Estudo da imunoexpressão de proteínas envolvidas na transição epitélio-mesênquima em tumores de glândula salivar / Study of the immunoexpression of proteins involved in the epithelial-mesenchymal transition in salivary gland tumors

Os tumores de glândula salivar (TGS) apresentam notável complexidade clínica e biológica, razão para a qual muitos estudos investigam os eventos envolvidos na sua progressão. Uma das dinâmicas envolvidas na invasão tumoral de diversos tipos de carcinomas é a transição epitélio-mesênquima (TEM). Neste processo, as células epiteliais sofrem transição para um estado mesenquimal móvel, favorecendo a invasão e metástase. Sendo assim, esta pesquisa analisou a expressão imuno-histoquímica de E-caderina, Twist1, Snail1, α-SMA, metaloproteinases de matriz 9 (MMP-9) e Vimentina (VM) em 90 casos de TGS, correlacionando-os entre si e com parâmetros clinicopatológicos. Foram selecionados 20 casos de Adenoma pleomórfico (AP), 20 casos de Carcinoma mucoepidermoide (CME), 20 casos de Carcinoma adenoide cístico (CAC), 10 casos de Adenocarcinoma polimorfo (ACP), 10 casos de Carcinoma epitelial-mioepitelial (CEME) e 10 casos de Carcinoma ex-adenoma pleomórfico (CexAP). A análise de E-caderina, Twist1, Snail1 foi realizada em parênquima tumoral sendo observado o percentual de células positivas (PP), com escores variando de 0 a 4, e a intensidade de expressão (IE), cujos escores variaram de 0 a 3. A avaliação de MMP-9 foi realizada em parênquima e estroma tumoral, também avaliando-se a PP e a IE, ambos baseados em escores que variaram de 0 a 3. A marcação para α-SMA e VM foi analisada em região de estroma tumoral. Células positivas para α-SMA foram contabilizadas em 10 campos, obtendo-se, então a média. A VM foi avaliada de forma qualitativa, utilizando-se 4 escores de acordo com a IE e se a marcação é difusa ou focal. Os dados obtidos foram analisados no software Statistical Package for Social Science, GraphPad Prism e STATA. O nível de significância de 5% foi adotado para os testes estatísticos. Foi verificada menor imunomarcação de E-caderina nos APs em relação às neoplasias malignas de glândula salivar (NMGS). Observou-se baixa imunoexpressão de Twist1 e Snail1 em APs. Em relação a expressão nuclear do Twist1, constatou-se maior expressão nas neoplasias malignas quando comparadas aos APs. Ainda, Twist1 em núcleo foi correlacionado à expressão citoplasmática de E-caderina nas NMGS. No que concerne aos parâmetros clinicopatológicos, esta proteína se relacionou estatisticamente com maiores chances de óbito. Foi evidenciada baixa imunoexpressão de Snail1 entre as NMGS. No entanto, na análise dos CACs, foi verificada maior expressão nuclear na variante sólida em relação às demais. A expressão de MMP-9 em parênquima demonstrou correlação positiva com Twist1 citoplasmático e Snail1nuclear nas NMGS. A MMP-9 também apresentou correlação positiva na comparação da sua imunoexpressão em região de parênquima e de estroma. A VM se apresentou como um biomarcador a ser considerado na avaliação clínica dos pacientes, já que esta apresentou relação significativa com tamanho do tumor (T3-T4) e maior frequência de óbito. Ademais, a alta expressão desta proteína se apresentou como um fator preditivo independente para piores taxas de sobrevida global (SG). A avaliação dos demais fatores clinicopatológicos apresentou estágios clínicos avançados como indicador de valor prognóstico independente para menores taxas de SG, enquanto que para a sobrevida livre da doença, estes foram a localização em glândula salivar menor e presença de metástase à distância. Os resultados deste estudo sugerem que o processo de TEM pode estar relacionado ao estágio de diferenciação celular em APs e à progressão tumoral nas NMGS. Ressalta-se, também, maior participação de Twist1 e MMP-9 no cenário da TEM em tumores malignos de glândula salivar, além da possibilidade de utilização da VM como indicador de valor prognóstico (AU).

