Sinonasal undifferentiated carcinoma: a 13-year experience at a single institution.

We present our experience with sinonasal undifferentiated carcinoma at the University of Michigan over 13 years and review prior published data. We conducted a retrospective review of 19 patients who presented to a tertiary care academic center multidisciplinary skull base clinic with sinonasal undifferentiated carcinoma between 1995 and 2008. Overall survival was 22% at 5 years, and the estimated 5-year distant metastasis-free survival was 35%. At 2 years, local control was 83%, regional control was 50%, and distant control was 83%. Local control was best in those patients treated nonsurgically, as was median survival, though this was not statistically significant. Nodal disease in the neck, either at presentation or at recurrence, was noted in 26% of patients. Survival for sinonasal undifferentiated carcinoma remains poor. It is possible that up-front radiation or chemoradiation will lead to better local control rates, though surgery remains a mainstay of treatment. In all cases, the cervical nodes should be addressed with primary treatment.

Malignant rhabdoid tumor of the parapharyngeal space.

Malignant rhabdoid tumor has been a somewhat controversial entity since it was first described in 1978 as a possible sarcomatous variant of Wilms tumor. Eventually, however, it was found to be a distinct neoplastic tumor with histologic characteristics similar to those of rhabdomyosarcoma. Malignant rhabdoid tumors affect children. Clinically, they occur primarily in the kidney, and they behave aggressively. Associated mortality is significant, even with combined-modality treatment regimens. We describe the case of a large extrarenal malignant rhabdoid tumor of the parapharyngeal space with extension to the infratemporal fossa and skull base in a previously healthy 2-year-old girl who had presented with a cervical mass and ipsilateral Horner syndrome. The patient underwent complete surgical extirpation of the lesion and received adjunctive cisplatin chemotherapy and radiation therapy, and she remained disease-free at 9 months of follow-up. Given the age group of the patients that these neoplasms most commonly affect and given the neoplasms' resemblance to rhabdomyosarcoma and other small round-cell tumors of the head and neck, discussion of the associated clinical pathology, imaging characteristics, histopathologic features, and mode of management are of particular importance, especially so in view of the uncommon location of the tumor in this specific case. Such a discussion may help lead to minimization of misdiagnosis and maximization of therapeutic benefit.

Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues.

The Cub and Sushi Multiple Domains-1 (CSMD1) is a tumor suppressor gene on 8p23.2, where allelic loss is both frequent and associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). To understand the extent of CSMD1 aberrations in vivo, we characterized 184 primary tumors from the head and neck, lung, breast and skin for gene copy number and analyzed expression in our HNSCCs and lung squamous cell carcinomas (SCCs). We detected loss of CSMD1 in a large proportion of HNSCCs (50%), lung (46%) and breast cancers (55%), and to a lesser extent in cutaneous SCCs (29%) and basal cell carcinomas (BCCs, 17%) using array-based comparative genomic hybridization (aCGH). Studying the region more closely with quantitative real-time PCR (qPCR), the loss of CSMD1 increased to 80% in HNSCCs and 93% in lung SCCs. CSMD1 expression was decreased in tumors compared to adjacent benign tissue (65%, 13/20) and was likely due to gene loss in 45% of cases (9/20). We also identified truncated transcripts lacking exons due to DNA copy number loss (30%, 5/17) or aberrant splicing (24%, 4/17). We show loss of CSMD1 in primary HNSCC tissues, and document for the first time that CSMD1 is lost in breast, lung and cutaneous SCCs. We also show that deletions of CSMD1 and aberrant splicing contribute to altered CSMD1 function in vivo.

Laser-assisted cerebrospinal fluid leak repair: an animal model to test feasibility.

