Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide.

PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ. RESULTS: The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009). CONCLUSION: Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM. CLINICALTRIALS: gov Identifier: NCT03344250.

Publisher Correction: Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease.

Change history: In this Article, Extended Data Fig. 9 was appearing as Fig. 2 in the HTML, and in Fig. 2, the panel labels 'n' and 'o' overlapped the figure; these errors have been corrected online.

Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease.

Ageing is a major risk factor for many neurological pathologies, but its mechanisms remain unclear. Unlike other tissues, the parenchyma of the central nervous system (CNS) lacks lymphatic vasculature and waste products are removed partly through a paravascular route. (Re)discovery and characterization of meningeal lymphatic vessels has prompted an assessment of their role in waste clearance from the CNS. Here we show that meningeal lymphatic vessels drain macromolecules from the CNS (cerebrospinal and interstitial fluids) into the cervical lymph nodes in mice. Impairment of meningeal lymphatic function slows paravascular influx of macromolecules into the brain and efflux of macromolecules from the interstitial fluid, and induces cognitive impairment in mice. Treatment of aged mice with vascular endothelial growth factor C enhances meningeal lymphatic drainage of macromolecules from the cerebrospinal fluid, improving brain perfusion and learning and memory performance. Disruption of meningeal lymphatic vessels in transgenic mouse models of Alzheimer's disease promotes amyloid-ß deposition in the meninges, which resembles human meningeal pathology, and aggravates parenchymal amyloid-ß accumulation. Meningeal lymphatic dysfunction may be an aggravating factor in Alzheimer's disease pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases.

Impact of histopathological classification of non-functioning adenomas on long term outcomes: comparison of the 2004 and 2017 WHO classifications.

PURPOSE: Outcomes of patients with non-functioning pituitary adenomas categorized using the 2004 and 2017 WHO classification systems are understudied. We report outcomes from the University of Virginia of patients with non-functioning pituitary adenomas categorized using both systems. METHODS: We constructed a database from all 239 patients who underwent resection of a non-functioning pituitary adenoma between 2003 and 2015 and had at least 5 years of follow-up. Pathologic diagnosis was determined under both the 2004 and 2017 WHO classification systems. We compared the rates of recurrence and progression between subtypes using univariate and multivariate Cox regression analyses. RESULTS: Nearly 30% of the tumors in our database were classified as null cell adenomas under the 2004 classification system, whereas only 10% of the tumors were classified as null cell adenomas using the 2017 classification system. Most of these tumors were reclassified as either corticotroph or gonadotroph adenomas. Despite our relatively large cohort and average follow-up of nearly 9 years, we did not detect a significant difference in recurrence and progression between subtypes. CONCLUSIONS: The majority of null cell adenomas diagnosed under the 2004 WHO classification system are reclassified as gonadotroph or corticotroph adenomas under the 2017 WHO classification system. Rates of progression and recurrence between subtypes are not as different as previously believed at our institution and require a larger cohort to further investigate.

Genetic and epigenetic characterization of posterior pituitary tumors.

Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.

Fluid attenuation in non-contrast-enhancing tumor (nCET): an MRI Marker for Isocitrate Dehydrogenase (IDH) mutation in Glioblastoma.

PURPOSE: The WHO 2016 update classifies glioblastomas (WHO grade IV) according to isocitrate dehydrogenase (IDH) gene mutation status. We aimed to determine MRI-based metrics for predicting IDH mutation in glioblastoma. METHODS: This retrospective study included glioblastoma cases (n = 199) with known IDH mutation status and pre-operative MRI (T1WI, T2WI, FLAIR, contrast-enhanced T1W1 at minimum). Two neuroradiologists determined the following MRI metrics: (1) primary lobe of involvement (frontal or non-frontal); (2) presence/absence of contrast-enhancement; (3) presence/absence of necrosis; (4) presence/absence of fluid attenuation in the non-contrast-enhancing tumor (nCET); (5) maximum width of peritumoral edema (cm); (6) presence/absence of multifocal disease. Inter-reader agreement was determined. After resolving discordant measurements, multivariate association between consensus MRI metrics/patient age and IDH mutation status was determined. RESULTS: Among 199 glioblastomas, 16 were IDH-mutant. Inter-reader agreement was calculated for contrast-enhancement (ĸ = 0.49 [- 0.11-1.00]), necrosis (ĸ = 0.55 [0.34-0.76]), fluid attenuation in nCET (ĸ = 0.83 [0.68-0.99]), multifocal disease (ĸ = 0.55 [0.39-0.70]), and primary lobe (ĸ = 0.85 [0.80-0.91]). Mean difference for peritumoral edema width between readers was 0.3 cm [0.2-0.5], p < 0.001. Multivariate analysis uncovered significant associations between IDH-mutation and fluid attenuation in nCET (OR 82.9 [19.22, ∞], p < 0.001), younger age (OR 0.93 [0.86, 0.98], p = 0.009), frontal lobe location (OR 11.08 [1.14, 352.97], p = 0.037), and less peritumoral edema (OR 0.15 [0, 0.65], p = 0.044). CONCLUSIONS: Conventional MRI metrics and patient age predict IDH-mutation status in glioblastoma. Among MRI markers, fluid attenuation in nCET represents a novel marker with high inter-reader agreement that is strongly associated with Glioblastoma, IDH-mutant.

