bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-25. CONSENSUS RECOMMENDATIONS FOR AN INTEGRATED DIAGNOSTIC APPROACH TO NERVE SHEATH TUMORS ARISING IN THE SETTING OF NEUROFIBROMATOSIS TYPE 1
Authors: Dehner Carina , Gross Andrea , Lazar Alexander , Lucas Calixto-Hope , Miettinen Markku , Pekmezci Melike , Perry Arie , Quezado Martha , Rodriguez Fausto , Romo Carlos , Stemmer-Rachamimov Anat , Viskochil David 
Published: November 2024

Abstract
NF1-associated nerve sheath tumors exist on a morphologically and molecularly diverse spectrum. Criteria for diagnosing neurofibroma, atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP), and malignant peripheral nerve sheath tumor (MPNST) developed by consensus in 2017 were codified in recent WHO guidelines. However, incorporation of molecular strata should be formalized to aid in early identification and appropriate intervention for patients with lesions at increased risk for malignant transformation. Here, we assembled a multi-institutional expert pathology working group to review molecular literature and formalize classification recommendations. In collaboration with clinical/surgical, imaging, and pre-clinical working groups during the “Symposium on Atypical Neurofibroma: State of the Science” held April 2024, we reached consensus on a potential integrated diagnostic approach. Based on strong preclinical and clinical evidence, we propose CDKN2A homozygous deletion as a sufficient molecular feature for diagnosing ANNUBP and either SUZ12, EED, or TP53 inactivating mutations or significant aneuploidy as sufficient molecular features for diagnosing MPNST, even in the absence of high-grade histologic features. In the absence of MPNST-defining molecular alterations, we also recommend reclassifying “low grade MPNST” as “ANNUBP with increased proliferation”. To facilitate molecular characterization of concerning tumors, we recommend at least six core biopsies be obtained and divided into two cores per block at time of grossing. Worrisome immunohistochemical features including reduced SOX10 or S100 immunoreactivity, decreased CD34 lattice-like network, minimal p16 expression, loss of H3K27me3 immunoreactivity, p53 overexpression, and increased Ki-67 labeling can guide region selection. A comprehensive next-generation sequencing panel that includes copy number and zygosity assessment is the preferred single assay, though a combination of multiple molecular techniques may provide similar information. In the spirit of the prior 2017 consensus agreement, we hope this refined integrated diagnostic approach for NF1-associated nerve sheath tumors will continue to evolve alongside our understanding of the spectrum of these neoplasms.
PATH-34. IT NEVER RAINS BUT IT POURS - DIAGNOSING ANAPLASTIC PLEOMORPHIC XANTHASTROCYTOMA TWICE IN A FORTNIGHT - OUR EXPERIENCE IN A RESOURCE CONSTRAINED SETTING
Authors: Menon Durgapoorna , Menon Supriya , SB Vigneswar , Santosh Vani , G Kiron , Panikar Dilip , S Shyamsundar 
Published: November 2024

Abstract
Grade 3 Pleomorphic Xanthastrocytoma is a rare tumour (less than 1% of all astrocytic glial neoplasms). Present most commonly with seizures. Surgery and Radiation remain the mainstay of treatment with no clear role for traditional systemic chemotherapies; BRAF inhibitors show some benefit. We report two cases who were diagnosed within a month of each other - one was initially diagnosed in 2017- presented with altered smell, headache and diplopia. Found to have a well-defined lobulated heterogeneously enhancing suprasellar parasellar lesion. After Gross Total Resection, was diagnosed from various centers as Anaplastic Ependymoma WHO Grade III; Gllioblastoma WHO Grade IV; Anaplastic Pleomorphic Xanthastrocytoma WHO Grade III. Based on immunohistochemistry, was considered Anaplastic Ependymoma WHO Grade III. Spine screening was negative; received adjuvant Radiation 60Gy in 30 fractions. After a disease free interval of 6 years, developed a recurrence at the post op site. He underwent repeat decompression and the histopathology showed Grade 3 Pleomorphic Xanthastrocytoma. Immunohistochemistry- OLIG2: diffuse positive; R132H p.IDH1: negative; ATRX: intact nuclear expression; Mismatch repair proteins (MSH2, MSH6, MLH1, PMS2); intact nuclear expression; MIB-1 labelling index: 10-12%; H3 p.K27M: negative; GFAP: variable positivity; Podoplanin and p53 shows focal positivity; EMA, CD 34 are negative. He competed Reirradiation in January 2024. He is asymptomatic and on follow up. The second case -15 year old boy presented with episodes of absence seizures. Imaging showed a predominantly extraaxial lesion at tentorial apex. He underwent decompression and histopathology showed Grade 3 Pleomorphic Xanthastrocytoma. Immunohistochemistry - cells positive for S100 and variably positive for GFAP, OLIG2 and vimentin; ATRX: Retained expression, IDH1p.R132H, EMA, Synaptophysin, Neu N: Negative, p53: Focally positive, CD34: Positive in few tumour cells, Ki-67: 14-16 %.V600 mutation detected in the BRAF gene. Had Adjuvant RT 60 Gy in 30 fractions -completed in March 2024. MRI at 1 month - no significant change in overall tumour burden compared to post operative MRI. Was offered Dabrafenib with Trametinib.
PATH-40. CLINICAL CHARACTERIZATION OF H3K27M-MUTANT GLIOMAS
Authors: Takezaki Tatsuya , Kuroda Jun-ichiro , Shinojima Naoki , Kai Keitaro , Yamamoto Takahiro , Fujimoto Kenji , Inoue Hirotaka , Sueyoshi Hiroyuki , Matsuzaki Keisuke , Takeshima Yuki , Matsuura Jin , Mukasa Akitake 
Published: November 2024