Salivary gland tumors (SGTs) present remarkable clinical and biological complexity; therefore, many studies investigate the events involved in their progression. One of the dynamics involved in the tumor invasion of different types of carcinomas is the epithelial-mesenchymal transition (EMT). In this process, epithelial cells undergo a transition to a mobile mesenchymal state, favoring invasion and metastasis. Therefore, this research analyzed the immunohistochemical expression of E-cadherin, Twist1, Snail1, α-SMA, vimentin (VM) and matrix metalloproteinase 9 (MMP-9) in 90 SGTs cases; correlations among the biomarkers, as well as between the biomarkers and clinicopathological parameters were made. We selected 20 cases of pleomorphic adenoma (PA), 20 cases of mucoepidermoid carcinoma (MEC), 20 cases of adenoid cystic carcinoma (ACC), 10 cases of polymorphous adenocarcinoma (PAC), 10 cases of epithelial-myoepithelial carcinoma (EMC) and 10 cases of carcinoma ex-pleomorphic adenoma (CXPA). E-cadherin, Twist1, and Snail1 were analyzed in tumor parenchyma, observing the percentage of positive cells (PP) using scores ranging from 0 to 4, and the expression intensity (EI), whose scores were ranged from 0 to 3. The evaluation of MMP-9 was performed in tumor parenchyma and stroma, also evaluating PP and IE, both based on scores that ranged from 0 to 3. The labeling for α-SMA and VM was analyzed in stromal cells. Positive cells for α-SMA were counted in 10 fields and the mean was calculated. VM was evaluated qualitatively, using 4 scores according to EI and whether the labeling was diffuse or focal. Obtained data were analyzed using Statistical Package for Social Science, GraphPad Prism, and STATA software. The significance level of 5% was adopted for the statistical tests. Patients were mostly female, with a mean age of 49.8 years; the major salivary glands were the most affected anatomical site, mainly the parotid gland. A lower E-cadherin immunostaining was verified in PAs in comparison to malignant neoplasms of salivary glands (MNSGs). Low immunoexpression of Twist1 and Snail1 was observed in PAs. Regarding the nuclear expression of Twist1, it was found greater expression in malignant neoplasms than in PAs. Furthermore, Twist1 in the nucleus was correlated with cytoplasmic expression of E-cadherin in MNSGs. Regarding clinicopathological parameters, this protein was statistically related to higher chances of death. Low immunoexpression of Snail1 was evidenced among the MNSGs. However, in the analysis of CACs, greater nuclear expression was observed in the solid variant compared to the others. Expression of MMP-9 in parenchyma showed a positive correlation with cytoplasmic Twist1 and Snail1nuclear in MNSGs. MMP-9 also showed a positive correlation when comparing its immunoexpression in the parenchyma and the stroma. VM was presented as a biomarker to be considered in the clinical evaluation of patients since it showed a significant correlation between greater tumor size and a higher frequency of death. Furthermore, the high expression of this protein appeared as an independent predictive factor for worse overall survival (OS) rates. The evaluation of the rest of the clinicopathological factors showed advanced clinical stages as an indicator of independent prognostic value for lower rates of OS. For disease-free survival, these indicators were the location in the minor salivary gland and the presence of distant metastasis. Our results suggest that the EMT may be related to myoepithelial differentiation in PAs and tumor progression in MNSGs. Also, Twist1 and MMP-9 appear to play a greater role in the scenario of EMT in MNSGs; finally, VM might be used as a prognostic value indicator (AU).

Venolymphatic malformation in lateral edge of the tongue: case report.

Vascular malformations are vascular anomalies that can affect veins, lymphatic vessels, and/or arteries in isolated or mixed form. When they present in the mixed form with venous and lymphatic involvement, they are called venolymphatic or lymphatic-venous malformations, depending on their predominant component. Although these are benign disorders with good prognosis, they are locally invasive and may lead to deformity, while there is also a propensity for local recurrence. This article presents a case of venolymphatic malformation with unusual localization on the lateral border of the tongue, addressing the clinical conduct and the current theoretical framework.

