Glomus jugulare tumor (GJT) is a rare paraganglioma arising from neural crest cells. Although the majority of cases are non-functional, a minority of GJTs can secrete catecholamines. Such functional variants are frequently overlooked due to their rarity and may trigger perioperative crises. The present report documents a 53-year-old female patient with a giant occult secretory GJT (65 mm) presenting with prolonged cranial nerve deficits. Preoperative blood pressure was normal, but the patient developed hypertensive crisis (220/130 mmHg) during embolization. Biochemical tests confirmed catecholamine excess. Hemodynamic stability was maintained using calcium channel blockers without α-blockade after embolization. Tumor resection was performed within 72 h, achieving total resection without intraoperative crisis. Catecholamine levels normalized postoperatively with marked neurological improvement. The present case highlights the importance of recognizing occult secretory GJTs and discusses key management considerations regarding preoperative preparation, timing of surgery and anesthetic management. Increased awareness may improve diagnosis and optimize outcomes in these challenging cases.

Hemorrhage from brainstem cavernous malformations (BSCMs) can cause severe neurological dysfunction. While surgery is effective, the optimal timing remains unclear. This retrospective study aims to identify the best timing for surgery after hemorrhage in BSCM patients. Data from patients who underwent surgery between 2012 and 2022 were analyzed. Patients were divided into groups with favorable and unfavorable outcomes based on their best post-treatment modified Rankin Scale (mRS) scores. They were further categorized into four groups according to the timing of surgery after hemorrhage: hyperacute (≤ 7 days), acute (8-20 days), subacute (21-56 days), and chronic (> 56 days). Clinical characteristics, imaging findings, prognosis, and outcomes were compared between the groups. A total of 135 BSCM patients were included, with most lesions located in the pons. Surgical timing distribution was as follows: hyperacute phase (12 cases), acute phase (42 cases), subacute phase (69 cases), and chronic phase (12 cases). Of these, 113 patients had favorable outcomes. Statistical analysis revealed a significant difference in mRS scores between the four groups, with the most pronounced differences observed between the acute/subacute phases and the hyperacute/chronic phases. In conclusion, performing surgery in the acute and subacute phases could improve neurological function in BSCM patients.

Two single-center Phase I trials evaluated safety (primary endpoint) and preliminary efficacy (secondary endpoint) of oncolytic adenovirus Ad-TD-nsIL12 in primary (Group A, NCT05717712) and progressive (Group B, NCT05717699) pediatric patients with IDH wild-type (WT) diffuse intrinsic pontine glioma (DIPG). Studies employed single-arm and 3 + 3 dose-escalation design. 9 patients were enrolled in Group A and 6 in Group B. Group A completed the dose escalation, and no severe adverse events were observed. Enrollment in Group B was halted after Group A completed escalation. All patients experienced drug-related adverse events. In Group A, three partial responses and five stable diseases were documented, with a median overall survival (mOS) of 10.3 months after the first virus and 11.3 months after onset. In Group B, three patients had stable diseases, and three had progressive disease, with an mOS of 6.4 months after the first virus and 12.7 months after onset. Both groups demonstrated improved mOS from onset compared to the DIPG patients in our center's retrospective study (mOS, 8.3 months). Both groups showed increased lymphocytes post-treatment, but only Group A decreased after radiotherapy. These trials confirmed the safety of Ad-TD-nsIL12 and provided preliminary efficacy evidence, offering insights for future clinical applications in DIPG.

Inflammatory myofibroblastic tumor (IMT) is a rare pathological entity first described in 1939. This lesion is most commonly found in the lungs, but cases involving other systems, such as the central nervous system known as intracranial IMT (IIMT), have also been reported. Diagnosis currently relies on pathological results due to the lack of characteristic imaging changes. Surgical resection is an effective treatment, though the disease is invasive and may recur. Previous literature has reported a high level of programmed death 1 (PD-1) expression in IMT tissues, suggesting that immunotherapy may be effective for this condition. In this case report, we present a middle-aged male who received PD-1 inhibitor and oncolytic adenovirus (Ad-TD-nsIL12) treatment after IIMT resection surgery. This successful approach provides a new direction for the treatment of IIMT.

