bluuebunny/crossref_metadata_2025_split huggingface dataset:
P18.44.B THE IMMUNE CELL INﬁLTRATION IN PERIVASCULAR AND INTRATUMORAL OF EPITHELIOID GLIOBLASTOMA
Authors: jiang s , yan q , wu y , zeng j , xi s 
Published: October 2024

Abstract

BACKGROUND
Epithelioid glioblastoma (eGBM) is a rare subtype of adult glioblastoma(GBM)and was proven to portend an extremely poor prognosis. Perivascular lymphocyte proliferation was commonly observed in eGBM. To disclose the relationship between the tumor’s microenvironment and survival and clinical implications in eGBM, we collected the eGBM cases and conducted a study on the tumor microenvironment of eGBM.

MATERIAL AND METHODS
We collected 38 cases of eGBM, 36 cases of typical adult glioblastoma with IDH and H3 wildtype (typical GBM), and 7 cases of inflammatory tumor-like demyelinating diseases (ITDD) from the Sun Yat-sen University Cancer Center, as well as 4 cases of ITDD from Guangzhou Sanjiu brain Hospital. Tumor-infiltrating immune cells including CD4, CD8, Foxp3, and CD20 positive cells, and tumor-associated macrophages (TAMs), including CD68, CD80, and CD163 positive cells, were performed by immunohistochemical staining (IHC). Under the high-power microscope, two hot spots were selected to quantify the positive immune cells of the tumor center and perivascular lymphocytes, respectively. PD-L1 was also detected by IHC and analyzed by combined positive score (CPS) in eGBM. Nonparametric and chi-square tests were used for intra-group and inter-group comparisons. Overall survival was calculated via Kaplan-Meier estimation using the log-rank test.

RESULTS
Compared with typical adult GBM, perivascular lymphocyte proliferation was more common in eGBM (23/38 vs 4/36, p &lt; 0.001). The counts of CD68+ and CD163+ macrophages in the intratumoral zone were significantly higher than in the perivascular zone in eGBM (Median(cells /HPF):29 vs 7.25, p=0.002, 184.75 vs 78, p&lt;0.001, respectively), while CD20+ lymphocytes were lower (Median(cells /HPF): 3.75 vs 27, P=0.03). Overall, the most common type of immune cells is CD163+ macrophages in both the perivascular zone and intratumoral zone of eGBM (Median=184.75 cells/HPF, P &lt; 0.001), and the higher intratumoral CD163 count is an unfavorable prognostic factor for eGBM (OS:11.1 months vs 15.09 months, p=0.023). We also found that the high CD4/CD8 ratio of perivascular lymphocytes predicted a worse prognosis of eGBM (OS:8.77 months vs 15.66 months, p=0.02). The incidence of PD-L1 expression in eGBM patients is frequent, with 16/38 cases showing a CPS score ≥1. Compared with typical GBM and IDD, the count of intratumoral CD163+ macrophages in eGBM was significantly higher than that in typical GBM (Median(cells /HPF):184.75 vs 141, p =0.048), and the number of perivascular Foxp3+ lymphocytes of eGBM was less than that of tumor-like IDD (Median(cells /HPF):0 vs 2, p =0.044).

CONCLUSION
The immune microenvironment of eGBM consisted of the immune cell inﬁltration in the perivascular and intratumoral zones, and significantly differed from that of typical GBM and tumor-like IDD, which may contribute to the poor prognosis of eGBM.
P18.46.B THE INVERSE PARADIGM OF IDH-WILDTYPE GLIOBLASTOMA EXPLAINS THE TWO DISTINCT MODALITIES OF MICRO-INFILTRATION AND PINPOINTS THE ANCESTRAL FOUNDER CELL AS THE KEY THERAPEUTIC TARGET
Authors: Brognaro E 
Published: October 2024

Abstract

BACKGROUND
The IDH-wildtype glioblastoma is the only brain tumor that originates from the ribbon layer of the SVZ and can spread quiescently across the supratentorial brain parenchyma before starting to grow. Moreover, due to indirect and direct experimental evidence, it is finally unquestionably clear that two diffuse micro-infiltrations occur in IDH-wildtype glioblastoma, the first long before the primary bulk growth (the only one able to originate the primary bulk and distant relapses) and the second during bulk growth and evolution. The recognition that the latter is ineffective in giving rise to distant recurrences is a fundamental and very recent breakthrough. As a crucial consequence, there are two causes of therapeutic resistance, and the second one has yet to be identified and challenged therapeutically.

