Freeze-fracture study of human brain tumors.

This freeze-fracture study was performed in 3 astrocytomas, 6 glioblastomas, 2 ependymomas, 3 medulloblastomas, 1 cerebellar sarcoma, 3 germinomas, and 1 medulloepithelioma. The number of nuclear pores/mum2 nuclear membrane was not correlated with biological malignancy. Fracture faces A and B were discernible in nuclear, Golgi and rough endoplasmic reticulum (ER), mitochondrial surface, and plasma membranes. Fenestrae were evident in Golgi and ER membranes. The transitional zone of cristae from the inner surface membrane appeared as a circular hole and broken-off neck on faces A and B of the inner surface membrane, respectively. The decrease in number of membrane particles in the plasma membrane seemed to correlate with the frequency of metastases, and, in addition, the membrane particles appeared to cluster in glioblastoma, medulloblastoma, and medulloepithelioma. The gap junctions were abundant in astrocytomas, moderate in number in ependymomas and germinomas, and rare in glioblastomas, cerebellar sarcoma, and medulloepithelioma. Tight junctions were often found in germinomas and medulloepithelioma, and rarely in ependymomas.     

Concanavalin A target cells in human brain tumours

Using a lectin-peroxidase method, Concanavalin A binding was examined on formalin-fixed paraffin-embedded biopsy specimens (n = 143) of the most frequent central nervous system tumours. The brain tumours included oligodendrogliomas, astrocytomas, glioblastomas, ependymomas, neurinomas, meningiomas, medulloblastomas and plexus papillomas. In oligodendroglioma cells, only a weak granular intracytoplasmic staining was observed. The astrocytomas showed a strong reaction in fibrillary astrocytes and in tumour areas undergoing small cystic degeneration. Staining of protoplasmic astrocytes was weaker; pilocytic astrocytes demonstrated poor perinuclear staining. Intracytoplasmic Con A binding in gemistocytic astrocytes was distinct but inconstant and rather diffuse. In the glioblastomas the lymphocyte-like small astrocytes were negative. Giant multinucleated astrocytes stained strongly. In ependymomas no or at most a weak perinuclear reaction was observed, whereas the acceptor density was as high as in the normal ependymocytes in areas where the tumour was capable of producing organotypical structures. Plexus papillomas showed a strong intracytoplasmic staining comparable to the normal plexus epithelial cell. This feature was preserved in the malignant variants. In general, meningiomas and neurinomas were negative. Xanthomatous-degenerated meningioma cells, however, showed a distinct to strong intracytoplasmic staining. This feature was characteristic for the xanthomatous subtype of meningiomas. Granular cells with strong intracytoplasmic Con A staining often occurred at the border of fibrillary to reticular differentiated areas of neurinomas. Medulloblastomas were completely negative. Our results indicate that Con A binding to human brain tumours is specific and rather cytotypical than histotypical . The Con A acceptor density is probably related to the grade of differentiation. Lectin mapping of tumours leads to cytotypical binding patterns which may contribute to the differential diagnosis of neoplasias.     

Posterior fossa lesions in childhood and infancy

Forty-three children with CT studies demonstrating abnormalities in the posterior fossa are presented. Tumors constitute the largest group of lesions (53.5%). Their mean size at time of diagnosis was 39.5 mm. Astrocytomas, medulloblastomas, and ependymomas were the most frequent tumors and their CT features are described and discussed. The congenital group of lesions comprised 18.6% of the cases — the most frequent anomaly being arachnoid cyst. In the miscellaneous group (23.3%), cases with atrophy were the most frequent. The cerebellar hemispheres were the most involved sites (39.5%). Lesions located at the tentorial hiatus or near the clivus were rather rare.     

Extraneural metastases of anaplastic oligodendroglioma

Extraneural metastases from primary central nervous system (CNS) tumors are unusual, and glioblastomas and medulloblastomas constitute the majority of these. That oligodendroglioma frequently seeds within the CNS is well known. However, extraneural metastases of anaplastic oligodendroglioma are rare. We report a 50-year-old woman who developed multiple lung and liver metastases 28 months after resection of a temporal lobe anaplastic oligodendroglioma.     

