Vestibular schwannoma microneurosurgery in patients over 70: a single institution experience and proposal of a treatment algorithm.

BACKGROUND: Elderly patients with vestibular schwannoma (VS) are commonly observed. OBJECT: Retrospective analysis of 25 patients aging ≥ 70 operated on in our neurosurgical department for unilateral VS. The purpose of our study is to propose an algorithm for the treatment of VS in elderly patients. METHODS: American Society of Anesthesiology (ASA) Grade I-II patients and Grade III with life-threatening tumors were enrolled. Karnofsky Performance Status Scale (KPS) was used for evalutation of the quality of life. The House-Brackmann (HB) scale for facial nerve (FN) outcome was used. Tumor size was categorized according to Koos' classification. A retrosigmoid approach was used in all cases, except one in which a translabyrinthine approach was performed. Surgical removal graduation: total (GTR), near total (NTR > 95%), subtotal (STR > 90%). The clinical and radiological follow-up period was set first at six months and then at one year after surgery. FN results evaluation was performed at one year, categorized according to House-Brackmann grades I-VI. RESULTS: Mean age: 74,4 years (70-83); 28% ASA I, 56% ASA II, 16% ASA III. Mean tumor size: 2,7 cm (1,5-4,2 cm). GTR/NTR: 68%, STR 32%. Mortality was zero. At last follow-up (one year after surgery) FN results were: HBI 81%, HBII 9.5%, HBIII 9.5%; HB IV 0%. Only 4 patients had preoperative HB IV, of whom one improved from HB IV to HB III. Transient complications occurred only in large VS. Re-growth of residue after STR was observed in 3 cases, treated with SRS in 2 cases and observed in 1. CONCLUSIONS: An algorithm of treatment of vestibular schwannoma in the elderly is proposed. In particular, in patients in general good conditions, age does not appear to be a major contraindication for microsurgery of VS. FN results at last follow-up are satisfactory and the complication rates are acceptable.

Documented Initial Growth Does Not Necessarily Indicate Treatment for Sporadic Vestibular Schwannomas.

OBJECTIVE: To report the natural history of vestibular schwannoma (VS) who elected an initial period of observation and identify prognostic factors. To describe the natural history of growing VS, identify prognostic factors, and review the most recent literature. STUDY DESIGN: Prospective cohort study and literature review. SETTING: Tertiary referral center. PATIENTS: Adult patients diagnosed with a VS between January 1998 and February 2023. INTERVENTION: Magnetic resonance imaging surveillance. MAIN OUTCOME MEASURES: Growth-free survival and subsequent growth-free survival considering significant growth as a change in size of ≥2 mm. RESULTS: Of 430 patients undergoing observation with serial magnetic resonance imaging, 193 (44.9%) demonstrated significant growth at a median of 1.6 years (interquartile range, 0.94-3.51). Of the 193 patients who presented an initial episode of growth, 137 elected to continue to be observed. Of those, 83 (60.6%) presented a second episode of growth at a median of 1.43 years (interquartile range, 1.00-2.49). The subsequent growth-free survival rates (95% confidence interval) at 1, 3, 5, 7, and 10 years were 91.79% (87.26-96.56%), 64.44% (56.56-73.42%), 52.52% (44.23-62.35%), 42.23% (33.92-52.56%), and 36.11% (27.89-46.76%), respectively. Univariate and multivariate Cox regression analyses showed that EC tumor location and initial growth rate were significant predictors of subsequent growth. CONCLUSIONS: Close observation after documentation of growth is an appropriate management in well-selected cases given that only around 56% of the tumor will continue to grow. Extracanalicular tumor location and initial growth rate are promising prognostic factors to help determine which patient would be a better candidate for close surveillance after initial documentation of growth.

The outcome of the retrosigmoid approach in the decompression of vestibular schwannomas - a retrospective cohort study of 60 consecutive cases.

