Enrichment of oligodendrocyte precursor phenotypes in subsets of low-grade glioneuronal tumours.

Current histological classification of low-grade glioneuronal tumours does not adequately represent their underlying biology. The neural lineage(s) and differentiation stage(s) involved and the cell state(s) affected by the recurrent genomic alterations are unclear. Here, we describe dysregulated oligodendrocyte lineage developmental programmes in three low-grade glioneuronal tumour subtypes. Ten dysembryoplastic neuroepithelial tumours, four myxoid glioneuronal tumours and five rosette-forming glioneuronal tumours were collected. Besides a comprehensive characterization of clinical features, known diagnostic markers and genomic alterations, we used comprehensive immunohistochemical stainings to characterize activation of rat sarcoma/mitogen-activated protein kinase pathway, involvement of neuronal component, resemblance to glial lineages and differentiation blockage along the stages of oligodendrocyte lineage. The findings were further complemented by gene set enrichment analysis with transcriptome data of dysembryoplastic neuroepithelial tumours from the literature. Dysembryoplastic neuroepithelial tumours, myxoid glioneuronal tumours and rosette-forming glioneuronal tumours occur at different ages, with symptoms closely related to tumour location. Dysembryoplastic neuroepithelial tumours and myxoid glioneuronal tumours contain oligodendrocyte-like cells and neuronal component. Rosette-forming glioneuronal tumours contained regions of rosette-forming neurocytic and astrocytic features. Scattered neurons, identified by neuronal nuclei antigen and microtubule-associated protein-2 staining, were consistently observed in all dysembryoplastic neuroepithelial tumours and myxoid glioneuronal tumours examined, but only in one rosette-forming glioneuronal tumour. Pervasive neurofilament-positive axons were observed only in dysembryoplastic neuroepithelial tumour and myxoid glioneuronal tumour samples. Alterations in B-Raf proto-oncogene, serine/threonine kinase, fibroblast growth factor receptor 1, fibroblast growth factor receptor 3 and platelet-derived growth factor receptor alpha occurred in a mutually exclusive manner, coinciding with strong staining of phospho-p44/42 mitogen-activated protein kinase and low apoptotic signal. All dysembryoplastic neuroepithelial tumours, myxoid glioneuronal tumours and the neurocytic regions of rosette-forming glioneuronal tumours showed strong expression of neuron-glia antigen 2, platelet-derived growth factor receptor alpha (markers of oligodendrocyte precursor cells) and neurite outgrowth inhibitor-A (a marker of developing oligodendrocytes), but lacked the expression of oligodendrocyte markers ectonucleotide pyrophosphatase/phosphodiesterase family member 6 and myelin basic protein. Notably, transcriptomes of dysembryoplastic neuroepithelial tumours were enriched in oligodendrocyte precursor cell signature, but not in signatures of neural stem cells, myelinating oligodendrocytes and astrocytes. Dysembryoplastic neuroepithelial tumour, myxoid glioneuronal tumour and rosette-forming glioneuronal tumour resemble oligodendrocyte precursor cells, and their enrichment of oligodendrocyte precursor cell phenotypes is closely associated with the recurrent mutations in rat sarcoma/mitogen-activated protein kinase pathway.

Clinical and pathologic features of Sturge-Weber syndrome in patients with refractory epilepsy.

OBJECTIVES: We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. METHODS: Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. RESULTS: Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P = .015). CONCLUSIONS: Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS.

Primary papillary epithelial tumor of the sella and posterior pituitary tumor show similar (epi)genetic features and constitute a single neuro-oncological entity.

BACKGROUND: "Primary papillary epithelial tumor of the sella (PPETS)" is a recently described rare tumor entity of the central nervous system (CNS) with stereotypic location in the sella. Comprehensive molecular investigations and epigenetic profiles of PPETS have not been performed to date. METHODS: We report a comprehensive clinical, histopathologic, and molecular assessment of 5 PPETS cases in comparison with a cohort composed of 7 choroid plexus papilloma (CPP), 7 central neurocytoma (CN), 15 posterior pituitary tumor (PPT) including 4 pituicytoma, 6 granular cell tumors of the sellar region (GCT), and 5 spindle cell oncocytoma. RESULTS: All PPETS had good outcomes. Immunohistochemically, PPETS tumors showed positive staining with TTF1, EMA, AE1/AE3, MAP2, and Vimentin, but were negatively stained with Syn, GFAP, CgA, and S100, and sporadically stained with Ki-67. In unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analyses of DNA-methylation data, PPETS and PPT tumors formed a distinct cluster irrespective of their histologic types. However, PPETS tumors did not cluster together with CPP and CN samples. Similar findings were obtained when our samples were projected into the reference cohort of the brain tumor classifier. Substantial fractions of the PPETS and PPT tumors shared broadly similar chromosomal copy number alterations. No mutations were detected using targeted next-generation sequencing. CONCLUSIONS: Though more cases are needed to further elucidate the molecular pathogenesis of these tumors, our findings indicate that PPETS and PPT tumors may constitute a single neurooncological entity.