OBJECTIVES: To test the feasibility of laser tissue welding as a method of creating an endonasal tissue bond for the purpose of cerebrospinal fluid leak repair. STUDY DESIGN AND SETTING: An 808 nm diode laser was used with a 42% albumin solder to create laser welds in sheep nasal septal mucosa, periosteum, and in situ rabbit maxillary sinus mucosa. Each condition was tested five times. Groups were compared with Kruskal-Wallis nonparametric analysis of variance (ANOVA) and post-hoc multiple-comparisons testing with the Bonferroni test. RESULTS: The burst pressures of sheep septal mucosa (34.88 +/- 3.49 mmHg) and periosteum (30.02 +/- 2.23 mmHg) were significantly higher than suture repair. A burst pressure of 69.58 +/- 2.85 mmHg was achieved in rabbit in situ maxillary sinus mucosa. CONCLUSION: Laser welding is capable of producing tissue bonds whose burst strength exceeds that of human intracranial pressure. SIGNIFICANCE: This is the first study to examine the feasibility of laser tissue welding in endonasal tissues. The ability to produce instant transnasal tissue bonds with burst pressures that exceed human intracranial pressure make this technology ideal for cerebrospinal fluid leak repair.

Chondrosarcoma of the arytenoid cartilage: a case report and review of the literature.

We report the case of a 56-year-old black woman with a locally aggressive chondrosarcoma at an unusual tumor site: the right arytenoid cartilage. The tumor extended from the superior pole of the right arytenoid cartilage to the soft-tissue areas of the right aryepiglottic fold, piriform sinus, and interarytenoid area. We undertook a conservative surgical approach by performing an endoscopic transoral CO2 laser resection, a right arytenoidectomy with wide soft-tissue margins, and a tracheotomy in anticipation of postoperative edema. Surgical exploration revealed that the tumor extended into the cricoid cartilage. Histopathology demonstrated a low-grade chondrosarcoma of the conventional variant. Clear margins were obtained by staged procedures. Chondrosarcomas of the larynx typically exhibit low-grade histopathology, and affected patients have a low incidence of metastasis and a good prognosis. Even so, these tumors can present diagnostic and therapeutic challenges. Surgical resection provides adequate airway protection and sound oncologic safety while preserving speech and swallowing, and these should be the surgeon's goals in this setting. Options include open laryngofissure, thyrotomy, organ preservation with partial laryngectomy, and endoscopic laser resection.

Intracranial complications of sinusitis in children and adolescents and their outcomes.

OBJECTIVE: To gain insight into patterns of presentation, imaging, microbiological aspects, therapy, disease course, and outcome of intracranial complications of sinusitis (ICS), which are challenging conditions with the potential to cause significant morbidity and mortality. We reviewed our experience with ICS in children and adolescents. DESIGN: Consecutive case series with a mean follow-up of 12 months. SETTING: Tertiary pediatric referral center. PATIENTS: Consecutive sample of 25 children and adolescents treated for 35 intracranial complications (mean age, 13.2 years [range, 4-18 years]). INTERVENTIONS: Medical and surgical management. MAIN OUTCOME MEASURES: Survival and temporary and permanent neurologic sequelae. RESULTS: Most patients were adolescents (n = 19; 76%) and male (n = 19; 76%). Epidural abscess was most common (13 complications), followed by subdural empyema (n = 9), meningitis (n = 6), encephalitis (n = 2), intracerebral abscess (n = 2), and dural sinus thrombophlebitis (n = 2). Abscesses were primarily located in the frontal or frontoparietal regions. Magnetic resonance imaging was extensively used and was superior to contrast computed tomography in diagnosis. All patients received intravenous antibiotics, 21 underwent endoscopic sinus surgery, and 13 underwent neurosurgical drainage. Only 1 death occurred from sepsis secondary to meningitis (mortality, 4%). Overall, neurologic outcome was excellent. Although 10 patients (40%) had neurologic deficits, most resolved within 2 months. Only 2 patients had permanent neurologic sequelae. Among ICS, epidural abscess appeared to be a distinct clinical entity. Epidural abscesses typically presented without specific neurologic symptoms or signs, were more often associated with orbital complications, and had outcomes considerably better than the other ICS. CONCLUSION: Intracranial complications of sinusitis are challenging, but prognosis can be favorable in children and adolescents by using aggressive medical and surgical management.

Intermediate crural overlay in rhinoplasty: a deprojection technique that shortens the medial leg of the tripod without lengthening the nose.

