Rare Central Nervous System Tumors Research Articles

BIOM-42. RESPONSE TO DABRAFENIB/TRAMETINIB IN A PATIENT WITH WHO-CNS GRADE 3 BRAF V600E-MUTATED PLEOMORPHIC XANTHOASTROCYTOMA

Abstract BACKGROUND Pleomorphic xanthoastrocytoma (PXA) is a rare central nervous system tumor. Mutations in BRAF V600E are present in 60-80% of cases. While traditionally managed with surgical resection and adjuvant radiation, emerging evidence suggests targeted therapies may be effective, particularly in cases harboring the BRAF V600E mutation. CASE SUMMARY A 35-year-old male with no significant medical history presented in November 2023 with diplopia and headache leading to the discovery of a large left temporal/parietal tumor. A partial resection was performed. Initial histopathological diagnosis was glioblastoma (GBM); thus, the patient was treated with concurrent radiation and temozolomide for 6 weeks. Molecular pathological analysis demonstrated the presence of BRAF V600E mutation and CDKN2A/B copy number loss. Methylation-based tumor profiling was performed at the National Cancer Institute, with composite methylation profile indicating a consensus match to pleomorphic xanthoastrocytoma. Following chemoradiation, a repeat brain MRI in March 2024 showed tumor progression, prompting the initiation of dabrafenib and trametinib therapy. After 1 month of targeted treatment, a repeat brain MRI demonstrated a partial response with a decrease in tumor size and enhancement. In April 2024, he underwent a planned repeat resection. Symptomatically, the patient experienced intermittent headaches and nausea that were responsive to oral steroids with no serious adverse effects to targeted therapy. DISCUSSION This case highlights the therapeutic potential of double BRAF/MEK blockade with dabrafenib and trametinib in BRAF V600E-mutant anaplastic PXA. The observed partial response on imaging suggests the efficacy of targeted therapy in this molecular subtype. These findings underscore the importance of molecular profiling in guiding treatment decisions.

INNV-08. PRE-CLINICAL AND CLINICAL EVIDENCE FOR THE TREATMENT OF DMG/DIPG USING EMULATE THERAPEUTICS’ ULTRA-LOW RADIO FREQUENCY MAGNETIC FIELD SIGNAL TECHNOLOGY

Abstract EMulate Therapeutics, Inc. (EMTx) has developed a technology that emulates the effects of chemical compounds via a magnetic field. Our research has led to the development of a radio frequency energy (RFE) signal (A1A) that emulates the effects of paclitaxel. Pre-clinical studies demonstrate an effect in slowing down and inhibiting tumor growth. The results of feasibility (Phase I/II) clinical trials testing the EMTx technology for treating recurrent GBM (rGBM) were published in CNS Oncology (CNS Oncol 2023 Pages CNS102, Accession Number: 37462385 DOI: 10.2217/cns-2022-0016). Reported results suggest that the A1A signal is non-inferior to best supportive care (BSC) and when the A1A signal is combined with BSC, a 3-month increase in overall survival (OS) was observed. Diffuse intrinsic pontine gliomas (DIPG) are a rare pediatric central nervous system (CNS) tumor. Survival is measured at under 12 months, with no clinical trials demonstrating a significant increase in OS in 20 years (9 months median survival post radiation therapy). EMTx’s compassionate use program (Hælo® medical device) demonstrated safety and suggested a clinical benefit, with 12 of 14 patients surviving more than 12 months, with median survival of 17 months. EMTx recently completed an orthotopic mouse model of DIPG at University of California San Francisco. The results from exposing the mice to the A1A signal demonstrated a significant survival advantage (P = 0.0163) via the slowing down of cell division. Data to be submitted for peer review publication. The animal model is encouraging and supports the observed results of our compassionate use program. EMTX will submit these results to the FDA for regulatory approval via the Humanitarian Device Exemption pathway. The company will conduct a study with DIPG patients from both the US and India. Subject to FDA protocol approval, 30-35 patients will be recruited to participate in this pediatric neuro-oncology trial, which will be a best supportive care + single therapy (Hælo®) clinical trial.

