Prevalence and natural history of schwannomas in neurofibromatosis type 2 (NF2): the influence of pathogenic variants.

This study explores the natural history of vestibular, trigeminal and lower cranial nerve schwannomas (VS, TS, LCNS) in patients with Neurofibromatosis type 2 (NF2), to understand how pathogenic variants (PVs) of the NF2 gene affect tumour burden and growth rate, via a retrospective analysis of a UK NF2 centre database and imaging. VS, TS and LCNS location and size were measured in accordance with a standardised protocol. PVs were categorised in accordance with the UK NF2 Genetic Severity Score (GSS). 153 patients (age 5-82) had 458 schwannomas, of which 362 were previously untreated comprising: 204 VS, 93 TS, and 65 LCNS (IX, X, XI). 322 schwannomas had sequential imaging allowing growth rate analysis with a mean follow-up of 45 months. VS were universally present, and bilateral in 146/153 cases. 65% of tumours grew >2 mm during the study period at mean rate 2.0 mm/year. Significant association was found between increasing GSS and growth rate. TS occurred in 66/153 patients (bilateral in 27/153); 31% of tumours showed growth (mean 1.8 mm/yr). Significant increase in tumour prevalence was noted with increasing GSS. LCNS were found in 47/153 patients (bilateral in 19/153); 27% of tumours showed growth (mean 1.9 mm/yr). The trend for increased prevalence with increasing GSS did not reach significance. VS growth rate was significantly influenced by GSS and they were much more likely to grow than TS and LCNS. TS prevalence also correlated with increasing GSS.

Schwannoma: A surgical epidemiology.

OBJECTIVE: To identify the surgical incidence and prevalence of schwannoma in our region and quantify the demographic, surgical, neoplastic, and outcome characteristics of the patients diagnosed with schwannoma.. METHODS: A retrospective cross-sectional study was conducted from January 1 to December 31, 2019. Enrolled were 32 of the highest volume neurosurgical centres in Pakistan. Patients with a histopathological diagnosis of schwannoma and radiological imaging were included in the study. Medical records were reviewed for data, and SPSS version 25 was used for statistical analysis. Patients were followed up for one year, which was the duration of the study. RESULTS: From 2750 patients diagnosed with brain tumours, 148 patients had schwannomas. Out of these, 84 (56.8%) patients were male, and 64 (43.2%) patients were female. The mean age of the patients was 39 ± 14 years. The socioeconomic statuses of the enrolled patients were lower in 72 (53.3%) patients, middle in 57 (42.2%) patients, and upper middle to upper in 6 (4.4%) patients. All patients underwent surgery, 14 patients received radiotherapy, and two patients received chemotherapy. In our cohort, 115 (77.7%) patients presented to public sector hospitals, with only 33 (22.3%) patients presenting to private hospitals. At the end of the study period, 60 (40.5%) patients had been lost to follow-up. Of the remaining 88 patients, 75 (85.2%) were alive. The mortality rate on a one-year follow-up was 14.8%. CONCLUSIONS: Schwannoma comprises a larger percentage of the brain tumours in our regions than reported in the literature. The high mortality rate is of particular concern and warrants further investigation to improve patient care and outcomes.

Neurofibromatoses.

The neurofibromatoses are a group of genetic disorders that cause development of nervous system tumors as well as various other tumor and systemic manifestations. Neurofibromatosis type 1 is the most prevalent of these conditions and has the most variable phenotype and highest risk of malignant tumor formation. Neurofibromatosis type 2 has no associated malignant tumors but does carry significant morbidity, including deafness, facial weakness, and physical disability. Schwannomatosis is the least prevalent of these disorders and is characterized primarily by nonvestibular schwannomas and pain.

Typical 22q11.2 deletion syndrome appears to confer a reduced risk of schwannoma.

