Immunohistochemical analysis of SHH, SMO and GLI-1 proteins in epithelial odontogenic lesions

Abstract The present study analyzed the expression of proteins involved in the sonic hedgehog signaling pathway (SHH, SMO, and GLI-1) in benign epithelial odontogenic lesions (odontogenic keratocyst - OKC, ameloblastoma - AB, and adenomatoid odontogenic tumor - AOT) in order to identify the role of these proteins in the pathogenesis of these lesions. The sample consisted of 20 OKCs, 20 ABs, and 10 AOTs. The Kruskal-Wallis, Mann-Whitney U, and Spearman's (r) tests were used for statistical analysis, with the level of significance set at 5% (p < 0.05). The membrane/cytoplasmic expression of SHH was significantly higher in AB compared to AOT (p = 0.022) and OKC (p = 0.02). No differences were found in the membrane/cytoplasmic expression of SMO between the lesions studied. Regarding GLI-1, significant differences were observed at the nuclear level for AB and OKC compared to AOT (p < 0.0001). In addition, significant positive correlations were found between cytoplasmic and nuclear GLI-1 in AB (r = 0.482; p = 0.031) and OKC (r = 0.865; p < 0.0001), and between membrane/cytoplasmic SMO and cytoplasmic GLI-1 in AOT (r = 0.667; p = 0.035) and OKC (r = 0.535; p = 0.015). The results of this study confirm the participation of the sonic hedgehog signaling pathway in the pathogenesis of the lesions studied. Overexpression of SHH in ABs and nuclear expression of GLI-1 in ABs and OKCs indicate that these proteins contribute to the more aggressive behavior of these two lesions when compared to AOT.

Resumo O presente estudo analisou a expressão de proteínas envolvidas na via de sinalização Sonic Hedgehog (SHH, SMO e GLI-1) em lesões benignas do epitélio odontogênico de comportamento biológico distintos, tais como ceratocistos odontogênicos (CO), ameloblastomas (AMB) e tumores odontogênicos adenomatoides (TOA), com o intuito de identificar o papel destas proteínas na patogênese destas lesões. A amostra foi constituída de 20 CO, 20 AMB e 10 TOA, analisada pela técnica da imuno-histoquímica de forma semiquantitativa por compartimento celular, onde foi feita uma análise da membrana e citoplasma das células nas proteínas SHH e SMO, enquanto que para a proteína GLI-1, foi feita uma análise nuclear e/ou citoplasmática. Para análise estatística, foram utilizados os testes de Kruskal-Wallis (KW), Mann-Whitney (U) e Spearman (r), com o nível de significância estabelecido em 5% (p < 0,05). Ao analisar a proteína SHH, observou-se que o AMB demonstrou expressão membranar/citoplasmática significativamente maior em comparação ao TOA (p = 0,022) e CO (p = 0,020). Com relação à análise membranar/citoplasmática da SMO, não foram identificadas diferenças entre as lesões estudadas. Para a proteína GLI-1, foram constatadas diferenças estatisticamente significativas, em nível nuclear, para o AMB e CO em comparação ao TOA (p< 0,0001). Além disso, foram observadas correlações positivas com significância estatística entre GLI-1 citoplasmático e GLI-1 nuclear para o AMB (r = 0,482; p = 0,031) e CO (r = 0,865; p< 0,0001), e entre o SMO membranar/citoplasmático e o GLI-1 citoplasmático para o TOA (r = 0,667; p = 0,035) e o CO (r = 0,535; p = 0,015). Os resultados deste estudo confirmam a participação da via de sinalização Sonic Hedgehog na patogênese das lesões estudadas e, a superexpressão de SHH em AMBs e GLI-1 nuclear em AMBs e COs, indica que estas proteínas contribuem com o comportamento biológico mais agressivo destas duas lesões quando comparado ao TOA.