SURG-02. ANAPLASTIC PLEOMORPHIC XANTHOASTROCYTOMA WITH LEPTOMENINGEAL DISSEMINATION PRESENTING WITH CRANIAL NEUROPATHY IN AN ADULT PATIENT: ILLUSTRATIVE CASE AND REVIEW OF THE LITERATURE

Abstract INTRODUCTION Anaplastic pleomorphic xanthoastrocytomas (APXA) are very rare, grade III malignant astrocytic glial neoplasms first described as a distinct entity in the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS). They are generally seen in pediatric and young adult patients as supratentorial lesions with both solid and cystic components and have a high propensity for recurrence despite local treatment. APXAs occasionally demonstrate leptomeningeal dissemination (LMD) but extremely seldom at the time of diagnosis. They are typically treated via surgical resection with adjuvant chemoradiation, although there is no standard of care for adjuvant therapy. Case Presentation: The authors describe the case of a 37-year-old male with a history of seizures since age 11 who presented with four months of worsening headache, increasingly frequent seizures, and diplopia with right cranial nerve III palsy. Imaging at the time of diagnosis of his seizure disorder as a child demonstrated a small left temporal lesion, which remained stable on imaging for over 20 years and was never biopsied, however MRI at current presentation showed significant interval enlargement with intralesional hemorrhage and leptomeningeal enhancement involving the left temporal and parietal lobes, left internal auditory canal, and right oculomotor nerve. He underwent surgical resection with gross total resection achieved and pathology revealed WHO Grade III pleomorphic xanthoastrocytoma with ATG7::RAF1 fusion, 9p21 deletion, and TERT promoter mutation on next generation sequencing. This was followed by adjuvant whole brain radiation with boost and treatment with MEK inhibitor cobimetinib. His postoperative course was remarkable for intermittent speech difficulty and improving right third nerve palsy. CONCLUSION We describe the unusual presentation of an already exceedingly rare primary CNS tumor, namely APXA in an adult patient with LMD and cranial neuropathy at the time of diagnosis, and detail tailored adjuvant therapy based on genomic profiling.

A patient with heterochronous double primary tumor of basal ganglia germ cell tumors followed by diffuse hemispheric glioma: a case report.

Basal ganglia germ cell tumor (BGGCT) is a rare central nervous system (CNS) tumor. Diffuse hemispheric gliomas, H3 G34-mutant (DHGs) is an invasive glioma involving the cerebral hemispheres. The diagnosis of DHGs depends on the integration of histopathology and molecular pathology. We reported a patient with an initial diagnosis of BGGCT that was sensitive to subsequent chemoradiotherapy. Unfortunately, a second high-grade glioma was found on magnetic resonance imaging (MRI) six years later. Subsequently, the tumor was completely removed after surgery and the following histopathology plus next generation sequencing (NGS) testing confirmed the diagnosis of DHGs. Interestingly, we found a germline likely pathogenic variant in FANCA. After surgery, the patient received Stupp regimen. The patient had a relapse 13months after the Stupp regimen and was doing well after surgery. This is the first report of a patient with heterochronous double primary tumor of BGGCT followed by DHGs.

Spinal Cord Astroblastoma With EWSR1-BEND2 Fusion in Female Patients : A Report of Four Cases From China and a Comprehensive Literature Review.

Astroblastoma is an extremely rare central nervous system tumor characterized by astroblastic pseudorosettes and vascular hyalinization. Despite these histologic hallmarks, its morphology can vary, occasionally resembling other central nervous system tumors such as ependymoma. A novel tumor entity, astroblastoma, meningioma 1 ( MN1 )-altered, has been identified, featuring MN1 gene rearrangements typically involving BEN-domain containing 2 ( BEND2 ) as a fusion partner. Most astroblastomas arise in the cerebral hemisphere. Here, we report 4 cases of spinal cord astroblastoma in female patients, all showing Ewing sarcoma RNA-binding protein 1 fusion with BEND2 , rather than MN1 . These tumors displayed growth patterns akin to traditional intracranial astroblastomas, with three cases demonstrating high-grade histology, including elevated mitotic activity and necrosis. Interestingly, some cases exhibited positive staining for pan-cytokeratin and hormone receptors. DNA methylation profiling clustered three of the four cases with the reference "AB_EWSR," whereas one case exhibited an independent methylation signature near the reference methylation group "AB_EWSR" and "pleomorphic xanthoastrocytoma." Together with the existing literature, we summarized a total of eleven cases, which predominantly affected children and young adults with female predilection. Eight of 10 patients experienced recurrence, underscoring the aggressive nature of this disease. We suggest recognizing a new molecular subgroup of spinal astroblastoma and recommend testing newly diagnosed infratentorial astroblastomas for Ewing sarcoma RNA-binding protein 1-BEND2 fusion.