2057 Background: Glioma is the most common primary central nervous system malignancy in adults, of which glioblastoma (GBM) accounts for more than 50% of the incidence and is the most aggressive subtype of glioma, with a median survival of about 15 months. Oncolytic virus emerges as a promising therapy for recurrent GBM (rGBM), but its safety and efficacy are not evaluated in patients with rGBM connecting to ventricular system. Methods: This is a dose-escalating trial to study the safety and efficacy of Ad-TD-nsIL12, a novel oncolytic adenovirus, in patients with rGBM connecting to the ventricular system. The assigned dose levels of Ad-TD-nsIL12 were 5x109vp, 1x1010vp, and 5x1010vp. Adverse events (AEs) associated with the virus were graded using the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), and Grade ≥ 3 AEs identified the dose-limiting toxicity (DLT). Tumor response was evaluated based on the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Eight patients, aged from 45 to 71 years, were enrolled between December 2019 and September 2022, with treatment doses ranging from 5x109 to 5x1010vp. Grade 3 seizure according to CTCAE occurred in two patients from Cohort 3 (5x1010vp) after AD-TD-nsIL12 injection. Minimal adverse events were observed at a treatment dose of 1x1010 vp, even after multiple injections. Complete response (CR) was demonstrated in one patient, partial response (PR) in one patient, stable disease (SD) in four patients and progressive disease (PD) in two patients. Immunohistochemical staining showed higher infiltrations of CD3+, CD4+ and CD8+ T cells and positivity of E1A and Hexon in virus post-treated tissues. Inflammation associated cytokines in the blood were not significantly elevated by Ad-TD-nsIL12. Conclusions: AD-TD-nsIL12 treatment was safe and effective in patients with rGBM and warrants examination in a phase II clinical study. Clinical trial information: ChiCTR2000032402.

Malignant glioma is a highly fatal central nervous system malignancy with high recurrence rates. Oncolytic viruses offer potential treatment but need improvement in efficacy and safety. Here we describe a phase I, dose-escalating, single arm trial (ChiCTR2000032402) to study the safety of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in patients with recurrent high-grade glioma that connects with the ventricular system. Eight patients received intratumoral treatment via stereotaxis or an Ommaya reservoir, with doses ranging from 5 x 109 to 5 x 1010vp. The primary end point was to determine the maximal tolerated dose. Secondary endpoints included toxicity and anti-tumour ability. Minimal adverse events were observed at doses of 5 x 109 and 1 x 1010vp. Grade 3 seizure was observed in two patients from Cohort 3 (5 x 1010vp). Therefore, the maximum tolerated dose was determined to be 1 x 1010vp. Four patients developed hydrocephalus during follow-up. Among them, symptoms in two patients were relieved after placement of a ventriculo-peritoneal shunt, and the other two only showed ventriculomegaly on MRI scan without neurological deterioration. Complete response (according to Response Assessment in Neuro-Oncology Criteria) in one patient, a partial response in one patient and post-treatment infiltrations of CD4+ and CD8 + T cells into the tumour were documented during this trial. In conclusion, Ad-TD-nsIL12 has demonstrated safety and preliminary efficacy in patients with recurrent high-grade glioma. Oncolytic viruses have been tested in patients with malignant glioma, however clinical efficacy remains limited. Here the authors report the results of a phase I trial of Ad-TD-nsIL12, an oncolytic adenovirus expressing a mutant (non-secreting) form of IL12, in patients with high-grade glioma.

