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PubMed1992

Alternative splicing of neurofibromatosis type 1 gene transcript in malignant brain tumors: PCR analysis of frozen-section mRNA.

The neurofibromatosis type 1 (NF1) gene encodes a 360-residue region showing significant homology to the catalytic domains of both mammalian GTPase-activating protein (GAP) and yeast IRA protein. The product of the GAP-related domain of the NF1 gene (NF1-GRD) has been shown to stimulate ras GTPase and consequently to inactivate ras protein. We previously reported that the NF1-GRD has two types of transcripts, type I and type II, which are generated by an alternative splicing mechanism, and that the differential splicing of the NF1-GRD may be related to differentiation of neuroectodermal cells. Here we examined the differential expression of type I and type II transcripts of NF1-GRD in clinical samples of supratentorial malignant brain tumors by the RNA-polymerase chain reaction (PCR) method using frozen tissue sections. Our observations revealed that normal cerebrum predominantly expressed the type II NF1-GRD transcript, whereas primitive neuroectodermal tumors predominantly expressed the type I transcript. Additionally, although the type I/type II ratio in astrocytomas varied widely among tissue samples, all glioblastomas showed higher type I/type II ratios than adjacent brain samples. The RNA-PCR analysis using frozen tissue sections is a useful and sensitive method for detecting genetic markers in clinical tissue samples.

Astrocytoma↗
PubMed1993

Central nervous system tumors in Mexican children.

Five hundred and seventy primary central nervous system (CNS) tumors from the Department of Pathology at the National Institute of Pediatrics in Mexico City, collected from 1970 to 1989, were histologically reclassified in order to find out their relative incidence as well as their outstanding features. With this, we could establish a frame of reference for our local population, contributing to the epidemiological analysis of these entities. All the tumors were examined independently by two pathologists (C.R. and M.R.), using the classification of Rorke et al. Histological type, patient age and sex, and tumor location were analyzed. CNS tumors were the secondmost frequently encountered solid tumors, after lymphomas, and were increasing in incidence at a rate of 2.2 annually. Children in the age group 0-9 years were most often affected, and there was a predominance of male patients. Astrocytoma and medulloblastoma were the most common tumor types. The infratentorial region was the most frequent tumor location in the 2- to 9-year age group. By contrast, in the under 2-year-olds a supratentorial location was more frequent, and the incidence of germ cell tumors was proportionally high. In general, some histological types seemed to be associated with particular age groups. Although we found primitive neuroectodermal tumors to be the fifth most common at all ages (except for medulloblastoma), many other authors do not report a similar finding.

Adolescent↗
PubMed1993

Use of recombinant granulocyte-colony stimulating factor to treat neutropenia occurring during craniospinal irradiation.

PURPOSE: To investigate the effectiveness of recombinant human Granulocyte-Colony Stimulating Factor, a hematopoietic growth factor which stimulates neutrophil production, in the treatment of neutropenia caused by Craniospinal Irradiation. METHODS AND MATERIALS: Four consecutive patients who developed neutropenia (neutrophils less than 1.5 X 10(9)/l in peripheral blood) during craniospinal irradiation for primary intracranial tumors received intermittent subcutaneous injections of Granulocyte-Colony Stimulating Factor. Two of the patients had medulloblastoma, one had a primitive neuroectodermal tumor and the other a pinealocytoma. No patient received prior or concurrent chemotherapy. RESULTS: In all cases peripheral blood neutrophil counts returned rapidly to normal levels following Granulocyte-Colony Stimulating Factor injections and treatment delays were therefore avoided. Platelet counts were unaffected by Granulocyte Colony Stimulating Factor treatment. In one case, slight elevation of peripheral blood monocyte and lymphocyte counts occurred after each Granulocyte-Colony Stimulating Factor injection. No toxicity was encountered. CONCLUSION: Our results suggest that Granulocyte-Colony Stimulating Factor is a safe and effective treatment for neutropenia caused by extended field radiotherapy.

