Immunohistochemical study of the plasminogen activator system in benign epithelial odontogenic lesions

Abstract: The aim of this study was to analyze and compare the immunohistochemical expression of plasminogen activator system (PAS) proteins (uPA, uPAR, and PAI-1) in ameloblastomas (AMBs), odontogenic keratocysts (OKCs), and dental follicles (DFs) representing normal odontogenic tissue, as well as to investigate possible correlations between these proteins. Twenty AMBs, 20 OKCs, and 10 DFs were selected for immunohistochemical analysis. In each case, the immunoexpression of uPA, uPAR, and PAI-1 was evaluated semiquantitatively based on the percentage of positivity in odontogenic epithelial and connective tissue cells. The epithelial immunoexpression of uPA was significantly lower in AMBs when compared to OKCs (p = 0.001) and DFs (p = 0.029). Significantly higher epithelial immunostaining for uPAR was observed in AMBs when compared to OKCs (p < 0.001). There were no significant differences in the epithelial immunoexpression of PAI-1 between AMBs and OKCs (p = 1.000). The correlations found for the expression of the studied proteins were not statistically significant (p > 0.05). However, the epithelial and connective tissue expressions of uPAR have a strong positive and statistically significant correlation in AMBs. The present results suggest that uPA is involved in the pathogenesis of OKCs and that uPAR may participate in tumorigenesis in AMBs. The high percentage of PAI-1-positive cells suggests a possible role for this protein in the development of AMBs and OKCs. Furthermore, the studied proteins do not seem to act synergistically in AMBs, OKCs, and DFs.

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.

ALDH1 expression and potential clinical implications in chronic inflammatory periapical lesions

Abstract: Aldehyde dehydrogenase 1 (ALDH-1) is a marker of stem cells in a variety of diseases, but its role in individuals with chronic inflammatory periapical lesions remains unknown. The aim of this study was to investigate the presence of cells with a stem cell profile based on the immunoexpression of ALDH-1 in periapical granulomas (PGs) and radicular cysts (RCs). A total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to immunohistochemical study. The anti-ALDH-1 antibody was applied using the immunoperoxidase technique. An immunoexpression score (intensity vs. percentage of cells) was used, with the cases being classified as low expression (score: 0 to 4) and high expression (score: 6 to 9). The Chi-square test was used with a 5% level of significance. Immunoexpression of ALDH-1 was detected in all cases of PGs and RCs. In PG cases, the expression was diffuse in connective tissue cells, with most cases exhibiting high expression (n = 18; 69.2%), while in RC cases the expression revealed focal distribution in cells of the capsule and epithelial cells of the cystic lining, with most cases classified as low expression (n = 18; 72%). Significant differences in the expression scores of ALDH-1 were observed in PGs (p = 0.003). The variable expression of ALDH-1 suggests the presence of cells with stem cell profiles in PGs and RCs. These findings suggest that periapical tissues infiltrated by chronic inflammation can recruit important cells for the repair or evolution of periapical lesions.

Prevalence of Lip and Tongue Squamous Cell Carcinoma (Scc) at a Pathological Anatomy Service in Northeast Brazil

ABSTRACT: The aim of this work was to trace an epidemiological and clinical profile of oral squamous cell carcinoma (SCC) cases diagnosed as lip and tongue SCC from June 2001 to 2018 at a pathology anatomy service located in Northeastern Brazil. Age, sex, duration, location, growth type, staining, metastasis, etiologic agents and lesion size data were obtained fr om patient clinical files and histopathological reports. A total of 124 cases were recorded, with tongue SCC being the most preval ent. The common characteristics of both assessed SCCs included higher frequency in men, mean age of 60 years old, evidence mostly of exophytic lesions and maximum size of 4 cm, predominantly diagnosed after a maximum of 1 year of appearance. Regarding divergent findings, lip SCC occurred mostly in the lower portion of the lip, presenting a predominantly leukoplastic color, with regular smoking habits and sunlight identified as the main etiological agents, and no strong relation to metastasis. On the other hand, tongue SCC mostly exhibiting predominantly erythroleukoplastic staining, with a greater relationship to alcohol - associated smoking and regular smoking habits. The highest percentage of patients with metastasis presented tongue SCC. Although lip and tongue SCC display a male preference, an increasing amount of female involvement has been noted over the years, due to the adoption of deleterious habits such as smoking and alcoholism. Tongue SCC presented a greater relationship with metastasis and clinical leukoeritroplastic evidence. This greater aggressiveness could be related to the unfavorable locat ion of these lesions in relation to lip SCC, sometimes making it difficult to identify in their early development stages.

