[Nontumoral epileptogenic lesions]. / Les lésions épileptogènes non tumorales.

Nontumoral epileptogenic lesions account for the major pathological group of surgical specimens obtained from patients with temporal or extratemporal drug-resistant epilepsy. Hippocampal sclerosis remains the predominant etiology, but cerebral cortical dysplasias actually make up the second major cause of nontumoral epilepsy and are increasingly recognized. The percentage of vascular lesions or glial/glio-mesodermal scars remains stable, but the minor or nonspecific lesion group is decreasing because of imaging investigation technique improvement.

[A rare lesion of the central nervous system: inflammatory pseudotumor]. / Une lésion rare du système nerveux central: la pseudotumeur inflammatoire.

Inflammatory pseudotumor is an uncommon tumor, initially described in the lung, but which can involve various organs. It is a controversial entity. We report the case of a 19-year-old-man with an inflammatory pseudotumor localized in the central nervous system, revealed by epilepsy. Characteristically, the inflammatory pseudotumor is an inflammatory mass leading to manifestations related to its localization. Relatively ubiquitous, this tumor is seldom described in the central nervous system. This uncommon lesion is part of a heterogeneous group of entities which are difficult to diagnose for both surgical pathologists and clinicians.

[Surgical resection of focal cortical dysplasias in the central region]. / Chirurgie des dysplasies corticales focales en région centrale.

BACKGROUND AND PURPOSE: Taylor-type focal cortical dysplasias (TTFCD) represent a particular pathological entity responsible for severe drug-resistant epilepsy of extratemporal location. Epilepsy can be surgically cured if complete removal of the lesion can be performed. However, identification on imaging may be difficult and negative standard MRIs are not rare. The frequent location of TTFCD in the central region restrains the possibilities of complete resection. We report a series of patients operated on for intractable epilepsy associated with TTFCD in the central area. PATIENTS AND METHODS: Between 2000 and 2006, of 34 consecutive patients with TTFCD, 17 had a lesion located in the central area. MRI was considered normal in eight, although in five a subtle gyral abnormality was disclosed on further analysis. A (18)FDG PET scan performed in 16 cases demonstrated focal hypometabolism in 15 that correlated with abnormalities on MRI when visible. SEEG performed in 13 cases revealed typical abnormalities for TTFCD in 10 cases. At resection, cortical and subcortical stimulations of the dysplastic cortex did not elicit a motor response. RESULTS: Postoperative motor or sensory deficit was observed in 13 patients--severe in four--which subsequently resolved completely in seven. Six patients had a minor permanent, motor or sensory deficit. Four patients were reoperated for seizure recurrence and residual dysplastic tissue was found at reoperation in three cases. Average postoperative follow-up was 3.7 years. Sixteen patients (94%) were in Engel Class I (65% in Class IA). CONCLUSION: This study suggests that surgical resection of central region TTFCD may be associated with favorable seizure outcome and no or minor functional permanent disability. In cases of seizure relapse, reoperation can be performed without further permanent deficit and lead to seizure-free outcome. Future techniques for intraoperative detection of these lesions could optimize their complete resection in functional areas.

Functional endothelin ET B receptors are selectively expressed in human oligodendrogliomas.

Endothelin-1 (ET-1), a vasoactive and mitogenic peptide mainly produced by vascular endothelial cells, may be involved in the progression of several human tumors. Here, we present an immunohistochemical analysis of the expression pattern of ET-1 receptor subtypes (ET(A)-R and ET(B)-R) and a functional study of their potential role in human oligodendrogliomas and oligoastrocytomas. By comparison, we assessed the corresponding expression patterns of glioblastomas. Interestingly, a nuclear localization of ET-1 receptor subtypes (associated or not with a cytoplasmic labeling) was constantly observed in tumor cells from all three glioma types. Moreover, we noted a distinct receptor distribution in the different gliomas: a nuclear expression of ET(B)-R by tumor cells was found to be restricted to oligodendrogliomas and oligoastrocytomas, while a nuclear expression of ET(A)-R was only detected in tumor cells from some glioblastomas. Using primary cultures of oligodendroglial tumor cells, we confirmed the selective expression of nuclear ET(B)-R, together with a plasma membrane expression, and further demonstrated that this receptor was functionally coupled to intracellular signaling pathways known to be involved in cell survival and/or proliferation: extracellular signal-regulated kinase and focal adhesion kinase activation, actin cytoskeleton reorganization. In addition, impairment of ET(B)-R activation in these cells by in vitro treatment with an ET(B)-R-specific antagonist induced cell death. These data point to ET-1 as a possible survival factor for oligodendrogliomas via ET(B)-R activation and suggest that ET(B)-R-specific antagonists might constitute a potential therapeutic alternative for oligodendrogliomas.

