Líquen Plano Oral e seu Potencial de Malignização / Lichen Planus and its potencial for malignancy

Objetivos: Instruir e orientar ao cirurgião dentista e demais profissionais de saúde a importância da detecção e rastreio precoce de lesões pré-malignas. Revisão de Literatura: O Líquen Plano Oral é uma condição dermatológica crônica, de origem auto-imune, relativamente comum na população, que atinge o epitélio de mucosa e pele, sendo considerada, pela Organização Mundial de Saúde (OMS), uma desordem potencialmente maligna quando associado a áreas de ulceração. A revisão de literatura foi realizada nas bases de dados PubMed e Lilacs. Buscamos investigar o potencial de malignização do Líquen Plano Oral associado a condições erosivas, analisando o processo de carcinogênese no processo inflamatório. Conclusão: Conclui-se que o objeto de estudo ainda é um assunto pouco explorado pela literatura, porém há indícios etiopatológicos que enfatizam o processo de malignização oriundo de uma lesão pré-maligna como o Líquen Plano Oral. Além disso, enfatizamos a importância do diagnóstico precoce das lesões estomatognáticas, para que assim possamos aumentar as chances de cura do paciente.(AU)

Objectives: To instruct and guide dentists and other health professionals on the importance of early detection and screening of pre-malignant lesions. Literature Review: Oral Lichen Planus is a chronic dermatological condition, of autoimmune origin, relatively common in the population, which affects the epithelium of the mucosa and skin, being considered, by the World Health Organization (WHO), a potentially fatal disorder. malignant when associated with areas of ulceration. A literature review was performed on the PubMed and Lilacs databases. We sought to investigate the potential for malignancy of Oral Lichen Planus associated with erosive conditions, analyzing the process of carcinogenesis in the inflammatory process. Conclusion: It is concluded that the object of study is still a subject little explored in the literature, but there are etiopathological accusations that emphasize the process of malignancy arising from a pre-malignant lesion such as Oral Lichen Planus. In addition, we emphasize the importance of early diagnosis of stomatognathic lesions, so that we can increase the patient's chances of cure.(AU)

Verruciform xanthoma associated with lichen planus

Verruciform xanthoma (VX) is a rare benign lesion of unknown etiology, with a rough or papillary aspect, painless, sessile, well-defined, most lesions do not exceed 2 cm in their largest diameter, the degree of keratinization of the surface influences color, varying white to red, affecting mainly the gingiva and alveolar mucosa, and can also be seen in skin and genital. Herein, we present a report a clinical case of oral verruciform xanthoma in the buccal mucosa associated with the lichen planus lesion, as well as the morphological and immunohistochemical characteristics of the lesion. The clinical diagnostic hypothesis of oral lichen planus of the white reticular lesions on the buccal mucosa and on the tongue was confirmed by histopathology before a subepithelial connective tissue exhibiting intense inflammatory infiltrate in a predominantly lymphocytic band. In contrast, the hypothesis of the verrucous lesion in the left buccal mucosa was leukoplakia, with histopathological evidence showing exophytic and digitiform proliferations with parakeratin plugs between the papillary projections. Subepithelial connective tissue was characterized by macrophages with foamy cytoplasm (xanthoma cells). An immunohistochemical examination was performed, showing positivity for CD68, a macrophage marker, in addition to testing by Schiff's periodic acid (PAS) with diastasis, which was detected the presence of lipids inside these macrophages. The patient is free of recurrences of verruciform xanthoma and is being monitored due to the presence of lesions of oral lichen planus.

Análise clínico-patológica e qualitativa da expressão de mediadores inflamatórios teciduais no líquen plano oral / Clinicopathological and qualitative analysis of the expression of tissue inflammatory mediators in oral lichen planus

O líquen plano oral (LPO) é uma condição imuno-inflamatória mucocutânea crônica que ainda possui etiologia e patogênese desconhecidas. Estudos mostrando a participação de citocinas no LPO, em especial, interleucinas (IL)-6, IL-17 e IL-18, são escassos, assim como a correlação das características clínicas e histológicas das lesões de LPO com a presença destes mediadores inflamatórios. Todas as lesões de LPO e de lesões liquenoides orais (LLO) foram revisadas a partir do arquivo do laboratório de Patologia Bucal da Faculdade de Odontologia da Universidade do Estado do Rio de Janeiro e as características clínico-patológicas dos casos foram analisadas. Foram selecionados 40 casos de LPO para realização adicional de reações imuno-histoquímicas para IL-6, IL-17 e IL-18. A amostra total foi composta por 221 casos e mostrou que o LPO apresentou predileção por mulheres adultas, mais frequentemente acometidas pelo padrão reticular e com lesões localizadas predominantemente na mucosa jugal. Os 40 casos selecionados para a avaliação imuno-histoquímica incluíram pacientes com média de idade de 53 anos, sem predileção por gênero, e com lesões localizadas preferencialmente na mucosa jugal (85%), na gengiva/mucosa alveolar (47%) e na língua (42%). Quanto ao padrão clínico, 14 pacientes (35%) mostravam lesões exclusivamente reticulares e 26 (65%) mostravam lesões reticulares associadas a lesões atrófico-erosivas. Sintomas foram relatados por 53% dos pacientes e incluíram principalmente ardência e desconforto local. A análise histológica mostrou que o epitélio das lesões mostrava espessura normal, atrófica ou hiperplásica em, respectivamente, 17 (43%), 9 (22%) e 14 (35%) casos. A presença de hiperqueratose foi observada em 21 casos (53%) e exocitose de linfócitos T CD4+ e T CD8+ estava presente em, respectivamente, 17 (42%) e 30 (75%) casos. A análise imuno-histoquímica revelou que a IL-6 foi, de forma geral, a mais expressa, tanto no epitélio, quanto no conjuntivo. A expressão de IL-17 se mostrou intensa no tecido conjuntivo, em 40% dos casos. A IL-18 mostrou intensidade mais frequente leve/moderada tanto no epitélio (40%), quanto no tecido conjuntivo (45%). A presença de exocitose mostrou relação com a maior expressão das ILs e a expressão de IL-17 foi maior no epitélio mostrando hiperqueratose. Os resultados do presente estudo mostraram que as características clínicas das lesões de LPO e de LLO são distintas e podem ser utilizadas para diferenciação entre as duas entidades. Os achados histológicos e imunohistoquímicos sugerem que as ILs estudadas mostram-se mais presentes quando há exocitose linfócitos T CD4+ e T CD8+ e que sua expressão pode ter relação com as alterações epiteliais encontradas no LPO, participando da patogênese e da modulação da expressão da doença.

