was treated in department for radiation therapy of Burdenko Neurosurgical Institute. The series consisted of 70 pediatric patients (below 17 years inclusively) and 31 adults, of them--51 male and 50 female patients. Mean age was 15.1 years (9.8 years in children and 28.7 in adults). In 90 patients (89.2%) tumors were previously histologically verified (tumor resection in 83 cases and biopsy in 7). In 11 (10.8%) patients diagnosis of PA was based on clinical and neurovisualization data. In most cases SRT (66 (66.3%) patients) was preformed, the rest 35 (34.7%) patients were treated by SRS. Median follow-up from the onset of disease reached 52 months (2-228 months). Catamnestic data were available in 88 (87%) patients. By the end of catamnestic follow-up (December 2010) 87 (98.8%) patients treated by SRS and SRT were alive. Median follow-up from the start of radiation treatment was 22.7 months (6-60 months). Progression of tumor was observed in 20 patients (22.7%), in 18 of them due to cyst growth. 18 patients were reoperated. In 12 operated patients histological examination and its comparative analysis were performed. We found that alterations in the tumor tissue, accompanied by regression of solid component and progression of cystic portion, represent reactive-degenerative changes in the tumor as a consequence of radiation-induced pathomorphism. SRS and STR are effective techniques for treatment of patients with primary and recurrent PA despite regardless of localization of the tumor. There procedures should be performed shortly after non-radical resection. Control of tumor growth by the present time (median follow-up is 22.7 months) reaches 98%. "Progression" of the tumor due to enlargement of cystic portion shortly after SRT and SRS represents reactive-degenerative alterations in the tumor tissue and should not be evaluated as true recurrence; without neurological deterioration these cases do not require special treatment.

[Influence of molecular-genetic factors on prognosis in patients with oligodendroglial tumors].

Previous studies demonstrated that patients with oligodendroglial tumors (OT) have longer overall and recurrence free survival than patients with other glial tumors of the same grade. Recent investigations showed high influence of genetic alterations on patients' outcome: overall and recurrence free survival increased in the case of presence 1p19q deletion and decreased in the presence of 9p or 10q deletion and/or EGFR amplification. In the series of 241 cases (107 male, 134 female patients, median age -- 38 years, (16-73)) we analyzed the impact of histology, tumor grade and genetic alterations on time to tumor progression (TTP). All patients underwent surgical resection of tumor or biopsy from 2000 to 2005. 70 patterns (oligodendroglioma (O) -- 13 cases, oligoastrocytoma (OA) -- 13, anaplastic oligodendroglioma (AO) -- 30, anaplastic oligoastrocytoma (AOA) -- 14) were assessed by fluorescent in situ hybridization. Median follow up was 24 months. The type of tumor (pure or mixed) didn't influence survival. TTP of patients with grade II and grade III tumors was 37.7 and 48.2 months, respectively (p = 0.035). Deletion 1p19q was noted in 34 (49%) cases. In pure O codeletion 1p19q was detected more frequently (in O -- 75%, in AO -- 56%) than in mixed tumors (in OA -- 31%, in AOA -- 35%). Deletions 9p, 10q and EGFR amplification were noted in 5, 6 and 4 cases, respectively. None of the tumors with 1pl9q deletion had other genetic alterations. Thus, we generated three prognostic groups: A -- deletion 1p19q; B -- balanced chromosomal profile; C -- deletion 9p. Median TTP in groups A, B and C was 46.6, 25.3 and 6.4 months, respectively (p < 0.001). The percentage of OT with 1p19q codeletion was lower than in previous studies. Pure O more frequently had 1p19q deletion than mixed tumors. Genetic alterations predict outcome stronger than histological criteria.

[Histobiological features of posterior cranial fossa meningiomas and their impact on follow-up].