Automated apparent diffusion coefficient analysis for genotype prediction in lower grade glioma: association with the T2-FLAIR mismatch sign.

PURPOSE: The prognosis of lower grade glioma (LGG) patients depends (in large part) on both isocitrate dehydrogenase (IDH) gene mutation and chromosome 1p/19q codeletion status. IDH-mutant LGG without 1p/19q codeletion (IDHmut-Noncodel) often exhibit a unique imaging appearance that includes high apparent diffusion coefficient (ADC) values not observed in other subtypes. The purpose of this study was to develop an ADC analysis-based approach that can automatically identify IDHmut-Noncodel LGG. METHODS: Whole-tumor ADC metrics, including fractional tumor volume with ADC > 1.5 × 10-3mm2/s (VADC>1.5), were used to identify IDHmut-Noncodel LGG in a cohort of N = 134 patients. Optimal threshold values determined in this dataset were then validated using an external dataset containing N = 93 cases collected from The Cancer Imaging Archive. Classifications were also compared with radiologist-identified T2-FLAIR mismatch sign and evaluated concurrently to identify added value from a combined approach. RESULTS: VADC>1.5 classified IDHmut-Noncodel LGG in the internal cohort with an area under the curve (AUC) of 0.80. An optimal threshold value of 0.35 led to sensitivity/specificity = 0.57/0.93. Classification performance was similar in the validation cohort, with VADC>1.5 ≥ 0.35 achieving sensitivity/specificity = 0.57/0.91 (AUC = 0.81). Across both groups, 37 cases exhibited positive T2-FLAIR mismatch sign-all of which were IDHmut-Noncodel. Of these, 32/37 (86%) also exhibited VADC>1.5 ≥ 0.35, as did 23 additional IDHmut-Noncodel cases which were negative for T2-FLAIR mismatch sign. CONCLUSION: Tumor subregions with high ADC were a robust indicator of IDHmut-Noncodel LGG, with VADC>1.5 achieving > 90% classification specificity in both internal and validation cohorts. VADC>1.5 exhibited strong concordance with the T2-FLAIR mismatch sign and the combination of both parameters improved sensitivity in detecting IDHmut-Noncodel LGG.

Pathology of prolactinomas: any predictive value?

Lactotroph adenomas, also called prolactinomas and prolactin-secreting adenomas, constitute nearly 80% of functioning pituitary tumors and about 30-50% of all adenomas in the clinical practice. Lactotroph adenomas occur in the general population at a prevalence of 45/100,000, are more common in women, but also involve men and children of both sexes. Most lactotroph adenomas are microadenomas occurring in reproductive-age women who present with oligo/amenorrhea, galactorrhea, and infertility. In men and elderly women, lactotroph adenomas are usually macroadenomas and are most commonly associated with symptoms of a tumoral mass, including headaches, neurologic defects, and visual loss. Although clinical and laboratory features may differ depending on patient's gender and age, the histopathology of the tumors is similar. Lactotroph adenomas are histologically classified into three subtypes: the common sparsely granulated lactotroph adenoma, and the rare densely granulated lactotroph adenoma and acidophilic stem cell adenoma. We will review the main pathological features of the lactotroph adenomas and some of their characteristics that may predict biological behavior and responsiveness to treatment.

Diagnostic histochemistry in neuropathology.