This multicenter retrospective cohort study aimed to evaluate the effectiveness of the retrosigmoid surgical approach in decompressing vestibular schwannomas, focusing on tumor decompression, neurological function preservation, and postoperative complications. A cohort of 60 patients, operated between 2016 and 2019, was analyzed for age, sex, symptoms, tumor size, surgery duration, complications, mortality, and facial/auditory functions using established criteria. Hearing loss was observed in 80% of patients, mainly progressive, with tumor size emerging as a critical prognostic factor. Facial weakness affected 10% of patients preoperatively; postoperatively, 35% of patients had affected facial nerve function, with 10% exhibiting poor or no facial nerve function, linked to resection extent rather than tumor size. Tinnitus was more prevalent with larger tumors, whereas headaches were common irrespective of size. Balance disorders improved after surgery, especially in case of larger tumors. Functional recovery varied, with 41.67% of patients returning to their previous activity within 4 months, 25% within 4-12 months, and 33.33% remaining inactive. The mortality rate was low at 3.3 %, with two deaths out of 60 patients after surgery. This analysis highlights surgery risks for vestibular schwannomas (e.g., facial nerve decline, tinnitus, headaches), but also emphasizes benefits like improved balance and low mortality. Many patients regain professional activity, stressing the importance of informed treatment decisions for this condition.

Analysis of the treatment planning metrics and their correlation with morphology of intracranial lesions in Gamma Knife stereotactic radiosurgery.

BACKGROUND: Gamma Knife Radiosurgery (GKRS) has established a role in treating various benign brain pathologies. The radiosurgery planning necessitates a proper understanding of radiation dose distribution in relation to the target lesion and surrounding eloquent area. The quality of a radiosurgery plan is determined by various planning parameters. Here, we have reviewed various GKRS planning parameters and analyzed their correlation with the morphology of treated brain lesions. METHOD: A total of 430 treatment plans (71 meningioma, 133 vestibular schwannoma/VS, 150 arteriovenous malformation/AVM, 76 pituitary adenoma/PA treated with GKRS between December 2013 and May 2023) were analyzed for target coverage (TC), conformity index (CI), homogeneity index (HI), and gradient index (GI). RESULT: The values of CIPaddick and CILomax for PA were lower and differed significantly from meningioma, VS, and AVM. The value of HI for PA was higher and differed significantly when compared with meningioma, VS, and AVM. The values of HI for AVM were also significantly higher than VS and meningioma. The mean GI was 3.02, 2.92, 3.03, and 2.88 for meningioma, VS, AVM, and PA, respectively. The value of GI for meningioma and AVM was significantly higher when compared with the values for VS and PA. The mean TC was 0.94 for meningioma, 0.96 for VS, 0.95 for AVM, and 0.90 for PA. The value TC of PA was lower and differed significantly when compared with VS, AVM, and meningioma. Lesions with a volume of ≤1 cc had poor planning metrics as the spillage of radiation may be higher. CONCLUSION: The GKRS planning parameters depend on the size, shape, nature, and location of intracranial lesions. Therefore, each treatment plan needs to be evaluated thoroughly and a long-term follow-up is needed to establish their relation with clinical outcome.

Clinicopathological characteristics of secondary trigeminal neuralgia due to cerebellopontine angle tumors. / æ¡¥å°è„‘è§’è‚¿ç˜¤ç»§å‘æ€§ä¸‰å‰ç¥žç»ç—›çš„ä¸´åºŠç— ç†ç‰¹å¾.

OBJECTIVES: Cerebellopontine angle (CPA) tumors are a common cause of secondary trigeminal neuralgia (TN), characterized by their concealed location, slow progression, and difficulty in early detection. This study aims to explore the clinicopathological characteristics of patients with secondary TN due to CPA tumors to enhance understanding and management of secondary TN. METHODS: A retrospective analysis was conducted on clinical data and pathological results of 116 patients with CPA tumor-related TN treated at Xiangya Hospital of Central South University from January 1, 2017 to December 31, 2022. The study analyzed the relationship of tumor pathological types with clinical manifestations, tumor location, surgical methods, and treatment outcomes. RESULTS: Among the cases, 95.7% (111/116) were benign tumors, 3.4% (4/116) were malignant tumors, and 0.9% (1/116) were borderline tumors. Benign tumors were predominantly acoustic neuromas, meningiomas, and schwannomas. Among the patients, 46.6% (54/116) presented with isolated TN, while 53.4% (62/116) exhibited other associated symptoms depending on factors such as tumor growth location and rate. The complete resection rate in this group was over 90%, with 41.4% (48/116) of patients undergoing concurrent microvascular decompression after tumor resection, predominantly for schwannomas. The overall effective rate of surgical treatment reached 93.9%, with schwannomas showing higher efficacy rates compared with acoustic neuromas and meningiomas (P<0.05). The recurrence rate of acoustic neuromas was significantly higher than that of meningiomas and schwannomas (P<0.05). CONCLUSIONS: CPA tumors are a major cause of secondary TN, predominantly benign, with occasional underdiagnosed malignant tumors. Early diagnosis and treatment significantly impact prognosis. Different tumor types vary in clinical symptoms, surgical approaches, and treatment efficacy. Surgical strategies should balance tumor resection extent and neural function preservation, with microvascular decompression as necessary.

