Frontal Lesions Research Articles

NCOG-36. CLINICAL AND DEMOGRAPHIC CHARACTERISTICS PREDICT POSTOPERATIVE BEHAVIORAL DYSFUNCTION FOLLOWING HIGH-GRADE (WHO 2-4) GLIOMA RESECTION

Abstract BACKGROUND Gliomas have the highest incidence (85%) of cancer-related cognitive and behavioral impairments. Few studies have explored preoperative clinical and demographic drivers/predictors of postoperative behavioral impairment. METHODS We analyzed prospectively collected data from patients 1) who underwent glioma (WHO 2-4) resection and 2) who had postoperative Flanker testing, an assessment of inhibitory control and selective attention (NIH Toolbox Cognition Battery). Patients whose age-adjusted Flanker score (last follow-up) was less than the cohort mean were classified as having “poor” outcomes. Univariate analysis, multivariate logistic, and LASSO regressions were performed to identify drivers of poor outcomes. RESULTS In total, 43 patients (mean age at diagnosis 45.9 [range 18-77] years, 35% female) met inclusion criteria. The average age-adjusted Flanker score was 83.3±13.6; twenty (46.5%) patients had below-average scores. On univariate analysis, there were no significant differences in demographic factors (age, sex, education, employment) and tumor characteristics (grade, location). Multivariate logistic regression identified having high school versus higher degree (OR:1.6x10^4, p=0.017), WHO Grade 4 versus Grade 2 (OR:2.36, p=0.026), and parietal lesion (OR:1.6x10^3, p=0.034) as risk factors, while increased age (OR per 1-year increase:0.71, p=0.009) and dominant language hemisphere lesion (OR 0.002, p=0.048) were protective against poor behavioral outcome. LASSO regression (efficiently narrows down predictors) identified higher WHO grade (4 vs. 2), lower education (high school vs. higher), and insular and parietal lesions as predictive of poor outcomes. Increased age at diagnosis, frontal lobe lesions, and lesions on the dominant language hemisphere were protective. CONCLUSION Lower education status, higher WHO grade, and insular and parietal lesions are risk factors for poor behavioral outcomes postoperatively following glioma resection. In contrast, increased age, frontal lobe lesions, and dominant language hemisphere lesions were positive prognostic factors. Neuro-oncologists may use these findings to preoperatively counsel patients and tailor care plans with necessary postoperative support.

PATH-38. INTRACRANIAL SARCOMA WITH DICER1 MUTATION IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1

Abstract A 16-year-old male with neurofibromatosis type 1 (NF1) and a history of low-grade gliomas presented for resection of a progressively enlarging, known low-grade glioma. On follow-up imaging for surgical planning of the low-grade glioma, a new area of concern was detected of a leptomeningeal-based lesion over the left frontal lobe. A biopsy of the frontal lobe lesion subsequently showed a primary intracranial sarcoma with DICER1 mutations, DICER1 p.Q1552 and p.D1709G. An important histology finding was that of prominent eosinophilic cytoplasmic globules, which are associated with intracranial sarcomas with DICER1 mutations. Additional molecular findings of this tumor included NF1 p.K1986fs and TP53 p.G279E mutations in the setting of this patient’s known history of NF1. A DICER mutation was not detected in the concurrent low-grade glioma at the time of his intracranial sarcoma diagnosis, thus thought not to be a germline-derived mutation. He went on to have a surgical resection with subsequent photon radiation therapy followed by consolidation chemotherapy. A Ewing sarcoma based regimen as per COG protocol AEWS1031 was selected for his therapy consisting of vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide (VDC-IE). This was chosen based on prior cases showing response to anthracycline-based regimens. This patient has overall shown improvement without signs of progression now 7 months out from his initial diagnosis. This case highlights the importance of recognizing the association of patients with NF1 being at an increased risk for the development of intracranial sarcomas with DICER1 mutations and correlation with histologic findings of eosinophilic cytoplasmic globules. It also points to the need for reporting these rare cases for optimization of therapy selection to provide a more standardized and evidence-based approach in the care for these patients.