[Criteria of diagnosis and grading of oligodendrogliomas or oligo-astrocytomas according to the WHO and Sainte-Anne classifications]. / Oligodendrogliomes et oligo-astrocytomes critères diagnostiques et grading de malignité selon l'OMS et l'hôpital Sainte-Anne.

Two main classification systems are used in France for the histological typing and grading of oligodendrogliomas: the WHO and Sainte-Anne Hospital (SA) classifications. According to the WHO, the typing of diffuse gliomas is based on the predominant cell type, oligodendroglial versus astrocytic. In contrast, the SA classification is based on the distinction of two patterns of tumor growth, solid tumor tissue versus isolated tumor cells and also relies on imaging and clinical features. According to this approach, the SA classification includes in the category of oligodendrogliomas, the fibrillary or gemistocytic diffuse astrocytomas (WHO grade II) as well as a substantial proportion of astrocytomas WHO grade III, 2) the WHO uses multiple histological criteria for the grading of oligodendrogliomas (grade II versus grade III), including the degree of differentiation, cellular atypia, mitotic activity and necrosis. In contrast, the SA grading of these tumors (grade A versus B) only uses two criteria: the presence or absence of endothelial hyperplasia, and the presence or absence of contrast enhancement. This last criterion allows overcoming the problems related to the representativeness of surgical samples. Difficulties and discrepancies regarding the diagnosis of oligodendrogliomas are in part due to the lack of immunomarker for the identification of tumoral oligodendrocytes. The potential interest of new markers of oligodendroglial precursors for the diagnosis of these tumors will further be discussed.

[Reappraisal of the Sainte-Anne Hospital classification of oligodendrogliomas in view of retrospective studies]. / Classification des oligodendrogliomes de l'hôpital Sainte-Anne. Mise au point à l'usage des études rétrospectives.

PURPOSE: Definition of homogeneous tumor groups of oligodendrogliomas or oligo-astrocytomas is a basic condition for an adequate evaluation and comparison of the results of treatments in patients from various institutions. However, increasing discordances are observed in the histological diagnosis of these tumors. The main goal of this study is to assess whether, for retrospective studies, MRI data may serve as a common basis for encompassing asymmetry in diagnosis established according to the WHO or Ste-Anne (SA) classification. PATIENTS AND METHODS: This study included 251 adult patients in whom a SA grade A or B oligodendroglioma or oligo-astrocytoma was newly diagnosed at our institution from 1984 to 2003. Routine histological preparations and post-contrast preoperative MRI/CT-scan were simultaneously reviewed in order to assess the impact on survival of the following features: presence or absence of a polymorphous or gemistocytic astrocytic component, of necrosis and of contrast enhancement (CH); endothelial hyperplasia (EH) assessed as absent, present minor (HE+) or (HE++) when conform to the threshold of HE defined in the SA grading system of oligodendrogliomas. The tumors were graded A: no CH and no EH; in B: CH and /or HE++, and A/B: EH + but no CE. RESULTS: 70.1% of the tumors were classified as "pure" oligodendroglioma, 19.5% as "polymorphous oligo-astroastrocytoma" and 10.3% as "gemistocytic oligo-astrocytoma". In grade A, or B tumors, the presence of a polymorphous or a gemistocytic component had no significant influence on survival; however respectively 53% and 65% of these tumours versus 32% of "pure" oligodendrogliomas were grade B at the time of diagnosis. In either histological subtypes, survival was not significantly different when HE was absent or minor (HE+). After regrouping of the histological subtypes and of the tumors with HE+ or absent, the series included 153 oligodendrogliomas grade A and 98 grade B. Survival in patients with grade A versus grade B tumors was respectively 142 versus 52 months (p<0.0001). In grade B tumors, necrosis had no significant influence on survival. Ring-shaped contrast enhancement surrounding large foci of necrosis was observed in only 4 cases. In tumors with or without CE, patient survival was respectively 148 versus 40 months (p<0.0001). On post contrast MRI done in 235 patients, only 7 tumors (3%) were grade A/B (EH++ but no CH). CONCLUSIONS: From these results and our previous observation that, according to the SA classification of gliomas, only oligodendrogliomas or oligo-astrocytomas may not show CE, we propose that for retrospective studies: 1) tumors diagnosed according to the Ste-Anne classification as oligodendroglioma or oligo-astrocytoma be regrouped in a unique category, 2) independent of their histological type and grade according to the WHO, gliomas that do not show CE be regrouped with SA oligodendrogliomas grade A, 3) concerning gliomas that show CE on MRI: oligodendrogliomas or oligo-astrocytomas WHO grade II or III, as well as WHO secondary glioblastomas or glioblastomas with an oligodendroglial component, be regrouped with SA oligodendrogliomas grade B; however tumors that show ring-like CE surrounding large foci of necrosis and finger-like "peritumoral" edema should be excluded or analysed separately.