AIMS:Gliomas are the most common central nervous system malignancies, with limited therapeutic options and poor prognosis, which are primarily attributed to the "immune desert" microenvironment. Previously, we constructed a three-gene-deleted oncolytic adenovirus (Ad-TD) loaded with non-secreting interleukin-12 (nsIL-12), which could be amplified in tumor cells and induce immunity to suppress tumors. However, the effects of this oncolytic virus on gliomas and their immune microenvironment remain unclear. There is an urgent need for further research.MATERIALS AND METHODS:We constructed a Syrian hamster brain tumor model and demonstrated the efficacy and mechanism of the novel oncolytic virus in treating brain tumors through a series of in vitro and in vivo experiments. We investigated the efficacy and safety (the number of hamsters in each group is either 5 or 10) of the oncolytic virus treatment in Syrian hamsters using a virus-treated group, a control virus-treated group, and a blank control group.KEY FINDINGS:In vitro assays showed that Ad-TD-nsIL-12 could specifically proliferate in brain tumor cells which induce tumor cell apoptosis and intracellular expression of interleukin (IL)-12. Moreover, in vivo experiments demonstrated that Ad-TD-nsIL-12 could effectively inhibit the progression of brain tumors and prolong survival. Ad-TD-nsIL-12 significantly enhanced T-cell infiltration in the brain tumor microenvironment.SIGNIFICANCE:Ad-TD-nsIL-12 can inhibit glioma progression and increase T-cell infiltration in the tumor tissue, particularly infiltration by cytotoxic T cells (CD8+). Ad-TD-nsIL-12 can amplify and produce IL-12, inducing anti-glioma immune responses to inhibit tumor progression.

AIMS:Chordoma is a rare and aggressive bone tumor with high-recurrence and lack of effective treatment methods. Tumor associated macrophages (TAMs) are abundant in tumor microenvironment (TME) and polarize toward M2 in chordoma. It has been observed that the high proportion of M2 cells is associated with chordoma rapid progression. However, the mechanism of TAMs polarization and promotion to tumor progression in chordoma is still unclear. The is an urgent need for further research. MATERIALS AND METHODS:Flow cytometry and immunohistochemical staining was used to detect the degree of macrophages infiltration in chordoma. A co-culture model of chordoma cells and macrophages was established in vitro to investigate the effects of their interaction on cell function, cytokine secretion, and RNA transcriptome expression. KEY FINDINGS:In this study, we found M2 macrophage was predominantly abundant immune cell population in chordoma, and its proportion was associated with the degree of bone destruction. We demonstrated that interleukin 6 (IL-6) derived from chordoma cells could induce TAMs polarization by activating STAT3 phosphorylation, and TAMs could enhance chordoma cells migration and invasion through TNFα/NF-κB pathway. The interaction of chordoma cells and TAMs could promote the bone destruction-related factor Cathepsin B (CTSB) and inhibitory immune checkpoints expression. We also confirmed blocking IL-6/STAT3 pathway could significantly attenuate the M2 polarization of TAMs and decrease the secretion of TNFα. SIGNIFICANCE:This study illustrates the dynamics between chordoma cells and TAMs in promoting chordoma invasion and suggests that IL-6/STAT3 pathway is a potential therapeutic target to reduce TAM-induced chordoma invasion.

Background: Gliomas are the most commonly-detected malignant tumors of the brain.They contain abundant long non-coding RNAs (lncRNAs), which are valuable cancer biomarkers.LncRNAs may be involved in genomic instability; however, their specific role and mechanism in gliomas remains unclear.LncRNAs that are related to genomic instability have not been reported in gliomas. Methods:The transcriptome data from The Cancer Genome Atlas (TCGA) database were analyzed.The co-expression network of genomic instability-related lncRNAs and mRNA was established, and the model of genomic instability-related lncRNA was identified by univariate Cox regression and LASSO analyses.Based on the median risk score obtained in the training set, we divided the samples into high-risk and low-risk groups and proved the survival prediction ability of genomic instability-related lncRNA signatures.The results were verified in the external data set.Finally, a real-time quantitative polymerase chain reaction assay was performed to validate the signature. Results:The signatures of 17 lncRNAs (LINC01579, AL022344.1,AC025171.5,LINC01116, MIR155HG, AC131097.3,LINC00906, CYTOR, AC015540.1,SLC25A21.AS1, H19, AL133415.1,SNHG18, FOXD3.AS1, LINC02593, AL354919.2and CRNDE) related to genomic instability were identified.In the internal data set and Gene Expression Omnibus (GEO) external data set, the low-risk group showed better survival than the high-risk group (p<0.001).In addition, this feature was identified as an independent risk factor, showing its independent prognostic value with different clinical stratifications.The majority of patients in the low-risk group had isocitrate dehydrogenase 1 (IDH1) mutations.The expression levels of these lncRNAs were significantly higher in glioblastoma cell lines than in normal cells. Conclusions:Our study shows that the signature of 17 lncRNAs related to genomic instability has prognostic value for gliomas and could provide a potential therapeutic method for glioblastoma.