Posterior cranial fossa surgery in 454 children Comparison of results obtained in pre-CT and CT era and after various types of management of dura mater

At the Department of Neurosurgery, Hradec Králové, 454 children (aged under 18 years) were operated on for posterior cranial fossa lesions in a period of 49 years (1948–1996). The majority (402) had tumours: cerebellar astrocytomas 149 (37.1%), medulloblastomas 139 (34.6%), brain stem gliomas 46 (11.4%), ependymomas 28 (7.0%), and others 40 (9.9%). Postoperative mortality was compared for the pre-CT era (1948–1977) and the CT era (1978–1996): astrocytomas (8.6%:4.7%), medulloblastomas (14.9%:2.9%), brain stem gliomas (21.7%:19.0%), ependymomas (18.2%:6.3%), and others (40.0%:7.4%). The initially high mortality was due to insufficient intracranial decompression, brain oedema and disturbances of cerebrospinal fluid circulation. Obstructive hydrocephalus was treated in 53 children with tumours and 25 with aqueduct stenoses, by Torkildsen's drainage in 5.5%, and/or by catheterisation of aqueduct in 12.3%. The main postoperative complications of medial posterior fossa surgery in 429 children operated on were: pseudomeningocele (12.3%), active hydrocephalus (6.2%) and CSF leakage (4.6%). Only 8.2% had shunts placed for these complications. We presume that this low percentage of shunts used results from a frequent use of duraplasties and drains installed at the primary operation. The dura mater was initially (1948–1954) left open (50 cases), and later (1955–1958) also sutured (37 cases), and from 1958, onward, and especially from 1961, reconstructed by a medial approach by means of various grafts (377 cases). In all, duraplasty was performed in 81.6% of cases. The grafts used for dura mater reconstruction were prepared from autogeneic (1.6%), allogeneic (72.3%), xenogeneic (24.8%), or synthetic (1.3%) material. They were successful in 99.2% of cases (all materials). Our own suture technique for posterior fossa duraplasty is presented. Received: 19 November 1997 Revised: 10 February 1998     

Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification

METHOD: The topography, sex distribution and histology of 340 primary CNS tumors in children up to 17 years of age were investigated and (re-)classified according to the latest WHO classification of nervous system tumors. RESULTS: Overall the prevalence for boys (60.9%) was higher and supratentorial locations predominated (53.3%); there was an even distribution of low-grade WHO I/II (51.5%) and high-grade WHO III/IV (48.5%) tumors. Boys were more commonly affected in all age groups throughout childhood and adolescence. Infratentorial location was more common between the ages of 3 and 11 years (57.5%). High-grade tumors were more frequently encountered up to the age of 5 years (53.2%). The main histological entities were pilocytic astrocytomas (23.5%), followed by medulloblastomas (16.3%), ependymomas (10.1%), anaplastic astrocytomas and glioblastomas (7.2% each), and craniopharyngiomas (5.6%); astrocytomas overall accounted for 47.3% of pediatric brain tumors. Rarer entities included germ cell tumors, gangliogliomas, and meningiomas (2.5% each), supratentorial PNET and pineal parenchymal tumors (1.9% each), atypical teratoid/rhabdoid tumors (1.3%), choroid plexus tumors (0.9%), and desmoplastic infantile astrocytomas and dysembryoplastic neuroepithelial tumors (0.6% each). A meta-analysis of 10,582 childhood brain tumors accumulated from 16 international surveys revealed a male-female ratio of 1.29 and a supra-/infratentorial ratio of 0.92. The most common histological diagnoses were astrocytomas (37.6%), medulloblastomas (17.7%), ependymomas (9.9%), craniopharyngiomas (7.3%), and germ cell tumors (4.4%). CONCLUSIONS: Pediatric brain tumors vary considerably in their histological, topographical and gender distribution throughout childhood and adolescence, reflecting different dynamics of individual tumor entities as well as a susceptibility to their occurrence during certain periods of a child's life. Although at times difficult to characterize, pediatric CNS tumors can be satisfactorily classified according to the latest WHO classification of nervous system tumors.     

Extracranial metastases of a supratentorial primitive neuroectodermal tumour.

Extracranial metastases from primary central nervous system (CNS) tumours have rarely been reported in the literature, and glioblastomas and medulloblastomas constitute the majority of these. The tendency of supratentorial primitive neuroectodermal tumours (PNET) to spread within the CNS is well-known, but few cases of extracranial metastases of supratentorial PNET have been reported. We report a 29-year-old man with a supratentorial PNET, which metastasized to his vertebral bodies and lung.     