PURPOSE: The LZTR1 gene has been associated with schwannomatosis tumor predisposition and is located in a region that is deleted in the great majority (89%) of patients with 22q11.2 deletion syndrome (22q11.2DS). Since it is known that approximately 1 in 500 people in the general population will develop a sporadic schwannoma and there are no reports of the occurrence of schwannoma in 22q11.2DS, we investigated whether whole-gene deletion of LZTR1 occurs in schwannomatosis and assessed the risk of schwannoma in 22q11.2DS. METHODS: We assessed the genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. RESULTS: There were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with an apparently sporadic vestibular schwannoma had a constitutional whole-gene deletion of LZTR1. CONCLUSION: People with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population.

What About Gastric Schwannoma? A Review Article.

PURPOSE: Gastric schwannomas (GSs) are rare mesenchymal neoplasms of the gastrointestinal tract. Diagnosis is often achieved postoperatively, based on pathology reports of retrieved specimens. The aim of the present study is to follow up all patients with gastric schwannoma (Gs) undergoing endoscopic, partial, or more extended surgery and to evaluate the appearance of local or distant recurrence. METHODS: A PubMed, Cochrane, and Embase systematic review of the literature has been performed. Original papers, review articles, and case reports published between 1988 and 2019 were considered eligible. All the studies who met the inclusion criteria were analyzed. Statistical analysis of data has been performed using GraphPad Prism 7 software. RESULTS: Three hundred twenty-eight articles were found, and a total of 102 were included and analyzed in depth. Fifty-three papers reported the follow-up information, ranging from 1 to 417 months across different studies. Among them, 31 patients underwent endoscopic removal of the gastric lesions; 140 patients underwent local surgery, including wedge resection or partial gastrectomy; and 148 patients underwent subtotal or total gastrectomy. The median follow-up was of 27-38-33 months, respectively. No recurrence or distant metastasis was detected in the endoscopy group. Among local surgery group, liver metastasis was reported in one case; in extended surgery group, one patient died for multiple liver metastases. CONCLUSIONS: Local or more extended surgery involved a larger cohort of patients and reported satisfactory long-term results compared with endoscopy group. Surgery in absence of a definite preoperative diagnosis is considered the gold standard treatment for resectable Gs.

Sporadic vestibular schwannoma: a molecular testing summary.

OBJECTIVES: Cases of sporadic vestibular schwannoma (sVS) have a low rate of association with germline pathogenic variants. However, some individuals with sVS can represent undetected cases of neurofibromatosis type 2 (NF2) or schwannomatosis. Earlier identification of patients with these syndromes can facilitate more accurate familial risk prediction and prognosis. METHODS: Cases of sVS were ascertained from a local register at the Manchester Centre for Genomic Medicine. Genetic analysis was conducted in NF2 on blood samples for all patients, and tumour DNA samples when available. LZTR1 and SMARCB1 screening was also performed in patient subgroups. RESULTS: Age at genetic testing for vestibular schwannoma (VS) presentation was younger in comparison with previous literature, a bias resulting from updated genetic testing recommendations. Mosaic or constitutional germline NF2 variants were confirmed in 2% of patients. Pathogenic germline variants in LZTR1 were found in 3% of all tested patients, with a higher rate of 5% in patients <30 years. No pathogenic SMARCB1 variants were identified within the cohort. Considering all individuals who received tumour DNA analysis, 69% of patients were found to possess two somatic pathogenic NF2 variants, including those with germline LZTR1 pathogenic variants. CONCLUSIONS: Undiagnosed schwannoma predisposition may account for a significant minority of apparently sVS cases, especially at lower presentation ages. Loss of NF2 function is a common event in VS tumours and may represent a targetable common pathway in VS tumourigenesis. These data also support the multi-hit mechanism of LZTR1-associated VS tumourigenesis.

