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OBJECTIVES: To examine the epidemiology, subtypes, trends over time, and predictive factors for recurrence and malignant transformation of sinonasal papillomas. METHODS: A retrospective chart review of 118 patients with sinonasal papillomas from 2009 to 2019 was conducted at the University of California, Los Angeles. This study is a follow-up to a previously published study from 2000 to 2009 at the same academic center. RESULTS: The mean age was at presentation was 58.5 years, with a 2:1 male to female ratio, and average follow-up of 30.1 months. The rate of recurrence after complete resection was 19% with an average of 32.6 months to recurrence. The time to recurrence followed a bimodal distribution with 57% of cases recurring within 24 months (mean = 10) and 43% from 40 to 103 months (mean = 61). The proportion of the inverted papillomas rose from 38% in 2000-2004 to 89.6% in 2015-2019. Patients presenting at a younger age had a higher chance of recurrence (mean age 52 with recurrence vs. 61 without recurrence). Age did not correlate with histopathologic transformation in surgical pathology. Furthermore, histopathological transformation did not raise the chance of recurrence. Smoking, alcohol use, chronic rhinosinusitis, and allergic rhinitis were not associated with any of the outcome measures in this study. The most significant factor predicting recurrence, beside age at presentation, was the history of two or more prior sinus surgeries for papillomas or other reasons (OR = 3.52 and 5.81). CONCLUSION: This study explored the features of sinonasal papillomas as well as the risk factors for recurrence and transformation. Younger age at presentation and two or more prior surgeries for papillomas were associated with recurrence. Time to recurrence followed a bimodal distribution, with late recurrences happenning from 40 to 103 months after surgery, emphasizing the importance of long-term follow-up for timely resection of tumors and prevention of malignancy.
Asunto(s)
Neoplasias Nasales , Papiloma Invertido , Neoplasias de los Senos Paranasales , Transformación Celular Neoplásica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Nasales/epidemiología , Neoplasias Nasales/patología , Neoplasias Nasales/cirugía , Papiloma Invertido/epidemiología , Papiloma Invertido/patología , Papiloma Invertido/cirugía , Neoplasias de los Senos Paranasales/epidemiología , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVES/HYPOTHESIS: To determine the impact of vestibular schwannoma (VS) position relative to the internal auditory canal (IAC) on postoperative facial nerve function and extent of surgical resection. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review of patients undergoing resection of large (≥25 mm) VSs. Outcome measures included early (≤1 month) facial function, long-term (≥1 year) facial function and extent of resection. Tumor measurements included the greatest dimension, dimension anterior to the IAC axis, dimension posterior to the IAC axis, and a ratio of posterior-to-anterior dimension (PA ratio). RESULTS: A total of 127 patients met inclusion criteria. In early follow-up, 60% patients had good (House-Brackmann I-II), and 40% patients had poor (House-Brackmann III-VI) facial function. In long-term follow-up, 71% patients had good, and 29% patients had poor facial function. A total of 72% of patients underwent gross total resection (GTR) of their tumors. Patients with good facial function had significantly larger PA ratios than patients with poor function both early and long term; however, greatest dimension was the more clearly significant independent predictor of facial outcomes. A larger PA ratio was observed in patients in whom GTR was achieved, but this association was potentially confounded by surgeon preferences and was not statistically significant after controlling for surgical site. CONCLUSIONS: This study demonstrates that VS position relative to the IAC axis can be used along with tumor size to predict postoperative facial outcomes. A greater proportion of tumor posterior to the IAC axis was associated with significantly better facial outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1093-1098, 2022.
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Oído Interno , Neuroma Acústico , Ángulo Pontocerebeloso/patología , Oído Interno/patología , Nervio Facial/patología , Nervio Facial/cirugía , Humanos , Neuroma Acústico/patología , Procedimientos Neuroquirúrgicos/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To identify perioperative factors that influence hospital length of stay (LOS) after resection of vestibular schwannoma (VS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary skull base referral center. PATIENTS: Patients who underwent acoustic neuroma resection between January 1, 2007 and January 1, 2014. INTERVENTIONS: Approaches used for VS resection included translabyrinthine and retrosigmoid. MAIN OUTCOME MEASURES: LOS and several perioperative factors that may delay hospital discharge were examined. Factors included were patient demographics (age and sex), tumor characteristics (size), surgical factors (operative time, approach, revision surgery, date of surgery), and immediate postoperative factors (presence of vertigo or immediate postoperative complications). RESULTS: Two hundred eighty-eight patients underwent VS resection during the study period. Two hundred fifty-five patients had complete charts available for review. LOS ranged from 1 to 10 days with an average of 2.66 days and mode of 2 days. One hundred thirty-one patients were admitted for ≤2 days and 124 patients stayed longer. Of the perioperative factors examined with univariate analysis, female gender (pâ=â0.0266) and presence of postoperative vertigo (pâ<â0.0001) were statistically significant factors associated with LOS >2 days. On multivariate logistic regression analysis with odds ratios (OR), older patient age (ORâ=â1.028, pâ=â0.0177), female gender (ORâ=â1.810, pâ=â0.0314), longer operative time (ORâ=â1.424, pâ=â0.0007), and presence of postoperative vertigo (ORâ=â4.904, pâ<â0.0001) carried a statistically significant increased odds toward a LOS >2 days. CONCLUSIONS: VS surgery and postoperative care can be carried out efficiently with a minimal LOS. Identifying factors that may prolong LOS may help the operative team anticipate and address needs to optimize LOS.