Background: Gliomas are the most commonly-detected malignant tumors of the brain. They contain abundant long non-coding RNAs (lncRNAs), which are valuable cancer biomarkers. LncRNAs may be involved in genomic instability; however, their specific role and mechanism in gliomas remains unclear. LncRNAs that are related to genomic instability have not been reported in gliomas. Methods: The transcriptome data from The Cancer Genome Atlas (TCGA) database were analyzed. The co-expression network of genomic instability-related lncRNAs and mRNA was established, and the model of genomic instability-related lncRNA was identified by univariate Cox regression and LASSO analyses. Based on the median risk score obtained in the training set, we divided the samples into high-risk and low-risk groups and proved the survival prediction ability of genomic instability-related lncRNA signatures. The results were verified in the external data set. Finally, a real-time quantitative polymerase chain reaction assay was performed to validate the signature. Results: The signatures of 17 lncRNAs (LINC01579, AL022344.1, AC025171.5, LINC01116, MIR155HG, AC131097.3, LINC00906, CYTOR, AC015540.1, SLC25A21. AS1, H19, AL133415.1, SNHG18, FOXD3.AS1, LINC02593, AL354919.2 and CRNDE) related to genomic instability were identified. In the internal data set and Gene Expression Omnibus (GEO) external data set, the low-risk group showed better survival than the high-risk group (P < 0.001). In addition, this feature was identified as an independent risk factor, showing its independent prognostic value with different clinical stratifications. The majority of patients in the low-risk group had isocitrate dehydrogenase 1 (IDH1) mutations. The expression levels of these lncRNAs were significantly higher in glioblastoma cell lines than in normal cells. Conclusions: Our study shows that the signature of 17 lncRNAs related to genomic instability has prognostic value for gliomas and could provide a potential therapeutic method for glioblastoma.

Objective:To investigate the efficacy of surgical therapy of acoustic neuromas after failed gamma knife treatment.Methods:The clinical data of 23 patients with acoustic neuromas treated in the Department of Neurosurgery, Sanbo Brain Hospital of Capital Medical University from January 2010 to December 2021 were retrospectively analyzed. Twenty-three patients who were previously treated with gamma knife (experimental group) underwent surgical resection because of tumor progression. Functional nerve preservation was performed during the operation. Another 23 patients who had not been treated with gamma knife were defined as the control group with matching sex composition ratio, age, tumor size, texture and location. The patients were clinically followed up and the facial nerve function was evaluated by House-Brackmann (HB) grading system. The recurrence or progression of the tumor was evaluated by imaging follow-up. The baseline data, degree of surgical resection, postoperative complications, outcome of facial nerve function and recurrence were compared between the two groups.Results:The degree of adhesion between facial nerve and tumor in the experimental group was greater than that in the control group ( P<0.001). The total tumor resection rate in the experimental group (21.7%, 5/23) was lower than that in the control group (73.9%, 17/23)( χ2=12.54, P<0.001). The anatomic preservation rate of facial nerve was 100% (23/23) in both groups. Postoperative HB gradeⅠ-Ⅱ in the experimental group accounted for 73.9% (17/23), which was not significantly different from that in the control group (91.3%, 21/23) ( P=0.189). The median follow-up time was 57 months (range: 12-133 months) in the experimental group and 52 months (range: 14-120 months) in the control group. There was no tumor recurrence or progression in the two groups. At the last follow-up, the patients with HB grade Ⅰ-Ⅱ in the experimental group and control group accounted for 82.6% (19/23) and 95.7% (22/23) respectively, and there was no significant difference between the two groups ( P=0.412). Conclusions:The degree of surgical resection of advanced acoustic neuromas after failed gamma knife treatment is relatively low. Functional nerve preservation resection can optimize the results of facial nerve function and doesn′t increase the risk of tumor recurrence.