Abstract
Diffuse midline gliomas, H3K27M-altered(DMGs) are a recently defined entity of gliomas, occur in midline, infiltrate diffusely and have poor prognosis. We reviewed our cases of DMGs to describe clinical, pathological, molecular characteristics, retrospectively. We detected 39 H3K27M-mutant cases of our 959 consecutive gliomas(4.1%). All H3K27M mutations were identified genetically. 23 datasets of these H3K27-mutant gliomas are available to detect their clinical, pathological, molecular characteristics. 5 young(8 - 18 y.o.) and 18 adult (28-80 y.o.) were included. All except one H3K27M-altered were WHO Grade III or IV pathologically. Most common location was thalamus(10/23, 43.4%), pons(6/23, 26.1%), brainstem(3/23, 13.0%). 2 non-midline gliomas were included. In this cohort, Median overall survival were 494 days in young patients, 464 days in adult patients. Current adjuvant chemotherapy and radiation-therapy have not prolonged poor prognosis of DMG patients. It is necessary to explore novel therapeutic targets.
PATH-43. MALIGNANT TRANSFORMATION OF MENINGEAL MELANOCYTOMA - GENETIC ALTERATIONS AND RESPONSE TO CHECKPOINT BLOCKADE IMMUNOTHERAPY
Authors: Silva Correia Carlos Eduardo , Kaplan Viktoria , Farooq Shama 
Published: November 2024

Abstract

INTRODUCTION
Meningeal melanocytomas are uncommon tumors that develop from leptomeningeal melanocytes. These tumors can exhibit aggressive behavior, leading to symptoms due to compression and potential invasion of nearby central nervous tissue. Case: In this report, we discuss the case of a 45-year-old man who was diagnosed 18 years ago with a meningeal melanocytoma in the right temporal region. He underwent complete resection with each recurrence and received focal intensity-modulated radiation therapy after a third recurrence in 2013. In May 2022, he developed progressive headaches and diplopia secondary to tumor recurrence on the right temporal region. Resection revealed that the tumor had progressed to malignant meningeal melanoma with 34 mitoses per 10 high-power fields. Next-generation sequencing (NGS) showed GNAQ mutation confirming tumor of central nervous system (CNS) origin, and also showed an SF3B1 mutation, indicating aggressive behavior. Several chromosomal abnormalities were also detected. Systemic workup revealed liver, lung, and bone metastasis. Liver biopsy confirmed meningeal melanoma of central origin. The patient received radiosurgery with a total of 30Gy over five fractions to intracranial surgical cavity, followed by three cycles of nivolumab and relatlimab. Unfortunately, the patient experienced severe intracranial and systemic progression, leading to his death six months after the malignant transformation.

DISCUSSION
Meningeal melanocytomas are rare however these tumors have a high recurrence rate with potential malignant transformation over time. NGS is a valuable tool for confirming the CNS origin of the tumor and predicting its aggressive behavior. Despite microscopic similarity with cutaneous melanomas, meningeal melanocytomas have different pathogenesis and do not seem to respond to immunotherapy, as observed in this case.
PATH-44. CLINICAL AND RADIOGRAPHIC PREDICTORS OF PROGNOSIS IN ASTROCYTOMA, IDH-MUTANT, WHO GRADE 4
Authors: Lasica Aleksandra B , Lan Zhou , Miller Julie J , Russ Alyssa , Westergaard Catharina , Lee Eudocia Q , Chukwueke Ugonma , Castro Luis Nicolas Gonzalez , Figueroa Jose Ricardo McFaline , Aquilanti Elisa , Nayak Lakshmi , Beroukhim Rameen , Batchelor Tracy , Nakhate Vihang , Lanman Tyler , Botero Juan Pablo Ospina , Stec Natalie , Reardon David A , Wen Patrick Y , Youssef Gilbert 
Published: November 2024