[Spatial delimitation of low grade oligodendrogliomas]. / Délimitation spatiale des oligodendrogliomes de bas grade.

Image-guided surgery is the central element of therapeutic management of low grade gliomas and consequently, a precise preoperative definition of their spatial extension is necessary. The question of the present work is: do the imaging abnormalities delineate the real spatial development of low grade oligodendrogliomas? A review of the literature showed that MRI on T2-weighted and FLAIR sequences are used to delineate the spatial developement of these tumours and that spectroscopic magnetic resonance imaging is more sensible to appreciate it. Moreover, mathematical models and histological studies suggest that MRI does not indicate the actual spatial extension of low grade oligodendrogliomas. This study focused on histological analysis of biopsy samples performed outside MRI imaging abnormalities in patients who harboured a low grade oligodendroglioma. It showed that isolated tumour cells were identified beyond imaging abnormalities in all of the 17 patients studied. In 15 of those 17 patients, isolated tumour cells were identified in the most distant biopsy samples taken outside imaging abnormalities. Thus, conventional imaging findings, including MRI on T2-weighted and FLAIR sequences, are not able to provide the real spatial development and boundaries of low grade oligodendrogliomas.

[Oligodendrogliomas: historical background of classifications]. / Oligodendrogliomes: historique des classifications.

The story of the classifications for gliomas is related to the development of the techniques used for cytological and histological examination of brain parenchyma. After a review of these techniques and the progressive discovery of the central nervous system cell types, the main classifications are presented. The first classification is due to Bailey and Cushing in 1926. It was based on histoembryogenetic theory. Then Kernohan introduced, in 1938, the concept of anaplasia. The WHO classification was published in 1979, then revised in 1993 and 2000. It took into account some data from both previous systems and introduced gradually the notion of histological criteria of malignancy. More recently; molecular genetics data and clinical evolution were retained. The Sainte-Anne classification for oligodendrogliomas is based on both histological and imaging data. It includes the notion of spatial histological structure of oligodendrogliomas. Contrast enhancement is closely related to endotheliocapillary hyperplasia. Gliomas classifications are changing and confusions can be made because of lack of reproductibility and misinterpretations of samples.

[Results of the Sainte-Anne - Lyons series of 318 oligodendroglioma in adults]. / Résultats de la série Sainte-Anne - Lyon de 318 oligodendrogliomes intracrâniens de l'adulte.

