Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma. A study of paraffin-embedded sections.

Comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), polymerase chain reaction-based microsatellite analysis, and p53 sequencing were performed in paraffin-embedded material from 18 oligodendrogliomas and histologically similar astrocytomas. The study was undertaken because of evidence that concurrent loss of both the 1p and 19q chromosome arms is a specific marker for oligodendrogliomas. Of the six lesions with a review diagnosis of oligodendroglioma, all had the predicted loss of 1p and 19q seen by CGH, FISH, and polymerase chain reaction. Other lesions, including some considered oligodendroglioma or mixed glioma by the submitting institution, did not. There were no p53 mutations in any of the six oligodendrogliomas, whereas 5 of the 10 remaining, successfully studied cases did have p53 mutations. The results suggest that CGH and FISH performed on current or archival tissue can aid in classification of infiltrating gliomas such as oligodendrogliomas and astrocytomas. The results of the p53 studies are consistent with findings of previous investigations that such mutations are less common in oligodendrogliomas than they are in astrocytomas.

Tau-associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to ApoE genotype.

Ganglion cell tumours, including gangliogliomas and gangliocytomas, are low grade neoplasms with a mature neuronal component. Ganglion cells within these lesions occasionally exhibit neurodegenerative changes including neurofibrillary tangles (NFT) similar to those in Alzheimer's disease. The frequency and spectrum of degenerative pathology in these lesions have not been defined, nor has their relation to patient age or factors such as apolipoprotein E (ApoE) genotype that predispose to Alzheimer's disease. We studied 72 ganglion cell tumours (61 gangliogliomas, 11 gangliocytomas) from patients 7 months to 72-years-old. Haematoxylin and eosin (H&E), silver stains (Hirano method) and immunohistochemistry for tau, alpha-synuclein and beta-amyloid were performed on formalin-fixed, paraffin-embedded tissue from surgical specimens. Tau-and silver-positive NFT and neuropil threads (NPT) were present in four of 26 ganglion cell tumours from patients over 30-years-old (ages 31, 38, 50, and 58 years). Neuronal granulovacuolar degeneration (GVD) was noted in five of 26 tumours from patients over 30-years-old (mean, 48 years). NFT, NPT, and GVD were not seen in ganglion cell tumours from patients under 30-years-old[0/46]. Cytoplasmic argentophilic bodies distinct from NFT were present in five of 26 tumours from patients over 30-years-old and in two of 46 under 30 years. Neither alpha-synuclein positive neuronal inclusions nor beta-amyloid immunoreactivity was noted in ganglion cell tumours from any age group. The distribution of ApoE genotypes was similar among those tumours that contained tau-associated neuropathology and those that did not. Neurodegenerative changes are uncommon in ganglion cell tumours, but increase in frequency with patient age. GVD, tau-positive NFT and NPT, and argentophilic bodies occur more often in ganglion cell tumours from patients over 30-yrs-old, but do not appear to be associated with a specific ApoE genotype.

Prognostic implications for gadolinium enhancement of the meninges in low-grade astrocytomas of childhood.

BACKGROUND: Persistent gadolinium enhancement on MRI of the meninges in some children with low-grade astrocytomas (LGA) is a widely recognized phenomenon. The relationship of this finding with the clinical course is unclear. METHODS: From a consecutive cohort of 282 children with pathologically confirmed LGA we identified all patients with asymptomatic gadolinium enhancement of the meninges found on surveillance MRI. A nested case-control study was performed, comparing patients with meningeal enhancement to controls without enhancement. RESULTS: Twenty-one children were identified with meningeal enhancement. The median follow-up was 5.2 years with enhancement noted for a median of 2.2 years. The 5-year overall survival for this cohort was 91.2% (Greenwood SE 8.0%), and the 5-year progression-free survival was 20.9% (SE 11.9%). Five patients are now free of disease, while 15 continue to have stable disease. The overall and progression-free survival was not significantly different compared to controls. CONCLUSIONS: Gadolinium enhancement of the meninges on MRI may occur in a significant number of children with LGA, particularly juvenile pilocytic astrocytoma, but does not appear to affect progression-free or overall survival. Change in management based on this finding alone is unwarranted.

"Large cell/anaplastic" medulloblastomas: a Pediatric Oncology Group Study.

