Involvement of tryptase-positive mast cells and angiogenesis in the growth of inflammatory odontogenic cysts.

Inflammatory periapical lesions are characterized by infiltration of different immune cell types, the functions of which depend on an effective vascular network. This study aimed to evaluate the mast cells density (MCD) in inflamatory odontogenic cysts capsules concerning microvascular density (MVD), microvascular area (MVA), and microvascular perimeter (MVP), and correlate such findings with the type of lesion, intensity of the inflammatory infiltrate, and thickness of the epithelial lining. Twenty inflamatory dentigerous cysts (IDCs), twenty radicular cysts (RCs), and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-tryptase and anti-CD34 antibodies. RCs exhibited the highest MCD, MVD, MVA, and MVP indexes (p = < 0.001, p = 0.008, p = 0.003 and p = < 0.001, respectively), and lesions with inflammatory infiltrate grade III showed the highest MVD (p = 0.044). Considering epithelial thickness, a higher MVP index was identified in lesions with hyperplastic epithelium (p = 0.018). In IDCs, RCs, and RRCs, a strong positive correlation was observed between MVA and MVP (r = 0.950 and p = < 0.001; r = 0.914 and p = < 0.001; r = 0.713 and p = < 0.001, respectively). In IDCs, a moderate correlation was observed between MCD and both MVA and MVP (r = 0.660 and p = 0.002; r = 0.634 and p = 0.003, respectively). These results suggest that tryptase-positive mast cells might play an important role in the angiogenic activity of IDCs, while RCs had the highest indexes. Our findings also confirmed that the intensity of the inflammatory infiltrate and epithelial thickness influence angiogenesis.

Involvement of tryptase-positive mast cells and angiogenesis in the growth of inflammatory odontogenic cysts

Abstract: Inflammatory periapical lesions are characterized by infiltration of different immune cell types, the functions of which depend on an effective vascular network. This study aimed to evaluate the mast cells density (MCD) in inflamatory odontogenic cysts capsules concerning microvascular density (MVD), microvascular area (MVA), and microvascular perimeter (MVP), and correlate such findings with the type of lesion, intensity of the inflammatory infiltrate, and thickness of the epithelial lining. Twenty inflamatory dentigerous cysts (IDCs), twenty radicular cysts (RCs), and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-tryptase and anti-CD34 antibodies. RCs exhibited the highest MCD, MVD, MVA, and MVP indexes (p = < 0.001, p = 0.008, p = 0.003 and p = < 0.001, respectively), and lesions with inflammatory infiltrate grade III showed the highest MVD (p = 0.044). Considering epithelial thickness, a higher MVP index was identified in lesions with hyperplastic epithelium (p = 0.018). In IDCs, RCs, and RRCs, a strong positive correlation was observed between MVA and MVP (r = 0.950 and p = < 0.001; r = 0.914 and p = < 0.001; r = 0.713 and p = < 0.001, respectively). In IDCs, a moderate correlation was observed between MCD and both MVA and MVP (r = 0.660 and p = 0.002; r = 0.634 and p = 0.003, respectively). These results suggest that tryptase-positive mast cells might play an important role in the angiogenic activity of IDCs, while RCs had the highest indexes. Our findings also confirmed that the intensity of the inflammatory infiltrate and epithelial thickness influence angiogenesis.

O Cripto-1 é um potencial biomarcador para o diagnóstico diferencial dos tumores ósseos benignos e malignos dos maxilares / Cripto-1 is a potential biomarker for the differential diagnosis of benign and malignant jaw bone tumors

O termo lesão fibro-óssea dos maxilares (LFOM) é uma designação inespecífica para um grupo de distúrbios caracterizados, morfologicamente, pela substituição do tecido ósseo por uma matriz de tecido conjuntivo fibrosa, a qual exibe neoformação de tecido ósseo com diferentes graus de mineralização. O diagnóstico preciso das LFOM não é fácil e só pode ser realizado após uma análise minuciosa dos aspectos clínicos, radiológicos e histológicos. No entanto, deve-se admitir que alguns casos desafiam a exatidão na emissão do diagnóstico. Considerando a diversidade do comportamento biológico das lesões e as pesquisas sobre a identificação de potenciais marcadores moleculares, o objetivo deste trabalho foi realizar uma análise imunohistoquímica do cripto-1 (CR-1) e da ß-catenina em uma série de casos diagnosticados microscopicamente como displasia fibrosa (DF) (n=30), fibroma ossificante central (FOC) (n=28) e osteossarcoma (OS) (n=5) armazenados nos arquivos do Serviço de Anatomia Patológica Oral de uma população brasileira. As expressões imuno-histoquímicas foram analisadas através de escore imunorreativo. Os dados obtidos foram inseridos em um arquivo do software Microsoft Excel® e, posteriormente, analisados no software Statistical Package for Social Science. Para todos os testes estatísticos utilizados, o nível de significância foi estabelecido em 5% (p<0,05). O CR-1 exibiu predominância de um padrão fortemente positivo para os casos de FOC e OS, e do padrão moderado para os casos de DF (p<0,001). A ß-catenina exibiu predominância do padrão negativo para os casos de FOC e DF, e do padrão fortemente positivo para os casos de OS (p=0,001). O teste de correlação de Spearman revelou correlação positiva entre os escores imunorreativos de CR-1 e ß-catenina. Os resultados desta pesquisa sugerem a participação do CR-1 na patogênese do FOC e OS, assim como o uso dessa proteína como potencial biomarcador molecular para o diagnóstico diferencial de LFOM (AU).