RESUMEN: El objetivo de este trabajo fue rastrear un perfil epidemiológico y clínico de los casos de carcinoma oral de células escamosas (CCE) diagnosticados como CCE de labios y lengua entre junio de 2001 y 2018 en un servicio de anatomía patológica ubicado en el Noreste de Brasil. Los datos de edad, sexo, duración, ubicación, tipo de crecimiento, tinción, metástasis, agentes etiológicos y tamaño de la lesión se obtuvieron de los archivos clínicos de los pacientes y los informes histopatológicos. Se revisaron un total de 124 casos, siendo el CCE de lengua el más prevalente. Las características comunes de ambos CCE evaluados incluyeron mayor frecuencia en hombres, edad promedio de 60 años, evidencia mayoritariamente de lesiones exofíticas y tamaño máximo de 4 cm, diagnosticado predominantemente después de un máximo de 1 año de aparición. En cuanto a los hallazgos divergentes, el CCE labial se presentó mayoritariamente en la porción inferior del labio, presentando un color predominantemente leucoplásico, con el hábito de fumar habitualmente y la luz solar identificados como los principales agentes etiológicos, sin una fuerte relación con las metástasis. Por otro lado, el CEC de la lengua presenta en su mayoría tinción predominantemente eritroleucoplásica, con una mayor relación con el tabaquismo asociado con el alcohol y con los hábitos habituales de tabaquismo. El mayor porcentaje de pacientes con metástasis presentó CCE de lengua. Aunque el CCE de labios y lengua muestra una preferencia en hombres, se ha observado una cantidad cada vez mayor prevalencia en mujeres a lo largo de los años, debido a la adopción de hábitos nocivos como el tabaquismo y el alcoholismo. El CCE de lengua presentó una mayor relación con la metástasis y la evidencia clínica leucoeritroplásica. Esta mayor agresividad podría estar relacionada con la ubicación desfavorable de estas lesiones en relación al CCE labial, dificultando en ocasiones su identificación en sus primeras etapas de desarrollo.

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.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma

Abstract Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Immunohistochemical expression of OCT4 and CD44 in major and minor salivary gland neoplasms

Abstract The aim of this study was to identify tumor parenchyma cells exhibiting immunohistochemical profile of stem cells by evaluating the immunoreactivity of OCT4 and CD44 in a number of cases of salivary gland neoplasms. The sample consisted of 20 pleomorphic adenomas, 20 mucoepidermoid carcinomas, and 20 adenoid cystic carcinomas located in major and minor salivary glands. The expression of OCT4 and CD44 was evaluated by the percentage of positive cells and the intensity of expression. All studied cases showed positive expression of OCT4 and CD44 and higher values than the control groups. For OCT4, luminal and non-luminal cells were immunostained in the case of pleomorphic adenomas and adenoid cystic carcinomas. Moreover, the immunoreactivity of CD44 was particularly evident in the non-luminal cells of these lesions. In mucoepidermoid carcinomas, there was immunoreactivity for both markers in squamous and intermediate cells and absence of staining in mucous cells. For both markers, a significantly higher immunostaining was verified in neoplasms located in the major salivary glands compared with lesions in minor salivary glands (p<0.001). In the total sample and in minor salivary glands, malignant neoplasms exhibited higher immunoreactivity for OCT4 than pleomorphic adenoma. A significant moderate positive correlation (r = 0.444 and p ≤ 0.001) was found between OCT4 and CD44 immunoexpression in the total sample. The high expression of OCT4 and CD44 may indicate that these proteins play an important role in identifying tumor stem cells.

