Brazilian Society of Otology task force - Vestibular Schwannoma - evaluation and treatment

Abstract Objective: To review the literature on the diagnosis and treatment of vestibular schwannoma. Methods: Task force members were educated on knowledge synthesis methods, including electronic database search, review and selection of relevant citations, and critical appraisal of selected studies. Articles written in English or Portuguese on vestibular schwannoma were eligible for inclusion. The American College of Physicians' guideline grading system and the American Thyroid Association's guideline criteria were used for critical appraisal of evidence and recommendations for therapeutic interventions. Results: The topics were divided into 2 parts: (1) Diagnosis - audiologic, electrophysiologic tests, and imaging; (2) Treatment - wait and scan protocols, surgery, radiosurgery/radiotherapy, and systemic therapy. Conclusions: Decision making in VS treatment has become more challenging. MRI can diagnose increasingly smaller tumors, which has disastrous consequences for the patients and their families. It is important to develop an individualized approach for each case, which highly depends on the experience of each surgical team.

Percepção auditiva e desenvolvimento de linguagem oral após cirurgia de implante auditivo de tronco encefálico: uma revisão de escopo / Auditory perception and oral language in brainstem auditory implant users: a scoping review

RESUMO Objetivo mapear as evidências atuais em relação à percepção auditiva da fala e desenvolvimento de linguagem oral em usuários de implante auditivo de tronco encefálico (auditory brainstem implant - ABI), para responder à seguinte questão norteadora: "O que se sabe sobre a habilidade de percepção auditiva da fala e de linguagem oral em indivíduos usuários de implante auditivo de tronco encefálico?" Estratégia de pesquisa a busca foi realizada nas bases de dados BVSalud, PubMed e SciELO e, para literatura cinzenta, utilizou-se a fonte de informação Google Acadêmico, por meio dos descritores: implante auditivo de tronco encefálico (auditory brainstem implantation), linguagem (language), audição (hearing) e percepção auditiva (auditory perception). Critérios de seleção foram incluídos estudos nos quais foram aplicados testes para avalição da percepção auditiva ou para verificar desenvolvimento de linguagem oral em crianças e/ou adultos usuários de ABI. Foram incluídos artigos publicados nos últimos cinco anos e excluídos estudos secundários. Resultados Foram encontrados 1767 artigos nas bases de dados e fonte de informação, dos quais, 27 foram incluídos na revisão. Observou-se que a maioria dos usuários de ABI torna-se capaz de perceber alguns sons ambientais, alguns tornam-se capazes de reconhecer vocábulos, porém, poucos atingem o reconhecimento de frases. Conclusão a maioria dos usuários de ABI não avança para a habilidade de reconhecimento auditivo em conjunto aberto e há unanimidade na recomendação de métodos de comunicação visual para esses indivíduos.

ABSTRACT Purpose This scope review aims to map current evidence in relation to auditory perception of speech and oral language development in users of Auditory Brainstem Implant - ABI, to answer the following guiding question: "what do we know about the ability of auditory perception of speech and oral language in auditory brainstem implants users?" Research strategy The search was performed in the BVSalud, PubMed and SciELO databases and for gray literature the source of information Google Academic, using the descriptors: auditory brainstem implantation , language, hearing and auditory perception. Selection criteria Studies were included in which tests were applied to assess auditory perception or to verify oral language development in children and/or adults using ABI. Articles published in the last five years were included and secondary studies were excluded. Results 1767 articles were found in the databases and source of information, of which 27 studies were included. It was observed that most users of ABI become able to perceive some environmental sounds, some become able to recognize words, but few reach the recognition of sentences. Conclusion Most ABI users do not advance towards the open set auditory recognition skill and there is unanimity in recommending visual communication methods for these individuals.

Síndrome de pseudo-Duane secundario a Schwannoma de nervio abducens: Reporte de caso y revisión / Pseudo-Duane syndrome secondary to abducens nerve schwannoma: Case report and review

Reporte de caso de síndrome de pseudo-Duane asociado a schwannoma de nervio abducens y neurofibromatosis tipo 2 (NF2). Este síndrome es raro, caracterizado por limitación en abducción, retracción ocular, disminución de hendidura palpebral en abducción y restricción del recto medial ipsilateral en test de ducción forzada. La NF2 es también una enfermedad infrecuente caracterizada por tumores de sistema nervioso central y periférico. Los schwannomas de nervio abducens son también poco frecuentes, y se presentan comúnmente con diplopia. Se revisan brevemente estas enfermedades. Es el primer caso reportado de pseudo-Duane secundario a schwannoma de nervio abducens y NF2 según nuestro conocimiento.