Reduced Cochlear MRI Signal and Hearing Outcomes in Conservatively Managed Vestibular Schwannoma Patients.

OBJECTIVE: This study aimed to determine if hypointense cochlear magnetic resonance imaging (MRI) constructive interference in steady-state (CISS) signal correlates with hearing outcomes in conservatively managed vestibular schwannoma (VS) patients. STUDY DESIGN: Retrospective review of 657 cases from 1992 to 2020. SETTING: Tertiary academic referral center. PATIENTS: A retrospective review was performed to identify conservatively managed VS patients with appropriate baseline MRI, audiology, and at least 12-month audiological follow-up. Patients were excluded if they progressed to surgery or radiotherapy in less than 12 months, bilateral tumors, or surgery on the contralateral ear. INTERVENTION: Conservatively managed patients with CISS imaging studies and audiology testing. MAIN OUTCOME MEASURES: Primary outcome measure change in pure-tone average (PTA) and word recognition score (WRS). Secondary outcome measures tumor size, presence of lateral fluid cap, or cystic changes. RESULTS: A total of 92 individuals (47% male, 58 ± 11.6 yr) met the inclusion criteria, with 36 (39%) of patients demonstrating abnormal cochlear CISS signal. At baseline, abnormal cochlear CISS signal was associated with higher intracanalicular (IC) length (7.9 versus 6.6 mm, p = 0.0177) and lower WRS (55.7 versus 78.8 dBHL, p = 0.0054). During follow-up, individuals with abnormal cochlear CISS signal had significantly higher PTA (62.4 versus 46.4 dBHL, p = 0.0010). After adjusting for baseline covariates, abnormal cochlear CISS signal was consistently associated with a greater increase in PTA of 8.3 dBHL (95% confidence interval, 2.9-13.7; p = 0.0032) from baseline when compared with the normal group. CONCLUSIONS: Abnormal cochlear signal on MRI CISS sequences is associated with poorer hearing outcomes in conservatively managed VS patients.

Age, preoperative tumor volume and widening of the internal acoustic meatus are independent factors associated with poor preoperative hearing in vestibular schwannoma patients - results of a single-center retrospective analysis.

Preoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. Besides the preoperative tumor size there are other factors that influence the preoperative hearing function that are frequently discussed. A comprehensive analysis of a large cohort of vestibular schwannomas has the potential to describe new insights and influence the preoperative management. We analyzed clinical factors, imaging data and the expression of the proliferation marker MIB1 as potential influencing factors on the preoperative hearing function in a retrospective cohort of 523 primary sporadic vestibular schwannomas. The results of the preoperative audiometry were quantified using the Gardner-Robertson Score. Uni- and multivariate analyses were performed. Serviceable hearing (Gardner-Robertson class 1 or 2) was documented in 391 patients (74.8%). Factors associated with non-serviceable hearing (Gardner-Robertson class 3-5) were patients of older age (p < 0.0001), larger preoperative tumor volume (p = 0.0013) and widening of the internal acoustic meatus compared to the healthy side (p = 0.0353). Gender and differences in the expression of the proliferation marker MIB1 had no influence on preoperative hearing. In the multivariate nominal logistic regression older age (OR 27.60 (CI 9.17-87.18), p < 0.0001), larger preoperative tumor volume (OR 20.20 (CI 3.43-128.58), p = 0.0011) and widening of the internal acoustic canal (OR 7.86 (CI 1.77-35.46), p = 0.0079) remained independent factors associated with non-serviceable hearing. Widening of the internal acoustic canal is an independent factor for non-serviceable preoperative hearing in vestibular schwannoma patients together with older age and larger preoperative tumor volume.

Structural connectivity changes in unilateral hearing loss.

Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss.

Tumor biomechanical stiffness by magnetic resonance elastography predicts surgical outcomes and identifies biomarkers in vestibular schwannoma and meningioma.

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

Hearing loss and its association with the proteome of perilymph, cerebrospinal fluid, and tumor tissue in patients with vestibular schwannoma.

This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.

Tumors of the nervous system and hearing loss: Beyond vestibular schwannomas.