Neuropathologists have a long and storied history of utilizing histochemistry in the characterization and diagnosis of neurological diseases. This review considers stains that are used for the identification of neurons, neuritic processes and axons, myelin sheaths, neuroglial cells, and connective tissue in the nervous system. Rapid histochemical-smear methods for intraoperative diagnosis are also discussed, along with possible roles for lectin-histochemistry in diagnostic neuropathology.

The 2017 World Health Organization classification of tumors of the pituitary gland: a summary.

The 4th edition of the World Health Organization (WHO) classification of endocrine tumors has been recently released. In this new edition, major changes are recommended in several areas of the classification of tumors of the anterior pituitary gland (adenophypophysis). The scope of the present manuscript is to summarize these recommended changes, emphasizing a few significant topics. These changes include the following: (1) a novel approach for classifying pituitary neuroendocrine tumors according to pituitary adenohypophyseal cell lineages; (2) changes to the histological grading of pituitary neuroendocrine tumors with the elimination of the term "atypical adenoma;" and (3) introduction of new entities like the pituitary blastoma and re-definition of old entities like the null-cell adenoma. This new classification is very practical and mostly based on immunohistochemistry for pituitary hormones, pituitary-specific transcription factors, and other immunohistochemical markers commonly used in pathology practice, not requiring routine ultrastructural analysis of the tumors. Evaluation of tumor proliferation potential, by mitotic count and Ki-67 labeling index, and tumor invasion is strongly recommended on individual case basis to identify clinically aggressive adenomas. In addition, the classification offers the treating clinical team information on tumor prognosis by identifying specific variants of adenomas associated with an elevated risk for recurrence. Changes in the classification of non-neuroendocrine tumors are also proposed, in particular those tumors arising in the posterior pituitary including pituicytoma, granular cell tumor of the posterior pituitary, and spindle cell oncocytoma. These changes endorse those previously published in the 2016 WHO classification of CNS tumors. Other tumors arising in the sellar region are also reviewed in detail including craniopharyngiomas, mesenchymal and stromal tumors, germ cell tumors, and hematopoietic tumors. It is hoped that the 2017 WHO classification of pituitary tumors will establish more biologically and clinically uniform groups of tumors, make it possible for practicing pathologists to better diagnose these tumors, and contribute to our understanding of clinical outcomes for patients harboring pituitary tumors.

Stereotactic radiosurgery for acromegaly: outcomes by adenoma subtype.

PURPOSE: The subtypes of somatotroph-cell pituitary adenomas have been correlated with clinical and histopathological variables. Densely granulated somatotroph-cell (DG) adenomas are typically highly responsive to somatostatin analog drugs, whereas sparsely granulated somatotroph-cell (SG) are less responsive. The aim of the study is to determine the effect of stereotactic radiosurgery (SRS) on remission and development of new pituitary deficiency according to the different subtypes of growth hormone (GH) secreting adenomas. METHODS: A total of 176 patients underwent SRS for acromegaly at the University of Virginia. Diagnosis of acromegaly was based on the combination of clinical features and biochemical assessment including the serum GH level, and age- and gender-matched serum insulin-like growth factor-1 level. All patients underwent endocrine and neuro-imaging evaluations before and after SRS. Histological specimens were available in 73 patients. RESULTS: The histopathological examination showed 34 patients had a DG adenoma, 19 had a SG adenoma, eight had a mixed DG/SG pattern, while other rare mixed subtypes were present in 12 patients. Patients who had a SG adenoma were more likely to be younger and female, and the SG adenomas appeared to be more invasive into the cavernous sinus. With a median follow-up of 67 months (range 6-188 months), 55/73 patients (75.3%) achieved remission. The median time to remission was 26 months (range 6-102 months). The actuarial remission rates in the DG adenoma group at 2, 4, and 6 years post-radiosurgery were 35.1, 71.4, and 79.3%, respectively, while those in SG adenoma group were 35.4, 73.1, and 82.1%, respectively. CONCLUSION: While patients who had a SG adenoma may be less responsive to medical therapy, they exhibited similar responses to SRS as patients with a DG adenoma. For SG adenomas, which respond less well to medical therapy, earlier SRS may be reasonable for consideration.

Feasibility and Safety of MR-Guided Focused Ultrasound Lesioning in the Setting of Deep Brain Stimulation.

