Faculty Bibliography

BACKGROUND: Typically, thyroid follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cases show moderate to marked cellularity and scant or absent colloid. Recently, cases have been noted with microfollicular cellularity in the background of moderate to abundant amount of colloid. The purpose of this study was to compare these "colloid-rich" FN/SFN cases to the typical FN/SFN cases. METHODS: Thyroid cytology specimens with the features of FN/SFN were searched in cytopathology files from September 2008 to June 2012. Cases with absent or minimal colloid were designated "typical colloid-poor" FN/SFN and cases with moderate to abundant colloid were designated "colloid-rich" FN/SFN. From these cases, those with surgical pathology resection follow-up were identified. Cytologic, surgical pathology resection, and molecular features (BRAF, RAS, RET/PTC, and PAX8-PPARgamma) were investigated for the typical colloid-poor FN/SFN cases and were compared with those of the colloid-rich FN/SFN cases. RESULTS: Of 431 FN/SFN cases with surgical pathology resection follow-up, 360 (83.5%) cases showed features of typical colloid-poor FN/SFN and 71 (16.5%) cases showed features of colloid-rich FN/SFN. Papillary carcinoma was the most common malignant outcome for the 2 groups. Although the proportion of malignant outcome was similar for the 2 groups, the "colloid-rich" FN/SFN cases showed a greater proportion of nodular hyperplasia among the cases with benign outcome. In addition, the "colloid-rich" FN/SFN cases demonstrated a greater proportion of cases with a mutation. CONCLUSIONS: Approximately one-sixth of cases of FN/SFN show "colloid-rich" features. Comparison to the typical colloid-poor FN/SFN demonstrated similar risk for malignancy but contrasting resection outcome and molecular characteristics.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To evaluate the transoral anatomy of the tonsillar fossa and lateral pharyngeal wall and to correlate these findings with radiographic measurements and transoral robotic surgery (TORS) of patients with early tonsillar tumor. STUDY DESIGN/METHODS:Preclinical cadaveric study and patient cohort. METHODS:Six complete cadaveric dissections were performed to identify key anatomic landmarks, and these landmarks were validated in two consecutive patients with T1 human papillomavirus-positive squamous cell carcinoma of the tonsil treated by TORS. For radiographic landmark analysis, 25 patients who underwent contrast-enhanced computed tomography (CT) of the neck for a variety of endoscopic skull base procedures were selected. Measurements were taken from the lateral pharyngeal wall at C2-C3 interspace and greater horn of hyoid (C6) to the external carotid artery (ECA). RESULTS:The glossopharyngeal (IX) nerve was consistently identified deep to the superior constrictor musculature and at the intersection of the posterior tonsillar pillar with the base of tongue. The styloglossus muscle forms the deep plane medial to the ECA. The mean measurements for left C2-C3 interspace to the ECA and right C2-C3 interspace to ECA were 17.6 ± 0.8 mm and 18.4 ± 0.8 mm, respectively. Similarly, the mean measurements for left hyoid to ECA and right hyoid to ECA were 3.4 ± 0.8 mm and 4.3 ± 0.6 mm, respectively. CONCLUSIONS:A systematic approach to dissect the tonsillar fossa and lateral pharyngeal wall can be performed using key anatomic landmarks. CT measurements taken at the C2-C3 interspace and greater horn of hyoid bone (C6 level) to the ECA are consistently and reliably achieved.

OBJECTIVES/OBJECTIVE:To evaluate the impact of margin sampling on local recurrence in patients with pT1-2 pN0 conventional squamous cell carcinoma of the oral tongue. MATERIALS AND METHODS/METHODS:Based on margin sampling, 126 cases were divided into group 1 (margins sampled from the glossectomy specimen only), group 2 (with revision of glossectomy margins), and group 3 (margins primarily sampled from the tumor bed). RESULTS:The probability of local progression-free survival at 3years was .90, .76 and .73 (p=.0389) in groups 1, 2, and 3, respectively. Groups differed by frequency of positive glossectomy specimen margins (p=<.0001) and by the average distance from carcinoma to the closest margin (4.5, 2.4, and 3.0mm for Groups 1, 2, and 3, respectively; p=.0009). Tumor bed margin status (positive vs. negative) and other parameters (e.g., pattern and depth of invasion) did not correlate with local recurrence. Status of the glossectomy specimen margins did correlate with outcome. A positive glossectomy margin conferred a relative risk of 2.5 (95% confidence interval, CI, 1 - 6.3) for local recurrence. A proportional hazards regression model for margin width found a hazard ratio of 0.67 (95% CI=.57-.98) comparable to a 33% decrease in risk of local recurrence for an increase of 1mm of margin width (p=.0271). CONCLUSIONS:Status of the glossectomy specimen margins rather than that of tumor bed margins was prognostically relevant. Reliance on tumor bed margins appears to be associated with worse local control, perhaps due to the narrower initial resection.

