Assessing Oral Epithelial Dysplasia Risk for Transformation to Cancer: Comparison Between Histologic Grading Systems Versus S100A7 Immunohistochemical Signature-based Grading.

While a 3-tier oral epithelial dysplasia grading system has been utilized for decades, it is widely recognized as a suboptimal risk indicator for transformation to cancer. A 2-tier grading system has been proposed, although not yet validated. In this study, the 3-tier and 2-tier dysplasia grading systems, and an S100A7 immunohistochemical signature-based grading system were compared to assess prediction of risk of transformation to oral cancer. Formalin-fixed, paraffin-embedded biopsy specimens with known clinical outcomes were obtained retrospectively from a cohort of 48 patients. Hematoxylin and eosin-stained slides were used for the 2- and 3-tier dysplasia grading, while S100A7 for biomarker signature-based assessment was based on immunohistochemistry. Inter-observer variability was determined using Cohen's kappa ( K ) statistic with Cox regression disease free survival analysis used to determine if any of the methods were a predictor of transformation to oral squamous cell carcinoma. Both the 2- and 3-tier dysplasia grading systems ranged from slight to substantial inter-observer agreement ( Kw between 0.093 to 0.624), with neither system a good predictor of transformation to cancer (at least P =0.231; ( P >>>0.05). In contrast, the S100A7 immunohistochemical signature-based grading system showed almost perfect inter-observer agreement ( Kw =0.892) and was a good indicator of transformation to cancer ( P =0.047 and 0.030). The inherent grading challenges with oral epithelial dysplasia grading systems and the lack of meaningful prediction of transformation to carcinoma highlights the significant need for a more objective, quantitative, and reproducible risk assessment tool such as the S100A7 immunohistochemical signature-based system.

Investigation of the Molecular Profile of Granular Cell Tumours and Schwannomas of the Oral Cavity.

Granular cell tumours (GCTs) are rare submucosal lesions, thought to develop from Schwann cells, characterised by large polygonal cells with abundant lysosomes. The objectives of this study are to investigate whether GCTs have an antigen-presenting cell (APC) phenotype or a neural crest phenotype using immunohistochemistry and to compare expression profiles with Schwannomas. Immunoreactivity to CD68, HLA-DR, CD163, CD40 and CD11c (APC phenotype) and markers of neural crest cell (NCC) origin S100, SOX10, NSE and GAP43 in 23 cases of GCTs and 10 cases of Schwannomas were evaluated. RT-qPCR was used to identify a possible NCC developmental phenotype in 6 cases of GCTs. GAP43 was identified as a new NCC marker for GCTs, and some evidence was found for an APC phenotype from CD68 and HLA-DR immunoreactivity. RT-qPCR failed to identify an NCC developmental phenotype of GCTs, likely due to technical issues.

Oral Hairy Leukoplakia in Patients With No Evidence of Immunosuppression: A Case Series and Review of the Literature.

OBJECTIVES: Oral hairy leukoplakia (OHL) is caused by Epstein-Barr virus (EBV) and is often associated with HIV and other immunosuppressive conditions. It is rare in HIV-negative patients, but has been reported in patients who use immune-modulating medications (e.g., cyclosporine). The objectives of this study were to determine the occurrence of OHL in HIV-negative patients and report Langerhans cell counts in these lesions. STUDY DESIGN: A series of 7 new cases of OHL among HIV-negative patients is described. Langerhans cells were counted using an immunoperoxidase stain for CD1a and light microscopy. RESULTS: The 7 patients were male, ranging in age from 26 to 69 years. Clinically, all lesions were diagnosed as leukoplakia on the lateral border of the tongue. Microscopic examination revealed hyperparakeratosis and candidiasis in some cases, acanthosis and a band-like zone with clearing of cells in the upper spinous layer, which were EBV-positive by in-situ hybridization. There was a significant decrease in Langerhans cell counts in OHL patients. CONCLUSION: OHL can occur in HIV-negative patients.

Geographic tongue: assessment of peripheral nerve status, Langerhans cell, and HLA-DR expression.

OBJECTIVES: The objectives of this study were to determine whether geographic tongue (GT) is an antigen-driven condition by assessing Langerhans cell numbers and the expression of human leukocyte antigen (HLA)-DP, -DQ, and -DR in the epithelium of GT and to assess peripheral nerve status for any possible damage/injury association by quantifying neurite area in connective tissue in GT. STUDY DESIGN: Randomly selected samples of GT were examined by using routine immunoperoxidase staining methods to S100 protein, neurofilament, CD1a, and HLA class II. The Student t test and Mann-Whitney U test were used to assess statistical significance. RESULTS: Langerhans cell numbers were found to be increased in GT. HLA expression was also seen in Langerhans cells and inflammatory cells and in the spinous layer and parabasal epithelial cells in 2 samples of GT. Total nerve tissue, based on area measurements, was not significantly different between GT and control tissues. CONCLUSIONS: The increase in Langerhans cells suggests that GT is a condition that is likely driven by an unknown external antigen. Peripheral nerve damage was not apparent, suggesting that this is not a mechanism whereby patients with GT become symptomatic.

Kallikrein-related peptidase expression in odontogenic cysts and tumors: An immunohistochemical comparative study.

AIM: The aim of the present study was to profile the expression of human kallikrein (KLK)-related peptidases (KLK) in odontogenic lesions. METHODS: Paraffin-embedded, formalin-fixed, non-odontogenic (control) and odontogenic lesions were stained for KLK using a standard immunohistochemical technique. The intensity and proportion of epithelial cells stained was scored. Reverse transcription-polymerase chain reaction was utilized to evaluate KLK 1-15 mRNA expression in ameloblastomas. RESULTS: KLK 3, 4, 9, 11, and 14 were present in all lesions. KLK 3 staining was increased in ameloblastomas and keratocystic odontogenic tumors. KLK 5 was present only in Keratocystic odontogenic tumor. KLK 6 was significantly higher in ameloblastomas than in other lesions. For KLK 7, keratocystic odontogenic tumors and nasopalatine duct cysts were significantly different. KLK 6, 8, 10, 11, and 13 were significantly higher in ameloblastomas than in other lesions. KLK 9 was increased in keratocystic odontogenic tumors and dentigerous cysts. The expression of KLK 1, 4, 7, 8, 10, and 12 mRNA was found in ameloblastomas. CONCLUSION: The results suggested that KLK 6, 8, 10, and 13 could be involved in the progression of ameloblastomas. KLK 10 could have a greater role in odontogenic lesions, rather than non-odontogenic lesions. Future studies aim to define the specific roles of KLK cascades in odontogenic lesions.