Transorbital Endoscopic Approach for Managing Challenging Frontal Sinus Lesions: Results and Operative Technique Description

Abstract Objective The aim of this study was to describe our experience using the transorbital endoscopic approach (TEA) in the frontal sinus and the step-by-step technique used. Materials and Methods We reviewed the charts from adult patients who underwent management of frontal sinus lesions with TEA performed from 2017 to 2022. Results Seven patients underwent eight surgeries for frontal sinus lesions using TEA in combination with the endoscopic transnasal approach (ETA), with the majority on the left side (5/8, 62.5%). The average age was 53.9 years, with six male patients and one female patient. Gross total resection (GTR) was achieved in all cases. The most common symptoms leading to surgery were headaches or a sensation of pressure in the forehead (5/8, 62.5%), followed by a decreased sense of smell (3/8, 37.5%), diplopia (3/8, 37.5%), proptosis (2/8, 20%), periorbital cellulitis (2/8, 20%), and decreased visual acuity (1/8, 12.5%). The most common etiology in this case series was mucocele (5/8, 62.5%), followed by osteoid osteoma (2/8, 20%), and inverted papilloma (1/8, 12.5%). The length of stay in all cases was 1 day. The most common complication was mild and transitory V1 numbness, which fully recovered after 6 months (5/8, 62.5%). The average follow-up period was 24.6 months (range of 3–48 months). Conclusion Transoral Endoscopic Approach (TEA) demonstrated being a valuable complement to ETA approaches for treating frontal sinus lesions, especially in challenging regions. The transorbital approach is feasible and can safely achieve GTR for a variety of pathologies while effectively controlling symptoms and resulting in a 1-day hospital stay.

Bihemispheric IDH-Wildtype Glioblastoma with Unilateral FGFR3-TACC3 Fusion in Patient with Breast Cancer History: A Case Report and Literature Review

Abstract Introduction/Objective Adult IDH-wild type glioblastomas comprise a heterogeneous spectrum of neoplasms, characterized by poor prognosis and resistance to the chemoradiotherapy. For WHO integrated diagnosis classification and to establish treatment options, molecular analysis is necessary. Herein, we present a case of a glioblastoma, IDH-wildtype with involvement of both cerebral hemispheres and an uncharacteristic in-frame fusion limited to one hemisphere. Methods/Case Report The patient is a 52-year-old woman with past medical history of metastatic breast cancer who presented with headache and worsening facial pain. Brain magnetic resonance imaging brain demonstrated a right frontal lobe lesion with vasogenic edema. The patient was treated with Gamma Knife radiosurgery. Scans revealed enlargement and a new left frontal lobe lesion. Bihemispheric tumor resection and GammaTile placement was undertaken. Results (if a Case Study enter NA) Histologically, the tumor was composed of hypercellular astrocytes, microvascular proliferation, and necrosis with no evidence of metastatic disease. Immunohistochemistically, neoplastic cells showed glial fibrillary acidic protein expression and elevated Ki-67 proliferation index. Molecular examination revealed in the right hemisphere lesion post-radiation (1) FGFR3::TACC3 (exon 17::exon 11) fusion and (2) TERT promoter, while the left hemisphere lesion which did not receive radiation showed clinically relevant variants in (1) TERT promoter, (2) TP53, (3) NF1, and (3) PIK3CA without identification of a fusion. An integrated diagnosis of glioblastoma, IDH- wildtype, CNS WHO grade 4 was established bilaterally. Conclusion The fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil 3 (TACC3) fusion is identified as a rare molecular feature in glioblastomas with an estimated prevalence of 4%. Clinical trials suggest that F3T3-positive tumors have a better prognosis than those without the translocation. The identification of the oncogenic FGFR3-TACC3 fusion highlights the possibility of identifying patients potentially responsive to targeted therapy with FGFR kinase inhibitors. The significance of the molecular differences in the right and left hemisphere lesions is uncertain; glioblastomas are heterogeneous tumors with intra-and intertumoral heterogeneity but it may suggest independent origins.

Surgical Management of 2,350 Pediatric Dermoid Cysts.