A pseudo-Duane syndrome case associated with abducens nerve schwannoma and neurofibromatosis type 2 (NF2) is presented. This syndrome is a rare disease characterised by abduction limitation, ocular retraction, narrowing of the palpebral fissure in abduction, and ipsilateral medial rectus restriction on forced duction test. NF2 is also an uncommon disease which is characterised by peripheral and central nervous system tumours. Abducens nerve schwannomas are also uncommon and presents usually as diplopia. A short review of these diseases is given. This is the first case of pseudo-Duane secondary to abducens nerve schwannoma, to our knowledge.

Expression of NF2 Modulates the Progression of BRAFV600E Mutated Thyroid Cancer Cells

BACKGROUND: We previously reported the frequent neurofibromatosis 2 (NF2) gene mutations in anaplastic thyroid cancers in association with the BRAF V600E mutation. We aimed to investigate the role of NF2 in thyroid cancer with BRAF mutation. METHODS: To identify the function of NF2 in thyroid cancers, we investigated the changes in cell proliferation, colon formation, migration and invasion of thyroid cancer cells (8505C, BHT101, and KTC-1) with BRAF V600E mutation after overexpression and knock-down of NF2. We also examined how cell proliferation changed when NF2 was mutagenized. Human NF2 expression in papillary thyroid carcinoma (PTC) was analyzed using the The Cancer Genome Atlas (TCGA) data. RESULTS: First, NF2 was overexpressed in 8505C and KTC-1 cells. Compared to control, NF2 overexpressed group of both thyroid cancer cells showed significant inhibition in cell proliferation and colony formation. These results were also confirmed by cell migration and invasion assay. After knock-down of NF2 in 8505C cells, there were no significant changes in cell proliferation and colony formation, compared with the control group. However, after mutagenized S288* and Q470* sites of NF2 gene, the cell proliferation increased compared to NF2 overexpression group. In the analysis of TCGA data, the mRNA expression of NF2 was significantly decreased in PTCs with lateral cervical lymph node (LN) metastasis compared with PTCs without LN metastasis. CONCLUSION: Our study suggests that NF2 might play a role as a tumor suppressor in thyroid cancer with BRAF mutation. More studies are needed to elucidate the mechanism how NF2 acts in thyroid cancer with BRAF mutation.

Treinamento auditivo computadorizado em uma adolescente portadora de neurofibromatose do tipo 2 / Computerized auditory training in an adolescent with neurofibromatosis type 2 / Entrenamiento auditivo computarizado en una adolescente portadora de neurofibromatosis tipo 2

A neurofibromatose do tipo 2 é uma doença genética que afeta o Sistema Nervoso Central, principalmente a via auditiva, sendo alguns dos principais sintomas a perda auditiva neurossensorial, o baixo reconhecimento de fala, zumbido e disfunção vestibular. Relata-se neste estudo um processo de intervenção terapêutica por meio do Treinamento Auditivo Computadorizado em uma adolescente com diagnóstico médico de Neurofibromatose tipo 2. Tal intervenção contou com 16 sessões de TA, realizadas com um software específico. Para o estudo realizou-se a avaliação, pré e pós-treinamento, por meio dos resultados da avaliação audiológica básica, Potencial Evocado Auditivo de Tronco Encefálico e avaliação da consciência fonológica, além de analisar os relatos referentes ao processo terapêutico. Os testes comportamentais de processamento auditivo não foram realizados, pois a paciente apresenta acentuada dificuldade de compreensão de fala. Paciente apresentou melhora no reconhecimento de fala e na habilidade de consciência fonológica, apesar do exame eletrofisiológico da audição não demonstrar tais benefícios diretamente na via auditiva em nível de tronco encefálico, para o estímulo clique. Destaca-se o relato da paciente de melhora na compreensão de fala após tal intervenção. Desse modo, observaram-se os efeitos positivos do treinamento auditivo na melhora da percepção auditiva, influenciando positivamente. na vida diária da paciente.