Adult↗
PubMed1988

Pathologic features of extraosseous Ewing's sarcoma: a report from the Intergroup Rhabdomyosarcoma Study.

Eighty-four cases of extraosseous Ewing's sarcoma (EOE) were found during the pathology review of the Intergroup Rhabdomyosarcoma Study I and II. Patients commonly presented during or after adolescence with the most common primary sites including the trunk, extremities, and retroperitoneum. Males were slightly more affected. Histologic sections of 74 tumors in the pathology repository were re-reviewed with attention to rosette formation (positive in 18 cases) and glycogen deposition (++ in 21, + in 36, +/- in 11, and - in 2 of 70 cases examined). Fourteen tumors (7 with rosettes and 7 without) were selected for immunohistochemical and ultrastructural studies, and 13 showed single or multiple neural markers (neuron-specific enolase in 8, S-100 protein in 6, and neurosecretory-type granules in 9). These possible cases of neural EOE could be divided into three subgroups: tumor with bidirectional neuroblastic and schwannian differentiation (5 cases), tumor with monodirectional neuroblastic differentiation (7 cases), and tumor with monodirectional schwannian differentiation (1 case). EOE with a neural nature may be categorized into a spectrum of peripheral primitive neuroectodermal tumors. Clinical, histopathologic, and biologic differences between this disease and conventional sympathetic neuroblastoma are discussed.

Child↗
PubMed1992

Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter.

We have previously shown that postnatal expression of the viral oncoprotein SV40 T antigen in rod photoreceptors (transgene MOT1), at a time when retinal cells have withdrawn from the mitotic cycle, leads to photoreceptor cell death (Al-Ubaidi et al., 1992. Proc. Natl. Acad. Sci. USA. 89:1194-1198). To study the effect of the specificity of the promoter, we replaced the mouse opsin promoter in MOT1 by a 1.3-kb promoter fragment of the human IRBP gene which is expressed in both rod and cone photoreceptors during embryonic development. The resulting construct, termed HIT1, was injected into mouse embryos and five transgenic mice lines were established. Mice heterozygous for HIT1 exhibited early bilateral retinal and brain tumors with varying degrees of incidence. Histopathological examination of the brain and eyes of three of the families showed typical primitive neuroectodermal tumors. In some of the bilateral retinal tumors, peculiar rosettes were observed, which were different from the Flexner-Wintersteiner rosettes typically associated with human retinoblastomas. The ocular and cerebral tumors, however, contained Homer-Wright rosettes, and showed varying degrees of immunoreactivity to antibodies against the neuronal specific antigens, synaptophysin and Leu7, but not to antibodies against photoreceptor specific proteins. Taken together, the results indicate that the specificity of the promoter used for T antigen and/or the time of onset of transgene expression determines the fate of photoreceptor cells expressing T antigen.

Animals↗
PubMed1999

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.

Animals↗
PubMed1995

Comparison of gadolinium-enhanced MR and thallium-201 single photon emission computed tomography in pediatric brain tumors.

Despite its usefulness in adults with cerebral gliomas, indications for thallium-201 single-photon emission computed tomography (SPECT) in pediatric brain tumor patients are not well defined. We prospectively compared thallium SPECT with gadolinium-enhanced MR (Gd-MR) to determine if thallium SPECT provides clinically useful information that cannot be derived from Gd-MR. We studied 24 pediatric brain tumor patients, 7 at presentation and 17 during therapy. MR imaging included T2 and pre- and postgadolinium T1 images. Thallium SPECT was done within 48 h of MR imaging; thallium indices were calculated for 12 of 14 lesions which showed thallium uptake. Surgery and/or clinical follow-up are available in all patients. The tumors included pilocytic astrocytoma (7), medulloblastoma (5), brainstem glioma or glioblastoma (4), germinoma (3), optic glioma (2), mixed glioma (1), primitive neuroectodermal tumor (1), and choroid plexus carcinoma (1). Among the primary tumors, compared to MR, thallium SPECT was false-negative for tumor in 1 patient and true-positive in 6 patients. Among the patients studied while on therapy, compared to MR, thallium SPECT was true-negative for tumor in 7, true-positive in 5, false-negative in 3, and false-positive in 2. In both groups of patients, thallium SPECT underestimated tumor burden as nonenhancing regions of the tumors were not thallium-avid. Thallium indices did not correlate with histologic grade, biologic aggressiveness, or tumor type. We were unable to establish indications for the use of thallium SPECT in this setting as there was little clinically useful information derived from thallium SPECT that was not provided by Gd-MR.

