176 research outputs found
Classification and controversies in pathology of ependymomas.
No full textPURPOSE: Bailey and Cushing established ependymoma as a brain tumour entity in the first brain tumour classification (1926). Diagnosis of ependymomas is not subject to controversy as long as other tumours presenting ependymoma-like features have been ruled out. Grading conversely is a source of debate. Description of histological features establishing diagnosis and grading of ependymomas may help to better understand this controversy. METHODS: Literature has been reviewed using PubMed with the following key words: ependymoma, +/- prognosis, +/- biomaker, +/- grading, +/- immunohistochemistry, +/- proliferative index. RESULTS: Grading controversy arises from elusive WHO features and individual characteristics of ependymomas including tumour location, tumour pattern/variant and variable expression of biomarkers. CONCLUSION: There is a need for a grading scheme with a proven general ability to dissociate grades, and to predict individual clinical evolution. Only then will stratified and targeted therapeutics for ependymal tumours be possible
Histopathological grading of pediatric ependymoma: Reproducibility and clinical relevance in European trial cohorts
No full textBackground: Histopathological grading of ependymoma has been controversial with respect to its reproducibility and clinical significance. In a 3-phase study, we reviewed the pathology of 229 intracranial ependymomas from European trial cohorts of infants (2 trials - SFOP/CNS9204) and older children (2 trials - AIEOP/CNS9904) to assess both diagnostic concordance among five neuropathologists and the prognostic utility of histopathological variables, particularly tumor grading. Results: In phase 1, using WHO criteria and without first discussing any issue related to grading ependymomas, pathologists assessed and independently graded ependymomas from 3 of 4 trial cohorts. Diagnosis of grade II ependymoma was less frequent than grade III, a difference that increased when one cohort (CNS9204) was reassessed in phase 2, during which the pathologists discussed ependymoma grading, jointly reviewed all CNS9204 tumors, and defined a novel grading system based on the WHO classification. In phase 3, repeat independent review of two cohorts (SFOP/CNS9904) using the novel system was associated with a substantial increase in concordance on grading. Extent of tumor resection was significantly associated with progression-free survival (PFS) in SFOP and AIEOP, but not in CNS9204 and CNS9904. Strength of consensus on grade was significantly associated with PFS in only one trial cohort (AIEOP). Consensus on the scoring of individual histopathological features (necrosis, angiogenesis, cell density, and mitotic activity) correlated with PFS in AIEOP, but in no other trial. Conclusions: We conclude that concordance on grading ependymomas can be improved by using a more prescribed scheme based on the WHO classification. Unfortunately, this appears to have utility in limited clinical settings. © 2011 Ellison et al; licensee BioMed Central Ltd
Morphological analysis of mouse hepatitis virus A59-induced pathology with regard to viral receptor expression
No full textMouse hepatitis virus, strain A59 (MHV-A59), is a coronavirus that triggers in susceptible mice a wide variety of pathologies, including hepatitis, thymus involution, B lymphocyte polyclonal activation and, after intra-cerebral inoculation, transient demyelination. A receptor that mediates entry of the virus into target cells has been identified: it is a glycoprotein of the carcinoembryonic antigen family, called Bgp1a. The availability of antibodies recognizing this molecule permits the analysis of its cellular expression and of the relationship between receptor expression and pathology induced by the virus. Bgp1a is found on epithelial and endothelial cells as well as on B lymphocytes and macrophages. In the liver, Bgp1a expression correlates well with infection of hepatocytes and endothelial cells, leading to the development of hepatitis. However, other cells expressing this molecule, such as central nervous system endothelial cells, are not infected by the virus. This observation may explain how the blood-brain barrier prevents dissemination of MHV-A59 from the general circulation into the brain. Thymic atrophy results from apoptosis of immature double-positive T lymphocytes that might be caused indirectly by infection of T cells that do not express the receptor. Finally, polyclonal activation of B lymphocytes, leading to increased secretion of antibodies of the IgG2a isotype, involves a cascade of events, including cytokine secretion, that may result from the interaction of MHV-59 with B cells and macrophages that express Bgp1a. Therefore, after viral infection, cellular expression of BGP1a may result in different outcomes: cell lysis, alteration of cellular functions that may lead to indirect death of other cell types, or resistance to infectionThèse d'agrégation de l'enseignement supérieur (Faculté de médecine) - UCL, 199
