Frédéric Beuvon

Oligodendrogliomas. Part I : Patterns of growth, histological diagnosis, clinical and imaging correlations : A study of 153 cases

The present study has attempted to demonstrate that the morphological spectrum of oligodendrogliomas includes tumors which are traditionally misinterpreted as ‘diffuse fibrillary astrocytoma’. We have shown that these tumors are in fact made of isolated neoplastic oligodendrocytes which are entrapped in a fibrillary background composed of axons and fibrillary reactive gliosis. Analysis in a series of 153 ‘pure’ supratentorial oligodendrogliomas composed of ‘classical’ or pseudo ‘diffuse fibrillary oligodendrogliomas’ diagnosed by imaging-based serial stereotactic biopsies showed that 2/3 of the tumors were exclusively made of isolated tumor cells (ITCs) (structure type III) and that only 1/3 of them exhibited both ITCs and solid tumor tissue components (structure type II). The tumor tissue destroys the brain parenchyma and contains new formed microblood vessels whereas ITCs do not destroy the parenchyma and are not associated with microangiogenesis. These fundamentally opposite morphological characteristics were reflected by the following findings: 1) contrast enhancement was observed in 64% of structure type II but was never seen in structure type III oligodendrogliomas. 2) a neurological deficit occurred in 57% of structure type II but in only 8% of structure type III oligodendrogliomas. 3) using the new grading system described in the companion paper to this study, we found that the biological behavior of oligodendrogliomas was also closely related to the patterns of tumor growth. From a synthesis of data gathered in this study it is suggested that emergence of microangiogenesis within a tumor which at first grows slowly with a structure type III pattern is a crutial event toward more aggressive behavior.

Dysembryoplastic neuroepithelial tumors: nonspecific histological forms -- a study of 40 cases.

Objective. To demonstrate that DNTs include a large morphological spectrum of tumors that cannot be histologically distinguished from conventional categories of gliomas.Methods. All tumors from patients who underwent epilepsy surgery in Sainte-Anne hospital (Paris) that histologically resembled gliomas and did not conform to current histological criteria for DNTs or gangliogliomas were entered in the study.Results. According to the WHO histological classification, the 40 tumors resembled: pilocytic astrocytomas (4 cases), astrocytomas (16 cases), anaplastic astrocytoma (1 case), oligodendrogliomas (10 cases), oligo-astrocytomas (8 cases) or anaplastic oligo-astrocytomas (1 case). However foci of cortical dysplasia could be observed in 47% of the cases. Clinical presentation and imaging features were strikingly similar to that observed in typical DNTs. Although surgical removal was incomplete in 28% of the cases and none of the patients underwent chemo or radiotherapy, none of the tumors recurred (mean follow-up: 7 years). Moreover, serial preoperative imaging in 26 patients (mean follow-up: 4.5 years) demonstrated that these lesions were perfectly stable.Conclusions. Whatever the histological appearance of a glial tumor, the diagnosis of DNT must be considered when all the following criteria are associated: (1) partial seizures, with or without secondary generalization, beginning before the age 20 years, (2) no neurological deficit or stable congenital deficit, (3) cortical topography of the lesion as better demonstrated by MRI and (4) no mass effect on imaging.

Oligodendrogliomas. Part II: A new grading system based on morphological and imaging criteria

This second part of our study of ‘pure’ oligodendrogliomas focuses on survival data analysis. In order to identify potentially useful prognostic factors and to assess the effectiveness of a new grading system, the 79 patients in the previously analyzed series for whom adequate follow-up could be obtained (52%) were entered in the present analysis. Statistical analysis demonstrated that contrast enhancement and endothelial hyperplasia had powerful and similar influence on survival. Median survival with and without contrast enhancement were: 3 versus 11 years, and with or without endothelial hyperplasia were: 3.5 versus 11 years. Conversely, the degree of nuclear atypia and presence or absence of mitosis or necrosis were not correlated with survival. These findings allowed us to devise a simple grading system which discriminates two malignancy grades as follows: absence of endothelial hyperplasia and of contrast enhancement=Grade A, presence of endothelial hyperplasia and/or of contrast enhancement=Grade B. Of the 79 oligodendrogliomas in this study, 59 tumors were categorized as grade A and 20 as grade B. Median survival were: 11 years in grade A and 3.5 years in grade B. Five-year and 8-year survival rates were: 89% and 60% in grade A and: 33% and 15% in grade B. Double blind grading between two independent observers was concordant in 96% of the cases. Application of this simple efficient and reproducible grading scheme should permit reliable comparison of retrospective or prospective therapeutic data emanating from various institutions.