Increased Human Chorionic Gonadotropin Level in a Nonsexually Active Young Female

BackgroundQuantitative and qualitative human chorionic gonadotropin (hCG) tests are obtained in the emergency department (ED) to determine if a female of child-bearing age is pregnant. A positive hCG result is commonly assumed to indicate an intrauterine or other form of pregnancy. However, elevated hCG levels can also result from various other conditions, such as ovarian tumors, pituitary tumors, and thyroid disorders. Intracranial germ cell tumors, rare central nervous system tumors capable of secreting hCG, primarily affect adolescent and young adult females. Case ReportA 16-year-old female student without significant past medical history presented to our ED with a complaint of intermittent bilateral frontal headache for two days. Last menstrual period started two days prior to presentation. The headache was associated with phonophobia, photophobia, nausea, and vomiting. Serum quantitative hCG was elevated. She denied history of sexual activity or sexual assault. Transabdominal ultrasound was negative for intrauterine pregnancy. Obstetrics and gynecology as well as pediatric oncology were consulted. Subsequent investigations, including brain imaging, revealed a 3.5 cm mass in the right caudate nucleus and corpus callosum. The patient was diagnosed with an intracranial nongerminomatous germ cell tumor, necessitating hospitalization and prompt initiation of chemotherapy. Why Should an Emergency Physician Be Aware of This?An elevated quantitative hCG is not always indicative of pregnancy, especially in a young patient without sexual history. In the case of a nonrevealing transabdominal ultrasound, obstetrics and gynecology should be consulted for discussion of further testing and imaging. Emergency physicians should include malignancy high on their differential since prompt initiation of chemotherapy, evaluation by surgical services, and family planning will be required.

Identifying associations between sample characteristics, symptoms, and self-efficacy differences in adult patients with rare tumors of the central nervous system who participated in a novel web-based natural history study.

High self-efficacy is associated with improved self-care and reduced symptoms in cancer patients but has not been fully interrogated in adults with central nervous system (CNS) cancers. We aimed to identify the relationship between self-efficacy levels in managing emotions (SEMEM) and social interactions (SEMSI) by examining sample characteristics and symptom burden. Sample characteristics and patient-reported outcome (PRO) measures addressing self-efficacy (PROMIS SEMEM & SEMSI) and symptom burden (MDASI BT or SP) were collected in a novel web-based study of 158 adult patients diagnosed with rare CNS tumors. The sample was predominantly female (73%), diagnosed with an ependymoma (66%), and had a median age of 45 (19-75). Low SEMEM was associated with a longer duration of symptoms before surgery (r = -0.26) and female gender (92%) among brain tumor (BT) participants and in spinal cord tumors (SCT), those with lower education (r = 0.29). Reporting low SEMSI was associated with being married (42%), lower education (r = 0.22), and a prolonged time with symptoms before surgery (r = 0.29) in those with BTs, with no associations identified in SCT. More severe mood-related interference (including mood, enjoyment of life, and relationship with others) was associated with lower SEMEM among both locations (r = -0.61 brain, r = -0.28 spine) and SEMSI in BT participants (r = -0.54). Low self-efficacy was linked to a prolonged time between symptom onset and initial surgery, education, gender, and marital status and was associated with higher mood-related interference. Understanding characteristics associated with low self-efficacy underscores a need for future studies to tailor interventions that enhance self-efficacy.

