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PubMedDate not supplied

Congenital brain tumors: a review of 45 cases.

Forty-five pathologically proved cases of neonatal brain tumors (diagnosed in neonates within 60 days after birth) were reviewed from the neuroradiology archives dating back to 1964. CT was performed in 24 cases, MR in five, sonography in six, and angiography in seven. Two-thirds of the lesions were supratentorial. The most common histology was a tumor composed of primitive or poorly differentiated tissues: 12 teratomas and 12 primitive neuroectodermal tumors, four of which were typical medulloblastomas. In addition, there were nine astrocytomas (grades I-III); four cases of glioblastoma multiforme (astrocytoma grade IV); three choroid plexus papillomas; and single cases each of ependymoma, medulloepithelioma, germinoma, angioblastic meningioma, and ganglioglioma. The dominant CT appearance, regardless of histology, was a large heterogeneous lesion with associated hydrocephalus. Coarse calcification was a constant feature in the teratomas. Prognosis was poor overall, with the longest survival seen in choroid plexus papilloma and astrocytoma. Imaging studies are most valuable in identifying and distinguishing potentially curable lesions such as choroid plexus papillomas (variably sized intraventricular lesions with homogeneous enhancement) from rapidly fatal tumors such as teratomas (large heterogeneous lesions with coarse calcifications and associated hydrocephalus).

Brain Neoplasms↗
PubMed1996

Olfactory neuroblastoma and other round cell lesions of the sinonasal region.

Sixty-nine round cell lesions of the sinonasal region (22 olfactory neuroblastomas [ONBs], 17 malignant lymphomas, nine Ewing's sarcomas [ES], nine rhabdomyosarcomas, three sinonasal undifferentiated carcinomas, five malignant melanomas, and four pituitary adenomas) were studied in an attempt to define the differential diagnostic capabilities of antibody to MIC2 and bcl-2 in paraffin-embedded tissue in the distinction of these lesions. In addition, antibody to p53 was applied in each case to define the incidence of p53 positivity among these various tumor types. Each of the ES cases was MIC2 positive; each of the other cases was MIC2 negative. Positivity for bcl-2 was confined to two cases, one of them a malignant lymphoma (85% of cells positive) and one an ONB (5% of cells positive). Small numbers of scattered p53-positive cells appeared in the majority of cases studied, without regard for the specific tumor type; only a single case, a malignant lymphoma, showed a majority (approximately 90%) of p53-positive cells. These results indicate that the MIC2 antibody is a useful method by which to distinguish ES from a variety of other round cell lesions that may be encountered in the sinonasal region. The practical applications of antibody to bcl-2 and p53 seem to be much more limited; by contrast, neither bcl-2 positive cells nor abundant p53 cells identified by immunohistochemical analysis seemed to be frequent findings in any of the tumor types studied. Although ONBs have been included with the peripheral primitive neuroectodermal tumors for classification purposes, these tumors diverge from the ES/primitive neuroectodermal tumor family in that they do not seem to share either the MIC2 positivity or the t(11;22) chromosomal translocation that typify the ES/primitive neuroectodermal tumor family of lesions. Although bcl-2 positivity has been associated with a light microscopic finding of an unfavorable histologic pattern in retroperitoneal neuroblastomas, it does not seem that bcl-2 positivity in ONB will select for a clinically distinctive subset of patients.

12E7 Antigen↗
PubMed1993

Characterization of thread proteins expressed in neuroectodermal tumors.

Neuronal thread protein is a novel 21-kDa protein that accumulates in brains with Alzheimer's disease and exhibits developmentally associated changes in the level of expression. Recently, we discovered that primary human primitive neuroectodermal tumor (PNETs), malignant astrocytomas, and several human PNET and glioblastoma cell lines also express thread protein immunoreactivity. However, in addition to the 21-kDa species, there are approximately 17- and approximately 14-kDa thread protein-immunoreactive molecules expressed in both PNET and glioblastoma cell lines and a fourth approximately 8-kDa thread protein detected in glioblastoma cell lines. Metabolic labeling studies demonstrated that the 21-kDa thread proteins are phosphorylated, whereas the approximately 17-, approximately 14-, and approximately 8-kDa thread proteins are not. Glycosylated residues were not detected in either the PNET- or glioblastoma-derived thread proteins. Using a panel of monoclonal antibodies, we observed differences between PNET and glioblastoma cells suggesting that the thread proteins expressed in neuronal and glial cells are distinct. The levels of thread protein immunoreactivity in both PNET and glial cells were highest during the log phase of cell growth and lowest in serum-starved, nonproliferating cultures. The findings suggest that there are several distinct neuronal and glial derived thread proteins expressed in the central nervous system and that their levels of expression may be modulated with cell growth.