IMPORTANCE/OBJECTIVE:At many institutions, computed tomography with iodinated intravenous contrast medium is the preferred imaging modality for staging of the neck in squamous cell carcinoma of the head and neck. However, few studies have specifically assessed the diagnostic accuracy of computed tomography for determining the presence or absence of extracapsular spread (ECS). OBJECTIVE:To determine the accuracy of modern, contrast-enhanced, multidetector computed tomography in the diagnosis of ECS of cervical lymph node metastases from squamous cell carcinoma of the head and neck. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Retrospective observational study at an academic tertiary referral center among 100 consecutive patients between May 1, 2007, and February 1, 2012, who underwent a lateral cervical neck dissection for squamous cell carcinoma of the head and neck with neck metastases of at least 1 cm in diameter on pathologic assessment. Exclusion criteria included malignant neoplasms other than squamous cell carcinoma, a delay in surgery longer than 6 weeks from the time of staging computed tomography, and prior treatment of the neck or recurrent disease or a second primary. MAIN OUTCOMES AND MEASURES/METHODS:Each patient was independently assigned a subjective score for the presence of ECS by 2 Certificate of Added Qualification-certified neuroradiologists according to a 5-point scale. Receiver operating characteristic curves were generated, and sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for each observer. RESULTS:The areas under the receiver operating characteristic curve for observers 1 and 2 are 0.678 (95% CI, 0.578-0.768) and 0.621 (95% CI, 0.518-0.716), respectively. For observer 1, the positive and negative predictive values for the detection of ECS were 84% (95% CI, 68%-93%) and 49% (95% CI, 36%-62%), respectively. For observer 2, the positive and negative predictive values for the detection of ECS were 71% (95% CI, 57%-82%) and 48% (95% CI, 32%-64%), respectively. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Computed tomography cannot be used to reliably determine the presence of pathologic ECS. Radiologic findings suggestive of ECS should not be relied on for treatment planning in squamous cell carcinoma of the head and neck.

IMPORTANCE/OBJECTIVE:Since technologic advances allow the use of robotic assistance in various surgical interventions performed to treat pediatric otolaryngology patients, the feasibility and outcomes of potential procedures must be assessed. OBJECTIVE:To assess the feasibility and outcomes of robotic-assisted lingual tonsillectomy in the pediatric population. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Retrospective medical record review in a tertiary care children's hospital of 16 pediatric patients who underwent robotic-assisted lingual tonsillectomy from March 1, 2011, through December 31, 2012. INTERVENTION/METHODS:All patients underwent robotic-assisted lingual tonsillectomy using the da Vinci Surgical System (Intuitive Surgical, Inc) at the Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center. MAIN OUTCOMES AND MEASURES/METHODS:Demographic data, comorbidities, robot docking time, operative time, estimated blood loss, and postoperative course, including complications in the immediate and longer-term postoperative period, were collected and analyzed. RESULTS:All patients successfully underwent lingual tonsillectomy using the da Vinci Surgical System. Endotracheal intubation was performed in all patients and did not interfere with visualization of the oropharynx. Optimal retraction allowed visualization of pertinent structures and maximized transoral access. A significant learning curve from the first 5 surgical cases to subsequent cases with respect to robot docking time was observed (9 vs 3 minutes, respectively; P < .05). Operative time, estimated blood loss, and postoperative complication profiles are within the expected and acceptable limitations for performing lingual tonsillectomy in the pediatric population. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Technologic advances have allowed miniaturization of robotic instrumentation and have expanded the scope of surgical options for the pediatric airway. Robotic-assisted lingual tonsillectomy is well tolerated and can be performed in the pediatric population with excellent success. It should be considered a feasible option for implementation at an institution-based level.

As minimally invasive surgery has become common in head and neck surgery, the role of robotic surgery has expanded from thyroid surgery and transoral robotic surgery (TORS) of the oropharynx and supraglottic to other areas. Surgeons have advanced the limits of TORS, adapting lasers to the Da Vinci robot for glottic cancer, and combining existing techniques for transoral supraglottic laryngectomy and hypopharyngectomy to perform transoral total laryngectomy. Skull base approaches have been reported with some success in case reports and cadaver models, but the current instrument size and configuration limit the applicability of the current robotic system. Surgeons have reported reconstruction of the head and neck via local and free flaps. Using the previously reported approaches for thyroidectomy via modified facelift incision, neck dissection has also been reported. Future applications of robotic surgery in otolaryngology may be additionally expanded, as several new robotic technologies are under development for endolaryngeal work and neurotology.

BACKGROUND AND PURPOSE/OBJECTIVE:Optimizing the utilization of surveillance PET/CT in treated HNSCC is an area of ongoing research. Our aim was to determine the negative predictive value of PET/CT in patients with treated head and neck squamous cell cancer and to determine whether negative PET/CT reduces the need for further imaging surveillance. MATERIALS AND METHODS/METHODS:We evaluated patients with treated HNSCC who underwent posttreatment surveillance PET/CT. During routine clinical readouts, scans were categorized as having negative, probably negative, probably malignant, or malignant findings. We followed patients clinically and radiographically for at least 12 months from their last PET/CT (mean, 26 months; median, 28 months; range, 12-89 months) to determine recurrence rates. All suspected recurrences underwent biopsy for confirmation. RESULTS:Five hundred twelve patients (1553 scans) were included in the study. Two hundred fourteen patients had at least 1 PET/CT with negative findings. Of the 214 patients with a scan with negative findings, 19 (9%) eventually experienced recurrence, resulting in a NPV of 91%. In addition, a subgroup of 114 patients with 2 consecutive PET/CT examinations with negative findings within a 6-month period was identified. Only 2 recurrences were found in this group, giving a NPV of 98%. CONCLUSIONS:In patients treated for HNSCC, a single PET/CT with negative findings carries a NPV of 91%, which is not adequate to defer further radiologic surveillance. Two consecutive PET/CT examinations with negative findings within a 6-month period, however, resulted in a NPV of 98%, which could obviate further radiologic imaging in the absence of clinical signs of recurrence.

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.