A phase II study of preradiotherapy chemotherapy followed by hyperfractionated radiotherapy for newly diagnosed high-risk medulloblastoma/primitive neuroectodermal tumor: a report from the Children's Oncology Group (CCG 9931).

Purpose: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT).

Methods And Materials: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm(2) postoperative residual disease, and all patients with noncerebellar PNET.

Patterns of treatment failure in infants with primitive neuroectodermal tumors who were treated on CCG-921: a phase III combined modality study.

Purpose: To analyze patterns of treatment failure in infants with primitive neuroectodermal tumors (PNETs) who were treated primarily with chemotherapy in a large multi-institutional study.

Materials And Methods: Sixty-five prospectively staged patients with PNET confirmed by central pathology review, who were 18 months or younger were treated on Children's Cancer Group Study 921 (CCG-921) primarily with chemotherapy. Forty-six patients had posterior fossa (PF) primary tumors and 19 patients had supratentorial (ST) primaries.

INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma.

Central nervous system atypical teratoid/rhabdoid tumor (AT/RT) and choroid plexus carcinoma (CPC) are rare, highly malignant tumors that predominantly arise in infants and young children. Overlapping clinical, histologic, ultrastructural, or immunophenotypic features may obscure the diagnosis in some cases. AT/RT is characterized by deletions and/or mutations of the INI1 tumor-suppressor gene on chromosome band 22q11.

Recurrent central nervous system medulloepithelioma: response and outcome following marrow-ablative chemotherapy with stem cell rescue.

Medulloepithelioma is a rare primitive neuroectodermal tumor of the central nervous system usually developing in childhood, displaying highly malignant behavior, with early progression or recurrence. Once a recurrence develops, death reportedly follows with invariable rapidity. The purpose of this study was to evaluate the efficacy of high-dose, marrow-ablative chemotherapy with autologous hemopoietic stem cell rescue in the treatment of recurrent central nervous system medulloepithelioma.

Losses of chromosomes 1p and 19q are rare in pediatric oligodendrogliomas.

Pediatric oligodendrogliomas are rare neoplasms and have not been characterized extensively either pathologically or genetically. Given the recent interest in the significance of chromosomal losses in predicting the clinical course and in establishing uniform diagnoses of adult oligodendrogliomas, we reviewed the pathological and clinical features of a series of pediatric oligodendrogliomas and determined their 1p and 19q status using fluorescence in situ hybridization. Of 19 tumors originally diagnosed as oligodendroglioma, 7 were oligodendroglioma, 3 were anaplastic oligodendroglioma, 3 were oligoastrocytoma, and 6 were reclassified.

Patterns of failure in supratentorial primitive neuroectodermal tumors treated in Children's Cancer Group Study 921, a phase III combined modality study.

Purpose: To analyze the patterns of failure in patients with supratentorial primitive neuroectodermal tumors (ST-PNETs) treated with combined modality therapy in a large, randomized, multi-institutional study.

Methods And Materials: A total of 44 prospectively staged patients with ST-PNET confirmed by central pathology review were treated in the Children's Cancer Group Study 921, which compared two chemoradiotherapy regimens. The patterns of initial sites of failure were analyzed.

Near complete surgical resection predicts a favorable outcome in pediatric patients with nonbrainstem, malignant gliomas: results from a single center in the magnetic resonance imaging era.

Background: Because few reports on outcome in patients with pediatric malignant gliomas during the magnetic resonance imaging era were available, the authors studied the outcomes of children with these tumors at their institution.

Methods: The medical records of 39 patients with nonbrainstem, malignant gliomas who were treated at the Hospital of the University of Pennsylvania/Children's Hospital of Philadelphia between February 1, 1989 and December 31, 2000 were reviewed retrospectively. Magnetic resonance imaging was used to assess tumors at presentation and at follow-up.

Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry.

Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is an extremely rare and aggressive tumor of early childhood. The poor outcome with conventional infant brain tumor therapy has resulted in a lack of clear treatment guidelines. A registry has been established to create an outcomes database and to facilitate biology studies for this tumor.

Double immunolabeling of central nervous system atypical teratoid/rhabdoid tumors.

The central nervous system atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant tumor with a heterogeneous immunohistochemical profile and with some morphologic similarity to central nervous system primitive neuroectodermal tumors (PNET). Although several studies have investigated double immunolabeling in PNET, we are aware of no studies of double labeling of ATRT. A total of 10 ATRT from surgical and consultation materials at the Children's Hospital of Philadelphia were selected and stained for a variety of antigens using indirect immunofluorescence to detect single and double labeling.

Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms.

Atypical teratoid/rhabdoid tumor (AT/RT) may be misdiagnosed as primitive neuroectodermal tumor/medulloblastoma (PNET) and occasionally as other tumors. Molecular genetic analysis of AT/RT demonstrates deletion and mutation of the hSNF5/INI1 gene in most cases, with decreased or absent expression at the RNA or protein level. Immunohistochemistry with an antibody to INI1 was performed to determine whether this would be a sensitive and specific means of assessing INI1 loss in pediatric brain tumors.

Technical communication: rationale and technique for examination of nervous system in suspected infant victims of abuse.

Most victims of fatal child abuse are under the age of 2 years and have a fairly typical pattern of injuries that involve the brain and spinal cord. Documenting these injuries in a systematic fashion is of paramount importance in establishing the cause and manner of death. Although the importance of recognizing these injuries is widely understood, there are few guidelines for the optimal examination of the central nervous system to document these changes.