Adolescent↗
PubMed1993

Experimental neurocytomas.

Four ethyl-nitrosourea (ENU)-induced oligodendroglioma-like tumors of the rat showing large rosettes on haematoxylin-eosin stain were studied by means of immunohistochemistry and electron microscopy, and their features compared with six human intraventricular neurocytomas. The similarities between the experimental and human tumors studied support the hypothesis that most of the so-called ENU-induced oligodendrogliomas in the rat are primitive neuroectodermal tumors with the tendency to differentiate toward a neuronal phenotype, and also suggest that the ENU-model of neurocarcinogenesis is useful for the induction of experimental neurocytomas.

Animals↗
PubMed1996

Cytogenetics and tissue culture of small round cell tumors of bone and soft tissue.

The variety of tumor-specific cytogenetic and genetic alterations among small round cell tumors (Ewing family of tumors, rhabdomyosarcoma, neuroblastoma, and lymphoma) increases the possibility of genotypic diagnosis of them. In Ewing's sarcoma and related peripheral primitive neuroectodermal tumors, a (11;22)(q24;q12) translocation is associated with hybrid transcripts of the EWS gene with the FLIl gene. In alveolar rhabdomyosarcoma, a (2;13)(q35;qt4) translocation is associated with a chimeric gene between PAX3 and FKHR. Specific genetic alterations of the short arm of chromosome 1 and amplification of the MYCN gene are diagnostically useful in neuroblastomas as the immunoglobulin or T-cell receptor gene rearrangements and chromosome translocations in lymphomas. Thus, cytogenetics and genetics provide an essential adjunct to diagnostic surgical pathology in the case of small round cell tumors, which often present substantial diagnostic challenges. Likewise, in vitro culture studies represent another approach in determining histogenetic origin, novel genes, novel mechanisms of gene dysregulation, and the biological characteristics of small round cell tumors.

Bone Neoplasms↗
PubMed1989

Neuroectodermal differentiation in "extraskeletal Ewing's sarcoma".

A small round cell tumor of soft tissue arising in the retroperitoneum of an 18-year-old woman is reported. The light and electron microscopic features of the tumor were mostly indistinguishable from Ewing's sarcoma of the bone and in some parts from differentiating neuroblastoma with mature neurons and Schwann cells. An immunohistochemical study using anti-NSE antibody showed many widespread NSE-positive cells lying singly and, more often, in clusters including the undifferentiated areas. The tumor was not anatomically related to the paravertebral sympathetic ganglia or adrenal glands. The present findings strongly suggest that certain extraskeletal Ewing's sarcomas are very primitive neuroectodermal tumors.

Adolescent↗
PubMed1995

Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood.

Clinical and morphological features of an apparently unique, biologically aggressive central nervous system tumor in 32 infants and children are presented. This neoplasm is formed wholly or partly by rhabdoid cells, areas resembling typical primitive neuroectodermal tumor, and, less frequently, malignant mesenchymal and/or epithelial tissue. The tumor has been named atypical teratoid/rhabdoid tumor (ATT/RhT) and is regarded as a unique class of primary central nervous system (CNS) tumors. It occurs most commonly in infants less than two years of age, has often metastasized throughout the CNS at presentation, dose not respond to therapy and causes death less than a year after diagnosis. These tumors may occur in any CNS site but almost 60% are located in the cerebellum. The most common chromosomal abnormality involves chromosome 22.