MATERIAL AND METHODS
By collecting multiple spatially separate samples in the tumor mass, we can reconstruct the phylogenetic tree of the primary tumor bulk. However, the therapeutic solution cannot be found in the tumor bulk (where the primordial cells are invariably extinct) but instead in the micro-infiltrated brain, where the ancestral founder CSCs lie quiescently in the perivascular niches. The codified ethical methods (as part of normal glioblastoma surgery) to sample the micro-infiltrated brain parenchyma are enabling us (and our research group is close to achieving this result) to isolate, identify and reproduce the dormant ancestral founder CSCs.

RESULTS
In the bulk, we can infer and reconstruct the phylogenetic tree of the tumor as well as driver and passenger events and the multitude of CSC variants by using multiple separated samples. The ethical methods for sampling micro-infiltrated brain parenchyma are now enabling us to identify and characterize the ancestral founder CSCs, which hibernate in the perivascular parenchymal niches of the supratentorial brain (their activation being the only cause of distant recurrences).

CONCLUSION
The first cause of therapeutic resistance is due to intratumor heterogeneity, while the second cause is the silent presence in the entire supratentorial brain of dormant ancestral founder CSCs from the pre-growth micro-infiltration. Only the identification and characterization of the ancestral founder CSC will enable us to simultaneously overcome both causes of resistance and provide an innovative therapeutic solution. Precisely, the ancestral founder CSC is identical to the premalignant progenitor of the SVZ and to the cell that activated in a single or multiple brain location, gave rise to the primary tumor bulk(s), and transmitted the ancestral driver genomic alterations to all subsequent evolutionary CSC variants.
P19.02.B CHALLENGES AND OUTCOME OF THE RESECTION OF A LEFT PETROCLIVAL MENINGIOMA IN A LOW INCOME COUNTRY
Authors: Ssembatya J , Tan E , Taremwa B 
Published: October 2024

Abstract

BACKGROUND
Petroclival meningiomas pose a surgical challenge due to their complex regional anatomy, with proximity to vital neurovascular structures and involvement of deep, narrow surgical corridors. Until 1970, they were generally considered unresectable due to high operative morbidity. However since the introduction of advanced microscopic surgery with neuronavigation and intraoperative neurophysiological monitoring, surgical outcomes have improved. Sadly, this technology is not available in most low income countries. We report a case of successful resection of a left petroclival meningioma in Mbarara Regional Referral Hospital in Uganda, despite the lack of advanced technology.

CASE REPORT
A 36 year old female presented with a 1 year history of intermittent vomiting and convulsions, worsening over 2 weeks. Neurological examination was normal except a Grade 2 left facial palsy. CT head was performed locally but a 7 hour journey was required for MRI brain; this confirmed a left petroclival meningioma. She returned for tumour resection 2 weeks later due to theatre capacity; neuronavigation, auditory brainstem response testing, sensory/motor evoked potentials and cranial nerve monitoring were not available. A left frontal EVD was initially inserted to control intracranial pressure, before placement in a right park bench position and head secured in a Mayfield clamp. Left retrosigmoid approach was used, with the meningioma visible on reflection of the dura. Under basic microscopic vision, gross total resection was performed with Simpson Grade 2 outcome. The EVD was replaced with an Ommaya reservoir. Postoperative CT head showed no tumour residual, with resolution of the facial palsy and all symptoms. Complications included CSF leak from the nose and Ommaya site, which resolved with conservative management, and DVT treated with anticoagulation. She was discharged at 3 weeks, is fully functioning and working in the community, with Modified Rankin Score 1. Neuropathology results reported meningothelial meningioma WHO Grade 1.

