Epstein-Barr Virus-Infected Plasma Cells Infiltrate Erosive Oral Lichen Planus.

Epstein-Barr virus (EBV), in addition to its transforming properties, contributes to the pathogenesis of several inflammatory diseases. Here, we investigated its involvement in oral lichen planus (OLP), a common autoimmune-like disease of unknown etiopathogenesis that can display a malignant potential. EBV-infected cells (EBV+ cells) were sought in a large series of clinically representative OLPs ( n = 99) through in situ hybridization to detect small noncoding EBV-encoded RNAs. Overall, our results demonstrated that EBV was commonly found in OLP (74%), with significantly higher frequency (83%) in the erosive form than in the reticular/keratinized type mild form (58%). Strikingly, many erosive OLPs were massively infiltrated by large numbers of EBV+ cells, which could represent a large part of the inflammatory infiltrate. Moreover, the number of EBV+ cells in each OLP section significantly correlated with local inflammatory parameters (OLP activity, infiltrate depth, infiltrate density), suggesting a direct relationship between EBV infection and inflammatory status. Finally, we characterized the nature of the infiltrated EBV+ cells by performing detailed immunohistochemistry profiles ( n = 21). Surprisingly, nearly all EBV+ cells detected in OLP lesions were CD138+ plasma cells (PCs) and more rarely CD20+ B cells. The presence of EBV+ PCs in erosive OLP was associated with profound changes in cytokine expression profile; notably, the expression of key inflammatory factors, such as IL1-ß and IL8, were specifically increased in OLP heavily infiltrated with EBV+ PCs. Moreover, electron microscopy-based experiments showed that EBV+ PCs actively produced EBV viral particles, suggesting possible amplification of EBV infection within the lesion. Our study thus brings conclusive evidence showing that OLP is commonly infiltrated with EBV+ PCs, adding a further puzzling element to OLP pathogenesis, given that PCs are now considered to be major regulatory immune cells involved in several autoimmune diseases (ClinicalTrials.gov NCT02276573).

[Optimizing biopsies of the oral mucosa]. / Optimisation des biopsies des muqueuses buccales.

We had for aim to describe and illustrate the artefacts observed in biopsies of the oral mucosa, as well as the impact of sending non-representative histological material to a laboratory. This article was based on an international literature review, as well as on our experience. We analysed the problems raised, for the pathologists and the histology lab-technicians, by these artefacts as well as their impact on the pathology report patient management. We suggest simple solutions.

Er:YAG Laser: A New Technical Approach to Remove Torus Palatinus and Torus Mandibularis.

Objective. The aim of this study was to assess the ability of Er:YAG laser to remove by excision torus mandibularis and to smooth torus palatinus exostosis. Materials and Methods. Torus mandibularis (TM) and torus palatinus (TP) were surgically eliminated via the Er:YAG laser using the following parameters: TM: output power ranging from 500 to 1000 mJ, frequency from 20 to 30 Hz, sapphire tips (diameter 0.8 mm), air-water spray (ratio 5/5), pulse duration 150 µsec, fluence ranging from 99592 J/cm(2) to 199044,586 J/cm(2). TP: a peeling technique was used to eliminate TP, as excision by slicing being impossible here. Results. TM: excision was obtained after 12730 pulses. TP: smoothing technique took more time compared with excision. Once peeling was considered to be accomplished, the use of a surgical rasp was necessary to eliminate bone spicules that could delay the wound to heal in good conditions. Conclusion. Er:YAG excision (TM) or Er:YAG peeling (TP) are safe clinical techniques easy to practice even if the time required for excision or surface smoothing is more than the time required with bony burs and high speed instruments.

Ki-67 expression in oral lichen planus.

PURPOSE: The monoclonal antibody Ki-67 detects a nuclear antigen that is present only in proliferating cells. This is of particular interest for the analysis of the proliferation rates of malignant tumors. The aim of this study was to investigate the malignant potential of oral lichen planus (OLP) on the basis of expression of Ki-67 in healthy individuals (HI), patients with OLP and patients with squamous cell carcinoma (SCC), and to see for any potential interdependence between Ki-67 expression and different clinical and histopathological parameters in OLP. METHODS: Immunohistochemistry for Ki-67 was carried out using an avidin-biotin peroxidase complex method. RESULTS: Ki-67 was more expressed in keratinocytes and lymphocytes of OLP patients compared with HI, but less compared with patients with SCC. Keratinocytes and lymphocytes stained with Ki-67 in OLP patients were significantly higher in males, and in OLP specimens showed less developed civatte bodies (CB) and thickening of the basal membrane (TBM). CONCLUSION: Ki-67 may not serve as prognostic biomarker in oral cancer development from the initially diagnosed OLP, but it could help selecting patients with higher need of follow up for prevention of malignancy.

Bcl-2 expression and its possible influence on malignant transformation of oral lichen planus.