Caliber persistent artery in the upper lip: a case report with unusual histopathological findings

Abstract Caliber persistent labial artery (CPLA) consists in a dilated portion of the main branch of the labial artery without loss of size. The aim of this study is to report a case of a patient diagnosed with CPLA in the upper lip, emphasizing unusual histopathological and immunohistochemical findings. A 67-year-old female patient with complaint of a pulsating upper lip lesion without painful symptomatology. Under a clinical diagnosis of CPLA, and considering that the patient was edentulous and used a total prosthesis, an excisional biopsy of the lesion was performed to avoid future traumas in the region and consequently possible exuberant local bleeding. At anatomopathological examination structures suggestive of lymphoid follicles and germinal centers were visualized. Immunohistochemistry showed positivity for CD20, CD68, desmin and CD34 and negativity for CD4. The patient did not have a history of allergies, cardiovascular, rheumatic or systemic diseases that could justified the findings. The case presents unusual histopathological structures, evidencing the necessity of more studies about this pathology so scarce in the literature.

Resumo Artéria labial de calibre persistente (ALCP) consiste em uma parte dilatada do ramo principal da artéria labial que penetra no tecido submucoso sem perda de calibre. O objetivo desse estudo é relatar um caso de uma paciente diagnosticada com ALCP em lábio superior, enfatizando os achados histopatológicos e imuno-histoquímicos incomuns. Paciente de 67 anos, sexo feminino, com queixa de lesão em lábio superior, pulsante, sem sintomatologia dolorosa. Diante do diagnóstico clínico de ALCP, e considerando que a paciente era edêntula e usuária de prótese total, foi realizada biópsia excisional para evitar futuros traumas na região e, consequentemente, sangramento local exuberante. Ao exame anatomopatológico foram visualizadas estruturas sugestivas de folículos linfoides e com formações sugestivas de centros germinativos. No exame imuno-histoquímico observou-se imunopositividade para CD20, CD68, desmina e CD34 e sem imunomarcação para CD4. A paciente relatou não possuir histórico de alergias, doenças cardiovasculares, reumáticas ou sistêmicas que justificassem os achados. O caso apresenta estruturas histopatológicas incomuns, corroborando a necessidade de mais estudos acerca dessa lesão tão pouco discutida na literatura.

Expression of urokinase-type plasminogen activator and its receptor in squamous cell carcinoma of the oral tongue

Abstract Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in the proteolysis of basement membrane and extracellular matrix structures, facilitating tumor invasion. The purpose of this study was to evaluate the relationship between these proteins and clinicopathological parameters in squamous cell carcinoma of the oral tongue (SCCOT). Sixty cases of SCCOT were submitted to immunohistochemistry and analyzed semiquantitatively at the invasion front and in the tumor core. The results were associated with lymph node metastasis, clinical stage, locoregional recurrence, clinical outcome and histological grade of malignancy. A higher expression of uPA was observed in cases of tumors of high-grade versus low-grade malignancy (p = 0.010). Moreover, the cases with the worst pattern of invasion presented an overexpression of uPA (p = 0.011). The presence of locoregional recurrence was associated with uPAR (p = 0.039), and the expression of both biomarkers was much higher at the invasion front than in the tumor core (p < 0.001). The results suggest uPA and uPAR are involved in the progression and aggressiveness of SCCOT, mainly at the tumor-host interface.

Giant Epignathus Teratoma Discovered at Birth: A Case Report and 7-Year Follow-Up

Abstract Teratomas are tumors composed by tissues derived from the three germ cell layers, and they are relatively uncommon in head and neck. The term epignathus has been applied to teratomas from the oropharynx. This paper reports the case of a giant epignathus teratoma discovered at birth, which was successfully managed and followed up for 7 years. A newborn boy presented a polypoid tumor mass exteriorizing through the mouth over a length of 9 cm, with some surface areas resembling skin and others exhibiting hair. Computed tomography showed that the mass arose deep from the left hemiface. Alpha-fetoprotein (AFP) levels were high (316,000 ng/mL). Surgery was performed and microscopic analysis confirmed the diagnosis of mature teratoma. Because of residual tumor and high AFP levels, the patient was submitted to chemotherapy, resulting in complete regression of the lesion and normalization of AFP levels. Surgical repair of a cleft palate was performed at 5 years of age. At 7 years of age, the patient was in good general health and showed no clinical signs of recurrence. Although epignathus is a rare condition, it should be diagnosed in the fetus as early as possible. Prenatal care provides unquestionable benefits, providing the early diagnosis of anomalies that can jeopardize the life of the fetus and contributing to the indication of cases that require treatment before birth.