Antibodies, Monoclonal↗
PubMed1998

Fine-needle aspiration cytology of extraskeletal Ewing's sarcoma.

Extraskeletal Ewing's sarcoma (EES) is a round-cell malignancy that manifests most commonly in the paravertebral and intercostal regions. It occurs predominantly in adolescents and young adults, between the ages of 10 and 30 yr, and follows an aggressive course with a high recurrence rate. Distant metastasis is also common. The tumor is often confused with other round, small-cell neoplasms, including primitive neuroectodermal tumor, neuroblastoma, embryonal rhabdomyosarcoma, and lymphoma. This report pertains to a fine-needle aspiration cytologic diagnosis of EES, supported by clinicopathologic and fine structural correlations in a 56-yr-old man who presented with a rapidly growing, massive, right groin mass. The smears showed a diffuse cellular population of malignant round cells composed of two types: one group of larger cell exhibiting a thin-rim, pale cytoplasm, less hyperchromatic nuclei, nucleoli, and diffusely dispersed chromatinic nuclear details; and the second group of smaller and darker cells with highly hyperchromatic and almost smudged nuclei. These are chief cells and dark cells, respectively. Special studies revealed significant intracytoplasmic glycogen and positive vimentin and HBA-71 immunostaining. Cytogenetic findings of chromosomal 11;22 translocation is also supportive of the diagnosis of EES.

Antigens, Neoplasm↗
PubMed1995

The role of spiral (helical) computerized tomography with three-dimensional reconstruction in pediatric solid tumors.

The ability to accurately assess tumor size and orientation to surrounding vital structures is an important consideration during preoperative evaluation. The authors report on nine children with solid tumors (hepatoblastoma [1], neuroblastoma [2], adrenal cortical carcinoma [2], liver adenoma [1], primitive neuroectodermal tumor [PNET] [1], and stage V Wilms' tumor [2]) for whom tumor resectability was questioned because of the tumors' close proximity to major blood vessels (noted through conventional radiographic imaging). The children had scanning with spiral volumetric acquisition computerized tomography, (CT) which obtains images during continuous rotation of the x-ray source while the patient moves at a constant velocity through the gantry. This technique is rapid (18 to 30 seconds), and is similar with respect to radiation exposure; little or no sedation is required, and the contrast dose is lower than that of conventional CT. Three-dimensional reconstruction of spiral CT imaging provided useful information that allowed successful resection in all nine cases. The authors suggest that spiral CT may become an important imaging modality in the preoperative evaluation of pediatric solid tumors and that further evaluation of this new methodology is warranted.

Adolescent↗
PubMed1998

Pediatric brain tumors: loss of heterozygosity at 17p and TP53 gene mutations.

Cytogenetic and molecular analyses of primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) have demonstrated material losses of 17p, the region that contains the TP53 gene, as the most frequent abnormality. Mutations in the TP53 gene are, however, very rare in these tumors. These findings strongly suggest that another, as yet unidentified, gene on 17p may be involved. We performed a search for loss of heterozygosity (LOH) on 17p by microsatellite markers on 26 childhood CNS tumors as well as TP53 gene mutations (exons 5-8) by single-strand conformational polymorphism analysis on 41 pediatric brain tumor samples of distinct histologic types. LOH was detected in 10 cases: 7 PNET, 2 astrocytomas, and 1 glioblastoma multiforme. In 4 of the PNETs the losses were limited to more distal markers. On the other hand, TP53 mutations were detected in 6 of 41 samples studied. Our results not only confirm the low penetrance of the TP53 gene on pediatric CNS tumors, but also provide further evidence of a putative tumor suppressor gene distal to TP53, between markers (D17S938, D17S926) and 17pter, specifically taking part in the development of PNET.

Adolescent↗
PubMed1998

Cryoextraction in the management of orbital tumors. An old technique revisited.

Four patients with relatively large orbital tumors are described. These patients had superomedial rhabdomyosarcoma, inferomedial cavernous hemangioma, lateral primitive neuroectodermal tumor, and superior neurofibroma, respectively. Continuing enlargement and encroachment upon vital ocular structures and suspicion of malignancy warranted surgical intervention. Following exposure of the anterior portions of these tumors, a cryoprobe was used for the complete removal of the mass. Cryoextraction greatly facilitates the excision of well-defined, solid, encapsulated, benign or malignant tumors excluding the lacrimal gland and thus minimizes trauma to adjacent tissues. More importantly, the tumor can be removed intact without capsular rupture and risk of tumor spill-over or hemorrhage. At the histopathological level, the application of a cryoprobe did not alter the microscopic structures of the lesions and did not cause any difficulty for histopathologic interpretation.

Journal Article↗
PubMed2006

Comparative analysis of germ cell transcription factors in CNS germinoma reveals diagnostic utility of NANOG.

The homeodomain transcription factor, NANOG, along with OCT3/4 (POU5F1) and SOX2, is part of the core set of transcription factors that maintain embryonic stem cell self-renewal and pluripotency. Expression of NANOG has been detected in fetal germ cells and in gonadal germ cell tumors. To assess the diagnostic utility of NANOG in central nervous system (CNS) germ cell tumors, we analyzed its expression by immunohistochemistry in a series of 12 CNS germinomas and compared its expression with other stem cell markers. Strong nuclear expression of NANOG was demonstrated in >90% of the tumor cells in all cases. In contrast, expression of OCT3/4 and placental alkaline phosphatase was inconsistent and SOX2 was expressed in only rare cells. NANOG was not detected in tumor types frequently considered in the differential diagnosis of CNS germinoma: pineoblastoma, primitive neuroectodermal tumors, medulloblastoma, lymphoma, pituitary adenoma, atypical teratoid/rhabdoid tumor, Langerhans cell histiocytosis, and gliomas. These findings demonstrate that NANOG is a sensitive and specific marker of CNS germinoma. Compared with other currently used markers, NANOG may have superior diagnostic characteristics and can facilitate identification of germinomas in minute surgical biopsies commonly obtained from these tumors. These findings also suggest a potential biologic role for NANOG in maintenance of CNS germinoma.

Adolescent↗
PubMedDate not supplied

Neoplasms of the spinal cord and filum terminale: radiologic-pathologic correlation.

Intramedullary spinal cord neoplasms are rare, accounting for about 4%10% of all central nervous system tumors. Despite their rarity, these lesions are important to the radiologist because magnetic resonance (MR) imaging is the preoperative study of choice to narrow the differential diagnosis and guide surgical resection. On contrast materialenhanced MR images, intramedullary spinal tumors almost always manifest as expansion of the spinal cord and show enhancement. Syringohydromyelia and cystic lesions are frequently associated with intramedullary tumors. Nontumoral cysts tend to be located at the poles of the tumors and do not enhance on contrast-enhanced MR images, whereas cysts within the substance of the tumor are considered tumoral cysts and typically demonstrate peripheral enhancement. Spinal cord ependymomas are the most common type in adults, and cord astrocytomas are most common in children. Both entities constitute up to 70% of all intramedullary neoplasms. A central location within the spinal cord, presence of a cleavage plane, and intense homogeneous enhancement are imaging features that favor an ependymoma. Intramedullary astrocytomas are usually eccentrically located within the cord, are ill defined, and have patchy enhancement after intravenous contrast material administration. Even with these characteristics, it may not be possible to differentiate these two entities on the basis of imaging features alone. Cord hemangioblastomas are the third most common type of intramedullary spinal tumor. Gangliogliomas commonly extend over more than eight vertebral segments. Paragangliomas and primitive neuroectodermal tumors have an affinity for the filum terminale and cauda equina. Other spinal cord tumors include metastatic disease, which is characterized by prominent cord edema for the size of the enhancing portion, and primary lymphoma.

Cauda Equina↗
PubMed1997

Effective chemotherapy for advanced CNS embryonal tumors in adults.

PURPOSE: Embryonal tumors of the CNS include, among others, medulloblastoma, cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors (PNETs). Almost all data on the treatment of embryonal CNS tumors are derived from the pediatric population, since these tumors are uncommon in adulthood. The purpose of this study was to examine the rate and duration of response to chemotherapy of advanced embryonal CNS tumors in adults. PATIENTS AND METHODS: We retrospectively studied all adult (> 18 years of age) patients with advanced embryonal tumors of the CNS who received chemotherapy at our institution between 1976 and 1994. Seventeen consecutive patients were treated with regimens that contained either nitrosourea or cisplatin or both sequentially, with no patients having received the combination of nitrosourea and cisplatin concurrently. RESULTS: In patients who received cisplatin-based chemotherapy, responses were observed in 84.5% (26% complete response [CR] rate), 10.5% remained stable, and 5% progressed. The median time to progression was 18 months for patients who had a CR, 6 months for those with partial response (PR), and 10 months for stable patients. Among patients who received nitrosourea-based chemotherapy, PR was observed in 27%, 36.5% remained stable, and 36.5% progress. The median time to progression was 6 months for patients who had a PR and 6.5 months for stable patients. CONCLUSION: In adults with advanced embryonal CNS tumors, conventional-dose intravenous cisplatin-based chemotherapy regimens are able to produce responses in the majority of the patients (84.5%), even as second- or third-line regimens. Nitrosourea-based regimens less frequently produce responses (27%).

Adolescent↗
PubMed2000

Type-B-IIIa hip rotationplasty: an alternative operation for the treatment of malignant tumors of the femur in early childhood.

BACKGROUND: The biological plasticity of the cartilaginous proximal part of the tibia in children makes it possible to use the tibia to reconstruct the lower extremity after excision of a sarcoma of the thigh. A type-B-IIIa rotationplasty is an alternative to prosthetic replacement in very young children who have a malignant tumor of the femur that requires extensive resection. METHODS: A type-B-IIIa rotationplasty was done in eight patients who had a femoral tumor: four had a Ewing sarcoma; three, an osteosarcoma; and one, a primitive neuroectodermal tumor. The ages ranged from two years and eight months to ten years and six months at the time of the procedure. RESULTS: All eight patients were able to bear full weight and had a good range of motion of the hip joint at a median of five years and one month (range, two years and four months to eight years) postoperatively. They also were able to participate in sports activities. Radiographs and magnetic resonance imaging studies confirmed that the lateral part of the tibial plateau had remodeled to form a structure that resembled a developing femoral head. Seven patients were operated on only once, and a second hospital stay was not necessary. The remaining patient had a prolonged hospitalization for revision of the wound. CONCLUSIONS: As an alternative to amputation or an extendable tumor prosthesis, a type-B-IIIa rotationplasty offers not only a better functional result but also biological reconstruction. Placement of the cartilaginous head of the tibia into the acetabulum permits development of a new femoral head. Thus, not only is the foot preserved as a functional knee joint but a newly formed hip joint develops as well.

Arthroplasty, Replacement, Hip↗
PubMed2001

Neuroectodermal and neuroendocrine tumors principally seen in children.

Neuroectodermal tumors comprise a large proportion of childhood neoplasms. Neuroblastic tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma, are the most frequent extracranial solid cancers of childhood, occurring primarily in infants and toddlers. Primitive neuroectodermal tumors, including Ewing sarcoma and peripheral neuroepitheliomas, occur most frequently in older children and adolescents, and as pediatric sarcomas are second in frequency only to rhabdomyosarcomas. Rarer neuroectodermal tumors include desmoplastic small cell tumors, esthesioneuroblastomas, and melanotic neuroectodermal tumors, the first two entities occurring as rather site-specific lesions in the abdomen and nose, respectively. Diagnosis can be difficult due to the undifferentiated nature of many of these cancers, but ancillary studies, including electron microscopy, immunohistochemistry, cytogenetics, and molecular genetics, enhance their recognition. The molecular nature of childhood neuroectodermal tumors is as diverse as their histology, ranging from the fusion genes characterizing the Ewing sarcoma family of tumors to the proto-oncogene amplification seen in aggressive neuroblastomas.