Craniospinal radiation in the treatment of biopsy-proven intracranial germinomas: twenty-five years' experience in a single center.

Purpose: The optimal treatment for intracranial germinomas remains controversial. We report on our 25-year experience using craniospinal irradiation (CSI) for this disease.

Methods And Materials: Between September 1976 and May 2001, 39 patients with biopsy-proven intracranial germinomas seen at the Children's Hospital of Philadelphia/Hospital of the University of Pennsylvania received CSI.

Prognostic limitations of the Daumas-Duport grading scheme in infratentorial neuroglial tumors in children.

The Daumas-Duport grading scheme (DDGS) utilizes four histologic features in an additive method (grade 1 if none present, grade 2 if only one is present, etc.). Its efficacy in achieving prognostically homogeneous groups of childhood infratentorial neuroglial tumors and its concordance with World Health Organization (WHO) diagnoses has not been evaluated.

Surgery with or without radiation therapy in the management of craniopharyngiomas in children and young adults.

Purpose: The optimal management of craniopharyngiomas remains controversial, especially in children and young adults. This study reports a single institution's experience with such patients.

Methods And Materials: Between 1974 and 2001, 76 patients were treated for craniopharyngioma at the Children's Hospital of Philadelphia and the Hospital of University of Pennsylvania (HUP).

Loss of caspase-8 protein expression correlates with unfavorable survival outcome in childhood medulloblastoma.

Purpose: Escaping apoptosis is a hallmark of cancer. In medulloblastoma (MB) cell lines, resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis was recently shown to correlate with loss of caspase-8 mRNA expression, because of aberrant gene methylation (M. A.

In vivo pyruvate detected by MR spectroscopy in neonatal pyruvate dehydrogenase deficiency.

We present a unique finding of an elevated level of pyruvate at 2.37 ppm revealed by in vivo MR spectroscopy of a female neonate. Low fibroblast pyruvate dehydrogenase (PDH) complex activity subsequently confirmed a diagnosis of PDH deficiency.

Expression of alpha-, beta-, and gamma-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.

Correction of hindbrain herniation and anatomy of the vermis after in utero repair of myelomeningocele in sheep.

Background/purpose: In utero repair of myelomeningocele (MMC) in humans spares distal neurologic function, reverses the hindbrain herniation component of the Arnold-Chiari II malformation (ACM), and reduces the rate of postnatal shunt placement. The authors hypothesized that extravasation of cerebrospinal fluid (CSF) from the lumbar spinal cord results in herniation. This hypothesis was tested by assessing the impact of a spinal cord myelotomy on hindbrain anatomy in fetal sheep.

Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors.

Germ-line and acquired mutations of the hSNF5/INI1 tumor suppressor gene have been reported in central nervous system (CNS), renal, and soft-tissue rhabdoid tumors. The present study was designed to compare the types of INI1 alterations among tumors from diverse anatomical sites and identify mutation hot spots. Fluorescence in situ hybridization and PCR-based microsatellite, heteroduplex, and sequence analysis were used to characterize chromosome 22 deletions and INI1 mutations among 100 primary rhabdoid tumors.

Clinical and survival covariates of eight classes of childhood supratentorial neuroglial tumors.

Background: In the current study, the authors investigated clinical, surgical, and histologic characteristics (covariates) and their interactions in eight previously identified classes of childhood supratentorial neuroglial tumors. The classes resulted from 5 factor score profiles on 703 supratentorial neuroglial tumors in the Childhood Brain Tumor Consortium database.

Methods: The Cox proportional models were used to identify class survival covariates.

Incidence and trends in pediatric malignancies medulloblastoma/primitive neuroectodermal tumor: a SEER update. Surveillance Epidemiology and End Results.

Background: It has been suggested that cerebellar medulloblastoma (M) and primitive neuroectodermal tumors (PNET) arising elsewhere in the nervous system, represent a single entity (M/PNET), although this concept is controversial. Cancer registries permit population-based description of cases reported as medulloblastoma, those reported as PNET and description of the aggregate, M/PNET.

Procedure: We reviewed the 768 cases of M/PNET (633 diagnosed medulloblastoma and 135 diagnosed PNET) among persons under 20 years of age in the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database.

Atypical teratoid/rhabdoid tumor of the central nervous system: report on workshop.

Childhood atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) is a recently described entity. Diagnosis is based on distinctive light microscopy and immunohistochemical findings, coupled with molecular genetic analysis. Most AT/RTs demonstrate monosomy 22 or deletions of chromosome band 22q11 with alterations of the hSNF5/INI1 gene.

Orbital neural-glial hamartoma associated with a congenital tonic pupil.

Tonic pupils in children are rare, and only a handful of reports exist in the literature. We present the case of an orbital neural-glial hamartoma in an infant with a congenital tonic pupil and no proptosis. We have previously described this association in another child.

The WHO classification of tumors of the nervous system.

The new World Health Organization (WHO) classification of nervous system tumors, published in 2000, emerged from a 1999 international consensus conference of neuropathologists. New entities include chordoid glioma of the third ventricle, cerebellar liponeurocytoma, atypical teratoid/rhabdoid tumor, and perineurioma. Several histological variants were added, including tanycytic ependymoma, large cell medulloblastoma, and rhabdoid meningioma.