Oral lichen planus (OLP) is a chronic immunoinflammatory mucocutaneous condition of unknown etiology and pathogenesis. Studies focusing on the presence of cytokines in OLP, especially interleukin (IL)-6, IL-17 and IL-18, are scarce, as well as the correlation of clinical and histological characteristics with the presence of inflammatory mediators. All lesions diagnosed as OLP and oral lichenoid lesions (OLL) were reviewed from the files of the Oral Pathology laboratory, Dental School, Rio de Janeiro State University, and their clinicopathological characteristics were analyzed. Forty cases diagnosed as OLP were selected for additional immunohistochemical reactions directed against IL-6, IL-17 e IL-18. The total sample was composed by 221 cases and showed that OLP presented a predilection for adult females, mostly affected by lesions with the reticular pattern and located in the buccal mucosa. The 40 cases selected for the immunohistochemical reactions included patients with a mean age of 53 years, with no gender predilection, and with lesions located mostly in the buccal mucosa (85%), gingiva/alveolar mucosa (47%) and tongue (42%). The clinical pattern showed reticular lesions in 14 patients (35%) and reticular and atrophic/erosive lesions in 26 patients (65%). Symptoms were reported by 53% of the patients and included mostly burning sensation and local discomfort. Histological analysis showed that the epithelial thickness was normal, atrophic, or hyperplastic in, respectively, 17 (43%), 9 (22%) and 14 (35%) cases. The presence of hyperkeratosis was observed in 21 cases (53%), and exocytosis of T CD4+ and T CD8+ lymphocytes was present in, respectively, 17 (42%) and 30 (75%) cases. Immunohistochemical analysis showed that, in general, IL-6 was the most expressed IL both in epithelium and connective tissue. IL-17 expression was considered intense in the connective tissue from 40% of the cases. IL-18 expression was considered mostly mild/moderate both in epithelium (40% of the cases) and connective tissue (45% of the cases). The presence of exocytosis was associated with a higher expression of the ILs and expression of IL-17 was higher in epithelium showing hyperkeratosis. The results from the present study showed that the clinical characteristics of OLP and OLL are distinct and can be useful in differentiating these two diagnostic entities. The histological and immunohistochemical features suggest that the studied ILs are more expressed when there is exocytosis of both T CD4+ and T CD8+ lymphocytes. Expression of the ILs can be associated with the epithelial alterations encountered in OLP, participating in the pathogenesis and modulating the expression of the disease.

Expression profile of salivary micro RNA-21 and 31 in oral potentially malignant disorders

Abstract Oral potentially malignant disorders (OPMD) possess significant chances of malignancy conversion. In order to develop an early diagnostic tool, the present study evaluated the expression of miRNA-21 and 31 as salivary markers. The case-control study was carried out in 36 healthy participants as controls and in 36 patients who were newly diagnosed as OPMD having four different lesions including leucoplakia, oral sub mucous fibrosis (OSMF)궱, oral lichen planus, and (OSMF)궱 with leucoplakia. The samples were also classified as non-dysplastic, or with mild, moderate, and severe dysplasia according to their histopathological reports. The salivary miRNA-21 and 31 expressions were studied using real-time PCR. The statistical analysis was carried out using SPSS version 22. Salivary miRNA-21 (p-value = 0.02) and 31 (p-value = 0.01) were significantly upregulated in severe dysplasia compared with control. Among the different lesions, leucoplakia had significant upregulation of miRNA-21 and 31. miRNA-21 can be used as a diagnostic marker with specificity of 66% and sensitivity of 69%. The area under the ROC curve was 0.820 for miRNA-21 and 0.5 for miRNA-31, which proved that miRNA-21 is a better diagnostic marker than miRNA-31 for OPMD.