Resumo Teratomas são tumores constituídos por tecidos derivados das três camadas de células germinativas e são relativamente incomuns em cabeça e pescoço. O termo epignathus tem sido utilizado para designar teratomas que se originam na orofaringe. Este artigo relata o caso de um teratoma epignathus gigante descoberto ao nascimento, o qual foi tratado com sucesso e proservado por 7 anos. Um menino recém-nascido apresentou uma massa tumoral polipoide que se exteriorizava através da boca por uma extensão de 9 cm, com regiões da superfície semelhantes à pele e outras exibindo pelos. Exame de tomografia computadorizada revelou que a massa se originava profundamente na hemiface esquerda. Os níveis de alfa-fetoproteína (AFP) se apresentavam elevados (316.000 ng/mL). Foi realizada cirurgia e a análise microscópica confirmou o diagnóstico de teratoma maduro. Por apresentar lesão residual e altos níveis de AFP, o paciente foi submetido à quimioterapia, resultando em regressão completa da lesão e normalização dos níveis de AFP. Correção cirúrgica de uma fenda palatina foi realizada aos 5 anos de idade. Aos 7 anos de idade, o paciente apresentava um bom estado de saúde geral, sem sinais clínicos de recorrência da lesão. Embora o epignathus seja uma condição rara, seu diagnóstico no feto deve ser realizado o mais precocemente possível. O cuidado pré-natal proporciona benefícios inquestionáveis, permitindo o diagnóstico precoce de anomalias que podem comprometer a vida do feto e contribuindo para a indicação de casos que requerem tratamento antes do nascimento.

Analysis of GLUT-1, GLUT-3, and angiogenic index in syndromic and non-syndromic keratocystic odontogenic tumors

Abstract The aim of this study was to evaluate the immunoexpression of glucose transporters 1 (GLUT-1) and 3 (GLUT-3) in keratocystic odontogenic tumors associated with Gorlin syndrome (SKOTs) and non-syndromic keratocystic odontogenic tumors (NSKOTs), and to establish correlations with the angiogenic index. Seventeen primary NSKOTs, seven recurrent NSKOTs, and 17 SKOTs were selected for the study. The percentage of immunopositive cells for GLUT-1 and GLUT-3 in the epithelial component of the tumors was assessed. The angiogenic index was determined by microvessel count. The results were analyzed statistically using the nonparametric Kruskal-Wallis test and Spearman’s correlation test. High epithelial immunoexpression of GLUT-1 was observed in most tumors (p = 0.360). There was a higher frequency of negative cases for GLUT-3 in all groups. The few GLUT-3-positive tumors exhibited low expression of this protein in epithelial cells. No significant difference in the angiogenic index was observed between groups (p = 0.778). GLUT-1 expression did not correlate significantly with the angiogenic index (p > 0.05). The results suggest that the more aggressive biological behavior of SKOTs when compared to NSKOTs may not be related to GLUT-1 or GLUT-3 expression. GLUT-1 may play an important role in glucose uptake by epithelial cells of KOTs and this process is unlikely related to the angiogenic index. GLUT-1 could be a potential target for future development of therapeutic strategies for KOTs.