Oral Alterations in a COVID-19 Patient: Case Report and Update of Main Findings

ABSTRACT: COVID-19 was characterized as a pandemic due to the worldwide dissemination and the severity with which the disease attacks the human organism. Some oral lesions have been observed in COVID-19 patients. However, there is still no concrete evidence of the real influence of SARS-CoV-2 on the human body, especially in the oral region. In this context, the present report discusses a case of a COVID-19 patient with oral alterations. The male patient presented ulcerative lesions of painful symptomatology and petechiae in the oral mucosa. This study also performed a literature review of the main oral alterations reported in the literature. Although more studies with a larger number of cases should be performe d, the present clinical case may have manifested signs of this pathology in the oral cavity since the epithelial cells of the oral mucosa have ACE2 receptors.

RESUMEN: El COVID-19 se caracterizó como una pandemia debido a la diseminación mundial y la gravedad con la que la enfermedad ataca al organismo humano. Se han observado algunas lesiones orales en pacientes con COVID-19. Sin embargo, todavía no hay evidencia concreta de la influencia del SARS-CoV-2 en el cuerpo humano, especialmente en la cavidad oral. En este contexto, el presente reporte analiza un caso de un paciente con COVID-19 con alteraciones orales. El paciente de sexo masculino presentó lesiones ulcerativas de sintomatología dolorosa y petequias en la mucosa oral. Este estudio también realizó una revisión de la literatura de las principales alteraciones orales reportadas en la literatura. Si bien se deben realizar más estudios con un mayor número de pacientes, el presente reporte de caso puede haber manifestado signos de esta patología en la cavidad oral ya que las células epiteliales de la mucosa oral tienen receptores ACE2.

Manifestações clínicas e opções terapêuticas do líquen plano oral: uma revisão de literatura / Clinical manifestations and therapeutic options of oral lichen planus: a literature review

O Líquen plano oral (LPO) é uma doença inflamatória crônica, caracterizada por uma resposta imune com agressão ao epitélio de revestimento, principalmente na camada basal. Por tratar-se de uma doença de etiopatogenia complexa, o LPO é comumente tratado com agentes anti-inflamatórios e corticosteroides tópicos, que buscam atenuar sinais e sintomas. Diante do exposto, este trabalho objetivou realizar uma revisão de literatura sobre o LPO, suas manifestações clínicas e opções terapêuticas. Foi realizada a busca eletrônica de publicações nas bases de dados Google Scholar, Pubmed e SciELO, utilizando os seguintes descritores: "líquen plano", "cavidade oral" e "estomatologia", e o operador booleano "AND". Em seguida, foi realizada análise a partir da leitura criteriosa dos artigos, realizou-se então a seleção de 60 trabalhos. Após o emprego dos critérios de elegibilidade, 29 artigos foram selecionados para o presente estudo. Os estudos demonstraram que o LPO possui etiologia indeterminada, tornando importante um amplo conhecimento de suas manifestações clínicas para melhor diagnóstico. Além dos corticosteroides, novas modalidades terapêuticas têm sido sugeridas e trazido bons resultados, como a laserterapia de baixa potência. Ademais, é importante para o cirurgião-dentista reconhecer suas diversas opções terapêuticas a fim de diminuir o agravo das lesões orais, visto que, a depender do quadro imunológico do paciente, poderão ocorrer remissões espontâneas... (AU)

Oral lichen planus (OLP) is a chronic inflammatory disease, characterized by an immune response with aggression to the lining epithelium, mainly in the basal layer. Since it is a disease of complex eti opathogenesis, OLP is commonly treated with anti-inflammatory agents and topical corticosteroids, which seek to decrease signs and symptoms. Thus, this study performed a literature review abour OLP, its clinical manifestations and therapeutic options. The electronic search for publications in the Google Scholar, Pubmed and SciELO databases was performed, using the following descriptors: "li chen planus", "oral cavity" and "stomatology", and the Boolean operator "AND". Then, an analysis was performed based on the careful reading of the articles, and then 60 articles were selected. After using the eligibility criteria, 29 articles were selected for the present study. Studies have shown that OLP has an undetermined etiology, making it important to have a broad knowledge of its clinical manifestations for a better diagnosis. In addition to corticosteroids, new therapeutic modalities have been suggested and brought good results, such as low-level laser therapy. In addition, it is important for the dentists to recognize their various therapeutic options to reduce the worsening of oral lesions, since, depending on the patient's immune status, spontaneous remissions may occur... (AU)