Expression of AQP1 and AQP4 in paediatric brain tumours

Aquaporins (AQP) are water-channel proteins with roles in tumour cell migration, angiogenesis, cerebral oedema and cell-cell adhesion. We aimed to determine the expression of AQP1 and AQP4 in paediatric brain tumours. Twenty tumour bank specimens were subject to Western blot analysis and quantitative polymerase chain reaction (PCR) to determine the expression of AQP1 and 4. Immunohistochemical staining was used to determine the distribution of AQP1 and 4 expression. Medulloblastomas, primitive neuroectodermal tumour, germinomas and higher grade gliomas did not express AQP1 and 4. Of the ependymomas, those in the posterior fossa all demonstrated markedly increased expression of AQP1 and 4. A supratentorial ependymoma demonstrated a moderate increase in AQP1 but not AQP4. Pilocytic astrocytomas demonstrated high levels of AQP1 and 4 but had a more variable pattern of staining. AQP1 and 4 have relevance to paediatric brain tumours and are worthy of further investigation in developing potential therapeutic strategies.     

Intracranial ependymomas in childhood. Survival and functional results of 47 cases

A pediatric series of 47 intracranial ependymomas (15 supra- and 32 infratentorial) is presented. All children were operated upon between 1969 and 1979. Among these children, 35 completed the treatment with radiotherapy. The irradiation was usually limited to the intracranial content but in 7 patients, it was extended to the spinal axis as well. Malignant ependymomas represented 69% of the whole series (86% of the supratentorial and 53% of the infratentorial ependymomas). The operative mortality rate was 17%. The 5-year survival rate was 39% in the whole series and 51% when excluding postoperative mortality. Recurrences developed in 41% of cases and metastases in 20%. The study of this series and of the literature points out that: (1) metastases from supratentorial ependymomas are not frequent, almost always supratentorial and secondary to a malignant ependymoma, and (2) metastases from infratentorial ependymomas are almost always intraspinal and occur in one third of these tumors. The rate of seeding is especially high in the case of malignant infratentorial ependymomas (50%) but is also 15% in the case of benign tumors. These data lead the authors to propose a craniospinal irradiation in the case of infratentorial ependymomas whether benign or malignant, an irradiation of only the brain in the case of malignant supratentorial ependymoma, an irradiation of only the tumoral bed when ependymomas are benign and supratentorial.     

Monoclonal antibody to human midkine reveals increased midkine expression in human brain tumors.

We produced a rat IgG2a monoclonal antibody against the carboxyl terminal region of human midkine (MK), a novel growth factor. This monoclonal antibody was used in immunohistochemical studies to compare the expression of MK, proliferating cell nuclear antigen (PCNA) and p53 protein in 133 primary brain tumors and 21 carcinoma metastases to the central nervous system. Approximately half of the glioblastomas multiforme (GBMs) (19/32), medulloblastomas (8/14), primitive neuroectodermal tumors (PNETs) (5/11), breast carcinoma metastases (Br-Mts) (6/10) and lung carcinoma metastases (L-Mts) (5/11) as well as some astrocytomas (2/14) had tumor cells that expressed MK; however, oligodendrogliomas, ependymomas, schwannomas, meningiomas, and pituitary adenomas did not express MK. The values of the PCNA-labeling index were statistically higher in GBMs, medulloblastomas, PNETs, Br-Mts, and L-Mts that expressed MK than in those that did not (Wilcoxon rank-sum test, p < 0.05). There was no correlation between MK and p53 protein in all tumor types. Normal and non-neoplastic brain tissues were negative for MK, PCNA, and p53 protein. We conclude that primary and metastatic tumors of the brain express MK and that the MK expression in brain tumors may depend, in part, on the proliferating potential.     

Flow-through fluorocytophotometry of different brain tumours

Summary The flow-through cytophotometric method was used to investigate the single-cell DNA content in 60 tumours of the CNS and allied structures (9 meningiomas, 5 ependymomas, 15 astrocytomas, 11 anaplastic astrocytomas, 8 glioblastomas, 7 medulloblastomas, 2 oligodendrogliomas, 1 anaplastic oligodendroglioma, and 2 neurinomas). The cytophotometric parameters were correlated with morphological and clinical data of the tumours. The results are summarised in Tables 1–7. With regard to the DNA content of their cell nuclei, the gliomas present a behaviour similar to tumours in other organs, but in the present study the cytophotometric signs of malignancy in gliomas are not so evident as in carcinomas or sarcomas. The information obtained by flow cytophotometric methods may be helpful in diagnosing the degree of malignancy in brain tumours.     