Estudo da imunoexpressão do VEGF165 e do VEGF165B em lesões orais de líquen plano e pênfigo vulgar / Study of VEGF165 and VEGF165B immunoexpression in oral lesions of lichen planus and pemphigus vulgaris

O Líquen Plano Oral (LPO) é uma doença mucocutânea mediada imunologicamente, de etiologia desconhecida, relativamente comum, com prevalências, na população mundial, que variam de 0,22 a 5%. O pênfigo vulgar é uma doença autoimue crônica que pode acometer a mucosa oral sendo o mais comum dos tipos de pênfigo. Entretanto, sua ocorrência é rara, com incidência estimada na população geral de um a cinco casos por milhão de pessoas diagnosticadas a cada ano. O VEGF-A é a proteína angiogênica mais potente tanto na angiogênese normal quanto na patológica. O splicing alternativo do éxon 8 do gene do VEGFA dá origem a duas famílias conhecidas de proteínas isofórmicas, uma desempenhando papel angiogênico, VEGFxxxa, e outra um papel antiangiogênico, VEGFxxxb. Este trabalho se propôs a avaliar a expressão imunoistoquímica do VEGF165 (angiogênico), do VEGF165b (antiangiogênico) em 46 casos de LPO reticular, 23 casos de LPO erosivo e 12 casos de PV, usando como controle 11 casos de hiperplasia fibrosa. Todos os espécimes das lesões e os casos controle foram divididos em e zonas para a análise das marcações, em zona superficial (Z1), média (Z2) e profunda (Z3). Os resultados deste experimento foram submetidos a testes estatístico não-paramétricos com nível de significância de 5%. Comparando apenas as lesões para o marcador anti-VEGF165 foram observadas diferenças significativas apenas nas zonas mais profundas entre as lesões de LPO reticular e PV, e entre as lesões de LPO erosivo e PV. Para o marcador anti-VEGF165b diferenças significativas foram observadas nas zonas médias entre as lesões de LPO reticular e PV; e nas zonas profundas entre LPO erosivo e PV e entre LPO reticular e PV. Avaliando o marcador VEGF165b nos espécimes sem categorizá-los por zonas foram observadas diferenças significativas entre as lesões de LPO reticular e PV. Na análise da correlação entre ambos os marcadores em cada lesão foram observadas correlação positiva fraca e significativa nas zonas média e profunda do LPO reticular e na zona superficial do LPO erosivo. Os resultados do presente estudo sugerem a participação do processo angiogênico na patogênese do LPO e na progressão das lesões de líquen plano oral e pênfigo vulgar, porém outros estudos devem ser realizados a fim de que esses achados, principalmente em relação ao pênfigo vulgar seja fundamentado, uma vez que a presente pesquisa é uma das primeiras que avalia a angiogênese na lesão já estabelecida dessa doença (AU).

Oral Lichen Planus is an immunologically mediated mucocutaneous disease of relatively unknown etiology with prevalences in the world population varying from 0.22 to 5%. Pemphigus vulgaris is a chronic autoimmune disease that may affect the oral mucosa being the most common type of pemphigus. However, its occurrence is rare, with an estimated incidence in the general population of one to five cases per million people diagnosed each year. Angiogenesis plays an important role in tumor growth and in the progression of chronic inflammatory diseases. VEGF-A is the most potent angiogenic protein in both normal and pathological angiogenesis. The alternative splicing of exon 8 VEGF-A gene gives rise to two known families of isoform proteins, one playing angiogenic role, VEGFxxxa, and another an antiangiogenic role, VEGFxxxb. The aim of this study was to evaluate the immunohistochemical expression of VEGF165 (angiogenic), VEGF165b (antiangiogenic) in 46 cases of reticular OLP, 23 cases of erosive OLP and 12 cases of PV, using as control 11 cases of fibrous hyperplasia. All specimens of the lesions and the control cases were divided into zones for the analysis of the immunohistochemical stains, in superficial (Z1), medium (Z2) and deep zones (Z3). The results of this experiment were submitted to non-parametric statistical tests with significance level of 5%. For all immunohistochemical stains the comparison between the lesions with the control group (HF) showed significant differences. Comparing only the lesions to the anti-VEGF165 stains, significant differences were observed only in the deeper zones between the reticular LPO lesions X PV; and between erosive LPO lesions X PV. For the anti-VEGF165b stains, significant differences were observed in medium zones between reticular OLP X PV lesions; and in deep zones between erosive LPO X PV and between reticular LPO and PV. And evaluating VEGF165b stains in specimens without categorizing them by zones was observed a significant difference between reticular LPO and PV lesions. In the analysis of the correlation between both markers in each lesion, a weak and significant positive correlation was observed in medium and deep zones of reticular OLP; and a weak positive correlation in superficial zone of erosive LPO. The present study results suggest angiogenic process participation in the pathogenesis and progression of lesions of oral lichen planus and pemphigus vulgaris. However other studies must be carried out in order that this implication, mainly in relation to pemphigus vulgaris be based once this is one of the first studies to evaluate angiogenesis in the already established lesion of this disease (AU).

P-glycoprotein expression in oral lichen planus

Abstract: Oral lichen planus (OLP) is a stress induced inflammatory condition with malignant potency. The mdr1 (multidrug resistance) is a stress gene overexpressed in cancerous conditions and its translated form, the p-glycoprotein efflux transporter is usually overexpressed with chemotherapy, leading to chemoresistance. OLP, a lesion with carcinogenic potency, is broadly classified into the asymptomatic reticular form and the aggressive erosive form. The objective of the study was to verify the expression level of p-glycoprotein in antifungal-treated and untreated reticular OLP, in untreated erosive OLP and erosive OLP patients treated with corticosteroid. Semi-quantitative reverse transcriptase polymerase chain reaction (SQ-RTPCR) and ELISA were performed on biopsy tissue samples to evaluate the mdr1 mRNA and protein expression of p-glycoprotein, respectively. The present study shows for the first time that mdr1 mRNA as well as its translated form p-glycoprotein are overexpressed in OLP subjects compared to healthy individuals. This overexpression is significantly higher in erosive than in reticular OLP patients, further confirming that the erosive form has higher risk for multidrug resistance. A higher expression is also observed in corticosteroid-treated erosive cases than similar untreated ones. The gradation of expression is in conformity with severity of the disease.

