Phase 1 study of EGFR-antisense DNA, cetuximab, and radiotherapy in head and neck cancer with preclinical correlatives.

BACKGROUND: Cetuximab combined with radiation therapy (RT) is an evidence-based treatment for locally advanced head and neck squamous cell carcinoma (HNSCC); however, locoregional failure remains the primary cause of cancer-related death in this disease. Intratumoral injection of epidermal growth factor receptor (EGFR)-antisense plasmid DNA (EGFR-AS) is safe and has been associated with promising lesional responses in patients who have recurrent/metastatic HNSCC. For the current study, the authors investigated the antitumor effects of cetuximab and EGFR-AS in preclinical HNSCC models and reported their phase 1 experience adding intratumoral EGFR-AS to cetuximab RT. METHODS: Antitumor mechanisms were investigated in cell line and xenograft models. Phase 1 trial eligibility required stage IVA through IVC HNSCC and a measurable lesion accessible for repeat injections. Patients received standard cetuximab was for 9 weeks. EGFR-AS was injected weekly until they achieved a lesional complete response. RT was delivered by conventional fractionation for 7 weeks, starting at week 3. Research biopsies were obtained at baseline and week 2. RESULTS: When added to cetuximab, EGFR-AS decreased cell viability and xenograft growth compared with EGFR-sense control, partially mediated by reduced EGFR expression. Six patients were enrolled in the phase 1 cohort. No grade 2 or greater EGFR-AS-related adverse events occurred. The best lesional response was a complete response (4 patients), and 1 patient each had a partial response and disease progression. EGFR expression decreased in 4 patients who had available paired specimens. CONCLUSIONS: In preclinical models, dual EGFR inhibition with cetuximab and EGFR-AS enhanced antitumor effects. In a phase 1 cohort, intratumoral EGFR-AS injections, cetuximab, and RT were well tolerated. A phase 2 trial is needed to conduct an extended evaluation of safety and to establish efficacy.

Dysplastic follicular dendritic cells in hyaline-vascular Castleman disease: a rare occurrence creating diagnostic difficulty.

Follicular dendritic cell (FDC) proliferations and dysplastic FDCs can be seen in Hyaline-vascular Castleman disease (HVCD). The association between HVCD and FDC sarcoma is well-documented; dysplastic FDCs may be precursors to FDC sarcoma. Herein, we describe a case of HVCD with strikingly large and dysplastic FDCs, which raised the differential of Hodgkin lymphoma and other neoplasms. Scattered dysplastic FDCs were predominantly in germinal centers and mantle zones, and rarely in interfollicular areas. Although occasional germinal centers contained increased FDCs, no mass forming proliferations were present to suggest FDC sarcoma. Immunostaining demonstrated that the atypical FDCs expressed CD21, clusterin and CXCL13, but not CD23, S100, pankeratin or CD30; they aberrantly expressed epidermal growth factor receptor (EGFR). The present case demonstrates that dysplastic FDCs may be present as isolated cells that require immunophenotyping to distinguish them from malignant entities with similar morphologic features. A variety of FDC markers is required to confirm their origin as the expression of any single marker is not assured, as occurred in this case. Pathologists need be aware of FDC proliferations in HVCD because of their association with FDC sarcoma. Aberrant EGFR expression by dysplastic FDCs may indicate that they are pre-neoplastic and necessitate long-term patient follow-up.

'Cytology-on-a-chip' based sensors for monitoring of potentially malignant oral lesions.

UNLABELLED: Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. OBJECTIVE: To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. MATERIALS AND METHODS: Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new 'cytology-on-a-chip' approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. RESULTS: Binary "low-risk"/"high-risk" models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity+specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. CONCLUSIONS: This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum.

Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials.

OBJECTIVE: Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. STUDY DESIGN: Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. RESULTS: Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. CONCLUSIONS: The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis.

Prevalence of HPV associated oropharyngeal cancer among south Texans.