Neurofibromatosis type 2 is a genetic disease that affects the Central Nervous System, mainly the auditory pathway, being some of the main symptoms: sensorineural hearing loss, low speech recognition, tinnitus and vestibular dysfunction. This study describes a process of therapeutic intervention through. Computerized Auditory Training in an adolescent with medical diagnosis of Neurofibromatosis type 2. This intervention was composed of 16 sessions of AT with a specific software. For this study, the pre and post-training evaluation was carried out through the results of basic audiological evaluation, Brainstem Evoked Response Audiometry and evaluation of phonological awareness, as well as analyzing the patient's reports regarding the therapeutic process. The auditory processing behavioral tests were not performed, since the patient presents difficulty in speech comprehension. Patient presented improvement in speech recognition and phonological awareness ability, although the electrophysiological test did not demonstrate such benefits directly in the auditory pathway at the brainstem level, for the click stimulus. Furthermore, the patient's report of improvement in speech comprehension after such intervention could also be highlighted. Thus, the positive effects of auditory training on the improvement of auditory perception could be observed, influencing positively the daily life of the patient.

La neurofibromatosis del tipo 2 es una enfermedad genética que afecta el Sistema Nervioso Central, principalmente la vía auditiva,siendo algunos de los principales síntomas la pérdida auditiva neurosensorial, el bajo reconocimiento de habla, zumbido e disfunción vestibular. En este estudio se relató un proceso de intervención terapéutica por medio de Entrenamiento Auditivo Computarizado en una adolescente diagnosticada con Neurofibromatosis tipo 2. La intervención contó con 16 sesiones de EA, realizadas con un software específico. Para el estudio se realizó la evaluación antes y después del entrenamiento, atreves de los resultados de la evaluación audiológica básica, Potenciales Evocados Auditivos del Tronco Encefálico y evaluación de la conciencia fonológica, además de analizar los relatos relacionados al proceso terapéutico. Los testes comportamentales de procesamiento auditivo no fueron realizados, pues la paciente presenta acentuada dificultad de comprensión de habla. La paciente presentó mejora en el reconocimiento de habla y en la habilidad de conciencia fonológica, por más que el examen electrofisiológico de la audición no tenga demostrado esos beneficios directamente en la vía auditiva en nivel de tronco encefálico, para el estímulo clic. Se destaca el relato de mejorapor la paciente en la comprensión de habla tras la intervención. De esa manera, se observaron los efectos positivos del entrenamiento auditivo en la mejora de la percepción auditiva, influyendo positivamente en la vida diaria de la paciente.

A case of schwannoglioma in skull plate barrier with left parietal vascular malformation / 天津医药

@#Schwannoma in skull plate barrier with left parietal vascular malformation, which is independent of the two adjacent lesions, is clinically rare. Clinical data of a case with schwannoma in skull plate barrier and left parietal vascular malformation hospitalized in our hospital on September 2016 were retrospectively analyzed. We report the coexistence of intracranial tumors and vascular malformations coexist.

Genetic and clinical characteristics of Korean patients with neurofibromatosis type 2

PURPOSE: Neurofibromatosis type 2 (NF2) is characterized by multiple tumors, including vestibular schwannoma (VS) and others affecting cranial and peripheral nerves. NF2 is caused by mutation of the NF2 gene. The mutation spectrum of NF2 has not been characterized in Korean patients. In the current study, the clinical and genetic characteristics of Korean NF2 patients were analyzed. MATERIALS AND METHODS: Twenty-five unrelated Korean families were enrolled according to the Manchester criteria. Genetic analysis was performed by direct sequencing and multiplex ligation-dependent probe amplification methods using genomic DNA from peripheral lymphocytes or tumor tissues. RESULTS: All patients had bilateral/unilateral VS and/or other cranial and peripheral nerve tumors. Two patients were familial cases and the other 24 patients were sporadic. Germline NF2 mutations were detected in peripheral lymphocytes from both familial cases, but only in 26.1% of the 23 sporadic families. Somatic mutations were also found in tumor tissues from two of the sporadic families. These somatic mutations were not found in peripheral lymphocytes. A total of 10 different mutations including 2 novel mutations were found in 40.0% of studied families. Five mutations (50.0%) were located in exon 6 of NF2, the FERM domain coding region. CONCLUSION: Family history was an important factor in identifying germline NF2 mutations. Further study is required to investigate whether exon 6 is a mutation hotspot in Korean NF2 patients and its correlation to phenotypic severity.

