Faculty Bibliography

Adenoid cystic carcinoma is an indolent, slow-growing tumor that may first cause low-grade pain in the affected region. This article describes a case involving adenoid cystic carcinoma of the maxilla that was present for approximately nine years. Prior to diagnosis, five dentists reported that the patient had anisocoria, migraine headaches, and low-to-moderate upper jaw pain that was refractory to conventional therapy. A surgical resection was performed; after a period of soft tissue healing, radiation therapy was initiated. The surgical defect was obturated using an interim removable prosthesis while awaiting final reconstruction by a maxillofacial prosthodontist. This article examines possible reasons why this lesion was not diagnosed sooner and discusses how this case should raise the general dentist's awareness of such lesions

PURPOSE: The aim of this study was to review and describe techniques for the reconstruction of large, complex perioral defects after resection of oral squamous cell carcinoma with emphasis on cosmetic and functional outcome. PATIENTS AND METHODS: A review of techniques and selected case presentations using different flap designs for the reconstruction of large perioral defects following resection of squamous cell carcinoma was performed. The Bernard and Karapandzic flaps were used for large lower lip defects. A Zisser flap technique was used to reconstruct a large commissure defect. RESULTS: All reconstructed patients had acceptable functional results and healed without complication. The large lower lip defects were easily closed with the Bernard and Karapandzic flaps. The commissure defect was reconstructed using the Zisser technique. While cosmesis was acceptable in all cases, the commissure was the most difficult region to reconstruct with a favorable appearance. There were no flap failures. The Karapandzic flap led to greater rounding of the commissure area and the composite resection resulted in a lack of lower lip support that was improved with prosthesis. Function was noted to be excellent in the Bernard and Karapandzic flaps, with the patients able to purse lips and blow up balloon-type devices. CONCLUSION: The Bernard, Karapandzic, and Zisser flaps provide a predictable method to reconstruct large perioral defects following resection for oral cancer. Subsequent fabrication of a prosthesis can aid in lip support for the resected area

Genomes of solid tumors are characterized by gains and losses of regions, which may contribute to tumorigenesis by altering gene expression. Often the aberrations are extensive, encompassing whole chromosome arms, which makes identification of candidate genes in these regions difficult. Here, we focused on narrow regions of gene amplification to facilitate identification of genetic pathways important in oral squamous cell carcinoma (SCC) development. We used array comparative genomic hybridization (array CGH) to define minimum common amplified regions and then used expression analysis to identify candidate driver genes in amplicons that spanned <3 Mb. We found genes involved in integrin signaling (TLN1), survival (YAP1, BIRC2), and adhesion and migration (TLN1, LAMA3, MMP7), as well as members of the hedgehog (GLI2) and notch (JAG1, RBPSUH, FJX1) pathways to be amplified and overexpressed. Deregulation of these and other members of the hedgehog and notch pathways (HHIP, SMO, DLL1, NOTCH4) implicates deregulation of developmental and differentiation pathways, cell fate misspecification, in oral SCC development

BACKGROUND: An increasing incidence of oral carcinoma among young adults has been reported in the U.S. and Europe. Although the association between human papillomavirus infection and tonsillar carcinoma is now well established, to the authors' knowledge little is known about incidence trends in tonsillar carcinoma among younger adults. The objective of the current study was to explore the trends in both oral cavity and pharyngeal squamous cell carcinoma (SCC) in younger U.S. populations, in particular tongue and tonsillar SCC. METHODS: Using the 1973-2001 Surveillance, Epidemiology and End Results (SEER) database, we computed age, race, and site-specific trends of oral and pharyngeal (excluding nasopharynx) carcinoma incidence rates. The percent change (PC) and annual percent change (APC) were computed to explore trends in incidence rates over time. RESULTS: There were 2262 SCC of the oral cavity and 1251 SCC of the pharynx reported to the SEER program from 1973 to 2001 in adults aged 20-44 years. There was a statistically significant increase in the incidence of oral tongue SCC (APC = +2.1; P < 0.001), base of tongue SCC (APC = +1.7; P = 0.04), and palatine tonsil SCC (APC = +3.9; P < 0.001) among younger white individuals, whereas the incidence of SCC in all other oral and pharyngeal sites decreased or remained constant. CONCLUSIONS: The increase in tonsil SCC incidence from 1973 to 2001 paralleled the increase in tongue SCC, whereas SCC in all other oral and pharyngeal sites remained constant or decreased. This may suggest similar etiologic factors for SCC affecting the palatine tonsils and tongue in younger populations