Total removal of posterior cranial fossa meningiomas often leads to complications due to localization, direction and nature of tumor growth. Radical excision as well as histological grade are the principal factors determining recurrence of disease in follow-up period. The paper evaluates the role of ki67 in progression of posterior cranial fossa meningiomas. We performed 189 immunohistochemical studies and katamnestic analysis of patients operated in Burdenko Neurosurgical Institute (Moscow). We showed that level of expression of ki67 correlates with histological grade of posterior fossa meningiomas. We established that recurrence-free survival depends on ki67. This allows prediction of prognosis. Low expression of ki67 corresponds longer recurrence-free survival. If ki67 expression is over 4% recurrence within 2 years after surgery is observed significantly more frequently. Multifactor statistical analysis confirmed prognostic value of ki67 especially in females and patients below 50 because terms of recurrences in these populations are significantly smaller. Obtained data prove versatility of ki67 in neurooncology which should enable its wider application in neurosurgical clinics.

[Chromosome 17 abnormalities in medulloblastomas and their prognostic value].

The cytogenetic profile of chromosome 17 was studied in 180 medlloblastomas by the interphasic FISH technique, which revealed the high incidence of this aberration and its association with the poor clinical course of the disease. The interphasic cytogenetic analysis of chromosome 17 abnormalities in medulloblastoma biopsy specimens may be recommended for its inclusion into a complex of laboratory diagnostic methods used in the examination of these tumors.

[Meningiomas: anatomical pathology and molecular biology].

In the past 5-10 years, there has been a considerable progress the understanding of the biology of meningioma. The most important advances have been made by comprehensive studies of the pathogenesis of meningioma in molecular genetics. Several target genes could be identified for mutation or inactivation. Additional chromosomal regions that are usually subject to deletion or amplification and point to the presence of tumor suppressor genes or proto-oncogenes were found. The revised and updated 2000 WHO Classification is a major innovation in the histopathology of meningiomas. The new classification system more precisely and objectively determines the grade of meningioma, which allows one to more logically make a prognosis of the recurrence and aggressive behavior of the tumor. The present overview places particular emphasis on recent advances in its molecular biology. It summarizes the most important aspects of the classification of meningiomas, which makes it possible to include the results of biological observations into the respective context, and also considers the mechanisms of angiogenesis and edema development and the role of hormonal receptors in meningiomas.

[Cytogenetic aberrations in histologically benign infiltratively growing sphenoid wing meningiomas].

Meningiomas of the sphenoid wing (SW) frequently show an invasive pattern of growth and cause destruction of the adjacent structures. As a result, the rate of recurrent SW meningiomas is as high as 30%. Cytogenetic investigations showed no aberrations specific to invasively growing meningiomas. During this study, the authors evaluated 10 invasive and 5 non-invasive SW meningiomas via comparative genome hybridization (CGH) (matrix CGH), by using the gene chips of GenoSensor Array micromatrixes. The mean number of aberrations in the tumor cells was much greater in case of invasive meningiomas (67.4 versus 40.5 in case of non-invasive SW meningiomas. Furthermore, in invasive SW meningiomas, there were frequently losses in loci 1p, 6q, and 14q and gains in loci 15q and 10, which had been predetermined as molecular markers of stepwise progression of meningioma. Thus, the presence of a complex cytogenetic profile and progression-associated chromosome aberrations in benign SW meningiomas is linked with the increase of their invasive potential. Due to the fact that there are no well-defined adjuvant therapy regimens for recurring meningiomas at present, the revealed genomic aberrations may become potential targets for searching for drugs and a therapeutic intervention in future.

[Results of surgical treatment in patients with neurocytomas of the brain].

