Textilome paravertebral revele par des lombalgies 14 ans apres une discectomie lombaire. Revue de la litterature

Le textilome est rare et surtout asymptomatique dans les cas chroniques. Il peut être confondu avec d’autres masses des parties molles. Cette complication peropératoire a rarement été rapportée dans une localisation intraspinale ou paraspinale. Nous présentons un patient chez qui une compresse chirurgicale conservée entre les muscles paravertébraux a été découverte 14 ans après une chirurgie lombaire. L’imagerie par résonance magnétique (IRM) a révélé une lésion de masse dans la région paravertébrale postérieure. Les textilomes devraient être inclus dans le diagnostic différentiel des masses de parties molles détectées chez les patients ayant des antécédents de chirurgie rachidienne postérieure.Mots clés: Textilome, chirurgie lombaire postérieure, complication chirurgicaleEnglish Title: Paraspinal textiloma revelated by lombalgia 14 year after lumbar discectomy. Review of the literatureEnglish AbstractTextiloma is rare and mostly asymptomatic in chronic cases. It can be confused with other soft tissue masses. This intraoperative complication has rarely been reported for an intraspinal or paraspinal location. We present a patient in whom a retained surgical sponge between the paraspinal muscles was encountered 14 years after lumbar surgery. Spinal magnetic resonance imaging (MRI) revealed a mass lesion in the posterior paravertebral region.textilomas should be included in the differential diagnosis of paraspinal softtissue masses detected in patients with a history of posterior spinal surgery.Keywords: Textiloma, Posterior lumbar surgery, surgical complicatio

CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma

Background The diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL. Methods We retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion. Results CSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P < .001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P < .001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P < .001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively. Conclusion Assessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these result

Staging of Neurofibrillary Pathology in Alzheimer's Disease: A Study of the BrainNet Europe Consortium

It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and β-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-µm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V–VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I–II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers

Assessment of β-amyloid deposits in human brain: a study of the BrainNet Europe Consortium

β-Amyloid (Aβ) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as ι and α synuclein related lesions, also Aβ related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of Aβ, i.e. phase 1 = deposition of Aβ exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of Aβ phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of Aβ-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer’s disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the Aβ phase in AD is feasible even in large scale retrospective studies

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit

The transcriptional landscape of Shh medulloblastoma

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.info:eu-repo/semantics/publishedVersio

Implication of collapsin response mediator protein (CRMP) and semaphorin pathways in tumor pathoglogy