We examined operative and pathologic findings of a large series of dermoid cysts at a high-volume pediatric hospital over 23 years. A retrospective review was performed of all dermoid cysts excised from 2000 to 2023 at the Children's Hospital of Philadelphia. Lesions were classified by location. Depth was stratified into Type 1, superficial; Type 2, subperiosteal or containing a stalk to a cranial suture; Type 3, intraosseous or intracartilaginous; Type 4, intracranial extradural; and Type 5, intracranial intradural. Of 2,350 lesions, 2,237 (95.2%) were in the head and neck. Most common locations were lateral brow and orbit, 892 (38%); anterior neck, 303 (12.9%); and frontal, 253 (10.8%). Among the series, 67.9% were Type 1, 10.1% were Type 2, 16.5% were Type 3, 2.3% were Type 4, and 3.2% were Type 5. Older age at surgery correlated with depth among locations demonstrating intracranial extension (r=.061, p=.016). Anterior fontanelle (59.1%), nasal (16.2%), occipital (5.6%), and temporal (4.7%) lesions had the highest intracranial extension rates. Temporal (49.4%), frontal (32.8%), nasal (29.9%), and occipital (22.2%) lesions had higher rates of osseous/cartilaginous involvement. On histopathologic examination, 403 (17.1%) were ruptured. Ruptured lesions were associated with giant cell reaction (46.4 versus 5.7%, p<.001). Anterior fontanelle, nasal, occipital, and temporal lesions are at higher risk of intracranial extension and may require preoperative imaging. Frontal and parietal lesions have a lower risk of intracranial involvement. Lateral brow and orbit, periauricular, and anterior neck lesions demonstrate a higher rate of osseous involvement without intracranial tracking.

Isolated central nervous system lymphomatoid granulomatosis in an older adult patient with systematic lupus erythematosus: A case report.

Lymphomatoid granulomatosis (LYG) is a rare, T-cell-rich Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative systemic disease. Only a few cases of LYG have been described in patients with autoimmune disorders, with only one case described in a patient with systemic lupus erythematosus (SLE). However, no cases of isolated central nervous system (CNS)-LYG have been reported in patients with autoimmune diseases. Since isolated CNS involvement is rare, its clinicopathological features remain incompletely understood. Herein, we report about an 85-year-old Japanese woman who was diagnosed with SLE 26 years ago and was stable and maintained on prednisone (5 mg/day) for 20 years. Twenty-six days before admission, she developed cognitive dysfunction. Brain magnetic resonance imaging (MRI) revealed multiple nodular lesions with ring-like enhancements seen on gadolinium-enhanced T1-weighted imaging. A brain biopsy was performed on the right frontal lobe lesion. Pathological findings revealed T-cell infiltration surrounding the blood vessels with fibrin deposition, a few multinucleated cells, and large atypical cells with prominent nucleoli. Large atypical cells positive for CD20 and EBV-encoded RNA (EBER) were seen at a density of >100 cells per high-power field. Based on laboratory testing, imaging, and pathology findings, the patient was diagnosed with grade III LYG. Treatment with tirabrutinib (480 mg once daily) was started. The patient achieved clinical response to treatment, as evidenced by improved mental status. In patients with SLE who present with multiple nodular or ring-like lesions on brain MRI, brain biopsy with histological diagnosis is crucial for the exclusion of CNS-LYG.

Factors associated with oropharyngeal dysphagia and unsuccessful nasogastric tube removal after endovascular thrombectomy for anterior circulation stroke.

To identify the predictive variables for post-stroke dysphagia (PSD) among anterior circulation large vessel occlusion (LVO) stroke patients who underwent endovascular thrombectomy (EVT). This retrospective cohort study enrolled hospitalized patients with anterior LVO stroke who underwent EVT between January 1, 2018 and October 31, 2022. PSD was defined as the unsuccessful removal of the nasogastric (NG) tube. Factors, such as premorbid characteristics, laboratory results, EVT, rehabilitation-related parameters, and neuro-imaging, were analyzed for correlations to PSD at 4 and 12weeks. The study enrolled 136 patients, with a mean age of 72.9 ± 13.0years, and 59 patients (43.4%) were male. At 4weeks, 47.1% of the patients needed an NG tube, and at 12weeks, 16.2% still required an NG tube. We found that lower albumin, lower body mass index (BMI), higher initial and 24-h post-EVT National Institute of Health Stroke Scale (NIHSS) scores, stroke-associated pneumonia, poor initial sitting balance and ability to sit up, insula or frontal operculum lesions, and bilateral hemisphere involvement were all associated with PSD at both 4 and 12weeks in the univariate logistic regression. Multivariate analysis revealed that significant predictors of unsuccessful NG tube removal at 4weeks included lower BMI (adjusted OR [aOR] 0.73, p = 0.005), hemorrhagic transformation (aOR 4.01, p = 0.0335), higher NIHSS scores at 24h post-EVT (aOR 1.13, p = 0.0288), poor initial sitting ability (aOR 0.52, p = 0.0231), insular cortex ischemia (aOR 7.26, p = 0.0056), and bilateral hemisphere involvement (aOR 41.19, p < 0.0001). At 12weeks, lower BMI (aOR 0.78, p = 0.0098), poor initial sitting balance (aOR 0.57, p = 0.0287), insular cortex lesions (aOR 4.83, p = 0.0092), and bilateral hemisphere involvement (aOR 4.07, p = 0.0139) remained significant predictors. In patients with anterior LVO following EVT, PSD was associated with lower BMI, higher NIHSS scores, poor initial sitting balance and sitting ability, insular lesions, and bilateral hemisphere involvement.