Estrés oxidativo en las enfermedades bucales / Oxidative stress in the oral illnesses

Introducción: toda enfermedad está basada en trastornos a nivel molecular, por lo que el profesional de la salud debe interpretar las variadas manifestaciones internas de las enfermedades producidas por alteraciones de las biomoléculas que interactúan sistémicamente, en las cuales tienen un papel importante el estrés oxidativo. Objetivo: realizar una revisión bibliográfica sobre el estrés oxidativo y las enfermedades que afectan a la cavidad bucal. Métodos: se realizó una revisión bibliográfica en el periodo comprendido entre septiembre de 2014 a enero de 2016. Se consultaron las bases de datos de sistemas referativos, como MEDLINE, PubMed y SciELO con la utilización de descriptores como oxidative stress in oral deseases y su contraparte en español. Se incluyeron artículos en idioma inglés y español y publicaciones de los últimos cinco años, solo seis con mayor tiempo de publicación. Se revisaron 110 artículos, y se circunscribió el estudio a 49 que enfocaron estas temáticas de manera más integral. Análisis e integración de los resultados: tiene el estrés oxidativo gran relación con la enfermedad periodontal, la mucositis, los estados pulpares, síndrome de Sjögren, síndrome de ardor bucal, aftas bucales y lesiones premalignas como leucoplasia y liquen plano bucal. Conclusiones: existe relación entre el estrés oxidativo y muchas enfermedades que afectan la cavidad bucal, lo que influye en la patogenia de estas.(AU)

Introduction: the basis of disease is the occurrence of disorders at the molecular level, so the health professional should be able to understand the varied internal manifestations of a disease caused by alterations in the biomolecules that systemically interact and the important role that the oxidative stress plays in this process. Objective: to make a literature review on the oxidative stress and the diseases affecting the oral cavity. Methods: a literature review was made in the period of September 2014 through January 2016. MEDLINE, PubMed and SciELO databases were consulted; the subject headings were oxidative stress in oral diseases in Spanish and in English. Several articles in English and Spanish and publications of the last five years, in addition to 6 articles published prior to this period, were all included. A total of 110 articles were reviewed, but for the study, 49 were selected on account of a more comprehensive approach on these topics. Data analysis and integration: the oxidative stress is closely related to periodontal disease, mucositis, pulpal diseases, Sjögren syndrome, burning mouth syndrome, oral aphthas and premalignant lesions such as leukoplakia and oral lichen planus. Conclusions: there is association of the oxidative stress and many other diseases affecting the oral cavity, which has an impact on the pathogenesis of many diseases(AU)

Oral lichen planus: clinical profile and determination of oral epithelial dysplasia / Liquen plano oral: perfil clínico y determinación de la displasia epitelial oral

Oral lichen planus (OLP) is the most common noninfectious oral disease and is considered a potentially malignant disorders (OPMDs). The etiology and pathogenesis of OLP are not completely understood and the malignant transformation remains under discussion. The aim was to asses the cytological and histological features of OLP, and establish relationship between clinical and microscopic profiles. A total of 10 patients diagnosed with OLP were investigated. Slides were prepared and stained with Hematoxylin­Eosin to identify 8 histological features and 8 cytological alterations. Finally, oral epithelial dysplasia degree was determined. Hyperplasia and loss of polarity of basal cells were detected in 90 % of cases. Anisonucleosis, nuclear pleomorphism and hyperchromasia affected 100 % of the sample. Six cases were classified as mild-grade OED, with no cases of severe-grade. Microscopic alterations were higher in women (P <0.0001) and moderate-grade OED was diagnosed only in this group (P <0.0014). The findings demonstrated that microscopic and clinical data association should be analyzed to a better understand of disease behavior. OED was absence only in one case, so the periodic follow-up of patients diagnosed with OLP is mandatory to avoid the malignant transformation.

El liquen plano oral (LPO) es la enfermedad no infecciosa más común y se considera un trastorno potencialmente maligno. La etiología y la patogénesis del LPO no se conoce y la transformación maligna sigue siendo objeto de debate. El objetivo de este estudio fue evaluar las características citológicas e histológicas del LPO y establecer la relación entre los perfiles clínicos y microscópicos. Un total de 10 pacientes diagnosticados con LPO fueron investigados. Secciones histológicas se prepararon y tiñeron con hematoxilina-eosina para identificar 8 características histológicas y 8 alteraciones citológicas. Finalmente, se determinó el grado de displasia epitelial. La hiperplasia y la pérdida de la polaridad de las células basales se detectaron en el 90 % de los casos. Anisonucleosis, pleomorfismo nuclear e hipercromasia afectaron al 100 % de las muestras. Seis casos fueron clasificados como displasia epitelial oral (DEO) de grado leve y no se reportaron casos de grado severo. Las alteraciones microscópicas fueron mayores en las mujeres (p <0,0001) y DEO de grado moderado fue diagnosticado sólo en este grupo (p <0,0014). Los resultados demostraron que la asociación de datos microscópicos y clínicos deben ser analizados para una mejor comprensión del comportamiento de la enfermedad. La DEO estuvo ausente sólo en un caso, por lo que el seguimiento periódico de los pacientes diagnosticados con LPO es necesario para evitar la transformación maligna.