Stalled oligodendrocyte differentiation in IDH-mutant gliomas.

BACKGROUND: Roughly 50% of adult gliomas harbor isocitrate dehydrogenase (IDH) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized. METHODS: Using bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers. RESULTS: Genes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and single-cell ATAC-seq data demonstrate that genes of myelination regulators and myelin components are hypermethylated and show inaccessible chromatin status, whereas regulators of OPC specification and maintenance are hypomethylated and show open chromatin status. Markers of astrocyte precursors are not enriched in IDH-mutant gliomas. CONCLUSIONS: Our studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas.

Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

DICER1-associated central nervous system sarcoma with neural lineage differentiation: a case report.

BACKGROUND: DICER1-associated central nervous system sarcoma (DCS) without evidence of other cancer-related syndromes is rare. Though the morphology of DCS was highly variable, the immunophenotype was predominant myogenic phenotype. Other lineage markers were consistently negative. CASE PRESENTATION: We report a case of DCS with neurogenic differentiation proved by immunohistochemical staining and whole-exome sequencing (WES). An 8-year-old female patient presented with 8-day history of headache, nausea and vomiting. Magnetic resonance imaging (MRI) revealed a heterogeneous mass in the left parietal lobe. The patient underwent the craniotomy via left parietal approach to resect the tumor completely. Histologically, the tumor predominately showed fibrosarcoma-like spindle cells with obvious cytoplasmic eosinophilic globules. Immunohistochemically, the tumor stained positively for DICER1, Desmin, and several neurogenic markers. DICER1 somatic hotspot mutation was confirmed by WES, as well as TP53 and RAF1 mutations which were commonly found in DCS, and other sarcoma-associated genes including AR, AXL and ETV5 mutations. Subsequently, the result of Gene Ontology (GO) analysis showed that the mutated genes in this case were involved in neuron development. All of these findings indicated the diagnosis of DCS with neurogenic differentiation. Postoperatively, the patient received high-dose radiotherapy (60 Gy) and chemotherapy. There was no MRI evidence of tumor recurrence at the 21-month postoperative follow-up. CONCLUSIONS: This unusual DCS case with neuronal differentiation is an important addition to the immuno-phenotypic spectrum of DCS. Although the prognosis for DCS is poor, gross tumor resection with high dose radiotherapy and chemotherapy may assist in prolonging survival.

Primary adult sellar SMARCB1/INI1-deficient tumor represents a subtype of atypical teratoid/rhabdoid tumor.

Loss of function in SMARCB1/INI1 has been observed in a group of malignancies collectively defined as SMARCB1/INI1-deficient neoplasms. Primary intracranial SMARCB1/INI1-deficient tumors in adults are extremely rare. We collected eight primary adult sellar SMARCB1/INI1-deficient tumors to study their clinicopathological and (epi)genetic characteristics. We performed a comprehensive assessment of the clinical, radiological, morphological and immunohistochemical features. FISH analysis for the SMARCB1 locus and target exome sequencing for 425 cancer relevant genes were performed. Furthermore, six bona fide proximal epithelioid sarcoma (PES), fourteen atypical teratoid/rhabdoid tumors (ATRT) in brain and five pediatric poorly differentiated chordomas (PDC) in the clivus were collected for comparative analysis of differential diagnostic maker expression and DNA methylation profile. The median age was 47.1 years, ranging from 26 to 73 years. On morphology, tumors were characterized by sheets of monomorphic larger epithelioid-like cells, in two cases with rhabdoid cells. "Stag-horn" vasculatures were observed in five cases. The loss of INI1 protein expression, co-expression of epithelial makers and mesenchymal markers were observed in all cases. CD34 expression was observed in six cases. Heterozygous deletion of SMARCB1/INI1 was confirmed using FISH in six cases. The results of target exome sequencing showed three patients harbored heterozygous point mutations in SMARCB1. The epigenetic features of the primary adult sellar SMARCB1/INI1-deficient tumors resembled the ATRT-MYC subgroup, but clustered apart from PES and PDC. Based on epigenetic characteristics, primary adult sellar SMARCB1/INI1-deficient tumors represent a subtype of ATRT with similar epigenetic characteristics of ATRT-MYC subgroup. Our findings suggest that DNA methylation profiling should be utilized for differential diagnosis for the majority of epithelioid sarcoma and (sellar) rhabdoid tumor.