A - 143 Organic Psychiatric Disorders Due to Frontal Lobe Neoplasms

Abstract Objective This current study seeks to explore the presentation of psychiatric disorders as a preliminary symptom in individuals who suffer from frontal lobe neoplasms. Data Selection The primary sources of information for this literature review were Google Scholar, PubMed, ScienceDirect, and the National Institute of Health (NIH). Search terms included frontal lobe tumors/neoplasms, primary brain tumors, psychiatric/psychological, acquired disorders, and pseudo-depression/mania. This search was limited to articles published in English from January 2014 to December 2023. Inclusion criteria were studies that focused on frontal lobe tumors and psychiatric manifestations as a result of illness. Exclusion criteria were studies older than nine years or studies that explored traits of psychiatric illness (i.e., aggression) as opposed to a psychiatric diagnosis. Data Synthesis Frontal lobe neoplasms, accounting for a significant percentage of PTBs, have been found to impact the psychological well-being of patients, leading to a range of psychiatric manifestations that may appear before physiological symptoms. These include mood disorders (i.e., depression, manic episodes), psychotic episodes, and personality disorders. Due to the complexities of the frontal lobe, these manifestations are not linearly linked to frontal lobe lesions. Conclusion This study’s findings advocate for a multidisciplinary approach to treatment, emphasizing the need for neuropsychological evaluations pre- and post-tumor resection. It calls for heightened awareness among clinicians to consider organic causes behind psychiatric presentations, especially in atypical cases or when traditional treatments fail. Ultimately, this research contributes to a deeper understanding of the neuropsychiatric consequences of frontal lobe neoplasms and paves the way for more targeted and effective interventions.

Pylorus-preserving pancreaticoduodenectomy with superior mesenteric vein resection and reconstruction in a child with recurrent hepatoblastoma after liver transplantation.

Pancreaticoduodenectomy with vascular reconstruction is rarely performed in children. We present a 3-year-old male with stage IV hepatoblastoma and pre-treatment extent of disease (PRETEXT) stage III with tumor into the portal vein and superior mesenteric vein (SMV), and with brain and lung metastases status post chemotherapy and stereotactic radiosurgery to left frontal brain lesion. He then underwent deceased donor liver transplant with Roux-en-Y hepaticojejunostomy complicated by two recurrences to bilateral lungs treated with wedge resections. His course lastly involved a third hepatoblastoma recurrence to the SMV that was managed with pylorus-preserving pancreaticoduodenectomy with SMV resection and reconstruction.

Novel case of ependymoma-like tumor with mesenchymal differentiation harboring ZFTA::RELA fusion in an adult.

High-grade supratentorial tumors harboring ZFTA::NCOA1/2 fusion in infants presenting with mixed histology of embryonal-appearing components resembling ependymoma and mesenchymal sarcomatous components have recently been reported as ependymoma-like tumors with mesenchymal differentiation (ELTMDs). In contrast, we describe herein a pathologically similar case with a novel ZFTA::RELA fusion in an adult. A frontal lobe lesion was resected from a 30-year-old woman and displayed mixed components on pathological examination, showing ependymoma-like and sarcomatous parts. The absence of perivascular pseudorosettes was inconsistent with a diagnosis of ependymoma. Fluorescence in situ hybridization analysis confirmed ZFTA::RELA fusion. The DKFZ methylation classifier (v12.8) did not categorize this case among established methylation classes. In addition, t-distributed stochastic neighbor embedding analysis using DNA methylation data revealed that the present case was distant from ependymomas but close to two previously reported cases of ELTMD involving ZFTA::NCOA1/2 fusion. Taken together, we concluded that this tumor should be considered under the entity of ELTMD. This represents the first description of an adult patient with ELTMD harboring ZFTA::RELA fusion analyzed by DNA methylation profiling, supporting the establishment of ELTMD as a possible new tumor type.