Saliva, implicações orais e biossegurança em Odontologia: principais aspectos do COVID-19 / Saliva, oral implications and biosafety in Dentistry: main aspects in COVID-19

Objetivo: Diante da importância do fluido salivar no contexto da odontologia, este trabalho objetivou realizar uma revisão de literatura sobre a relação da saliva e a COVID-19, bem como as suas principais implicações na Odontologia. Métodos: Foi realizada a busca eletrônica de publicações nas bases de dados SciELO, PubMed, Scopus, EMBASE e Cochrane Central Register of Controlled Trials, utilizando os seguintes descritores: "Saliva", "oral cavity", "oral mucosa", "oral lesions", "Dentistry", e o operador booleano "AND" entre todas as palavras-chave citadas individualmente com o termo "COVID-19". Os estudos foram publicados no período de dezembro de 2019 a setembro de 2020. Resultados: Os estudos demonstraram que a saliva representa um importante meio de transmissão do SARS-CoV-2, o que torna necessário o cumprimento de medidas de biossegurança pelos cirurgiões-dentistas a fim de reduzir a possibilidade de infecção pelo SARS-CoV-2. Ao mesmo tempo, a alta carga viral encontrada na saliva possibilita que a mesma possa ser utilizada como um meio para diagnóstico da COVID-19. Pesquisas têm demonstrado eficácia similar da análise da saliva quando comparada a outras técnicas convencionais. Por sua vez, mais investigações precisam ser realizadas a fim de validar a metodologia aplicada nos estudos atuais. Conclusão: A detecção do SARS-CoV-2 através da saliva é bastante promissora e apresenta vantagens em comparação a outros fluidos biológicos, pois a coleta deste fluido não envolve uma intervenção invasiva, facilitando o manejo pelos profissionais e pacientes.

Aim: Due to the importance of the salivary fluid in dentistry, this study aimed to carry out a literature review on the relationship between saliva and COVID-19, as well as its main implications in Dentistry. Methods: An electronic search for publications was performed in the SciELO, PubMed, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials databases using the following descriptors: "Saliva", "oral cavity", "oral mucosa", "oral lesions ", and "Dentistry", using the Boolean operator "AND" between all keywords cited individually with the term "COVID-19". The studies were published from December 2019 to September 2020.Results: The studies have shown that saliva represents an important means of transmission of SARS-CoV-2, which makes it necessary for dentists to comply with biosafety measures in order to reduce the possibility of SARS-CoV-2 infection. Likewise, the high viral load found in saliva allows it to be used as a path to COVID-19 diagnosis. Investigations have shown similar effectiveness in the saliva analysis compared to other conventional techniques. In this regard, more investigations need to be carried out to validate the methodology applied in current studies. Conclusion: The detection of SARS-CoV-2 through saliva is very promising and has advantages in comparison to other biological fluids, as the collection of this fluid does not involve an invasive intervention, thus facilitating management by professionals and patients.