Intralesional recordings and epileptogenic zone in focal polymicrogyria

Purpose: Polymicrogyria (PMG) is recognized as an epileptogenic lesion but few data concerning organization of the epileptogenic zone (EZ) are available.

Neuropathological and Reelin Deficiencies in the Hippocampal Formation of Rats Exposed to MAM; Differences and Similarities with Schizophrenia

Background Adult rats exposed to methylazoxymethanol (MAM) at embryonic day 17 (E17) consistently display behavioral characteristics similar to that observed in patients with schizophrenia and replicate neuropathological findings from the prefrontal cortex of psychotic individuals. However, a systematic neuropathological analysis of the hippocampal formation and the thalamus in these rats is lacking. It is also unclear if reelin, a protein consistently associated with schizophrenia and potentially involved in the mechanism of action of MAM, participates in the neuropathological effects of this compound. Therefore, a thorough assessment including cytoarchitectural and neuromorphometric measurements of eleven brain regions was conducted. Numbers of reelin positive cells and reelin expression and methylation levels were also studied. Principal Findings Compared to untreated rats, MAM-exposed animals showed a reduction in the volume of entorhinal cortex, hippocampus and mediodorsal thalamus associated with decreased neuronal soma. The entorhinal cortex also showed laminar disorganization and neuronal clusters. Reelin methylation in the hippocampus was decreased whereas reelin positive neurons and reelin expression were unchanged. Conclusions Our results indicate that E17-MAM exposure reproduces findings from the hippocampal formation and the mediodorsal thalamus of patients with schizophrenia while providing little support for reelins involvement. Moreover, these results strongly suggest MAM-treated animals have a diminished neuropil, which likely arises from abnormal neurite formation; this supports a recently proposed pathophysiological hypothesis for schizophrenia.

Cavernomes intracrâniens, épilepsie et crises d'épilepsie : Histoire naturelle et modalités thérapeutiques

PURPOSE To review, from a retrospective series of 48 patients presenting with seizures associated with one or more supratentorial cavernoma(s), the natural history of the seizures and outcome according to medical and surgical treatment. METHODS Patients were divided into two groups: group A included patients presenting with a single seizure or rare seizures (n=21), and group B patients having intractable epilepsy (n=27). All received antiepileptic drugs and 35 were operated on (12 in the group A and 23 in the group B). Stereo-EEG was performed in 8 patients in group B. Surgery included lesionectomy alone (n=16), resection of the cavernoma and perilesional tissue (n=7) or tailored corticectomy including the cavernoma (n=12). RESULTS The natural history of seizures was different in the two groups: mean age at seizure onset was 25 years in group B and 33 years in group A (p<0.05), seizures were partial in all patients in group B and 8 patients in group A (p<0.05). Seizure frequency and periodicity also varied. Prolonged seizure-free periods were observed. The cavernoma was temporal in 17 patients in group B and 4 patients in group A (p<0.01). In group A, seizure outcome was favorable following surgery or with antiepileptic medication only (7 patients out of 12 operated were seizure-free, as were 5 out of 7 non-operated). In group B, seizure outcome was better after surgery than with medication only (17 patients out of 23 operated were in Engels Class I, while 3 patients of 4 non-operated patients had persisting seizures despite antiepileptic polytherapy). CONCLUSION Variations in seizure severity in patients harboring cavernomas suggest different therapeutic approaches. In case of unique or rare seizures, surgical resection of the cavernoma is appropriate, but benefits of surgery over antiepileptic medication in terms of seizure control remains unclear. Intractable epilepsy associated with cavernomas is better controlled after surgery rather than with medication only. In these patients, a detailed preoperative work-up is necessary and should be followed by wide resection associated or not with corticectomy, especially in the temporal lobe. Evaluation of outcome after surgery should consider the surgical strategy, antiepileptic medications and the patients seizure history.

Neuronal immunoexpression and a distinct subtype of adult primary supratentorial glioblastoma with a better prognosis