Abstract

BACKGROUND
Astrocytoma, IDH-mutant, WHO grade 4, are classified as a separate entity in the 2021 WHO classification of central nervous system tumors and have been poorly characterized in the literature. In this study, we report on the clinical outcomes in a large cohort of newly diagnosed grade 4 IDH-mutant astrocytoma.

METHODS
We retrospectively identified adult patients with astrocytoma, IDH-mutant, WHO grade 4, treated for their initial diagnosis at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2010 and 2021. Clinical, molecular, and radiological characteristics were recorded, and their association with overall survival (OS) and progression-free survival (PFS) was measured by a log-rank test. If a proportional hazard assumption was violated, we compared the median OS and PFS between groups by the bootstrap method instead.

RESULTS
We identified 140 patients, with a median age at diagnosis of 37.9 years (range: 19-87) and male predominance (60.7%). MGMT promoter was methylated in 51.4%, and CDKN2A/B homozygous deletion was present in 40 cases (28.6%). Most tumors showed enhancement on the preoperative scan (n=108; 77.1%). Seventy percent of patients had subtotal resection, 25.7% had a gross total resection, and 4.3% had a biopsy. Most patients received standard chemoradiation followed by adjuvant temozolomide (n=103; 73.6%). The median OS was 6.9 years (95% CI: 4.5-9.2), and the median PFS was 3.3 years (95% CI: 2.1-4.4). OS and PFS were not associated with MGMT promoter methylation or the presence of enhancement on the preoperative scan. CDKN2A/B homozygous deletion was associated with worse OS (5.5 vs. 7.8 years, log-rank test-based p-value=0.036) but had no association with PFS (3.4 vs 2.6 years, bootstrap method-based p-value=0.488).

CONCLUSIONS
In our cohort of astrocytoma, IDH-mutant, WHO Grade 4, CDKN2A/B homozygous deletion had a negative prognostic impact, whereas MGMT promoter methylation status and enhancement on the preoperative scan did not affect survival outcomes.
NIMG-02. DEVELOPING A RADIOMIC HIERARCHICAL GAUSSIAN PROCESS BOOSTING MODEL TO PREDICT PRIMARY TUMOR ORIGIN FROM MULTICENTRIC LONGITUDINAL MRI DATA OF BRAIN METASTASES
Authors: Panchawagh Suhrud 
Published: November 2024

Abstract
Focal neurologic deficits due to brain metastases might be the initial presentation in patients with cancer. Common approaches to investigate the occult primary malignancy include a whole-body PET-CT, whole-body MRI, studying tumor markers, or histopathological examination. Most of these modalities are expensive, time-consuming, invasive, and delay treatment. The field of radiomics leverages quantitative features extracted from images to improve the decision-making process in clinical practices. Although not easily understandable, these features are proxies for the tumor’s shape, contour, texture, and intensity patterns. They can help understand tumor heterogeneity, predict tumor behavior, and assess treatment response. We propose a robust radiomic workflow using longitudinal MRI data from 914 high-resolution imaging studies from 12 different centers (Ocaña-Tienda et al. (2023), Ramakrishnan et al. (2023), Wang et al. (2023)) to predict the origin of brain metastases from brain MRI scans. After using ensemble feature selection methods, we trained three fixed-effects and one mixed-effects multiclass classification model to account for longitudinal data. Fixed-effects logistic regression and support vector kernel models performed the worst (AUC 0.74 and 0.75, respectively), while the random forest performed better (AUC 0.97). The mixed-effects hierarchical Gaussian process boosting (GPBoost) model performed the best with an accuracy of 85.8%, precision of 85.4%, sensitivity of 85.8%, specificity of 95.7%, and an AUC of 0.98. In one-versus-rest classification, the GPBoost model identified the primary tumor as melanoma with the highest accuracy (96.1%) and non-small cell lung cancer with the lowest accuracy (89.0%). Developing such models holds great promise in reducing patient and institutional costs, improving time to effective treatment, and enhancing overall survival rates through personalized therapy approaches. In the future, we hope that incorporating newer patient data and refining the model to improve external validity would enable more accurate and generalizable predictions, leading to better clinical outcomes across diverse populations.
NIMG-04. MASSIVE THORACIC MENINGOCELE IN A PATIENT WITH NF1
Authors: Dasgupta Pushan , McCutcheon Ian , Slopis John 
Published: November 2024