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Tiempo de Internación , Neuroma Acústico/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Tempo Operativo , Adolescente , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Reoperación , Estudios Retrospectivos , Adulto JovenRESUMEN
A number of studies of predictive factors for lymph node metastasis in papillary thyroid microcarcinoma have been published. We conducted a systematic meta-analysis of some of these studies, and we present our findings herein. We searched the PubMed database and found 13 eligible studies and case series of papillary thyroid microcarcinoma that were published in the English-language literature from January 2001 through December 2012, and we analyzed their findings. The most commonly investigated tumor characteristics associated with lymph node metastasis were size, multifocality, capsular invasion, and lymphovascular invasion. With regard to the risk of developing lymph node metastasis, patients with larger tumors had a 1.93 greater chance (95% confidence interval [CI]: 1.36 to 2.73, p < 0.001), those with multifocal tumors had a 3.03 greater chance (95% CI: 2.05 to 4.47; p < 0.001), those with capsular invasion had a 4.13 greater chance (95% CI: 2.40 to 7.10; p < 0.001), and those with lymphovascular invasion had a 2.76 greater chance (95% CI: 1.50 to 5.07; p = 0.005). We conclude that patients with larger and/or multifocal papillary thyroid microcarcinomas and tumors associated with capsular or lymphovascular invasion have a significantly greater risk of developing lymph node metastasis.
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Carcinoma Papilar/patología , Ganglios Linfáticos/patología , Neoplasias de la Tiroides/patología , Carcinoma Papilar/secundario , Humanos , Metástasis Linfática , Cuello , Invasividad Neoplásica , Factores de RiesgoAsunto(s)
Conducto Auditivo Externo/patología , Neuroma Acústico/patología , Hueso Temporal/patología , Craneotomía , Conducto Auditivo Externo/cirugía , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neuroma Acústico/cirugía , Hueso Temporal/cirugía , Resultado del TratamientoRESUMEN
Neuroglobin (Ngb) is an oxygen-binding protein with a demonstrated role in endogenous neuroprotective mechanisms. It has been shown to function as a scavenger for reactive oxidizing species thereby assisting in cellular defense against oxidative stress. In the present study, we characterized the presence of Ngb in the human cochlea. Immunohistochemical staining was performed on formalin fixed celloidin human cochlea sections obtained from human temporal bones, using affinity purified polyclonal antibodies against Ngb. Thirty-six temporal bones were analyzed, 15 with normal otologic histories and 21 diagnosed with different inner ear pathologies. Ngb immunoreactivity (Ngb-IR) was consistently expressed in the neurons of spiral ganglia (SG) and supporting cells of the organ of Corti. There was a significant decrease of Ngb-IR in SGNs from specimens with inner ear pathologies when compared to normal specimens. In contrast, Ngb-IR in the organ of Corti did not show significant changes between pathological and normal specimens. The differential pattern of Ngb expression in these cochlear structures suggests that Ngb may participate in defense mechanisms in inner ear pathologies where oxidative stress is involved.