The goal of this study was to begin to assess the prevalence of oropharyngeal cancer among all oral cancers and thus the potential role of human papillomavirus (HPV) in this disease in the south Texas Region served by the University of Texas Health Science Center at San Antonio (UTHSCSA), and University Health System (UHS) in San Antonio, Texas. This health system represents the largest catchment area for oral cancer serving the south Texas populations, extending from the U.S.-Mexico border, north to Williamson County, west to Eagle Pass, and east to Gonzales County. With the move towards electronic medical records (EMR) nationwide, our team conducted a feasibility study to answer this question utilizing electronic record coding data across both local networks.

Role of (18)F-FDG PET/CT in pre and post treatment evaluation in head and neck carcinoma.

Head and neck cancer (HNC) ranks as the 6(th) most common cancer worldwide, with the vast majority being head and neck squamous cell carcinoma (HNSCC). The majority of patients present with complicated locally advanced disease (typically stage III and IV) requiring multidisciplinary treatment plans with combinations of surgery, radiation therapy and chemotherapy. Tumor staging is critical to decide therapeutic planning. Multiple challenges include accurate tumor localization with precise delineation of tumor volume, cervical lymph node staging, detection of distant metastasis as well as ruling out synchronous second primary tumors. Some patients present with cervical lymph node metastasis without obvious primary tumors on clinical examination or conventional cross sectional imaging. Treatment planning includes surgery, radiation, chemotherapy or combinations that could significantly alter the anatomy and physiology of this complex head and neck region, making assessment of treatment response and detection of residual/ recurrent tumor very difficult by clinical evaluation and computed tomography (CT) or magnetic resonance imaging (MRI). (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography/CT ((18)F-FDG PET/CT) has been widely used to assess HNC for more than a decade with high diagnostic accuracy especially in detection of initial distant metastasis and evaluation of treatment response. There are some limitations that are unique to PET/CT including artifacts, lower soft tissue contrast and resolution as compared to MRI, false positivity in post-treatment phase due to inflammation and granulation tissues, etc. The aim of this article is to review the roles of PET/CT in both pre and post treatment management of HNSCC including its limitations that radiologists must know. Accurate PET/CT interpretation is the crucial initial step that leads to appropriate tumor staging and treatment planning.

Review of accessory parotid gland tumors: pathologic incidence and surgical management.

OBJECTIVE: The current study presents our experience with accessory parotid gland masses and reviews the literature on accessory parotid tumor incidence and surgical management. Based on our results, we advocate a standard parotidectomy approach with routine facial nerve dissection at the time of excision. STUDY DESIGN: We performed a retrospective chart review and comprehensive literature review on incidence of accessory parotid gland neoplasms. METHODS: A retrospective chart review of all patients with mid-cheek masses treated by the senior author was conducted from January 2003 to January 2009. The tumor size at presentation, FNA biopsy, pathologic diagnosis, and surgical treatment were recorded for 13 patients. RESULTS: In the case series, 54% of lesions were benign (n=7) and 46% were malignant (n=6) including benign pathologies of 4 pleomorphic adenomas, 2 lymphadenitis, 1 monomorphic adenoma and malignant pathologies of 2 mucoepidermoid carcinoma, 2 B-cell lymphomas, 1 adenocarcinoma, and 1 myofibrosarcoma. Surgical intervention was performed on all patients with standard parotidectomy incision for accessory parotid mass excision after identification and tracing of facial nerve and its branches. CONCLUSION: The present study provides support for a standard parotid incision with identification of the facial nerve at the time of surgical incision as this resulted in successful excision of accessory parotid tumors with favorable cosmetic results and without facial paralysis or tumor recurrence. Literature review of 152 cases of accessory parotid gland lesions, revealed a pooled incidence of 70% benign and 30% malignant.

Hemangiopericytoma of the parapharyngeal space.

Hemangiopericytomas of the head and neck are rarely found in the parapharyngeal space. We report the case of a 53-year-old woman who presented with a globus sensation in her throat. Imaging detected a left submucosal oropharyngeal mass that extended into the prestyloid parapharyngeal space. The tumor was surgically excised en bloc. Histopathologic examination identified it as a hemangiopericytoma. We discuss the diagnosis and management of this rare entity.

The role of nerve monitoring to predict postoperative recurrent laryngeal nerve function in thyroid and parathyroid surgery.