Malignant melanotic schwannoma of the cervical spinal cord: a case report

Spinal cord malignant melanotic schwannoma (MMNST) is a rare central nervous system tumor that originates from the spinal cord or spinal myelin sheath cells and can produce melanin. This type of tumor is usually highly aggressive and malignant, with a poor prognosis. The clinical manifestations of spinal cord MMNST are mainly pain, paresthesia, muscle weakness, muscle atrophy, etc., and symptoms of spinal cord compression, such as intestinal and bladder dysfunction, paraplegia, etc. Early detection of tumor lesions can facilitate tumor removal, improve patients’ quality of life, and prolong patients’ survival. In this case report, a 27-year-old young woman was diagnosed with MMNST of the cervical spinal cord due to weakness of her limbs in our hospital, and underwent surgical resection. The patient’s limbs returned to normal after surgery. It is worth mentioning that the patient visited our hospital 7 months ago for “right upper limb pain for 3 days” and was diagnosed with a cervical spine space-occupying lesion at the same position this time, but the pathology report was “hemosiderosis”. This case report aims to raise awareness of the problem of spinal cord MMNST and contribute to greater knowledge of this rare tumor.

Construction and Validation of Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Primary Anaplastic Oligodendroglioma

Anaplastic oligodendroglioma (AOD) is a rare high-grade central nervous system tumor. The current research on prognostic prediction of AOD remains limited. This study aimed to identify prognostic factors and establish the nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with AOD. Patients diagnosed with AOD between 1992 and 2020 were extracted from the Surveillance, Epidemiology, and End Result database. We performed univariate and multivariate Cox regression analyses to identify independent prognostic factors based on the training group. Kaplan-Meier survival curves were used to compare the impact of various independent factors on patient prognosis. For OS and CSS, the nomograms were constructed and verified by the validation group. Harrell''s concordance index, receiver operating characteristic curves, calibration curves, and decision curve analyses were used to assess the discrimination, consistency, and clinical value of the nomograms. A total of 1202 AOD patients were enrolled, being randomly divided into training (n= 841) and validation (n= 361) groups (7:3 ratio). Univariate and multivariate Cox analysis identified 4 significant independent factors (tumor site, age, surgery, and chemotherapy). For OS and CSS, Harrell''s concordance index were 0.731 (0.705-0.757) and 0.728 (0.701-0.754) in the training group, 0.688 (0.646-0.731) and 0.684 (0.639-0.729) in the validation group, respectively. Receiver operating characteristic curves and Calibration curves showed good discrimination and consistency, respectively. In addition, the decision curve analyses curves showed the nomograms have good clinical benefits. We successfully established the nomograms to predict the OS and CSS for AOD patients. The nomograms showed good performance in prognostic prediction, assisting clinicians in evaluating patient prognosis and personalizing treatment plans.

Genetically Distinct Oligosarcoma Arising from Oligodendroglioma: Systematic Review & Illustrative Case Example

BackgroundOligosarcoma is a rare central nervous system (CNS) neoplasm that may arise following oligodendroglioma resection, which demonstrates a unique genetic profile and aggressive clinical phenotype. We present a systematic review and illustrative case example emphasizing the clinical and prognostic features of this unusual and unfavorable neuro-oncologic disease. MethodsSystematic literature review and illustrative case report. ResultsA 41-year-old man who had undergone two neurosurgical resections for a WHO grade II oligodendroglioma (Ki-67=5-10%, 1p/19q co-deleted, IDH2 mutated), without adjuvant chemoradiation, presented with seizures seven years after resection. An extra-axial mass was identified adjacent to the resection cavity, in which gross total resection was achieved. Pathology confirmed WHO grade IV oligosarcoma (Ki-67=20%). Adjuvant chemoradiation was initiated, with disease control observed over 6 months of follow-up.7 publications met inclusion criteria. Oligosarcoma has been confirmed in 36 lesions, arising in 35 patients; 5 were primary oligosarcoma, while 31 occurred in the setting of prior resected oligodendroglioma or oligoastrocytoma. Features shared by these lesions include re–gain of H3K27me3 expression, 1p/19q codeletion, homozygous deletion of CDKN2A/B, loss of 6q, loss of NF1 and YAP1, and attenuation of CpG island methylator (G-CIMP). Median survival after oligosarcoma diagnosis was 1.3 years (range, 0-5.2; n=35). ConclusionOligosarcoma is a prognostically unfavorable CNS neoplasm with characteristic imaging and pathologic features, and a strong association with previously resected oligodendroglioma. Aggressive treatment is recommended, including gross total resection and adjuvant chemoradiation. Further study is required to define optimal treatment protocol for this CNS malignancy.

Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors

PurposeMultidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers.MethodsWe retrospectively reviewed records from virtual MTBs held between 04/2020–03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions.ResultsDuring 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions.ConclusionVirtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management.

Epidemiology, Characteristics, and Prognostic Factors of Primary Atypical Teratoid/Rhabdoid Tumors in the Spinal Canal: A Systematic Review.

Primary atypical teratoid/rhabdoid tumors (AT/RTs) in the spinal canal are rare central nervous system (CNS) neoplasms that are challenging to diagnose and treat. To date, there has been no standard treatment regimen for these challenging malignant tumors. Thus, we conducted this research to explore potential prognostic factors and feasible treatment modalities for improving the prognosis of these tumors. Articles were retrieved from the PubMed, MEDLINE, and Embase databases, using the keywords "atypical teratoid/rhabdoid tumor," "rhabdoid tumor," "spine," "spinal," "spinal neoplasm", and "spinal cord neoplasm." All eligible cases demonstrated SMARCB1-deficient expression validated by pathological examination. We collected and analyzed data related to clinical presentation, radiological features, pathological characteristics, treatment modalities and prognosis via Kaplan-Meier and Cox regression analyses. Thirty-six articles comprising 58 spinal AT/RT patients were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 18 and 22 months, respectively. Kaplan-Meier analysis demonstrated significant survival improvements for OS in the nonmetastasis, male, radiotherapy and intrathecal chemotherapy groups as well as for PFS in the chemotherapy and radiotherapy groups. Multivariate analysis revealed that chemotherapy and radiotherapy were prognostic factors for improved PFS, and that intrathecal chemotherapy reduced the risk of mortality. Spinal AT/RTs are uncommon malignant entities with a dismal survival rate. Although our review is limited by variability between cases, there is some evidence revealing potential risk factors and the importance of systematic chemotherapy, intrathecal chemotherapy and radiotherapy in spinal AT/RT treatment modalities.

Epidemiology and survival of patients with spinal meningiomas: a large retrospective cohort study.

Spinal meningiomas (SMs) are relatively rare central nervous system tumors that usually trigger neurological symptoms. The prevalence of SMs is increasing with the aging of the global population. This study aimed to perform a systematic epidemiologic and survival prognostic analysis of SMs to evaluate their public health impact and to develop a novel method to estimate the overall survival at 3-year, 5-year, and 10-year in patients with SMs. Five thousand one hundred fifty eight patients with SMs were recruited from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Firstly, descriptive analysis was performed on the epidemiology of SMs. Secondly, these individuals were randomly allocated to the training and validation sets in a ratio of 7:3. Kaplan-Meier method and Cox regression analysis were utilized in the training set to identify independent prognostic factors and to construct a nomogram for survival prognosis. Subsequently, the discriminative power, predictive performance, and clinical utility of the nomogram were evaluated by receiver operating characteristic curve and decision curve analysis. Finally, a mortality risk stratification system and a web-based dynamic nomogram were constructed to quantify the risk of mortality in patients with SMs. The annual age-adjusted incidence rates of SMs increased steadily since 2004, reaching a rate of 0.40 cases per 100000 population in 2019, with a female-to-male ratio of ~4:1. The age groups of 50-59, 60-69, and 70-79 years old were the most prevalent ages for SMs, accounting for 19.08, 24.93, and 23.32%, respectively. In addition, seven independent prognostic factors were identified to establish a prognostic nomogram for patients with SMs. The decision curve analysis and receiver operating characteristic curve indicated that the nomogram had high clinical utility and favorable accuracy. Moreover, the mortality risk stratification system effectively divided patients into low-risk, middle-risk, and high-risk subgroups. SMs are relatively rare benign spinal tumors prevalent in the white elderly female population. Clinicians could use the nomogram to personalize the prediction of the overall survival probability of patients with SMs, categorize these patients into different mortality risk subgroups, and develop personalized decision-making plans. Moreover, the web-based dynamic nomogram could help to further promote clinical application and assist clinicians in providing personalized counseling, timely monitoring, and clinical assessment for patients.