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Cóclea/metabolismo , Globinas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Cóclea/citología , Cóclea/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neuroglobina , Especificidad de la EspecieRESUMEN
OBJECTIVE: To compare outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL) treated with intratympanic (IT) dexamethasone (DEX) at either 10 mg/mL or 24 mg/mL. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Thirty-seven adults with ISSNHL. INTERVENTIONS: In addition to concurrent prednisone taper, patients received a series of IT DEX injections for 2 weeks with either 10 mg/mL or 24 mg/mL. MAIN OUTCOME MEASURE: Greater than 30-dB improvement in pure-tone average (PTA). RESULTS: Baseline characteristics were similar between groups. Mean follow-up was 10 weeks. Ten (53%) of 19 patients treated with 24 mg/mL had greater than 30-dB improvement in PTA compared with 3 (17%) of 18 treated with 10 mg/mL (p = 0.0382, Fisher's exact test). There was a trend toward improved word recognition score outcome with 24 mg/mL. The interval between onset and initiation of IT DEX significantly affected outcome, with earlier treatment resulting in greater improvement in PTA and word recognition score. Multivariate logistic regression confirmed that IT DEX dose and interval to starting treatment were both independent predictors of PTA outcome. Change in PTA was not significantly affected by age, sex, pretreatment hearing levels, or concurrent treatment with hyperbaric oxygen. CONCLUSION: To our knowledge, this is the first demonstration of superiority of IT DEX at 24 mg/mL for the treatment of ISSNHL, with significantly better recovery of PTA. Our data suggest that treatment should be initiated as soon as possible. A prospective randomized trial to confirm the optimal dose is warranted.
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Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Súbita/tratamiento farmacológico , Membrana Timpánica , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Audiometría de Tonos Puros , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Femenino , Humanos , Oxigenoterapia Hiperbárica , Inyección Intratimpánica , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Percepción del Habla , Prueba del Umbral de Recepción del Habla , Resultado del TratamientoRESUMEN
OBJECTIVE: Using three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI), our goal was to correlate quantifiable measures of endolymphatic hydrops (EH) with auditory function in the setting of Meniere's disease (MD). MATERIALS AND METHODS: Forty-one ears were analyzed in 21 subjects (12 ears with MD, 29 without MD). Vestibular endolymphatic space size measurements obtained with two different techniques were referenced against clinical data. RESULTS: EH was better evaluated on 3D maximum intensity projections (MIPs) than on two-dimensional (2D) images. Using MIPs, quantitative assessments EH correlated with severity of hearing impairment. CONCLUSION: 3D MIPs were superior to 2D images for evaluating EH in the setting of MD.
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Oído Interno/patología , Hidropesía Endolinfática/patología , Audición/fisiología , Imagen por Resonancia Magnética/métodos , Enfermedad de Meniere/patología , Adulto , Anciano , Oído Interno/fisiopatología , Hidropesía Endolinfática/fisiopatología , Femenino , Pruebas Auditivas , Humanos , Imagenología Tridimensional/métodos , Masculino , Enfermedad de Meniere/fisiopatología , Persona de Mediana EdadRESUMEN
OBJECTIVES: The objective is to present clinical outcomes of subglottic and tracheal stenosis treated by flexible bronchoscopic delivery of carbon dioxide (CO2) laser via laryngeal mask airway (LMA). METHODS: All consecutive, nontracheotomy dependent cases of subglottic and tracheal stenosis treated endoscopically over a 4-year period were retrospectively reviewed. The surgical approach consisted of radial incisions using a flexible fiber-based CO2 laser, balloon dilation, and topical application of mitomycin C. Ventilation during the procedure occurred through the LMA, and the CO2 laser fiber was delivered through the working channel of a flexible bronchoscope passed through the LMA. Number of dilations, period between dilations, and operative times were reviewed. RESULTS: Eleven patients who underwent airway intervention during the study period were identified. Average follow-up was 28 months. Etiologies of airway stenosis included intubation injury (6), idiopathic (4), or autoimmune disease (1), requiring an average of 1.3, 1.5, and 3 dilations, respectively. Average operative time was 67 minutes. Autoimmune etiology correlated with more frequent dilations. CONCLUSION: LMA is an effective way to manage ventilation while simultaneously allowing unencumbered flexible bronchoscopic access for laser surgery, balloon dilation, and mitomycin C application for airway stenosis. Long-term success in treating stenosis is achievable using this technique.
