Time to diagnosis of intraspinal tumors.

The aim of this study was to assess the time to diagnosis in patients with intraspinal tumors and to assess factors contributing to a long delay in some patients. Patients who were admitted at our hospital over a 15-year period (1986-2000) with an intraspinal (either intradural or extradural) tumor were included. Records of patients were studied for variables such as sex, age, diagnosis, date of diagnosis, initial symptoms, symptoms at diagnosis, level of tumor, original diagnosis and diagnostic technique [CT-myelography, CT-caudography or magnetic resonance imaging (MRI)]. The median time to diagnosis of 108 patients with an intraspinal tumor was 12.3 months (range: 4 days-14.4 years). Most common initial symptoms were back and/or neck pain, pain radiating to one extremity and walking disturbances. There was no distinctive clinical pattern between intramedullary and extramedullary tumors regarding initial symptoms. At the time of diagnosis, patients presented with moderate to severe neurological deficits: weakness in one extremity in 26%, sphincter disturbance (20%) and paraparesis (12%). Improved imaging of the spinal cord by MRI did not result in earlier detection of the intraspinal tumor. The time to diagnosis is explained by non-specific and slowly progressing signs and symptoms. A high rate of clinical suspicion should be present to diagnose an intraspinal tumor at an early stage.

Subtyping of oligo-astrocytic tumours by comparative genomic hybridization.

Oligo-astrocytic tumours (OAs) histologically show both oligodendroglial and astrocytic differentiation. Unequivocal criteria for delineation of OAs from pure oligodendroglial (Os) and astrocytic (As) tumours and for grading of OAs are lacking. Molecular genetic analysis may allow for a better characterization of OAs and thereby guide prognostic and therapeutic decisions. Comparative genomic hybridization (CGH) was performed on 39 gliomas with variable phenotypic expression of histological features characteristic of both astrocytic and oligodendroglial differentiation. The results show that OAs are genetically more heterogeneous than Os. In addition to the "-1p/-19q" and "+7/-10" subtypes that have been previously recognized, two additional genetic subtypes, "intermediate" and "other", were identified in the present study. "Intermediate" OAs likely represent progression from "-1p/-19q" tumours. The "other" subtype appears to represent an additional, heretofore unrecognized, genetic pathway(s). Application of rigorously "strict" histopathological criteria, as opposed to "relaxed" criteria, for the selection of oligo-astrocytic tumours resulted in a higher percentage of "-1p/-19q" tumours, but some "-1p/-19q" tumours might be missed. The results suggest that molecular genetic analysis is a useful and valid additional tool for the classification of gliomas, particularly for the significant subset of tumours in which subjective histopathological criteria are insufficient for an unequivocal distinction between Os, As, and mixed OAs.

On the pathogenesis of brain tumour cysts: a volumetric study of tumour, oedema and cyst.

Chemical analysis of brain tumour cyst contents has invalidated the concept of cyst formation being the result of tumour necrosis, and a common mechanism of vasogenic brain oedema and cyst formation, namely blood-brain barrier (BBB) disruption, has been suggested. To analyse a possible relationship between the occurrence of vasogenic oedema and the presence of cysts, we performed a volumetric analysis on the MRI and CT studies of 60 patients with primary or metastatic brain tumours. We compared four groups of tumours: 30 gliomas, of which 15 were cystic and 15 not and 30 metastatic brain tumours of which 15 were cystic and 15 not. Although the mean volume of oedema was similar for cystic and noncystic tumours, the ratio of oedema to tumour volume was approximately four times as high in cystic supratentorial tumours. This would support the view that cyst formation may be related to relatively greater production of oedema, possibly due to fusion of microcysts containing oedema fluid. The ratio of oedema to tumour volume is not greater in cystic cerebellar and intraventricular tumours. This may be due to the different anatomical organization of the cerebellar white matter, and the fact that the intraventricular tumours are bordered by subcortical grey matter. In these cases, spread of oedema is impeded. Formation of a large amount of brain oedema is therefore not an essential prerequisite for cyst formation.

Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization.

In contrast to astrocytic tumors, approximately two thirds of anaplastic oligodendrogliomas are reported to be chemosensitive. Relatively little is known about the genetic aberrations in oligodendroglial tumors (OTs). In order to elucidate oligodendroglial oncogenesis and to find specific genetic aberrations that may have prognostic and therapeutic implications, we performed comparative genomic hybridization (CGH) to detect chromosomal copy number changes in 17 low-grade OTs (LG-OTs) and 12 high-grade OTs (HG-OTs) lacking a prominent astrocytic component. Loss of chromosome 1p (79%) and 19q (76%) were most frequently detected by CGH, all LG-OTs and 50% of the HG-OTs contained -1p (including 1p36-32), -19q (including 19q13.3), or both, and the rest of the HG-OTs showed +7, -10, or both. Since losses of 1p36-32 and 19q13.3 were mutually exclusive with +7 or -10, the HG-OTs could be divided in -1p/-19q and +7/-10 tumors. While the -1p/-19q tumors can be considered as pure anaplastic oligodendrogliomas, the +7/-10 tumors may rather be glioblastomas with prominent oligodendroglial differentiation. We conclude that CGH is a powerful tool to assist in the identification of 2 major subgroups of HG-OTs with prognostic and possibly therapeutic relevance.