目的 分析总结原发中枢神经系统(central nervous system,CNS)恶性黑色素瘤的临床、影像、治疗及预后特点.方法 对首都医科大学三博脑科医院神经外科 2011 年 5 月至 2021 年 5 月收治并经病理证实的 17 例原发性CNS恶性黑色素瘤患者的临床资料进行回顾性分析,将其分为 4 种类型,分析不同类型患者的年龄、影像特点及治疗和预后情况.结果 17 例患者中 6 例为A型(脑表型),5 例为B型(脑池型),4 例为C型(深部孤立型),2 例为D型(椎管及其他型).表现为颅高压症状者 11 例、局部神经功能障碍者9 例、癫痫者3 例.磁共振(magnetic resonance imaging,MRI)平扫出现T1 高信号者12 例.播散转移 13 例,其中 11 例呈线片状.手术切除 14 例、活检 3 例,6 例术后进行了抗肿瘤治疗.总体中位生存期 7 个月,综合治疗的患者较单纯手术治疗的患者生存期明显延长[(20.6±7.9)个月vs(3.3±0.9)个月].各分型间症状、影像及治疗方式均有明显差别.结论 原发CNS恶性黑色素瘤发病率低,多具有较明显的影像特点,临床可分为 4 种类型.该病需手术联合放射治疗等进行综合治疗,但其恶性程度高,预后差.

Glioblastoma is one of the most fatal malignancies of the central nervous system, with high mortality and post-treatment recurrence rates. Oncolytic viruses are attractive treatment options for this disease, but must be improved to enhance efficacy and safety. Here we describe a phase I, dose-escalating trial to study the safety of Ad-TD-nsIL12, a novel oncolytic adenovirus expressing a mutant form of interleukin-12, in patients with recurrent glioblastoma that connects with the ventricular system. Eight patients, were enrolled, with treatment doses ranging from 5x10 9 vp to 5x10 10 vp. Grade 3 seizure was observed in two patients from Cohort 3 (5x10 10 vp). Minimal adverse events were observed at a treatment dose of 1x10 10 vp, even after multiple injections. Complete response in one patient, a partial response in one patient and post-treatment infiltrations of CD3 + , CD4 + and CD8 + T cells into the tumor were documented during this trial. AD-TD-nsIL12 treatment was safe and effective and warrants examination in a phase II clinical study.

Background Medulloblastoma (MB) is a malignant tumor associated with a poor prognosis in part due to a lack of effective detection methods. Extrachromosomal circular DNA (eccDNA) has been associated with multiple tumors. Nonetheless, little is currently known on eccDNA in MB. Methods Genomic features of eccDNAs were identified in MB tissues and matched cerebrospinal fluid (CSF) and compared with corresponding normal samples using Circle map. The nucleotides on both sides of the eccDNAs’ breakpoint were analyzed to understand the mechanisms of eccDNA formation. Bioinformatics analysis combined with the Gene Expression Omnibus (GEO) database identified features of eccDNA-related genes in MB. Lasso Cox regression model, univariate and multivariate Cox regression analysis, time-dependent ROC, and Kaplan–Meier curve were used to assess the potential diagnostic and prognostic value of the hub genes. Results EccDNA was profiled in matched tumor and CSF samples from MB patients, and control, eccDNA-related genes enriched in MB were identified. The distribution of eccDNAs in the genome was closely related to gene density and the mechanism of eccDNA formation was evaluated. EccDNAs in CSF exhibited similar distribution with matched MB tissues but were differentially expressed between tumor and normal. Ten hub genes prominent in both the eccDNA dataset and the GEO database were selected to classify MB patients to either high- or low-risk groups, and a prognostic nomogram was thus established. Conclusions This study provides preliminary evidence of the characteristics and formation mechanism of eccDNAs in MB and CSF. Importantly, eccDNA-associated hub genes in CSF could be used as diagnostic and prognostic biomarkers for MB.