The relationship between swallowing oral hesitation and cognition in frontal lobe stroke.

Oral stage dysphagia mostly caused by frontal lobe lesions. We investigated the relationship between oral hesitation and cognitive impairment after frontal lobe stroke. We consecutively collected 946 patients with stroke from January 2016 to December 2020. Among them, 38 patients had only frontal lobe lesions. Video fluoroscopic swallowing study (VFSS) was performed in 5 stages from water to solid food. Patients who progressed to solid food are very rare, so we focused on liquid and soft food. Diagnosis of stroke was limited to cases in which cerebral infarction or haemorrhage had been verified by magnetic resonance imaging (MRI). Cognitive impairment was evaluated by MMSE in patients with frontal lobe lesions. Of the total 946 patients, 35 patients with frontal lobe lesions were enrolled in the study. Of them, 22 were judged to have cognitive impairment. The oral hesitation of the liquid component was analysed, and a conclusion was drawn that the group with cognitive impairment showed significant oral hesitation than the group without cognitive impairment. On the other hand, in the case of soft food, it was found that there was no correlation between cognition and oral hesitation. It was confirmed that oral hesitation during swallowing in patients with frontal lobe stroke had a meaningful relationship with cognition, and oral hesitation during swallowing was significantly higher in liquid swallowing rather than soft food.

AB039. Malignant transformation of intracranial germinoma to non-germinomatous germ cell tumors-incidence, treatment strategy and outcome: a case report and literature review.

Intracranial germ cell tumors are rare neoplasms seen mainly in children and adolescents. Compared to non-germinomatous germ cell tumors (NGGCTs), germinomas typically respond well to chemo-radiotherapy and portend a better prognosis. We report here a patient with intracranial germinoma which showed complete remission following chemo-radiotherapy but re-presented with malignant transformation to NGGCT thirteen years later. We then performed a literature review to understand the treatment strategy and outcome of this rare phenomenon. Review of the patient's case note, followed by a literature review of the topic. A 13-year-old male presented with 6 weeks of polyuria and polydipsia. Imaging showed bifocal (suprasellar and pineal) lesions. Histology from an open biopsy diagnosed a germinoma. He underwent extended whole ventricular irradiation with local boost and chemotherapy, which led to complete resolution on imaging. Thirteen years later, he re-presented with headaches and diabetes insipidus. Imaging showed a new right frontal lesion with elevated serum beta-human chorionic gonadotropin (β-hCG) and alpha-fetoprotein (AFP). The tumor was excised with histology confirming a mixed tumor comprising germinoma, yolk sac, and choriocarcinoma. A literature review returned eight case reports of malignant transformation of intracranial germinoma to NGGCTs, covering eight patients (seven males, and one female; aged 5-23 years old). Four had the primary tumor located in the pineal region, three in the suprasellar region, and one at both sites. Recurrence with malignant transformation occurred at a median of 24.5 months after initial diagnosis (range, 5 months to 14 years). Five patients had recurrences intra-abdominally, all of whom had a ventriculoperitoneal shunt (VPS) inserted during the treatment of the initial tumor. Of the remaining three intracranial recurrences, two were at the same site while one at a distant site. The most common histology was yolk sac tumor (five patients), followed by two each of immature teratoma, choriocarcinoma, and embryonal carcinoma (some were mixed germ cell tumors). Of those with intra-abdominal recurrence, four died within 2 months of diagnosis. Those with intracranial recurrences survived longer, with a median survival of 15 months, and one longer than 27 months. Malignant transformation to NGGCTs is rare. Relapse can occur intracranially, or in cases where VPS was present, intraabdominally. Outcomes following transformation were poor despite aggressive treatment, with those intra-abdominal recurrences faring much worse.

