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Purpose: To review interpathologist diagnosis variability and survival of children treated for either anaplastic mixed glioma (AMG) or anaplastic oligodendroglioma (AO) with surgery, irradiation and chemotherapy., Patients and Methods: Two hundred and fifty patients with an institutional diagnosis of malignant glioma were enrolled on Children's Cancer Group CCG-945 between 1985 and 1991, and administered vincristine during involved field radiotherapy, then six cycles of prednisone, lomustine and, vincristine; or two cycles of "eight-drugs-in-one-day" (8-in-1) chemotherapy then involved-field radiotherapy followed by six cycles of 8-in-1 chemotherapy. Central review of institutional pathology was post hoc by five experienced neuropathologists., Results: Twenty-six children had institutional diagnoses of AMG and four had AO. Complete resection and cerebral tumor location was associated with better overall survival (OS) in patients with institutional diagnoses of AMG. However, central review established that only nine of 26 children had AMG: either mixed oligoastrocytoma (MOA) or anaplastic mixed oligoastrocytoma (AOA) and only one had AO. Central review revealed five more patients with AMG, but none with AO. Institutional and CCG central review diagnoses of AMG or AO had poor Jaccard reliabilities of 0.29 and 0.25 respectively. Five-year EFS and OS for five children with centrally confirmed MOA was 50 +/- 20%, with four centrally confirmed AOA was 37.5 +/- 17%. After central review, small samples made tests for differences in survival between regimes impossible., Conclusion: Diagnosis of these tumors is challenging, with only 35% of institutional diagnoses confirmed for AMG and 25% for AO, and survival among children with these tumors is poor, despite intensive therapy. This suggests reliable diagnostic markers and new therapeutic approaches are needed.

Purpose: To evaluate academic and behavioral outcome in radiated survivors of posterior fossa (PF) tumors., Patients and Methods: Fifty-three patients (36 males) treated for malignant PF tumors were seen for evaluation of academics and/or behavioral functioning. Forty-six patients were treated for medulloblastoma, and seven patients were treated for ependymoma. Fourteen patients were treated with reduced-dose cranial radiation, and 34 patients were treated with standard-dose cranial radiation (dose was not available for four patients). All patients received an additional boost to the PF. One patient was treated with PF radiation only. Standardized achievement tests and behavioral questionnaires were administered at different times after diagnosis for each child. First, the influence of demographic and medical variables on outcome was examined. Second, the rate of change in scores was determined using mixed model regression for patients seen for serial assessment., Results: The presence of hydrocephalus was related to poorer academics, but outcome was not related to radiation dose, extent of surgery, or treatment with chemotherapy. Younger age predicted poor reading ability and lower parent rating of academic achievement. Children's performance declined for spelling, mathematics, and reading. Significant declines were also evident in parent and teacher's ratings of academic ability. Behavioral functioning was generally not related to medical and demographic variables, and few clinically significant problems in externalizing behavior were evident. Increases in social and attention problems emerged over time., Conclusion: Cranial radiation is associated with declines in academic ability, social skills, and attention. However, neither psychological distress nor behavior problems were a significant concern for this sample.

Tumor suppressor gene "knockout" models would predict that children who present with hemangioblastoma are likely to harbor germline mutation of the von Hippel-Lindau gene. We screened 6 pediatric patients with cerebellar hemangioblastoma for germline or somatic mutations of the von Hippel-Lindau gene. Two had prior clinical manifestations of von Hippel-Lindau disease and, as expected, had germline von Hippel-Lindau gene mutations. Four children with solitary hemangioblastoma did not have a detectable germline deletion, rearrangement, or point mutation in their von Hippel-Lindau gene, and tumor specimens in 3 of these 4 showed no somatic von Hippel-Lindau allelic loss. Solitary cerebellar hemangioblastoma in children does not predict a germline or somatic mutation in the von Hippel-Lindau tumor suppressor gene. The tumorigenesis of hemangioblastoma in younger patients may differ from that in adults, and may involve a molecular process unrelated to the von Hippel-Lindau tumor suppressor pathway.

Hermann von Helmholtz's distinction between "pure intuitive" and "physical" geometry must be counted as the most influential of his many contributions to the philosophy of science. In a series of papers from the 1860s and 70s, Helmholtz argued against Kant's claim that our knowledge of Euclidean geometry was an a priori condition for empirical knowledge. He claimed that geometrical propositions could be meaningful only if they were taken to concern the behaviors of physical bodies used in measurement, from which it followed that it was posterior to our acquaintance with this behavior. This paper argues that Helmholtz's understanding of geometry was fundamentally shaped by his work in sense-physiology, above all on the continuum of colors. For in the course of that research, Helmholtz was forced to realize that the color-space had no inherent metrical structure. The latter was a product of axiomatic definitions of color-addition and the empirical results of such additions. Helmholtz's development of these views is explained with detailed reference to the competing work of the mathematician Hermann Grassmann and that of the young James Clerk Maxwell. It is this separation between 1) essential properties of a continuum, 2) supplementary axioms concerning distance-measurement, and 3) the behaviors of the physical apparatus used to realize the axioms, which is definitive of Helmholtz's arguments concerning geometry.

Objective: A group of choroid plexus tumors fit the cellular criteria for choroid plexus papilloma (CPP) except for invasion into the adjacent parenchyma, with associated loss of the normal villus architecture at the site of invasion. These tumors retain a benign cellular appearance. In the existing literature, it is unclear whether these tumors are classified as choroid plexus carcinomas or as CPPs. In our experience, although evidence of invasion is present, these tumors tend to exhibit benign behavior. We suggest that stromal invasion of this type remains consistent with a benign clinical course, although surgical results may demonstrate higher morbidity rates, given the invasive nature of the tumors. The failure to classify these tumors as CPPs may explain some of the variability in outcomes reported for various studies., Methods: To study this question, clinical and histological data for children diagnosed with CPPs (either with or without stromal invasion) between 1985 and 1995 were examined. Only cases with pre- and postoperative magnetic resonance imaging data were included in the series., Results: A total of 12 patients with CPPs were identified, with 4 tumors being notable for stromal invasion. After gross total tumor removal, none of the eight children with CPPs received adjuvant therapy at our institution; all are alive without evidence of tumor recurrence after surgical excision (mean, 108 mo). Of the four patients with stromal invasion, three underwent gross total resection. The one patient who underwent subtotal resection received chemotherapy at another facility. All four of these patients are alive, after a mean of 100 months of follow-up monitoring., Conclusion: It is recommended that CPPs with a benign cellular appearance but with evidence of local parenchymal invasion and loss of the normal villus architecture at the site of invasion be classified as CPPs. Patients with these tumors respond to surgical therapy alone, without the need for adjuvant treatment.