CONCLUSION
Lack of advanced technology in low income countries results in more difficulty locating lesions, increased risk of injury to neurovascular structures and longer operative time. Reduced availability of MRI delays diagnosis, whilst the low resourced hospital wards, together with reliance on patients’ families to fund medication and investigations, results in a challenging perioperative period. Despite this, we report the successful gross total resection of a petroclival meningioma in Uganda. We rely on an in depth understanding of skull base neuroanatomy, three dimensional mental imagery, detailed clinical examination and thorough review of preoperative imaging. We aspire to adopt more advanced technology and collaborate with higher income countries, but hope this case will inspire other low income countries who face similar challenges.
P19.03.A CHARACTERIZATION OF THE IMMUNE MICROENVIRONMENT IN ATYPICAL MENINGIOMAS
Authors: Del Bene M , Agistri F , Patanè M , Carone G , D’Angeli E , Porto E , Stroppa A , Calatozzolo C , Di Meco F , Pollo B 
Published: October 2024

Abstract

BACKGROUND
Meningiomas are the most frequent primary intracranial tumors. The high incidence of grade 2 meningiomas (or atypical meningiomas) and their tendency to recur make them a challenge for patients and healthcare systems. Treatment is based primarily on surgical resection, which may be followed by radiotherapy and, seldom and only in extreme cases, chemotherapy. The most controversial topic regarding the treatment concerns the use of adjuvant radiotherapy. To evaluate if a better knowledge of the immune microenvironment of meningioma may help in planning treatments, we carried out a study on the tumor immune infiltrate (TII) looking for a role as a prognostic/predictive marker, suggesting tailored therapies. With this aim our study proposes the development of a panel including demographic, clinical, and pathological data, focusing on the TII, with the highest goal of adding a tool useful for guiding the indication and timing of adjuvant treatments.

MATERIAL AND METHODS
For this purpose, we carried out a histological review of 53 atypical meningiomas following The 2021 World Health Organization (WHO) Classification of CNS Tumors. Through an immunohistochemical analysis, with an expert pathologist, we evaluated the presence of different classes of immune infiltrates. The panel includes different immune infiltrate markers, microglia, monocytes and macrophages biomarkers and NK cells. We also evaluated the loss of H3K27-me3 as prognostic marker of aggressiveness.

RESULTS
27/53 samples showed a massive presence of lymphocytic infiltrate, mostly CD3+ and CD8+ T cells, which is widespread in the tumor and not only in the interface with the healthy nervous tissue. In a large number of cases, these data were also correlated to the presence of PD1 (Programmed death-1). CD4+ T lymphocytes and CD20+ B lymphocytes in the majority of cases were poorly represented, while microglia and macrophages were widely present in tumors.Furthermore, we noticed a discrete or high presence of NK cells, widespread throughout the tumor mass. CD11b+ monocytes were mostly expressed in blood vessels, in adjacent nervous tissue (when present in the sample) and in the interface between the latter and the tumor. Suppressive myeloid immune cells CD14+ were found in most samples, with a degree of labeling ranging from weak to strong.

CONCLUSION
The data we obtained lead us to assume that atypical meningiomas present a “hot” tumor microenvironment characterized by a high immune infiltrate, however, the meaning and the role of this profile will be correlated with clinical data, investigating the impact on the tumor progression. Moreover, we are also looking to understand if meningiomas with abundant TII may be potentially responsive to immuno-oncological therapies.
P19.14.A TARGETING TUMOR-ASSOCIATED MACROPHAGES IN THE IMMUNE-MICROENVIRONMENT OF MENINGIOMAS
Authors: Lotsch C , Warta R , Dao Trong P , Krieg S , Sahm F , Unterberg A , Herold-Mende C 
Published: October 2024

Abstract

BACKGROUND
Meningiomas represent the most common primary brain malignancies in adults with a subset of tumors exhibiting aggressive clinical behavior. Immunotherapy might present a new treatment strategy but is highly dependent on the immunological composition of the tumor microenvironment. Our previous data have shown that tumor-associated macrophages (TAMs) make up the main immune cell population in meningiomas with a significant negative impact on patient outcome. In this study, we investigated whether TAMs from meningioma tissue could be reprogrammed to an immunologically active and tumoricidal phenotype.