Retrospective Analysis of 20 Patients Affected by Schwannomas in the Upper and Lower Limbs / Análise retrospectiva de 20 pacientes acometidos por schwannoma nos membros superior e inferior

Abstract Objective To analyze the epidemiological profile and evolution of 20 patients diagnosed with upper- and lower-limb schwannomas. Methods A group of patients was defined for a retrospective evaluation comprising the period between February 2002 and June 2018, in which we studied and evaluated 20 medical records of patients undergoing surgery due to schwannoma; the diagnosis was confirmed by an anatomopathological examination. Results Male and female patients were equally affected. The average age was 50.85 years, ranging from 12 to 77 years. There was a predominance of the upper limb and of the flexor face. The most affected nerve was the ulnar nerve. In total, 6 (30%) patients had transient postoperative complications. No cases of tumor recurrence were identified. Conclusion Schwannoma is a rare and difficult-to-diagnose lesion. It should always be considered as a hypothesis when facing a soft-tissue tumor affecting the limbs. The Tinel sign should be regarded, given its higher correlation with complications. The patients should be informed of the possible postoperative complications, which are frequent but usually transient.

Resumo Objetivo Analisar o perfil epidemiológico e a evolução de 20 pacientes diagnosticados com schwannoma nos membros superiores e inferiores. Métodos Definiu-se um grupo de pacientes para avaliação retrospectiva, compreendendo o período entre fevereiro de 2002 e junho de 2018, no qual foram estudados e avaliados 20 prontuários de pacientes submetidos a procedimento cirúrgico devido a schwannoma; a confirmação diagnóstica foi feita pelo exame anatomopatológico. Resultados Tanto os pacientes do sexo masculino quanto do feminino foram igualmente acometidos, e a média de idade foi de 50,85 anos, variando de 12 a 77 anos. Houve predomínio do membro superior e da face flexora. O nervo mais acometido foi o ulnar, e 6 (30%) pacientes apresentaram complicações pós-operatórias transitórias. Não foi identificado nenhum caso de recidiva tumoral. Conclusão O schwannoma é uma lesão rara e de difícil diagnóstico. Deve sempre ser considerada como hipótese quando se estiver diante de um tumor de partes moles acometendo os membros. O sinal de Tinel deve ser levado em consideração por conta de sua maior correlação com as complicações. Os pacientes devem ser informados quanto às possíveis complicações pós-operatórias, que são frequentes, mas, geralmente, transitórias.

Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958-2009.

Radiation exposure is among the few factors known to be associated with risk of central nervous system (CNS) tumors. However, the patterns of radiation risk by histological type, sex or age are unclear. We evaluated radiation risks of first primary glioma, meningioma, schwannoma, and other or not otherwise specified (other/NOS) tumors in the Life Span Study cohort of atomic bomb survivors. Cases diagnosed between 1958 and 2009 were ascertained through population-based cancer registries in Hiroshima and Nagasaki. To estimate excess relative risk per Gy (ERR/Gy), we fit rate models using Poisson regression methods. There were 285 CNS tumors (67 gliomas, 107 meningiomas, 49 schwannomas, and 64 other/NOS tumors) among 105,444 individuals with radiation dose estimates to the brain contributing 3.1 million person-years of observation. Based on a simple linear model without effect modification, ERR/Gy was 1.67 (95% confidence interval, CI: 0.12 to 5.26) for glioma, 1.82 (95% CI: 0.51 to 4.30) for meningioma, 1.45 (95% CI: - 0.01 to 4.97) for schwannoma, and 1.40 (95% CI: 0.61 to 2.57) for all CNS tumors as a group. For each tumor type, the dose-response was consistent with linearity and appeared to be stronger among males than among females, particularly for meningioma (P = 0.045). There was also evidence that the ERR/Gy for schwannoma decreased with attained age (P = 0.002). More than 60 years after the bombings, radiation risks for CNS tumors continue to be elevated. Further follow-up is necessary to characterize the lifetime risks of specific CNS tumors following radiation exposure.

Peripheral Nerve Schwannomas: A Literature Review

Introduction Schwannomas are benign tumors originating from the cells, which wrap around axons that are usually encapsulated and solitary. These tumors usually lead to little or no symptomatology. They are usually the most common peripheral nerve tumors in adults, with their highest incidence between the third and fifth decades of life. Objective To perform a review about schwannoma of the peripheral nerves, presenting its definition, epidemiology, diagnosis, symptomatology and treatment. Methodology This is a descriptive work, based on a review of articles available in the PubMed database with the descriptors schwannoma and peripheral nerves. Results and Discussion Only papers published between 1981 and 2019, describing studies in humans, and that were available as full articles were selected. A total of 391 articles were included; after reading the titles, we noted that 67 articles fit the topic of the present study. Among the articles selected for reading, 33 fit the objectives of the present work, and were considered for the writing of the present article. Conclusion Schwannomas are benign myelin sheath tumors that develop with local symptomatology or asymptomatic and present a good surgical prognosis with generally reduced rates of surgical complications.

