Audrey P. Calzada

Otolithic membrane damage in patients with endolymphatic hydrops and drop attacks.

Objectives 1. Evaluate the otolithic membrane in patients with endolymphatic hydrops (EH) and vestibular drop attacks (VDA) undergoing ablative labyrinthectomy. 2. Correlate intraoperative findings to archival temporal bone specimens of patients with EH. Study Design Retrospective case review. Setting Tertiary referral center. Specimen Source 1. Patients undergoing labyrinthectomy for incapacitating Ménière’s disease (MD), delayed EH, VDA, or acoustic neuroma (AN) between 2004 and 2011. 2. Archival temporal bone specimens of patients with MD. Interventions Ablative labyrinthectomy. Main Outcome Measures Examination of the utricular otolithic membrane. Results The otolithic membrane of the utricle was evaluated intraoperatively in 28 patients undergoing labyrinthectomy. Seven (25%) had a history of VDA, 6 (21%) had delayed EH, 9 (32%) had MD, and 6 (21%) had AN. All patients with VDA showed evidence of a disrupted utricular otolithic membrane, whereas only 50% and 56% of patients with delayed EH and MD, respectively, demonstrated otolithic membrane disruption (p = 0.051). None of the patients with AN showed otolithic membrane disruption (p = 0.004). The mean thickness of the otolithic membrane in 5 archival temporal bone MD specimens was 11.45 micrometers versus 38 micrometers in normal specimens (p = 0.001). Conclusion The otolithic membrane is consistently damaged in patients with VDA. In addition, there is a significantly higher incidence of otolithic membrane injury in patients with MD and delayed EH compared with patients without hydrops, suggesting that the underlying pathophysiology in VDA results from injury to the otolithic membrane of the saccule and utricle, resulting in free-floating otoliths and atrophy.

Adenoid cystic carcinoma of the airway: a 30-year review at one institution

PURPOSE The purpose of the study was to evaluate the treatment results of adenoid cystic carcinoma (ACC) of the airway at a single institution during a 30-year period. MATERIALS AND METHODS All cases of ACC of the airway over a 30-year period at one tertiary care institution were reviewed retrospectively. The demographics, treatment modalities, pathologic characteristics, and outcomes were evaluated. RESULTS Eleven patients were treated for ACC of the airway with an age range of 25 to 72 years (median, 48 years). Six patients presented with ACC in the larynx, and 5 patients had ACC of the trachea. All patients underwent surgical excision and radiation; 9 of 11 patients had postoperative external beam radiation, 1 patient had preoperative external beam radiation, and the remaining patient had postoperative neutron beam therapy. Four patients with tracheal ACC and none with laryngeal ACC had microscopic or grossly positive margins after surgery (P = .048). Eighty percent of patients had perineural invasion on pathology. Two patients with tracheal ACC had local recurrence of disease, which occurred at 1 and 10 months postoperatively. One patient with laryngeal ACC died of distant metastatic disease at 16 months. Follow-up varied from 4 to 168 months (median, 31 months). CONCLUSIONS We report high disease-free survival rates for ACC of the airway in patients who underwent definitive surgical resection followed by postoperative radiation. There is a higher risk for local recurrence and positive surgical margins with distal tracheal location. Distant disease ultimately determines survival.

Cochlin expression in vestibular endorgans obtained from patients with Meniere’s disease

The distribution of cochlin and its associated basement membrane proteins (collagen IV, collagen II, laminin-β2, and nidogen-1) were evaluated in the vestibular endorgans of subjects with Meniere’s disease and compared with normal specimens. Cochlin mRNA expression in vestibular endorgans from Meniere’s disease specimens was also investigated. Specimens were obtained from patients who had Meniere’s disease and who were undergoing ablative labyrinthectomy. Control specimens were obtained both from autopsy specimens with documented normal audiovestibular function and from patients undergoing labyrinthectomy for acoustic neuroma excision. In the normal control specimens, cochlin immunoreactivity was found evenly distributed in the stroma of the cristae ampullaris and maculae of the utricle. In Meniere’s specimens, cochlin immunoreactivity was markedly increased; this was associated with an increase in cochlin mRNA expression as shown by real-time reverse transcription with the polymerase chain reaction. Collagen IV and laminin-β2 immunoreactivity was significantly decreased in Meniere’s specimens. Nidogen-1 and collagen II immunoreactivity was unchanged in Meniere’s specimens when compared with normal samples. Cochlin upregulation has been implicated in the hereditary audiovestibulopathy, DFNA9. The increased expression of cochlin and decreased expression of collagen IV and laminin in Meniere’s disease are suggestive that the overexpression of cochlin contributes to the dysfunctional inner ear homeostasis seen in this disease.

