Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenomas in Patients Presenting With Monocular Blindness.

BACKGROUND AND OBJECTIVES: Suprasellar tumors, particularly pituitary adenomas (PAs), commonly present with visual decline, and the endoscopic endonasal transsphenoidal approach (EETA) is the primary management for optic apparatus decompression. Patients presenting with complete preoperative monocular blindness comprise a high-risk subgroup, given concern for complete blindness. This retrospective cohort study evaluates outcomes after EETA for patients with PA presenting with monocular blindness. METHODS: Retrospective analysis of all EETA cases at our institution from June 2012 to August 2023 was performed. Inclusion criteria included adults with confirmed PA and complete monocular blindness, defined as no light perception, and a relative afferent pupillary defect secondary to tumor mass effect. RESULTS: Our cohort includes 15 patients (9 males, 6 females), comprising 2.4% of the overall PA cohort screened. The mean tumor diameter was 3.8 cm, with 6 being giant PAs (>4 cm). The mean duration of preoperative monocular blindness was 568 days. Additional symptoms included contralateral visual field defects (n = 11) and headaches (n = 10). Two patients presented with subacute PA apoplexy. Gross total resection was achieved in 46% of patients, reflecting tumor size and invasiveness. Postoperatively, 2 patients experienced improvement in their effectively blind eye and 2 had improved visual fields of the contralateral eye. Those with improvements were operated within 10 days of presentation, and no patients experienced worsened vision. CONCLUSION: This is the first series of EETA outcomes in patients with higher-risk PA with monocular blindness on presentation. In these extensive lesions, vision remained stable for most without further decline and improvement from monocular blindness was observed in a small subset of patients with no light perception and relative afferent pupillary defect. Timing from vision loss to surgical intervention seemed to be associated with improvement. From a surgical perspective, caution is warranted to protect remaining vision and we conclude that EETA is safe in the management of these patients.

Pediatric Orbital and Skull Base Pathology.

Pediatric orbital and skull base pathologies encompass a spectrum of inflammatory, sporadic, syndromic, and neoplastic processes that require a broad and complex clinical approach for both medical and surgical treatment. Given their complexity and often multicompartment involvement, a multidisciplinary approach for diagnosis, patient and family counseling, and ultimately treatment provides the best patient satisfaction and clinical outcomes. Advances in minimally invasive surgical approaches, including endoscopic endonasal and transorbital approaches allows for more targeted surgical approaches through smaller corridors beyond more classic transcranial or transracial approaches.

Clinical Implications of Pituitary Adenomas Exhibiting Dual Transcription Factor Staining: A Case Series of 27 Patients.

OBJECTIVE: According to the 2017 World Health Organization classification of neuro-endocrine tumors, pituitary adenomas (PAs) are classified according to immunoexpression of the pituitary-specific transcription factors (TFs). A small subset of PAs exhibit multiple TF staining on immunohistochemistry and we present a series of 27 pathologically-confirmed cases of dual TF staining PAs (dsTF-PAs), and report clinically relevant implications. METHODS: A retrospective chart review of a multi-institutional database of patients with PAs surgically resected between 2008-2021 was performed. PAs expressing immunopositivity 2+ TFs. Patient demographics, neuro-imaging characteristics, histopathologic findings, and clinical data were collected. RESULTS: Twenty-seven patients had pathologically verified dsTF-PAs, of whom 17 were female (63%), with ages ranging from 20-84 years. Twenty-three (85.2%) patients harbored functional PAs, with acromegaly being the most common functional subtype (86.4%). The most common combination of TFs within a single tumor was PIT-1/SF-1 (85.2%). Six PAs exhibited Knosp cavernous sinus invasion grades of 3 or 4 and the Ki-67 labeling index was ≥3% in 6 patients (24.0%) and all stained for PIT-1/SF-1. Hormonal remission was achieved in 78% of functional dsTF-PAs. No PAs showed evidence of recurrence or progression over the mean follow-up period of 28.5 months. CONCLUSIONS: PAs exhibiting dsTF-PAs represent a small but clinically relevant diagnostic subset of PAs according to the 2021 World Health Organization criteria, as a majority are GH-producing. Precise classification using TF staining plays a key role in understanding the biology of these tumors. Favorable outcomes can be achieved in this subset of PAs with evolving TF classification.