A Case of Cochlear Implantation in Neurofibromatosis Type II / 대한이비인후과학회지

Patients with neurofibromatosis type 2 (NF2) develop bilateral vestibular schwannomas that can cause binaural progressive hearing loss in most individuals. Auditory rehabilitation for bilateral profound sensorineural hearing loss in patients with NF2 poses a great therapeutic challenge. An auditory brainstem implantation may be an option after tumor excision, but its hearing results are still relatively unsatisfactory. A cochlear implantation (CI) may be another option in those cases where the cochlear nerve has been left intact after tumor excision or in those cases that have been kept stable after treating with Gamma-Knife. Here we report a case of undergoing CI after having been treated with Gamma-Knife in NF2 and showing improved open-set speech perception.

Schwannomatose - primeiros casos relatados no Brasil / Schwannomatosis - first reported cases in Brazil

A dor neuropática pode ser decorrente de diversas causas, entre elas a schwannomatose (SCH), uma doença que acomete cerca de cinco mil brasileiros. A SCH é caracterizada por schwannomas múltiplos e intensamente dolorosos. O diagnóstico diferencial de SCH inclui especialmente as neurofibromatoses do tipo 1 e 2. Um caso típico de SCH, provavelmente o primeiro registrado no Brasil, é apresentado e discutido em detalhes e dois outros casos subsequentes são comparados quanto a determinados aspectos clínicos e radiológicos. Paciente feminina de 33 anos de idade foi admitida com queixas de dor e diminuição progressivada força no membro inferior esquerdo, havia cinco anos, associadas ao surgimento de nodulações muito dolorosas naquela região. Apresentava também duas manchas café com leite (<1 cm). A RNM detectou tumores de partes moles em região subcutânea e intracavitárias. Foram realizadas duas biópsias em regiões distintas e o exame microscópico de dois nódulos revelou células de Schwann envoltas por abundante estroma mixóide. O exame imuno-histoquímico mostrou marcação forte e difusa para proteína S-100. O exame ultraestrutural demonstrou nas áreas centrais células de Schwann, com restos membranosos intracitoplasmáticos e, focalmente, membrana basal redundante. A sintomatologia álgica, o padrão de crescimento neoplásico intraneural, com acentuado edema peritumoral, hialinização vascular e reatividade imuno-histoquímica para proteína S-100 nas células de Schwann no centro das lesões possibilitaram o diagnóstico de schwannomatose. O tratamento farmacológico para a dor foi a opção possível, obtendo-se remissão parcial da dor...

Neuropathic pain stems various sources including schwannomatosis (SCH), a disease that affects about five thousand Brazilians. SCH is characterized by multiple and intensely painful schwannomas. Differential diagnosis of SCH includes, especially, neurofibromatosis types 1 and 2. A typical case of SCH, possibly the first recorded in Brazil, is presented and discussed in detail and compared with two other subsequent cases with regards to selected clinical and radiological aspects. A 33 year-old female patient was admitted with pain and progressive loss of strength in the left lower limb for the past five years. These complaints were associated withthe appearance of very painful nodules in the same region. She also had two light brown (café-au-lait) spots (<1 cm). MRI detected soft tissue tumors in the subcutaneous and intracavitary regions. Two distinct biopsies of different regions and microscopic examination of two nodulesrevealed Schwann cells surrounded by abundant myxoid stroma. Immunohistochemical examination showed strong and diffuse markers of S-100 protein. Ultrastructural examination showed Schwann cells in the core areas with traces of intracytoplasmic membranes and foci of redundant basement membrane. The pain symptoms, the pattern of intraneural neoplastic growth with marked peritumoral edema, vascular hyalinization, and immunohistochemical reactivity for S-100 protein in Schwann cells in lesion cores suggested the diagnosis of schwannomatosis. Pharmacological pain treatment achieved partial remission of pain...