Histone H3.3 G34-mutant Diffuse Gliomas in Adults.

The characteristics of H3.3 G34-mutant gliomas in adults have yet to be specifically described. Thirty adults with H3.3 G34-mutant diffuse gliomas were retrospectively reviewed for clinical and pathologic information. Molecular profiling using next-generation sequencing was performed in 29 of the 30 H3.3 G34-mutant patients with 1 patient lacking available tumor samples, as well as 82 IDH/H3 wild-type adult diffuse glioma patients. The age at diagnosis of H3.3 G34-mutant diffuse gliomas was significantly younger than IDH/H3 wild-type gliomas (24 vs. 57 y, P<0.001). Overall, 19 of the 30 patients were diagnosed of glioblastoma with the primitive neuronal component, and 8 were glioblastoma. The molecular profiling analysis revealed higher frequencies of Olig-2 loss of expression, TP53 mutation, ATRX mutation, PDGFRA mutation, and MGMT promoter methylation (P<0.05) in H3.3 G34-mutant gliomas than IDH/H3 wild-type gliomas. No TERT promoter mutation and only 1 case of EGFR amplification were detected in the H3.3 G34-mutant cohort, the frequencies of which were significantly higher in the IDH/H3 wild-type cohort. A dismal prognosis was observed in H3.3 G34-mutant patients comparing to IDH/H3 wild-type cohort (overall survival: 14 vs. 22 mo; P=0.026). Univariate and multivariate analyses showed that the extent of resection and TP53 mutation were independently affecting prognosis. The distinct pathologic and molecular features of H3.3 G34-mutant diffuse gliomas in adult patients demonstrated the clinical importance of detecting H3.3 G34R/V mutations. The dismal prognosis of this rare high-grade glioma disease we reported here would further promote the investigation of dedicated therapeutic strategies.

Low-grade epilepsy-associated neuroepithelial tumors: Tumor spectrum and diagnosis based on genetic alterations.

Brain tumors can always result in seizures when involving the cortical neurons or their circuits, and they were found to be one of the most common etiologies of intractable focal seizures. The low-grade epilepsy-associated neuroepithelial tumors (LEAT), as a special group of brain tumors associated with seizures, share common clinicopathological features, such as seizure onsets at a young age, a predilection for involving the temporal lobe, and an almost benign course, including a rather slow growth pattern and thus a long-term history of seizures. Ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNET) are the typical representatives of LEATs. Surgical treatments with complete resection of tumors and related epileptogenic zones are deemed the optimal way to achieve postoperative seizure control and lifetime recurrence-free survival in patients with LEATs. Although the term LEAT was originally introduced in 2003, debates on the tumor spectrum and the diagnosis or classification of LEAT entities are still confusing among epileptologists and neuropathologists. In this review, we would further discuss these questions, especially based on the updated classification of central nervous system tumors in the WHO fifth edition and the latest molecular genetic findings of tumor entities in LEAT entities.

Prognostic value of histopathologic pattern for long-term surgical outcomes of 198 patients with confirmed mesial temporal lobe epilepsy.

Hippocampal sclerosis (HS) is the most common neuropathologic findings in patients with intractable temporal lobe epilepsy (TLE). The international league against epilepsy has proposed a new classification of HS based on pyramidal cell loss on different subfields to facilitate the study of HS pathology in patients after anterior temporal lobectomy (ATL), and the influence of these HS patterns on the prognosis of patients with TLE is contradictory. This study aims to investigate the relationship between different HS subtypes and postoperative seizure outcomes for intractable patients with TLE. From January 2008 to December 2018, we retrospectively reviewed 198 TLE patients with ATL surgery, and all patients had a complete preoperative evaluation, a specimen of hippocampal tissue after surgery, cognitive test after surgery, and more than 2 years of postoperative follow-up. The main findings were as follows: 1) temporal neocortical gray matter heterotopia were more common in the no-HS group; 2) HS type 1 was associated with a longer duration of epilepsy; 3) history of meningitis was the independent predictor of HS type 1; 4) no-HS patients experienced worse postoperative seizure outcomes than those with HS type1 and type 2, whereas no difference in seizure outcomes was obtained between HS type 1 and type 2; 5) no-HS patients were at increased risk for verbal memory decline after left hippocampal resection. The HS subtypes were associated with the prognosis of patients with TLE, and other variables were the predictors of different HS types. `Further study was to identify the HS subtypes by noninvasive evaluation to approve better postoperative outcomes.