Anatomic Considerations Guiding Single Versus Multiportal Endoscopic Approaches for Resection of Juvenile Nasopharyngeal Angiofibroma: Cases Series With Graded Multicorridor Resections.

BACKGROUND: Juvenile nasopharyngeal angiofibromas (JNAs) are characterized by expansive and destructive growth, often invading the midline/paranasal sinuses, pterygopalatine fossa, and infratemporal fossa and can extend into the orbit, cavernous sinus, or intracranially. OBJECTIVE: To evaluete the major benefits of the extended endoscopic endonasal approach (EEA) for JNA resection as compared with more traditional and invasive transpalatal and transfacial approaches. When JNAs extend into lateral anatomic compartments, the optimal operative trajectory often requires additional approach strategies or surgical staging. METHODS: We retrospectively reviewed 8 cases of large JNAs arising in symptomatic adolescent boys (University of Pittsburgh Medical Center Stages II, III, and V) and discuss anatomic and tumor considerations guiding the decision of a pure EEA vs combined EEA and sublabial transmaxillary approach (Caldwell-Luc). RESULTS: A pure extended EEA was used in 6 JNA cases (UPMC Stages II-III); a multiportal EEA + Caldwell-Luc maxillotomy was used in 2 cases. One of the 2 patients (UPMC Stage V) previously treated with multiportal EEA + Caldwell-Luc maxillotomy underwent staged left temporal/transzygomatic craniotomy, obtaining gross total resection. Seven patients ultimately underwent complete removal without recurrence. One patient with a small residual JNA (UPMC II) underwent stereotactic radiosurgery without progression to date. CONCLUSION: JNAs with lateral extension into the infratemporal fossa often benefited from additional lateral exposure using a Caldwell-Luc maxillotomy. Cases with significant skull base and/or dural involvement may undergo staged surgical treatment; temporalis + transzygomatic craniotomy is often useful for second-stage approaches for residual tumor in these lateral infratemporal or intracranial regions. SRS should be considered for residual tumor if additional surgery is not warranted.

Endoscopic Endonasal and Keyhole Surgery for Skull Base Meningiomas.

Traditionally, resection of anterior skull base meningiomas has been achieved by transcranial approaches; however, morbidity related (ie, brain retraction, sagittal sinus damage, optic nerve manipulation, and cosmetic healing) represent a limit of the approach. Minimally invasive techniques including supraorbital and endonasal endoscopic approaches (EEA) have gained consensus as surgical corridors provide direct access to the tumor via a midline approach in carefully selected patients . The supraorbital approach requires some retraction of the rectus gyrus, but it offers minimal risk of postoperative CSF leak or sinonasal morbidity compared to EEA.

Validation of Myc-Associated Protein X (MAX) regulation in growth hormone secreting and nonfunctional pituitary adenoma.

INTRODUCTION: Many patients with growth hormone-secreting pituitary adenoma (GHPA) fail to achieve biochemical remission, warranting investigation into epigenetic and molecular signatures associated with tumorigenesis and hormonal secretion. Prior work exploring the DNA methylome showed Myc-Associated Protein X (MAX), a transcription factor involved in cell cycle regulation, was differentially methylated between GHPA and nonfunctional pituitary adenoma (NFPA). We aimed to validate the differential DNA methylation and related MAX protein expression profiles between NFPA and GHPA. METHODS: DNA methylation levels were measured in 52 surgically resected tumors (37 NFPA, 15 GHPA) at ~100,000 known MAX binding sites derived using ChIP-seq analysis from ENCODE. Findings were correlated with MAX protein expression using a constructed tissue microarray (TMA). Gene ontology analysis was performed to explore downstream genetic and signaling pathways regulated by MAX. RESULTS: GHPA had more hypomethylation events across all known MAX binding sites. Of binding sites defined using ChIP-seq analysis, 1,551 sites had significantly different methylation patterns between the two cohorts; 432 occurred near promoter regions potentially regulated by MAX, including promoters of TNF and MMP9. Gene ontology analysis suggested enrichment in genes involved in oxygen response, immune system regulation, and cell proliferation. Thirteen MAX binding sites were within coding regions of genes. GHPA demonstrated significantly increased expression of MAX protein compared to NFPA. CONCLUSION: GHPA have significantly different DNA methylation and downstream protein expression levels of MAX compared to NFPA. These differences may influence mechanisms involved with cellular proliferation, tumor invasion and hormonal secretion.