Malformação venolinfática em borda lateral de língua: relato de caso / Venolymphatic malformation in lateral edge of the tongue: case report

Resumo As malformações vasculares são anomalias que podem acometer veias, vasos linfáticos e artérias de forma isolada ou mista. Quando se apresentam de forma mista, com componentes venosos e linfáticos, são denominadas malformação venolinfática ou linfático-venosa, de acordo com sua constituição predominante. Embora seja um distúrbio benigno de bom prognóstico, é localmente invasivo, podendo levar a deformidade e havendo, ainda, a propensão de recorrência local. O presente artigo traz um caso de malformação venolinfática com localização incomum em borda lateral de língua, abordando-se a conduta clínica e o referencial teórico vigente.

Abstract Vascular malformations are vascular anomalies that can affect veins, lymphatic vessels, and/or arteries in isolated or mixed form. When they present in the mixed form with venous and lymphatic involvement, they are called venolymphatic or lymphatic-venous malformations, depending on their predominant component. Although these are benign disorders with good prognosis, they are locally invasive and may lead to deformity, while there is also a propensity for local recurrence. This article presents a case of venolymphatic malformation with unusual localization on the lateral border of the tongue, addressing the clinical conduct and the current theoretical framework.

COVID-19 in dental practice ­ an overview of challenges and preventive measures / COVID-19 na prática odontológica ­ uma revisão sobre os desafios e medidas preventivas

COVID-19 was identified to be caused by a new coronavirus named as SARS-CoV-2. Since the outbreak of this disease, World Health Organization (WHO) declared a global public health emergency. SARS-CoV-2 has a high estimate rate of human-tohuman transmission mainly through inhalation/ingestion/direct mucous contact with respiratory droplets. Considering this high transmission capacity, several countries have already registered cases of infection by health professionals. Even though dentists are not directly involved in the diagnosis and therapy of COVID-19 they represent undoubtedly a risk group due to high exposure and their work environment is a contagion factor for patients and staff. In this manner, the objective of this article is to approach important aspects of COVID-19 concerning dental care and provides an overview of its challenges on dental practice. For this, we used these following keywords in our research: COVID-19; dental general practice; prevention and control; infectious disease transmission; infectious disease transmission, patient to professional. Taking into account the global concern with patient care in midst of this pandemic, we address valid concerns regarding the potential means of contamination in the dental office and highlight practices and guidelines adopted in different countries to minimize risks in dental care in this global public health crisis, thus, reinforcing the challenges of dentistry in this context, highlighting the importance of rigorous preventive measures. However, there is still a lack of standardization of dental care protocols and consequently, reduce the risk of contagion.

COVID-19 foi identificada como sendo causada por um novo coronavírus denominado SARS-CoV-2. Desde o surgimento da doença, a Organização Mundial da Saúde (OMS) declarou uma emergência global de saúde pública. O SARS-CoV-2 tem uma alta taxa estimada de transmissão de pessoa para pessoa, principalmente por inalação/ingestão/contato direto da mucosa com gotículas respiratórias. Considerando essa alta capacidade de transmissão, vários países já registraram casos de infecção por profissionais de saúde. Mesmo que os dentistas não estejam diretamente envolvidos no diagnóstico e terapia do COVID-19, eles representam, sem dúvida, um grupo de risco devido à alta exposição e seu ambiente de trabalho é um fator de contágio para pacientes e equipe. Dessa forma, o objetivo deste artigo é abordar aspectos importantes do COVID-19 no que diz respeito à assistência odontológica e apresentar um panorama de seus desafios na prática odontológica. Para isso, utilizamos as seguintes palavras-chave em nossa pesquisa: COVID-19; clínica odontológica geral; prevenção e controle; transmissão de doenças infecciosas; transmissão de doenças infecciosas do paciente para o profissional. Levando em consideração a preocupação global com o atendimento ao paciente em meio a esta pandemia, foram abordadas preocupações válidas sobre os meios potenciais de contaminação no consultório odontológico e destacadas as práticas e diretrizes adotadas em diferentes países para minimizar os riscos na assistência odontológica nesta crise global de saúde pública, reforçando assim os desafios da odontologia neste contexto, evidenciando a importância de medidas preventivas rigorosas. Porém, ainda falta padronização dos protocolos de atendimento odontológico e, consequentemente, redução do risco de contágio.