Role of twist and podoplanin in partial epithelial-mesenchymal transition in oral squamous cell carcinoma

Abstract The aim of this study was to perform a comparative analysis of podoplanin (PDPN) and Twist immunoexpressions in lower lip and oral tongue squamous cell carcinomas (LLSCC and OTSCC, respectively). PDPN and Twist immunoexpressions were semi-quantitatively evaluated by analyzing the invasion front, the compressive areas, the large islands and nests and dissociated cells of the chosen carcinomas. Their statistical associations and correlations with clinical-pathological characteristics were verified by the Mann-Whitney and Spearman's test. Twist expression was low in both carcinomas, with <25% labeling on the invasive front. Significant differences were observed for LLSCC (p=0.032) and OTSCC (p=0.025) regarding PDPN immunoexpression in relation to the worst invasion patterns determined by a histological malignancy gradation system. Statistically significant negative correlations between PDPN membrane expression and general (r=-0.356, p=0.024) and cytoplasmic Twist expressions (r=-0.336; p=0.034) in LLSCC were also observed. Twist and PDPN are suggested to be associated to a more aggressive invasion pattern in both LLSCC and OTSCC cases but not related to the different biological behaviors on these anatomical sites. Also, it was seen that PDPN membrane expression is inversely related to general and cytoplasmic Twist expression in LLSCC cases.

Resumo O objetivo deste estudo foi realizar uma análise comparativa das imunoexpressões de podoplanina (PDPN) e Twist em carcinomas de células escamosas de lábio inferior e língua oral (CCELI e CCELO, respectivamente). As imunoexpressões de PDPN e Twist foram avaliadas semi-quantitativamente através da análise do front invasivo, das áreas compressivas, das grandes ilhas e ninhos e das células dissociadas dos carcinomas escolhidos. Suas associações estatísticas e correlações com características clínico-patológicas foram verificadas pelos testes de Mann-Whitney e Spearman. A expressão de Twist foi baixa nos dois carcinomas, com marcação <25% no front invasivo. Diferenças significativas foram observadas para CCELI (p=0,032) e CCELO (p=0,025) em relação à imunoexpressão de PDPN em relação aos piores padrões de invasão determinados por um sistema de gradação histológica de malignidade. Também foram observadas correlações negativas estatisticamente significantes entre a expressão membranar de PDPN e as expressões geral (r=-0,356, p=0,024) e citoplasmática do Twist (r=-0,336; p=0,034) no CCELI. Sugere-se que o Twist e o PDPN estejam associados a um padrão de invasão mais agressivo nos casos de CCELI e CCELO, mas não relacionados aos diferentes comportamentos biológicos nesses sítios anatômicos. Também foi observado que a expressão membranar de PDPN está inversamente relacionada à expressão geral e citoplasmática de Twist em casos de CCELI.

Immunohistochemical expression of DNA repair proteins in oral tongue and lower lip squamous cell carcinoma

Abstract The DNA repair system involves genes and proteins that are essential for the maintenance of genome integrity and the consequent control of various cellular processes. Alterations in these genes and proteins play a role in tumor development and progression and might be associated with prognosis. The aims of this study were to analyze the immunoexpression of two DNA repair proteins, XPF and XRCC1, in lower lip squamous cell carcinoma (LLSCC) and oral tongue squamous cell carcinoma (OTSCC), and to investigate possible associations with clinical and histopathological parameters. The immunohistochemical expression of XPF and XRCC1 was analyzed semi-quantitatively in 40 cases each of LLSCC and OTSCC. The chi-squared test or Fisher's exact test, when appropriate, was used to investigate the association between expression of the proteins and clinicopathological characteristics. The cytoplasmic immunoexpression of XPF was high in OTSCC (95% of the cases analyzed) but low in LLSCC (52.5%). Among the clinicopathological parameters evaluated, a statistically significant association was observed between high nuclear expression of XRCC1 and the absence of regional lymph node metastasis in patients diagnosed with OTSCC (p=0.006). The high protein expression of XPF and XRCC1 in OTSCC and LLSCC suggests an important role in the development and progression of these tumors. Our study found an association between high nuclear expression of XRCC1 and the absence of loco-regional metastasis in cases diagnosed as OTSCC, suggesting a role of this protein in tumor progression.