INTRODUCTION: Incidence of cerebral oligodendrogliomas is increasing because of better recognition made possible by improved classifications. We studied a homogeneous series using the Sainte-Anne grading scale in order to better understanding the history of these tumors with or without treatment and to assess prognosis and associated factors. PATIENTS AND METHODS: A retrospective series of 318 adult patients with oligodendroglioma (OLG) treated at Hôpital Sainte-Anne, Paris (SA) and Hôpital Neurologique, Lyons (L) between 1984 and 2003 was analyzed: 182 grade A OLG (SA + L), 136 grade B among which a homogenous series of 98 (SA) were included. For grade A: age at diagnosis ranged from 21 to 70 (mean: 41), sex ratio was 1.28. For grade B: age at diagnosis ranged from 12 to 75 (mean: 45.5), sex-ratio was 1.58. The main first symptoms were: epilepsy (A: 91.5%; B: 76%), intracranial hypertension (A: 7.9%; B: 14.6%), neurological deficit (A: 5.1%; B: 17.7%). The most frequent locations were: frontal, insular and central for both A and B. Mean size was 55 mm for grade A, 62 mm for B. Calcifications were found in 20% of A, 48.5% of B. No tumor was enhanced on imaging (CT/MRI) in grade A, all but 7 in grade B. All patients underwent surgery either for biopsy (A: 47.2%; B: 53%), or removal which was partial (A: 26.4% vs B: 19.4%) or extended (A: 36.3% vs B: 37.8%). Fifty-six patients underwent 2 procedures and 12 three procedures. Radiotherapy was performed in 76.9% of grade A, and 91% of B patients, in the immediate postoperative period for 71% A and 82.7% B. Chemotherapy was delivered for 36% of grade A (in the event of transformation to grade B or failure of radiotherapy) and 67.5% of B patients. Among grade A tumors, 38% transformed into grade B within a mean delay of 51 months with a mean follow-up of 78 months. RESULTS: Median survival was 136 months for grade A and 52 for grade B. Survival at 5, 10 and 15 was 75.5%, 51% and 22.4% for grade A vs 45.2%, 31.3% and 0% for grade B respectively. In univariate and multivariate analysis, grade A survival was associated with age at diagnosis, tumor size, large removal and response to radiotherapy. Grade B survival was associated with age at diagnosis, wide removal and sharply defined limits of the tumor on imaging. CONCLUSIONS: Analysis of both published data and this series underlines many prognostic parameters. It shows that OLG are heterogeneous tumors even in each grade (A and B). Treatment should consequently progress towards more targeted procedures for patients mainly with postoperative radiotherapy and chemotherapy.

Dysembryoplastic neuroepithelial tumours.

Dysembryoplastic neuroepithelial tumours (DNTs) are a group of supratentorial cortical benignant lesions that superficially resemble mixed oligo-astrocytomas, oligodendrogliomas or astrocytomas. Clinically these tumours are associated with partial seizures beginning before the age of 20 years, with no neurologic deficit and no stigmata of phacomatosis. In the revised WHO classification, DNTs have been incorporated among the category of neuronal and mixed neuronoglial tumours. This classification describes a histologic variant characterized by the following criteria: cortical location, multinodular architecture--the nodule being made of multiple variants looking like astrocytomas, oligodendrogliomas or oligo-astrocytomas, foci of dysplastic cortical disorganization and the presence of a glioneuronal element showing a columnar structure perpendicular to the cortical surface. A study of 14 cases for which only a specific glioneuronal element could be identified demonstrated that this specific element is sufficient for diagnosing DNTs and that the spectrum of DNTs includes a simple form with a unique glioneuronal element. Preoperative imaging follow-up data, in the series of 23 simple and complex forms, indicated that DNTs are perfectly stable. However, these tumours may show a high MIB 1 labeling index.

Postoperative radiotherapy of supratentorial low-grade gliomas.

Forty-nine patients with supratentorial low-grade gliomas underwent surgery (biopsy or subtotal resection) and postoperative radiotherapy at the Mayo Clinic between 1976 and 1983. The median, 5-, and 10-year overall survivals for the total group were 6.5 years, 62%, and 14%, respectively. Nine prognostic variables were examined for their possible association with survival, including age, sex, site, size, CT enhancement, histologic type, extent of resection, radiation volume, and radiation dose. Of these variables, only histologic type was significantly associated with survival. The estimated 5-year survival was 100% for the 5 patients with pilocytic astrocytomas, 83% for the 20 patients with oligodendrogliomas or mixed oligo-astrocytomas, and 40% in the 24 patients with ordinary astrocytomas (log rank p = 0.001). Other possible prognostic variables, such as radiation volume or total dose, showed no association with survival. Twenty-seven patients had a documented treatment failure. For the 20 patients in whom the pattern of failure could be determined, all failed within their radiation portals. Eleven patients had additional tissue obtained following suspected disease recurrence. Tumor was found in ten of these patients, and radionecrosis in one.

Central neurocytomas. Critical evaluation of a small-cell neuronal tumor.