Central Nervous System Neoplasms↗
PubMed1998

Cross-sectional imaging with CT and/or MRI of pediatric chest tumors.

The purpose of this study was to provide an overview of the spectrum of pediatric chest masses, to present the results of cross-sectional imaging with CT and/or MRI, and to define diagnostic criteria to limit differential diagnosis. Seventy-eight children with thoracic mass lesions were retrospectively evaluated using CT (72 patients) and/or MR imaging (12 patients). All masses were evaluated for tissue characteristics (attenuation values or signal intensity, enhancement, and calcification) and were differentiated according to age, gender, location, and etiology. Twenty-eight of 38 (74 %) mediastinal masses were malignant (neuroblastoma, malignant lymphoma). Thirty of 38 (79 %) pulmonary masses were metastatic in origin, all with an already known primary tumor (osteosarcoma, Wilms tumor). With one exception, all remaining pulmonary lesions were benign. Seventeen of 21 (81 %) chest wall lesions were malignant (Ewing sarcoma, primitive neuroectodermal tumor). The majority of mediastinal and chest wall tumors in children is malignant. Lung lesions are usually benign, unless a known extrapulmonary tumor suggests pulmonary metastases. Cross-sectional imaging with CT and/or MRI allows narrowing of the differential diagnosis of pediatric chest masses substantially by defining the origin and tissue characteristics. Magnetic resonance imaging is preferred for posterior mediastinal lesions, whereas CT should be used for pulmonary lesions. For the residual locations both modalities are complementary.

Adolescent↗
PubMed2003

Stereotactically-guided biopsies of brainstem tumors.

INTRODUCTION: More than 10 years ago, the goal of our work had been to obtain a tissue sample of infiltrating lesions of the brainstem that had been diagnosed using computerized axial tomography (CAT). At that time, biopsies were believed to be indispensable when starting treatment of tumors. With time our objectives changed. Biopsies remained necessary, since until 1 year before the writing of this article we had not had the benefits of magnetic resonance imaging (MRI) at our Hospital. We also decided that carrying out sound statistics, confirmed by biopsies, was in itself a good procedure, especially in a country in which, to date, no serial studies of brainstem tumors had been undertaken. METHODS: We analyzed all of the patients diagnosed with posterior fossa tumors between March 1989 and March 2002 at the Hospital Infantil de México Federico Gómez (HIM). A preoperative TAC of the cranium was performed on every patient. Stereotactically-guided biopsies during tomography allowed precise control of penetration. Material obtained was sent to the Department of Pathology for analysis. RESULTS: Fifty patients were diagnosed with infiltrating tumors of the brainstem: 30 cases of low-grade astrocytomas, 13 cases of high-grade astrocytomas, 2 cases of primitive neuroectodermic tumors, 2 cases of rhabdoid tumors, 1 case of ependymoma, and 2 patients had non-specified tumors. The most frequent symptoms and signs were ataxia and disturbances of the cranial nerves. There was no mortality caused by penetration, and follow-up studies of more than 5 years were carried out. DISCUSSION: The results from our series were similar to those in the literature. In our case, follow-up studies were undertaken for longer periods. In the first section of our work, we suggest the need for stereotactic biopsies in order to arrive at a precise diagnosis in environments in which MRI may be unavailable. CONCLUSION: At present, presumptive diagnosis of infiltrating brainstem lesions may be adequately undertaken with imaging methods, such as MRI. However, we believe that a stereotactically-guided biopsy provides an accurate method for diagnosing lesions of the brainstem. In our case, this procedure has been carried out entirely in the tomography room, without any complications of disease or mortality.

Adolescent↗
PubMed1991

O6-alkylguanine-DNA alkyltransferase activity in human brain tumors.