Potentially malignant oral lesions: clinicopathological correlations / Lesões orais potencialmente malignas: correlações clínico-patológicas

ABSTRACT Objective To determine the incidence of potentially malignant oral lesions, and evaluate and correlate their clinical and pathological aspects. Methods The sample consisted of cases clinically diagnosed as oral leukoplakia, oral erythroplakia, erythroleukoplakia, actinic cheilitis, and oral lichen planus treated at a diagnostic center, between May 2012 and July 2013. Statistical tests were conducted adopting a significance level of 5% (p≤0.05). Results Out of 340 patients, 106 (31.2%) had potentially malignant oral lesions; and 61 of these (17.9%) were submitted to biopsy. Actinic cheilitis was the most frequent lesion (37.5%) and the lower lip was the most affected site (49.6%). Among 106 patients in the sample, 48 (45.3%) reported nicotine consumption, 35 (33%) reported alcohol intake and 34 (32.1%) sun exposure while working. When clinical and histopathological diagnoses were compared, oral erythroplakia and atypical ulcer were the lesions that exhibited greater compatibility (100% each). Conclusion In most cases, clinical and histopathological diagnoses were compatible. An association between the occurrence of erythroplakia, leukoplakia and erythroleukoplakia with smoking was observed. Similarly, an association between actinic cheilitis and sun exposure was noted. Erythroleukoplakia presented the highest malignancy grade in this study. Finally, dental surgeons should draw special attention to diagnosis of potentially malignant oral lesions, choose the best management, and control the lesions to avoid their malignant transformation.

RESUMO Objetivo Verificar a incidência das lesões orais potencialmente malignas, e avaliar e correlacionar seus aspectos clínico-patológicos. Métodos A amostra foi composta pelos casos diagnosticados clinicamente como leucoplasia oral, eritroplasia oral, eritroleucoplasia, queilite actínica e líquen plano oral em um serviço de diagnóstico no período entre maio de 2012 e julho de 2013. Foram realizados testes estatísticos adotando-se nível de significância de 5% (p≤0,05). Resultados Dos 340 pacientes examinados, 106 (31,2%) se apresentaram com lesões orais potencialmente malignas; destes, 61 (17,9%) biópsias foram realizadas. A lesão mais frequente foi a queilite actínica (37,5%), e o sítio anatômico mais acometido foi o lábio inferior (49,6%). Entre os 106 pacientes da amostra, 48 (45,3%) relataram consumo de nicotina, 35 (33%) ingeriam bebidas alcoólicas e 34 (32,1%) trabalhavam expostos ao sol. Comparando o diagnóstico clínico com o histopatológico, as lesões que apresentaram maior compatibilidade foram a eritroplasia oral e a lesão ulcerada atípica (100% ambas). Conclusão Na maioria dos casos, houve compatibilidade do diagnóstico clínico com o histopatológico. Notou-se correlação entre a ocorrência de eritroplasia, leucoplasia e eritroleucoplasia com o hábito de fumar, e entre a queilite actínica com a exposição solar. A eritroleucoplasia foi a lesão que demonstrou maior grau de malignização neste estudo. Diante do exposto, recomenda-se maior atenção por parte dos cirurgiões-dentistas ao diagnóstico das lesões orais potencialmente malignas, para aplicação da melhor conduta e controle da lesão, impedindo sua transformação maligna.

Potencial de transformación maligna del liquen plano oral: estudio retrospectivo / Potential malignant transformation of oral lichen planus: retrospective study

El liquen plano oral (LPO) es una enfermedad mucocutánea inflamatoria más común en las mujeres. Su etiología aún no es bien definida y esta condición puede estar relacionada, por ejemplo, a la ansiedad, estrés, diabetes, las enfermedades autoinmunes, infecciones y predisposición genética. El LPO se manifiesta en dos formas principales: reticular y erosivo. El objetivo de esta investigación es, a través de un estudio retrospectivo, analizar el posible potencial maligno del LPO. Se analizaron los registros de los pacientes atendidos en dos proyectos de lesiones bucales de dos diferentes instituciones en el período de 1995 a 2014. Se recogieron datos como género, edad, presencia de enfermedad sistémica, presencia de lesiones en la piel, tabaquismo, duración de la lesión, localización, síntomas, tratamiento, proservación y transformación maligna. Los resultados mostraron que, de los 3488 analizados, 85 (2,4%) tuvieron un diagnóstico confirmado de LPO, que afecta fundamentalmente a pacientes de sexo femenino (85%) siendo el LP reticular más común. En relación a la transformación maligna del LPO, 1 paciente (0,85%) tenía carcinoma de células escamosas 4 años después del diagnóstico inicial de LPO. Además, 3 pacientes mostraron atipia celular moderada en el diagnóstico. Los resultados refuerzan el potencial de transformación maligna del LPO. Aunque esta asociación es especulativa, la posibilidad debe ser considerada por los profesionales, que deben presentar estos pacientes a largos periodos de preservación.

Oral lichen planus (OLP) is an inflammatory mucocutaneous disease, more common in females. Its etiology is not yet well defined; this condition may be related, for example, to anxiety, stress, diabetes, autoimmune diseases, infections and genetic predisposition. The OLP manifests itself in two main forms: reticular and erosive. This work aims to perform a retrospective study analyzing the possible malignant potential of OLP. Records of the patients were analyzed in two projects of oral lesions in two different institutions in the period from 1995 to 2014. Data as gender, age, presence of systemic disease, presence of skin lesions, smoking, duration of the injury, location, symptoms, treatment, follow-up time and malignant transformation were collected. The results showed that, of the 3488 analyzed, 85 (2.4%) had a confirmed diagnosis of OLP, which mainly affected female patients (85%) being the most common the reticular LP. Regarding the malignant transformation of OLP, one patient (0.85%) had squamous cell carcinoma 4 years after the initial diagnosis of OLP. In addition, 3 patients showed moderate cellular atypia. The results reinforce the potential of malignant transformation of OLP. Although this association is speculative, this possibility must be considered by the dental practitioners, who must submit these patients to long periods of monitoring.

In situ carcinoma developed over oral lichen planus: a case report with analysis of BUB3, p16, p53, Ki67 and SOX4 expression

AbstractOral lichen planus (OLP) represents a common mucocutaneous disease. Various authors have suggested that OLP has malignant potential; however, the mechanisms involved in malignant transformation have not yet been elucidated. A 79-year-old man presented a white lesion for five months in the buccal mucosa diagnosed as OLP. After two months using 0.05% clobetasol ointment for treatment, the lesion became ulcerated. A new biopsy of the same lesion was performed, and histological analysis showed an in situ oral carcinoma (ISOC). An immunohistochemistry panel was performed, and p16 expression was negative in OLP, however, it showed weak cytoplasmic staining in ISOC. There was strong nuclear BUB3 staining in both OLP and ISOC areas. p53 showed less intense nuclear staining in both regions. Ki67 was negative in OLP area, but showed nuclear staining in the ISOC. SOX4 was negative in both studied areas. BUB3 expression, first reported in this case, and the p16 expression may suggest some influence of these genes on pathogenesis or malignant potential of OLP.

TNF-α, TNF-ß and IL-10 gene polymorphism and association with oral lichen planus risk in Saudi patients

Objectives Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. Various reports have implicated cytokine gene polymorphisms in susceptibility to develop some immune mediated conditions including OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk. Material and Methods Forty two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. Results The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P<0.001). The frequency of GA genotype of TNF-β (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-β (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P>0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. Conclusion It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease. .

Oral lichen planus: study of 21 cases

Abstract BACKGROUND: Lichen planus is considered to be the most common dermatological disease involving the oral mucosa. OBJECTIVE: To investigate the profile, clinical features, and the presence of dysplasia and candidiasis in patients with oral lichen planus. METHODS: A total of 21 patients were selected from 258 patients at risk for oral cancer development. RESULTS: Most of the patients were white (76,2%), female (66,6%), with mean age of 58.8 years. Eight were smokers and seven were alcohol consumers. The buccal mucosa was the most affected site, followed by the tongue and the gingiva. The reticular pattern was the most common appearance. Histopathology depicted dysplasia in nine cases and cytopathology was positive for Candida in eight cases in the first appointment. CONCLUSION: Our data are similar to the literature. Cytopathology was important for the diagnosis of candidiasis. Although the presence of dysplasia was verified, further studies are necessary to clarify the importance of this finding. .

Differential expression of stem cell-like proteins in normal, hyperplastic and dysplastic oral epithelium

Objective The identification of stem cells (SC) remains challenging. In the human oral mucosal epithelium, these cells are believed to be in the basal layer (stem cell niche), but their exact location is unclear. The aim of this study was to examine the dysplastic oral epithelium for these SC-like proteins in order to assess their diagnostic value as biomarkers complementing the histological grading of dysplasia. Material and Methods Thirty oral epithelial dysplasia (OED), 25 oral lichen planus (OLP), 10 oral hyperkeratosis and 5 normal oral epithelium (OE) were immunohistochemically examined for four SC markers [integrin β1, neuron-glial-2 (NG2), notch 1 (N1) and keratin 15 (K15)]. Results Three of four SC markers were heterogeneously detected in all samples. K15 overexpression in the lower two-thirds of severe OED suggests an expanded SC niche. Integrin β1 distribution pattern was not measurably different between OEDs and control. NG2 was almost negative to absent in all samples examined. N1 expression was weak and highly variable in normal and dysplastic epithelium, making it an unreliable epithelial stem cell marker. Conclusions Present findings suggest that these markers were unable to identify individual epithelial stem cells. Instead, subpopulations of cells, most probably stem cells and transit amplifying cells with stem cell-like properties were identified in the dysplastic oral epithelium. The characteristic expressions of K15 might be of diagnostic value for oral dysplasia and should be investigated further. .

Syndrome in Question

Multiple autoimmune syndrome is a rare condition, described by Humbert and Dupond in 1988. It is defined by the association of at least 3 autoimmune diseases in the same patient. Vitiligo is the most common skin condition in this syndrome. This article presents the case of a 31-year-old male with vitiligo, alopecia areata, Crohn's disease, psoriasis vulgaris and oral lichen planus. The rarity of this case is highlighted by the coexistence of four autoimmune skin diseases in association with Crohn's disease, never described in the literature.