Poorly differentiated adenocarcinoma arising from a cervical bronchial cyst

Bronchogenic cysts with malignant change are rarely reported. We describe a case of poorly differentiated adenocarcinoma arising from a cervical bronchial cyst in a patient presenting with a thyroid mass, cervical lymphadenopathy, and initial biopsy suggestive of papillary thyroid carcinoma. The clinical presentation, intraoperative findings, radiographic images, and pathology slides are presented. To our knowledge, this is the first report of a poorly differentiated adenocarcinoma arising from a bronchial cyst in the cervical region.

Cerebellopontine angle and intracanalicular masses mimicking vestibular schwannomas.

Objective To describe the clinical and radiographic characteristics in a series of patients with non-vestibular schwannoma cerebellopontine angle (CPA) and intracanalicular (IAC) masses, who underwent microsurgery for presumed vestibular schwannoma (VS). Study Design Retrospective case series. Setting Tertiary neurotologic referral center. Patients One thousand five hundred ninety-three patients underwent microsurgery for apparent VS from 2002 to 2013. Of these, 53 patients (3%) were discovered to have a diagnosis other than VS. Interventions Middle fossa, translabyrinthine, and retrosigmoid craniotomy. Main Outcome Measures Clinical presentation, radiologic analysis, and histopathology examination. Results There were 17 facial schwannomas, 15 meningiomas, 9 hemangiomas, 6 lipochoristomas, 3 inflammatory reactions, and one each of lymphoma, glial heterotopia, solitary fibrous tumor, ependymoma, and a non-diagnostic mass. Excluding facial schwannomas, 23 cases were misdiagnosed as VS in the first half of the study period, compared to only 15 cases in the latter half (p = 0.09). Ninety-six percent of patients presented with some combination of sensorineural hearing loss, balance disturbance, and tinnitus. In the subset of patients with available preoperative MRI scans for retrospective review, only 4 of 28 patients had radiologic findings suggestive of pathology other than VS. The most common missed radiologic diagnoses were facial schwannoma, lipochoristoma, and meningioma. Conclusion A subgroup of patients with CPA and IAC masses who present with radiologic findings diagnostic of VS will have an alternative histopathologic diagnosis. Optimal radiologic imaging and experienced interpretation can improve diagnostic accuracy. The most common tumors that mimic VS despite ideal radiologic imaging are facial schwannomas, meningiomas, and hemangiomas.

An open label study to evaluate the safety and efficacy of intratympanic golimumab therapy in patients with autoimmune inner ear disease.

Objective To evaluate the safety and efficacy of intratympanically injected golimumab (GLM), a TNF-&agr; inhibitor, as a steroid-sparing agent for patients with steroid-dependent autoimmune inner ear disease (AIED). Study Design Open label. Setting Tertiary referral center. Patients Ten patients with steroid-dependent AIED were enrolled in Stage 2. The average patient age at enrollment was 59, with an average of 12.5 years from the start of bilateral hearing loss symptoms. The average dose of daily prednisone at the start of injections was 18 mg. Intervention Intratympanic injection of GLM. Main Outcome Measure Hearing loss progression (treatment failure) was defined as either an increase in pure-tone thresholds by frequency or a decrease in word recognition score. Results There were no serious adverse events. Five of seven per-protocol subjects experienced stable pure-tone thresholds in the injected ear, whereas 4 had stable word recognition scores. Two subjects experienced an improvement in word recognition scores. The results support the hypothesis that GLM may be a promising treatment. Conclusions The TNF-&agr; inhibitor GLM stabilized hearing in 3 of 7 per-protocol subjects with AIED and allowed a complete tapering off of prednisone in those 7 subjects. Studies with larger samples sizes are warranted.