Immunoexpression of cell proliferation markers in oral squamous cell carcinoma / Inmunoexpresiones de marcadores de proliferación celular en carcinoma de células escamosas orales

This study aimed to assess the immunoexpression of cell proliferation markers (Ki-67 and Mcm-2) in oral tongue cancer, correlating it with patients' age and prognostic indicators. Sample was composed of 22 cases under 40 years and 22 over 50 years of age. Clinical staging and histological grade of malignancy were obtained. Cell proliferation was evaluated through labeling indices. Statistical analysis was performed (p<0.05 for statistical significance). Most young patients were stages III/IV (n=13/65 %) and most older patients were stages I/II (n=11/61.1 %) (p>0.05). Mean Ki-67-LI in young and older patients was 42.4 % and 44.15 %, respectively (p>0.05). Mean Mcm-2-LI was higher in older (63.6 %) than in young patients (55.75 %) (p<0.05). We found that young patients presented more aggressive lesions in comparison to older patients, however Mcm-2 expression was significantly higher in older than in young patients. SCC of tongue can be more aggressive in young patients, and this may not be related to cell proliferation. Our findings for Mcm-2 LI and Ki-67 LI suggests that Mcm-2 could be a more sensitive marker for cell proliferation.

Este estudio tuvo como objetivo evaluar la inmunoexpresión de marcadores de proliferación celular (Ki-67 y Mcm-2) en el cáncer de lengua oral, correlacionándolo con la edad de los pacientes y los indicadores pronósticos. La muestra estuvo compuesta por 22 personas menores de 40 años y 22 personas mayores de 50 años. Se identificaron los estadios clínicos y el grado histológico de malignidad. La proliferación celular se evaluó mediante índices de marcado. Se realizó análisis estadístico (p <0,05 para significación estadística). La mayoría de los pacientes jóvenes eran estadios III / IV (n = 13/65 %) y la mayoría de los pacientes mayores eran estadios I / II (n = 11 / 61,1 %) (p> 0,05). La media de Ki-67-LI en pacientes jóvenes y mayores fue 42,4% y 44,15%, respectivamente (p> 0,05). La media de Mcm-2-LI fue mayor en pacientes mayores (63,6 %) que en pacientes jóvenes (55,75 %) (p <0,05). Se encontró que los pacientes jóvenes presentaron lesiones más agresivas en comparación con los pacientes mayores, sin embargo la expresión de Mcm-2 fue significativamente mayor en pacientes mayores que en pacientes jóvenes. SCC de la lengua puede ser más agresivo en pacientes jóvenes, y esto no puede estar relacionado con la proliferación celular. Nuestros hallazgos para Mcm-2 LI y Ki-67 LI sugieren que Mcm-2 podría ser un marcador más sensible para la proliferación celular.

Expressão imunoistoquímica da endoglina (CD105) e do fator de von Willebrand em carcinoma epidermoide oral e sua relação com parâmetros clinicopatológicos / Immunohistochemical expression of endoglin (CD105) and von Willebrand factor in oral squamous cell carcinoma and its relationship with clinicopathological parameters

CONTEXTO: A angiogênese tem sido associada à progressão de neoplasias malignas e, embora haja estudos acerca de marcadores angiogênicos no carcinoma epidermoide oral (CEO), existem resultados conflitantes na literatura. OBJETIVOS: Avaliar a expressão imunoistoquímica do CD105 e do fator de von Willebrand (FvW) em CEO e sua relação com parâmetros clínicos do tumor. MÉTODOS: A imunoexpressão dos referidos biomarcadores foi analisada em 30 casos de CEO e correlacionada a parâmetros clínicos do tumor (idade e sexo dos pacientes, localização anatômica e estadiamento clínico Tumor, Nodo e Metástase, TNM). RESULTADOS: A imunomarcação com o anticorpo anti-FvW foi mais efetiva que a do CD105 no CEO. No que concerne à localização anatômica, o assoalho bucal e a região retromolar apresentaram diferenças estatisticamente significativas quanto aos índices angiogênicos (p = 0,004), determinados pela técnica de contagem microvascular (MVC). Não houve relação estatisticamente significativa entre o estadiamento clínico TNM e os índices angiogênicos, com os dois biomarcadores. CONCLUSÕES: Com base nos achados deste estudo, sugere-se um envolvimento da neoformação vascular na carcinogênese oral, embora não tenha sido evidenciada associação significativa com o estágio clínico da lesão.