Background: Based on the literature and data on its clinical trials, the incidence of venous thromboembolism (VTE) in patients undergoing neurosurgery has been 3.0%~26%. We used advanced machine learning techniques and statistical methods to provide a clinical prediction model for VTE after neurosurgery. Methods: All patients (n = 5867) who underwent neurosurgery from the development and retrospective internal validation cohorts were obtained from May 2017 to April 2022 at the Department of Neurosurgery at the Sanbo Brain Hospital. The clinical and biomarker variables were divided into pre-, intra-, and postoperative. A univariate logistic regression (LR) was applied to explore the 67 candidate predictors with VTE. We used a multivariable logistic regression (MLR) to select all significant MLR variables of MLR to build the clinical risk prediction model. We used a random forest to calculate the importance of significant variables of MLR. In addition, we conducted prospective internal (n = 490) and external validation (n = 2301) for the model. Results: Eight variables were selected for inclusion in the final clinical prediction model: D-dimer before surgery, activated partial thromboplastin time before neurosurgery, age, craniopharyngioma, duration of operation, disturbance of consciousness on the second day after surgery and high dose of mannitol, and highest D-dimer within 72 h after surgery. The area under the curve (AUC) values for the development, retrospective internal validation, and prospective internal validation cohorts were 0.78, 0.77, and 0.79, respectively. The external validation set had the highest AUC value of 0.85. Conclusions: This validated clinical prediction model, including eight clinical factors and biomarkers, predicted the risk of VTE following neurosurgery. Looking forward to further research exploring the standardization of clinical decision-making for primary VTE prevention based on this model.

N6-methyladenosine (m6A) modification is the most abundant modification in long noncoding RNAs (lncRNAs). Current studies have shown that the abnormal expression of m6A-related genes is closely associated with the tumorigenesis and progression of glioma. However, the role of m6A-related lncRNAs in glioma development is still unclear. Herein, we screened 566 m6A-related lncRNAs in glioma from The Cancer Genome Atlas (TCGA) database. The expression pattern of these lncRNAs could cluster samples into two groups, in which various classical tumor-related functions and the tumor immune microenvironment were significantly different. Subsequently, a nine-factor m6A-related lncRNA prognostic signature (MLPS) was constructed by using a LASSO regression analysis in the training set and was validated in the test set and independent datasets. The AUC values of the MLPS were 0.881, 0.918 and 0.887 for 1-, 3- and 5-year survival in the training set, respectively, and 0.856, 0.916 and 0.909 for 1-, 3-, and 5-year survival in the test set, respectively. Stratification analyses of the MLPS illustrated its prognostic performance in gliomas with different characteristics. Correlation analyses showed that the infiltrations of monocytes and tumor-associated macrophages (TAMs) were significantly relevant to the risk score in the MLPS. Moreover, we detected the expression of four MLPS factors with defined sequences in glioma and normal cells by using RT-PCR. Afterwards, we investigated the functions of LNCTAM34A (one of the MLPS factors) in glioma cells, which have rarely been reported. Via in vitro experiments, LNCTAM34A was demonstrated to promote the proliferation, migration and epithelial-mesenchymal transition (EMT) of glioma cells. Overall, our study revealed the critical role of m6A-related lncRNAs in glioma and elucidated that LNCTAM34A could promote glioma proliferation, migration and EMT.

Glioma is the most common tumor with the worst prognosis in the central nervous system. Current studies showed that glucose metabolism could affect the malignant progression of tumors. However, the study on the dysregulation of glucose metabolism in glioma is still limited. Herein, we firstly screened 48 differentially expressed glucose metabolism-related genes (DE-GMGs) by comparing glioblastomas to low-grade gliomas. Then a glucose metabolism-related gene (GMG)-based model (PC, lactate dehydrogenase A (LDHA), glucuronidase beta (GUSB), galactosidase beta 1 (GLB1), galactose mutarotase (GALM), or fructose-bisphosphatase 1 (FBP1)) was constructed by a protein–protein interaction (PPI) network and Lasso regression. Thereinto, the high-risk group encountered a worse prognosis than the low-risk group, and the M2 macrophage was positively relevant to the risk score. Various classical tumor-related functions were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Since protein GALM was rarely studied in glioma, we detected high expression of GALM by western blot and immunohistochemistry in glioma tissues. And experiments in vitro showed that GALM could promote the epithelial-to-mesenchymal transition (EMT) process of glioma cells and could be regulated by TNFAIP3 in glioma cells. Overall, our study revealed the critical role of glucose metabolism in the prognosis of patients with glioma. Furthermore, we demonstrated that GALM was significantly related to the malignancy of glioma and could promote glioma cells’ EMT process.