MATERIAL AND METHODS
For this purpose, CD11b+ sorted macrophages derived from tumor samples from &gt; 40 patients including a substantial number of clinically aggressive meningiomas were treated with small molecule inhibitors targeting the colony-stimulating factor-1 receptor (CSF-1R). In a first analysis, the direct treatment response of CD11b+ patient-derived macrophages has been investigated by various techniques including flow cytometry and bulk RNA-sequencing of treated TAMs and further analysis of the macrophage-conditioned media after treatment. In addition, we studied the influence of CSF-1R-targeted macrophage treatment on the phenotype and functional activity of T cells to assess a potential indirect treatment response in the tumor microenvironment.

RESULTS
Our data revealed that CSF-1R-targeted treatment of CD11b+ TAMs induced significant changes in the protein and gene expression of macrophage polarization markers towards a more immunologically active state and a significantly higher metabolic nitric oxide production as another sign of immunological activation. Subsequent analysis of indirect effects on T cells showed not only a significantly increased expression of the T cell activation marker CD69+, but also a significantly increased tumor cell killing by autologous T cells after macrophage-targeted treatment.

CONCLUSION
Together these data suggest both a direct and indirect CSF-1R-targeted macrophage treatment response in the local tumor microenvironment and give first promising results on the efficacy of macrophage-targeted immunotherapy in human meningiomas.
P19.15.B TERT PROMOTOR MUTATIONS IN ATYPICAL MENINGIOMAS
Authors: Meta R , Dai H , Sjursen W , Torp S 
Published: October 2024

Abstract

BACKGROUND
In human meningiomas TERT promotor mutations have been shown to be associated with a potentially worse prognosis, thus favouring a CNS WHO grade 3. In this study we wanted to investigate whether this genetic event could distinguish between atypical meningiomas with variable clinical course.

METHODS
In our archives we found twenty human meningiomas among which 10 cases experienced recurrence and 10 cases did not. Formalin-fixed and paraffin-embedded (FFPE) material was analysed by means of Sanger sequencing to assess the occurrence of TERT promotor mutations.

RESULTS
No mutations were found in 17 cases. In 3 cases the DNA quality was too poor for sequencing.

CONCLUSION
We found no TERT promotor mutations in our series of atypical meningiomas, so the prognostic value of this genetic event in these tumours requires further studies. Since there were cases with poor DNA quality, such sequencing analyses on FFPE meningioma tissue may be problematic and may therefore represent a limitation in retrospective studies.
P20.04.A ATYPICAL TERATOID/RHABDOID TUMOR ARISING FROM THE THIRD VENTRICLE IN YOUNG ADULT
Authors: Hwang J , Lee C , Yoon S , Park K , Park S 
Published: October 2024

Abstract

BACKGROUND
Atypical teratoid/rhabdoid tumor (AT/RT) Is a high-grade CNS malignancy predominantly seen in infants and children. AT/RTs occur throughout the neuraxis but have high predilection for midline structure such as pineal gland and brainstem. Suprasellar location is rare and pure third ventricular AT/RT is exceptional. We report a case of AT/RT in a young adult with third ventricle origin. This is the second documented case of adult third ventricle AT/RT.

MATERIAL AND METHODS
A 24-year-old male presented with two-week-long dizziness and diplopia. Magnetic resonance imaging (MRI) of the brain showed a heterogeneously enhancing large lesion in the third ventricle with isointense on T1WI and T2WI. Supratentorial ventricular space was enlarged with Evan’s ration of 33%. He underwent anterior transcallosal transchoroidal approach with gross tumor resection.

RESULTS
Postoperative course was uneventful with no hormonal deficiency. CSF diversion was not needed. Histopathological examination revealed AT/RT, WHO grade 4, with loss of SMARCB1 (INI 1) protein. H3 mutation was not found. He later underwent cranio-spinal irradiation with local booster followed by high dose chemotherapy (carboplatin, thiotepa and etoposide) with autologous stem cell transplantation. No recurrence was found on follow-up MRI at 10 months after operation.