We report herein the clinical and pathological features of 20 patients with central neurocytomas. Investigations for various differentiation antigens and cell type-specific markers were performed by immunohistochemistry using paraffin-embedded tissue. In addition, the expression of L1 adhesion molecule and of the various N.CAM (neural cell adhesion molecule) isoforms were investigated by immunoblotting studies in two frozen specimens. Central neurocytomas are clinically characterized by their intraventricular localization, occurrence in young adults, and good prognosis. It rarely occurs in patients over 50, but such cases have a poor prognosis. Total surgical excision is the best treatment. Radiotherapy is appropriate if surgery is incomplete or contraindicated. Histologically, central neurocytomas display the following features: an oligo-like pattern, usually associated with large fibrillary rosettes or perivascular arrangement, and a rich endocrine-type vasculature. Central neurocytomas have a remarkably homogeneous antigenic profile. GFAP expression is only found in scattered reactive astrocytes, S100 protein in reactive astrocytes and rare tumor cells. Among the pan-neuroendocrine markers, central neurocytomas always express neuron-specific enolase; they frequently express synaptophysin but never chromogranin A. Synaptophysin is the most reliable immunohistological marker for central neurocytomas; however, immunoreactivity could be lost with long formalin fixation. In these cases, electron microscopy is used to support the neuronal nature of the tumor cells. The expression of L1 adhesion molecule and the isoform 180 of N.CAM, indicates that central neurocytomas are formed by cells committed to neuronal phenotype. Nevertheless, advanced neuronal differentiation may be absent, as suggested by the persistence of embryonic N.CAM, the nonexpression of neurofilament proteins, and the absence of mature synapses in numerous cases. Central neurocytomas and neuroblastomas share some biochemical properties, but their respective clinicopathological features and biological behavior are dramatically different.

A histologic and cytologic method for the spatial definition of gliomas.

Because of the increasing application of stereotactic neurosurgical techniques not only in the diagnosis but also in the treatment of brain tumors, a demand for data regarding the spatial delimitation of gliomas is being created. Traditional histologic criteria were not established for detecting isolated tumor cells located at the boundaries of gliomas. Standard histologic techniques used for processing surgical specimens result in preparations of insufficient quality to allow the detection of minimal tumor infiltrates within normal brain parenchyma. Consequently, histologic examination has been considered an unreliable method of determining the boundaries of gliomas. In this study, we describe in detail an improved technique of biopsy specimen preparation that involves the use of glutaraldehyde-fixed and hemalum-phloxine-stained paraffin sections as well as alcohol-fixed and hemalum-phloxine-stained smears. In concert, these methods allow visualization of delicate cytologic details and are complementary in assessing the presence of isolated tumor cells at the periphery of gliomas. We define morphologic criteria for the accurate identification of isolated neoplastic cells and for their distinction from normal or reactive glial elements. These morphologic criteria include classic cytologic features of malignant lesions (such as nuclear pleomorphism and hyperchromasia) as well as the assessment of tumor architecture and cellular spatial relationships.

Stereotactic histologic correlations of computed tomography- and magnetic resonance imaging-defined abnormalities in patients with glial neoplasms.

In 39 patients who harbored previously untreated astrocytomas (21 patients), oligoastrocytomas (9 patients), or oligodendrogliomas (9 patients), computed tomographic (CT) and magnetic resonance imaging (MRI) findings were correlated with stereotactic serial biopsy findings. The 39 patients were classified as having one of three types of tumor: type I (1 patient), which consisted only of circumscribed tumor tissue; type II (26 patients), which consisted of tumor tissue and isolated tumor cells; or type III (11 patients), which consisted of intact parenchyma infiltrated by isolated tumor cells. (In one patient, the biopsy sampling was inadequate for determining the type of tumor.) In high-grade lesions, tumor tissue was obtained from CT contrast-enhancing regions, and the area of enhancement accurately defined the tumor tissue volume. In low-grade lesions, tumor tissue was hypodense and indistinguishable from parenchyma infiltrated by isolated tumor cells on both CT and MRI. Isolated tumor cells usually extended as far as the prolongation of T2 on T2-weighted MRI of high-grade and low-grade tumors. CT and MRI detection of boundaries and stereotactic serial biopsies are necessary for the demarcation of glial neoplasms into tumor tissue and isolated tumor cell volumes as well as for the determination of the spatial extent of each component. This information is important for determining appropriate treatment.

Comparison of somatostatin receptor expression in human gliomas and medulloblastomas.