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Manejo de la Vía Aérea/métodos , Broncoscopía , Máscaras Laríngeas , Laringoestenosis/terapia , Terapia por Láser , Estenosis Traqueal/terapia , Adulto , Anciano , Alquilantes/administración & dosificación , Dilatación , Femenino , Humanos , Laringoestenosis/etiología , Laringoestenosis/patología , Láseres de Gas/uso terapéutico , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Estudios Retrospectivos , Estenosis Traqueal/etiología , Estenosis Traqueal/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Sinonasal melanoma (SNM) is a rare cancer with extremely poor prognosis. Detecting melanoma on frozen section has historically been considered to be unreliable. A review of cases of sinonasal melanoma treated at a tertiary referral center was conducted to analyze treatment outcomes and identify prognostic factors for survival. In addition, an investigation was performed correlating sinonasal melanoma on frozen section and permanent analysis. METHODS: An institutional review board-approved search of the pathology database for cases of primary sinonasal melanoma treated between 1991 and 2011 was performed. Fourteen cases were identified and the medical charts were reviewed. RESULTS: Eleven patients had tumors arising from the nasal cavity, 2 arose from the maxillary sinus, and 1 from the ethmoid sinuses. Mean duration of follow-up was 20.7 (range, 1.4 to 84.5) months. Overall, 5-year recurrence-free survival and overall survival was 23% and 35%, respectively. All patients had surgical resection with intent for cure and all but 1 patient had adjuvant therapy. Survival analysis showed that positive margin status (log rank p = 0.031) and the presence of perineural/lymphovascular invasion (log rank p = 0.021) negatively affected recurrence-free survival and overall survival, respectively. Nine cases had evaluation of intraoperative frozen sections with 32 total sections submitted for analysis. When compared with final pathology, there was a 0% false negative rate. CONCLUSION: Based on this series, positive margins and the presence of perineural/lymphovascular invasion are negative predictors of survival. In addition, intraoperative frozen section analysis of sinonasal mucosal melanoma correlates well with final pathology.
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Neoplasias del Seno Maxilar/diagnóstico , Melanoma/diagnóstico , Anciano , Femenino , Estudios de Seguimiento , Humanos , Vasos Linfáticos/patología , Linfocitos/inmunología , Masculino , Neoplasias del Seno Maxilar/patología , Neoplasias del Seno Maxilar/cirugía , Melanoma/patología , Melanoma/cirugía , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Recurrencia , Factores de Riesgo , Atención Terciaria de Salud , Resultado del TratamientoRESUMEN
Methadone, a long-acting opiate agonist, and naltrexone, an opiate receptor antagonist, are both commonly used to treat patients with morphine and heroin addiction. We present a rare case of methadone-induced persistent bilateral sensorineural hearing loss (SNHL) after chronic naltrexone use and review opioid-induced hearing loss in the literature. Methadone-induced hearing loss has been described previously described in the literature with all reported cases recovering functional hearing. This is the first description of persistent bilateral severe SNHL following methadone ingestion. We propose opiate receptor sensitization from prolonged naltrexone use as a predisposing factor for methadone-induced irreversible cochlear injury.
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Pérdida Auditiva Bilateral/inducido químicamente , Pérdida Auditiva Sensorineural/inducido químicamente , Metadona/efectos adversos , Narcóticos/efectos adversos , Humanos , Masculino , Metadona/administración & dosificación , Narcóticos/administración & dosificación , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Glutamate plays an important role in the central nervous system as an excitatory neurotransmitter. However, its abundance can lead to excitotoxicity which necessitates the proper function of active glutamate transporters. The glutamate-aspartate transporter (GLAST) has been shown to exist and function within non-human cochlear specimens regulating the inner ear glutamate concentration. In this study, we examined human cochleas from formalin-fixed celloidin-embedded temporal bone specimens of three different types of patients (Meniere's disease, normal controls, and other otopathologic conditions) and examined the differential expression of GLAST in the spiral ligament of the basal, middle, and apical turns of the cochlea. Immunohistochemical staining was performed with polyclonal antibodies against GLAST and image analysis was carried out with the Image J analysis software. In contrast to other studies with non-human specimens, GLAST was expressed in the spiral ligament fibrocytes but was not detected in the satellite cells of the spiral ganglia or supporting cells of the Organ of Corti in the human cochlea. Our data also showed that GLAST expression significantly differs in the basal and apical turns of the cochlea. Lastly, post-hoc analysis showed a difference in the GLAST immunoreactive area of patients with Meniere's disease when compared to that of patients with other otopathologic conditions-such as presbycusis or ototoxicity. These results may potentially lead to further understanding of different disease states that affect hearing.