OBJECTIVE: To review the indications for, surgical techniques of, and results of intermediate crural overlay of the alar cartilages in rhinoplasty. DESIGN: Prospective study of patients undergoing intermediate crural overlay of the lower lateral cartilages. The setting was a facial plastic surgery private practice. Patients included 10 primary rhinoplasty patients and 1 revision rhinoplasty patient who underwent intermediate crural overlay of the lower lateral cartilages. The main outcome measures were postoperative photographs and patient records, which were reviewed for tip projection and rotation, preservation of the double break, bossae, and knuckling. RESULTS: Intermediate crural overlay decreased projection in all 11 patients and increased the nasolabial angle in 7 patients. One patient had no change in the nasolabial angle, and 3 patients had counterrotation of 1 degrees , 3 degrees , and 4 degrees . A postoperative physical examination revealed that no patient had developed bossae, tip asymmetries, or knuckling. In addition, the double break was maintained in all the study patients. CONCLUSIONS: Intermedial crural overlay is a reliable technique for achieving tip deprojection. Overall, the nasolabial angle is maintained (although in 3 patients, clinically insignificant counterrotation did occur). In addition, the length of the intermediate crura is reduced, but the double break is preserved. In the group of patients with thin skin and tip overprojection secondary to overdevelopment of the lower lateral cartilages, intermediate crural overlay achieves tip deprojection while controlling the nasolabial angle and preserving the natural curvature of the dome.

Low-grade mucoepidermoid carcinoma of the subglottis treated with organ-preservation surgery.

Mucoepidermoid carcinoma of the subglottis is infrequently reported in the literature. This tumor subtype is more commonly associated with the major and minor salivary glands. Mucoepidertoid carcinoma of the larynx can be difficult to diagnose, and there is no consensus as to appropriate management. We report a case of a low-grade mucoepidermoid carcinoma that was confined to the subglottis and treated with organ-preservation surgery. A conservative surgical approach was taken because of the tumor's low-grade histology and its location and in order to preserve the patient's laryngeal function. At follow-up 15 months postoperatively, the patient remained disease-free, and laryngeal function was intact.

Genome-wide profiling of oral squamous cell carcinoma by array-based comparative genomic hybridization.

OBJECTIVES: Array-based comparative genomic hybridization (aCGH) was used to develop a genome-wide molecular profile of oral squamous cell carcinoma (OSCC). Copy number alterations (CNAs) were identified by chromosomal region, mapped to specific genes, and compared with several previously documented CNAs associated with head and neck squamous cell carcinoma (HNSCC). The status of 512 commonly altered cancer genes was assessed and evaluated as potential correlates of tumor behavior. METHODS: Tumor tissue DNA was isolated for aCGH from 21 prospectively collected fresh-frozen OSCC specimens. aCGH was performed at 0.9-Mb resolution to identify distinct regions of genomic alteration and their associated genes. Cancer genes commonly altered were then correlated with clinicopathologic tumor data. RESULTS: Genomic regions most frequently amplified (>35%) were located on 3q, 5p, 8q, 9q, and 20q, although regions most frequently deleted (>40%) involved chromosomes 3p, 8p, 13q, and 18q. Minimal regions of CNA identified, by aCGH narrowed larger, previously documented CNAs associated with HNSCC to significantly smaller regions, yielding shorter lists of candidate genes. Cancer-related genes altered in greater than 25% OSCC samples were identified (22 amplified, 17 deleted). Several genes associated with the Fanconi anemia DNA-damage response pathway were frequently altered, including BRCA1, BRCA2, FANCD2, and FANCG. Other cancer-related genes linked to hereditary cancer syndromes include VHL, MLH1, XPC, and RB1. CONCLUSIONS: Genome-wide aCGH can be used to detect and map CNAs in OSCC tissue specimens with high resolution. These data implicate several candidate genes and gene pathways in the tumorigenesis of sporadic OSCC.

Predictors of thyroid gland invasion in glottic squamous cell carcinoma.

OBJECTIVE: This study examines preoperative clinical and intraoperative histopathologic characteristics that can be used to predict thyroid gland invasion in the setting of squamous cell carcinoma (SCC) of the glottis. STUDY DESIGN: The study was retrospectively performed using 30 serially sectioned whole-organ total laryngectomy with thyroidectomy specimens with associated preoperative clinical data. METHODS: Histopathologic and clinical variables including true vocal cord (TVC) fixation, cricoarytenoid joint invasion, subglottic extension (SGE) of tumor, patterns of laryngeal spread, and prior radiation were examined as univariate and multivariate correlates of thyroid gland invasion. RESULTS: Twenty-three percent of thyroid gland specimens demonstrated SCC invasion. Five were T4 stage, two were T3 stage, and all demonstrated direct extension to the thyroid gland. Of these, all had a fixed ipsilateral TVC (P = .003) and SGE of tumor greater than 15 mm (P = .003). Using multivariate analysis, SGE of tumor and TVC fixation contribute independently as correlates of thyroid gland invasion. Prior radiation of the larynx did not correlate with thyroid gland invasion and did not significantly influence the predictive capacity of these variables. Tumors invading the thyroid gland also invaded the cricothyroid membrane (100%), anterior commissure (100%), laryngeal ventricle (100%), and thyroid cartilage (86%). CONCLUSION: Preoperative assessment of TVC mobility and extent of SGE are significant correlates of thyroid gland invasion by SCC of the glottis. Distinct patterns of laryngeal spread are associated with thyroid gland invasion. Prophylactic hemithyroidectomy with isthmusectomy is indicated for glottic SCC in the preoperative setting of a fixed TVC and SGE greater than 15 mm. Additional study correlating patterns of laryngeal spread with thyroid gland invasion will add to these data in determining when to selectively perform thyroidectomy in this setting.

Extending the inferior limits of supracricoid partial laryngectomy: a clinicopathological correlation.

OBJECTIVES/HYPOTHESIS: The study examined preoperative clinical characteristics that can be used to predict secure inferior margins of glottic squamous cell carcinoma extending toward the cricoid cartilage when performing organ preservation surgery of the larynx. STUDY DESIGN: The study was retrospectively performed using 31 serially sectioned whole-organ total laryngectomy specimens with associated preoperative clinical data. METHODS: Histopathologic and clinical variables including true vocal cord (TVC) fixation, cricoarytenoid joint invasion, subglottic extension (SGE) of tumor, and prior radiation were examined as independent and multivariate correlates of cricoid cartilage invasion. RESULTS: All tumors with subglottic extension of 15 mm or less and without arytenoid fixation were free of cricoid invasion. Of tumors invading cricoid with subglottic extension of 15 mm or less, all had a fixed arytenoid cartilage and local cricoid invasion type only. Correcting for subglottic extension using multivariate analysis, cricoarytenoid joint invasion and fixed true vocal cord independently predicted cricoid invasion. However, in a multivariate model together, true vocal cord mobility adds no predictive power to cricoarytenoid joint invasion. Prior radiation of the larynx did not significantly change the predictive capacity of these variables. CONCLUSION: Preoperative assessment of arytenoid mobility and extent of subglottic extension are reliable predictors of cricoid invasion by glottic squamous cell carcinoma. Organ preservation surgery is oncologically safe in the setting of glottic squamous cell carcinoma with subglottic extension of 15 mm or less and without arytenoid fixation.

Modulation of Th1 and Th2 cytokine profiles and their association with advanced head and neck squamous cell carcinoma.

OBJECTIVE: Plasma cytokine concentrations from patients with head and neck squamous cell carcinoma (HNSCC) were measured to determine whether the potential modulation of host Th1 vs Th2 immune responses are associated with advanced clinical disease. STUDY DESIGN AND SETTING: The concentrations of IL-4, IL-6, IL-10, and IL-12 were measured in the plasma of 58 patients with histologically proven HNSCC. These data were examined with respect to the histologic size (T-stage) of the primary tumor, and presence of nodal metastasis. RESULTS: The concentrations of IL-12 were greater from patients without nodal metastasis, and with T(1)/T(2)-stage tumors. IL-10 levels were greater from patients with nodal metastasis, and with T(3)/T(4)-stage tumors. The concentrations of IL-6 were greater from patients with T(3)/T(4)-stage tumors. CONCLUSIONS: Using parameters of primary tumor size and presence of nodal metastasis, patients with advanced HNSCC have significantly less plasma IL-12 levels, and greater plasma IL-10 and IL-6 levels. SIGNIFICANCE: Patients with advanced HNSCC have a potentially diminished Th1 immune response, and a stronger potential Th2 immune response when compared to that of patients with less advanced disease. EBM RATING: D-5.