Environmental risk factors of primary brain tumors: A review.

Adult primary tumors of the central nervous system are rare, but the incidence is increased in some European countries. Several environmental exposures have been investigated as potential risk factors, but for most, scientific evidence is still lacking. Here we review studies of environmental factors potentially involved in the carcinogenesis of brain tumors: the potential association between primary central nervous system tumors and ionizing radiation, some toxic agents (N-nitroso compounds, pesticides), air pollution, and radiofrequency electromagnetic waves. Brain-ionizing irradiation, especially during childhood, constitutes a well-established risk factor for brain tumors. Exposure to environmental toxins has been poorly explored and data give inconsistent clues about N-nitroso compounds or pesticides as risk factors of brain tumors even for prenatal exposure. For out-door pollution and risk of brain tumour, results of large prospective studies are contradictory. The effect of mobile phones on the risk of developing brain tumors has not been established for glioma and meningioma in adults, but the link with acoustic neurinoma is becoming robust. The effect of mobile phones has still not been explored in children.

Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.

BACKGROUND: Schwannomas encompassing the superior parapharyngeal space are challenging lesions because of the anatomical complexity of this region and the frequent involvement of the neurovascular structures of the jugular foramen. The purpose of this study is to report the technical aspects and the advantages of the anterolateral approach, here proposed for schwannomas of this complex area. METHODS: The main steps of the anterolateral approach are described in detail, along with the results of a consecutive series of 38 patients with a retrostyloid superior parapharyngeal schwannoma involving the jugular foramen operated on by means of this route between 1999 and 2019. RESULTS: The supine position is generally preferred. The medial border of the sternocleidomastoid muscle, mastoid tip, and superior nuchal line are the landmarks for the hockey-stick skin incision. The accessory nerve is retrieved and mobilized cranially. Detachment of the sternocleidomastoid, digastric, and nuchal muscles allows for a 180° exposure of the extracranial side of the jugular foramen. Three working corridors, namely the pre-carotid, pre-jugular, and retro-jugular, allow access to the deeper part of the jugular foramen area and the superior parapharyngeal space. In the present series, a gross total resection was achieved in 89.4% of the patients. Three recurrences occurred after an average follow-up of 80.5 ± 51 months. CONCLUSIONS: The anterolateral approach is highly effective in the treatment of retrostyloid superior parapharyngeal space schwannomas involving the jugular foramen. Its simplicity of execution, versatility, and very low morbidity are among its main strengths.

Palatal Schwannoma: An Analysis of 45 Literature Reports and of an Illustrative Case

Abstract Introduction Schwannomas are benign tumors originating from differentiated Schwann cells. Being the least common intraoral neoplasm of neural origin, it is rarely seen in the palate. The literature lacks an extensive review of intraoral schwannoma confined to the palate. Objective To review previously reported cases of palatal schwannoma along with an illustrative case, and to provide a better insight regarding clinicopathological and radiological features of this neural tumor in a rare intraoral site. Data Synthesis We present a case of palatal schwannoma in a 16-year-old female. An additional 45 cases were identified in 2 medical database searches (PubMed and Google Scholar) published fromthe year 1985 onwards, and from13 countries, in the 5 continents. The ages of the patients ranged from3 to 84 years old. Palatal schwannoma showed a slight predilection to females, with a male/female ratio of ~ 1:1.81. Hard palate involvement is almost twice greater than soft palate involvement. Surgical excision was employed inalmost all of the cases, and recurrence was reported only once. Conclusion Palatal schwannomas, although rare, have been reported both over the hard and the soft palate. They mostly present as a painless, firm, well-encapsulated, slow-growing solitary lesion over the lateral palatal aspect. Imaging can add to suspicion and can delineate a differential diagnosis, but the diagnosis is confirmed by pathological examination. Fine-needle aspiration cytology (FNAC) is almost always inconclusive. Immunohistochemistry can assist in confirming a diagnosis, but is more important to rule out close differentials. Complete surgical excision is the treatment of choice, and recurrence or malignant transformation are extremely rare.