Mutation de LZTR1 et fusion YAP1::MAML2, des anomalies génétiques associées aux NF2, identifiées pour la première fois dans un cas d'ETMR non C19MC
No full textContexte : le méthylome, une technique d’analyse du profile de méthylation du génome, a permis une nouvelle approche de classification des tumeurs, notamment du système nerveux central. Elle fait partie intégrante de la dernière classification OMS des tumeurs du système nerveux central (2021). Les tumeurs embryonnaires à rosettes multicouches (ETMR) sont, dans 90 % des cas, caractérisées par une amplification de la région chromosomique 19q13.42 (C19mc). En l’absence de cette amplification, l’autre anomalie génétique classiquement retrouvée, est une mutation de DICER1. De très rares cas d’ETMR ne présentent aucune de ces deux anomalies génétique (2 %).Objectif : décrire de nouvelles anomalies génétiques dans le cadre d’une ETMR sans C19mc et montrer l’impact du méthylome dans le diagnostic de cette lésion.Méthode : analyse histo-moléculaire d’une tumeur de la fosse postérieure affectant un nourrisson âgé de 4 mois.Résultat : les analyses histologique et immunohistochimique suggèrent un diagnostic d’ETMR mais d’autres hypothèses restent plausibles. Le méthylome classe cette lésion dans les EMTR sans C19mc (V12.5) mais avant, seul un UMAP réalisé sur un site public, agrège la lésion avec les ETMR. La CGH confirme l’absence d’amplification de la région 19q13.42. Une mutation de LZTR1 est identifiée sur un panel ADN en l’absence de mutation de DICER1. Une fusion de YAP1::MAML2 est retrouvée par RNAseq.Conclusion : le méthylome, aidé au départ d’un UMAP, a permis d’assoir le diagnostic d’ETMR sans C19 devant une lésion d’aspect histologique inhabituel qui, de plus, démontrait la présence d’anomalies génétiques non encore décrites dans ce cadre. Il s’agissait de mutation de LZTR1 et de fusion de YAP1::MAML2, deux anomalies récemment associées aux neurofibromatoses de type 2
Ectomesenchymome, être ou ne pas être : revue de la littérature et discussion à propos d'une tumeur supra-tentorielle chez un adulte
No full textEctomesenchymoma is a rare sarcoma defined in the 5th edition of the WHO classification of soft tissue and bone tumours. It’s a biphasic lesion constituted of cells of mesenchymal lineage that most frequently resemble to rhabomyosarcoma, and of cells of neuronal lineage presenting a differentiation ranging from ganglionic cells to neuroblastic elements. This tumour most frequently affects children and is located in the peripheral region but adult cases and central nervous system located ones have been published. Reported genetic data are scarce and have not allowed the identification of a genetic signature. Herein, we report a case of an unusual adult thalamic and intra-ventricular malignant tumour constituted of a muscular component intermingled with a neuronal one. Genetic data are provided including methylation profile. A literature review based on 98 published cases of ectomensenchymoma questioned about the present tumour diagnosis, ectomesenchymoma or not, and the definition of this tumoral entity.L’ectomésenchymome malin est un sarcome rare défini par l’OMS dans la 5ème édition de la classification des tumeurs des tissus mous et de l’os. Il s’agit d’une lésion biphasique constituée d’une composante mésenchymateuse avec des aspects de rhabdomyosarcome et d’une composante neuronale ou neuroblastique. Cette tumeur affecte très majoritairement des enfants et les localisations sont variables, principalement génito-abdomino-pelviennes. Les données génétiques rapportées sont rares et n’ont à ce jour pas permis d’identifier une signature spécifique.Nous rapportons le cas d’un ectomésenchymome inhabituel, survenu chez un homme de 43 ans et de localisation cérébrale supratentorielle. Sa comparaison avec une revue de la littérature basée sur 98 cas publiés d’ectomésenchymomes ainsi que son analyse génétique et son profil de méthylation nous amène à nous questionner sur la définition et la classification de cette entité
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