-
American Journal of Clinical Pathology Mar 2024Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report,...
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.
PubMed: 38527168
DOI: 10.1093/ajcp/aqae027 -
Scientific Reports Mar 2024NF2-related schwannomatosis (NF2-SWN) is a rare genetic disorder and is associated with progressive morbidities. This study aimed to investigate the relationship between...
NF2-related schwannomatosis (NF2-SWN) is a rare genetic disorder and is associated with progressive morbidities. This study aimed to investigate the relationship between NF2-SWN disease severity, health-related Quality of Life (QoL), and mental health aspects of patients. Standardised questionnaires assessing mental health problems (symptoms of depression, anxiety, and somatic burden), psychological factors (resilience, loneliness, and personality functioning), and health-related QoL were administered to 97 patients with NF2-SWN. The results of these questionnaires were compared with physician-rated disease severity. Questionnaires were completed by 77 patients. Physician-rated disease severity scores were available for 55 patients. NF2-SWN patients showed a high prevalence of clinically relevant symptoms of depression (30%), anxiety (16%), and somatic burden (32%). Almost all variables showed moderate to high correlations with NF2-SWN-related QoL. NF2-SWN-related QoL was associated with physician-reported disease severity (r = 0.614). In the stepwise hierarchical linear regression analysis, a significant model with four predictors (disease severity type, depression symptoms, personality functioning, and gender) explained 64% of the variance in NF2-SWN-related QoL. Our results showed a strong association between NF2-SWN-related QoL and depression symptoms. Moreover, personality functioning is an important influencing factor, representing a modifiable construct that can be targeted by prevention programs or psychotherapy.
Topics: Humans; Quality of Life; Mental Health; Neurofibromatoses; Neurofibromatosis 2; Neurilemmoma; Skin Neoplasms
PubMed: 38521834
DOI: 10.1038/s41598-024-57401-7 -
European Archives of... May 2024The expanded transpromontorial transcanal approach (ExpTTA) represents a recent addition to the surgical approaches available for the treatment of vestibular schwannoma....
BACKGROUND
The expanded transpromontorial transcanal approach (ExpTTA) represents a recent addition to the surgical approaches available for the treatment of vestibular schwannoma. An initial purely endoscopic version has been complemented by the use of the microscope and it is now one of the possible surgical options for small to medium-sized vestibular schwannomas with a predominantly intracanalar development.
METHODS
This is a series of 54 patients who underwent microsurgical resection of sporadic, unilateral vestibular schwannoma, mainly Koos I-II with non-serviceable hearing, between January 2016 and January 2023 using the expanded transcanal transpromontorial approach. We describe the surgical technique, focusing on anatomical landmarks, and analyzing its advantages and shortcomings. Retrospective analysis of clinical outcomes is presented, including early and late complications. The mean follow-up was 46.7 months.
RESULTS
We achieved gross total resection of the lesion in all cases, confirmed on the first follow-up MRI at least 6 months after each procedure. We did not record any intraoperative complication nor disease recurrence. We recorded two postoperative severe facial nerve palsies, one of which was permanent. No cases of disabling vertigo or imbalance were reported, and all patients reported full recovery of autonomy in daily activities. Three cases of otoliquorrhea were managed conservatively successfully.
CONCLUSIONS
The transcanal transpromontorial approach combines the advantages of endoscopy with the possibilities provided by microsurgery. Our experience confirms its safety in terms of surgical complications and facial nerve outcome. This approach is amongst the treatment options for small-medium schwannomas in patients with impaired hearing, especially in young patients, ensuring radical resection, disease control, and minimal morbidity.
Topics: Humans; Neuroma, Acoustic; Retrospective Studies; Neoplasm Recurrence, Local; Neurilemmoma; Endoscopy; Treatment Outcome
PubMed: 38519593
DOI: 10.1007/s00405-024-08565-5 -
The Annals of Otology, Rhinology, and... Jun 2024Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS...
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.
Topics: Humans; Male; Female; Neuroma, Acoustic; Middle Aged; Safety-net Providers; Academic Medical Centers; Retrospective Studies; Healthcare Disparities; Tertiary Care Centers; Adult; United States; Aged
PubMed: 38517145
DOI: 10.1177/00034894241241201 -
Journal of Clinical Neuroscience :... May 2024People diagnosed with Vestibular Schwannoma (VS) can experience several symptoms both pre and post-treatment. These, alongside the diagnosis experience, can...
People diagnosed with Vestibular Schwannoma (VS) can experience several symptoms both pre and post-treatment. These, alongside the diagnosis experience, can significantly impact their daily life. The present research is a continuation of a larger study aiming to explore the impacts of symptomology and body image/fear of negative evaluation (FNAE) on the quality of life (QOL) for people with VS. The research design was exploratory and involved a nationwide survey with a total of 52 participants. FNAE was assessed using a measurement of the same name, and QOL was assessed using the Penn Acoustic Neuroma Quality of Life scale (PANQOL). Comparing management groups revealed a significant difference in FNAE with higher scores for surgery compared to radiation treatment. Regression analyses revealed that FNAE significantly accounted for 10.9% of the variance in QOL. However, no symptom was significantly predictive of FNAE. In conclusion, VS is associated with several symptoms that can persist post-treatment. Body satisfaction contributes to QOL and may differ between management types. However, due to inconclusive findings on the predictability of symptoms on FNAE, other moderator factors could influence these direct relationships. Future studies should evaluate the variables that could mitigate or protect from the impacts of FNAE for this population.