Intradural extramedullary spinal masses treated at the Wits teaching hospitals between 2014 - 2017.

BACKGROUND: Intradural extramedullary (IDEM) spinal masses are common lesions with varying histological diagnoses often associated with significant neurological deficits. This study aimed to describe the epidemiology, management and perioperative outcome of IDEM tumours seen at the teaching hospitals of the University of the Witwatersrand, Johannesburg, between 2014 and 2017. RESULTS: 92 patients were included in the study. The ages ranged from 21 to 87 years, sex ratio was M:F 1:1.4, and duration of symptoms prior to diagnosis ranged between 3 days to 18 months. Local and radicular type pain as well as motor weakness were the commonest symptoms. 67% had severe neurological deficit McCormick Grade III and IV. Schwannoma (26) Neurofibromas (21) and Meningiomas (16) and were the most frequent tumour types. Meningiomas predominantly occurred at the cranio-cervical and thoracic levels. Nerve sheath tumours were mostly found at the cervical and lumbar levels while filum terminale ependymomas occurred at the thoracolumbar area. Laminectomy was the commonest surgical approach employed, and the extent of resection varied, with total excision in half the cases. Neurological function was regained in 3 patients, deteriorated in two and was unchanged in the remainder. CONCLUSION: IDEM tumours are an important subset of spinal cord compressive lesions Presentation with severe neurological deficit is common and though resection is feasible neurological deficit remains in the vast majority. Earlier detection should improve the results of surgery.

Characteristics and outcomes in patients with primary intraspinal tumours.

INTRODUCTION: We report a retrospective cohort study aimed at presenting data on incidence, patient char-ac-teristics, tumour type, level of pathology, clinical status before and after surgery and complications in patients with surgically treated primary intraspinal tumours (PIST) in Western Denmark. METHODS: Population-based data were retrieved from hospital files from 1 January 2010 to 31 December 2015. RESULTS: In total, 78 males and 88 females with PIST were included in the study. Incidence per 100,000 persons per year in the population-based cohort was 2.18. The incidence of malignant PIST was 0.14 and the incidence of non-malignant PIST was 2.03. We found 25 extradural tumours, 100 intradural extramedullary tumours and 41 intramedullary tumours. Eleven were malignant and 155 were benign tumours. Schwannoma, meningioma and ependymoma were more common in adults, whereas haemangioblastoma, neurofibroma and epidermoid cysts were seen in 14 paediatric cases. Motor function disturbances were found in 38% of cases. Sensory disturbances were found in 54% of cases, and worsening of sensory functions was the most frequent post-operative sequela. Ataxia and neurogenic bowel/bladder dysfunction seem to constitute the highest risk in cases of intramedullary tumours. Pain was found in 75% of cases and was the most common symptom among all patients with PITS with a 58% improvement after surgery. Complications were recorded in 12% of cases. CONCLUSIONS: The incidence of PIST seems to be higher in Western Denmark than in other European studies. PIST are rare in children. FUNDING: none. TRIAL REGISTRATION: not relevant.

Recent Trends in Vestibular Schwannoma Management: An 11-Year Analysis of the National Cancer Database.

