Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours.

INTRODUCTION: The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the -1p/-19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy. METHODS: Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation (exons 5-8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33). RESULTS: 1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student's t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The -1p/-19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss. CONCLUSION: rCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the -1p/-19q genotype.

Meningeal melanocytoma.

BACKGROUND: Meningeal melanocytoma was first described over 30 years ago as a benign tumour derived from melanocytes. Since then, data suggest that its mode of presentation is variable without a clear predilection for any particular site in the neuroaxis. Although classified as a benign tumour, this tumour shows a marked tendency towards reduced survival following subtotal resection and transformation over time in a limited number to malignant melanoma. Incomplete resection of these tumours without postoperative radiotherapy has only a 42% 5-year survival rate. Its classification as a benign tumour should be revised, given the published 5-year survival data. ILLUSTRATIVE CASE: We report a fatal case of meningeal melanocytoma in the cerebello-pontine angle in a 10-year-old child. This case exemplifies the vascular nature of these lesions even with minimal vascular blush on angiography. An updated literature search is presented, the results of which highlight the need for close follow-up and adjuvant treatment following subtotal resection.

Traumatic cerebral aneurysm formation following ventriculoperitoneal shunt insertion.

INTRODUCTION: Iatrogenic intracranial aneurysms are rare in children. CASE REPORT: A 15-year-old girl presented in coma with a fixed dilated left pupil six weeks following removal of a long-standing left-sided ventriculoperitoneal shunt. Computed tomography (CT) and cerebral angiography revealed a left temporoparietal intracerebral haemorrhage with a fusiform distal middle cerebral artery aneurysm. The patient underwent image-guided localisation of the aneurysm to enable evacuation of the haemorrhage and resection of the fusiform aneurysm. CONCLUSION: A high index of suspicion is required for diagnosis and early treatment to prevent unnecessary morbidity and mortality.

Molecular pathology and clinical characteristics of oligodendroglial neoplasms.

To evaluate the role of molecular genetics in the routine clinic, we investigated allelic imbalance at 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation in 100 oligodendroglial neoplasms diagnosed at a single treatment center between 2000 and 2003. The -1p/-19q genotype, seen in 64, 34, 77, and 30% of OII, OAII, OIII, and OAIII respectively, was inversely related to p53 mutation and 17p13 loss. Genotype was unrelated to tumor location and could not distinguish high-grade tumors that presented de novo from those that progressed from a previous lower grade malignancy. Presentation with seizures was more common in cases with the -1p/-19q genotype, and these remained stable for longer before treatment. In longitudinal samples, 74% retained their initial histological differentiation, whereas 29% showed new genetic alterations, the -1p/-19q genotype being acquired in three cases. Loss of 1p36 and 19q13, 17p13, chromosome 10, and p53 mutation were significantly associated with survival from presentation in Kaplan-Meier analysis (p < 0.01), and loss of 1p36 and 19q13 and loss of 17p13 retained significance in multivariate analysis. In this recently diagnosed unselected series, clinical differences in tumors with and without the -1p/-19q genotype support a genetic approach to aid diagnosis and prognostication for oligodendroglial neoplasms.

Correlation of molecular genetics with molecular and morphological imaging in gliomas with an oligodendroglial component.

PURPOSE: Since the recognition that oligodendrogliomas may be chemosensitive, their diagnosis and clinical management has become highly controversial. Histopathology diagnosis remains challenging and new tools such as molecular genetics or molecular imaging require evaluation. EXPERIMENTAL DESIGN: In a single-center, population-based prospective study, allelic imbalance in chromosomes 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 has been investigated in 19 oligodendroglioma WHO grade 2 (OII), 20 oligoastrocytoma WHO grade 2 (OAII), 8 oligodendroglioma WHO grade 3 (OIII), and 12 oligoastrocytoma WHO grade 3 (OAIII), and compared with pretherapy histopathology, computed tomography and/or magnetic resonance (CT and/or MR), [fluorine-18]fluoro-2-deoxyglucose (18F-FDG), and thallium-201 single-photon emission computed tomography (201Tl SPECT). RESULTS: In 50 cases, 18F-FDG uptake correlated with 201Tl uptake; however, 8 cases had increased 201Tl uptake but were hypometabolic for 18F-FDG, and 1 case was hypermetabolic with normal 201Tl uptake. Sixteen cases enhanced on CT/MR but failed to show 201Tl uptake; and 2 low-grade non-enhancing oligodendrogliomas had increased 201Tl uptake. Increased metabolism was more likely in high-grade cases, with 201Tl uptake more strongly correlated with grade than was 18F-FDG uptake. Tumors with 1p/19q loss were more likely to show increased 201Tl uptake and, to a lesser degree, increased 18F-FDG uptake than those without these losses. Elevated metabolism in 28% of low-grade tumors was significantly more common in tumors with 1p/19q loss, and increased uptake of both 18F-FDG and 201Tl in low-grade cases was found only in those with 1p/19q loss. CONCLUSIONS: In this study, dissociation of uptake of contrast agents and radiotracers suggests independent deregulation of the blood-brain barrier breakdown and metabolism during disease progression of oligodendroglial neoplasms, and the association of elevated metabolism with 1p/19q loss, particularly in low-grade tumors, may have implications for clinical management.

