Faculty Bibliography

Autonomic neurons and chromaffin cells, which constitute the autonomic nervous system, are derived from a common progenitor from the neural crest, and its development is controlled by a network of transcription factors, including the master regulator, Phox2b, and its downstream, Gata3. Anti-Phox2b and anti-Gata3 antibodies were applied to a total of 77 autonomic nervous system tumors, including 35 paragangliomas, 21 pheochromocytomas, 9 neuroblastomas, 4 ganglioneuroblastomas, and 8 ganglioneuromas, as well as their potential morphologic mimics, including tumors of the small round cell tumor group, neuroendocrine carcinomas of lung and gastrointestinal tract (carcinoid tumors/neuroendocrine tumors, large cell neuroendocrine carcinomas, and small cell carcinomas), Merkel cell carcinomas, benign and malignant tumors of thyroid, parathyroid, and adrenal cortex, and malignant melanomas. A variety of nonendocrine/neuroendocrine carcinomas were also studied. Gata3 expression was seen in 89% of paragangliomas, 95% of pheochromocytomas, and all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, as well as in all parathyroid tumors, a majority of urothelial and mammary carcinomas, and a subset of squamous cell carcinomas, but all other tumors were negative. Phox2b expression was seen in all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas and in 40% of paragangliomas, but pheochromocytomas and all other tumors were negative. Gata3 is a highly reliable marker for paragangliomas, pheochromocytomas, and neuroblastic tumors to distinguish from their simulators. This is an additional utility for this marker, which is used for the diagnosis of urothelial and mammary carcinomas. Phox2b is also highly specific, but its low sensitivity to paragangliomas and pheochromocytomas would limit the utility only to neuroblastic tumors.

PURPOSE OF REVIEW: Alloplasts have long been used in rhinoplasty, but their use remains controversial. Many complications are associated with their implementation in rhinoplasty. This article elucidates these complications and provides recommendations for management. RECENT FINDINGS: Several recent articles have been published presenting experience and outcomes regarding alloplast use in rhinoplasty. In many of these studies, a specific section has been dedicated to outlining the complications encountered by the authors. Oftentimes, a short summary of the complications and their management is provided. By examining the data from these studies, one can conclude several things about the management of complications involving alloplastic implants in rhinoplasty: each case must be approached on an individual basis; clinical decision-making is dictated by physical exam findings and severity of the complication; removal of the implant must be strongly considered; and revision rhinoplasty after an alloplastic complication usually necessitates an autologous graft. SUMMARY: Alloplasts continue to be a controversial option in rhinoplasty. The surgeon must be cognizant of the risks and benefits of their use. A frank preoperative discussion of possible complications with the patient is important. Additionally, prompt recognition and appropriate management of complications is essential to minimize permanent sequelae.

Fanconi anemia (FA) is a rare disorder inherited in an autosomal recessive fashion, with an estimated incidence of 1:360,000 births. Although hematologic complications are the most common manifestation of this disease, cancers, especially of the head and neck, are also prominent. The chromosomal fragility of patients with FA necessitates careful planning of therapy and monitoring, and awareness of this rare disorder is crucial to recognizing it in the clinic.

BACKGROUND: Treatment for head and neck cancer can reduce peripheral sensory input and impair oropharyngeal swallow. This study examined the effect of enhanced bolus flavor on liquid swallows in these patients. METHODS: Fifty-one patients treated for head and neck cancer with chemoradiation or surgery and 64 healthy adult control subjects served as subjects. All were randomized to receive sour, sweet, or salty bolus flavor. Patients were evaluated at 7-10 days, 1 month, and 3 months after completion of tumor treatment. Control subjects received 1 assessment. RESULTS: All bolus flavors affected oropharyngeal swallow; sour flavor significantly shortened pharyngeal transit time across all evaluations. CONCLUSIONS: Sour flavor influenced the swallow of patients treated for head and neck cancer, as well as that of control subjects in a manner similar to those with neurologic impairment observed in an earlier study. Sour flavor may improve the speed of pharyngeal transit regardless of whether a patient has suffered peripheral or central sensory damage. (c) 2012 Wiley Periodicals, Inc. Head Neck, 2013.

Sensory deprivation, such as developmental hearing loss, leads to an adjustment of synaptic and membrane properties throughout the central nervous system. These changes are thought to compensate for diminished sound-evoked activity. This model predicts that compensatory changes should be synergistic with one another along each functional pathway. To test this idea, we examined the excitatory thalamic drive to two types of cortical inhibitory interneurons that display differential effects in response to developmental hearing loss. The inhibitory synapses made by fast-spiking (FS) cells are weakened by hearing loss, whereas those made by low threshold-spiking (LTS) cells remain strong but display greater short-term depression (Takesian et al. 2010). Whole-cell recordings were made from FS or LTS interneurons in a thalamocortical brain slice, and medial geniculate (MG)-evoked postsynaptic potentials were analyzed. Following hearing loss, MG-evoked net excitatory potentials were smaller than normal at FS cells but larger than normal at LTS cells. Furthermore, MG-evoked excitatory potentials displayed less short-term depression at FS cells and greater short-term depression at LTS cells. Thus deprivation-induced adjustments of excitatory synapses onto inhibitory interneurons are cell-type specific and parallel the changes made by the inhibitory afferents.