OBJECT In this study, the authors address whether neurofilament protein (NFP) expression can be used as an independent prognostic factor in primary glioblastoma multiformes (GBMs). METHODS Three hundred and two consecutive adult patients with newly diagnosed supratentorial primary GBMs were analyzed (January 2000-August 2008). Detailed data regarding clinical, imaging, and pathological findings, oncological treatments, and outcomes were recorded. Neurofilament protein immunoexpression served to identify NFP-positive tumor cells (normal entrapped neurons and mature ganglion-like cells excluded). RESULTS Neurofilament-positive cells were identified in 177 GBMs (58.6%). Patients with NFP-positive GBMs were younger (p < 0.0001), and their GBMs presented with more temporal lobe tumor localization (p = 0.029) and more cortical involvement (p = 0.0003). Neurofilament-negative GBMs presented with more ventricular contact (p < 0.0001) and more tumor midline crossing (p = 0.03). Median overall survival and progression-free survival (PFS) were 13.0 and 7.6 months, respectively, for NFP-positive GBMs, and 7.0 and 5.1 months, respectively, for NFP-negative GBMs. Multivariate analysis revealed NFP immunoexpression, tumor midline crossing, complete resection, and radiotherapy combined with chemotherapy as independent factors associated with overall survival. Neurofilament protein-positive immunoexpression was associated with longer overall survival (hazard ratio [HR] 0.54, 95% CI 0.40-0.74; p < 0.0001) and longer PFS (HR 0.71, 95% CI 0.53-0.96; p = 0.02). CONCLUSIONS Neurofilament protein-positive immunoexpression represents a strong, therapeutically independent prognostic factor for primary supratentorial GBM clinical outcome among adult patients. Neurofilament protein-GBMs unique pathological features are not only associated with distinct clinical and anatomical behavior, but are also predictive of overall patient survival and PFS. Neurofilament protein immunoexpression may help identify a distinct subgroup of primary GBMs with a favorable prognosis, which should be considered in the design of future targeted therapies.

Oligodendrogliomes : historique des classifications

Resume L’histoire des classifications des tumeurs gliales se confond avec celle de l’evolution et du developpement des techniques d’etude cytologique et histologique du parenchyme cerebral. Apres une revue de ces techniques et des decouvertes progressives des differents types cellulaires du systeme nerveux central, les principales classifications des tumeurs gliales sont presentees par ordre chronologique. Les premieres classifications sont dues a Bailey et Cushing en 1926 et sont basees sur une theorie histo-embryogenetique. Puis Kernohan introduit, en 1938, puis 1949, le concept d’anaplasie. Les classifications de l’OMS, en 1979, puis 1993 et 2000, retiennent des elements de ces deux systemes et introduisent progressivement mais implicitement la notion de criteres histologiques de malignite. Plus recemment, des elements de genetique moleculaire puis d’evolutivite clinique sont retenus. La classification des oligodendrogliomes de Sainte-Anne est basee sur la confrontation de l’histologie et de l’imagerie, et inclut la notion de structure spatiale histologique. La prise de contraste en imagerie est etroitement liee au degre d’hyperplasie endothelio-capillaire. Les classifications des tumeurs gliales sont evolutives et des confusions peuvent encore survenir en raison du manque de reproductibilite et des variations d’interpretation des prelevements.

Diffusion-weighted imaging of the prostate: should we use quantitative metrics to better characterize focal lesions originating in the peripheral zone?

AbstractPurposeTo compare inter-reader concordance and accuracy of qualitative diffusion-weighted (DW) PIRADSv2.0 score with those of quantitative DW-MRI for the diagnosis of peripheral zone prostate cancer.Materials and methodsTwo radiologists independently assigned a DW-MRI-PIRADS score to 92 PZ-foci, in 74 patients (64.3±5.6 years old; median PSA level: 8 ng/ml, normal DRE in 70 men). A standardised ADCmean and nine ADC-derived parameters were measured, including ADCratios with the whole-prostate (WP-ADCratio) or the mirror-PZ (mirror-ADCratio) as reference areas. Surgical histology and MRI-TRUS fusion-biopsy were the reference for tumours and benign foci, respectively. Inter-reader agreement was assessed by the Cohen-kappa-coefficient and the intraclass correlation coefficient (ICC). Univariate-multivariate regressions determined the most predictive factor for cancer.ResultsFifty lesions were malignant. Inter-reader concordance was fair for qualitative assessment, but excellent for quantitative assessment for all quantitative variables. At univariate analysis, ADCmean, WP-ADCratio and WL-ADCmean performed equally, but significantly better than the mirror-ADCratio (p<0.001). At multivariate analysis, the only independent variable significantly associated with malignancy was the whole-prostate-ADCratio. At a cut-off value of 0.68, sensitivity was 94–90 % and specificity was 60–38 % for readers 1 and 2, respectively.ConclusionThe whole-prostate-ADCratio improved the qualitative inter-reader concordance and characterisation of focal PZ-lesions.Key Points• Inter-reader concordance of DW PI-RADSv2.0 score for PZ lesions was only fair. • Using a standardised ADCmean measurement and derived DW-quantitative parameters, concordance was excellent. • The whole-prostate ADCratio performed significantly better than the mirror-ADCratio for cancer detection. • At a cut-off of 0.68, sensitivity values of WP-ADCratio were 94–90 %. • The whole-prostate ADCratio may circumvent variations of ADC metrics across centres.

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.