PRKCA D463H Mutation in Chordoid Glioma of the Third Ventricle: A Cohort of 16 Cases, Including Two Cases Harboring BRAFV600E Mutation.

Chordoid gliomas (CG) of the third ventricle are characterized by chordoid and glial features, but the extent of histological variations across CG is not fully understood. Herein, we report 16 consecutive cases of CG. All 16 patients had histories of headache and vision loss; their median age was 41.7 years at the surgery. Histological examination revealed typical features of CG, including cords of epithelioid cells within the mucinous stroma and lymphoplasmacytic infiltration. Two cases exhibited atypical histological features including histiocyte-like cells. PRKCA mutation was found in 14 cases, including the 2 with histiocytic features. BRAFV600E mutation was found only in the 2 cases with histiocytic features. The patients underwent gross total tumor resection without radiotherapy or chemotherapy. Three patients died between 1 and 4 months postsurgery. Only one had a recurrence. Eleven were alive at the most recent follow-up (range: 2-58 months). These data indicate that PRKCA mutation was a good diagnostic marker for CG and additionally suggest that histiocyte-like features can be present in CG in association with BRAF mutations.

OLIG2 Immunolabeling of Mesenchymal Chondrosarcoma: Report of 14 Cases.

Mesenchymal chondrosarcoma (MC) is a rare aggressive mesenchymal sarcoma. Specific markers for the differential diagnosis of MCs remain to be developed. OLIG2 expression has been reported only in neuroepithelial tumors. Recently, OLIG2 expression was found to be involved in the development of NCOA2 fusion-positive alveolar rhabdomyosarcomas. Therefore, we investigated whether OLIG2 expression could be used as a diagnostic marker for MC. We report the clinical pathological and immunohistochemical features of 14 MCs. All tumors showed typical pathological features including biphasic patterns with sheets of primitive round mesenchymal cells and interspersed islands of cartilage. These tumors expressed BCL2, SOX9, and CD99. OLIG2 was robustly expressed in 12/14 of MCs. NCOA2 rearrangement was found in 12 cases. OLIG2 expression was not found in the NCOA2 rearrangement-negative MCs. Notably, OLIG2 expression was not detected in 52 neoplasms (8 Ewing sarcomas, 23 hemangiopericytomas, and 21 chondrosarcomas) that are frequently misdiagnosed as MC. Our findings provide convincing evidence that OLIG2 can serve as a reliable marker in the differential diagnosis of MC and may be a unique neurodevelopmental gene expression signature for the NCOA2 rearranged MCs.

Detection of H3K27M mutation in cases of brain stem subependymoma.

Subependymomas are rare, slow-growing, grade I glial tumors of the central nervous system. Recently, diffuse midline gliomas with mutations in the H3.1 or H3.3 genes at the position of amino acid 27, resulting in the replacement of lysine by methionine (K27M), were defined as the new grade IV entity. As H3K27M mutations have been reported in midline gliomas, gangliogliomas, and pilocytic astrocytomas, whether they occur in midline subependymomas has been unclear. We determined whether any such mutations can be found in them and analyzed the prognostic relevance of any such mutations in subependymomas. Four subependymomas, all in the brain stem, harbored H3K27M mutations. No such mutation was found in any of the subependymomas from other locations. The mutations were identified by immunohistochemical stains and confirmed with Sanger sequencing. The median follow-up of the patients with the mutations in their tumors was 3.2 years, and 3 are still alive, having received no adjuvant therapy. We demonstrate that H3K27M mutation can occur in brainstem subependymomas; despite the presence of H3K27M mutation, these cases should not be diagnosed or treated as grade IV tumors because they showed a better outcome than the outcome of diffuse midline H3K27M mutant glioma. Our conclusion is not only that brainstem subependymomas can have H3K27M mutations but that they do not carry the rapidly lethal prognosis with which these mutations are usually associated because of their discovery in diffuse intrinsic pontine gliomas.