Abstract
Thoracic meningoceles are uncommon but when seen are often associated with neurofibromatosis 1 (NF1). Here we present a unique case where a massive thoracic meningocele presented with chest pain in a patient with NF1. A 56-year-old female with a diagnosis of NF1 presented with pain in the entire chest wall. She described the pain as circumferential around the entire chest “like a barrel”. Cardiology evaluation (with echocardiography) revealed no pulmonary hypertension or other cardiac disorder. MR angiogram of the chest also revealed no intrathoracic vascular structural abnormality. Inflammatory myopathy was considered to explain the pain but electromyography was unremarkable as were creatine kinase and erythrocyte sedimentation rate. MRI of thoracic spine demonstrated a large thoracic meningocele involving the spinal canal from T5-T10 and extending into the left hemithorax with measurements of 11.5 x 6.1 x 12.5 cm. Imaging was also notable for leftward displacement of the spinal cord toward the meningocele starting at the T6 level and extending to the T9 level with kyphosis of the thoracic spine centered on the block vertebral bodies forming the T7-T8 levels. Significant posterior scalloping was evident from T6-T10 with attendant dural ectasia. Neurosurgical consultation recommended no intervention to correct the meningocele as plication carried a risk of producing a subarachnoid-pleural fistula from the meningocele into the pleural space of the thoracic cavity. This case adds to our understanding of how unique and diverse the presentations of NF1 can be, and of the surgical challenges posed by NF1-associated meningoceles.
NIMG-06. AUTOMATED VOLUMETRY OF MENINGIOMAS IN CONTRAST-ENHANCED T1-WEIGHTED MRI USING DEEP LEARNING
Authors: Hirayama Ryuichi , Iwata Takamitsu , Yamada Shuhei , Yokota Chisato , KIjima Noriyuki , Kishima Haruhiko 
Published: November 2024

Abstract

BACKGROUND
With the widespread use of MRI equipment and brain docks, there are more opportunities to perform follow-up observation for meningiomas. In recent years, attempts have been made to predict prognosis by using tumor volume as a highly objective imaging biomarker. On the other hand, manual lesion extraction by a reader with anatomical knowledge is indispensable for volume measurement, which requires a certain amount of labor and time. This is a major barrier to the generation of evidence and clinical application in this field.

OBJECTIVE
To establish the clinical significance of tumor volume as an imaging biomarker in meningiomas, and to develop a simple and highly reproducible application for automated volume measurement using artificial intelligence, and to investigate its accuracy and potential for clinical application.

METHODS
178 patients with meningiomas who underwent MRI at Osaka University Hospital were included in the study. Contrast-enhanced T1-weighted images were used for manual lesion extraction by two neurosurgeons. These annotated image data were randomly divided into training (90%) and testing (10%). The deeplabV3 model was used to train the artificial intelligence, and leave-one-out cross-validation was used to train and validate the automated model. The test data were used for comparison, and the agreement rate (Dice index) on the images of the automatically extracted regions and the error rate of the calculated tumor volume (mean square error rate: RMSPE) were used as indices of measurement performance.

RESULTS
The average agreement rate between the automatically extracted area and the test data was 92.3±5.1%. The error rate of tumor volume was 9.5±1.2%.

CONCLUSION
This application using artificial intelligence was considered to have a certain validity in the accuracy of automatic lesion extraction. This method, which enables simple tumor volume measurement, is expected to create new imaging biomarkers that will contribute to the optimization and personalization of meningioma treatment.
NIMG-12. EVALUATING THE SUPER T2-FLAIR MISMATCH SIGN IN OLIGODENDROGLIOMA, IDH-MUTANT AND 1P/19Q CODELETED
Authors: Ozono Iori , Yamasaki Fumiyuki , Onishi Shumpei , Yonezawa Ushio , Taguchi Akira , Khairunnisa Novita Ikbar , Horie Nobutaka 
Published: November 2024

Abstract

BACKGROUND
We reported the super T2-FLAIR mismatch sign as a prognostic imaging biomarker for non-enhanced astrocytoma, IDH-mutant, CNS WHO grade 2 or 3. However, it remains unclear whether this novel imaging biomarker is applicable for oligodendroglioma, IDH-mutant and 1p/19q codeleted.