Hearing loss is a common side effect of many tumor treatments. However, hearing loss can also occur as a direct result of certain tumors of the nervous system, the most common of which are the vestibular schwannomas (VS). These tumors arise from Schwann cells of the vestibulocochlear nerve and their main cause is the loss of function of NF2, with 95 % of cases being sporadic and 5 % being part of the rare neurofibromatosis type 2 (NF2)-related Schwannomatosis. Genetic variations in NF2 do not fully explain the clinical heterogeneity of VS, and interactions between Schwann cells and their microenvironment appear to be critical for tumor development. Preclinical in vitro and in vivo models of VS are needed to develop prognostic biomarkers and targeted therapies. In addition to VS, other tumors can affect hearing. Meningiomas and other masses in the cerebellopontine angle can compress the vestibulocochlear nerve due to their anatomic proximity. Gliomas can disrupt several neurological functions, including hearing; in fact, glioblastoma multiforme, the most aggressive subtype, may exhibit early symptoms of auditory alterations. Besides, treatments for high-grade tumors, including chemotherapy or radiotherapy, as well as incomplete resections, can induce long-term auditory dysfunction. Because hearing loss can have an irreversible and dramatic impact on quality of life, it should be considered in the clinical management plan of patients with tumors, and monitored throughout the course of the disease.

Automatic Segmentation of Vestibular Schwannomas: A Systematic Review.

BACKGROUND: Vestibular schwannomas (VSs) are benign tumors often monitored over time, with measurement techniques for assessing growth rates subject to significant interobserver variability. Automatic segmentation of these tumors could provide a more reliable and efficient for tracking their progression, especially given the irregular shape and growth patterns of VS. METHODS: Various studies and segmentation techniques employing different Convolutional Neural Network architectures and models, such as U-Net and convolutional-attention transformer segmentation, were analyzed. Models were evaluated based on their performance across diverse datasets, and challenges, including domain shift and data sharing, were scrutinized. RESULTS: Automatic segmentation methods offer a promising alternative to conventional measurement techniques, offering potential benefits in precision and efficiency. However, these methods are not without challenges, notably the "domain shift" that occurs when models trained on specific datasets underperform when applied to different datasets. Techniques such as domain adaptation, domain generalization, and data diversity were discussed as potential solutions. CONCLUSIONS: Accurate measurement of VS growth is a complex process, with volumetric analysis currently appearing more reliable than linear measurements. Automatic segmentation, despite its challenges, offers a promising avenue for future investigation. Robust well-generalized models could potentially improve the efficiency of tracking tumor growth, thereby augmenting clinical decision-making. Further work needs to be done to develop more robust models, address the domain shift, and enable secure data sharing for wider applicability.

Natural history of hearing and tumor growth in vestibular schwannoma in neurofibromatosis type 2-related schwannomatosis.

OBJECTIVES: To determine the natural history of hearing loss and tumor volume in patients with untreated neurofibromatosis type 2 (NF2)-related schwannomatosis. Moreover, we statistically examined the factors affecting hearing prognosis. METHODS: This retrospective cohort study was conducted on 37 ears of 24 patients with NF2-related vestibular schwannomatosis followed up without treatment for more than 1 year. We obtained detailed chronological changes in the PTA and tumor volume in each case over time, and the rate of change per year was obtained. Multivariate analysis was also conducted to investigate factors associated with changes in hearing. RESULTS: The average follow-up period was approximately 9 years, and hearing deteriorated at an average rate of approximately 4 dB/year. The rate of maintaining effective hearing decreased from 30 ears (81%) at the first visit to 19 ears (51%) at the final follow-up. The average rate of change in tumor growth for volume was approximately 686.0 mm3/year. This study revealed that most patients with NF2 experienced deterioration in hearing acuity and tumor growth during the natural course. A correlation was observed between an increase in tumor volume and hearing loss (r = 0.686; p < 0.001). CONCLUSIONS: Although the hearing preservation rate in NF2 cases is poor with the current treatment methods, many cases exist in which hearing acuity deteriorates, even during the natural course. Patients with an increased tumor volume during the follow-up period were more likely to experience hearing deterioration. Trial registration number 20140242 (date of registration: 27 October 2014).

Clinical and radiological features of intracranial ancient schwannomas: a single-institution, retrospective analysis.

