Explore the vast range of titles available.

ATRX immunostaining constitutes a routinely used biomarker for the practice of neuropathology. The loss of ATRX expression correlating with ATRX gene alterations is implicated in a wide variety of pediatric and adult gliomas, and has been indexed as a desirable or essential diagnostic criterion for four tumor types featured in the latest world health organization classification of central nervous system Tumors. In adult-type diffuse glioma, the loss of ATRX expression is a hallmark of astrocytoma, IDH-mutant. Recently, novel tumor types and alterations have been referenced in the literature. These include the high-grade astrocytoma with piloid features (HGAP), for which no consistent clinicopathological features have been defined, and the presence of other alterations in the Krebs cycle genes (variants of the Fumarate hydratase - FH- gene) found in gliomas resembling astrocytomas, IDH-mutant. Because of this rapidly evolving classification and histomolecular landscape, we retrospectively analyzed adult gliomas diagnosed over a four consecutive year period to identify supratentorial gliomas, lacking H3 alterations or IDH mutations and harboring a loss of ATRX expression, in order to update their diagnoses in terms of histopathology, genetics and epigenetics. Four specimens (from 620 adult gliomas, 0.7%) were reclassified at the end of the molecular workup, as: 1/ one HGAP, 2/ one malignant transformation with a primitive neuronal component of an astrocytoma, IDH-mutant which lost the IDH2 mutation at recurrence, 3/ a glioma, FH- mutant for which the histopathological and epigenetic features were similar to an astrocytoma, IDH-mutant, and 4/ a glioblastoma, IDH-wildtype. To conclude, these exceptional cases extend the spectrum of ATRX loss in gliomas, beyond the astrocytoma, IDH-mutant and the diffuse hemispheric glioma, H3 G34-mutant.

A novel histomolecular tumor, the “intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive”, has recently been identified and added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System. One of the essential diagnostic criteria defined in this classification is the intracranial location of the tumor. Herein, we report a spinal case of IMT with a classical EWSR1::CREM fusion . We compare its clinical, histopathological, immunophenotypical, genetic and epigenetic features with those previously described in IMT, FET::CREB fusion-positive. The current case presented histopathological (epithelioid morphology with mucin-rich stroma, and expression of EMA and desmin), radiological (an extraparenchymal lobulated mass without dural tail), genetic (fusion implicating the EWSR1 and CREM genes), and epigenetic (DNA-methylation profiling) similarities to previously reported cases. This case constitutes the third “extracranial” observation of an IMT. Our results added data suggesting that the terminology “IMT, FET::CREB fusion-positive” is provisional and that further series of cases are needed to better characterize them.

The Central Nervous System (CNS) tumor with BCOR internal tandem duplication (ITD) has recently been added as a novel embryonal histomolecular tumor type to the 2021 World Health Organization (WHO) Classification of CNS Tumors. In addition, other CNS tumors harboring a BCOR/BCORL1 fusion , which are defined by a distinct DNA-methylation profile, have been recently identified in the literature but clinical, radiological and histopathological data remain scarce. Herein, we present two adult cases of CNS tumors with EP300::BCOR fusion. These two cases presented radiological, histopathological, and immunohistochemical homologies with CNS tumors having BCOR ITD in children. To compare these tumors with different BCOR alterations, we performed a literature review with a meta-analysis. CNS tumors with EP300::BCOR fusion seem to be distinct from their BCOR ITD counterparts in terms of age, location, progression-free survival, tumor growth pattern, and immunopositivity for the BCOR protein. CNS tumors from the EP300::BCOR fusion methylation class in adults may be added to the future WHO classification.