Self-Medication for Toothache and its Associated Factors in Children and Adolescents

Objective: To evaluate self-medication for toothache and its associated factors in children and adolescents. Material and Methods: A cross-sectional study was carried out with 252 children/adolescents aged 6-16 years. A questionnaire was applied with questions related to demographic and socioeconomic characteristics; experience of, and self-medication for, toothache; as well as aspects related to the condition. Descriptive and inferential statistical analyses (Pearson's Chi-square test and Fisher's exact test) were performed, with a 5% significance level. Results: The prevalence of toothache was 41.7%. In 96 cases analyzed, there was prevalence of 69.8% of self-medication for toothache. There were no statistically significant associations between self-medication for toothache and variables related to the children/adolescents (gender and age), their parents or guardians (age and schooling), socioeconomic characteristics (family income and number of people in the household) and aspects related to toothache (fever, crying and school absenteeism) (p>0.05). The most commonly used drug was paracetamol (60.7%), whose choice was based to its previous use by the study population for conditions not related to toothache (47.8%). Conclusion: There was a high prevalence of self-medication for toothache in the study population. No independent variable was associated with self-medication practice.

Análise da imunoexpressão de proteínas de reparo do DNA envolvidas nas vias BER e NER em lesões odontogênicas epiteliais benignas / Immunoexpression analysis of DNA repair proteins involved in BER and NER pathways in benign epithelial odontogenic lesions

As lesões odontogênicas epiteliais benignas apresentam comportamento biológico heterogêneo e patogênese ainda não totalmente esclarecida. As vias de reparo do ácido desoxirribonucleico (DNA) atuam em tipos específicos de danos ao material genético, realizando o reparo e regulando diversos processos celulares. Dentre as principais vias de reparo do DNA, destacamse o reparo por excisão de bases (BER) e o reparo por excisão de nucleotídeos (NER). Investigações têm demonstrado que as proteínas envolvidas nessas vias se encontram desreguladas e, por vezes, altamente expressas em algumas neoplasias malignas, contribuindo para a progressão tumoral. Levando em consideração a heterogeneidade do comportamento biológico das lesões odontogênicas epiteliais benignas e a escassez de estudos que tenham avaliado a expressão de proteínas de reparo do DNA nestas lesões, este trabalho avaliou a imunoexpressão de proteínas da via BER (APE-1 e XRCC-1) e NER (XPF) em ameloblastomas (AMEs) sólidos (n = 30), ceratocistos odontogênicos não sindrômicos (CONS) (n = 30), ceratocistos odontogênicos sindrômicos (COS) (associados à Síndrome de Gorlin) (n = 29), cistos dentígeros (CDs) (n = 30) e folículos dentários (FDs) (n = 20). A análise da expressão imunoistoquímica de APE-1, XRCC-1 e XPF foi realizada de forma quantitativa por um avaliador previamente calibrado e sem acesso aos dados clínicos dos casos. Em cinco campos de maior imunorreatividade, foram quantificadas as células positivas e negativas para as proteínas no componente epitelial de todos os casos, sendo estabelecido o percentual de células positivas em relação ao número total de células contadas para cada anticorpo. As marcações nucleares e citoplasmáticas foram analisadas separadamente para APE-1 e XPF, enquanto apenas a imunoexpressão nuclear foi considerada para XRCC-1. As comparações das medianas dos percentuais de imunorreatividade em relação aos grupos estudados foram realizadas por meio dos testes não paramétricos de Kruskal-Wallis e Mann-Whitney. Possíveis correlações entre a expressão de APE-1, XRCC-1 e XPF foram avaliadas por meio do teste de correlação de Spearman. O nível de significância foi estabelecido em 5% (p < 0,05). Foi verificada uma maior imunoexpressão nuclear de APE-1 nos CONSs, COSs e AMEs sólidos, em comparação com os CDs (p < 0,001). Dentre todos os grupos avaliados, a expressão citoplasmática de APE1 só foi encontrada em 4 CONSs e 6 COSs. A expressão nuclear de XRCC-1 foi estatisticamente maior nos CONSs e COSs em relação aos CDs (p < 0,05). Em nível nuclear, a expressão de XPF foi significativamente maior nos CONSs e COSs em relação aos CDs e AMEs (p < 0,05) e, embora sem significância estatística, foi observada uma maior expressão nuclear dessa proteína nos AMEs quando comparado aos CDs. Em relação à expressão citoplasmática de XPF, foi observada uma maior expressão nos COSs em relação aos CDs (p = 0,04). Nenhuma diferença estatisticamente significativa foi encontrada entre as expressões nucleares de APE-1, XRCC-1 e XPF entre CONSs e COSs (p > 0,05). Além disso, todas as lesões odontogênicas estudadas revelaram uma maior expressão estatisticamente significativa de APE-1 (nuclear), XRCC-1 (nuclear) e XPF (nuclear e citoplasmática) quando comparados aos FDs (p < 0,05). Para todas as lesões, o teste de correlação de Spearman mostrou uma correlação positiva entre a expressão nuclear de APE-1 e XRCC-1 ou XPF, em nível nuclear (p < 0,05). Os resultados deste estudo sugerem um potencial envolvimento das proteínas APE-1, XRCC-1 e XPF na patogênese das lesões odontogênicas epiteliais benignas, com destaque para aquelas com comportamento biológico mais agressivo (AU).