Topics: Humans; Neuroma, Acoustic; Quality of Life; Female; Male; Middle Aged; Adult; Fear; Body Image; Aged; Surveys and Questionnaires
PubMed: 38508019
DOI: 10.1016/j.jocn.2024.03.011 -
Vestnik Otorinolaringologii 2024Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disease (frequency 1 in 25-90 000) characterized by the formation of tumors of the central nervous system due...
Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disease (frequency 1 in 25-90 000) characterized by the formation of tumors of the central nervous system due to a mutation in the gene on chromosome 22q12. Bilateral vestibular schwannomas are recognized as absolute diagnostic criteria of NF2 and occur in 95% of patients, are accompanied by hearing impairment, manifest at the age of 18-24 years. Skin manifestations can precede vestibular schwannomas for several years and predict the course of the disease: neurofibromas, cafe-au-lait macules, hypopigmented spots, recently described mesh capillary malformations. Despite the benign nature of schwannomas, they can lead to hearing loss, vestibular dysfunction, facial nerve paralysis, gait disorders, pain and convulsions, there is a risk of early death from compression of the brain stem. The probability of progressive hearing loss is partly determined by the type of mutation. We described a clinical case of NF2 in a 21-year-old patient with bilateral vestibular schwannomas without hearing loss, whose skin examination by ENT specialist revealed this disease. The importance of the presented observation is that the doctor should assume neurofibromatosis type 2 in a young patient with bilateral vestibular schwannomas. It is necessary to undertake a further examination of this patient, including: skin examination for the identification of characteristic neurofibromas and cafe-au-lait macules, consultation with an ophthalmologist, neurologist, MRI of the brain and spinal cord with contrast, genetic analysis - for timely initiation of therapy that prevents hearing loss and vestibular disorders.
Topics: Humans; Adolescent; Young Adult; Adult; Neurofibromatosis 2; Neuroma, Acoustic; Mutation; Hearing Loss
PubMed: 38506024
DOI: 10.17116/otorino20248901137 -
Cureus Feb 2024Acoustic neuroma excision in patients with cerebellopontine angle (CPA) tumours offers particular rehabilitation problems due to the complicated architecture of the...
Acoustic neuroma excision in patients with cerebellopontine angle (CPA) tumours offers particular rehabilitation problems due to the complicated architecture of the cerebellum and brainstem tissues involved. CPA tumours (acoustic neuromas) are slow-growing tumours that arise from the vestibulocochlear nerve. Surgical excision of these tumours can cause neurological abnormalities that compromise motor coordination, balance, and facial nerve function. The case study emphasises the importance of a comprehensive physiotherapeutic approach in rehabilitating a patient following acoustic neuroma excision, with a focus on particular CPA tumour deficits. The rehabilitation programme focuses on improving functional outcomes through balance, proprioception, and vestibular rehabilitation that is customised to the demands and deficiencies of the patient. Our comprehensive approach seeks to improve patients' quality of life, promote neurological healing, and support easy reintegration into normal activities following CPA tumour surgery.
PubMed: 38496073
DOI: 10.7759/cureus.54208 -
Journal of Neurosurgery Mar 2024
Topics: Humans; Treatment Outcome; Neuroma, Acoustic; Hearing
PubMed: 38489806
DOI: 10.3171/2023.12.JNS232876 -
Otolaryngology--head and Neck Surgery :... Jul 2024To evaluate long-term hearing outcomes following cochlear implantation in patients with neurofibromatosis type 2 and ipsilateral vestibular schwannoma.
OBJECTIVE
To evaluate long-term hearing outcomes following cochlear implantation in patients with neurofibromatosis type 2 and ipsilateral vestibular schwannoma.
STUDY DESIGN
Retrospective study.
SETTING
Tertiary general hospital.
METHODS
Twenty-two patients undergoing cochlear implantation between 2004 and 2018 with at least 1 year of follow-up were included. Patients were categorized as "users" or "nonusers" of their cochlear implant (CI). For users, speech perception (disyllabic words) without lip-reading was assessed in quiet conditions 1-year postimplantation, and annually thereafter. CI users were classified into 2 groups on the basis of speech intelligibility (≥40% or <40%). Demographic data, treatment options, and tumor size were also recorded.
RESULTS
One year after implantation, 16 (73%) patients used their CI daily. Twelve of these patients had a speech intelligibility ≥40% (mean: 74 ± 21.9%). Three had a Koos stage IV tumor. At the last visit (mean duration of follow-up: 6 ± 5 years), 12 of these 16 patients were still using their implant daily, and 6 had a speech intelligibility ≥40%. No predictive factors for good performance at 1 year or performance stability were identified.
CONCLUSION
Neurofibromatosis type 2 is a complex disease profoundly affecting patient quality of life, and cochlear implantation should always be considered on a case-by-case basis. In some individuals, cochlear implantation can provide good speech intelligibility for extended periods, even posttreatment or in cases of large tumors.
Topics: Humans; Neurofibromatosis 2; Male; Retrospective Studies; Female; Cochlear Implantation; Middle Aged; Adult; Neurofibromatoses; Speech Perception; Treatment Outcome; Skin Neoplasms; Aged; Neurilemmoma; Neuroma, Acoustic; Speech Intelligibility; Follow-Up Studies
PubMed: 38482961
DOI: 10.1002/ohn.702 -
British Journal of Cancer Jun 2024Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS...
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-1β. AREG and PLAUR were expressed in the CD68+CD163+IL-1β+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1β- subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163-IL-1β+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1β, 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.
Topics: Humans; Neuroma, Acoustic; Single-Cell Analysis; Macrophages; Sequence Analysis, RNA; Tumor Microenvironment; Female; Male; Middle Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Interleukin-1beta
PubMed: 38480935
DOI: 10.1038/s41416-024-02646-2