Oral lichen planus: a look from diagnosis to treatment / Liquen plano oral: una mirada desde el diagnóstico al tratamiento

Oral lichen planus (OLP) is a chronic mucocutaneous disease of unknown etiology. Its pathogenesis is multifactorial and it may affect the oral mucosa, skin and other mucous membranes. Diagnosis is based on clinic and histopathology; direct immunofluorescence techniques can also be of use. It affects about one to two percent of the population, mainly women between the fifth and sixth decades of life. In the mouth, the most affected area is the buccal mucosa, followed by the gums, tongue and/or palate. Its three most representative clinical forms are reticular, erythematous and erosive; evolution depends on the type it is. Lesion treatment is determined by the clinical form and, since no fully effective treatment has been found yet, it is directed towards controlling the disease. The treatment of choice involves topical or systemic corticosteroids, but other drugs may also be used. The aim of this paper is to gather current and relevant information about oral lichen planus: its pathogenesis, diagnosis, treatment and management.

El liquen plano oral (LPO) es una enfermedad crónica mucocutánea de etiología poco conocida, cuya patogénesis es multifactorial, y puede afectar a la mucosa oral, piel y otras mucosas. El diagnóstico está basado en la clínica y la histopatología. Además, técnicas como la inmunofluorescencia directa pueden contribuir al diagnóstico de la enfermedad. Afecta del 1 al 2 por ciento de la población, principalmente mujeres, entre la quinta y sexta décadas de la vida. En boca, la zona más afectada es la mucosa yugal, seguido de encías, lengua y/o paladar. Las tres formas clínicas más representativas son: reticular, eritematosa y erosiva, cuya evolución varía según el tipo. El tratamiento de las lesiones depende de la forma clínica y está dirigido hacia un control de la enfermedad, ya que en la actualidad no se conoce un tratamiento del todo efectivo. El tratamiento de elección es la utilización de corticoides, en forma tópica o sistémica, aunque otros fármacos también pueden ser utilizados para el manejo de la enfermedad. El objetivo del presente artículo es recopilar información actualizada y relevante del liquen plano oral en su etiopatogenia, diagnóstico, tratamiento y manejo de la enfermedad.

Liquen plano bucal y displasia epitelial / Oral lichen planus and epithelial dysplasia

Introducción: el liquen plano bucal es una enfermedad inflamatoria, crónica y recurrente considerada como una respuesta inmune anormal mediada por células T. Uno de los aspectos más importantes es su posible carácter premaligno y el papel de la displasia epitelial. Objetivo: describir los desórdenes celulares característicos de la displasia en las lesiones del liquen plano bucal y su relación con las formas clínicas y otras variables histopatológicas. El universo estuvo constituido por el registro de 14,977 pacientes sometidos a estudio anatomopatológico en el Servicio de Anatomía Patológica en el Departamento de Patología de la Facultad de Estomatología de La Habana, en el período comprendido de 1970 al 2008 del que se extrajo una muestra integrada por 115 pacientes con diagnóstico histopatológico de liquen plano de la mucosa bucal. Se revisaron los archivos de biopsias tomándose aquellas solicitudes con suficientes datos clínicos en las cuales estuviera consignada la presencia de lesiones bilaterales o, en su defecto, más de una lesión distribuida en una o en más de una región anatómica. Las variables clínicas fueron: Liquen plano tipo reticular, atrófico erosivo e hipertrófico y las variables histopatológicas: tipo de queratinización, grosor epitelial, presencia de displasia epitelial. Se realizó observación microscópica de las láminas obtenidas del archivo. Se obtuvieron fotomicrografías. Para las variables cualitativas se calculó la frecuencia absoluta y el porcentaje. Para la estadística analítica se utilizó el test de Chi Cuadrado, aplicando la corrección de Yates, cuando esta era necesaria o bien la Prueba exacta de Fisher. Conclusiones: la presencia de displasia ligera es un hallazgo posible en el liquen plano bucal, más frecuente en el tipo erosivo y que, hasta tanto no se demuestre convincentemente lo contrario, el liquen plano bucal debe ser una lesión tributaria de un seguimiento a corto, mediano y largo plazo(AU)

Introduction: oral lichen planus is an inflammatory, chronic and recurrent disease which is considered an abnormal T- cell mediated immune response. One of the most important aspects is its possible pre-malignant character and the role of epithelial dysplasia. Objective: to describe cellular disorders characteristic of dysplasia in lesions in the oral lichen planus and their relation with clinical forms and other histopathological variables Method: the universe was composed of the registration of 14 977 patients who underwent an anatomopathological study in the Department of Pathology of the Faculty of Stomatology of Havana during the period 1970-2008, from which a sample composed of 115 patients with histopathological diagnosis of oral lichen planus was taken. The records of biopsies were reviewed, taking those requests with enough clinical data in which the presence of bilateral lesions were recorded or, in its absence, more than one lesion spread through one or more than one anatomic region. The clinical variables were: reticular, atrophic, erosive and hypertrophic types of lichen planus, and the histopathological variables were: type of keratinization, epithelial thickness, presence of epithelial dysplasia. Microscope observation of the lamina obtained from the records was performed. Photomicrographs were obtained. For qualitative variables, absolute frequency and percentages were calculated. For analytical statistics, the Chi-square test was used, applying, if needed, the Yates´ correction or Fisher's exact test. Conclusions: the presence of mild dysplasia is a possible finding in the oral lichen planus, which is more frequent in the erosive type and, until proven otherwise, the oral lichen planus should have a short-term, medium-term and long-term follow-up(AU)

Oral lichenoid lesions: Clinico-pathological mimicry and its diagnostic implications.