OBJECTIVES/HYPOTHESIS: To determine the role and efficacy of intraoperative recurrent laryngeal nerve (RLN) stimulation in the prediction of early and permanent postoperative nerve function in thyroid and parathyroid surgery. STUDY DESIGN: A retrospective review of thyroid and parathyroid surgeries was performed with calculation of sensitivity and specificity of the response of intraoperative stimulation for different pathological groups. METHODS: Normal electromyography (EMG) response with 0.5 mAmp stimulation was considered a positive stimulation response with postoperative function determined by laryngoscopy. No EMG response at >1-2 mAmps was considered a negative response. The rates of early and permanent paralysis, as well as sensitivity, specificity, and positive and negative predictive values for postoperative nerve function were calculated for separate pathological groups. RESULTS: The number of nerves at risk analyzed was 909. The overall early and permanent paralysis rates were 3.1% and 1.2%, respectively, with the highest rate being for Grave's disease cases. The overall sensitivity was 98.4%. The specificity was lower at 62.5% but acceptable in thyroid carcinoma and Grave's disease patients. The majority of nerves with a positive stimulation result and postoperative paralysis on laryngoscopy recovered function in 3 to 12 weeks, showing positive stimulation to be a good predictor of eventual recovery. CONCLUSIONS: Stimulation of the RLN during thyroid and parathyroid surgery is a useful tool in predicting postoperative RLN function. The sensitivity of stimulation is high, showing positive stimulation to be an excellent predictor of normal nerve function. Negative stimulation is more predictive of paralysis in cases of thyroid carcinoma and Grave's disease. LEVEL OF EVIDENCE: 2b.

Intraoperative relationship of the spinal accessory nerve to the internal jugular vein: variation from cadaver studies.

PURPOSE: Conflicting locations of the spinal accessory nerve (SAN) with respect to the internal jugular vein (IJV) are reported in the literature and anatomy texts. The objective of this study is to analyze this anatomic relationship specifically at the level of the posterior belly of the digastric muscle where it is encountered most often during surgery. MATERIAL AND METHODS: This study is a case series with planned chart review of all operative reports for neck dissections/explorations performed between June 2002 to June 2008 at an academic tertiary care referral center. Inclusion criteria required intraoperative identification of the SAN at the level of the posterior belly of the digastric muscle. Patients undergoing revision neck dissection were excluded. Data is presented using descriptive statistics. RESULTS: One hundred ninety-seven patients were identified; 175 met inclusion criteria. Thirty-two patients received bilateral neck dissections/explorations, resulting in a total of 207 SANs for analysis. The most common location of the SAN was lateral to the IJV (198; 95%). In 6 (2.8%) cases the SAN was identified medial to the IJV and 2 nerves pierced the IJV. A new variant of the SAN splitting around the SAN was identified. CONCLUSION: The majority of SANs course lateral to the IJV at the level of the posterior belly of the digastrics muscle (95%). This intraoperative finding differs from cadaveric studies. Discrepancies may reflect variation in the level at which the nerve was identified, as well as tissue changes related to cadaver versus in vivo studies.

Hypopharyngeal diverticulum after cervical spine surgery; the role of endoscopic management.

PURPOSE: The purpose of this study was to assess the role of minimally invasive endoscopic diverticulostomy in patients who develop hypopharyngeal diverticulum after cervical spine surgery/fixation. MATERIALS AND METHODS: This is a retrospective case series of seven patients who underwent endoscopic management of a symptomatic hypopharyngeal diverticulum. The patients were analyzed for diverticulum size, pre-operative and post-operative dysphagia and regurgitation scores, and complications. The overall success with the endoscopic approach was compared to the prior experience with traditional Zenker's diverticulum. RESULTS: Of the seven patients with hypopharyngeal diverticulum, four were successfully managed with minimally invasive endoscopic diverticulostomy (57%). These four patients all demonstrated clinically significant improvement in both dysphagia and regurgitation scores at a minimum of 6 months postoperatively. Complications were minimal and consisted of one case with postoperative subcutaneous air. There were no cases of fistula, mediastinitis, or nerve injury. CONCLUSIONS: Minimally invasive endoscopic diverticulotomy can be successfully applied to patients who develop hypopharyngeal diverticulum after cervical spine surgery/fixation.