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Sistema de Transporte de Aminoácidos X-AG/metabolismo , Cóclea/metabolismo , Regulación de la Expresión Génica , Enfermedad de Meniere/patología , Anciano , Análisis de Varianza , Biopsia , Femenino , Humanos , Masculino , Ganglio Espiral de la Cóclea/metabolismo , Ganglio Espiral de la Cóclea/patología , Hueso Temporal/metabolismo , Hueso Temporal/patología , Nervio Vestibular/metabolismo , Nervio Vestibular/patologíaRESUMEN
BACKGROUND: Sinonasal papillomas are benign epithelial neoplasms arising from Schneiderian mucosa. The three subtypes, exophytic, oncocytic, and inverted (inverted papilloma [IP]), should be distinguished from one another histopathologically. This study (1) highlights the histopathological and clinical differences between the Schneiderian papilloma subtypes and (2) identifies clinical features that potentially predict papilloma subtypes. METHODS: A retrospective review was performed of patients with Schneiderian papillomas over an 11-year period. RESULTS: Seventy patients with sinonasal papillomas who underwent sinus surgery were identified. There were 50 (71%) male and 20 (29%) female subjects diagnosed at an average age of 53 years (range, 13-80 years). Exophytic (n = 25), oncocytic (n = 9), and IP (n = 37) were identified. IP was associated with transformation into squamous cell carcinoma in three (8%) cases and dysplasia in three (8%) cases. Neither oncocytic nor exophytic subtypes were associated with dysplasia or malignancy. On multivariate analysis of potential predictors of papilloma subtype, history of chronic rhinosinusitis (CRS) and location of papilloma were significantly associated with papilloma subtype. Using classification and regression tree model, papilloma subtypes can be predicted based on presence or absence of CRS and papilloma location with nominal 82.4% accuracy. CONCLUSION: The inverted and exophytic type are the most common sinonasal papillomas, with the inverted type having an 8% rate of malignant transformation in this study. In contrast, the oncocytic type was not associated with dysplasia or malignancy in our series despite reports in the literature indicating malignant potential. History of CRS and papilloma location can provide clues to the histological subtype, which is important for surgical planning and patient counseling.
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Neoplasias del Seno Maxilar/patología , Neoplasias del Seno Maxilar/cirugía , Papiloma/patología , Papiloma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Transformación Celular Neoplásica/patología , Células Epiteliales/patología , Femenino , Humanos , Masculino , Neoplasias del Seno Maxilar/clasificación , Persona de Mediana Edad , Mucosa Nasal/patología , Neoplasias Nasales/patología , Neoplasias Nasales/cirugía , Papiloma/clasificación , Papiloma Invertido/patología , Papiloma Invertido/cirugía , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Actinomycosis is a rare anaerobic bacterial infection typically caused by Actinomyces israelii. Although part of normal flora in the oral cavity, and respiratory and digestive tracts, A israelii can give rise to pathologic infections most commonly reported in the oral cavity from odontogenic causes. We present a rare case of invasive actinomycosis presenting with extensive midface destruction involving the maxilla and paranasal sinuses, with mucosal necrosis mimicking an aggressive neoplasm. The diagnosis is usually reached only after histopathologic analysis showing characteristic sulfur granules with filamentous gram-positive, non-acid-fast bacteria. We review the literature on its epidemiology, clinical presentation, diagnosis, treatment, and prognosis.
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Actinomicosis/diagnóstico , Actinomicosis/tratamiento farmacológico , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Enfermedades de los Senos Paranasales/diagnóstico , Enfermedades de los Senos Paranasales/tratamiento farmacológico , Enfermedades de los Senos Paranasales/microbiología , Penicilina G/uso terapéutico , Adyuvantes Farmacéuticos/uso terapéutico , Diagnóstico Diferencial , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Probenecid/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To review the literature on glossopharyngeal schwannomas with a focus on clinical presentation, radiologic/audiologic characteristics, and management options, and to propose a mechanism explaining the nature of vestibulocochlear dysfunction seen with these tumors. STUDY DESIGN: Contemporary review. METHODS: English literature search for cases of primary isolated glossopharyngeal schwannomas and chart review of two new cases. RESULTS: A total of 42 glossopharyngeal schwannoma cases between 1908-2008 were reviewed. Of these 84% presented with vestibulocochlear symptoms whereas only 30% presented with glossopharyngeal symptoms. Tumors can occur anywhere along the CNIX; however, the majority of symptomatic cases are intracranial/intraosseous, which present with vestibulocochlear dysfunction. Reviewed cases typically described the caliber of CNVII and VIII on CT/MRI as normal. We present a case where notching and displacement of CNVIII by the tumor can be appreciated on MRI, allowing for the first correlation between clinical symptoms and imaging findings. Mid frequency SNHL was prevalent in contrast to the high-frequency pattern typical of vestibular schwannomas. Tonotopic studies of CNVIII mapped low-to-mid frequency fibers along the posterior medial surface corresponding to the area of greatest compression by glossopharyngeal schwannomas. CONCLUSION: Glossopharyngeal schwannomas usually present with vestibulocochlear rather than glossopharyngeal symptoms, likely due to CNVIII compression and displacement by tumor, which can be better appreciated with modern imaging. The tumor's location posterior and medial to CNVIII combined with the complex CNVIII tonotopic organization may account for the preferential mid-frequency hearing loss seen in these patients.