Multivariate predictors of occult neck metastasis in early oral tongue cancer.

OBJECTIVES: The elective dissection of cervical lymph nodes from patients with early oral tongue cancer and a clinically negative neck (T1/T2N0), remains an unsettled issue that continues to be investigated. This study examines clinical and histopathologic factors through univariate and multivariate analysis to correlate the risk of neck micrometastasis in patients with T1/T2N0 squamous cell carcinoma of the oral tongue. STUDY DESIGN AND METHODS: The clinical files and histologic sections of tumor from 45 clinically determined N0 patients were retrospectively analyzed. The factors examined include degree of tumor cell differentiation, T1/T2 staging, presence of perineural invasion, presence of angiolymphatic invasion, type of invasion front, depth of muscle invasion, and tumor thickness. RESULTS: Independent correlates of positive occult neck metastasis included greater tumor thickness ( P = 0.01), greater depth of muscle invasion ( P = 0.01), T2 stage ( P = 0.01), poorly differentiated tumors ( P = 0.007), infiltrating-type invasion front ( P = 0.03), presence of perineural invasion ( P = 0.001), and presence of angiolymphatic invasion ( P = 0.005). The final multivariate model for estimation of an increased probability of occult neck disease included greater tumor thickness, presence of perineural invasion, infiltrating-type invasion front, poorly differentiated tumors, and T2 stage. CONCLUSIONS: The clinical and histopathologic factors studied herein permit greater selectivity and more informed decision-making than does presurgical evaluation, when addressing elective neck treatment for early N0 oral tongue cancer. The multivariate model derived from this study appears to be a more reliable method for determining the patients most likely to benefit from elective neck dissection.

Effects of stapedectomy on tinnitus in patients with otosclerosis.

Tinnitus frequently accompanies hearing loss in patients with otosclerosis and has been correlated with distinct otosclerotic pathologies. The objective of our study was to evaluate the effect of stapedectomy on tinnitus in patients with otosclerosis. Forty patients were retrospectively interviewed for assessment of preoperative versus postoperative levels of tinnitus distress using the standardized Klockhoff-Lindblom (K/L) classification system. Audiometric data also were examined with respect to tinnitus grades. Of the 40 patients, 34 (85%) had improved K/L tinnitus grades after stapedectomy, 5 (12.5%) had no change, and 1 (2.5%) had a worse K/L grade postoperatively. Twenty-one (52.5%) patients reported complete resolution of tinnitus. Postoperative air-bone gap was less for patients with decreased tinnitus than for those with no change. Significant improvement was seen in the degree of tinnitus distress after stapedectomy for otosclerosis.

Voice rehabilitation after external partial laryngeal surgery.

Excising part or all of a larynx as a cancer operation results in changes that transgress anatomic, physiologic, psychologic, and social common principles. The treatment of laryngeal cancer has evolved significantly over the prior 5 decades, and better diagnostic procedures, combined with an improved understanding of the anatomico-clinical behavior of laryngeal tumors, has allowed the development of external partial or "organ-preservation" laryngeal surgery. When total or partial laryngectomy procedures are performed,profound changes in anatomy and physiology and, thus,voice are inevitable. Because the spectrum of these changes maybe broad, the role of professional rehabilitation therapy has taken an involved, multidisciplinary approach, with an integrated understanding of anticipated and potential functional outcomes.

Diagnostic and surgical endoscopy in functional septorhinoplasty.

Endoscopy has altered our ability to diagnose pathology accurately during the preoperative assessment, and it has also offered surgeons the ability to perform surgeries in a minimally invasive manner. In this article, we review the senior author's experience with diagnostic and surgical endoscopy in functional septorhinoplasty. A thorough examination of the nasal cavity in the patient seeking cosmetic rhinoplasty along with correction of nasal obstruction is enhanced by the performance of office nasal endoscopy. Endoscopically guided septoplasty is useful as a minimally invasive approach for isolated septal deformities, and it is an indispensable approach in difficult revision nasal surgeries in which obstructing septal deviation persists. Endoscopy is a critical diagnostic and surgical tool in patients seeking cosmetic nasal surgery who also have functional nasal complaints.