BACKGROUND: Angiogenesis has been linked with progression of malignant neoplasms and although studies have been conducted investigating angiogenic markers in oral squamous cell carcinoma (OSCC), contradictory results are reported in the literature. OBJECTIVES: To evaluate immunohistochemical expression of CD105 and von Willebrand factor (vWF) in OSCC and their relationships with clinical parameters of the tumors. METHODS: Immunoexpression of these biomarkers was analyzed in 30 cases of OSCC and correlated with clinical parameters of the tumors (age and sex of patients, anatomic site and Tumor, Node and Metastasis clinical staging [TNM]). RESULTS: In OSCC specimens, immunostaining was more effective using the anti-vWF antibody than using the anti-CD105 antibody. Angiogenic indices, determined by microvascular count (MVC) technique, were different for the floor of the mouth and the retromolar region, with statistical significance (p = 0.004). There were no statistically significant relationships between results for the two biomarkers and TNM clinical staging or angiogenic indices. CONCLUSIONS: The findings of this study suggest that vascular remodeling is involved in oral carcinogenesis, although there was no evidence of a significant association with clinical stage of lesions.

Clinicopathological analysis of salivary gland tumors over a 15-year period

Abstract Salivary gland tumors (SGT) are rare neoplasms that generate interest due to their histopathological diversity and clinical behavior. The aims of the present study were to investigate clinicopathological aspects of SGTs diagnosed at a tertiary health center and compare the findings with epidemiological data from different geographic locations. Cases of tumor in the head and neck region at a single health center in the period between 1995 and 2010 were reviewed. Patient gender, age and ethnic group as well as anatomic location, histological type and clinical behavior of the tumor were recorded. Availability of complete information about these aspects was considered the inclusion criteria. Descriptive statistical analysis of the data was performed using the frequencies of categorical variables. Among the 2168 cases of tumors in the head and neck region, 243 (11.20%) cases were diagnosed in the salivary glands, 109 of which met the inclusion criteria: 85 (78%) benign tumors and 24 (22%) malignant tumors. Mean patient age was 46.47 years. The female gender accounted for 56 cases (51.4%) and the male gender accounted for 53 (48.3%). The major salivary glands were affected more (75.2%) than the minor glands. The most frequent benign and malignant SGTs were pleomorphic adenoma (81.2%) and adenoid cystic carcinoma (58.3%), respectively. In conclusion, pleomorphic adenoma and adenoid cystic carcinoma are the most frequent benign and malignant lesions, respectively. Comparing the present data with previous studies on SGTs, one may infer that some demographic characteristics and the predominance of malignant tumors vary in different geographic regions.

Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas

Abstract: The aim of this study was to determine the number of FoxP3+ regulatory T (Treg) cells in the microenvironment of lower lip squamous cell carcinomas (LLSCCs) and to correlate the findings with clinicopathological parameters (tumor size/extent, regional lymph node metastasis, clinical stage, and histopathological grade of malignancy). Fifty cases of LLSCC were selected. Lymphocytes exhibiting nuclear immunostaining for FoxP3 were quantified in 10 microscopic fields at the deep invasive front of LLSCCs. The results were analyzed statistically using the nonparametric Mann-Whitney test and Fisher's exact test. FoxP3+ lymphocytes were observed in all cases studied. The number of these cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (p > 0.05). Low-grade tumors contained a larger number of FoxP3+ lymphocytes than high-grade tumors (p = 0.019). Tumors with an intense inflammatory infiltrate exhibited a larger number of Treg cells (p = 0.035). On the other hand, the number of FoxP3+ lymphocytes was smaller in tumors arranged in small cell clusters (p = 0.003). No significant differences in the number of FoxP3+ lymphocytes were observed according to the degree of keratinization (p = 0.525) or nuclear pleomorphism (p = 0.343). The results suggest the participation of Treg cells in immune and inflammatory responses in the microenvironment of LLSCCs. These cells may play a more important role in early stages rather than in advanced stages of lip carcinogenesis.