The benign epithelial odontogenic lesions present a heterogeneous biological behavior and their pathogenesis are not fully understood. The deoxyribonucleic acid (DNA) repair pathways act on specific types of damage to the genetic material, performing the repair and regulating several cellular processes. Among the main DNA repair pathways, the most notable are the base excision repair (BER) and the nucleotide excision repair (NER). Investigations have shown that the proteins involved in these pathways are deregulated and sometimes highly expressed in some malignancies, contributing to tumor progression. Taking into account the heterogeneity of the biological behavior of benign epithelial odontogenic lesions and the scarcity of studies that have evaluated the expression of DNA repair proteins in these lesions, this study evaluated the immunoexpression of BER (APE-1 and XRCC-1) proteins and NER (XPF) in solid ameloblastomas (AMEs) (n = 30), non-syndromic odontogenic keratocysts (NSOKCs) (n = 30), syndromic odontogenic keratocysts (SKOCs) (associated with Gorlin's Syndrome) (n = 29), dentigerous cysts (DCs) (n = 30) and dental follicles (DFs) (n = 20). The immunohistochemical analysis of APE-1, XRCC-1 and XPF was performed quantitatively by a previously calibrated evaluator and without access to the clinical data of the cases. In five fields of higher immunoreactivity, positive and negative cells were quantified for the proteins in the epithelial component of all cases, and the percentage of positive cells was established in relation to the total number of cells counted for each antibody. Nuclear and cytoplasmic markers were analyzed separately for APE-1 and XPF, while only nuclear immunoexpression was considered for XRCC-1. The comparisons of the median percentages of immunoreactivity in relation to the studied groups were performed using the non-parametric Kruskal-Wallis and MannWhitney tests. Possible correlations between the expression of APE-1, XRCC-1 and XPF were assessed by Spearman's correlation test. The level of significance was set at 5% (p < 0.05). A higher nuclear immunoexpression of APE-1 in the NSOKCs, SOKCs and solid AMEs was verified in comparison with the DCs (p < 0.001). Among all the evaluated groups, the cytoplasmic expression of APE-1 was only found in 4 NSOKCs and 6 SOKCs. Nuclear expression of XRCC-1 was statistically higher in NSOKCs and SOKCs than in DCs (p < 0.05). At the nuclear level, XPF expression was significantly higher in NSOKCs and SOKCs than in DCs and AMEs (p < 0.05) and, although without statistical significance, a higher nuclear expression of this protein was observed in AMEs when compared to CDs. Regarding the cytoplasmic expression of XPF, a greater expression was observed in the SOKCs in relation to the DCs (p = 0.04). No statistically significant difference was found between the nuclear expressions of APE-1, XRCC-1 and XPF between NSOKCs and SOKCs (p > 0.05). In addition, all the odontogenic lesions studied revealed a statistically significant expression of APE-1 (nuclear), XRCC-1 (nuclear) and XPF (nuclear and cytoplasmic) when compared to DFs (p < 0.05). For all lesions, Spearman's correlation test showed a positive correlation between nuclear expression of APE-1 and XRCC-1 or XPF at the nuclear level (p < 0.05). The results of this study suggest a potential involvement of APE-1, XRCC-1 and XPF proteins in the pathogenesis of benign epithelial odontogenic lesions. The role played by these proteins may be more important in odontogenic lesions with more aggressive biological behavior (AU).

