Oral Biopsy Service Research Articles

Marginal linear gingival leukoplakia progressing to "ring around the collar"-An ominous sign of proliferative verrucous leukoplakia.

Potentially malignant lesions of the gingiva may frequently present as well-demarcated white lesions confined to the marginal gingiva. These lesions often become thick and verrucoid and spread along the marginal gingiva to encircle the tooth. Some cases of marginal gingival leukoplakia, over time, progress to extensively involve the gingiva fulfilling the criteria for proliferative verrucous leukoplakia (PVL). The objective of this study is to raise awareness of this pattern of leukoplakia by reporting a series of cases of marginal gingival leukoplakia. An Institutional Review Board approved retrospective search of University of Florida and University of Nebraska Medical Center oral biopsy services was performed for all gingival biopsies. Inclusion criteria included cases exhibiting marginal gingival leukoplakia, and with accompanying clinical images. A total of 30 cases of marginal gingival leukoplakia were included. All cases presented as well-demarcated leukoplakias, either on the buccal or lingual gingival margin, or circumferentially forming a "ring around the collar" of single or multiple teeth. Eight patients had recurrent lesions and 12 had multifocal involvement. Six of the 12 patients with multifocal involvement presented with a "ring around the collar." The histopathologic diagnoses were representative of benign lesions in seven cases, premalignant in 13, and malignant or suggestive of malignancy in 10 cases. Seven patients had carcinoma at the time of first biopsy, whereas 6 cases showed progression at time of follow-up. This study aims to raise awareness that marginal gingival leukoplakia may represent potentially malignant lesions, and if circumferential and/or thick, may be the first manifestation of PVL.

The prevalence of pseudoxanthoma elasticum–like connective tissue changes in an oral biopsy service and review of the literature

The objective of this pilot study is to determine the prevalence of pseudoxanthoma elasticum (PXE)-like connective changes in an oral biopsy service and compare it with the estimated prevalence of PXE as well as to the prevalence of the mutated PXE gene ABCC6. This prevalence study utilized 500 oral mucosal biopsy specimens received from the biopsy service of the Oral Pathology Consultants at the Ohio State University. Each specimen was microscopically evaluated using hematoxylin and eosin, Verhoeff-van Gieson and von Kossa stains. A prevalence of 9.8% was identified for PXE-like changes in the connective tissue of oral biopsy specimens submitted to this service. The overall prevalence of PXE-like connective tissue changes found in routine oral mucosal biopsy specimens (9.8%) was much higher than either the suspected prevalence of PXE (0.001%-0.004%) or the estimated prevalence of the mutated gene ABCC6 (0.625%-1.25%).

Abstract CN02-02: Malignant risk prediction for patients with oral premalignant lesions

Abstract Oral cancers remain both a challenge and an opportunity for clinicians and scientists working with this disease. Worldwide, it represents a significant global challenge, with close to 300,000 new cases diagnosed each year. The disease is potentially preventable: we have knowledge of its risk factors; it is also at an easily accessible site and is often preceded by oral premalignant lesions (OPLs). The challenge has been to develop a framework that would let us both detect and better manage such lesions. Unfortunately, only a small proportion of OPLs will progress to a cancer and histology alone has not allowed clinicians to differentiate high- from low-risk lesions. This uncertainty has also meant that, even when OPLs are detected, there is no consensus on who to treat and how. In 1999, we established the Oral Cancer Prevention Program in British Columbia to develop an integrated knowledge translation approach to facilitate systematic change for prevention, detection and management of this disease across the continuum of care throughout the province. This effort has involved optimization of screening in community dental practices, creation of a triage pathway from a centralized oral biopsy service to oral dysplasia clinics where patients are assessed, and formation of linkages to the cancer agency and local hospitals to facilitate both treatment and follow-up. A new Canadian Partnership Against Cancer-funded Oral Dysplasia Surveillance System has been developed in BC to monitor natural history of the disease. This province-wide structure has facilitated the formation of the Oral Cancer Prediction Longitudinal (OCPL) study, a unique resource for development and validation of biomarkers of risk of malignant progression. To date, ∼ 450 low-grade (mild and moderate) dysplasia cases have been accrued to this study and are in follow-up. In September of this year, we published results from the first 296 patients accrued to the OCPL study (Zhang et al., Cancer Prevention Research). We focused on the validation of a LOH risk model proposed by our group in 2000 that utilized a set of microsatellite markers at key chromosomal loci to predict progression of low-grade dysplasia in a retrospective cohort (Rosin et al., Clin Cancer Res 2000; 6:357–62). In the new study, cases were classified into high- or low-risk profiles to validate the 2000 model. Risk models were further refined using recursive partitioning and Cox regression analyses. The study showed that the high-risk lesions (3p &/or 9p LOH) had a 22•6 -fold increase in risk (P = 0•002) compared to low-risk lesions (3p & 9p retention). Addition of another two markers (loci on 4q/17p) further improved the risk prediction, with five-year progression rates of 3•1%, 16•3%, and 63•1% for the low-, intermediate-, and high-risk lesions, respectively. Compared to the low-risk group, intermediate- and high-risk groups had 11•6-fold and 52•1-fold increase in risk (P < 0•001). The new LOH profiles in the refined model were validated as risk predictors by using the initial retrospective cohort from 2000. Multi-covariate analysis with clinical features showed LOH models to be the most significant predictors of progression. The importance of this study is that it has direct implication for standard of care in the community setting, providing a tool by which patients could be triaged to different levels of intervention. Patients with elevated risk would be guided towards increased surveillance with this risk providing a rationale for the targeting of intervention regimes, even if these were associated with some morbidity. Two of three patients with such high-risk profiles progressed to cancer in 5 years. In contrast, patients with low-risk profiles could be spared in from aggressive monitoring and intervention. In our study, low-risk patients represented close to half of those individuals that were accrued to the study. Future research should be aimed towards exploring such possibilities, as an initial step towards personalizing oral cancer prevention strategies. LOH is currently being used in two chemoprevention trials of patients with OPLs to guide patient accrual: the phase III Erlotinib Prevention of Oral Cancer study and the Phase II Cetuximab for Treatment of High-Risk Pre- Malignant Upper Aerodigestive Lesions trial. The results of these studies should provide even greater knowledge upon which to build new strategies for patient triage that could better focus risk reduction programs for this disease. (Supported by grants from the NIH and the National Institute of Dental and Craniofacial Research (R01DE13124 and R01DE17013). Citation Format: Miriam P. Rosin, Lewei Zhang, Catherine Poh, Michele Williams, Denise M. Laronde, Ken Berean, Pamela J. Gardner, Huijun Jiang, Lang Wu, J. Jack Lee. Malignant risk prediction for patients with oral premalignant lesions. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN02-02.