Retrolabyrinthine approach for cochlear nerve preservation in neurofibromatosis type 2 and simultaneous cochlear implantation

Few cases of cochlear implantation (CI) in neurofibromatosis type 2 (NF2) patients had been reported in the literature. The approaches described were translabyrinthine, retrosigmoid or middle cranial fossa. OBJECTIVES: To describe a case of a NF2- deafened-patient who underwent to vestibular schwannoma resection via RLA with cochlear nerve preservation and CI through the round window, at the same surgical time. RESUMED REPORT: A 36-year-old woman with severe bilateral hearing loss due to NF2 was submitted to vestibular schwannoma resection and simultaneous CI. Functional assessment of cochlear nerve was performed by electrical promontory stimulation. Complete tumor removal was accomplishment via RLA with anatomic and functional cochlear and facial nerve preservation. Cochlear electrode array was partially inserted via round window. Sound field hearing threshold improvement was achieved. Mean tonal threshold was 46.2 dB HL. The patient could only detect environmental sounds and human voice but cannot discriminate vowels, words nor do sentences at 2 years of follow-up. CONCLUSION: Cochlear implantation is a feasible auditory restoration option in NF2 when cochlear anatomic and functional nerve preservation is achieved. The RLA is adequate for this purpose and features as an option for hearing preservation in NF2 patients...

Neurofibromatose 2: opções de restauração auditiva / Neurofibromatosis 2: hearing restoration options

Neurofibromatose 2 (NF2) é uma doença autossômica dominante que, invariavelmente, cursa com surdez. Restauração auditiva pode ser realizada por meio do implante coclear (IC) ou implante auditivo de tronco encefálico (ABI). OBJETIVO: Avaliar resultados auditivos de IC e ABI em pacientes com NF2 e revisão de literatura. MÉTODO: Foram avaliados prospectivamente quatro pacientes com NF2 submetidos à exérese tumoral e implantação de IC ou ABI ipsilateral simultâneo, dependendo se o nervo coclear foi preservado ou não cirurgicamente. São descritos resultados auditivos em longo prazo (12-48 meses). RESULTADOS: Todos pacientes implantados obtiveram percepção sonora, com melhora dos limiares tonais. A paciente com IC não discrimina vogais nem sentenças. Os três pacientes com ABI apresentam discriminação média de vogais de 70% e teste 4-choice 86%. Um paciente não discrimina sentenças. Os outros dois discriminam 100% de sentenças em formato fechado e em formato aberto 10% e 20%. CONCLUSÃO: A escolha do tipo de implante usado na restauração auditiva de portadores NF2 dependerá da preservação anatômica e funcional do nervo coclear na cirurgia de ressecção tumoral. Embora nossa experiência mostre o contrário, a literatura mostra que, se essa condição for alcançada, IC fornecerá melhores resultados auditivos. Caso contrário, ABI trará maiores benefícios.

Neurofibromatosis 2 (NF2) is an autosomal dominant disease in which hearing loss is predominant. Auditory restoration is possible using cochlear implants (CI) or auditory brainstem implant (ABI). OBJECTIVE: To assess the auditory results of CI and ABI in NF2 patients and review the literature. METHODS: Four NF2 patients were prospectively evaluated. They were submitted to tumor resection followed by ipsilateral CI or ABI depending on cochlear nerve preservation. Long term auditory results were described for CI (12 months) and ABI (48 months). RESULTS: All patients achieved auditory perception improvements in their hearing thresholds. The CI patient does not recognize vowels or sentences. The 3 ABI patients discriminate 70% of vowels and 86% in the 4-choice test. One of them does not recognize sentences. The other two recognize 100% of closed sentences and 10% and 20% of open sentences. CONCLUSION: The choice of implant type to restore hearing to NF2 patients will relay on anatomical and functional cochlear nerve preservation during tumor resection surgery. Although our experience was different, the literature shows that if this condition is achieved, CI will offer better auditory results. If not, ABI is recommended.

Diagnóstico por neuroimagen de Neurofibromatosis tipo 2. Reporte de un caso clínico / Diagnostic imaging of neurofibromatosis type 2. Report of a case

La neurofibromatosis tipo 2, es una patología poco frecuente caracterizada por presentar tumores cerebrales de tipo benigno los cuales están centralmente localizados. Debido a que crecen lentamente, éstos pueden estar inertes durante muchos años antes de empezar a presentar síntomas. La presencia de schwannomas vestibulares bilaterales o unilaterales, es el patrón médico para diagnosticar la NF2 acompañándose también de meningioma, glioma y cataratas subcapsulares. Presentamos el caso clínico de una paciente de 80 años de sexo femenino que presenta un cuadro clínico de 4 meses de evolución de inicio progresivo, caracterizado por cefalea tipo opresiva en región frontal, pérdida paulatina de la audición, tinnitus, dismetría, déficit motor, paraparesias, estados de confusión, acompañados de náuseas y vómitos en varias oportunidades. Se realizaron estudios de imágenes donde la TAC reportó masa tumoral frontal izquierda, lesión mixta en fosa posterior derecha e hidrocefalia supratentorial con edema transependimario. La RMN reportó imagen compatible con meningioma de la fosa cerebral izquierda anterior y neurinoma acústico derecho con importante efecto de masa sobre el tronco encefálico y cuarto ventrículo. Se decide realizar la resección de ambos tumores en dos tiempos quirúrgicos; finalmente el examen de patología reporta meningioma y schwannoma acústico.