Management of lateral cervical metastases in papillary thyroid cancer: patterns of lymph node distribution.

In this article we discuss the management of lateral cervical lymph node metastases in papillary thyroid cancer (PTC). We conducted a retrospective analysis of cases of PTC at our tertiary academic medical center involving 32 patients who underwent 39 neck dissections for the management of lateral cervical metastases from 2000 to 2007. Of these patients, 18 underwent primary neck dissections at the time of thyroidectomy after fine-needle aspiration biopsy confirmed the PTC. Secondary neck dissections for delayed metastases were performed in 14 patients who had previously undergone thyroidectomy for confirmed PTC. All 32 patients had positive nodes in at least one level. Our results highlight the high incidence of multilevel cervical metastasis associated with PTC and suggest the importance of including level II-B (submuscular recess) when performing a neck dissection; the upper posterior triangle (level V-A) is less likely to harbor occult tumor. Lateral neck metastasis from PTC is common and predictable; locoregional control is improved with a formal, comprehensive neck dissection at the time of thyroidectomy.

Predicting hypocalcemia after total thyroidectomy: parathyroid hormone level vs. serial calcium levels.

A 24- to 48-hour in-hospital observation period to monitor for hypocalcemia is common after total thyroidectomy. Because most thyroidectomy patients do not experience this potentially serious complication, investigators have searched for methods and clinical indicators that may help stratify thyroidectomy patients according to their risk of developing hypocalcemia and identify those who can be safely discharged earlier. We conducted a retrospective study to compare the value of an immediate postoperative intact parathyroid hormone (PTH) level and serial calcium levels in predicting the development of hypocalcemia following total thyroidectomy. Our study population was made up of 69 consecutive patients who had undergone total thyroidectomy from January 2004 through March 2005. These patients were divided into two groups on the basis of their postoperative calcium levels; 11 patients (16%) had developed transient hypocalcemia (serum calcium level: <7.5 mg/dl) and 58 (84%) had remained normocalcemic. A model was developed to assess the relationship between early (<60 min) postoperative PTH levels and serial (6 and 18 hr) calcium levels, and the two-sample Student t test was used to identify differences between the two groups. Analysis showed that hypocalcemia was associated with a postoperative PTH level of less than 14 pg/ml and a negative serum calcium slope between 6 and 18 hours postoperatively. A single early postoperative intact PTH measurement may be the most cost-effective screening tool for hypocalcemia, but even greater specificity can be achieved by combining those findings with a serum calcium measurement taken 6 hours postoperatively. The combination of the two measurements represents the safest method of assessing risk and identifying those patients who can be discharged on the day of surgery.

Nano-bio-chip sensor platform for examination of oral exfoliative cytology.

Oral cancer is a deadly and disfiguring disease that could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a noninvasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the epidermal growth factor receptor (EGFR) biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros, including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (P < 0.0001), the nuclear-to-cytoplasmic ratio (P < 0.0001), and EGFR biomarker expression (P < 0.03). Further examination using logistic regression and receiver operating characteristic curve analyses identified morphologic features as the best predictors of disease (area under the curve < or =0.93) individually, whereas a combination of all features further enhanced discrimination of oral cancer and precancerous conditions (area under the curve, 0.94) with high sensitivity and specificity. Further clinical trials are necessary to validate the regression model and evaluate other potential biomarkers, but this pilot study supports the NBC sensor technique as a promising new diagnostic tool for early detection of oral cancer, which could enhance patient care and survival.

Intraoperative therapy with liposomal drug delivery: retention and distribution in human head and neck squamous cell carcinoma xenograft model.