INNV-27. LOW/ULTRA-LOW RADIO FREQUENCY MAGNETIC FIELD THERAPIES FOR THE TREATMENT OF CNS TUMORS: RGBM AND DIPG – PAST AND CURRENT RESULTS USING THE EMULATE THERAPEUTICS INC. TECHNOLOGY

Abstract EMulate Therapeutics, Inc. (EMTx) has developed a technology that emulates the effects of chemical compounds, via an alternating magnetic field. Our research has led to the development of a radio frequency energy (RFE) signal (A1A) that emulates the effects of paclitaxel. Pre-clinical and animal studies demonstrate an effect in slowing down and inhibiting tumor growth. EMTx has developed a portable medical device that allows for continuous delivery of our A1A signal for up to 14 hours before recharging. The device can be used in combination with current best-supportive-care (BSC) and new investigational treatments. Our technology has been tested in recurrent glioblastoma (rGBM) with very encouraging results in overall survival (OS), especially in combination with BSC. Phase II OS alone was equivalent to BSC (7.2 months BSC OS vs. 7.0 months A1A alone OS) and a considerably improved OS when combined with conventional drug treatment (7.2 months BSC OS versus 10.0 months A1A + BSC OS). EMTx is in the process of seeking humanitarian device exemption (HDE) from the US Food & Drug Administration (FDA) for the Hælo® therapeutic system, our pediatric treatment option. Diffuse intrinsic pontine gliomas (DIPG) are a rare pediatric central nervous system (CNS) tumor. Survival is measured in under 12 months, with no clinical trials demonstrating a significant increase in overall survival in 20 years (9 months median survival post radiation therapy). EMTx’s compassionate use program demonstrated safety and suggested a clinical benefit, with 12 of 14 patients surviving more than 12 months. EMTx is committed to run and complete a pivotal pediatric trial for children diagnosed with DMG/DIPG. The trial will recruit study patients from both the US and India. A total of 35-40 patients will be recruited to participate in this pediatric neuro-oncology trial, which will be a best-supportive-care + single therapy (Hælo®) clinical trial.

A rare case of large retropharyngeal pre-vertebral chordoma presented as oropharyngeal swelling

Posterior oropharyngeal swelling can result from various pathologies, including chordomas. Chordoma is a notochordal remnant origin tumor. It is a rare bone and central nervous system tumor, especially in the cervical region. Chordoma is a tumor with properties such as slowly growing and frequently recur in most patients. This case report aims to comprehensively understand the clinical presentation and radiological features of a rare C2 retropharyngeal pre-vertebral chordoma. A 24-year-old male with a two-year history of dysphagia presented with progressively worsening symptoms, including dyspnea, dysphonia, and weight loss. On examination, a large mass was observed in the posterior oropharynx. Radiologically, a large soft tissue mass involves the C2 vertebral body, extending into the pre-vertebral soft tissue and compromising the airway. The mass appears hypointense in T1 weighted images, heterogeneously hyperintense in T2, and shows heterogeneous contrast enhancement. The chordoma was confirmed through histopathological analysis, showing characteristic physaliferous cells within a myxoid stroma. Posterior oropharyngeal masses require prompt and accurate evaluation. Radiological evaluation is crucial in identifying the tumor's origin, extent, and vascularity, aiding in diagnosis and treatment planning. Surgical resection is the primary treatment, but chordomas have a high recurrence rate even after complete removal. Radiotherapy can improve survival and reduce recurrence. This case highlights the importance of multidisciplinary collaboration in providing individualized care for rare chordoma presentations.

A Pineal Parenchymal Tumor of Intermediate Differentiation in an Octogenarian Contains a Rare KBTBD4 Insertion.

Pineal parenchymal tumors are rare central nervous system tumors that pose diagnostic challenges for surgical pathologists. Due to their paucity, their clinicopathologic features are still being defined. We report an 86-year-old woman with a remote history of breast lobular carcinoma who presented with a 2-month neurologic history that included gait instability, blurry vision, and headaches. Magnetic resonance imaging revealed a lobular, heterogeneously enhancing pineal region mass compressing the aqueduct of Sylvius. A biopsy performed concomitant with endoscopic third ventriculostomy consisted of small sheets of cells with eosinophilic to clear cytoplasm, multipolar processes, and ovoid nuclei with stippled chromatin. Whole exome sequencing revealed a small in-frame insertion (duplication) in exon 4 of KBTBD4 (c.931_939dup, p.P311_R313dup/ p.R313_M314insPRR), which has very recently been reported in 2 pineal parenchymal tumors of intermediate differentiation (PPTID). Additionally, variants of uncertain significance in CEBPA (c.863G > C, p.R288P) and MYC (c.655T > C, p.S219P) were identified. Although PPTID is considered a disease of young adulthood, review of 2 institutional cohorts of patients with pineal region tumors revealed that 25% of individuals with PPTID were over 65 years of age. In conclusion, PPTID should be considered in the differential diagnosis of pineal region tumors in older adults.