Unique FISH Patterns Associated with Cancer Progression of Oral Dysplasia

Subgroups of patients with oral pre-malignant lesions (OPLs) are at extremely high risk for developing invasive cancer in spite of surgical excision. The objective of this study was to evaluate the utility of specific genes and their associated centromeres as markers to stratify OPLs for their cancer risk. Samples used in this study included 35 oral dysplasia with known outcome and 20 normal oral mucosa. Of the dysplasias, 20 were from an ongoing longitudinal study showing progression. The remaining 15 cases (2 of which progressed) were chosen from the population-based, provincial BC Oral Biopsy Service (OBS). Copy number alterations at EGFR, CEP7, CCND1, and CEP11 were evaluated by fluorescent in situ hybridization (FISH). There was no significant difference in demographics between progressors and non-progressors. Specific FISH profiles at these genes and their corresponding centromeres were associated with progression. High gene gain of CCND1 was associated with an 8-fold elevated risk of progression compared with those with no gain in time-to-progression analysis. Numerical alterations of EGFR and CCND1 and their centromeres might be an effective means for identifying OPLs at risk. Future studies will expand on this analysis and set the stage for application of this approach in routine clinical practice.

Abstract PL05-04: From basic science to public health: The Canadian approach to oral leukoplakia

Abstract PL05-04: From basic science to public health: The Canadian approach to oral leukoplakia

Dentigerous cyst: a retrospective clinicopathological analysis of 2082 dentigerous cysts in British Columbia, Canada

The aim of this research is to analyze the prevalence of dentigerous cysts (DCs) in a population-based cohort in British Columbia, Canada, and to report unusual cases associated with DC. The database of the British Columbia Oral Biopsy Service was searched from 1998 to 2007. 2082 histologically confirmed DCs from 2029 patients were retrieved and retrospectively analyzed for incidence, age, gender and ethnicity. The results show that this is a common jaw cyst with male predilection, has a peak incidence in younger adults and is more common in Caucasians. Multiple DCs, representing 2.5% of the cases, are not associated with any syndromes or systemic conditions. 0.5% DCs were associated with other cysts or tumours at the same site or the opposite side of the jaw. The authors report the first series of cases presenting clinically as bilateral DCs, but histologically as an odontogenic tumour or another type of odontogenic cyst. DCs can co-exist with other more serious conditions, such as odontogenic keratocyst or cystic ameloblastoma. This association with more significant conditions indicates the importance of histologically confirming any jaw cyst, even when it presents clinically as a classic DC.