Oral cavity is commonly affected by number of lichenoid lesions, whose clinical and histopathologic features overlap due to the presence of inflammatory cells in connective tissue. Segregation of these lichenoid lesions is mandatory as each may embody a distinct disease entity in terms of cause, diagnosis and prognosis. The literature discussed in the article is an attempt to segregate individual lichenoid lesions by defining clinical and histopathologic variations among each other, which avoids the diagnostic problem.

Estudo epidemiológico das doenças dermatológicas imunologicamente mediadas na cavidade oral / An epidemiological study of immune-mediated skin diseases affecting the oral cavity

FUNDAMENTO: As doenças dermatológicas imunologicamente mediadas compõem diversas patologias que apresentam formas variadas de manifestação no organismo. OBJETIVO: Foi proposição desta pesquisa, estabelecer a prevalência das principais doenças dermatológicas imunologicamente mediadas que apresentam manifestação oral. MÉTODOS: Foram avaliados laudos histopatológicos de 10.292 casos arquivados no Serviço de Anatomia Patológica da Disciplina de Patologia Oral da Universidade Federal do Rio Grande do Norte, no período de 1988 a 2009. Dos casos diagnosticados como algum tipo de doença em estudo, coletaram-se dados clínicos como sexo, idade, raça, sítio anatômico e sintomatologia das doenças. RESULTADOS: Do total de casos registrados, no serviço supracitado, 82 (0,8 por cento) corresponderam a doenças dermato lógicas imunologicamente mediadas com manifestação na cavidade oral. As doenças encontradas neste estudo foram: líquen plano oral, pênfigo vulgar e penfigoide benigno das membranas mucosas, sendo o líquen plano oral a lesão mais prevalente, representando 68,05 por cento dos casos analisados, dos quais 64,3 por cento apresentavam-se em mu lheres, sendo a mucosa jugal o sítio anatômico mais acometido (46,8 por cento). CONCLUSÃO: A ocorrência de doenças dermatológicas imunologicamente mediadas que apresentam manifestação oral ainda é um fato incomum, semelhante ao observado na maioria das regiões mundiais. No entanto, a busca pelo diagnóstico precoce é um requisito essencial para a condução do tratamento dessas doenças, tendo em vista o possível comprometimento sistêmico do organismo nos pacientes.

BACKGROUND: Immune-mediated skin diseases encompass a variety of pathologies that present in different forms in the body. OBJECTIVE: The objective of this study was to establish the prevalence of the principal immune-mediated skin diseases affecting the oral cavity. METHODS: A total of 10,292 histopathology reports stored in the archives of the Anatomical Pathology Laboratory, Department of Oral Pathology, Federal University of Rio Grande do Norte, covering the period from 1988 to 2009, were evaluated. For the cases diagnosed with some type of disease relevant to the study, clinical data such as the gender, age and ethnicity of the patient, the anatomical site of the disease and its symptomatology were collected. RESULTS: Of all the cases registered at the above-mentioned service, 82 (0.8 percent) corresponded to immune-media ted skin diseases with symptoms affecting the oral cavity. The diseases found in this study were: oral lichen planus, pemphigus vulgaris and benign mucous membrane pemphigoid. Oral lichen planus was the most common lesion, comprising 68.05 percent of the cases analyzed. Of these cases, 64.3 percent were women and the cheek mucosa was the anatomical site most commonly affected (46.8 percent). CONCLUSION: Immune-mediated skin diseases affecting the oral cavity continue to be rare, the prevalence found in this study being similar to that reported for the majority of regions worldwide. Nevertheless, early diagnosis is indispensable in the treatment of these diseases, bearing in mind that systemic involvement is possible in these patients.

Changes in peripheral innervation and nociception in reticular type and erosive type of oral lichen planus.

Background: Oral lichen planus (OLP) is a chronic inflammatory lesion in oral mucosa. Reticular (OLP-R) and erosive (OLP-E) types of OLP are the common forms that have been found in dental clinics. The aim of this investigation is to determine the correlation between neurogenic inflammation and nociception associated with OLP-R and OLP-E. Materials and Methods: The oral mucosal lesions from six patients with OLP-E, four with OLP-R and three with noninflamed oral mucosa, which represent normal mucosa, were identified by morphometric analysis of nerve fibers containing immunoreactive protein gene product (PGP) 9.5. The level of inflammation was measured with hematoxylin and eosin staining and the level of nociception was analyzed with visual analog scale measurement. Results: We found that 1) an increase in peripheral innervation was related to the size of the area of inflammatory cell infiltration from both OLP-R and OLP-E; 2) the pattern of PGP 9.5-immunoreactivity among OLP-R and OLP-E was not significantly different (P=0.23); and 3) the correlation between nociception and an increase in PGP 9.5-immunoreactivity was not found in OLP-E and in OLP-R. Conclusions: Our findings suggest that an increase in peripheral innervation may lead to increased inflammation, which is part of the immunopathogenesis of OLP. Differences in nociception between OLP-R and OLP-E arise from the pathogenesis of each lesion, not from the differences in peripheral innervation.