Multicompartmental Paranasal Sinus Osteoma Complicated by Frontal Bone Hyperostosis, Intracranial Mucocele, and Inflammatory Pseudotumor

Parasinusal osteoma complicated by intracranial and orbit extension, cranial vault hyperostosis, intracranial mucocele and inflammatory pseudotumor is exceptional. A 68-year-old man complaining a long history of progressive proptosis and recurrent episodes of keratoconjunctivitis of the left eye, with restriction in upward gaze, was observed. Contrast-enhanced magnetic resonance imaging revealed a frontal sinus lesion extending to the left anterior fossa and orbit, featuring intracranial cystic component and heterogeneous contrast-enhancement. Head computed tomography confirmed the double calcific-cystic nature of the lesion. A left supraorbital-pterional approach allowed the complete resection of mucocele and drilling of intracranial and orbital osteoma, including the intra-sinusal component. The frontal sinus was cranialized and a flap of pericranium, reinforced by Gelfoam sponge, was reflected on the anterior cranial base/orbital roof. The postoperative course was uneventful; MRI depicted resolution of the proptosis. The histologic examination was in favor of parasinusal osteoma associated to intracranial mucocele, frontal bone hyperostosis and inflammatory pseudotumor.

NFS-19. ATYPICAL PRESENTATION OF GLIOMAS IN ADOLESCENTS WITH NEUROFIBROMATOSIS TYPE 1 (NF1): A CASE SERIES

Abstract BACKGROUND Patients with NF1 are at risk for developing gliomas, usually low-grade in childhood but may be high-grade in adults. In children, the most common sites of disease are the optic pathway and brainstem; tumors in these regions often arise in young children and display histological features characteristic of pilocytic astrocytoma (PA) when biopsied. Typical MRI findings include T2 hyperintense, T1 hypointense lesions with minimal contrast enhancement and no diffusion restriction. Due to the well-established pattern of low-grade tumor formation in children with NF1, as well as the surgically challenging areas in which these tumors develop, low-grade glioma (LGG) therapy is often initiated without histologic confirmation of the diagnosis in classic cases. In cases with atypical disease location, older age at presentation or imaging appearance, a biopsy may be considered to exclude higher-grade lesions. METHODS Retrospective chart review, case series RESULTS Four adolescent patients with NF1 presented with atypical suspected gliomas. All four patients underwent surgical biopsy/resection. Case 1 was a left temporal lesion in the previous radiation field for optic pathway glioma; biopsy confirmed LGG with MAP2K1 mutation and increased focal proliferation index (28%), but methylation did not match with any established classification. The patient progressed through multiple rounds of therapy and succumbed to her tumor. Case 2 was a left occipital lesion; biopsy confirmed PA with CDKN2A deletion. The tumor displayed rapid regrowth, but subsequently stabilized. Case 3 was a right frontal lesion; confirmed PA. The tumor demonstrated some regrowth but then stabilized. Case 4 was a basal ganglia lesion; confirmed PA. The patient has demonstrated stable MRI findings and has not required further intervention. CONCLUSIONS Biopsy yielded helpful prognostic information (additional mutations, proliferation rate) in half of these atypical cases. Biopsy should be carefully considered for NF1 patients with atypical presentation or a history of radiation.

ETMR-21. PRIMARY DIFFUSE LEPTOMENINGEAL MELANOMATOSIS (PDLM) ASSOCIATED WITH INTRACRANIAL BLEEDING AND RAPID PROGRESSION IN A CHILD

Abstract BACKGROUND PDLM is a rare and aggressive disease with limited cases reported worldwide and few cases in the pediatric population. Herein we report on clinical, histologic, and molecular/genetic findings of a young child with PDLM and rapid clinical progression. CASE STUDY A 12-year-old right-handed male presented with two months of intermittent fevers, progressive frontal headaches, lethargy, vomiting, and weight loss, and one month of focal seizures with altered awareness, speech arrest, eye deviation, and tonic posturing. Examination revealed bilateral papilledema and signs of increased intracranial pressure. A brain CT demonstrated increased density of the anterosuperior right frontal lobe and punctate focus of increased density along the left frontal lobe suggestive of hemorrhage. MRI revealed diffuse leptomeningeal thickening and enhancement throughout the brain and spinal cord. At biopsy, the frontal lesion was noted to be grossly abnormal and discolored, and on pathology demonstrated a melanocytic neoplasm infiltrating the subarachnoid space and extending into Virchow-Robin spaces. Tumor cells stained strongly for HMB45, vimentin, Melan-A, and PRAME and were BRAFV600E negative. RNA sequencing was negative for structural variants, Whole exome sequencing revealed a Tier I missense variant in NRAS (c.181C&amp;gt;A) among other copy number variations and loss of heterozygosity. Comprehensive ophthalmologic and dermatologic examinations as well as whole body PET/CT did not reveal any other sites of disease. He was due to commence immunotherapy with combination PD-1/CTLA-4 inhibitors but developed status epilepticus and raised intracranial pressure, warranting ventriculoperitoneal shunt insertion. Three days later, he had further deterioration with altered level of consciousness, hypertension, eye deviation, and vomiting. CT brain revealed large bifrontal hematomas with mass effect and care was redirected to palliation. CONCLUSION PDLM can be challenging to diagnose with a rapidly progressive course. Advanced molecular diagnostics may provide new targets for precision therapy, though overall outcomes remain dismal.