L'expansion d'une tumeur résulte d'une multiplication non contrôlée des cellules tumorales, de l'acquisition de leur capacité à migrer, ainsi que de la genèse du réseau vasculaire nécessaire à leur survie. Ces propriétés reposent en partie sur la mise en jeu de molécules impliquées dans le guidage cellulaire telles que les sémaphorines, initialement décrites pour leur implication dans le guidage axonal au cours du développement du système nerveux. Leurs fonction s'étendent actuellement au contrôle de l'angiogénèse de la migration des précurseurs nerveux ainsi que du cycle cellulaire. Les voies de signalisation intra-cellulaires des sémaphorines ne sont que partiellement connues. Les CRMP (CollapsinResponse Mediator Protein) font partie de leurs médiateurs intracytoplasmiques, décrites au cours de la rétraction du cône de croissance induit par la sémaphorine 3A (Sema3A). L'implication en pathologie tumorale de ces voies de signalisation a été découverte par l!étude de gènes tel que celui de la sémaphorine 3F (Sema3F), présents dans les régions délétées du chromosome 3 de certains types de tumeurs non neuroendocrines du poumon L'implication des CRMP a été également révélée par les syndromes neurologiques paranéoplasiques (SNP). Ces syndromes résultent d'une auto-immunisation humorale des patients contre des antigènes exprimés par la tumeur dont ils sont atteints. C'est le cas de CRMP5, protéine, identifiée dans notre laboratoire comme cible des auto-anticorps anti-CV2/ CRMP5 dans le cadre des SNP associés à des tumeurs neuroendocrines du poumon, les carcinomes à petites cellules (CPC) ainsi qu'à des thymomes. Alors que les thymomes sont des tumeurs bénignes, les CPC représentent 20% des carcinomes pulmonaires et sont, avec les carcinomes neuroendocrines à grandes cellules, les formes les plus agressives des tumeurs du poumon. Notre objectif était d'étudier l'implication physiopathologique des CRMP dans les différents types de carcinomes du poumon et dans les thymomes ainsi que dans les tumeurs du système nerveux central en relation avec la signalisation des sémaphorines. Nous avons ainsi démontré une expression exclusive de CRMP5 par les carcinomes neuroendocrines du poumon et les gliomes de haut grade par comparaison aux carcinomes non neuroendocrines et aux thymomes. CRMP5 n'est pas exprimée dans les carcinomes non neuroendocrines du poumon desquels sont dérivés les lignées H460 et H157. Ces observations ont été complétées par deux collaborations à des études portant sur les voies de signalisation des sémaphorines dans des modèles cellulaires de ces tumeurs. La première étude a montré que Sema3F, surexprimée dans la lignée H157 possède un effet anti-tumoral. La voie de signalisation de Sema3F nécessite neuropiline 2, l'inactivation de la MAPK (Mitogen Activated Protein Kinase) Erk 1/2 et entraîne l!inhibition de l'adhésion des intégrines !vß3, avec participation de CRMP1 et CRMP4 mais pas de CRMP5. La deuxième étude a établi que sous Sema3A la voie de signalisation d'Erk ½ est activée par le complexe de récepteur NRP1/VEGFR1 lors de la migration de précurseurs nerveux. Dans ces conditions Sema3A entraîne des modulations des expressions des CRMP2, CRMP4 et CRMP5 suggérant leur implication. Ainsi, ce travail montre que l!activation de certaines voies de signalisation des sémaphorines sont spécifiques des types histopathologiques et des grades des tumeurs. Ces voies de signalisations sont médiées par des complexes de récepteurs précis et mettent souvent en jeu les CRMPTumour growth is a consequence of uncontrolled cell proliferation, cell migration and angiogenesis. These functions are partly controlled by molecules involved in cellular guidance. Among these molecules, the semaphorins, previously described in axonal guidance during development, interestingly control cell migration, angiogenesis, apoptosis and proliferation. Signalling pathways of Semaphorins are only partially known. CRMP (Collapsin Response Mediator Protein) are involved in the signalling semaphoring pathway, precisely as mediator of Sema3A induced growth cone collapse. Implication of these signalling pathways in tumour growth was initially discovered with Sema3F localised in frequently deleted regions of the third chromosome found in non neuroendocrine lung carcinoma. CRMP involvement was also discovered in neurological paraneoplastic syndromes (NPS). These syndromes result of an auto-immunisation against tumour antigens present in some patients. CRMP5 was identified by our laboratory as a target of anti-CV2/CRMP5 auto-antibodies seen in some NPS associated with small cell lung carcinoma (SCLC) and thymoma. While thymoma are benign tumours, SCLC account for 20% of all lung tumour pathological subtypes and represent with large cell neuroendocrine carcinoma the most clinically aggressive subtypes of lung tumours. Our aim was to study the physiopathological role of CRMP among the different subtypes of lung carcinoma, thymoma and central nervous system tumours and their relationship with semaphorin signalling pathways. We showed a specific diffuse expression of CRMP5 by high grade neuroendocrine carcinoma and high grade glioma tumour cells. CRMP5 is neither expressed by non neuroendocrine lung carcinoma nor H460 or H157 derived cell lines, nor thymoma. Additionally, 2 collaborative studies were undertaken, focusing on semaphorin cell signalling in tumour derived cell lines. The first study showed an anti tumour effect of Sema3F over-expressed in H157 cell line mediated by neuropilin 2, CRMP2 and CRMP4 but not by CRMP5. It showed that Sema3F stimulation led to the inactivation of Erk1/2 MAPK (Mitogen Activated Protein Kinase) and inhibition of !vß3 integrin mediated adhesion. The second study showed that Sema3A induced DEV cells migration was mediated by neuropilin1/VEGFR1 receptor complex and activated Erk1/2 pathway. CRMP2, CRMP4 and CRMP5 expression changes suggested their involvement in that pathway. Thus, these data show that some semaphorin pathways activation were specific of tumour pathological subtype and grade. These signalling pathways were precisely mediated by specific receptor complexes and different CRMPs isoform