Ancient schwannoma (AS) is a subtype of schwannoma characterized by slow progression despite degenerative changes in pathology. Although it is considered a benign tumor, most previous reports have focused on extracranial AS; therefore, the clinical characteristics of intracranial AS is not clear. We included 174 patients who underwent surgery for sporadic intracranial schwannoma, and 13 patients (7.5%) were diagnosed with AS. Cysts were significantly more common in patients with AS than conventional schwannomas (92.3% vs. 44.7%, p < 0.001), as was bleeding (38.5% vs. 6.9%, p = 0.003) and calcification (15.4% vs. 1.3%, p = 0.029). The maximum tumor diameter was also larger in patients with AS (35 mm vs. 29 mm, p = 0.017). The median duration from symptom onset to surgery (7.0 vs. 12.5 months, p = 0.740) did not significantly differ between groups, nor did the probability of postoperative recurrence (p = 0.949). Intracranial AS was strongly associated with cyst formation and exhibited a benign clinical course with a lower rate of recurrence and need for salvage treatment. Extracranial AS is reportedly characterized by a slow progression through a long-term clinical course, whereas intracranial AS did not progress slowly in our study and exhibited different clinical features to those reported for extracranial AS.

Tumor shape as a prognostic factor for the growth of intracanalicular vestibular schwannoma: a long-term observational study.

PURPOSE: To evaluate the predictive factors of tumor growth in patients with vestibular schwannoma (VS) managed with the wait-and-scan approach. METHODS: The data of 31 patients diagnosed with intracanalicular VS and followed for > 5 years were retrospectively analyzed. VS was diagnosed according to MRI findings and tumor growth was monitored. Tumor growth was defined as an increase of 2 mm or more in the maximal tumor diameter. The association between the initial tumor size and shape and tumor growth was assessed. RESULTS: Tumor growth was observed in 16 of 31 patients (51.6%) over a mean follow-up duration of 7.3 years. The initial tumor size was not statistically correlated with tumor growth. However, fusiform or cylindrical tumors exhibited higher growth rates than oval or round tumors. Additionally, a significant correlation was observed between cerebellopontine angle extension and tumor shape. CONCLUSION: In this study, 51.6% of the patients with intracanalicular VS who were managed with the wait-and-scan strategy over a follow-up period of > 5 years showed tumor growth. Tumor shape, especially fusiform or cylindrical shape, was found to be a significant predictor of tumor growth.

Disparities in Sporadic Vestibular Schwannoma Initial Presentation Between a Public Safety Net Hospital and Tertiary Academic Medical Center at the Same Zip Code 2010 to 2020.

INTRODUCTION: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings. METHODS: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69). Ethnicity, insurance, maximum tumor size, audiometry, initial treatment recommendation, treatment received, and follow up were recorded and statistical analysis performed to determine differences. RESULTS: Average age at diagnosis (51.7 ± 13.6 TAMC vs 52.3 ± 12.4 PSNH) and gender (58.4% TAMC vs 52.2% PSNH female) were similar. Patients' insurance (TAMC 75.9% privately insured vs PSNH 82% Medicaid) and racial/ethnic profiles (TAMC 67.7% White and 10.0% Hispanic/Latinx, vs PSNH 4.8% White but 59.7% Hispanic/Latinx) were significantly different. Tumor size was larger at PSNH (20.2 ± 13.3 mm) than TAMC (16.6 ± 10.0 mm). Hearing was more impaired at PSNH than TAMC (mean pure tone average 58.3 dB vs 43.9 dB, word recognition scores 52.3% vs 68.2%, respectively). Initial treatment recommendations and treatment received may include more than 1 modality. TAMC patients were offered 66.7% surgery, 31.2% observation, and 5.2% radiation, while PSNH patients offered 50.7% observation, 49.3% surgery, and 8.7% radiation. TAMC patients received 62.9% surgery, 32.5% observation, and 5.3% radiation, while PSNH patients received 36.2% surgery, 59.4% observation, and 14.5% radiation. Follow up and treatment at the same facility was not significantly different between hospitals. CONCLUSIONS: Hearing was worse and tumor size larger in patients presenting to PSNH. Despite worse hearing status and larger tumor size, the majority of PSNH patients were initially offered observation, compared to TAMC where most patients were initially offered surgery.

Four distinct ipsilateral vestibular schwannomas: A case of mosaic NF2-related schwannomatosis.

OBJECTIVES: Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis. METHODS: We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM). RESULTS: Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors ("first hit") but distinct "second hit" NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis. CONCLUSIONS: Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.

Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets.

BACKGROUND: Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown. OBJECTIVES: The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq). METHODS: scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules. RESULTS: scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1ß. AREG and PLAUR were expressed in the CD68+CD163+IL-1ß+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1ß- subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163-IL-1ß+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1ß, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume. CONCLUSIONS: Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS.