Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype.

Oral potentially malignant disorders (OPMD) are clinical presentations that carry an increased risk of cancer development. Currently, epithelial dysplasia grade is based on architectural and cytological epithelial changes and is used to predict the malignant transformation of these lesions. However, predicting which OPMD will progress to a malignant tumor is very challenging. Inflammatory infiltrates can favor cancer development, and recent studies suggest that this association with OPMD lesions may be related to the etiology and/or aggressive clinical behavior of these lesions. Epigenetic changes such as histone modifications may mediate chronic inflammation and also favor tumor cells in immune resistance and evasion. This study aimed to evaluate the relationship between histone acetylation (H3K9ac) and DNA damage in the context of dysplastic lesions with prominent chronic inflammation. Immunofluorescence of "low-risk" and "high-risk" OPMD lesions (n = 24) and inflammatory fibrous hyperplasia (n = 10) as the control group was performed to assess histone acetylation levels and DNA damage through the phosphorylation of H2AX (γH2AX). Cell co-culture assays with PBMCs and oral keratinocyte cell lines (NOK-SI, DOK, and SCC-25) were performed to assess proliferation, adhesion, migration, and epithelial-mesenchymal transition (EMT). Oral dysplastic lesions showed a hypoacetylation of H3K9 and low levels of γH2AX compared to control. The contact of dysplastic oral keratinocytes with PBMCs favored EMT and the loss of cell-cell adhesion. On the other hand, p27 levels increased and cyclin E decreased in DOK, indicating cell cycle arrest. We conclude that the presence of chronic inflammation associated to dysplastic lesions is capable of promoting epigenetic alterations, which in turn can favor the process of malignant transformation.

Macrophages CD163+ and Factor XIIIa+ Provide a First-Line Defence against Proliferative Verrucous Leukoplakia Antigens.

This study aimed to evaluate the density of the dendritic cells (DCs) and macrophages in oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) by immunohistochemical analysis. We analysed paraffined tissue samples of PVL (n = 27), OL (n = 20), and inflammatory fibrous hyperplasia (n = 20) as the control group using the immunomarkers for DCs (CD1a, CD207, CD83, CD208 and CD123) and macrophages (CD68, CD163, FXIIIa and CD209). A quantitative analysis of positive cells in the epithelial and subepithelial areas was determined. Our results showed a reduction in CD208+ cells in the subepithelial area of the OL and PVL compared to the control. Additionally, we found a higher density of FXIIIa+ and CD163+ cells in the subepithelial area in PVL compared to the OL and control. Four-way MANOVA revealed a relationship between increased CD123+ cell density in the subepithelial area of "high-risk" samples regardless of disease. Macrophages provide the first line of defence against PVL antigens, suggesting a distinct pattern of innate immune system activation in PVL compared to OL, which may contribute to the complexity and the high rate of malignant transformation in the PVL.

Clinical profile of oral mucosa lesions in elderly patients: a 20-year retrospective study / Perfil clínico das lesões da mucosa oral em pacientes idosos: um estudo retrospectivo de 20 anos

Background: Life expectancy has considerably increased resulting in population aging. Studies evaluating the outcomes of aging in oral health are scarce. Objective: Evaluate retrospectively the profile of elderly patients from a public Oral Medicine Center during a period of 20 years. Methods:A qualitative and quantitative retrospective observational study was conducted analyzing medical records from an oral medicine service from January 1994 to December 2014. Results were reported as mean ± standard deviation for quantitative variables and percentages for categorical variables. The Chi-square test and T-student test was applied with significance level of 5%. Results: 2,690 medical records were retrieved, comprising of 61% women and 39% men with an average ageof 68.8 ± 6.79 years. Xerostomia was significantly associated, hypoglycemic usage (p<0.0001), anticoagulantusage (p<0.0001), psychotropic usage (p<0.0001) and analgesics and anti-inflammatory usage (p<0.0001). Forcandidiasis, an association with age, xerostomía (p<0.0001), and use of complete dentures was found(p<0.0001). For oral squamous cell carcinoma and oral leukoplakia the tabacco (p<0.0001) and alcohol consumption (p<0.0001) were significant associated. Conclusion:The elderly population was comprised mostly by women that use a large of drugs which wereassociated with xerostomia development. In addition, tabaco and alcohol consumption were associated withoral leukoplakia and OSCC being these two diseases more frequently in men. Dental care services should aimto prevent and treat these complications as way to improve the elderly's quality of life.

Introdução: A expectativa de vida aumentou consideravelmente, resultando no envelhecimento da população. Estudos avaliando os desfechos do envelhecimento na saúde bucal são escassos. Objetivo: Avaliar retrospectivamente o perfil dos pacientes idosos de um Centro de Medicina Oral público durante um período de 20 anos. Materiais e métodos: Estudo observacional retrospectivo qualitativo e quantitativo, analisando os prontuários de um serviço de medicina bucal no período de janeiro de 1994 a dezembro de 2014. Os resultados foram expressos em média ± desvio padrão para variáveis quantitativas e percentuais para variáveis categóricas. Aplicou-se o teste Qui-quadrado e o teste T-student com nível de significância de 5%. Resultados: Foram recuperados 2.690 prontuários, sendo 61% mulheres e 39% homens com idade média de 68,8 ± 6,79 anos. Xerostomia foi significativamente associada, uso de hipoglicemiantes (p<0,0001), uso de anticoagulantes (p<0,0001), uso de psicotrópicos (p<0,0001) e uso de analgésicos e anti-inflamatórios (p<0,0001). Para candidíase, foi encontrada associação com idade, xerostomia (p<0,0001)e uso de prótese total (p<0,0001). Para carcinoma espinocelular oral e leucoplasia oral, o uso de tabaco (p<0,0001) e consumo de álcool (p<0,0001) estiveram associados significativamente. Conclusão: A população idosa foi composta em sua maioria por mulheres que fazem uso de grande quantidade de medicamentos associados ao desenvolvimento de xerostomia. Além disso, o consumo de tabaco e álcool foram associados com leucoplasia oral e OSCC sendo essas duas doenças mais frequentes em homens. Os serviços odontológicos devem ter como objetivo prevenir e tratar essas complicações como forma de melhorar a qualidade de vida dos idosos.

High density of CD8 T cell and immune imbalance of T lymphocytes subsets are associated with proliferative verrucous leukoplakia.

Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1ß and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.

Usefulness of protein-based salivary markers in the diagnosis of oral potentially malignant disorders: A systematic review and meta-analysis.

By using a meta-analytical approach, this study aimed to analyse the diagnostic capacity of protein-based biomarkers in saliva for the differential diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) from healthy individuals as control group (HCG).Articles on protein-based biomarkers in saliva, which provided quantitative expression in individuals with clinical and histopathological diagnosis of OPMD or oral leukoplakia (OL) were considered eligible. Searches were conducted in eight electronic databases. The methodological quality was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). Functional analysis was also performed. Meta-analyses were performed using the OpenMeta tool (Analyst).Meta-analysis was possible for 4 of the 11 biomarkers studied. Only the carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21) were significant for the OSCC/OPMD subgroup, both with a very low heterogeneity. CEA had an OE = 25.854 (CI95%: 13.215-38.492, p< 0.001, I2 = 0) and CYFRA21 had an OE = 9.317 (CI95%: 9.014-9.619, p< 0.001, I2 = 0). For the OPMD/HCG subgroup, only CYFRA21 was significant, with an OE = 3.679 (CI95%: 0.663-6.696, p= 0.017) although with high heterogeneity (I2 = 91.24).The CEA and CYFRA21 markers proved very useful when differentiating OSCC from OPMD. The CYFRA21 was the only protein that was capable of distinguishing between OPMD and healthy controls.

Ecstasy Abuse and Its Effects on the Oral Mucosa.

Ecstasy is an illicit drug that has been increasingly abused by young people. This synthetic drug has both stimulant and hallucinogenic effects and is usually consumed in a tablet. The side effects of ecstasy use include nausea, muscle cramping, fever, and symptoms mostly linked to muscular tension including jaw pain, facial pain, and headaches. There are few studies assessing the ecstasy effects on the oral mucosa, both clinically and histopathologically. The authors report 2 young women (22- and 27-year-old) who presented multifocal oral erosions and ulcerations. The lesions were painful and covered by a yellow-white pseudomembrane with a bright erythematous halo. By microscopy, it was observed superficial ulceration surrounded by acanthotic squamous epithelium with marked spongiosis, interstitial edema within the corion and perivascular lyphoid infiltrate, suggesting drug-induced oral mucositis. In conclusion, ecstasy use may be associated with the development of oral ulcers, which should be considered in the differential diagnosis when assessing multifocal oral ulcerations, especially in young people.

Glycogenic acanthosis on mouth clinically present as white plaque / Acantose glicogênica na boca clinicamente presente como placa branca

ABSTRACT Glycogenic acanthosis is a benign condition, commonly observed during endoscopic procedures in older patients, which present as slightly elevated whitish plaques often on the lower third of the oesophagus. Microscopically, glycogenic acanthosis is composed of hyperplastic squamous epithelium with intracytoplasmic glycogen deposits. The extraoesophageal glycogenic acanthosis is extremely rare, with only three case reports in the English-language literature. We report a white lesion showing glycogenic acanthosis-like features located on the left posterolateral border of the tongue, affecting a 56-year-old male patient. The medical history was non-contributory and the patient did not show any lesions during endoscopic examination of the oesophagus, stomach, and upper duodenum. Glycogenic acanthosis is a benign condition, which should be included in the differential diagnosis when assessing oral white lesions. It is important also to recognize this benign condition early and rule out the possibility of other more severe diseases, but further studies were necessary for better define their potential for persistence or recurrence, as observed in the current case.

RESUMO A acantose glicogênica é uma condição benigna, comumente observada durante procedimentos endoscópicos em pacientes idosos, e se apresenta como placas brancas levemente elevadas, freqüentemente encontrada no terço inferior do esôfago. Microscopicamente, a acantose glicogênica é composta por epitélio escamoso hiperplásico com depósitos de glicogênio intracitoplasmático. A acantose glicogênica extra-esofágica é extremamente rara, com apenas três relatos de casos na literatura em língua inglesa. Apresentamos um caso com uma lesão branca diagnosticada como acantose glicogênica, localizada na borda póstero-lateral esquerda da língua, afetando um paciente do sexo masculino de 56 anos. A história médica não foi contribuitória e o paciente não apresentou lesões durante o exame endoscópico do esôfago, estômago e duodeno superior. A acantose glicogênica é uma condição benigna, que deve ser incluída no diagnóstico diferencial na avaliação de lesões brancas orais. É importante também reconhecer precocemente essa condição benigna e descartar a possibilidade de outras doenças mais graves, porém mais estudos são necessários para melhor definir seu potencial de persistência ou recorrência, como observado no presente caso.

Squamous cell carcinoma antigen as a prognostic marker and its correlation with clinicopathological features in head and neck squamous cell carcinoma: Systematic review and meta-analysis.

BACKGROUND: Several studies investigate the prognostic value of squamous cell carcinoma antigen (SCC-Ag) in head and neck squamous cell carcinoma (HNSCC) patients, with contradicting findings. Considering this, the aim of this study was to evaluate the prognostic value of high SCC-Ag levels and its association with clinicopathological features of HNSCC. MATERIAL AND METHODS: PubMed, SCOPUS, and Cochrane Library were searched for relevant studies up to December 2015. English-language publications assessing clinicopathological features of HNSCC and the prognostic significance of SCC-Ag in this disease were included. A meta-analysis was performed using Review Manager 5.3 and STATA version 14 software to clarify a possible association between SCC-Ag and clinical outcomes. RESULTS: A total of 11 studies met inclusion criteria, comprising 1901 cases of HNSCC. The results of the meta-analysis showed that there was significant correlation between high SCC-Ag levels and males (odds ratio [OR]=2.99, 95% CI: 1.18-7.57, P=.02 fixed-effect), and advanced TNM stages (OR=3.18, 95% CI: 1.88-5.38, P<.0001 random-effect). The survival meta-analysis showed a pooled hazard ratio for disease-free survival (DFS) and overall survival (OS) of 1.01 (95% CI: 0.70-1.31) and 0.86 (95% CI: 0.54-1.17), respectively. CONCLUSION: Our meta-analysis suggests that elevated SCC-Ag levels have a significant correlation with males and TNM stage, but may not be used as predictive marker for OS and DFS in HNSCC patients.

Chronic paracoccidioidmycosis in a woman with Crohn Disease.

We report a rare case of chronic paracoccidioidomycosis(PCM) in a woman with Crohn disease in the setting of treatment with azathioprine and mesalazine. Serum tests for antigens to Paracoccidioides brasiliensis, Histoplasma capsulatum, and Aspergillus fumigatus were negative. An incisional biopsy of an oral lesion with periodic acid-schiff and Grocott-methenamine silver stains revealed chronic granulomatous inflammation with multinucleated giant cells with Paracoccidioides brasiliensis within the cytoplasm, confirming the diagnosis of PCM.

Cryotherapy for localized juvenile spongiotic gingival hyperplasia: preliminary findings on two cases.