To capture patterns in the environment, neurons in the auditory brainstem rapidly alter their firing based on the statistical properties of the soundscape. How this neural sensitivity relates to behavior is unclear. We tackled this question by combining neural and behavioral measures of statistical learning, a general-purpose learning mechanism governing many complex behaviors including language acquisition. We recorded complex auditory brainstem responses (cABRs) while human adults implicitly learned to segment patterns embedded in an uninterrupted sound sequence based on their statistical characteristics. The brainstem's sensitivity to statistical structure was measured as the change in the cABR between a patterned and a pseudo-randomized sequence composed from the same set of sounds but differing in their sound-to-sound probabilities. Using this methodology, we provide the first demonstration that behavioral-indices of rapid learning relate to individual differences in brainstem physiology. We found that neural sensitivity to statistical structure manifested along a continuum, from adaptation to enhancement, where cABR enhancement (patterned>pseudo-random) tracked with greater rapid statistical learning than adaptation. Short- and long-term auditory experiences (days to years) are known to promote brainstem plasticity and here we provide a conceptual advance by showing that the brainstem is also integral to rapid learning occurring over minutes.

Recent molecular studies have described a number of abnormalities associated with the pathogenesis of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development and may serve as prognostic factors and therapeutic targets. A better understanding of the mechanisms involved in thyroid cancer pathogenesis, will hopefully help translate these discoveries to improved patient care.

OBJECTIVES/HYPOTHESIS: To characterize the anatomic distribution of lymphatic malformations of the upper airway. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care referral center specializing in the diagnosis and treatment of vascular anomalies. METHODS: A 7-year (2004-2011) retrospective chart review of patients with lymphatic malformations was performed at a tertiary care referral center. Patients with airway lymphatic malformations were identified. The anatomic distribution of lymphatic malformations within the airway was reviewed. RESULTS: A total of 141 patients with lymphatic malformations of the upper aerodigestive tract (UADT) were studied. Of these, 15 (11%) had laryngeal (supraglottic) involvement. In all of these patients, the disease was above the true vocal folds. Seventy-four (52%) patients had involvement of 1 anatomic zone (most common was the oral cavity), and 67 (48%) had involvement of multiple zones. With regard to each zone, 105 (75%) patients had involvement of the oral cavity, 50 (36%) the oropharynx, 8 (6%) the hypopharynx, 42 (30%) the parapharynx, and 12 (9%) had retropharygeal disease (some patients had multiple zones involved). No patients were identified with glottic, subglottic, or tracheal involvement. CONCLUSIONS: Based on our large series, airway involvement in head and neck lymphatic malformations may occur at multiple sites above the glottis. A high percentage of these patients have involvement of the oral cavity (75%) and oropharynx (35%). None involve the glottis, subglottis, or trachea.

BACKGROUND:Paragangliomas are rare, vascular, and predominantly benign neoplasms of neural crest origin. They typically arise in the head and neck from the carotid body, jugulotympanic, or vagal paraganglia. Rarely, paragangliomas occur in the larynx. Only 2 cases of hypopharyngeal paraganglioma have been reported. We discuss the case of a hypopharyngeal paraganglioma and review the literature concerning laryngopharyngeal paragangliomas. METHODS AND RESULTS/RESULTS:We present the case of a woman with 2 months of dysphagia and hoarseness that was found to have a hypopharyngeal paraganglioma. The patient underwent embolization and resection of the mass via a lateral thyrotomy approach. Pathologic analysis and selective staining confirmed the presence of a paraganglioma. CONCLUSIONS:Proper histopathologic identification of these tumors is tantamount to guiding treatment. The preferred operative approach is a lateral thyrotomy to minimize patient morbidity. We present the third documented case of a hypopharyngeal paraganglioma and the first in the English-language literature.

Genomic findings underscore the heterogeneity of head and neck squamous cell carcinoma (HNSCC). Identification of mutations that predict therapeutic response would be a major advance. We determined the mutationally altered, targetable mitogenic pathways in a large HNSCC cohort. Analysis of whole-exome sequencing data from 151 tumors revealed the phosphoinositide 3-kinase (PI3K) pathway to be the most frequently mutated oncogenic pathway (30.5%). PI3K pathway-mutated HNSCC tumors harbored a significantly higher rate of mutations in known cancer genes. In a subset of human papillomavirus-positive tumors, PIK3CA or PIK3R1 was the only mutated cancer gene. Strikingly, all tumors with concurrent mutation of multiple PI3K pathway genes were advanced (stage IV), implicating concerted PI3K pathway aberrations in HNSCC progression. Patient-derived tumorgrafts with canonical and noncanonical PIK3CA mutations were sensitive to an mTOR/PI3K inhibitor (BEZ-235), in contrast to PIK3CA-wild-type tumorgrafts. These results suggest that PI3K pathway mutations may serve as predictive biomarkers for treatment selection.