Inflammation of the atherosclerotic cap and shoulder of the plaque is a common and locally observed feature in unruptured plaques of femoral and coronary arteries.

-Retrospectively, plaque rupture is often colocalized with inflammation of the cap and shoulder of the atherosclerotic plaque. Local inflammation is therefore considered a potential marker for plaque vulnerability. However, high specificity of inflammation for plaque rupture is a requisite for application of inflammation markers to detect rupture-prone lesions. The objective of the present study was to investigate the prevalence and distribution (local versus general) of inflammatory cells in nonruptured atherosclerotic plaques. The cap and shoulder of the plaque were stained for the presence of macrophages and T lymphocytes in 282 and 262 cross sections obtained from 74 coronary and 50 femoral arteries, respectively. From most cases, 2 atherosclerotic arteries were studied to gain insight into the local and systemic distribution of the inflammatory process. In 45% and 41% of all cross sections, staining for macrophages was observed in the femoral and coronary arteries, respectively. Rupture of the fibrous cap was observed in 2 femoral and 3 coronary artery segments and was always colocalized with inflammatory cells. At least 1 cross section stained positively for CD68 or acid phosphatase in 84% and 71% of all femoral and coronary arteries, respectively. Only 1 femoral and 6 coronary arteries revealed a positive stain for CD68 in all investigated segments. Inflammation of the cap and shoulder of the plaque is a common feature, locally observed, in atherosclerotic femoral and coronary arteries. The high prevalence of local inflammatory responses should be considered if they are used as a diagnostic target to detect vulnerable, rupture-prone lesions.

A uniform histological cluster scheme for ICD-O-coded primary central nervous system tumors.

Comparability of population-based measures of risk and prognosis for primary central nervous system (CNS) tumors, which exhibit marked histological diversity, may be hampered by differences in detection and case ascertainment and by the lack of unequivocal and uniform histological criteria for pathological diagnoses. Furthermore, many cancer registries do not include benign tumors as defined by the International Classification of Diseases for Oncology (ICD-O), such as meningiomas, schwannomas and pituitary adenomas. We propose both a detailed and a rough uniform histological cluster scheme for data coded according to the first or second edition of the ICD-O, published in 1976 and 1990, respectively. Primary CNS tumors, typed and graded according to (modified) classification systems of Bailey and Cushing, Kernohan, Ringertz, the WHO and Daumas-Duport, are clustered as clinically relevant entities on the basis of the second edition of the WHO classification system, published in 1993. The proposed scheme identifies some of the (potential) pitfalls in the descriptive epidemiology of CNS tumors and may facilitate temporal and geographical comparability of population-based data.

Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy.

Because glioblastoma multiforme (GBM) frequently shows striking, glomeruloid microvascular proliferation (MVP), this tumor has become a strong candidate for anti-angiogenic therapy. However, the efficacy of anti-angiogenic treatment may rather be determined by the extent of classic angiogenesis with the formation of delicate microvascular sprouts. Therefore, this study differentially quantifies the microvascular changes in supratentorial diffuse astrocytic neoplasms by computerized image analysis of histological sections in which the microvessels were highlighted by a combined anti-collagen IV/MIB-1 staining. Four microvascular parameters (number, area, perimeter, diameter), the cellularity of the glial tissue, and the MIB-1 labeling index were assessed in biopsies of astrocytoma (A, n = 13), anaplastic astrocytoma (AA, n = 14), and GBM (n = 20), and in normal cerebral cortex (n = 7) and white matter (n = 7). In As and AAs, the microvascular parameters were not significantly different from each other, and the microvascular changes were generally limited compared with WM and CX. In contrast, in GBMs the microvascular parameters were highly variable, and their overall mean value was significantly increased compared with As and AAs (ranging from 1.3x for vessel diameter to 3.3x for vessel area). Our study indicates that not only glomeruloid MVP, but also classic angiogenesis, occurs mainly and only locally in GBMs. Thus, this study provides evidence that As and AAs are not good candidates for anti-angiogenic therapy. The efficacy of such therapy for GBMs awaits further evaluation.