From white to blue light: evolution of endoscope-assisted intracranial tumor neurosurgery and expansion to intraaxial tumors.

OBJECTIVE: Intraoperative use of the endoscope to assist in visualization of intracranial tumor pathology has expanded with increasing surgeon experience and improved instrumentation. The authors aimed to study how advancements in endoscopic technology have affected the evolution of endoscope use, with particular focus on blue light-filter modification allowing for discrimination of fluorescent tumor tissue following 5-ALA administration. METHODS: A retrospective analysis of patients undergoing craniotomy for tumor resection at a single institution between February 2012 and July 2021 was performed. Patients were included if the endoscope was used for diagnostic tumor cavity inspection or therapeutic assistance with tumor resection following standard craniotomy and microsurgical tumor resection, with emphasis on those cases in which blue light endoscopy was used. Medical records were queried for patient demographics, operative reports describing the use of the endoscope and extent of resection, associations with tumor pathology, and postoperative outcomes. Preoperative and postoperative MR images were reviewed for radiographic extent of resection. RESULTS: A total of 52 patients who underwent endoscope-assisted craniotomy for tumor were included. Thirty patients (57.7%) were men and the average age was 52.6 ± 16.1 years. Standard white light endoscopes were used for assistance with tumor resection in 28 cases (53.8%) for tumors primarily located in the ventricular system, parasellar region, and cerebellopontine angle. A blue light endoscope for detection of 5-ALA fluorescence was introduced into our practice in 2014 and subsequently used for assistance with tumor resection in 24 cases (46.2%) (intraaxial: n = 22, extraaxial: n = 2). Beyond the use of the surgical microscope as the primary visualization source, the blue light endoscope was used to directly perform additional tumor resection in 19/21 cases as a result of improved fluorescence detection as compared to the surgical microscope. No complications were associated with the use of the endoscope or with additional resection performed under white or blue light visualization. CONCLUSIONS: Endoscopic assistance to visualize intracranial tumors had previously been limited to white light, assisting mostly in the visualization of extraaxial tumors confined to intraventricular and cisternal compartments. Blue light-equipped endoscopes provide improved versatility and visualization of 5-ALA fluorescing tissue beyond the capability of the surgical microscope, thereby expanding its use into the realm of intraaxial tumor resections.

The abscopal effect: systematic review in patients with brain and spine metastases.

Background: The abscopal effect is a rare phenomenon whereby local radiation induces a proposed immune-mediated anti-tumor effect at distant sites. Given the growing use of immunotherapies and systemic immune checkpoint inhibitors in neuro-oncologic practice, we aimed to review prior studies pertaining to this phenomenon in the context of tumor shrinkage both within the central nervous system as well as distant disease sites. Methods: A systematic review in accordance with the PRISMA guidelines was conducted to identify all studies which assessed the abscopal effect in patients with treated metastatic cancer to the brain and/or spine. Articles were included if they reported the abscopal effect in patients (case studies) or if the abscopal effect was explicitly analyzed in case series with cohorts of patients with metastatic brain or spine tumors. Laboratory investigations and clinical trials investigating new therapies were excluded. Results: Twenty reports met inclusion criteria [16 case reports, 4 case series (n = 160), total n = 174]. Case reports of the abscopal effect were in relation to the following cancers: melanoma (6 patients), breast cancer (3), lung adenocarcinoma (2), non-small-cell lung cancer (2), hepatocellular carcinoma (1), and renal cell carcinoma (1). Eleven patients had irradiation to the brain and 2 to the spine. Patients undergoing whole brain radiotherapy (6) had an average dose of 33.6 Gy over 8-15 fractions, and those undergoing stereotactic radiosurgery (5) had an average dose of 21.5 Gy over 1-5 fractions. One patient had radiation to the body and an intracranial abscopal effect was observed. Most common sites of extracranial tumor reduction were lung and lymph nodes. Ten case studies (57%) showed complete resolution of extra-CNS tumor burden. Median progression-free survival was 13 months following radiation. Four papers investigated incidence of abscopal effects in patients with metastatic melanoma to the brain who received immune checkpoint inhibitor therapy (n = 160); two papers found an abscopal effect in 35% and 52% of patients (n = 16, 21 respectively), and two papers found no evidence of abscopal effects (n = 61, 62). Conclusions: Abscopal effects can occur following radiotherapy in patients with brain or spine metastases and is thought to be a result of increased anti-tumor immunity. The potential for immune checkpoint inhibitor therapy to be used in combination with radiotherapy to induce an abscopal effect is an area of active investigation.