CONCLUSION
AT/RT is a rare primary CNS tumor but their incidence among adults is being increased. We report a case of young adult AT/RT with very rare third ventricle location. AT/RT maybe considered as a differential diagnosis for suprasellar-third ventricle lesion in young adults.
P20.06.B CHOROID PLEXUS TUMORS IN ADULT: RETROSPECTIVE MONO-INSTITUTIONAL STUDY
Authors: Anghileri E , Gaviani P , Amato A , Pollo B , Marchetti M , Doniselli F M , Eoli M , Redaelli V , Botturi A G L , Di Meco F , Ferroli P , Farinotti M , de Oliveira Muniz Koch L , Paterra R , Silvani A 
Published: October 2024

Abstract

BACKGROUND
Choroid plexus tumors (CPT) are rare entities, mainly affecting childhood, including three grade subtypes.

MATERIAL AND METHODS
A mono-institutional retrospective series of adult CPT patients was collected. The database contains demographic and clinical details, diagnostic (radiological and histological/molecular), therapeutic, recurrence information, and survival data.

RESULTS
We described twenty-four adult CPT, with a median age of 43.29 years [Interquartile range (IR) 37.31-53.30]. Clinical onset (n=20/24) included cerebellar signs (n=11), intracranial hypertension signs (n=8), cranial nerves impairment (n=5), seizures (n=1), spinal signs (n=1) (multiple symptoms in some patients). Remarkably, in 17% the radiological detection was occasional.The tumors were mostly located in the ventricular system at first diagnosis: 79.2% were infratentorial, but any other locations can occur, including the spine (one case); meningeal involvement was present in one case. Only one case presented a pre-surgical hydrocephalus. CPT histological grade ranged from grade 1 (n=17), grade 2 (n=6), and grade 3 (n=1). TERTp mutations were detected in 17.6% (n=3/17). TP53 mutation in 5.9% (n=1/17). Complete resection was achieved in n=16/24 (66.7%), gross-total resection in n=3/24 (12.5%), partial resection in n=3/24 (12.5%), biopsy in one case, and no information on surgery extension in one case. 76% of the cases (n=16/21) experienced clinical worsening suddenly after surgery for different reasons, and mostly gradually recovered. Adjuvant therapy was performed only for grade 2 and 3 tumors, and included conformational radiotherapy (RT) in one disseminated grade 2 and in one grade 3 case. At recurrence, surgery, RT, and chemotherapy had been considered. The median Overall Survival from surgery was 108.1 months [IR 62.5-143.4].

CONCLUSION
We could confirm that CPT can occur in adults, and are mostly grade 1 tumors and located in the ventricular system. The surgical approach is the gold standard, although a substantial number of clinical worsening occurred, but often transient. Adjuvant treatment is limited to higher grade CPT; however, no consensus has already been achieved about adjuvant therapy.

FUNDING
RRC Italian Ministry of Health
P20.08.B CLINICAL SEVERITY GRADING OF NF2-RELATED SCHWANNOMATOSIS
Authors: Lawson McLean A , Löschner D , Farschtschi S , Dengler N , Neumeister A , Senft C , Rosahl S 
Published: October 2024

Abstract

BACKGROUND
Nf2-related schwannomatosis (NF2) is a genetic disorder linked to tumours in the nervous system, but the extent of radiological tumour burden doesn’t always align with the diverse disabilities patients face. Additionally, there lacks a validated clinical classification for assessing disease severity.This study proposes a clinical classification comprising three severity grades, aiming to enhance communication among caregivers regarding individual patients and aid in clinical management.

MATERIAL AND METHODS
The records of 196 patients were reviewed to identify the most common diagnoses with significant impacts on daily tasks, social interactions, and life expectancy, resulting in seven main categories. Each category was assigned one point. Using a training set, three severity grades were established: grade 1 (mild NF2) with 0 points, grade 2 (moderate NF2) with less than 3 points, and grade 3 (severe NF2) with 3 or more points. The grading system was then evaluated for inter-rater reliability and clinical significance.

RESULTS
Substantial inter-rater reliability was observed among three raters with varying levels of clinical experience (Fleiss’ kappa = 0.62). The severity grades showed significant correlations with hospitalization rates, number of operations, and reliance on implants such as cochlear implants, auditory brain-stem implants, or ventriculoperitoneal shunts.

CONCLUSION
This simple and rater-independent scoring system comprising three grades effectively reflects the clinical disease severity of NF2 patients. This system may facilitate communication among medical personnel of diverse backgrounds and experience levels and provides a valuable clinical tool for decision-making and research in NF2 management.