It is well known that resistance in tumor cells to alkylating agents and, in particular, chloroethylnitrosoureas (CENUs), which are widely used in the chemotherapy of brain tumors, correlate well with activity of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (O6-AT). We measured O6-AT activity in human brain tumors in order to obtain basic knowledge of whether or not CENU chemotherapy can be applied selectively on brain tumors. The subjects included 17 gliomas (seven malignant astrocytomas, two glioblastomas, two medulloblastomas, two oligodendrogliomas, two ependymomas, one fibrillary astrocytoma, one primitive neuroectodermal tumor) and five non-glial tumors (three meningiomas, two neurinomas). The value of O6-AT activity for the gliomas varied widely and indicated 111 +/- 65 fmol of 3H-methyl adducts transferred/mg protein extract/hr (mean +/- S.D., range 0-258, 18 tumors), while the non-glial tumors showed a relatively high value of 270 +/- 43 fmol/mg/hr (range 225-330, 5 tumors). A significant difference in the O6-AT activity was noted between the gliomas and the nonglial tumors at the p-value of 0.001. Six (38%) out of 17 glioma cases showed a value below 100 fmol/mg/hr and four cases (24%) a value below 60 fmol/mg/hr. These results provide a biological basis for applying CENU chemotherapy on glioma patients with a lower value of O6-AT enzyme.

Brain Neoplasms↗
PubMed1994

Medulloblastoma in adults.

Seventeen adult patients (16 years of age and over) with medulloblastoma were managed at King Faisal Specialist Hospital and Research Centre between 1981 and 1992. Nine patients were males and eight were females. The average age at diagnosis was 26.7 years; the females were younger than the males. The average duration of history before diagnosis was 14.5 weeks, the females presenting earlier than the males. The tumors were located in the midline (9) and the hemispheres (8). Nine patients had the desmoplastic variant and eight had standard primitive neuroectodermal tumor. Hydrocephalus developed in 14 of the patients only seven of whom required a shunting procedure. All patients had either subtotal or gross total removal of the tumor. Sixteen patients had postoperative radiation therapy; one patient refused radiation therapy. Two patients had chemotherapy following recurrence of the tumor. The clinical presentation, radiological studies, histological variants, treatment and outcome are discussed in this report.

Adolescent↗
PubMed2005

Proton-decoupled 31P MRS in untreated pediatric brain tumors.

Proton-decoupled (31)P and (1)H MRS was used to quantify markers of membrane synthesis and breakdown in eight pediatric patients with untreated brain tumors and in six controls. Quantitation of these compounds in vivo in humans may provide important indicators for tumor growth and malignancy, tumor classification, and provide prognostic information. The ratios of phosphoethanolamine to glycerophosphoethanolamine (PE/GPE) and phosphocholine to glycerophosphocholine (PC/GPC) were significantly higher in primitive neuroectodermal tumors (PNET) (16.30 +/- 5.73 and 2.97 +/- 0.93) when compared with controls (3.42 +/- 1.62, P < 0.0001 and 0.45 +/- 0.13, P < 0.0001) and with other tumors (3.93 +/- 3.42, P < 0.001 and 0.65 +/- 0.30, P < 0.0001). Mean PC/PE was elevated in tumors relative to controls (0.48 +/- 0.11 versus 0.24 +/- 0.05, P < 0.001), but there was no difference between PNET and other tumors. Total choline concentration determined with quantitative (1)H MRS was significantly elevated (4.78 +/- 3.33 versus 1.73 +/- 0.56 mmol/kg, P < 0.05), whereas creatine was reduced in tumors (4.89 +/- 1.83 versus 8.28 +/- 1.50 mmol/kg, P < 0.05). A quantitative comparison of total phosphorylated cholines (PC+GPC)/ATP measured with (31)P MRS and total choline measured with (1)H MRS showed that in tumors a large fraction of the choline signal (>54 +/- 36%) was not accounted for by PC and GPC. The fraction of unaccounted choline was particularly large in PNET (>78 +/- 7%). The pH of tumor tissue was higher than the pH of normal brain tissue (7.06 +/- 0.03 versus. 6.98 +/- 0.03, P < 0.001).

Brain↗
PubMedDate not supplied

Meningeal melanocytoma: a case report and literature review.