Inducible nitric oxide synthase (iNOS) is responsible for generating high levels of nitric oxide (NO) in tissues. Increased iNOS expression has been demonstrated in a number of carcinomas including head and neck squamous cell carcinoma (SCC). However, iNOS levels have not been evaluated specifically in oral cavity SCC, or in the precancerous lesions that progress to oral SCC. Also, NO levels have not been measured in oral precancerous or cancerous tissues. We therefore measured iNOS mRNA, iNOS protein and NO in oral SCC, oral dysplasias and normal oral epithelium. We used RT-PCR to quantify and compare iNOS mRNA levels in these oral tissue specimens. We found that iNOS mRNA was overexpressed in 41% of oral SCC but in only 8% of dysplasia specimens (P = 0.003). Immunohistochemistry was used to evaluate iNOS protein levels in oral SCC, oral dysplasias and normal oral epithelium. A significantly higher percentage of oral SCC specimens showed the highest level of iNOS staining relative to the oral dysplasias and normal oral epithelial samples (95% of oral SCC, 50% of dysplasias, and only 0% of normal epithelial controls, P < 0.0001). The positive staining for iNOS was limited to the SCC cells. Production of NO from iNOS was quantified using HPLC and found to be significantly higher in oral SCC (1.45 +/- 0.56 microg/ml) than normal epithelial controls (0.43 +/- 0.26 microg/ml) (P = 0.0013). We conclude that iNOS mRNA levels and NO production are significantly increased, in oral SCC compared to oral dysplasias and normal epithelial controls. These findings suggest that increased iNOS expression and the generation of high NO levels might have a role in oral SCC development

Beta-6 Integrin, tenascin-C, and MMP-1 (matrix metalloproteinase-1) are invasion-related proteins that are frequently overexpressed in many human malignancies. The objective of this study was to determine whether there is overexpression of these molecules in three types of salivary neoplasms showing markedly different behavior. A total of 55 formalin-fixed, paraffin-embedded archived specimens comprising 19 adenoid cystic carcinomas (ACC), 18 polymorphous low-grade adenocarcinomas (PLGA) and 18 pleomorphic adenomas (PA) were utilized in this study. A standard immunohistochemical technique was used to determine the expression levels of beta-6 integrin, tenascin-C, and matrix metalloproteinase-1 (MMP-1) proteins. Sections were assessed semiquantitatively, and tumors were divided into two groups, low-expressors (0-1+) and high-expressors (2-3+) for statistical analysis. Staining was graded as 0 (<1% positive tumor cells), 1+ (<25% positive tumor cells), 2+ (25-50% positive tumor cells), and 3+ (>50% positive cells). The results showed that the malignant tumors were higher expressors of beta-6 than the benign tumors. ACCs showed significantly higher expression of beta-6 than PAs (p=0.04). No significant difference was observed between ACCs and PLGAs. beta-6 expression was rarely seen in normal salivary gland epithelium and was occasionally present in mucosa overlying the tumors. PAs were high-expressors of tenascin-C with a significant difference relative to ACCs (p=0.03). A majority of tumors in all three tumor types showed high expression of MMP1 with expression significantly greater in the PAs compared to ACCs (p=0.008). We conclude that ACCs and PLGAs express beta-6, tenascin-C, and MMP-1, but that their expression patterns are not significantly different. beta-6 appears to be more closely associated with the malignant tumors, and MMP-1 more closely associated with the benign tumors. We believe that beta-6, tenascin-C, and MMP-1 proteins are part of the molecular repertoire used by salivary tumors for malignant invasion and benign tumor expansion

In this study we have developed and tested a novel pain questionnaire to measure the pain experienced by patients with oral squamous cell carcinoma. The questionnaire consisted of 8 questions rated by the patient on a visual analog scale. Patients completed the questionnaire at the time of initial presentation before surgical treatment. None of the patients were taking analgesics. The responses were then scored and compiled with patient data and pathology reports. Of the 15 completed questionnaires, 14 patients reported some level of functional restriction from pain (mean, 46.6 +/- 25.2, scale of 0 to 100 mm). On average, patients experienced significantly higher function-related, rather than spontaneous, pain intensity and sharpness. Men (n = 8) had a significantly higher level of function-related pain intensity and sharpness than women had (n = 7). There was a strong correlation between nodal disease and increased levels of spontaneous intensity, sharpness, throbbing, and overall functional restriction. PERSPECTIVE: The results of this study indicate the heterogeneous nature and function dependence of oral cancer pain. The questionnaire we have developed in this study will allow for correlations between pain parameters and specific tumor biology in future studies