BACKGROUND: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a distinct subtype of inflammatory gingival hyperplasia that shows lack of response to traditional periodontal treatment, and after surgical excision, recurrence rate of 6-16% has been reported. CASE REPORT: Two girls (11- and 9-year-old) with multifocal red patches along the maxillary and mandibular labial gingiva showed no regression of the lesions after basic periodontal treatment. Surgical excision of focal lesion in each case was performed, which showed typical features of LJSGH. In both cases, the lesions presented recurrence. Hence, cryotherapy sessions in all lesions were performed. CONCLUSION: Cryotherapy appears to be successfully in LJSGH and well received by paediatric patients.

Pathological Mandibular Fracture Associated With Diffuse Large B-Cell Lymphoma in HIV-Positive Patient.

This article describes the occurrence of diffuse large B-cell lymphoma in a 39-year-old human immunodeficiency virus-positive patient. The patient sought medical care complaining of increased volume in the right mandibular angle and imaging tests showed an extensive radiolucency with undefined boundaries compromising the mandibular border. After the incisional biopsy, the patient had a pathological fracture in the region, which was properly treated in a second surgical procedure using a 2.4-mm reconstruction plate. Immunohistochemical analysis revealed positive marking for CD3, CD79a, Ki67, and Epstein-Barr virus-encoded RNA. The treatment consisted of concurrent antiretroviral therapy with chemotherapy with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone. Examinations of images (2 years postoperatively) revealed complete bone repair and absence of injury recurrence. This work is important because it describes an unusual location of diffuse large B-cell lymphoma and shows the importance of diagnosis and treatment of the injury at an early stage in order to promote the prognosis and survival of patients.

Oral Intravascular Papillary Endothelial Hyperplasia Associated with an Organizing Thrombus: Case Report and Immunohistochemical Analysis.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign lesion of the skin and mucosa of vascular origin characterized by reactive proliferation of endothelial cells. A 76-year-old woman was referred presenting a painless nodule on the lip. Intraoral examination revealed bluish submucosal nodular proliferation, measuring 10 × 5 × 5 mm, affecting the lower labial mucosa. The lesion had a firm consistency and it was not fixed to the adjacent tissues. The main differential diagnoses were mucocele/mucus retention cyst, sialolith, or salivary gland neoplasia. An incisional biopsy was performed and during the intraoperative procedure an encapsulated red-bluish nodular mass was observed. Microscopic analysis revealed papillary endothelial proliferation in the center of the lesion and fibrin admixed with inflammatory cells in organization peripherally. There was no nuclear atypia, mitotic figures, or necrosis. The endothelial cells were CD34 positive, with low Ki-67 proliferation index (4%). α-SMA highlighted the vessel walls, whereas negativity for D2-40 excluded lymphatic origin. Final diagnosis was IPEH associated with an organizing thrombus. Dentists should be aware about this rare benign vascular lesion, whose final diagnosis is achieved only after histopathology analysis. Surgical removal is the treatment of choice and no recurrence is expected.

Effect of surface roughness on the hydrophobicity of a denture-base acrylic resin and Candida albicans colonization.

AIM: The aim of the present study was to evaluate the effect of surface roughness (roughness average [Ra] µm) on the hydrophobicity of a denture-base acrylic resin and the initial adherence and biofilm formation of Candida albicans (C. albicans). METHODS: Disk-shaped specimens were divided into six groups: Ra 0.05, Ra 0.2, Ra 0.4, Ra 0.8, Ra 1.5, and Ra 3.0. Water contact angles (WCA) were measured, and the specimens incubated with C. albicans for 90 min (initial adherence, n = 108) or 48 h (biofilm formation, n = 108). Adhered and biofilm cells were evaluated by c.f.u./mL and 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), and the correlation between the two methods was evaluated. The surface of the specimens and cells (adhered and biofilm) were also analyzed by scanning electron microscopy (SEM). RESULTS: Groups Ra 0.05 and 3.0 exhibited the lowest (~75°) and the highest (~100°) WCA mean values, respectively. For both initial adherence and biofilm formation, no statistically-significant differences were observed among all groups, as determined by c.f.u./mL and XTT. A positive correlation between these two methods was found. SEM analysis showed the presence of scratches and valleys on the acrylic specimens and densely-packed yeast cells covering the entire surface. CONCLUSIONS: Roughness significantly increased hydrophobicity (WCA), but had no effect on the number and metabolic activity of adherent and biofilm cells of C. albicans.