Intracranial Solitary Fibrous Tumor/Hemangiopericytoma Treated with Microsurgical Resection: Retrospective Cohort Analysis of a Single-Center Experience.

Objective: To provide benchmarks for further studies of solitary fibrous tumor/hemangiopericytoma (SFT/HPC) of the central nervous system (CNS), we investigated the association of baseline demographic, clinico-pathologic, and treatment factors with outcomes in those treated at our center. Methods: We conducted a retrospective, cohort analysis of patients treated for SFT/HPC at the University of Washington 1990-2020. Kaplan-Meier and univariable Cox analyses assessed relationships between baseline variables and local or global CNS recurrence, extraneural recurrence, progression-free survival (PFS) and overall survival (OS). Results: Among 34 eligible patients, median duration of follow-up was 79 months (range 13-318 months). Local and global CNS recurrence occurred at a median of 81 m (95% CI 48-151) and 81 m (95% CI 47-112), respectively. Extraneural metastases occurred at a median 248 m (95% CI 180-Not Reached) and only in grade 3 tumors. Median PFS and OS were 76 months (95% CI: 47-109 months) and 210 months (95% CI 131-306 months), respectively. Univariable Cox analyses showed that age at diagnosis was associated with local (p = 0.01) and global CNS relapse (p = 0.01), and PFS (p = 0.03). Gross total resection was associated with decreased local or global CNS relapse (p = 0.02) and improved PFS (p = 0.03); peri-operative radiation was associated with decreased local CNS relapse (p = 0.02). Conclusion: Following microsurgical resection of SFT/HPC, CNS relapse is common and associated with age, extent of resection, and adjuvant radiation. Extraneural relapse occurs in some patients. Delayed time-to-initial relapse justifies prolonged surveillance, but optimal approaches have not been defined.

The role of frailty in the clinical management of neurofibromatosis type 1: a mixed-effects modeling study using the Nationwide Readmissions Database.

OBJECTIVE: Frailty embodies a state of increased medical vulnerability that is most often secondary to age-associated decline. Recent literature has highlighted the role of frailty and its association with significantly higher rates of morbidity and mortality in patients with CNS neoplasms. There is a paucity of research regarding the effects of frailty as it relates to neurocutaneous disorders, namely, neurofibromatosis type 1 (NF1). In this study, the authors evaluated the role of frailty in patients with NF1 and compared its predictive usefulness against the Elixhauser Comorbidity Index (ECI). METHODS: Publicly available 2016-2017 data from the Nationwide Readmissions Database was used to identify patients with a diagnosis of NF1 who underwent neurosurgical resection of an intracranial tumor. Patient frailty was queried using the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator. ECI scores were collected in patients for quantitative measurement of comorbidities. Propensity score matching was performed for age, sex, ECI, insurance type, and median income by zip code, which yielded 60 frail and 60 nonfrail patients. Receiver operating characteristic (ROC) curves were created for complications, including mortality, nonroutine discharge, financial costs, length of stay (LOS), and readmissions while using comorbidity indices as predictor values. The area under the curve (AUC) of each ROC served as a proxy for model performance. RESULTS: After propensity matching of the groups, frail patients had an increased mean ± SD hospital cost ($85,441.67 ± $59,201.09) compared with nonfrail patients ($49,321.77 ± $50,705.80) (p = 0.010). Similar trends were also found in LOS between frail (23.1 ± 14.2 days) and nonfrail (10.7 ± 10.5 days) patients (p = 0.0020). For each complication of interest, ROC curves revealed that frailty scores, ECI scores, and a combination of frailty+ECI were similarly accurate predictors of variables (p > 0.05). Frailty+ECI (AUC 0.929) outperformed using only ECI for the variable of increased LOS (AUC 0.833) (p = 0.013). When considering 1-year readmission, frailty (AUC 0.642) was outperformed by both models using ECI (AUC 0.725, p = 0.039) and frailty+ECI (AUC 0.734, p = 0.038). CONCLUSIONS: These findings suggest that frailty and ECI are useful in predicting key complications, including mortality, nonroutine discharge, readmission, LOS, and higher costs in NF1 patients undergoing intracranial tumor resection. Consideration of a patient's frailty status is pertinent to guide appropriate inpatient management as well as resource allocation and discharge planning.