The expression of the five somatostatin receptor subtypes, sst1-5 was compared on tissue containing glial tumours (glioblastomas or oligodendrogliomas), medulloblastomas, and on normal human cortex. By semiquantitative reverse transcription coupled to polymerase chain reaction, the receptor expression profiles were high in cortex and in tissue containing oligodendrogliomas. It was moderate in medulloblastomas. Tissue containing glioblastomas displayed lower expression of somatostatin receptor subtypes, sst1 and sst3 being mostly expressed. By 125I-Tyr0DTrp8 somatostatin-14 or 125I-Leu8DTrp22 Tyr25 somatostatin-28 autoradiography combined with synaptophysin immunohistochemistry, it was possible to differentiate between isolated tumoral cell component infiltrating the cerebral parenchyma (cortex or white matter) and tumoral tissue (without residual parenchyma) in glioblastomas or oligodendrogliomas. Glial tumoral tissue per se presented few somatostatin receptors. By contrast, medulloblastoma tumoral cells exhibited numerous octreotide sensitive somatostatin receptors. sst2 immunocytochemistry demonstrated immunostaining of neuronal cells and neuropile; sst2 and sst3 immunostaining was identified on glioblastoma proliferating vessels endothelial cells and on medulloblastomas tumoral cells. Faint sst2 immunostaining among glial tumoral cells was due to microglia, while glioma cells did not significantly stain. In summary, medulloblastoma tumoral cells express sst2/sst3 receptors at a high level while glioma cells do not. In gliomas, sst expression is restricted to endothelial cells on proliferating vessels (displaying both sst2 and sst3 receptors), including parenchyma and reactive microglia (only sst2). The differential expression of sst2/sst3 receptors on gliomas and medulloblastomas has implications for the therapy of these tumours.

Modulated release of IdUrd from poly (D,L-lactide-co-glycolide) microspheres by addition of poly (D,L-lactide) oligomers.

This paper reports the release characteristics of a radiosensitizer, 5-iodo-2'-deoxyuridine (IdUrd), from poly (D,L-lactide-co-glycolide) 50: 50 (PLGA) microparticles obtained by a phase separation technique. Poly (D,L-lactide) oligomers (D,L-PLA) were incorporated into the PLGA matrix in order to accelerate the overall drug release rate and regulate the triphasic release profile exhibited by the standard PLGA microparticles. For D,L-PLA (800), the burst effect was large and the IdUrd release was complete between 28 and 35 days. These results were attributed to rapid pore formation on the periphery of the microsphere in the early stages of incubation, due to hydrosolubility of the smallest oligomers (D,L-PLA (800)). In the case of D,L-PLA (1,100), drug release occurred over a six week period, the standard time course of conventional radiation therapy. The period during which the radiosensitizer was incorporated in human brain tumor cell nuclei after its entrapment in biodegradable microspheres was determined by using an organotypical tissue culture. The presence of radiosensitizer in the DNA of tumor cell nuclei was detected by immunohistochemical labelling of tumor fragments. IdUrd release from standard microspheres (7+/-0.5 weeks) was longer than from oligomer-containing batches. For D,L-PLA (800)-containing microspheres, the radiosensitizer was entirely released within 4. 5+/-0.5 weeks. The microspheres containing D,L-PLA (1,100) allowed an IdUrd release over a 5 to 6 week period. The ex vivo data were consistent with the in vitro findings in terms of release duration.

Dysembryoplastic neuroepithelial tumors located in the caudate nucleus area: report of four cases.

OBJECTIVE AND IMPORTANCE: Dysembryoplastic neuroepithelial tumors (DNTs) histologically resemble gliomas but behave as stable lesions. These tumors initially were considered to be located exclusively within the supratentorial cortex. The four reported cases demonstrate that DNTs may also arise in the area of the caudate nuclei. Moreover, the peculiar topography of these lesions, which suggests a derivation from the subependymal plate, is in accordance with the putative origin of DNTs from secondary germinal layers. CLINICAL PRESENTATION: The patients experienced partial seizures (two patients), generalized seizures (one patient), or headaches (one patient). All patients were young (17-26 yr) at the onset of symptoms, and all had normal results from their neurological examinations. INTERVENTION: All lesions demonstrated a pseudocystic appearance on computed tomographic scans, were hypointense on T1-weighted magnetic resonance imaging scans, hyperintense on T2-weighted magnetic resonance imaging scans, and did not show contrast enhancement. The four tumors similarly lined the left or right caudate nuclei and expanded within the homolateral ventricle (three patients) or both lateral ventricles (one patient). In one patient, the tumor also involved the adjacent paraolfactory cortex. CONCLUSION: In all patients, stereotactic biopsies helped to identify a specific glioneuronal element of DNTs. None of the tumors was operated on. Radiotherapy was performed in only one patient. A long pre- and/or postbiopsy imaging follow-up, which was available in two nontreated patients (3 yr and 16 yr), demonstrated the perfect stability of the lesion. The occurrence of DNTs in this peculiar location needs to be considered to avoid misidentification as "ordinary" gliomas and prevent useless aggressive treatment.

Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Report of thirty-nine cases.

This report concerns the clinicopathological features of 39 cases of a morphologically unique and surgically curable group of neuroepithelial tumors associated with medically intractable partial complex seizures. All were supratentorial and characterized by intracortical location, multinodular architecture, and heterogeneity in cellular composition. The constituent cells included astrocytes, oligodendrocytes, and neurons. Because neuronal atypia was often inapparent, the tumors superficially resembled mixed oligoastrocytomas. The term "dysembryoplastic neuroepithelial tumor" (DNT) is proposed for these distinctive lesions, the clinicopathological features of which suggest a dysembryoplastic origin. With the exception of the occurrence of headaches in 2 patients, partial complex seizures were the exclusive symptom. Age at onset of symptoms ranged from 1 to 19 years (mean 9 years). In addition to the chronic nature of the seizures (range, 2 to 18 years; mean, 9 years), one-third of the patients showed radiological features, such as focal cranial deformity, indicating that the tumors had an early onset and were of long standing. In most cases, computed tomography showed a "pseudocystic," well-demarcated, low density appearance associated in some cases with focal contrast enhancement (18%) or calcific hyperdensity (23%). The tumor involved the temporal lobe in 24 patients (62%), the frontal lobe in 12 (31%), and the parietal and/or occipital lobe in 3 cases. Although tumor removal was considered incomplete or subtotal in 17 patients (44%), long term follow-up (range, 1 to 18 years; mean, 9 years) showed neither clinical nor radiological evidence of recurrence in any patient. Comparison of the survival data of the 13 subjects who had undergone postoperative radiotherapy with 26 who had not indicated that radiation therapy was of no obvious benefit. The identification of DNT has therapeutic and prognostic implications because aggressive therapy can be avoided, thus sparing these young patients the deleterious long term effects of radio- or chemotherapy.

Histological grading and bromodeoxyuridine labeling index of astrocytomas. Comparative study in a series of 60 cases.

The histological grade and the bromodeoxyuridine (BUdR) labeling index of 60 astrocytomas of "ordinary" cell types (fibrillary, protoplasmic, gemistocytic, and anaplastic astrocytomas and glioblastomas) were compared to determine whether the grading system reflects the proliferative potential of the tumors. The tumor grade was based on the presence or absence of four criteria (nuclear abnormalities, mitosis, necrosis, and vascular endothelial proliferation): Grade 1, no criterion, Grade 2, one criterion, Grade 3, two criteria; and Grade 4, three or four criteria. The BUdR labeling index, or percentage of S-phase cells, was calculated in paraffin-embedded tumor sections after in situ labeling by intraoperative intravenous infusion of BUdR, 200 mg/sq m. Exponential regression analyses showed a positive correlation between the histological grade and labeling index (r = 0.88, p less than 0.001) that was stronger than the correlations between log labeling index and age (r = 0.55, p less than 0.001) and between grade and age (r = 0.55, p less than 0.001). These results indicate that the histological grading system reflects the proliferative potential of "ordinary" astrocytomas.

Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms.

Forty patients with previously untreated intracranial glial neoplasms underwent stereotaxic serial biopsies assisted by computerized tomography (CT) and magnetic resonance imaging (MRI). Tumor volumes defined by computer reconstruction of contrast enhancement and low-attenuation boundaries on CT and T1 and T2 prolongation on MRI revealed that tumor volumes defined by T2-weighted MRI scans were larger than those defined by low-attenuation or contrast enhancement on CT scans. Histological analysis of 195 biopsy specimens obtained from various locations within the volumes defined by CT and MRI revealed that: contrast enhancement most often corresponded to tumor tissue without intervening parenchyma; hypodensity corresponded to parenchyma infiltrated by isolated tumor cells or in some instances to tumor tissue in low-grade gliomas or to simple edema; and isolated tumor cell infiltration extended at least as far as T2 prolongation on magnetic resonance images. This information may be useful in planning surgical procedures and radiation therapy in patients with intracranial glial neoplasms.