A novel histomolecular tumor of the central nervous system, the “intracranial mesenchymal tumor (IMT), FET-CREB fusion-positive” has recently been identified in the literature and will be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System. However, our latest study using DNA-methylation analyses has revealed that intracranial FET-CREB fused tumors do not represent a single molecular tumor entity. Among them, the main subgroup presented classical features of angiomatoid fibrous histiocytoma, having ultrastructural features of arachnoidal cells, for. Another tumor type with clear cell component and histopathological signs of aggressivity clustered in close vicinity with clear cell sarcoma of soft tissue. Herein, we report one case of IMT with a novel SMARCA2-CREM fusion which has until now never been described in soft tissue or the central nervous system . We compare its clinical, histopathological, immunophenotypic, genetic and epigenetic features with those previously described in IMT, FET-CREB fusion-positive. Interestingly, the current case did not cluster with IMT, FET-CREB fusion-positive but rather presented histopathological (clear cell morphology with signs of malignancy), clinical (with a dismal course with several recurrences, metastases and finally the patient’s death), genetic (fusion implicating the CREM gene), and epigenetic (DNA-methylation profiling) similarities with our previously reported clear cell sarcoma-like tumor of the central nervous system. Our results added data suggesting that different clinical and histomolecular tumor subtypes or grades seem to be included within the terminology “IMT, FET-CREB fusion-positive”, and that further series of cases are needed to better characterize them.

The outcomes of adolescents/young adults with osteosarcoma have not improved in decades. The chaotic karyotype of this rare tumor has precluded the identification of prognostic biomarkers and patient stratification. We reasoned that transcriptomic studies should overcome this genetic complexity. RNA sequencing (RNA-seq) of 79 osteosarcoma diagnostic biopsies identified stable independent components that recapitulate the tumor and microenvironment cell composition. Unsupervised classification of the independent components stratified this cohort into favorable (G1) and unfavorable (G2) prognostic tumors in terms of overall survival. Multivariate survival analysis ranked this stratification as the most influential variable. Functional characterization associated G1 tumors with innate immunity and G2 tumors with angiogenic, osteoclastic, and adipogenic activities as well as PPARγ pathway upregulation. A focused gene signature that predicted G1/G2 tumors from RNA-seq data was developed and validated within an independent cohort of 82 osteosarcomas. This signature was further validated with a custom NanoString panel in 96 additional osteosarcomas. This study thus proposes new biomarkers to detect high-risk patients and new therapeutic options for osteosarcoma. Significance: These findings indicate that the osteosarcoma microenvironment composition is a major feature to identify hard-to-treat patient tumors at diagnosis and define the biological pathways and potential actionable targets associated with these tumors.

Background and objectives Contrast enhancement in glioblastoma, IDH -wildtype is common but not systematic. In the era of the WHO 2021 Classification of CNS Tumors, the prognostic impact of a contrast enhancement and the pattern of contrast enhancement is not clearly elucidated. Methods We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre (January 2006 - December 2022). We screened adult patients with a newly-diagnosed glioblastoma, IDH -wildtype in order to assess the prognosis role of the contrast enhancement and the pattern of contrast enhancement. Results We included 1149 glioblastomas, IDH -wildtype: 26 (2.3%) had a no contrast enhancement, 45 (4.0%) had a faint and patchy contrast enhancement, 118 (10.5%) had a nodular contrast enhancement, and 960 (85.5%) had a ring-like contrast enhancement. Overall survival was longer in non-contrast enhanced glioblastomas (26.7 months) than in contrast enhanced glioblastomas (10.9 months) ( p  < 0.001). In contrast enhanced glioblastomas, a ring-like pattern was associated with shorter overall survival than in faint and patchy and nodular patterns (10.0 months versus 13.0 months, respectively) ( p  = 0.033). Whatever the presence of a contrast enhancement and the pattern of contrast enhancement, surgical resection was an independent predictor of longer overall survival, while age ≥ 70 years, preoperative KPS score < 70, tumour volume ≥ 30cm 3 , and postoperative residual contrast enhancement were independent predictors of shorter overall survival. Conclusion A contrast enhancement is present in the majority (97.7%) of glioblastomas, IDH -wildtype and, regardless of the pattern, is associated with a shorter overall survival. The ring-like pattern of contrast enhancement is typical in glioblastomas, IDH -wildtype (85.5%) and remains an independent predictor of shorter overall survival compared to other patterns (faint and patchy and nodular).