Neurofibromatosis type 2 is a pathology characterized by presenting benign cerebral tumors centrally located. Due to slow growing, they may be inert for many years before symptoms begin. The presence of bilateral or unilateral vestibular schwannomas, is the patron to diagnose NF-2 also see a meningioma, glioma and subcapsular cataracts. We enter the clinical case of a 80 year-old patient, received presenting a clinical diagnosis of 4 months of evolution of progressive start, characterized by oppressive migraine in the front-end area, progressive lost of the hearing, tinnitus, dysmetria, motor deficit, paraparesias, lost of the memory, states of confusion, accompanied by nauseate and vomits in different opportunities. Imaging studies were performed where the TAC reported left frontal tumor, and mixed lesion in right posterior fossa, supratentorial hydrocephalus edema reported transependimario and MRI image compatible with meningioma of the left anterior cranial fossa with significant mass effect and right acoustic neuroma with significant mass effect on the brain stem and fourth ventricle. It was decided to perform resection of both tumors in two surgical sessions; finally the pathology is confirmed compatible with meningioma and acoustic neuroma.

Shwannoma unilateral do acústico em criança sem associação com neurofibromatose / Unilateral acoustic schwannoma in child without neurofibromatosis

Schwannomas do acústico representam 8% dos tumores intracranianos primários do adulto, havendo apenas 20 casos relatados em crianças sem associação com neurofibromatose. Aqueles que ocorrem em crianças geralmente são ricamente vascularizados, sendo preconizada por alguns autores a embolização da lesão antes da cirurgia. Relata-se e discute-se o terceiro caso da literatura nacional de schwannoma do acústico em uma criança sem associação com neurofibromatose. Paciente feminina, de 10 anos, apresentando ataxia, cefaleia e diminuição da acuidade auditiva à direita. A ressonância magnética (RM) mostrou massa tumoral no ângulo pontocerebelar direito sugestiva de meduloblastoma/ependimoma. A análise histopatológica do espécime cirúrgico fez o diagnóstico de schwannoma do acústico. Na investigação clínica, a criança não apresentava neurofibromatose. Embora seja raro em crianças sem associação com neurofibromatose, a hipótese de schwannoma não deve ser descartada em casos de diminuição da acuidade auditiva com RM demonstrando massa tumoral no ângulo pontocerebelar.

Acoustic schwannomas account for 8% of primary adult intracranial tumors, and there are only 20 cases reported in children without neurofibromatosis. These tumors are extremely vascular in children, and some authors recommend a preoperative angiographic embolization. We report and discuss the third case of the national literature of an acoustic schwannoma in a child without neurofibromatosis. 10 year-old female, with ataxia, headache and deafness in the right ear. Magnetic resonance imaging (MRI) revealed a tumor mass in the right cerebellopontine angle suggestive of medulloblastoma/ependimoma. The histopathological analyses diagnosed an acoustic schwannoma. None clinical evidence of neurofibromatosis was seen. Although schwannoma is rare in children without neurofibromatosis, this hypothesis can not be dismissing in patients with deafness and MRI reveling tumor mass in the cerebellopontine angle.

Merlin; NF2 Tumor Suppressor and Regulator of Receptor Distribution/Signaling / 대한이비인후과학회지