Expression of Glucose Transporters 1 and 3 in Metastatic and Non-Metastatic Lower Lip Squamous Cell Carcinoma

This study aimed to evaluate the immunoexpression of glucose transporters 1 (GLUT-1) and 3 (GLUT-3) in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). Twenty LLSCCs with regional nodal metastasis and 20 LLSCCs without metastasis were selected. The distribution of staining and the percentage of GLUT-1 and GLUT-3 staining in each tumor core and at the deep invasive front were assessed. Most tumors (70%) exhibited peripheral staining for GLUT-1 in nests, sheets and islands of neoplastic cells, whereas predominantly central staining was observed for GLUT-3 (72.5%). A high percentage of GLUT-1-positive cells was observed at the deep invasive front and in the tumor core of metastatic and non-metastatic tumors (p>0.05). The percentage of GLUT-1-positive cells was much higher than that of GLUT-3-positive cells both in the deep invasive front (p<0.001) and in the tumor core (p<0.001) of LLSCCs. No significant differences in the percentage of GLUT-1- and GLUT-3-positive cells were observed according to nodal metastasis, clinical stage or histological grade of malignancy (p>0.05). In conclusion, the results of the present study suggest an important role of GLUT-1 in glucose uptake in LLSCCs, although this protein does not seem to be involved in the progression of these tumors. On the other hand, GLUT-3 expression may represent a secondary glucose uptake mechanism in LLSCCs.

Este estudo objetivou avaliar a imunoexpressão dos transportadores de glicose 1 (GLUT-1) e 3 (GLUT-3) em carcinomas de células escamosas de lábio inferior (CCELI) metastáticos e não-metastáticos. Vinte CCELIs com metástase nodal regional e 20 CCELI sem metástase foram selecionados. Foram analisados a distribuição da imunomarcação e o percentual de imunorreatividade para GLUT-1 e GLUT-3 no centro tumoral e no front de invasão tumoral. A maioria dos tumores (70%) revelou marcação para GLUT-1 em áreas periféricas dos ninhos, lençóis e ilhas de células neoplásicas, ao passo que GLUT-3 revelou predomínio de marcação em áreas centrais (72.5%). Um alto percentual de células positivas para GLUT-1 foi observado no front de invasão e no centro tumoral das lesões metastáticas e não-metastáticas (p>0,05). O percentual de células positivas para GLUT-1 foi superior ao percentual de células positivas para GLUT-3, tanto no front de invasão (p<0,001) quanto no centro tumoral (p<0,001) dos CCELIs. Não foram observadas diferenças significativas no percentual de células positivas para GLUT-1 e GLUT-3 em relação à mestástase nodal, ao estádio clínico ou ao grau histológico de malignidade (p>0,05). Em conclusão, os resultados do presente estudo sugerem um importante papel para GLUT-1 na absorção de glicose nos CCELIs, embora esta proteína não pareça estar envolvida na progressão destes tumores. Por outro lado, a expressão de GLUT-3 pode representar um mecanismo secundário para a absorção de glicose nos CCELIs.

Immunohistochemical expression of protein 53, murine double minute 2, B-cell lymphoma 2, and proliferating cell nuclear antigen in odontogenic cysts and keratocystic odontogenic tumor.

Introduction: Even though odontogenic cysts share a similar histogenesis, they show different growth and differentiation profile due to differences in the proliferative cellular activity. Aims: We perform an immunohistochemical assessment of protein 53 (p53), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (bcl-2), and murine double minute 2 (MDM2) expression in odontogenic cysts and keratocystic odontogenic tumor analyzing their correlation with the biological behavior of these lesions. Materials and Methods: By the streptavidin-biotin-peroxidase method with antibodies against p53, PCNA, bcl-2, and MDM2 proteins, 11 radicular cysts, 11 dentigerous cysts, and 11 keratocystic odontogenic tumor were analyzed. The non-parametric Mann-Whitney U-test and Kruskall-Wallis test (P ≤ 0.05) were used to analyze the data. Results: Immunopositivity for PCNA was observed in all cases appraised, predominantly in the suprabasal layer of keratocystic odontogenic tumor epithelial lining (SD ± 19.44), but no significant differences were found among the groups of lesions. Bcl-2 immunoexpression was observed especially in the basal layer of keratocystic odontogenic tumor. PCNA LI was significantly higher than bcl-2 LI in keratocystic odontogenic tumor. MDM2 and p53 immunoexpression were not detected in the lesions studied. Among the evaluated lesions, the keratocystic odontogenic tumor showed different immunoexpression of the proliferation and apoptosis markers. Conclusion: The results of this study suggest that the keratocystic odontogenic tumor presents distinct biological behavior of the odontogenic cysts, as for the processes of proliferation, apoptosis, and differentiation, reinforcing the information in favor of the neoplastic nature of this lesion.