Adolescent↗
PubMed1989

Biological aspects of brain tumors in infancy and childhood.

Notwithstanding the definitive systematization of the clinical features of childhood brain tumors, many biological laws governing this vast area of pathology still escape us. There are no sure explanations for the fickleness of supratentorial/subtentorial distribution in fetal life and in the first 15 years of life--something not found in later years. Another focus of discussion is the tendency of brain tumors in infancy to concentrate along the midline due to the fact that most infantile neuroectodermal tumors arise from the phylogenetically older structures of the CNS (periventricular regions, brainstem, cerebellum), in contrast to tumors of adulthood. Neuroepithelial tumors, much more frequent in childhood than in later years, exhibit substantial histological differences in infancy: mixed gliomas and primitive neuroectodermal tumors (not otherwise specified, or with astrocytic, ependymal, oligodendrocytic...cells) are the best examples. As to the question of whether a given oncotype exhibits different biological behavior according to patient age, there is no single answer: some malignant tumors (medulloblastomas, ependymomas, neuroblastomas) are more aggressive in infancy, in line with Collins' law, while others (optic gliomas) offer a better prognosis in younger patients. The most peculiar and disquieting aspect of brain tumors in infancy/childhood, however, is what emerged from a recent epidemiological survey. The survey was conducted on the close relatives of a boy with a brain tumor from point of view of a possible "second malignancy" in this boy. Since a brain tumor is a rare occurrence in the very young, it may signal heightened susceptibility to malignancy in the individual, extending to other tumors in the patient himself and even to other members of his family.

Brain↗
PubMedDate not supplied

Molecular genetic studies in medulloblastomas: evidence for tumor suppressor genes at the chromosomal regions 1q31-32 and 17p13.

BACKGROUND: Medulloblastoma represents a common primitive neuroectodermal tumor of the cerebellum, the molecular pathogenesis of which has not been identified. Previous cytogenetic observations disclosed aberrations of chromosome 1 and 17 in medulloblastomas. In the present study, we have molecularly characterized the affected chromosomal segments. PATIENTS AND METHODS: A panel of microsatellites on chromosomes 1 and 17 was used to assess allelic loss in 30 medulloblastomas and to characterize putative tumor suppressor loci. RESULTS: 36% of the medulloblastomas showed an interstitial loss of heterozygosity (LOH) on chromosome 1q. The common region of overlap was mapped between D1S1604 and D1S237 and included the locus F13B in the chromosomal region 1q31-q32.1. None of the MBs exhibited LOH of the telomeric portion of chromosome 1p which has been associated with several other human malignancies. 47% of the tumors showed LOH on chromosome 17p with a common region of overlap at 17p13.3. The lissencephaly gene 1 (LIS-1) was excluded as a candidate gene in this region. CONCLUSION: Our data strongly suggest the involvement of putative tumor suppressor genes located on the chromosome arms 1q and 17p in the molecular pathogenesis of medulloblastoma.

Adolescent↗
PubMed1994

Stereotactic radiosurgery for recurrent gliomas.

BACKGROUND: The treatment of recurrent gliomas is palliative; however, the local pattern of tumor recurrence permits retreatment with single fraction, high dose stereotactic radiotherapy or radiosurgery (RS). METHODS: Twenty patients (median Karnofsky performance status, 80), aged 8-62 years with recurrent gliomas, were treated with RS after failing adjuvant therapy. Tumor histologies included glioblastoma multiforme (5), anaplastic astrocytoma (10), fibrillary astrocytoma (4), and primitive neuroectodermal tumor (1). Tumor volumes ranged from 3-53.5 cc, with a median of 17 cc. RESULTS: Seven early and one late radiation complication were seen. All seven early radiation complications were due to raised intracranial pressure and resolved in all but one patient who died. Median follow-up in 19 evaluable patients was 8 months (range, 2-29 months). Fourteen patients died from progressive tumor (median survival, 7 months). Five patients, four with recurrent tumor, were alive (median follow-up, 19 months) with a median time-to-tumor progression of 9 months. CONCLUSIONS: Radiosurgery demonstrates modest efficacy with acceptable toxicity in selected patients with recurrent gliomas and warrants further investigation.