Central neurocytoma (CN) is a rare brain neoplasm which is characterized by certain clinical, radiological, and morphological characteristics. This tumor was first described in 1982 by J. Hassoun et al. who found neurosecretory granules and microtubules while microscopically studying 2 patients with oligodendrogliomas of lateral ventricles and concluded that these neoplasms were of neuronal origin. Materials and methods. In 1992 to 2004, a total of 84 patients diagnosed as having CN were treated at the Academician N. N. Burdenko Research Institute of Neurosurgery, Russian Academy of Medical Sciences. In most cases, the tumor showed a clinical picture as elevated intracranial pressure that was detected in 80 (more than 90%) cases. In this series, all neurocytomas were located in the ventricles, mainly in the pellucid septal region; tumor infiltration of the lateral ventricular ependyma and medullary substance invasion into the region of the thalamus and corpus callosum. Computed tomographic scans displayed central neurocytomas as space-occupying lesions of mixed (heterogeneous) density, which frequently contained single and multiple petrificates and cysts. TI-weighted magnetic resonance imaging (MRI) indicated that in most cases (n=56, 66%), the intensity of a signal from the tumor was mixed and similar to that of the white matter of the brain. These masses were characterized by the presence of tumor structural cysts that were better visualized on T2-weighted tomograms. The tumor was removed in 83 cases; 2 out of them had previously undergone stereotactic biopsy (STB). STB was performed alone in one case. Transcallous, transcortical-through-premotor-area, combined, and transcallous-transcortical approaches were applied when the neurocytomas were removed. Results. Total removal of a tumor (when its remains were not visualized by postoperative MRI) was achieved in 11 (13%) patients. Its subtotal removal was accomplished in 48 (58%) patients. Partial removal was done in 24 (29%) patients. In the early postoperative period after tumor removal, there was a worse health status along with a transient progression of cerebral and focal symptoms in most patients with CN. The magnitude, pattern, and duration of these changes differed. Conclusion. The long (from several months to several years) history of the disease and young age (14 to 59 years) are typical of patients with CN. The tumors are located intraventricularly, more commonly along the midline, and they have well-defined X-ray signs: these are well-circumscribed tumors of heterogeneous density, which frequently contain single and/or multiple cysts and petrificates; there is a moderate contrast enhancement. The basic way of improving the results of treatment in patients with CN is the latter's early diagnosis and surgery when the tumor is locally advanced within the ventricular system.

[Comparative study of prolactin-secreting and hormonally inactive pituitary adenomas in patients with moderate hyperprolactinemia].

The present paper deals with the differential prolactin diagnosis of pituitary adenomas with moderate prolactin hyperproduction and hormonally inactive pituitary adenomas. Sixty patients with gross pituitary adenomas were examined. Morphological analysis of in-traoperative samples included histological, immunohistochemical studies with antibodies to hormones of the adenohypophysis. There was a probable frequency of prolactin-secreting tumors among gross pituitary adenomas proceeding with moderate hyperprolactinemia (25%) and that of hormonally inactive pituitary adenomas among the tumors regarded as prolactinomas (16%) in the preoperative period.

[Neuronal heterotopy].

The diagnosis of most volumetric processes of the brain presents no difficulty today; however, there are a number of brain diseases whose clinical manifestations are similar to those of tumors. Despite the development of neurovisualization techniques (application of currently available computer and magnetic resonance tomographs and special programs, such as MR imaging and CT spectroscopy, diffusion and perfusion, etc.), some of these processes are difficult to differentiate from neoplasms noninvasively. It is evident that treatment policy should be quite different in these or those cases. Neuronal nodular heterotopy (ectopy) may be considered as one of such pseudotumorous processes. This case illustrates the rare abnormality that has the clinical and X-ray picture similar to that of neoplasms of the brain. Current noninvasive method do not always allow one to significantly verify the nature of brain tissue changes, which shows it necessary to use CT-stereotactic biopsy in some cases.

[Analysis of the results of surgical treatment for symptomatic epilepsy caused by temporal lobar neoplasms]. / Analiz rezul'tatov khirurgicheskogo lecheniia simptomaticheskoi épilepsii, obuslovlennoi novoobrazovaniiami visochnoi oblasti.

The present study involves the analysis of the results of surgical treatment in 35 patients with drug-resistant epilepsy caused by local temporal lobar lesions: glioma without growth (n = 31), gliosis (n = 1), and cavernoma (n = 3). The medial location of neoplasms involving the hippocampus was noted in 25 cases, their extrahippocampal location was observed in 10 cases. The history of seizures was 2 to 18 years; the duration of a postoperative follow-up was 1 to 6 years. Electrocorticographic and EEG findings indicated that in all cases the eliptogenic zone was located in the medial portions of the temporal lobes at the site of lesion. The first stage of surgery was to remove a neoplasm; the adjacent portions of an epileptogenic zone were resected only with preserved convulsive activity in the surrounding areas. Good results (Classes I-II) were observed in cases of the medial location of a lesion in both total removal of a neoplasm and additional resections; in the group of patients the results were better than in routine removal (seizures ceasing in 4 of 5 and in 3 of 12 patients, respectively). Bad results (Classes III-V) were noted with partial removal of a neoplasm from the medial portions (n = 4), there were much better results (Classes I-II) with its total removal from the medial portions and with its partial removal from other areas. With total removal of extrahippocampal neoplasms, seizures were retained (Classes III-IV); additional resections of neocortical zones (n = 2) failed to improve the results of treatment. With resections in the entorial cortical area, the results were better (Class II). Our findings confirm that hippocampal removal plays an important role in symptomatic temporal epilepsy for an adequate monitoring of seizures.