Phenotype versus genotype in gliomas displaying inter- or intratumoral histological heterogeneity.

PURPOSE: Molecular classification of gliomas is becoming increasingly important clinically as an adjunct to histopathological diagnosis. Whereas histological heterogeneity of gliomas is well recognized, less is known of the relationship between histological heterogeneity and genetic alterations. Our objective was to investigate the relationship between genotype and phenotype for markers of potential clinical utility in histologically heterogeneous gliomas. EXPERIMENTAL DESIGN: We have used laser capture microdissection to sample the various histological phenotypes present in 42 tumors from 25 glioma cases with either inter- or intratumoral histological heterogeneity, and multiple simultaneous PCR amplification of microsatellite markers and capillary electrophoresis to determine allelic imbalance in chromosomes 1p, 19q, 17p, 10p, and 10q. RESULTS: Loss of 1p36 and 19q13 was seen only in oligodendroglial histology in 7 of 13 oligodendrogliomas. 17p13 loss was found in 14 of 41 tumors in astrocytic, oligoastrocytic, oligodendroglial, and glioblastomatous histologies. Chromosome 10 loss was seen in all of the high-grade histologies in 7 of 7 glioblastomas with an oligodendroglial component and in 1 of 5 low-grade oligodendroglial regions present within high-grade tumors. Seven tumors from 5 cases had no detectable losses of any markers investigated. In 13 tumors with intratumoral heterogeneity, identical genetic losses were present in all areas of histological differentiation. Additional losses were seen in some but not all of the histologies within 2 tumors and were associated with progression in 3 cases. CONCLUSIONS: The gliomas in this study were more homogeneous in their genotype than their histological phenotype with regions of differing histological subtype indistinguishable by the genetic markers investigated, supporting a monoclonal origin of these tumors.

Papillary endothelial hyperplasia associated with cortical dysplasia.

We report a unique case of papillary endothelial hyperplasia (PEH) presenting as a subcortical mass lesion intimately associated with focal cortical dysplasia (CD) and consider a possible causal relationship. A 6-year old girl presented with a 6-month history of a painless, frontoparietal skull "bump" associated with slowly progressive localised bossing followed by a 4-month history of absence attacks. Magnetic resonance imaging (MRI) revealed an adjacent parietal enhancing mass lesion beneath abnormal appearing cortex. A haemorrhagic vascular lesion with histology consistent with that of papillary endothelial hyperplasia was completely resected. Biopsies of the adjacent cortex showed CD. The patient has been symptom free post-surgery for 12 months with no MRI evidence of recurrence. Intracranial PEH is very rare and, in contrast to extracranial examples, half of the reported cases lacked a demonstrable vascular origin. Given that CD may be associated with intrinsic capillary hypervascularity, vascular malformations and tumours (e.g. dysembryoplastic neuroepithelial tumour) of a potential hypervascular or haemorrhagic nature, the association between PEH and CD may not be incidental. The abnormal vascularity not uncommonly found in CD may predispose to haemorrhage and/or thrombosis, the organisation of which may rarely be complicated by PEH. Alternatively, PEH and CD may both represent local, independent complications of a pre-existing vascular event or trauma.

Selecting people randomly.

KIE: This article considers what justification can be found for selecting randomly and in what circumstances it applies, including that of selecting patients to be treated by a scarce medical procedure. The author demonstrates that balancing the merits of fairness, common good, equal rights, and equal chance as they apply in various situations frequently leads to the conclusion that random selection may not be the most appropriate mode of selection. Broome acknowledges that, in the end, we may be forced to conclude that the only merit of random selection is the political one of guarding against partiality and oppression.^ieng