Les tumeurs neuroendocrines du thymus : À propos de 6 cas

National audienceAim: the aim of our study was to analyze a series of 6 thymic neuroendocrine tumors (TNET). Methods: we report the clinical and pathological features of 6 TNET reclassified according to the last WHO classification (2004). Results: there were 4 men and 2 women, (mean age of 61.3 years), presenting with local symptoms in 4 cases. The tumors were reclassified as 3 atypical carcinoids (AC), 2 small cell carcinomas (SCC) and 1 large cell neuroendocrine carcinoma (LCNEC). Cytokeratin, EMA and neuroendocrine markers were expressed in poorly-differentiated tumors. Two patients were lost of follow-up. Two patients with AC died of disease at 20 and 36 months. One patient with SCC died of disease at 2 years and the patient with the LCNEC died of disease in 3 months. Conclusion:TNET are poor prognosis tumors with a prognosis similar to thymic carcinomas. Adequate surgical resection is a strong prognosis factor.Objectifs : l’objectif de ce travail était l’étude de 6 tumeurs neuroendocrines du thymus (TNET). Méthodes : nous rapportons les données cliniques, anatomo-pathologiques et évolutives de 6 TNET reclassées selon la dernière classification OMS (2004). Résultats : il s’agissait de 4 hommes et 2 femmes, âgés en moyenne de 61,3 ans avec des signes locaux dans 4 cas. Les tumeurs étaient classées en 3 carcinoïdes atypiques (CA), 2 carcinomes à petites cellules (CPC) et 1 carcinome neuroendocrine à grandes cellules (CNEGC). Les pancytokératines, l’EMA et les marqueurs neuroendocrines étaient exprimés par les carcinomes peu différenciés. Deux patients ont été perdus de vue. Les 2 patients porteurs d’un CA sont décédés de leur maladie à 20 et 36 mois. Le patient avec un CPC est décédé de sa maladie à 2 ans et le patient porteur du CNEGC est décédé à 3 mois. Conclusion : les TNET sont des tumeurs de mauvais pronostic avec un pronostic proche des carcinomes thymiques. La qualité de l’exérèse chirurgicale est un facteur pronostique majeur

Intratumoral Myeloid Cells Regulate Responsiveness and Resistance to Antiangiogenic Therapy

Antiangiogenic therapy is commonly used in the clinic, but its beneficial effects are short-lived, leading to tumor relapse within months. Here, we found that the efficacy of angiogenic inhibitors targeting the VEGF/VEGFR pathway was dependent on induction of the angiostatic and immune-stimulatory chemokine CXCL14 in mouse models of pancreatic neuroendocrine and mammary tumors. In response, tumors reinitiated angiogenesis and immune suppression by activating PI3K signaling in all CD11b+ cells, rendering tumors nonresponsive to VEGF/VEGFR inhibition. Adaptive resistance was also associated with an increase in Gr1+CD11b+ cells, but targeting Gr1+ cells was not sufficient to further sensitize angiogenic blockade because tumor-associated macrophages (TAMs) would compensate for the lack of such cells and vice versa, leading to an oscillating pattern of distinct immune-cell populations. However, PI3K inhibition in CD11b+ myeloid cells generated an enduring angiostatic and immune-stimulatory environment in which antiangiogenic therapy remained efficient