[Skull base meningiomas spreading into the infratemporal fossa: clinical picture, diagnosis, and treatment policy]. / Meningiomy osnovaniia cherepa, rasprostraniaiushchiecia v podvisochnuiu iamku: klinika, diagnostika, taktika lecheniia.

From 1997 to 2004, the Academician N. N. Burdenko Research Institute of Neurosurgery has operated on 54 patients with intracranial meningiomas spreading into the infratemporal fossa. Fifteen patients were operated on for the first time. Thirty-nine patients had undergone surgical interventions on the average 3 times (from 2 to 8). All the patients were operated on via different orbitozygomatic approaches depending on the extent of the process. Opening the upper and lower palpebral fissures and the round foramen with resection, if required, the pterygoid processes suffice to remove tumors from the areas of the upper and lower palpebral fissures, which spread into the sphenoid and maxillary sinuses. If there are tumors at the site of the base of the anterior surface of the pyramid, and the articular bursa, it is expedient to open the oval and spinous foramens, to resect the external portions of the fundus of the middle cranial fossa and, if required, the articular process of the lower jaw. By taking into account the X-ray and histological patterns, it may be stated that invasion of meningiomas is not always accompanied by the development of hyperostosis. According to our findings, extracranial growth of meningiomas points to the invasion of osseous structures of the middle cranial fossa. Furthermore, if meningiomas grow into the infratemporal fossa, they frequently involve the muscles, nerves, and mucosa. After removing the tumors spreading to the infratemporal fossa, the optimum plastic repairs of defects of the base of the skull are as follows: hermetic closure of basal defect of the dura mater with a free fat flap, by fixing it with sutures and fibrin-thrombin glue with additional plastic repair of skull base defect with local displaced tissues on a pedicle (with a temporal muscular fascioperiosteal flap, a Bisch fat flap). Further policy of management of these patients is a complicated problem. It depends on the radicalism of an operation and the invasiveness of the process. The histobiological features of infiltrative meningiomas should be studied and this will determine management policy. Conceivably, the use of postoperative radiation therapy will be substantiated in a definite group of patients.

[Iatrogenic metastasis of pineal tumors]. / Iatrogennoe metastazirovanie opukholei pineal'noi oblasti.

Malignant pineal tumors (PT) tend to metastasize. In rare cases, this process is provoked by surgery. This paper describes four cases of iatrogenic metastasis of PT. Metastasis occurred: a) along the surgical approach path after tumor removal in 2 cases; b) along the biopsy cannula path; and c) along the ventriculoperitoneal catheter into the abdomen. The sources of metastases were pineoblastoma (n = 1), malignant teratoma (n = 1), germinoma (n = 1), and malignant germ-cell tumor of unknown genesis (n = 1). To prevent this complication due to high-grade PT, such as malignant germ-cell tumors and pineoblastomas, radiation of the whole brain, besides the sites of a tumor should be performed and, in some cases, in combination with chemotherapy.

[Malignant transformation of epidermoid cyst]. / Zlokachestvennaia transformatsiia épidermoidnoi kisty.

The paper presents a rare case of malignant transformation of an epidermoid cyst to the keratinizing type of squamous cell carcinoma. In a 47-year-old female patient with severe visual disturbances, MRI scans revealed a large supracellular tumor spreading to the third ventricle and medial portions of temporal lobes. The tumor was removed. A histological study of its biopsy specimen showed signs of both a benign process (epidermoid cysts) and its malignant epidermoid degeneration to the keratinizing type of squamous cell carcinoma. After 12-month combined therapy there was a continuous tumor growth with a significant dissemination within the base of the skull. The pathogenesis of epidermoid cysts, possible causes of malignant transformation, modalities of treatment and prognosis are briefly discussed.