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.

Objective:To investigate the surgical implications and morphologic type of upward bulging of the planum sphenoidale (PS) in anterior skull base meningiomas involving the tuberculum sellae area. Methods:Between January 2014 and June 2021, 96 patients with anterior skull base meningiomas underwent surgery at the Sanbo Brain Hospital of Capital Medical University. A total of 96 patients with nonintracranial space-occupying lesions were selected as the control group. The height of upward bulging of the PS was measured and classified. The authors performed univariate and multivariate analyses to evaluate the rate and effects of upward bulging of the PS. Results:The PS upward bulging rate was 23.00% versus 66.70% (P<0.001) between the control and meningioma groups. Multiple linear regression showed that it was correlated with the tumor midsagittal anteroposterior length (P=0.025) and the midsagittal height diameter (P=0.012). According to the height of PS upward bulging, it was divided into types 1, 2, and 3. The tumor gross-total resection rates were 96.9%, 92.3%, and 76.0%, respectively (P=0.042). Conclusions:Anterior skull base meningiomas involving the tuberculum sellae area can cause PS upward bulging, which lowers the tumor resection rate and should be considered while determining the treatment approach.

Objective:To investigate the factors influencing prognosis of patients with giant invasive pituitary adenomas who underwent surgical treatment.Methods:Clinical data of 84 patients with giant invasive pituitary adenomas who underwent surgical treatment at Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University from April 2011 to December 2016 were retrospectively analyzed. Univariate and multivariate logistic regression analysis were used to explore the influencing factors of the degree of tumor resection. Kaplan-Meier analysis and multivariate Cox regression analysis were used to investigate the influencing factors of tumor progression.Results:Among 84 patients, total resection was achieved in 13 cases (15.5%), near-total resection in 40 cases (47.6%) and subtotal resection in 31 cases (36.9%). There were 89.3% (75/84) of the patients who had been followed up for 15-83 months (46.8±19.0 months). There was no perioperative death, and 2 patients (2.4%) died due to surgical complications within 3 months. Univariate analysis showed that previous surgery or radiotherapy, maximal diameter of tumor, tumor shape, tumor invasion degree to the cavernous sinus, whether the tumor invaded the posterior cranial fossa, the enhancement characteristics of the lesions on MRI and the tumor texture could affect the degree of tumor resection (all P<0.05). Multivariate logistic regression analysis showed that the tumor invasion degree to the cavernous sinus ( OR=0.089, 95% CI: 0.009-0.850, P=0.036) and tumor texture ( OR=0.246, 95% CI: 0.077-0.786, P=0.018) were independent risk factors for tumor resection. Among 84 patients, 14 cases had tumor progression during the follow-up period. Log-rank analysis showed that the tumor resection degree, the presence of mitosis and Ki-67 index in pathological examination might be related to tumor progression (all P<0.05). Multivariate Cox analysis showed that the tumor resection degree ( HR=0.316, 95% CI: 0.107-0.932, P=0.037) was a protective factor for tumor progression, and the presence of mitosis ( HR=5.064, 95% CI: 1.726-14.859, P=0.003) was an independent risk factor for tumor progression. Conclusions:For giant invasive pituitary adenomas, it is not easy to achieve total resection for those with a high degree of invasion to the cavernous sinus (Knosp grade 3-4) and tough texture. The tumor with high degree of tumor resection is not liable to progress, while the tumor with mitotic appearance in pathological examination has a tendency to progress.