BACKGROUND: Patients treated with deep brain stimulation (DBS) often develop symptom progression. If safe, focused ultrasound (FUS) lesioning could be used for patients unable to undergo further DBS surgery. OBJECTIVE: To test the feasibility and safety of MR-guided FUS surgery in the setting of a previously implanted DBS system. METHODS: Three preclinical experiments were designed to test feasibility and safety. Hydrogels were implanted with an electrode, and FUS lesions were targeted adjacently. Cadavers were implanted with a thalamic electrode, and FUS lesions were targeted in the contralateral thalamus. Finally, DBS systems were implanted in swine, and FUS lesioning was targeted to the contralateral thalamus, MRI was used to assess the treatments, and histological analyses were performed at 2 days and at 1 month. RESULTS: In gel experiments and cadavers, FUS resulted in target heating to 29-32°C without any heating at the electrode. In animal experiments, there were no FUS-related MRI signal changes near the electrode. Histological analysis showed typical FUS lesions with no evidence of damage surrounding the electrode tracts. CONCLUSIONS: FUS is feasible in the setting of a preimplanted DBS device. There was minimal heating of the device during the procedure and no apparent FUS-related tissue injury. © 2015 S. Karger AG, Basel.

Effect of neoadjuvant temozolomide upon volume reduction and resection of diffuse low-grade glioma.

Maximal safe resection is associated with prolonged survival in patients with low-grade glioma (LGG). It has been suggested that neoadjuvant temozolomide may provide sufficient tumor shrinkage to facilitate aggressive surgical debulking. We examined the impact of temozolomide upon volume reduction and resectability of LGG. We retrospectively identified 20 adult patients with biopsy-proven, deemed not totally resectable LGGs, treated initially with temozolomide. Volumetric 3D (calculated from serial FLAIR images) and 2D tumor measurements were obtained prior to treatment and at 3 months post-treatment. The anticipated extent of resection (EOR) at the 2 time points was measured based on anatomical limitations, calculated as: [(total tumor volume - unresectable tumor volume)/total tumor volume] ×100. Eloquent cortex, deep structures and corpus callosum were considered unresectable. Mean tumor volume was 68.4 cm(3) pre-treatment and 49.5 cm(3) at 3 months post-treatment. The mean change from baseline to 3 months after treatment was -32.5 % (p < 0.001). Mean 2D pre-treatment area was 28.6 and 23.3 cm(2) at 3 months post-treatment. The 2D change was also significant, with mean change of -17% (p < 0.001). 5% had partial response; 40% minor response; 45% stable disease; and 10% progressive disease by RANO criteria. Mean pre-treatment anticipated EOR was 67.2 and 71.5% at 3 months post-treatment. The mean change from baseline was 4.3% (p = 0.10). Our findings demonstrate significant volumetric and 2D reduction of LGG with temozolomide. Although this tumor shrinkage might facilitate radical surgical resection in some cases, our data failed to show statistically significant improvement in anticipated EOR.

Multimodal MR imaging model to predict tumor infiltration in patients with gliomas.

INTRODUCTION: Gliomas remain difficult to treat, in part, due to our inability to accurately delineate the margins of the tumor. The goal of our study was to evaluate if a combination of advanced MR imaging techniques and a multimodal imaging model could be used to predict tumor infiltration in patients with diffuse gliomas. METHODS: Institutional review board approval and written consent were obtained. This prospective pilot study enrolled patients undergoing stereotactic biopsy for a suspected de novo glioma. Stereotactic biopsy coordinates were coregistered with multiple standard and advanced neuroimaging sequences in 10 patients. Objective imaging values were assigned to the biopsy sites for each of the imaging sequences. A principal component analysis was performed to reduce the dimensionality of the imaging dataset without losing important information. A univariate analysis was performed to identify the statistically relevant principal components. Finally, a multivariate analysis was used to build the final model describing nuclear density. RESULTS: A univariate analysis identified three principal components as being linearly associated with the observed nuclear density (p values 0.021, 0.016, and 0.046, respectively). These three principal component composite scores are predominantly comprised of DTI (mean diffusivity or average diffusion coefficient and fractional anisotropy) and PWI data (rMTT, Ktrans). The p value of the model was <0.001. The correlation between the predicted and observed nuclear density was 0.75. CONCLUSION: A multi-input, single output imaging model may predict the extent of glioma invasion with significant correlation with histopathology.