ETMR-32. SUPRATENTORIAL NEUROEPITHELIAL TUMOR WITH PLAGL1 FUSION: A CASE REPORT

Abstract BACKGROUND Supratentorial neuroepithelial tumor with PLAGL1 fusion has emerged as a novel subgroup within pediatric brain tumors. Despite its recent identification, critical aspects such as optimal clinical characteristics and management strategies remain elusive. This case report aims to contribute essential insights to the growing body of literature surrounding this enigmatic tumor entity, providing a detailed exploration of its clinical presentation and histopathological features. METHODS A retrospective chart review was conducted, and relevant data were analyzed. RESULTS An 11-year-old female presented with a two-week history of headaches, vomiting, lethargy, and decreased oral intake. Neuroimaging revealed a left frontal lesion with conspicuous mass effect and midline shift, prompting urgent craniotomy due to sudden onset altered mental status. Histopathological analysis revealed a hypercellular glial neoplasm characterized by perivascular pseudorosettes, scattered microcalcifications, microcysts, and areas of necrosis. Immunohistochemical staining revealed GFAP positivity in a substantial subset of tumor cells, rare dot-like positivity for EMA, and diffuse membranous and focal dot-like positivity for D240. Olig2 was mostly negative, indicating the absence of Oligodendrocyte lineage differentiation. The tumor exhibited an elevated Ki-67 proliferation index (approximately 20-30%). Fluorescence in situ hybridization (FISH) studies were negative for RELA, YAP1, and C19MC rearrangements. Targeted next-generation sequencing unveiled an EWSR1-PLAG1 fusion and methylation profiling classified the tumor as “Neuroepithelial tumors, PLAG1-fused” with high confidence. Given the morphological resemblance to anaplastic ependymoma, the therapeutic recommendation included focal irradiation (54 Gy) with proton therapy. The patient, now 12 months post-therapy, is showing favorable clinical outcomes. CONCLUSION This case report underscores the clinical and histopathological intricacies of supratentorial neuroepithelial tumors with PLAGL1 fusion. The identification of EWSR1-PLAG1 fusion and associated molecular alterations informs diagnostic considerations and treatment strategies for this novel entity, emphasizing the importance of continued research to enhance our understanding of its clinical behavior and optimal management approaches.

Spontaneous Subdural Hematoma associated with Meningioma : Two case reports

Introduction: Spontaneous subdural hematoma rarely presents with a hyper vascular or malignant tumor but even less frequently in a benign tumor like meningioma. We encountered two cases with spontaneous subdural hematoma associated with benign meningioma. Case Description: A 47-year-old Asian woman presented with severe headache and forgetfulness, initiated 3 months before, with no other complaints, denying any previous head trauma. Head computed tomography revealed a chronic left hemisphere subdural hematoma for this issue she underwent burr hole and evacuation of hematoma 1 month before. However her symptoms was not relieved and her magnetic resonance imaging of brain showed left frontal lesion , suggestive of meningioma. Surgical treatment was performed. The tumor was histologically confirmed as a transitional meningioma grade I. After surgery, no neurological deficits were registered, and headache subsided. Similarly, second case, a 56-year-old woman presented with complaints of severe headache for 6 hours. There is no history of seizure like activities, any previous history of head trauma. On examination, no neurological deficits noted. Computed Tomography (CT) of head showed a hyper dense extradural lesion with acute subdural lesion on left hemisphere. MRI brain revealed well defined extra axial round to oval lesion measuring 3.1 X 3.5 X 2.5 cm with areas of heterogeneous enhancement of the left parietal parasagittal area .She underwent left parietal craniotomy and en-bloc tumor resection done. Post operatively there was no neurological deficits and she was discharged on 5th post-operative day. Conclusions: As we could not identify any other cause for the subacute subdural hematoma, hemorrhage from the meningioma was the most probable cause. Although meningiomas are commonly benign according to their histological traits, they can lead to spontaneous bleeding and cause neurologically unstable condition. Therefore, meningiomas need to be considered as a cause of spontaneous subdural hematoma if radiologically suspicious, which should be reflected by proper management for a positive outcome.