Abstract C31: Identification of causal genetic events in oral cancer progression

Abstract Background: Oral cancer is one of the world's leading causes of cancer death, with late stage disease diagnoses and high rates of recurrence accounting for poor survival rates. Like many solid tumors, oral cancer develops through a series of histopathological stages from dysplasia, to carcinoma in situ (CIS), to invasive disease. Escalating genomic instability and the accumulation of critical gene alterations is thought to drive disease progression. Causal gene changes remain to be identified for oral cancer. The objective of this study is to determine the essential gene alterations underpinning oral cancer progression. Hypothesis: Since cancers arise through the accumulation of genetic alterations, gene changes detected in the earliest stages of disease are the foundation of observed cancer phenotypes and essential for oral tumorigenesis. Experimental Approaches: Oral premalignant lesions and tumor samples were obtained from the Oral Biopsy Service of British Columbia and are associated with well annotated patient information (including disease outcomes). High resolution tiling-path array comparative genomic hybridization was used to define segmental DNA changes for each sample. Recurring regions of DNA alteration detected in premalignant lesions known to progress and preserved in later stage disease were flagged as critical events. Our list of candidate genes within these regions will be refined by analysis of publicly available genomic and gene expression data from oral tumors. Results: Whole genome copy number profiles from over 100 oral lesions and tumors have been successfully generated using array comparative genomic hybridization. From this data we have identified several molecular subgroups associated with initiation and progression of oral cancer. Significance: With knowledge of the key genes fueling oral tumorigenesis, we will be able to derive novel biomarkers capable of predicting disease behavior as well as gain a better understanding of the molecular pathways and gene networks responsible for driving oral cancer progression. Citation Information: Cancer Res 2009;69(23 Suppl):C31.

Squamous cell carcinoma of the gingiva: A case series analysis

Recent studies suggest that patients with carcinoma of the gingiva exhibit demographic features that differ from those of persons with squamous carcinoma at other intraoral sites. In this study, we sought to explore this hypothesis in greater detail. Records from the University of Connecticut Oral Biopsy Service from 1975 through 1992 inclusive were surveyed for cases of oral carcinoma. A total of 577 cases were retrieved and analyzed with respect to prevalence, gender distribution, and age at diagnosis. We found that the gingiva (alveolar ridge included) was the third most common site for oral squamous carcinoma after carcinoma of the floor of the mouth and tongue. Further, the relative proportion of gingival cancer versus carcinoma at other intraoral subsites remained essentially constant throughout the study period. Male-to-female ratios were significantly greater for cancer of the floor of the mouth as compared with both cancer of the tongue and cancer of the gingiva (ridge included). Age was not a significant predictor of oral cancer subsite, and there were no apparent differences between carcinoma of the dentate gingiva and that of the edentulous ridge. Results of this study indicate that gender-specific predilections exist for squamous cell carcinoma at different intraoral subsites. These differences suggest the possibility of different etiologic factors and pathogenetic mechanisms involved in carcinoma of the gingiva compared with surface carcinoma at other intraoral sites.

Leiomyoma of the oral cavity: a light microscopic and immunohistochemical study with review of the literature from 1884 to 1992.

Leiomyoma is the most common benign neoplasm in the uterus and stomach but is rare in the oral cavity. There were only 5 oral cases in a series of 7748 leiomyomas of all sites. Benign smooth muscle neoplasms are classified into leiomyoma (solid leiomyoma), angiomyoma (vascular leiomyoma) and epithelioid leiomyoma (leiomyoblastoma). 6 cases diagnosed as leiomyoma were retrieved from the files of two oral biopsy services over the past 25 years. A light microscopic study including trichrome and phosphotungstic acid haematoxylin (PTAH) stains, and an immunohistochemical study with the following markers: desmin, muscle specific actin, myoglobin, vimentin, S-100 protein, neuron-specific enolase, factor VIII and Ulex europeus were done with suitable controls. The haematoxylin and eosin and Masson's trichrome stains supported a diagnosis of leiomyoma in all 6 cases but PTAH was positive in only 3 of them. The immunohistochemical study confirmed the diagnosis of leiomyoma in 3 cases. The other 3 were identified as granular cell tumour, myofibroma and neurofibroma, respectively. The review of the literature contributed the following data: mean age was 41 and median age 39 in 134/142 patients. A male sex prevalence 72/137 patients (54.0%) was noted. The lips were the most common site with 39 cases (27.46%) followed by the tongue 26 (18.30%), cheeks and palate 22 (15.49%), gingiva 12 (8.45%), and mandible 8 (5.63%). Prognosis of oral leiomyomas is excellent. Immunohistochemistry is a precise and reliable method for definitive diagnosis of oral leiomyoma.

Microcomputer use in an oral biopsy service

The need for rapid and accurate retrieval of the data generated by an oral biopsy service and the adjacent medical center was met with the purchase and programming of a microcomputer and hard disk drive. The planning phase involved an assessment of the needs of the department, creation of an ideal form to be displayed on the video screen that can be easily used to enter the information, selection of coding systems, and selection of compatible hardware and software. Customized in-house programming using a commercially available database management system has created an entry form and menu-driven information retrieval system tailored to the needs of the department.

Computer utilization in an oral biopsy service

In order to improve our knowledge about the biological activity of oral lesions, a computer-based system of oral biopsy data recall has been established. The program is utilized in eight United States dental schools and is adaptable to almost any oral biopsy service with an available computer. This article deals with the implementation of the program at Washington University School of Dental Medicine.