495 medulloblastomas (MBs) from 6 Pediatric Oncology Group (POG) protocols were reviewed to assess the incidence and prognostic significance of "large cell" and "anaplastic" variants. "Large cell" medulloblastomas (LC MBs) were those with focal or diffuse, large, round neoplastic cells with prominent nucleoli. "Anaplastic" MBs (A MBs) were those with nuclei that were also large but markedly atypical with coarse chromatin and irregular shapes. Twenty-one cases were identified in the combined LC/A MB group, comprising about 4% of all MBs. Survival curves and Kaplan-Meier estimates of survival probabilities were examined separately for the LC/A MB and control groups. The logrank test for detecting poorer survival in the 21 cases was significant (p < 0.0001). Fluorescence in situ hybridization for c-myc showed amplification in 4 of 11 cases of the LC/A phenotype and 1 additional case of high level gain at 8q24 was disclosed by comparative genomic hybridization. Comparative genomic hybridization confirmed c-myc amplification and found evidence for isochromosome 17q in 3 of 4 LC/A cases studied successfully. One additional tumor showed high level gain restricted to 2p13 consistent with n-myc amplification. Monosomy 22, common in atypical teratoid/rhabdoid tumors, was not found. These results suggest that LC/A MB phenotype could be, at least in part, a correlate of c-myc, and possibly n-myc, amplification. The study thus confirms original observations about the LC MB in regard to histological features, immunohistochemical findings, c-myc amplification, cytogenetic findings, and poor prognosis.

A clinicopathologic reappraisal of brain stem tumor classification. Identification of pilocystic astrocytoma and fibrillary astrocytoma as distinct entities.

BACKGROUND: Brain stem tumors in children have been classified pathologically as low grade or high grade gliomas and descriptively as diffuse gliomas, intrinsic gliomas, midbrain tumors, tectal gliomas, pencil gliomas, dorsal exophytic brain stem tumors, pontine gliomas, focal medullary tumors, cervicomedullary tumors, focal gliomas, or cystic gliomas. METHODS: To search for a simplified and prognostic clinicopathologic scheme for brain stem tumors, the authors reviewed a consecutive cohort of patients younger than age 21 years with tumors diagnosed from 1980 through 1997. Pathology specimens and neuroimaging were classified by masked review. Statistical and survival analysis along with Cox proportional hazards regression was performed. RESULTS: Seventy-six patients were identified, with initial diagnostic magnetic resonance imaging available for 51 and pathology specimens for 48 patients. Twenty cases were classified histologically as pilocytic astrocytoma (PA), 14 as fibrillary astrocytoma (FA), and 14 as other tumors or indeterminate pathology. For all tumors, characteristics significantly associated with a worse survival rate were: symptom duration less than 6 months before diagnosis (P = 0.004); abducens palsy at presentation (P < 0.0001); pontine location (P = 0.0002); and engulfment of the basilar artery (P = 0.006). Pilocytic astrocytoma was associated with location outside the ventral pons (P = 0.001) and dorsal exophytic growth (P = 0.013); Fibrillary astrocytoma was associated with symptoms less than 6 months (P = 0. 006), abducens palsy (P < 0.001), and engulfment of the basilar artery (P = 0.002). Pilocytic astrocytoma showed 5-year overall survival (OS) of 95% (standard error [SE], 5%) compared with FA 1-year OS of 23% (SE, 11%;P < 0.0001). CONCLUSIONS: Brain stem tumors can be succinctly and better biologically classified as diffusely infiltrative brain stem gliomas-generally FA located in the ventral pons that present with abducens palsy, often engulf the basilar artery, and carry a grim prognosis-and focal brain stem gliomas-frequently PA arising outside the ventral pons, often with dorsal exophytic growth, a long clinical prodrome, and outstanding prognosis for survival. Our findings emphasize the individuality of PA as a distinct clinicopathologic entity with an exceptional prognosis.

Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome.

Among tumors classified as pilocytic astrocytoma (PA) in the Johns Hopkins Hospital Department of Pathology files, we identified 18 cases with a distinctive monomorphous pilomyxoid histological pattern and a higher recurrence rate than that of PA with classical histological features (classical PA). The majority of the tumors occurred in infants and young children and involved the hypothalamic/chiasmatic region. The tumors were histologically similar to PA, but they were more monomorphous and more myxoid. Rosenthal fibers were not seen and only 1 of 18 tumors had eosinophilic granular bodies. At the end of the follow-up period, 6 patients were dead and 12 were alive with evidence of disease. Progression free survival (PFS) at 1 year was 38.7%. In comparison, we identified a control group of 13 classical PAs in the same age range and location as the study group. In this group, PFS at 1 year was 69.2%, which was significantly better than that for pilomyxoid tumors (p = 0.04). There was no CSF dissemination or death due to tumor progression among patients with classical PA. Eight of these patients are alive with recurrent disease, and 4 have no evidence of disease. While the monomorphous pilomyxoid tumors have some resemblance to classical PA, our results suggest that the former is a more aggressive variant or a separate entity that needs to be recognized for prognostic purposes.