Neurilemmoma of the oral cavity in pediatric patient / Neurilemoma em cavidade oral acometendo paciente pediátrico

Neurilemmomas arising from Schwann cells, rarely found in oral cavity, are characterized by solitary occurrence, slow growth and smooth surface with variable clinical aspects, depending on the nerve origin. Most instances are typically asymptomatic. Microscopically, the histopathological characteristic consists of alternating regions of hypercellularity and hypocellularity such as Antoni A and Antoni B, respectively. The prognosis is favorable; complete surgical removal is the treatment of choice, no recurrence should be expected. The present report shows the case of neurilemmoma in bucal mucosa, in a 9-year-old child. Patient was referred to the Stomatology Clinic of School of Dentistry, Universidade Federal do Rio Grande do Norte, with complaint of nodular mass, with approximately one year development. Patient was submitted to excisional biopsy, with histopathological exam showing diagnosis of neurilemmoma. After 1 year follow-up there has been no recurrence of lesion.

Os neurilemomas se originam das células de Schwann e raramente são encontrados na cavidade oral, sendo caracterizados por uma ocorrência solitária de crescimento lento e superfície lisa com aspectos clínicos variáveis dependendo do nervo de origem, sendo tipicamente assintomático. Microscopicamente, as características histopatológicas consistem de regiões alternadas de hipercelularidade e hipocelularidade, conhecidas como Antoni A e Antoni B respectivamente. Apresentando um prognóstico favorável, onde o tratamento de escolha é a excisão cirúrgica completa, não sendo esperada recorrência. O presente relato descreve a presença de um neurilemoma em mucosa jugal, acometendo uma criança de 9 anos de idade, que compareceu ao Serviço de Estomatologia da Faculdade de Odontologia da Universidade Federal do Rio Grande do Norte, queixando-se de uma massa nodular, há aproximadamente 1 ano. O paciente foi submetido a biópsia excisional, sendo diagnosticado através do exame histopatológico como neurilemoma e há 1 ano vem sendo acompanhado por nossa equipe sem recorrência da lesão.

Eosinophilic ulcer of the lateral tongue: case report

Introduction: Eosinophilic ulcer of the oral mucosa (EUOM) is a lesion manifesting as ulcer with elevated margins. The lesion is self-limiting and develops rapidly usually disappearing after several weeks. The exact pathogenetic mechanisms implicated in its development are poorly understood, however, the possibility that trauma may play a role has been often postulated. Case report: A 63 year-old male patient had presented whit a chief complaint of painful ulcerated nodule on the tongue. Oral examination revealed a firm, raised and indurated erythematous nodule with a central ulcer that had a yellow fibrinous base. Clinical diagnosis hypothesis was either traumatic ulcer or oral squamous cell carcinoma. Histopathologic analysis revealed an ulcerated lesion with a dense mixed infiltrate of eosinophils, variably sized lymphocytes and epithelioid cells extending into submucosa. These cells exhibited pleomorphism, voluminous cytoplasm and nucleus with prominent nucleolus and were identified by immunohistochemical method as CD68+ cells. The histological diagnosis was EUOM. At 1-year follow-up there was no recurrence. Conclusion: Our case provides useful information on clinical and pathological features, diagnosis, treatment, and prognosis of EUOM, as suggesting the possible etiology of this uncommon lesion because it is poorly described in the literature.