Primary intraosseous xanthoma of the frontal bone in a child: illustrative case.

Skull lesions are a common finding in children, with dermoid cysts and eosinophilic granulomas observed most frequently. However, primary intraosseous xanthomas of the calvaria, which are lytic, expansile lesions that develop without underlying hyperlipidemic disease, are rare in children, with only one prior case reported. The authors describe the case of a healthy 6-year-old male who presented with a 2-month history of an enlarging midline skull mass that developed after a recent minor trauma. Imaging showed a full-thickness, lytic frontal bone lesion with an aggressive appearance and heterogeneous contrast enhancement. The patient underwent gross-total resection of the lesion with placement of a mesh cranioplasty. Histopathology revealed a primary intraosseous xanthoma. The patient was discharged on postoperative day 2 and required no further treatment at the 1-month follow-up. This is the first reported case of a primary intraosseous xanthoma in the frontal bone of a pediatric patient. It emphasizes the need to include primary xanthomas in the differential diagnosis for pediatric skull lesions, particularly when the lesion has an aggressive radiographic appearance or the patient has a history of focal trauma. Furthermore, our findings indicate that resection, together with subsequent monitoring for lesion reccurrence, is an adequate first-line treatment.

Verbal learning in frontal patients: area 9 is critical for employing semantic strategies.

Learning is a long-term memory process heavily influenced by the control processes implemented by working memory, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. The aim of this study is to investigate the verbal learning strategies of patients affected by a tumor in the left frontal lobe to highlight the role of area 9. Ten patients with frontal low-grade gliomas and ten healthy control subjects, matched for age, sex and education, were recruited and then evaluated with a two-part verbal learning test: multi-trial word list learning in free recall, and multi-trial word list learning preceded by an explicit semantic strategy cue. Frontal patients were divided into two groups: those either with frontal lesions involving or sparing area 9. In comparison to healthy control subjects, frontal patients with lesions involving area 9 memorized fewer words and displayed difficulty in using semantic strategies. When the strategy was suggested by the examiner, their performance improved, but to a lesser extent than the healthy control. Conversely, frontal patients with lesions sparing area 9 showed similar results to healthy control subjects. The results suggested that, while the identification of the categorical criterion requires the integrity of the entire dorsolateral prefrontal area, only area 9, and not the surrounding areas, could be responsible for the effective use of semantic strategies in learning tasks.

Audit of Presentation, Primary Site, and Pattern of Treatment in 778 Indian Patients with Brain Metastasis in 15 Years (2007–2022)

Background and Aim: Audit of brain metastasis (BM) patients treated with radiation therapy (RT) in a tertiary cancer center from South India was carried out to assess the incidence of BM by site with a specific focus on their primary origin, with an aim to evaluate the relationship between the primary site and the site of metastases, pattern of care, and RT over the years. Materials and Methods: All consecutive BM patients who received RT with whole-brain radiation therapy (WBRT), hippocampal avoidance WBRT (HA-WBRT), and radiosurgery SRS between 2007 and 2022 after radiologic confirmation of a known case of malignancy or histology-proven BM were audited. Results: From January 2007 to December 2022, hospital information system (HIS)-identified 778 patients with BM treated with RT were audited. Incidence of BM was 0.64% in 2008 and over the years, it had increased to 0.89% in 2020, 0.93% in 2021, and 1.24% in 2022. Usage of SRS was almost nil in 2007, whereas in 2022, it was 40%. Also, 593 (76%) patients were treated with WBRT, 157 (20%) with SRS, and only 23 (3%) received HA-WBRT. Lung and breast cancers (40%) were the most common primary, and among rare primary tumors were those of larynx (two), tonsil (one), tongue (three), pancreas (one), and blood disorders (two). Lung primary presented with frontal lesion in 51%, parietal lesion in 43%, cerebellar lesion in 38%, and temporal lesion in 33% of cases. Conclusions: Audit of BM in the Indian population suggests a shift in treatment paradigm from WBRT to SRS as a primary modality in oligo-brain metastasis with a good performance status. This audit provides us information regarding geographic variation in presentation and primary site.