Extracapsular invasion: A potential prognostic marker for Carcinoma ex-pleomorphic adenoma of the salivary glands? A Systematic Review.

BACKGROUND: The aim of the present study was to integrate available data published in the literature on extracapsular invasion in cases of CXPA that correlated findings with the prognosis of analysed patients. METHODS: An electronic search was carried out at the MEDLINE/PubMed, EMBASE and Cochrane Collaboration Library databases. Articles that assessed the relationship between extracapsular invasion and survival of patients diagnosed with CXPA were selected for the systematic review. Quality assessment was performed, in duplicate, for each eligible study by independent reviewers who used the operationalized prognostic biomarker reporting the REMARK guidelines. RESULTS: Eight published articles met all the inclusion criteria and were selected. Extracapsular invasion was evaluated in all selected studies and was correlated with clinical and pathological parameters. Recurrence and death due to the neoplastic process became a frequent finding in cases of tumours with extracapsular invasion >1.5 mm, being an important cut-off point in the prognostic analysis of cases diagnosed as CXPA. CONCLUSIONS: This systematic review demonstrates the importance of evaluating extracapsular invasion in cases diagnosed as CXPA, considering that tumours with invasion >1.5 mm, regardless of histopathological subtype, are associated with a worse prognosis. It is important to analyse the extracapsular invasion, especially as an auxiliary method to assess the prognosis of cases diagnosed in the initial clinical stages, thus identifying the possible biological behaviour of the neoplastic process and guiding the most appropriate patient management.

Salivary gland tumors in a Brazilian population: A 20-year retrospective and multicentric study of 2292 cases.

PURPOSE: Neoplasms of the salivary glands comprise more than thirty subtypes of lesions with various clinical behaviors. The present study aimed to describe the incidence and main features of salivary gland tumors in Brazil. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed (1997-2017). A total of 88,430 biopsy records of oral and maxillofacial lesions from 5 pathology referral centers were analyzed. All cases of salivary gland tumors were reviewed and data such as gender, age, skin color, anatomical location, symptomatology, tumor size and histopathological diagnosis were collected. RESULTS: Among all lesions, there were 2,292 (2.6%) cases of salivary gland tumors. The most frequent benign and malignant neoplasm was pleomorphic adenoma (n = 1,086; 47.4%) and mucoepidermoid carcinoma (n = 322; 14.0%), respectively. The majority of the patients were white (n = 757; 33%) and female (n = 1,391; 60.7%), and most cases involved the parotid gland (n = 933; 40.7%; p < 0.001). Age ranged from 1 to 101 years, occurring more in the fourth decade of life. Tumor size varied from 0.3 to 15 cm and the presence of symptomatology (pain/swelling) occurred more in patients with malignant tumors (p < 0.001). CONCLUSION: The incidence profile and clinical findings of salivary gland tumors were similar to those described worldwide; nevertheless, multicenter studies are valuable to better characterize these neoplasms.

Subgemmal neurogenous plaque of the tongue: a report of three cases.

Subgemmal neurogenous plaque (SNP) is a biphasic neural structure associated with the taste buds. Clinically, SNP usually presents as an asymptomatic, normally colored, papule located in the posterior lateral border of the tongue. Accurate diagnosis is based only on histopathological examination, which shows a superficial neurofibroma-like pattern and a neuroma-like in the deep zone. Appropriate recognition of clinical and morphological aspects of SNPs can avoid their misdiagnosis as neural neoplasms. We report three cases of SNP with detailed clinical, histopathological, and immunohistochemical features.