Neuroepithelial tumor with EWSR1::PATZ1 fusion: A literature review.

We present the clinicopathological and molecular genetic characteristics of a neuroepithelial tumor (NET), EWSR1::PATZ1 fusion-positive with a literature review. This fusion has recently been discovered in rare central nervous system tumors and soft tissue sarcomas and was not included in the fifth edition of the WHO classifications. We identified this fusion in 2 NETs. The first case involved a 7-year-old girl and the second case occurred in a 53-year-old man; both presented with headaches and vomiting. The pediatric case initially showed an intermediate grade of the tumor, but upon recurrences, it transformed into a high-grade tumor with 2 relapses in 8.3 years. This case exhibited high mitotic activity (20/10 high-power fields), and a high Ki-67 index (21%). The TERT promoter (TERTp) mutation was present in both initial and recurrent tumors. In contrast, the adult case was a low-grade tumor with no mitotic activity or recurrence over 13.5 months after subtotal resection and gamma knife surgery. Interestingly, the pediatric case demonstrated a longer survival time compared to conventional glioblastoma. The TERTp mutation, similar to being a molecular signature in adult-type glioblastoma, could also be an indicator of high-grade behavior in PATZ1 fusion NET.

FRI337 Progressive Suprasellar Chordoid Glioma Presenting With Panhypopituitarism, Diabetes Insipidus And Encephalopathy

Abstract Disclosure: J.D. Gatillo: None. M.D. Maningat-Goco: None. F.K. Co: None. Chordoid glioma is a rare central nervous system neoplasm of uncertain origin, with most cases seen at anterior wall or roof of the third ventricle. It is described as a perplexing lesion as it tends to mimic benign lesions at the onset but eventually some develop with threatening complications. We present a case of a 39 year old Filipino, female, who initially presented with a 1- year history of memory lapses, behavioral changes, and blurring of vision. MRI showed 4.3 x 3 x 4.2 cm heterogeneously enhancing suprasellar mass and was initially worked-up as pituitary macroadenoma. The imaging also showed heterogeneously enhancing extra-axial lesion along the right anteromedial temporal convexity. She underwent pterional craniotomy and sub temporal craniectomy with excision biopsy of tumor. Histopathology confirmed the diagnosis of chordoid glioma WHO Grade 2. However, only a few days after the surgery, she began to experience emotional lability and more behavioral changes. She then received oral Temozolomide for 4 cycles and whole brain radiotherapy for 32 cycles. Approximately 10 months since diagnosis was made, patient eventually developed seizures and manifested progressive drowsiness and generalized weakness. Patient was diagnosed and clinically presented with Panhypopituitarism and Diabetes Insipidus. She was maintained on levothyroxine, prednisone and desmopressin. A repeat MRI was done which showed apparent progression in the size (4.6 x 3.7 x 4.1 cm) of the heterogeneously enhancing suprasellar mass with signs of tumor infiltration and extension in the left lateral ventricle. Further, patient was treated with Bevacizumab and Nimotuzumab. Repeat MRI showed regression in size of the known suprasellar mass and improvement of symptoms. Little is still known about chordoid gliomas especially in the Asian population - their initial presentation as well as the best diagnostic approach and treatment strategy for this elusive disease. There is no formally recognized treatment protocol for chordoid glioma, and postoperative mortality and morbidity is high. More case reports are needed in order to ascertain the best diagnostic and treatment strategy for patients with chordoid glioma and its endocrine complications. Presentation: Friday, June 16, 2023

P21.05.B CAPTURING EVOLVING DEFINITIONS OF 12 SELECT RARE CNS TUMORS: A TIMELY REPORT FROM CBTRUS AND NCI-CONNECT

Abstract BACKGROUND Histopathology-specific incidence, prevalence, and survival are essential population-based cancer statistics that describe cancer burden. The National Cancer Institute’s Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) aims to improve understanding of tumor biology and patient outcomes for 12 selected rare brain and other central nervous system (CNS) tumor types to improve approaches to care and treatment. These types included atypical teratoid/rhabdoid tumor, brainstem and midline gliomas, choroid plexus tumors, ependymomas, high grade meningiomas, gliomatosis cerebri, medulloblastoma, oligodendrogliomas, pineal region tumors, pleomorphic xanthoastrocytomas, CNS embryonal tumors, NEC/NOS and primary CNS sarcoma. The analysis aimed to estimate the incidence (new cases per year), prevalence (currently living cases), and survival rates for these selected rare brain and other CNS tumor types. MATERIAL AND METHODS The Central Brain Tumor Registry of the United States (CBTRUS) data, which contains data from the Centers for Disease Control and Preventions National Program of Cancer Registries (NPCR) and National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) data, from 2008-2019 were used to calculate average annual age-adjusted incidence rates (AAAIR) per 100,000 population overall and by sex, race/ethnicity, and age. Incidence time trends were calculated for diagnosis years 2004-2019. NPCR survival data from 2001-2018 were used to calculate relative survival (RS) estimates. Estimated prevalence counts as of December 31, 2019 were estimated using incidence from CBTRUS and overall survival rates from SEER. RESULTS Overall AAAIR for all 12 subtypes combined was 1.51 per 100,000 population, with the highest subtype-specific incidence in ependymomas (AAAIR=0.41/100,000). Overall, most subtypes were more common in males and people who are non-Hispanic White. Incidence of all subtypes varied by age. Ependymomas were most prevalent with 19,339 cases; followed by oligodendrogliomas with 15,070 cases. Time trends in incidence varied by subtype, with significant decreases in incidence of gliomatosis cerebri, CNS embryonal tumor, and primary CNS sarcoma. RS for all subtypes combined at 1, 5, and 10 years was 86.6%, 71.9%, and 65.3%, respectively. Ependymomas had the highest RS (1-year=96.1%, 5-years=90.6%, 10-years=86.6%) and primary CNS sarcomas had the lowest RS (1-year=48.2%, 5-years=7.7%, 10-years=5.2%). CONCLUSION Incidence, prevalence, and survival patterns for these 12 selected rare cancer subtypes varied significantly by type. Population based data are critical to guiding effective design of and accrual expectations for clinical trials in rare cancers.

Ependymoma in WHO Classification of Tumours 5th Edition

Ependymoma is a rare central nervous system tumor that occurs in all age groups and is one of the most common childhood malignant brain tumors. Until the 3rd edition of the WHO Classification of Brain Tumours, ependymoma was classified based solely on histologic findings, but advances in molecular analysis led to the incorporation of molecular information into the diagnosis of ependymoma for the first time in the 2016 WHO Classification, 4th edition. However, the low correlation between tumor grade and survival prognosis remained a problem. Unlike other malignant brain tumors, ependymoma is genetically and epigenetically characterized with few identified point mutations. Methylation profiling was found to classify ependymoma into distinct subgroups, and the 2021 WHO Classification, 5th Edition, adopted new classifications by histologic findings, genetic alterations, methylation patterns, and anatomic location. This new classification includes 10 diagnostic entities: 1)supratentorial subependymoma; 2)supratentorial ependymoma, ZFTA-fusion positive; 3)supratentorial ependymoma, YAP1-fusion positive; 4)posterior fossa subependymoma; 5)posterior fossa group A ependymoma; 6)posterior fossa group B ependymoma; 7)spinal subependymoma; 8)spinal ependymoma; 9)spinal myxopapillary ependymoma; and 10)spinal ependymoma, MYCN-amplified. The previously accepted term "anaplastic ependymoma" was dropped. As with other CNS tumors, a new classification was introduced based on an integrated diagnosis that incorporates histologic and molecular diagnosis. In this article, we summarize the molecular classification of ependymoma in the WHO Classification of Brain Tumours, 5th edition.