OBJECTIVE: A better understanding of the natural history of vestibular schwannoma (VS) has resulted in a change in treatment paradigms. It has also been proposed that increased use of high-resolution magnetic resonance imaging has allowed for an increased identification of small tumors. The aim of this study was to evaluate recent trends in the presentation and primary management of VS in the United States. STUDY DESIGN: Retrospective analysis of the National Cancer Database (NCDB). SETTING: NCDB database. SUBJECTS AND METHODS: All patients with a diagnosis of VS between 2004 and 2014 were included. Data were analyzed with univariable and multivariable logistic regression. RESULTS: In total, 28,190 patients (mean age 55 years, 52.9% female) with VS were analyzed. Linear regression showed a small decrease in average tumor size over time (-0.06 mm/year, P = .03). Overall, 11,121 patients (40%) received surgery, 8512 (30%) radiation, and 7686 (27%) observation. Controlling for patient, tumor, and treatment center factors, the odds ratio (OR) for receiving surgery in 2014 was 0.60 (confidence interval [CI], 0.50-0.71) while the OR for receiving radiation was 0.75 (CI, 0.64-0.87) as compared to those diagnosed in 2004. The largest increases in observation rates occurred among tumors ≤2 cm (P < .001). CONCLUSION: There was not a clinically significant change in the average tumor size at diagnosis. Although surgery remained the most common treatment modality in the United States, there was a strong shift in the management of VS away from primary surgery and radiation and toward a "wait-and-scan" approach.

Cauda equina schwannoma with concomitant intervertebral disc herniation: A case report and review of literature.

The coexistence of lumbar intervertebral disc (IVD) herniation and cauda equina schwannoma in symptomatic patients is uncommon. We experienced a case with a surgically treated cauda equina schwannoma with concomitant lumbar IVD herniation (L2/L3); both were relatively small but presented with painful symptoms in combination. A 45-year old man complained of low back pain and right anterior thigh pain six months prior to surgery. He underwent conservative treatment; however, his pain suddenly worsened three months before surgery, with abnormal sensations and pain in his right buttock and posterior thigh. A magnetic resonance imaging (MRI) scan revealed an L2/L3 disc herniation extruding to the center of the lumbar spinal canal and compressing the thecal sac. Incidentally, an intrathecal tumor was suspected, and enhanced MRI revealed a round tumor measuring 10-mm in diameter at the L2/L3 intervertebral level, which was uniformly enhanced by gadolinium chelate, radiologically diagnosed as a schwannoma. Microscopic discectomy and tumor resection were performed and the patient's symptoms disappeared immediately. Schwannoma is generally slow-growing, and usually asymptomatic when the tumor size is small. Therefore, we suspected that the tumor occasionally impinged on the left L3 root with L2/3 IVD herniation, leading to acute worsening of the patient's symptoms. Altogether, in case of tumor in patients undergoing conservative treatment for cauda equina schwannoma, we should consider that symptoms can acutely worsen with the occurrence of lumbar IVD herniation.

Infratemporal fossa tumors: When to suspect a malignant tumor? A retrospective cohort study of 62 cases.

OBJECTIVES: Infratemporal fossa (ITF) tumors are rare and little is known about their general epidemiology, making it sometimes difficult for clinicians, who seldom encounter them, to distinguish between benign and malignant forms on the basis of the initial clinical and radiological work-up alone. The objectives of this retrospective study were: (i) to determine the respective prevalences of the various histologic types of ITF tumor, and (ii) to assess associations between certain clinical and radiological features and malignancy. METHODS: A single-center observational study in a university hospital included all new consecutive cases of ITF tumor treated from January 2000 to December 2016. Histologic type, demographics, clinical presentation and imaging findings were analyzed. RESULTS: In total, 62 patients were included. 74% of tumors were benign (n=46) and 26% malignant. Juvenile nasopharyngeal angiofibroma, adenoid cystic carcinoma and schwannoma were the most frequent histologic types, accounting for 47%, 16% and 10% of cases, respectively. The only clinical or imaging signs significantly associated with malignancy were trismus, facial pain, facial hypoesthesia and neural invasion on magnetic resonance imaging (all P-values<0.05). CONCLUSION: This study provides general epidemiological data on ITF tumors, and identified several clinical and radiologic signs to help clinicians suspect malignancy.

Schwannomatosis: a genetic and epidemiological study.