The focus of this study is to investigate the retention and biodistribution of technetium-99m ((99m)Tc) labeled liposomes in a human head and neck squamous cell carcinoma (HNSCC) positive surgical margin animal xenograft model. Positive surgical margin (with margin<1mm) in HNSCC is associated with significant higher mortality and recurrence rate when compared to clear margin. An immediate intraoperative application of liposome-carried therapeutic agents may treat the residual disease intraoperatively and improve long term survival in these patients. To understand the feasibility of this intraoperative therapy in HNSCC, the in vivo behavior of liposomes after intraoperative administration of (99m)Tc-labeled liposomes using non-invasive nuclear imaging was investigated in an animal xenograft model. Neutral and cationic (99m)Tc-labeled liposomes of 100 nm, 1 microm and 2 microm in diameter (6 study groups with 4 rats per study group) were injected into a nude rat HNSCC positive surgical margin xenograft model. Intratumoral, locoregional, and systemic retention and distribution of the (99m)Tc-liposomes were determined using non-invasive nuclear imaging and post-mortem organ distribution. The (99m)Tc-liposomes demonstrated high locoregional retention rate of 55.9+/-3.7% to 72.9+/-2.4% at 44 h after intraoperative injection to allow significant radiation to the surgical cavity if therapeutic radionuclides were used. Overall, the cationic liposomes demonstrated higher intratumoral retention rate, and the neutral liposomes showed greater retention in the paratumoral cavity (p<0.05 respectively). In conclusion, intraoperative therapy with liposome carried radionuclide drug delivery system carries great potential in treating unresectable HNSCC, and further study using therapeutic radionuclide should be explored.

Intraoperative 186Re-liposome radionuclide therapy in a head and neck squamous cell carcinoma xenograft positive surgical margin model.

PURPOSE: Positive surgical margins in advanced head and neck squamous cell carcinoma (HNSCC) have a well-documented association with an increased risk of locoregional recurrence and significantly poorer survival. Traditionally, unresectable tumor is treated with postoperative radiotherapy and/or chemotherapy. However, these therapeutic options can delay treatment and increase toxicity. The potential value of intraoperative injection of liposomal therapeutic radionuclides as a locoregional, targeted therapy in unresectable advanced HNSCC was assessed in a nude rat xenograft positive surgical margin model. EXPERIMENTAL DESIGN: The therapeutic effects of beta-emission rhenium-186 (186Re) carried by liposomes into the tumor remnants in a nude rat squamous cell carcinoma xenograft model were studied. Following the partial resection of tumor xenografts, the animals were intratumorally injected with 186Re-labeled or unlabeled (control) neutrally charged or positively charged 100-nm-diameter liposomes. Tumor size, body weight, hematology, and toxicity were monitored for 35 days posttherapy. RESULTS: The neutral (n = 4) and cationic (n = 4) liposome control groups showed an increase in tumor growth of 288.0 +/- 37.3% and 292.2 +/- 133.7%, respectively, by day 15. The 186Re-neutral-liposome group (n = 8) and the 186Re-cationic-liposome group (n = 8) presented with an average final tumor volume of 25.6 +/- 21.8% and 28.5 +/- 32.2%, respectively, at the end of the study (day 35). All groups showed consistent increases in body weight. No significant systemic toxicity was observed in any of the animals. CONCLUSIONS: With excellent tumor suppression and minimal side-effect profile, the intraoperative use of liposomal therapeutic radionuclides may play a role in the management of positive surgical margins in advanced HNSCC.

Management of the unknown primary carcinoma: long-term follow-up on a negative PET scan and negative panendoscopy.

BACKGROUND: The unknown primary carcinoma in the head and neck has been estimated to represent up to 7% of all head and neck carcinomas. In an attempt to identify the occult primary tumor the evaluation of this patient population has included a complete head and neck examination, flexible fiberoptic endoscopy, and imaging with CT/MRI. More recently, positron emission tomography (PET) has been advocated as a tool to detect primary tumors. METHODS: A cohort of 31 patients with fine-needle aspiration biopsy-confirmed squamous cell carcinoma were prospectively entered into a diagnostic protocol to identify the occult primary tumor. The diagnostic protocol included a comprehensive head and neck examination (including flexible endoscopy) and CT and/or MRI. If the initial diagnostic evaluation failed to identify a primary tumor, the patients then underwent whole body PET imaging followed by staging endoscopy with biopsy of the at-risk occult tumor sites. The outcome measures included the accuracy of the PET to predict the presence of occult tumor at staging endoscopy and the accuracy of the negative PET and negative panendoscopy in predicting the subsequent development of a primary tumor in the upper aerodigestive tract during follow-up. RESULTS: The PET detected 9 occult primary tumors in the 31 patients (detection rate, 29%). Five occult primary tumors (2 base of tongue and 3 palatine tonsil) were detected during panendoscopy despite a negative PET. The combination of PET and panendoscopy detected 45.2% of the unknown primary tumors. Seventeen patients (N1, n = 7; N2a, n = 4; N2b, n = 2; N3, n = 4) had no primary tumor detected and were treated as an unknown primary carcinoma with primary neck dissection +/- radiation therapy +/- chemotherapy. In this series of 17 patients, there were 3 neck recurrences (17.6%). In addition, only 1 patient (5.8%) developed a primary tumor of the upper aerodigestive tract with a mean follow-up of 31.1 months (range, 21-60 months). CONCLUSION: A negative PET study in patients with an occult primary head and neck carcinoma does not preclude the need for panendoscopy with biopsy to detect the occult primary tumor. The risk of subsequent primary tumor appears to be low in the patients with a negative PET and a negative panendoscopy (<6%).