Temporal bone histopathology and immunoglobulin deposition in Sjogren's syndrome.

Hypothesis The histopathology of Sjogren’s syndrome (SS) in the human inner ear correlates with mouse models of autoimmune inner ear disease. Background SS is an autoimmune disease in which 25% of patients have sensorineural hearing loss (SNHL). The inner ear histology in a SS mouse model has shown degeneration of the stria vascularis (SV) and immunoglobulin G deposition on the basement membrane of SV blood vessels. Correlation with human temporal bone histopathology has not been addressed. Methods The histopathology and immunohistochemistry of the inner ear in 4 patients with SS is described and compared with SS mouse models. Results The histopathology of the inner ear in 3 patients with SS and SNHL showed severe loss of the intermediate cells of the SV and immunoglobulin G deposition on the basement membrane of SV blood vessels. These results parallel those of known SS mouse models. Additionally, there was shrinkage of the spiral ganglia neurons in 2 patients, whereas vestibular ganglia neurons were preserved. The fourth patient with SS and normal hearing showed only mild SV atrophy. Conclusion This is the first study describing the pathologic changes in the inner ear of 4 patients with SS. The 3 SS specimens with SNHL showed pathologic changes in the SV similar to the mouse model of autoimmune inner ear disease. Additionally, we propose that spiral ganglia neurons may be directly affected by SS pathology. These results highlight the importance of correlating the histopathology of human temporal bones with animal models to better understand inner ear disease in future research.

Methadone-induced bilateral severe sensorineural hearing loss

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.

Molecular Pathology of Head and Neck Cancer

Recent advances in molecular biology have changed the way we approach, diagnose, and treat cancers of the head and neck. Notable advances in head and neck squamous cell carcinomas (HNSCC) include the association of tumor suppressor genes with the human papilloma virus (HPV) in a subset of patients without the traditional risk factors of smoking and alcohol use. The detection of viruses in head and neck malignancies lends not only important diagnostic but also prognostic information as in the case of both HPV in oropharyngeal squamous cell carcinoma and Epstein bar virus in nasopharyngeal carcinoma. Multiple gene mutations have now been detected in various head and neck cancers, including EGFR and p16 in HNSCC and BRAF and RET gene mutations in thyroid carcinomas. Novel molecular therapies are being developed specifically targeting these genes. The future of state of the art therapy in head and neck cancer is based on further advances in molecular biology. This chapter provides an overview of the most up to date understanding of the molecular biology underlying head and neck cancer pathology. We also highlight future directions in both diagnosis and treatment of head and neck cancers based on the most recent research advances.

Cochlin Expression in Patients with Ménière Disease

Objective: 1) Determine the distribution of cochlin in the vestibular endorgans of patients with Ménière disease (MD) through quantitative immunohistochemistry and real-time PCR (RT-PCR). 2) Compare cochlin expression in the vestibular endorgans in normal vs MD patients. 3) Correlate changes in cochlin expression with underlying pathophysiology in MD. Method: Vestibular endorgans were obtained from 8 patients with MD who underwent ablative labyrinthectomy from 1997 to 2010. Control specimens were obtained from 8 patients undergoing labyrinthectomy for acoustic neuroma excision and 5 autopsy specimens with normal audiovestibular function. Quantitative immunohistochemistry of cochlin expression and RT-PCR were performed in vestibular endorgans. Results: In the normal control specimens, cochlin immunoreactivity (IR) was found evenly distributed in the stroma of the cristae ampullaris and maculae of the utricle. In the MD specimens, cochlin IR was markedly increased and intense. Diffuse cochlin precipitate was found within the stroma and basement membrane underlying the sensory epithelium in both the maculae of the utricle and the cristae ampullaris in vestibular endorgans from MD patients. Increased cochlin expression in MD specimens was confirmed with RT-PCR. Conclusion: Cochlin upregulation has been implicated in DFNA9, a hereditary audiovestibulopathy with similar symptomatology to MD. The overexpression of cochlin in vestibular endorgans of MD patients may contribute to dysfunctional inner ear homeostasis. These findings warrant the future study of cochlin and its associated extracellular matrix molecules in MD pathology.