BackgroundDiagnosing probable cerebral amyloid angiopathy (CAA) after lobar intra-cerebral hemorrhage (l-ICH) currently relies on the MR-based modified Boston criteria (mBC). However, MRI has limited availability and the mBC have moderate sensitivity, with isolated l-ICH being classified as “possible CAA”. A recent autopsy-based study reported potential value of finger-like projections (FLP) and subarachnoid hemorrhage (SAH) on acute CT. Here we assessed these markers’ performance in a cohort most of whom survived the index episode.MethodsWe included all patients from a prospective pathology database with non-traumatic l-ICH, admission CT and available tissue sample showing no alternative cause. CT was assessed by two blinded independent neuroradiologists. Interobserver reproducibility was almost perfect for SAH and substantial for FLP.ResultsSixteen patients were eligible [age 65.8 ± 7.2 yrs; hematoma volume: 39(26, 71)mls; hematoma evacuation sample 15 patients; autopsy one patient]. MRI was available in 11 patients. ICH-related death affected six patients. Aβ40–42 immunohistochemistry revealed CAA in seven patients (44%). SAH and FLP were present in 12/16 (75%) and 10/16 (62%) patients, respectively. SAH had 100% sensitivity for CAA but low specificity; FLP had lower performance. Using either pathology or MRI as reference standard yielded essentially similar results. All patients with possible CAA on MRI but CAA on pathology had SAH.ConclusionsIn patients with moderate-size l-ICH who mostly survived the index event, SAH had perfect sensitivity and better performance than FLP. In addition, SAH appeared to add onto MRI in possible CAA, the clinically most relevant scenario. Studies in larger samples are however warranted.

Purpose Frailty increases the risk of mortality among patients. We studied the prognostic significance of frailty using the modified 5-item frailty index (5-mFI) in patients harboring a newly diagnosed supratentorial glioblastoma, IDH -wildtype. Methods We retrospectively reviewed records of patients surgical treated at a single neurosurgical institution at the standard radiochemotherapy era (January 2006 - December 2021). Inclusion criteria were: age ≥ 18, newly diagnosed glioblastoma, IDH -wildtype, supratentorial location, available data to assess the 5-mFI index. Results A total of 694 adult patients were included. The median overall survival was longer in the non-frail subgroup (5-mFI < 2, n  = 538 patients; 14.3 months, 95%CI 12.5–16.0) than in the frail subgroup (5-mFI ≥ 2, n  = 156 patients; 4.7 months, 95%CI 4.0-6.5 months; p  < 0.001). 5-mFI ≥ 2 (adjusted Hazard Ratio (aHR) 1.31; 95%CI 1.07–1.61; p  = 0.009) was an independent predictor of a shorter overall survival while age ≤ 60 years (aHR 0.78; 95%CI 0.66–0.93; p  = 0.007), KPS score ≥ 70 (aHR 0.71; 95%CI 0.58–0.87; p  = 0.001), unilateral location (aHR 0.67; 95%CI 0.52–0.87; p  = 0.002), total removal (aHR 0.54; 95%CI 0.44–0.64; p  < 0.0001), and standard radiochemotherapy protocol (aHR 0.32; 95%CI 0.26–0.38; p  < 0.0001) were independent predictors of a longer overall survival. Frailty remained an independent predictor of overall survival within the subgroup of patients undergoing a first-line oncological treatment after surgery ( n  = 549) and within the subgroup of patients who benefited from a total removal plus adjuvant standard radiochemotherapy ( n  = 209). Conclusion In newly diagnosed supratentorial glioblastoma, IDH -wildtype patients treated at the standard combined radiochemotherapy era, frailty, defined using a 5-mFI score ≥ 2 was an independent predictor of overall survival.