METHODS
We conducted a retrospective evaluation of non-enhanced oligodendroglioma, IDH-mutant and 1p/19q codeleted, including 14 cases from at our institute and 15 cases from TCGA/TCIA database. We defined “super T2-FLAIR mismatch sign” positivity as having a significantly strong low signal comparable to cerebrospinal fluid, rather than just a pale FLAIR low-signal tumor region as in regular T2-FLAIR mismatch. We evaluated the presence or absence of T2-FLAIR mismatch sign and super T2-FLAIR mismatch sign using preoperative MRI and statistically analyzed the progression-free survival (PFS) and overall survival (OS) using log-rank test.

RESULTS
The median age of this patient group was 47 (ranging 20-77) years and consisted with 16 males and 13 females. There were 27 cases of grade 2 and two cases of grade 3. The regular T2-FLAIR mismatch sign was observed in three cases (10%) (grade 2: 2 cases, grade 3: 1 case). While the super T2-FLAIR mismatch sign was observed in three cases (10%) (grade 2: 2 cases, grade 3: 1 case). One case had both regular and super T2-FLAIR mismatch signs. The mean follow-up period was 33.4 months, during which there were 3 cases of progression and 1 death. Both regular and super T2-FLAIR mismatch sign were not associated with PFS, OS.

CONCLUSIONS
The presence of the super T2-FLAIR mismatch sign was not associated with prognosis in oligodendroglioma, IDH-mutant and 1p/19q codeleted. Because the sample size was insufficient, further larger investigation through is needed to assess the utility of this sign.
NIMG-36. PERFUSION, DIFFUSION, AND ANATOMICAL MRI BIOMARKERS FOR ASSESSING HISTOLOGICALLY-CONFIRMED MALIGNANT TRANSFORMATION IN MOLECULAR SUBTYPES OF IDH-MUTANT GLIOMAS
Authors: Cho Nicholas , Le Vien , Teraishi Ashley , Liu Vicki , Sanvito Francesco , Nakajo Masanori , Wang Chencai , Oshima Sonoko , Eldred Blaine , Yao Jingwen , Nghiemphu Phioanh , Salamon Noriko , Lai Albert , Cloughesy Timothy , Ellingson Benjamin 
Published: November 2024

Abstract

BACKGROUND
Isocitrate dehydrogenase-mutant (IDHm) gliomas often initially present as low-grade (grade 2) gliomas but are expected to later progress into more aggressive higher-grade (grade 3-4) gliomas through malignant transformation (MT). MT is often determined non-invasively by emergence of contrast-enhancement on post-contrast T1-weighted magnetic resonance imaging (MRI), but contrast-enhancement is an imperfect surrogate for histologically-confirmed MT. This study explored perfusion, diffusion, and anatomical MRI biomarkers besides contrast-enhancement to study histologically-confirmed MT in IDHm 1p/19q-intact astrocytomas (IDHm-A) and IDHm 1p/19q-co-deleted oligodendrogliomas (IDHm-O).

METHODS
N=64 patients with initial histopathological grade 2 IDH-mutant glioma diagnosis who underwent repeated tissue sampling and were classified as histologically-confirmed MT (n=35) or non-MT (n=29) were retrospectively studied. Pre-surgical anatomical MRI (n=64) and, if available, diffusion-weighted imaging (n=61) and dynamic susceptibility contrast perfusion MRI (n=53) were analyzed. Tumor volumes of interest were segmented on the whole T2/FLAIR-hyperintense tumor. Measurable contrast enhancement (&gt;1000mm3), tumor volume, sphericity, median apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) were compared between MT vs. non-MT IDHm-A and IDHm-O.

RESULTS
81% of contrast-enhancing IDHm-A and 100% of contrast-enhancing IDHm-O underwent MT, while 41% of MT IDHm-A and 62% of MT IDHm-O were non-enhancing. Tumor volumes were significantly larger in the MT vs. non-MT groups for both IDHm-A (P=0.02) and IDHm-O (P=0.04). Whole tumor nrCBV was significantly higher (P=0.002), whole tumor ADC trended lower (P=0.06), and non-enhancing tumor sphericity was significantly lower (P=0.03) in MT vs. non-MT IDHm-A. There were no significant differences in ADC, nrCBV, nor sphericity when comparing MT vs. non-MT IDHm-O (P&gt;0.05).

CONCLUSIONS
Many MT IDHm-gliomas remain non-enhancing. Tumor volumes can determine MT for both IDHm-A and IDHm-O. Diffusion and perfusion MRI show differences for MT in IDHm-A but not IDHm-O, which may reflect the different tumor biology of these IDHm molecular subtypes and their need for separate imaging biomarkers.