Association between socioeconomic status and presenting characteristics and extent of disease in patients with surgically resected nonfunctioning pituitary adenoma.

OBJECTIVE: The aim of this study was to evaluate the association between zip code-level socioeconomic status (SES) and presenting characteristics and short-term clinical outcomes in patients with nonfunctioning pituitary adenoma (NFPA). METHODS: A retrospective review of prospectively collected data from the University of Southern California Pituitary Center was conducted to identify all patients undergoing surgery for pituitary adenoma (PA) from 2000 to 2021 and included all patients with NFPA with recorded zip codes at the time of surgery. A normalized socioeconomic metric by zip code was then constructed using data from the American Community Survey estimates, which was categorized into tertiles. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were constructed to estimate mean differences and multivariable-adjusted odds ratios for the association between zip code-level SES and presenting characteristics and outcomes. RESULTS: A total of 637 patients were included in the overall analysis. Compared with patients in the lowest SES tertile, those in the highest tertile were more likely to be treated at a private (rather than safety net) hospital, and were less likely to present with headache, vision loss, and apoplexy. After multivariable adjustment for age, sex, and prior surgery, SES in the highest compared with lowest tertile was inversely associated with tumor size at diagnosis (-4.9 mm, 95% CI -7.2 to -2.6 mm, p < 0.001) and was positively associated with incidental diagnosis (multivariable-adjusted OR 1.72, 95% CI 1.02-2.91). Adjustment for hospital (private vs safety net) attenuated the observed associations, but disparities by SES remained statistically significant for tumor size. Despite substantial differences at presentation, there were no significant differences in length of stay or odds of an uncomplicated procedure by zip code-level SES. Patients from lower-SES zip codes were more likely to require postoperative steroid replacement and less likely to achieve gross-total resection. CONCLUSIONS: In this series, lower zip code-level SES was associated with more severe disease at the time of diagnosis for NFPA patients, including larger tumor size and lower rates of incidental diagnosis. Despite these differences at presentation, no significant differences were observed in short-term postoperative complications, although patients with higher zip code-level SES had higher rates of gross-total resection.

Growth hormone secreting pituitary adenomas show distinct extrasellar extension patterns compared to nonfunctional pituitary adenomas.

PURPOSE: Patterns of extension of pituitary adenomas (PA) may vary according to PA subtype. Understanding extrasellar extension patterns in growth hormone PAs (GHPA) vis-a-vis nonfunctional PAs (NFPAs) may provide insights into the biology of GHPA and future treatment avenues. METHODS: Preoperative MR imaging (MRI) in 179 consecutive patients treated surgically for NFPA (n = 139) and GHPA (n = 40) were analyzed to determine patterns of extrasellar growth. Extension was divided into two principal directions: cranio-caudal (measured by infrasellar/suprasellar extension), and lateral cavernous sinus invasion (CSI) determined by Knosp grading score of 3-4. Suprasellar extension was defined as tumor extension superior to the tuberculum sellae- dorsum sellae line, and inferior extension as invasion through the sellar floor into the sphenoid sinus or clivus. Categorical analysis was performed using Fisher's exact test. RESULTS: GHPAs were overall more likely to remain purely intrasellar compared to NFPA (50% vs 26%, p < 0.001). GHPAs, however, were 7 times more likely to exhibit isolated infrasellar extension compared to NFPA (20% vs 2.8%, p = 0.001). Conversely, NFPAs were twice as likely to exhibit isolated suprasellar extension compared to GHPA (60% vs 28%, p < 0.001), as well as combined suprasellar/infrasellar extension (25% vs 3%, p = 0.011). There were no overall differences in CSI between the two subgroups. DISCUSSION: GHPA and NFPA demonstrate distinct extrasellar extension patterns on MRI. GHPAs show proclivity for inferior extension with bony invasion, whereas NFPAs are more likely to exhibit suprasellar extension through the diaphragmatic aperture. These distinctions may have implications into the biology and future treatment of PAs.