Brain metastases in paediatric patients: characteristics of a patient series and review of the literature

In contrast to the occurrence of brain metastases advanced malignant tumours in adult cancer patients, the dissemination of solid tumours to the brains of paediatric cancer patients is very uncommon. We present a neuro-pathological and clinical study of a group of children and adolescents with brain metastases (BM) from extracranial solid malignancies. The analysed patients were diagnosed with soft tissue sarcomas (three), germ cell tumours (three), or osteosarcoma, neuroblastoma, clear cell sarcoma of the kidney, or pleuropulmonary blastoma (one each). In our series, BM frequently coexisted with pulmonary metastases. Three different metastatic patterns were discernible: a solitary tumour, multiple lesions and diffuse parenchymal dissemination. Two cases showed haemorrhagic presentation. Most of the children died due to BM progression, while children with germ cell tumours showed the best prognosis. The histopathological pictures of BM can be different from the primary tumour, showing dedifferentiation or a diverse neoplastic component. The autopsy examination can still be helpful in the final diagnosis of certain cases with atypical clinical presentations.     

Survival of children with brain tumors: SEER Program, 1973-1980

Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (1973-1980). Twenty-five percent were low-grade supratentorial astrocytomas, medulloblastomas were 23%, cerebellar astrocytomas 12%, high-grade supratentorial astrocytomas 11%, brainstem gliomas 9%, and ependymomas 8%. The worst survivals were in children less than 2 years of age, and the best were in those aged 10 to 14 years. Five-year survivals of children with cerebellar astrocytomas were 91%, low-grade supratentorial astrocytomas 71%, high-grade supratentorial astrocytomas 35%, medulloblastomas 39%, ependymomas 28%, and brainstem gliomas 18%.     

Estrogen receptors in brain tumors

We examined the cytosolic estrogen receptor (ER) level in tumor tissue from 77 patients: 36 meningiomas, 20 gliomas (12 glioblastomas, 2 cerebellar astrocytomas, 2 ependymomas, and 4 medulloblastomas), 8 neurinomas, 7 pituitary adenomas (2 prolactin-producing adenomas, 1 growth hormone-producing adenoma, and 4 nonfunctioning adenomas), and 6 metastatic brain tumors (1 from breast cancer, 4 from lung cancers, and 1 from colon cancer). Nuclear ER levels were assayed in 11 meningiomas and 2 glioblastomas. ER was determined by the dextran-coated charcoal method and calculated by Scatchard analysis. Cytosolic ER was detected in 100% of the pituitary adenomas, 50% of the meningiomas, 50% of the metastatic brain tumors, 25% of the neurinomas, and 15% of the gliomas. In gliomas, only medulloblastomas had ER activity. Nuclear ER was found in three premenopausal women with meningioma. The dissociation constant of the ER complex was, in each case, less than 10(-9) M. These observations suggest that some brain tumors may be responsive to estrogen via the cellular ER.     

Expression of α-, β-, and γ-synuclein in glial tumors and medulloblastomas

alpha-, beta- and gamma-synuclein are highly homologous proteins that are found predominantly in neurons. Abnormal accumulation of synucleins has been associated with diseases of the central nervous system particularly Parkinson's disease. Immunoreactivity of alpha-synuclein is demonstrated in brain tumors with neuronal differentiation and in schwannomas, whereas gamma-synuclein has been demonstrated in breast and ovarian carcinomas. The immunoreactivity of synucleins has not been described in glial tumors. Immunoreactivity of synucleins in glial cells in culture and in pathological conditions, however, suggests that synucleins may be expressed by glial tumors. We studied the expression of alpha-, beta-, and gamma-synuclein in 84 human brain tumors (24 ependymomas, 31 astrocytomas, 8 oligodendrogliomas, and 21 medulloblastomas) by immunohistochemistry. Our study demonstrates immunoreactivity for gamma-synuclein in high-grade glial tumors; immunoreactivity is found in all anaplastic ependymomas but in only 33% of ependymomas and 16% of myxopapillary ependymomas. Immunoreactivity for gamma-synuclein is noted in 63% of glioblastomas but not in other astrocytic tumors. Of medulloblastomas, 76% have immunoreactivity for either alpha- or beta-synuclein or both; no immunoreactivity for gamma-synuclein is seen in medulloblastomas.     