Immunoexpression of human leukocyte antigen-DR in actinic cheilitis and lower lip squamous cell carcinoma

Abstract The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.

Clinicopathological and immunohistochemical analysis of spindle cell squamous cell carcinoma of the tongue: a rare case / Análise clinicopatológica e imuno-histoquímica do carcinoma de células escamosas de células fusiformes da língua: um caso raro

ABSTRACT Spindle cell squamous cell carcinoma of the tongue is a rare variant of squamous cell carcinoma. This paper reports the case of a spindle cell squamous cell carcinoma of the tongue, in a 64-year-old male patient, and presents a review of the etiopathogenesis, clinicopathological and immunohistochemical features and treatment of the malignancy. The patient presented for evaluation of a painful swelling on his tongue. Extraoral examination revealed palpable submandibular and superior cervical lymph nodes. Based on the presumptive diagnoses of squamous cell carcinoma or malignant salivary gland neoplasm, an incisional biopsy was performed. Histopathological analysis showed a proliferation of atypical spindle cells, exhibiting extensive pleomorphism. Tumor cells were positive for vimentin, P53 and alpha-smooth muscle actin, focally positive for epithelial membrane antigen and P63, and negative for pan-cytokeratin (AE1/AE3), CK7, CD138, CD34, CD56, and S-100. The positivity index for Ki-67 was approximately 40%. The diagnosis of spindle cell squamous cell carcinoma was established and the patient was referred to a head and neck surgery service. In the oral cavity, spindle cell squamous cell carcinoma of the tongue is an aggressive variant of squamous cell carcinoma, which usually presents as an exophytic mass located on the tongue of elderly males. Due to its distinct histopathological characteristics, immunohistochemistry is a valuable and helpful tool to establish the diagnosis of spindle cell squamous cell carcinoma of the tongue.

RESUMO O carcinoma de células escamosas de células fusiformes da língua, é uma variante rara do carcinoma de células escamosas. Este trabalho relata o caso de um paciente do sexo masculino de 64 anos de idade com carcinoma de células escamosas de células fusiformes da língua. Foi feita uma revisão dos aspectos relacionados a etiopatogenia, características clinicopatológicas e imuno-histoquímicas, além do tratamento dessa neoplasia. O paciente procurou atendimento para avaliação de tumefação dolorosa na língua. O exame extraoral revelou linfonodos cervicais submandibulares e cervicais superiores palpáveis. Foi realizada biópsia incisional com base nas hipóteses diagnósticas de carcinoma de células escamosas ou neoplasia maligna de glândula salivar. A análise histopatológica demonstrou proliferação de células fusiformes atípicas, exibindo extenso pleomorfismo. As células tumorais foram positivas para vimentina, p53 e alfa-actina de músculo liso, focalmente positivas para antígeno de membrana epitelial e P63, e negativas para pancitoqueratina (AE1/AE3), CK7, CD138, CD34, CD56 e S-100. O índice de positividade para o Ki-67 foi de aproximadamente 40%. Foi feito o diagnóstico de carcinoma de células escamosas, de células fusiformes, e o paciente foi encaminhado para um serviço de cirurgia de cabeça e pescoço. Na cavidade oral, o carcinoma de células escamosas de células fusiformes da língua, é uma variante agressiva do carcinoma de células escamosas, que geralmente se apresenta como massa exofítica localizada na língua de homens idosos. Devido às suas distintas características histopatológicas, a imuno-histoquímica é uma ferramenta valiosa e útil para estabelecer o diagnóstico de carcinoma de células escamosas de células fusiformes da língua.