Evaluating the predictive value of comorbidity indices in pituitary surgery: a mixed-effects modeling study using the Nationwide Readmissions Database.

OBJECTIVE: Although pituitary adenomas (PAs) are common intracranial tumors, literature evaluating the utility of comorbidity indices for predicting postoperative complications in patients undergoing pituitary surgery remains limited, thereby hindering the development of complex models that aim to identify high-risk patient populations. We utilized comparative modeling strategies to evaluate the predictive validity of various comorbidity indices and combinations thereof in predicting key pituitary surgery outcomes. METHODS: The Nationwide Readmissions Database was used to identify patients who underwent pituitary tumor operations (n = 19,653) in 2016-2017. Patient frailty was assessed using the Johns Hopkins Adjusted Clinical Groups (ACG) System. The Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI) were calculated for each patient. Five sets of generalized linear mixed-effects models were developed, using as the primary predictors 1) frailty, 2) CCI, 3) ECI, 4) frailty + CCI, or 5) frailty + ECI. Complications of interest investigated included inpatient mortality, nonroutine discharge (e.g., to locations other than home), length of stay (LOS) within the top quartile (Q1), cost within Q1, and 1-year readmission rates. RESULTS: Postoperative mortality occurred in 73 patients (0.4%), 1-year readmission was reported in 2994 patients (15.2%), and nonroutine discharge occurred in 2176 patients (11.1%). The mean adjusted all-payer cost for the procedure was USD $25,553.85 ± $26,518.91 (Q1 $28,261.20), and the mean LOS was 4.8 ± 7.4 days (Q1 5.0 days). The model using frailty + ECI as the primary predictor consistently outperformed other models, with statistically significant p values as determined by comparing areas under the curve (AUCs) for most complications. For prediction of mortality, however, the frailty + ECI model (AUC 0.831) was not better than the ECI model alone (AUC 0.831; p = 0.95). For prediction of readmission, the frailty + ECI model (AUC 0.617) was not better than the frailty model alone (AUC 0.606; p = 0.10) or the frailty + CCI model (AUC 0.610; p = 0.29). CONCLUSIONS: This investigation is to the authors' knowledge the first to implement mixed-effects modeling to study the utility of common comorbidity indices in a large, nationwide cohort of patients undergoing pituitary surgery. Knowledge gained from these models may help neurosurgeons identify high-risk patients who require additional clinical attention or resource utilization prior to surgical planning.

5-Aminolevulinic acid-enhanced fluorescence-guided treatment of high-grade glioma using angled endoscopic blue light visualization: technical case series with preliminary follow-up.

OBJECTIVE: 5-Aminolevulinic acid (5-ALA)-enhanced fluorescence-guided resection of high-grade glioma (HGG) using microscopic blue light visualization offers the ability to improve extent of resection (EOR); however, few descriptions of HGG resection performed using endoscopic blue light visualization are currently available. In this report, the authors sought to describe their surgical experience and patient outcomes of 5-ALA-enhanced fluorescence-guided resection of HGG using primary or adjunctive endoscopic blue light visualization. METHODS: The authors performed a retrospective review of prospectively collected data from 30 consecutive patients who underwent 5-ALA-enhanced fluorescence-guided biopsy or resection of newly diagnosed HGG was performed. Patient demographic data, tumor characteristics, surgical technique, EOR, tumor fluorescence patterns, and progression-free survival were recorded. RESULTS: In total, 30 newly diagnosed HGG patients were included for analysis. The endoscope was utilized for direct 5-ALA-guided port-based biopsy (n = 9), microscopic to endoscopic (M2E; n = 18) resection, or exoscopic to endoscopic (E2E; n = 3) resection. All endoscopic biopsies of fluorescent tissue were diagnostic. 5-ALA-enhanced tumor fluorescence was visible in all glioblastoma cases, but only in 50% of anaplastic astrocytoma cases and no anaplastic oligodendroglioma cases. Gross-total resection (GTR) was achieved in 10 patients in whom complete resection was considered safe, with 11 patients undergoing subtotal resection. In all cases, endoscopic fluorescence was more avid than microscopic fluorescence. The endoscope offered the ability to diagnose and resect additional tumor not visualized by the microscope in 83.3% (n = 10/12) of glioblastoma cases, driven by angled lenses and increased fluorescence facilitated by light source delivery within the cavity. Mean volumetric EOR was 90.7% in all resection patients and 98.8% in patients undergoing planned GTR. No complications were attributable to 5-ALA or blue light endoscopy. CONCLUSIONS: The blue light endoscope is a viable primary or adjunctive visualization platform for optimization of 5-ALA-enhanced HGG fluorescence. Implementation of the blue light endoscope to guide resection of HGG glioma is feasible and ergonomically favorable, with a potential advantage of enabling increased detection of tumor fluorescence in deep surgical cavities compared to the microscope.