The clinicopathologic, immunocytochemical, and electron microscopic features of a case of meningeal melanocytoma arising in the phylum terminale are reported. Meningeal melanocytoma is an uncommon tumor that must be distinguished from metastatic or primary malignant melanoma, meningeal melanocytic nevi, pigmented meningioma, pigmented schwannoma or neurofibroma, and pigmented primitive neuroectodermal tumor. This is a difficult differential diagnosis that can be best archived by complementing histological examination with a selected panel of antibodies and, most important, electron microscopic study. The distinctive ultrastructural appearance of most of these lesions point to this technique as the gold standard in pigmented proliferations of the nervous system.

Aged↗
PubMedDate not supplied

Morphologic characterization of spontaneous nervous system tumors in mice and rats.

Spontaneous rodent nervous system tumors, in comparison to those of man, are less well differentiated. Among the central nervous system (CNS) tumors, the "embryonic" forms (medulloblastoma, pineoblastoma) occur both in rodents and humans, whereas the human "adult" forms (gliomas, ependymomas, meningiomas) have fewer counterparts in rodents. In general, the incidence of spontaneous CNS tumors is higher in rats (>1%) than in mice (>0.001%). A characteristic rat CNS tumor is the granular cell tumor. Usually it is associated with the meninges, and most meningeal tumors in rats seem to be totally or at least partly composed of granular cells, which have eosinophilic granular cytoplasm, are periodic acid-Schiff reaction (PAS)-positive, and contain lysosomes. Such tumors are frequently found on the cerebellar surface or at the brain basis. Rat astrocytomas are diffuse, frequently multifocal, and they invade perivascular spaces and meninges. The neoplastic cells with round to oval nuclei and indistinct cytoplasm grow around preexisting neurons, producing satellitosis. In large tumors, there are necrotic areas surrounded by palisading cells. Extensive damage of brain tissue is associated with the presence of scavenger cells that react positively with histiocytic/macrophage markers. The neoplastic astrocytes do not stain positively for glial fibrillary acidic protein; they probably represent an immature phenotype. In contrast to neoplastic oligodendroglia, they bind the lectin RCA-1. Astrocytomas are frequently located in the brain stem, especially the basal ganglia. Rat oligodendroglial tumors are well circumscribed and frequently grow in the walls of brain ventricles. Their cells have water-clear cytoplasm and round, dark-staining nuclei. Atypical vascular endothelial proliferation occurs, especially at the tumor periphery. Occasionally in the oligodendrogliomas, primitive glial elements with large nuclei occur in the form of cell groups that form rows and circles. Primitive neuroectodermal tumors of rats, such as pineal tumors or medulloblastomas, appear to have features similar to those found in man. In mice, the meningeal tumors are mostly devoid of granular cells and the astrocytomas are similar to those occurring in rats, whereas spontaneous oligodendrogliomas are observed extremely rarely. Tumorlike lesions, such as lipomatous hamartomas or epidermoid cysts, are occasionally encountered in the mouse CNS. It is suggested that we classify rodent CNS lesions as "low grade" and "high grade" rather than as "benign" and "malignant." The size of CNS tumors is generally related to their malignancy. Tumors of the peripheral nervous system are schwannomas and neurofibromas or neurofibrosarcomas consisting of Schwann cells, fibroblasts, and perineural cells. Well-differentiated schwannomas are characterized by S-100 positivity and the presence of basement membrane. They show either Antoni A pattern with fusiform palisading cells or Antoni B pattern, which is sparsely cellular and has a clear matrix. The rat develops specific forms of schwannomas in the areas of the submandibular salivary gland, the external ear, the orbit, and the endocardium. Spontaneous ganglioneuromas occur in the rat adrenal medulla or thyroid gland. Compared to experimentally induced neoplasms, the spontaneous tumors of the rodent nervous system are poor and impractical models of human disease, although they may serve as general indicators of the carcinogenic potential of tested chemicals.

Animals↗