Proliferating cell nuclear antigen immunoreactivity in human central nervous system neoplasms

Summary Formalin-fixed, paraffin-embedded surgical specimens from 140 primary human central nervous system tumors, including 51 meningiomas, 26 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 5 ependymomas, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained using a streptavidin/peroxidase method and the PC10 monoclonal antibody, which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above neoplasms: meningiomas, 3.80±7.35%; astrocytomas, 0.65±1.03%; anaplastic astrocytomas, 8.46±7.95%; glioblastomas, 10.26±11.21; gliosarcoma, 46.34%; oligodendrogliomas, 2.31±3.59%; ependymomas, 1.12±2.10%; medulloblastomas, 23.91±11.95%; and paragangliomas, 2.07±1.86%. Collectively, our findings indicate that while benign central nervous system tumors generally have low PCNA LI values, consistent over-expression of PCNA epitopes was noted in some examples, especially in a number of meningiomas. Among the malignant neuroectodermal tumors, medulloblastomas were found to have the highest PCNA LI values, corresponding to their histological grade of malignancy, and malignant glial tumors generally displayed significantly higher PCNA LI values, than their benign counterparts. Although in our study mean PCNA LI values seemed to reflect histological grading, large discrepancies were noted in all tumor groups. Our data, therefore, suggest than PCNA immunoreactivity can not be considered reliable for predicting the prognosis of the disease in individual cases.Presented in part at the 14th Meeting of Swiss Neuropathologists with International Participation, Saint-Moritz, Switzerland, March 1992     

Primary intracranial germ cell tumours

Summary A histological study has been made of a retrospective series of 17 primary intracranial germ cell tumours found in a collection of 3550 intracranial neoplasms (incidence of 0.48%). All, except for two differentiated teratomas (one extracerebral in a neonate and another in the lateral ventricle), were situated in the midline in persons aged 5 to 37 years (13 males, 4 females). 12 tumours were located in or originated from the (para)pineal region, two of them also invaded the hypothalamus, while three germinomas occupied the retrochiasmal (supra/intrasellar) region without pineal involvement. There were 11 rather pure tumours (7 germinomas, 4 teratomas of various differentiation) and six mixed neoplasms (2 germinomas with teratoid areas, 3 embryonal carcinomas containing elements of endodermal sinus tumour, choriocarcinoma and germinoma, and one teratocarcinoma with endodermal sinuses). Only one case showed prominent features of endodermal sinus tumour, but characteristic elements of this type were present in four other mixed tumours. All germinomas and germinomatous parts of mixed neoplasms showed an inflammatory reaction of varying intensity, in 6 cases associated with multinucleated giant cells, which may be related to the prognosis of these tumours (one patient with hypothalamic germinoma is alive 6 years after radiotherapy). The close structural similarities between the various types of intracranial and gonadal dysgerminomas and their frequent combination within the same tumour support the concept of a common histogenesis of germ cell tumours regardless of their site of origin. Difficulties of classification may arise from the rather frequent occurrence of mixed germ cell neoplasms.Dedicated to E. Frauchiger, on the occasion of his 70th anniversary.     

Intracranial neoplasms in children in Ibadan,Nigeria

Analysis of 89 intracranial tumors in children presenting at the University College Hospital, Ibadan, Nigeria, between 1960 and 1982 is reported. These tumors are commonest in the first decade of life and occur more in males than in females. Fifty-three per cent of the primary brain tumors are supratentorial. The commonest sites are cerebellum, cerebrum, and the pons. The common histological types are astrocytomas, medulloblastomas, ependymomas, and oligodendrogliomas. Craniopharyngiomas are among the most frequent supratentorial neoplasms in Ibadan children and the central nervous system involvement in cases of Burkitt's lymphoma is a frequent complication.     

Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1,195 cases from a single institution

Object The purpose of this study is to determine the epidemiology of tumors of the nervous system diagnosed according to the WHO 2000 classification in a single Brazilian institution.Patients and method One thousand one hundred ninety-five tumors in children between 0 and 21 years of age diagnosed between 1974 and 2003 were classified according the sex, topography, and age distribution.Results In all ages, males were slightly more affected. In the first 2 years, the prevalence for boys was higher (68.3%). In the whole series, 58.7% were supratentorial, 31.4% infratentorial, and 9.9% spinal (44% intra- and 56% extramedullary). Among these latter, ependymomas and schwannomas were the most frequent. In the cerebral compartment, pilocytic astrocytomas were the single most frequent tumors (18%), followed by diffuse astrocytomas (14%), medulloblastomas (11%), and craniopharyngiomas (11%). In the posterior fossa, there was an even distribution among medulloblastomas and pilocytic astrocytomas, but the former was much more frequent in the first 2 years of age. High-grade (III and IV) diffuse astrocytomas were slightly more frequent than low grades (II), and this difference becomes more evident as the child grows older. Due to the new development of the surgery of epilepsy, the frequency of neuronal and mixed neuronal–glial tumors is increasing (8%).Conclusion Classified according to the latest WHO classification, by a single neuropathologist in a single institution, this large series of pediatric neurological tumors may reflect fairly well their real incidence. Our results obtained in a developing country do not differ substantially from other similar series reported in the literature from the First World.