Adolescent↗
PubMed1995

Central neuronal tumors in childhood: relationship to dysplasia.

A survey of 1,500 brain tumors at The Hospital for Sick Children in Toronto reveals that about 20-25% of tumors demonstrate some form of neuronal differentiation. At one end of the spectrum are the well-defined ganglionic tumors, sometimes difficult to differentiate from cortical dysplasia. At the other extreme are primitive neuroectodermal tumors with neuronal differentiation often confined to immunohistochemical observations. Of the total number of tumors, approximately 5% have a definitive ganglionic component, the majority being ganglioglioma, and others include dysembryoplastic neuroepithelial tumor, infantile ganglioglioma, paraganglioma, central neurocytoma, and gangliocytoma. Some tumors such as subependymal giant cell tumor associated with tuberous sclerosis occasionally have evidence of neuronal differentiation with immunoreactivity with antisera to neuron-specific enolase and negativity with antisera to GFAP. In children with epilepsy, improved brain imaging has identified lesions which on examination following temporal lobectomy show varying degrees of cortical dysplasia. At this site, there is also a high incidence of gangliogliomas. Is there a relationship between cortical dysplasia and neuronal tumors? Following a primary induction event during development, embryonal dysplasia and/or neoplasia may occur. The lesion may be malformative as in unilateral megalencephaly, hamartomatous as in tuberous sclerosis, neoplastic as in congenital tumors, or a combination of malformative and neoplastic.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed2002

Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue.

Pediatric small round cell tumors still pose tremendous diagnostic problems. In difficult cases, the ability to detect tumor-specific gene fusion transcripts for several of these neoplasms, including Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumor (DSRCT) using reverse transcriptase-polymerase chain reaction (RT-PCR), can be extremely helpful. Few studies to date, however, have systematically examined several different tumor types for the presence of multiple different fusion transcripts in order to determine the specificity and sensitivity of the RT-PCR method, and no study has addressed this issue for formalin-fixed material. The objectives of this study were to address the specificity, sensitivity, and practicality of such an assay applied strictly to formalin-fixed tissue blocks. Our results demonstrate that, for these tumors, the overall sensitivity for detecting each fusion transcript is similar to that reported in the literature for RT-PCR on fresh or formalin-fixed tissues. The specificity of the assay is very high, being essentially 100% for each primer pair when interpreting the results from visual inspection of agarose gels. However, when these same agarose gels were examined using Southern blotting, a small number of tumors also yielded reproducibly detectable weak signals for unexpected fusion products, in addition to a strong signal for the expected fusion product. Fluorescence in situ hybridization (FISH) studies in one such case indicated that a rearrangement that would account for the unexpected fusion was not present, while another case was equivocal. The overall specificity for each primer pair used in this assay ranged from 94 to 100%. Therefore, RT-PCR using formalin-fixed paraffin-embedded tissue sections can be used to detect chimeric transcripts as a reliable, highly sensitive, and highly specific diagnostic assay. However, we strongly suggest that the final interpretation of the results from this assay be viewed in light of the other features of the case, including clinical history, histology, and immunohistochemistry, by the diagnostic pathologist. Additional studies such as FISH may be useful in clarifying the nature of equivocal or unexpected results.

Blotting, Southern↗
PubMed2006

Expression of SOX9 and SOX10 in central neuroepithelial tumor.

The SOX group E transcription factors play an integral role in the specification and differentiation of astrocytes and oligodendrocytes. We have examined the pattern of expression for SOX9 and SOX10 in primary brain tumors by immunohistochemistry. Pediatric and adult high grade tumors display strong nuclear staining for both SOX9 and SOX10 (astrocytic, oligodendroglial and primitive neuroectodermal tumors). In comparison pediatric pilocytic astrocytoma express much less SOX9 and SOX10. Reactive astrogliosis is characterized by an increase of SOX9 only.

Adolescent↗