PURPOSE: The aim of this study was to investigate the malignant potential of oral lichen planus (OLP) on the basis of the expression of the Bcl-2 marker in healthy individuals (H), patients with OLP and patients with squamous cell carcinoma (SCC), and to establish potential interdependence between expression of Bcl-2 and the different clinical and histopathological parameters in H, OLP, and SCC. METHODS: Immunohistochemistry for Bcl-2 was carried out using an avidin-biotin peroxidase complex method. Tissue sections were treated with mouse monoclonal antibody against Bcl-2 (124, DAKO A/S, Denmark; dilution 1/100). Immunohistochemical parameters measured included total tissue area, total stained area and intensity of stain. RESULTS: Keratinocytes were not Bcl-2 positive in H and were sparsely positive in OLP. The number of lymphocytes stained with Bcl-2 was significantly lower in H as compared to patients with SCC and OLP. Bcl-2 staining was weak to moderate in OLP, and moderate to intense in SCC. Bcl-2-positive lymphocytes were more expressed in older OLP patients (>55 years), and in OLP specimens with orthokeratinized epithelium, less developed acanthosis and highest grade of lymphocyte expression. CONCLUSION: Bcl-2 may not serve as a prognostic biomarker in oral cancer development from OLP, but it could help in selecting patients with higher need of follow up to prevent malignancy.

Expression of Fas/FasL in patients with oral lichen planus.

PURPOSE: To investigate the malignant potential of oral lichen planus (OLP) on the basis of expression of the Fas/FasL markers in healthy individuals (H), OLP patients and patients with squamous cell carcinoma (SCC). PATIENTS AND METHODS: 40 patients with OLP and two control groups were included in this research (H and patients with SCC). Immunohistochemistry for Fas and FasL was carried out using an avidin-biotin peroxidase complex method. RESULTS: Only a low percentage of infiltrating lymphocytes and no keratinocytes were Fas-positive in OLP specimens. The highest percentage of Fas-staining keratinocytes in our survey was identified mostly in H and patients with well-differentiated SCC. In most cases of SCC, OLP and H a high percentage of keratinocytes and lymphocytes were FasL-positive. FasL expression was negatively correlated with the degree of cell differentiation and apoptosis. Taking into consideration that all carcinomas in this survey were highly differentiated, it is not surprising that no statistically significant differences in FasL expression between H, OLP and SCC specimens were detected. CONCLUSION: Downregulation of Fas expression in keratinocytes and lymphocytes of OLP specimens, together with upregulation of FasL, may serve as initial prognostic biomarker in oral cancer development.

[Genic alterations in oral and head and neck squamous cell carcinomas: analysis of international literature]. / Anomalies géniques dans les carcinomes épidermoïdes des voies aérodigestives supérieures : analyse de la littérature internationale.

The development of oral and head and neck squamous cell carcinomas occurs in relation with multiple events including mainly: loss of cycle cell control, evasion from apoptosis, telomerase reactivation. Complex interactions between a set of molecules, cell cycle proteins, tumour suppressor genes, oncogenes and the telomerase, occur in the multiple step process of carcinogenesis. The 2 main ways of control of the cell cycle rely on 2 tumour suppressor genes: the P53 gene and the retinoblastoma gene or RB gene. One of the regulation pathways or the 2 regulation pathways are disabled during the development of oral and head and neck squamous cell carcinomas. Most of the time, the inactivation of the P53 pathway results from a loss of function of the p53 protein, secondary to mutation and/or deletion of the P53 gene; It may also result of the amplification of the MDM2 gene and of the inactivation of the arf protein. The RB pathway leads to cell proliferation by loss of the p16 protein, by amplification of the cyclin D1 gene and less frequently by mutation of the RB gene or loss of the retinoblastoma protein. In India and South-East Asia, the activation of RAS and MYC oncogenes appears to be related with the presence of specific carcinogens in snuff and tobacco. By blocking apoptosis, the Bcl2 protein seems to increase the resistance of tumours to radiotherapy and chemotherapy.

Nuclear DNA content, an adjunct to p53 and Ki-67 as a marker of resistance to radiation therapy in oral cavity and pharyngeal squamous cell carcinoma.

Factors of prognosis and radioresistance in oral cavity and pharyngeal squamous cell carcinoma (OCPSCC) are limited. In the present study, the usefulness of tumor DNA content in predicting radioresistance in patients with OCPSCC has been investigated. Radioresistance has been defined as local recurrence or tumor persistence after radiation therapy. DNA-ploidy analysis was performed by static cytometry on smears of cell suspensions obtained from formalin-fixed paraffin-embedded material and stained with Feulgen. DNA-ploidy was correlated with the proliferation rate (Ki-67) and p53 protein accumulation obtained by immunohistochemistry. The follow-up of patients ranged from 8 to 62 months. Radioresistance was more common in non-diploid tumors; 14/28 (50%) non-diploid tumors recurred, whereas only 3 (10.7%) out of 28 diploid tumors had local failure (P=0.0019). Proliferation rate and p53 accumulation, evaluated by immunohistochemistry, also added prognostic information. Twelve out of 14 failures were from non-diploid tumors with a low proliferation rate (Ki-67<20%), whereas none of 20 p53-negative diploid tumors developed recurrences. This study showed that non-diploid tumors responded poorly to radiotherapy. DNA content appeared, therefore, as a significant prognostic marker for the evaluation of OCPSCC in patients receiving radiation therapy. This study also showed that DNA content adds information to p53 accumulation and the proliferation rate (Ki-67) for the purposes of determining patient management.

Occurrence of oral mucosal necrosis in a patient with barbiturate-induced coma.

Although dermal lesions in patients with drug poisoning have been widely documented, similar oral conditions are seldom reported. A case of cutaneous and oral mucosal necrosis related to barbiturate-induced coma is reported.