Preoperative Changes in Hematological Markers and Predictors of Glioma Grade and Survival.

Background: Preoperative hematological markers that indicate nutritional, coagulation, and inflammation statuses have prognostic value for gliomas. This study aimed to investigate hematological markers with regard to tumor grades, isocitrate dehydrogenase mutations (IDH), age, and sex in patients with gliomas. Methods: From 2008 to 2017, patients with a pathological diagnosis of glioma who underwent surgery were retrospectively enrolled in this study. Information from clinical records, including age, sex, preoperative experiment tests (routine blood tests, biochemistry, and coagulation examinations), pathological results, and IDH status, was collected. A univariable survival analysis was performed. Hematological factors such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte-ratio (PLR), and albumin-to-globulin (AGR) were calculated. The prognostic nutrition index (PNI) was calculated as 10 × serum albumin value (g/dl) + 0.005 × peripheral lymphocyte count (per mm3). Results: Our study included 706 patients. The univariate analysis showed that age, IDH-1, and hematological factors were all significantly associated with overall survival (OS) in patients with gliomas. Our results showed that inflammation markers (NLR, PLR, and fibrinogen) were positively associated with age, whereas AGR was negatively associated with age. The PLR was significantly increased, whereas the AGR and PNI were decreased in women with gliomas, as compared with men. We found that inflammation markers increased and nutrition markers decreased with gliomas grade. However, these hematological markers did not significantly differ with IDH status. NLR was the best single hematological marker for distinguishing glioblastoma (GBM) [0.684 (0.645-0.723)], IDH-wt GBM [0.672 (0.631-0.71)] from other gliomas subtypes. Combinations of age with PNI and age with AGR were the best predictors of GBM [0.750 (0.713-0.786)] and IDH-wt GBM [0.759 (0.719-0.798)], respectively. Conclusion: Preoperative hematological marker levels vary among glioma grades and have high predictive values for GBM.

Higher Plasma Fibrinogen Levels are Associated with Malignant Phenotype and Worse Survival in Patients with Glioblastomas.

Preoperative plasma fibrinogen levels were associated with poor clinical outcomes in malignancies. There were few data about the prognostic value of plasma fibrinogen in glioblastomas (GBMs). The objective of our study was to investigate the association between fibrinogen and patients' clinicopathological factors and overall survival (OS). From 2008 to 2016, 315 patients with GBMs who had a surgical treatment at our institute, were retrospectively involved in this study. IDH (isocitrate dehydrogenase) mutations and ATRX (alpha thalassemia/mental retardation syndrome X-linked) loss were detected with IHC (Immunohistochemistry). The preoperative plasma fibrinogen levels ranged from 1.00 to 5.22 g/L, with a mean of were 2.57 g/L. There were increased levels of plasma fibrinogen in patients aged ≥ 65 years, secondary GBMs, IDH mutation (p = 0.033) and ATRX loss (p = 0.040). Moreover, the plasma fibrinogen level was the highest in the subtype of IDH-1R132H wildtype - ATRX expression, which showed a shorter OS compared to the group of IDH-1R132H mut and IDH-1R132H wildtype - ATRX loss (p = 0.001, log-rank test). ROC curves for fibrinogen and IDH-1R132H wildtype - ATRX expression was also plotted, and indicated a potential diagnostic value of fibrinogen in molecular pathology. Univariate analysis found that younger age, higher KPS (Karnofsky Performance Score), gross total resection, complete chemoradiotherapy, IDH-1R132H mutations and lower levels of fibrinogen were associated with favorable outcomes. Multivariate analysis proved that chemoradiotherapy, IDH-1R132H and fibrinogen were independent prognostic factors. In conclusion, plasma fibrinogen could predict clinical outcome and molecular subtype in GBMs.

Concurrence of chordoid gliomas with Rosai-Dorfman component: report of two rare cases.

Chordoid glioma (CG), which often originated from the third ventricle, was a type of rare and slowly growing low grade glioma with chordoid appearance. So far, concurrent occurrence of third ventricule chordoid gliomas with Rosai-Dorfman disease (RDD) has never been observed. In this study, the clinical features, pathological characteristics as well as their prognosis of two CG with RDD component cases were discussed. Herein, we reported two cases of CG with RDD component from a 45-year-old female and a 38-year-old male respectively. Radiologically, the two lesions were located on the region of suprasellar-third ventricular with homogenous contrast enhancement. They underwent gross total resection and remained free of disease progress till now. Microscopically, both lesions showed the classic morphology of CG and RDD component. A morphologic curiosity is presented in tumors manifested by CG with RDD component in the suprasellar-third ventricular region. To the best of our knowledge, this is the first presentation of two collision tumors consisting of CG and RDD on the suprasellar-third ventricular region. Awareness of this entity is important to distinguish it from other CGs. More examples and a timely follow-up are required for understanding the biological features of these cases.