Accuracy of cone beam computed tomography in determining the location of the genial tubercle.

OBJECTIVE: To determine the accuracy of cone beam computed tomography (CT) to predict the location of the genial tubercle. STUDY DESIGN AND SETTING: Cadaver study for anatomic analysis of 17 adult human cadaver heads. Each skull/cadaver head underwent radiographic imaging with cone beam CT and cadaver dissection. Measurements, including mandibular height (MH), genial tubercle width (GTW), genial tubercle height (GTH), distance from inferior border of mandible to genial tubercle (IBM/GT), and mandibular thickness (MT) were recorded. RESULTS: Statistical analysis with paired t test showed no significant difference between cadaver dissections versus cone beam measurements. Ninety-five percent confidence intervals (CI) were as follows: GTW (-0.2 to 1.0), GTH (-0.1 to 0.9), distance IBM/GT (-0.8 to 5.0), MH (-1.3 to -2.6), and MT (-0.1 to 0.3). CONCLUSION: These results show the accuracy of the 3D cone beam CT in the anatomic location of the genial tubercle. SIGNIFICANCE: This radiographic technique may prove useful in pre-operative planning for the mandibular osteotomy in genioglossus advancement procedures.

Occult primary head and neck carcinoma.

Unknown primary carcinoma presenting as cervical lymph node metastasis accounts for approximately 5% of all head and neck malignancies. The typical presentation involves a middle-aged man with a painless neck mass that has been present for several months. Over 90% of these malignancies represent squamous cell carcinoma originating within Waldeyer's ring (lymphoid tissue of the nasopharynx, tonsil, and base of tongue). The remainder are comprised of adenocarcinoma, melanoma, and other rare histologic variants. The ability to identify the occult primary tumor is imperative because identification allows site-specific therapy and avoidance of wide-field radiation side effects. Following confirmation of metastatic cervical disease with fine-needle aspiration, all patients presenting with an unknown primary carcinoma require a thorough head and neck history and physical examination, radiographic imaging, panendoscopy with directed biopsies of Waldeyer's ring, and bilateral tonsillectomy. Positron emission tomography has proved helpful in identifying occult primary tumors of the head and neck region.

Setup and characterization of a human head and neck squamous cell carcinoma xenograft model in nude rats.

OBJECTIVE: To develop and characterize a new head and neck cancer animal model. STUDY DESIGN: A human head and neck squamous cell carcinoma (HNSCC) xenograft model in nude rats was established via subcutaneous inoculation of a human-origin HNSCC cell line, SCC-4. The tumor was evaluated for growth characteristics, pathologic features by hematoxylin-eosin (HE) staining, and immunohistochemistry of epidermal growth factor receptor (EGFR). 2-[18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging characteristics were studied too. RESULTS: A new HNSCC animal model was successfully established. Tumor sizes reached about 1 cm3 on day 15 after tumor cell inoculation. HE staining pathology has confirmed that this tumor is a typical SCC. EGFR immunohistochemistry demonstrated this tumor model to be strongly EGFR positive. 18F-FDG PET study has shown that 18F-FDG accumulated in tumors. CONCLUSIONS: This study has demonstrated that this tumor model is an appropriate HNSCC tumor model for animal studies on HNSCC.