Stereotactic radiosurgery for the treatment of a distant recurrence of ependymoma on the optic nerve: illustrative case.

BACKGROUND: Ependymomas rarely disseminate to other central nervous system areas distant from the original site. Stereotactic radiosurgery (SRS) provides high control rates for recurring ependymomas. The treatment of optic nerve tumors carries high morbidity, but SRS is an acceptable option to manage these cases to reduce risks. OBSERVATIONS: The authors report the case of a 31-year-old male with a cervical spinal ependymoma who had a disseminated pattern of recurrence including the optic nerve after initial resection of the cervical lesion. The optic nerve tumor was treated with SRS, and the authors discuss the technical aspects of the treatment and its outcomes. At the last follow-up, the optic nerve tumor was controlled with SRS, and visual function was preserved. LESSONS: High-grade ependymomas such as the one in the presented case can have unpredictable patterns of recurrence. SRS provides excellent control of the distant recurring ependymoma with a low complication profile given the location of the tumor in this case.

A proposed clinical classification for pituitary neoplasms to guide therapy and prognosis.

No comprehensive classification system that guides prognosis and therapy of pituitary adenomas exists. The 2022 WHO histopathology-based classification system can only be applied to lesions that are resected, which represent few clinically significant pituitary adenomas. Many factors independent of histopathology provide mechanistic insight into causation and influence prognosis and treatment of pituitary adenomas. We propose a new approach to guide prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative score that reflects disease severity and can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple manageable classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenomas.

Co-occurrence of Functional Gonadotroph Adenoma and Lactotroph Adenoma: A Case Report and Literature Review.

Background/Objective: Functional gonadotroph adenomas (FGAs) are adenomas producing active gonadotropins, follicle-stimulating hormone or luteinizing hormone. Double pituitary adenomas are 2 distinct adenomas occurring in an individual. This report aimed to present an extremely rare case of an FGA, itself an uncommon disorder, co-occurring with a lactotroph adenoma. Case Report: A 33-year-old woman presented with menorrhagia and was found to have ovarian enlargement, large uterine leiomyomas, and bitemporal hemianopsia. Initially, the levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and prolactin were 73.3 mIU/mL (midcycle peak, 2.3-20.9 mIU/L), 3.74 mIU/L (midcycle peak, 8.7-76.3 mIU/L), 1071 pg/mL (midcycle peak 38-649 pg/mL), and 402 ng/mL (2-30 ng/mL), respectively. Pituitary magnetic resonance imaging demonstrated a single sellar mass (2.0 × 2.2 cm). Two months of cabergoline did not reverse visual field deficits; therefore, transsphenoidal resection was performed. Diagnosis of 2 separate adenomas, a gonadotroph and lactotroph adenoma, was confirmed on pathology. Discussion: In this case, gonadotropins did not suppress in response to hyperprolactinemia. Although marked hyperprolactinemia has been associated with functional and clinically silent gonadotroph adenomas in prior cases, this is the first case to confirm an FGA co-occurring with a lactotroph adenoma. Conclusion: In patients who present with elevated gonadotropin levels despite hyperprolactinemia, we suggest considering FGA. Further research is needed to clarify whether there is underdiagnosis of lactotroph adenomas co-occurring with gonadotroph adenomas.

Subependymal seeding of low-grade oligodendroglial neoplasms: a case series.

The CSF dissemination of low-grade glial tumors is a known albeit rare entity. Few cases have been reported in the literature. We describe a unique series of six patients with supratentorial low-grade gliomas who presented to our institution at ages 20-41 years, and developed signal abnormality along the margin of the fourth ventricle without enhancement at variable times during their disease course (0 to 95 months). MR spectroscopy and perfusion-weighted imaging through the region of abnormality in two of these patients were consistent with a low-grade glial tumor. We hypothesize that this finding represents dissemination of the supratentorial low-grade glioma along the ventricular ependyma or through the ventricular CSF. Although the small size of our series does not allow us to draw statistically significant conclusions, this abnormality correlates with progression of the supratentorial disease with or without features of a higher grade malignancy. Additional variables that were present in all six patients include the presence of an oligodendroglial component within the supratentorial tumor, mutated IDH1, and the supratentorial tumor contacting the ventricular margin. All six patients were males.