Acoustic tumor is the most common tumor originating from cerebellopontine angle. Acoustic tumor is benign and main origin of this tumor is vestibular nerve. This tumor arises in Schwann cell (SC) and is encapsulated. Recently, the tumor is called vestibular schwannoma (VS). VS is classified to two type by epidemiology, sporadic form and neurofibromatosis type 2 (NF2). NF2 is autosomal dominant inherent disorder. This tumor is characterized bilateral VS, brain tumors such as meningioma and ependymoma, and spinal or cranial nerve schwannoma. Genetic studies suggested that NF2 is caused by abnormality or mutation of NF2 gene in chromosome 22q12. Both of them are known to develop the tumor by mutation of NF2 gene. Merlin is the cytoskeletal protein product of the NF2 tumor suppressor gene that mediates cell to cell contact information to regulate SC proliferation and survival. And merlin is highly homologous to ERM proteins. Merlin function is regulated by its conformation, adopting an inactive, growth permissive state following serine 518 (S518) phosphorylation. In NF2 patients, the precise mechanisms of developing the VS are unclear. But, the abnormalities of merlin are confirmed by many studies. And now, a lot of research about merlin function is progressing. In this study, the author would introduce about merlin (structure, function, molecular pathway, tumorigenesis and regulation) which leads to VS and molecular studies about merlin, and suggest the future direction of research.

Case of Breast Cancer in a Neurofibromatosis 2 Patient / 대한내과학회지

Neurofibromatosis 2 is a multiple neoplasia syndrome that is caused by mutations in the NF2 tumor suppressor gene on chromosome 22q12. Bilateral vestibular nerve schwannomas are the distinctive feature of neurofibromatosis 2. There have been no reported cases of breast cancer in patients with neurofibromatosis 2. We recently encountered a case of breast cancer in a 46-year-old woman with neurofibromatosis 2. She had had a palpable right beast mass for the previous year andtinnitus in her left ear for the previous 6 months. She was diagnosed with breast cancer (invasive ductal carcinoma) with metastasis to the lungs, bones and stomach. MRI of the brain revealed nodules in both internal auditory canals, indicating that she was suffering from neurofibromatosis 2. After radiation therapy for compression fractures in T8 and L1, and one cycle of chemotherapy, the patient died of febrile neutropenia and pneumonia.

Mixed schwannoma with meningioma of the trigeminal nerve.

Mixed tumors composed of schwannoma and meningiomas are extremely rare and are usually associated with neurofibromatosis-2 (NF-2). So far, all the cases reported have involved the cerebello-pontine angle. Only two cases did not have a clear association with NF-2. We report a mixed tumor comprising of meningioma admixed with schwannoma in a 33-year-old male with bilateral trigeminal nerve schwannomas. The patient did not fit the existing diagnostic criteria of NF-2. The relevant literature, along with diagnostic criteria for NF-2 is discussed.

Intraneural Perineurioma in the Tongue: A Case Report

We report a case of an intraneural perineurioma that developed in an unusual location, the tongue. A 16-year-old male presented with a 1 cm sized protruding submucosal mass in his tongue without any sensory or motor signs or symptoms. The mass was excised. The mucosa was intact, with an ill-defined firm mass measuring 1.0 x 0.8 x 0.6 cm in the submucosa and muscle. The cut surface of the mass was pinkish gray and fibrotic. Microscopically, the mass contained tortuous and thickened peripheral nerve bundles in the submucosa, showing onion bulb like structures. The onion bulb like structures consisted of centrally located S-100 protein positive Schwann cells surrounded by Glut-1 positive perineurial cells. The FISH study did not reveal any genetic aberrations in chromosome 22.

Decompression of Internal Auditory Canal via Middle Fossa Approach in Neurofibromatosis Type II with Only Hearing Ear / 대한이비인후과학회지

Neurofibromatosis type II (NF2) is a genetic disease and is transmitted as an autosomal dominant trait. NF2 is characterized by bilateral acoustic neuroma with multiple tumors of central nervous system. Progressive hearing loss is a significant problem in patients with NF2, and hearing preservation is an important factor for choice of treatment plan, especially in a NF2 patient with only one hearing ear. We report an experience of preservation of hearing in a NF2 patient with only one hearing ear through decompression of the internal auditory canal via middle cranial fossa approach.

Multiple schwannomas / 中华骨科杂志

Objective To study the clinical features and treatment of multiple schwannomas (neurilemmomas). Methods 9 patients with multiple schwannomas treated with surgery from 1975 to 1999 were reviewed retrospectively. Results In 7 of the 9 cases of schwannomas, the number of tumor lesions was seen more than that diagnosed preoperatively. All the patients had surgical resection; 5 had enucleation and 4 had tumors excised with the invovled nerve. Recurrence occured in 4 patients. Conclusion Because of the difficulty in predetermination of the exact lesional number, thoroughly preoperative examination including MRI is nessesary. Enucleation is recommended to those tumors involving important nerves. There is a high rate of recurrence.