Somatic Mosaicism of a PDGFRB Activating Variant in Aneurysms of the Intracranial, Coronary, Aortic, and Radial Artery Vascular Beds.

Background Activating variants in platelet-derived growth factor receptor beta (PDGFRB), including a variant we have previously described (p.Tyr562Cys [g.149505130T>C [GRCh37/hg19]; c.1685A>G]), are associated with development of multiorgan pathology, including aneurysm formation. To investigate the association between the allele fraction genotype and histopathologic phenotype, we performed an expanded evaluation of post-mortem normal and aneurysmal tissue specimens from the previously published index patient. Methods and Results Following death due to diffuse subarachnoid hemorrhage in a patient with mosaic expression of the above PDGFRB variant, specimens from the intracranial, coronary, radial and aortic arteries were harvested. DNA was extracted and alternate allele fractions (AAF) of PDGFRB were determined using digital droplet PCR. Radiographic and histopathologic findings, together with genotype expression of PDGFRB were then correlated in aneurysmal tissue and compared to non-aneurysmal tissue. The PDGFRB variant was identified in the vertebral artery, basilar artery, and P1 segment aneurysms (AAF: 28.7%, 16.4%, and 17.8%, respectively). It was also identified in the coronary and radial artery aneurysms (AAF: 22.3% and 20.6%, respectively). In phenotypically normal intracranial and coronary artery tissues, the PDGFRB variant was not present. The PDGFRB variant was absent from lymphocyte DNA and normal tissue, confirming it to be a non-germline somatic variant. Primary cell cultures from a radial artery aneurysm localized the PDGFRB variant to CD31-, non-endothelial cells. Conclusions Constitutive expression of PDGFRB within the arterial wall is associated with the development of human fusiform aneurysms. The role of targeted therapy with tyrosine kinase inhibitors in fusiform aneurysms with PDGFRB mutations should be further studied.

Anatomical and topographical variations in the distribution of brain metastases based on primary cancer origin and molecular subtypes: a systematic review.

BACKGROUND: While it has been suspected that different primary cancers have varying predilections for metastasis in certain brain regions, recent advances in neuroimaging and spatial modeling analytics have facilitated further exploration into this field. METHODS: A systematic electronic database search for studies analyzing the distribution of brain metastases (BMs) from any primary systematic cancer published between January 1990 and July 2020 was conducted using PRISMA guidelines. RESULTS: Two authors independently reviewed 1957 abstracts, 46 of which underwent full-text analysis. A third author arbitrated both lists; 13 studies met inclusion/exclusion criteria. All were retrospective single- or multi-institution database reviews analyzing over 8227 BMs from 2599 patients with breast (8 studies), lung (7 studies), melanoma (5 studies), gastrointestinal (4 studies), renal (3 studies), and prostate (1 study) cancers. Breast, lung, and colorectal cancers tended to metastasize to more posterior/caudal topographic and vascular neuroanatomical regions, particularly the cerebellum, with notable differences based on subtype and receptor expression. HER-2-positive breast cancers were less likely to arise in the frontal lobes or subcortical region, while ER-positive and PR-positive breast metastases were less likely to arise in the occipital lobe or cerebellum. BM from lung adenocarcinoma tended to arise in the frontal lobes and squamous cell carcinoma in the cerebellum. Melanoma metastasized more to the frontal and temporal lobes. CONCLUSION: The observed topographical distribution of BM likely develops based on primary cancer type, molecular subtype, and genetic profile. Further studies analyzing this association and relationships to vascular distribution are merited to potentially improve patient treatment and outcomes.