Clinical and immunohistochemical study of melanotic neuroectodermal tumor of infancy in the maxilla / Estudo clínico e imuno-histoquímico de tumor neuroectodérmico melanocítico da infância em maxila

ABSTRACT Melanotic neuroectodermal tumor of infancy is a rare and fast-growing neoplasm. In this study, we describe the case of a 6-month-old female patient, who presented swelling in the anterior maxilla. Tomographic reconstruction showed an unilocular hypodense and expansive area associated with the upper right central primary incisor. The presumptive diagnoses were dentigerous cyst, adenomatoid odontogenic tumor, melanotic neuroectodermal tumor of infancy and rhabdomyosarcoma, and an incisional biopsy was performed. Microscopically, the lesion revealed a biphasic cell population, consisting of small, ovoid, neuroblastic-like cells and epithelioid cells containing melanin. Immunohistochemically, the melanocyte-like component was strongly and diffusely positive for HMB-45 and Melan-A, but weakly positive for S100. Based on these findings, definitive diagnosis of melanotic neuroectodermal tumor of infancy was established. Then, enucleation of the lesion was performed by careful curettage. After 2 year follow-up, no clinical or radiographical evidence of recurrence was verified. The present case highlights the importance of early diagnosis and therapeutic intervention at the appropriate time to achieve a favorable outcome for the patient.

RESUMO O tumor neuroectodérmico melanocítico da infância é uma neoplasia rara e de crescimento rápido. Neste estudo, relata-se o caso de uma paciente do sexo feminino de 6 meses de idade, que apresentou tumefação na região anterior de maxila. A reconstrução tomográfica revelou área unilocular hipodensa e expansiva associada ao incisivo central superior direito decíduo. Realizou-se biópsia incisional, considerando as hipóteses diagnósticas de cisto dentígero, tumor odontogênico adenomatoide, tumor neuroectodérmico melanocítico da infância e rabdomiossarcoma. Microscopicamente, a lesão revelou população celular bifásica, consistindo de células pequenas, ovoides, de aparência neuroblástica, e de células epitelioides, contendo melanina. A análise imuno-histoquímica demonstrou que o componente celular contendo melanina era positivo de forma intensa e difusa para HMB-45 e Melan-A, mas levemente positivo para S100. Com base nestes achados, foi estabelecido o diagnóstico definitivo de tumor neuroectodérmico melanocítico da infância. Em seguida, foi realizada a enucleação da lesão com curetagem cuidadosa. Após 2 anos de acompanhamento, não foram verificadas evidências clínicas ou radiográficas de recorrência. O presente caso destaca a importância do diagnóstico precoce e da intervenção terapêutica no momento apropriado, a fim de alcançar um desfecho favorável para o paciente.

Antifungal Activity of Eugenol and its Association with Nystatin on Candida albicans

Objective: To evaluate the anti-Candida effect of eugenol and its antimicrobial interaction with nystatin. Material and Methods: The antimicrobial potential was assessed by microdilution technique (M27A3 reference method), by determining the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) against C. albicans (ATCC 90028). The possible action of eugenol on the fungal cell wall was evaluated with the assistance of the osmotic protector sorbitol (0.8 M). The antimicrobial interaction with nystatin was assessed through the checkerboard method. All tests were performed in triplicate. Results: All groups showed reductions in PI and GBI values and improvements in oral health knowledge, but IG1 and IG2 showed statistically significant differences in these variables compared to CG. Conclusion: The eugenol has antifungal activity against C. albicans and its mechanism of action is probably not related to damage to the fungal cell wall. Association between eugenol and nystatin was not found to be an advantageous possibility for growth inhibition of C. albican.