Spinal cord gliosarcoma with rhabdomyoblastic differentiation: a case report.

Very few cases of gliosarcoma (GS) in the spinal cord with or without rhabdomyoblastic differentiation have been reported at young ages, leading to limited information on the clinical, pathological and prognosis of this type of tumors. We report a case of GS with rhabdomyoblastic differentiation in a 6-year-old girl in C1-C6 level spinal cord. This is, to the best of our knowledge, the first report of GS with rhabdomyoblastic differentiation primarily developed in spinal cord at such a young age. Histologically, GS is composed of both glioblastoma components and malignant mesenchymal components. In the present case, the mesenchymal portion displayed a typical pattern of rhabdoid morphology. The rhabdomyoblastic-differentiated cells were confirmed by desmin, MyoD1, myogenin and Vimentin immunopositivity. Loss of PTEN (phosphatase and tensin homolog) and amplification of EGFR (epidermal growth factor receptor) were not detected in both parts of GS (glioblastoma component and rhabdomyosarcoma component). Interestingly, in this case rhabdomyoblastic-differentiated cells (rhabdomyosarcoma component) were focally negative for integrase interaction 1 (INI-1) protein and glial cells (glioblastoma component) were positive, and monosomy 22 in the former and absence in the latter. The patient only received low-dose radiotherapy and survived only 6 months after diagnosis. GSs with rhabdomyoblastic differentiation have a worse prognosis than common GSs and high-dose radiotherapy is suggested to considerer.

Clinical and immunohistochemical characteristics of type II and type I focal cortical dysplasia.

Focal cortical dysplasia (FCD) II and I are major causes for drug-resistant epilepsy. In order to gain insight into the possible correlations between FCD II and FCD I, different clinical characteristics and immunohistochemical expression characteristics in FCD I and II were analyzed. The median age of onset and duration of epilepsy in FCD I and FCD II patients were 2.1 years and 5.3 years vs 2.4 years and 4.5 years. Therefore, the median age of onset and duration of epilepsy were similar in the two groups. Pathological lesions were predominantly located in frontal lobe in FCD II and temporal in FCD I. Significantly more signal abnormalities in FLAIR and T2 images were demonstrated in FCD II than FCD I. The rate of satisfied seizure outcome was relative higher in FCDII patients (95.12%) than that in FCDI group (84.6%). Furthermore, we detected expressions of progenitor cell proteins and the mammalian target of rapamycin (mTOR) cascade activation protein in FCDs. Results showed that sex-determiningregion Y-box 2(SOX2) , Kruppel-likefactor 4 (KLF4) and phospho-S6 ribosomal proteins (ser240/244 or ser235/236) were expressed in FCDII group but not in FCD I. Overall, this study unveils FCD I and II exhibit distinct clinical and immunohistochemical expression characteristics, revealing different pathogenic mechanisms.

A rare case of malignant pediatric ectomesenchymoma arising from the cerebrum.

Malignant ectomesenchymoma is a rare tumor that contains both ectodermal and mesenchymal elements. So far, only 7 patients with a manifestation in the cerebrum (with confirmed clinicopathological data) have been reported. A 4-year-old girl was present at our hospital with a 3-week history of intermittent sudden dizzy with no apparent cause. MRI showed an irregular enhanced lesion in the left frontal-parietal lobe and lateral ventricle with peripheral gadolinium-enhancement with a significant surrounding edema. Total removal of the tumor was performed. Histological examination of the resected tumor revealed a mixed astrocytoma and anaplastic ependymoma component with undifferentiated mesenchymal spindle cell component. Generally speaking, the main malignant part in most cases of malignant ectomesenchymoma (MEM) is the mesenchymal component. In the present case, the malignant component was both in the mesenchymal and ectodermal part. In particular, the mesenchymal part was mainly composed of spindle cells, and the ectodermal part primarily consisted of gliomatous component and anaplastic ependymoma component. The patient was then treated with chemotherapy and as regard to the prognosis, there was no evidence of tumor recurrence at the 5 months' follow-up. The long term follow-up is still in progress.