OBJECTIVES: Schwannomatosis is a dominantly inherited condition predisposing to schwannomas of mainly spinal and peripheral nerves with some diagnostic overlap with neurofibromatosis-2 (NF2), but the underlying epidemiology is poorly understood. We present the birth incidence and prevalence allowing for overlap with NF2. METHODS: Schwannomatosis and NF2 cases were ascertained from the Manchester region of England (population=4.8 million) and from across the UK. Point prevalence and birth incidence were calculated from regional birth statistics. Genetic analysis was also performed on NF2, LZTR1 and SMARCB1 on blood and tumour DNA samples when available. RESULTS: Regional prevalence for schwannomatosis and NF2 were 1 in 126 315 and 50 500, respectively, with calculated birth incidences of 1 in 68 956 and 1 in 27 956. Mosaic NF2 causes a substantial overlap with schwannomatosis resulting in the misdiagnosis of at least 9% of schwannomatosis cases. LZTR1-associated schwannomatosis also causes a small number of cases that are misdiagnosed with NF2 (1%-2%), due to the occurrence of a unilateral vestibular schwannoma. Patients with schwannomatosis had lower numbers of non-vestibular cranial schwannomas, but more peripheral and spinal nerve schwannomas with pain as a predominant presenting symptom. Life expectancy was significantly better in schwannomatosis (mean age at death 76.9) compared with NF2 (mean age at death 66.2; p=0.004). CONCLUSIONS: Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.

Incidence of Intralabyrinthine Schwannoma: A Population-based Study Within the United States.

OBJECTIVE: To describe the incidence of intralabyrinthine schwannoma (ILS) utilizing the Rochester Epidemiology Project (REP), a unique medical consortium in the United States that covers a complete population of all ages in a well-defined geographic area over the past half-century. PATIENTS: All patients with ILS diagnosed between January 1, 1966 and December 31, 2016 in Olmsted County, Minnesota, identified using the REP medical records-linkage system. MAIN OUTCOME MEASURES: Incidence of ILS. RESULTS: Fourteen incident cases of ILS were identified in Olmsted County since 1966-a period spanning 5.9 million person-years. Over the past decade, the incidence rate of ILS was 0.81 per 100,000 person-years and 1.1 over the last 5 years. Since 1966, the cumulative incidence rate of ILS over the past 50 years was 0.26 per 100,000 person-years. The median age at diagnosis was 60 years (interquartile ranges, 39-70). Incidence increased with age: over the last 5 years, those aged 60 to 69 exhibited an incidence rate of 2.7 per 100,000 person-years and those 70+ displayed a rate of 4.1. All patients had varying levels of asymmetrical sensorineural hearing loss with 64% of patients presenting with class D hearing. Four (29%) patients had a history of sudden sensorineural hearing loss, five (36%) reported imbalance and/or vertigo, and four (29%) reported aural fullness. Three of the 14 (21%) patients had neurofibromatosis type 2. CONCLUSION: The incidence of ILS exceeds 1 per 100,000 person-years with modern diagnostic imaging. The rising incidence of ILS in recent years most likely reflects improved capacity for disease detection rather than a true increase in tumor development. Given the reputability of the REP consortium, these data suggest that ILS comprises a more common entity than previously considered.

Frequency of the Loss of Heterozygosity of the NF2 Gene in Sporadic Spinal Schwannomas.

BACKGROUND/AIM: Individuals with type 2 Neurofibromatosis are predisposed for the appearance of schwannomas. In the present study we analyzed the loss of heterozygosity and mutations in the NF2 gene in patients with sporadic Schwannoma without Neurofibromatosis type 2. MATERIALS AND METHODS: We analyzed 39 patients with sporadic spinal schwannoma. We quantified the number of alleles by FISH and sequenced the NF2 gene. RESULTS: We identified 16/39 patients with point mutations and/or LOHs in the tumor samples analyzed. The LOHs were found in 7/39 patients. Two homozygous mutations were detected in 4/39 tumors, and the presence of the mutation in heterozygosis was revealed in 3/39 patients. In two tumors, we detected the loss of one allele of the NF2 gene, with no mutation. CONCLUSION: The genetic alterations observed in the NF2 gene indicated that spinal schwannomas are associated with genetic alterations also found in other schwannomas and type 2 Neurofibromatosis, which reinforces the etiological role of this gene.