Fibro-osseous lesions of maxilar (FOLM) is a non-specific designation for a group of disorders characterized, morphologically, by replacement of bone tissue by a matrix of fibrous connective tissue, showing neoformation of bone tissue with varying degrees of mineralization. Precise diagnosis of FOLM is not easy, and requires careful analyisis of clinical, radiological and histological aspects. Even so, some cases still challenge accuracy in diagnosis. Considering the diversity of biological behaviour of the lesions and the research regarding identification of potential molecular markers, this study aims to perform immunohistochemical analysis of crypto-1 and ß-catenin in a series of cases diagnosed microscopically as fibrous dysplasia (FD) (n=30), central ossifying fibroma (COF) (n=28) and osteossarcoma (OS) (n=5), stored in archives of Oral Pathological Anatomy Service of a Brazilian population. Immunohistochemical expressions were analysed by imunorreactive score. All data obtained was inserted into a file of Microsoft Excel® software (Microsoft Corporation, USA) and then transferred to a database of SPSS® for Windows software (Statistical Package for Social Sciences; IBM, USA), version 20.0. For all statistical tests used, the significance level established was p ≤ 0.05. CR-1 showed a predominant pattern of strong positive in COF and OS cases, and a moderate positive in FD cases (p<0,001). ß-catenin showed a predominant negative pattern for COF and FD cases, and a predominant strong positive pattern for OS cases (p=0,001). Spearman correlation tests showed positive correlation of the imunoreative scores of CR-1 and ß-catenin. Those results suggests CR-1 could be involved in the pathogenesis of COF and OS, and this protein could be used as a potential molecular biomarker for diferential diagnosis of FOLM (AU).

Ameloblastic carcinoma arising from a preexistent ameloblastoma / Carcinoma ameloblástico decorrente de um ameloblastoma preexistente

ABSTRACT Ameloblastic carcinoma (AC) is a rare odontogenic tumor that represents the malignant counterpart of an ameloblastoma. There are few cases of AC in the English-language literature, with only 16 cases arising from preexisting ameloblastomas reported in the last 10 years. Multiple local recurrences of ameloblastomas precede this transformation. In the current report, we describe a case of AC at the posterior maxilla in a 42-year-old female submitted to surgical resection, with three recurrences of ameloblastoma in a period of four years. Imaging exams showed a radiodense mass with cortical bone disruption and maxillary sinus invasion. Histologic analysis demonstrated features of islands and nests of malignant epithelium transformation, atypia, pleomorphic cells, nuclear hyperchromatism, necrosis and desmoplasia. AC represents a rare and challenging histologic diagnosis. Surgical access with adequate hard and soft tissue margins is essential for influencing survival. The description of new cases may reveal, through of treatment and clinical follow-up, characteristics that allow us better understanding of AC behavior.

RESUMEN El carcinoma ameloblástico (CA) es un tumor odontogénico raro que representa el equivalente maligno de un ameloblastoma. Hay pocos casos de CA en la literatura en lengua inglesa: en los últimos 10 años, sólo se reportaron 16 casos originados de ameloblastomas previos. Múltiples recidivas locales de este tumor preceden esa transformación. En este reporte, describimos un caso de CA en región posterior de maxila en una mujer de 42 años de edad, sometida a resección quirúrgica. En un periodo de cuatro años, se produjeron tres recurrencias del ameloblastoma. Exámenes de imagen muestran una masa radiodensa con destrucción cortical e invasión del seno maxilar. El análisis histológico ha revelado islas y nidos característicos de transformación epitelial maligna, atipias, pleomorfismo celular, hipercromatismo nuclear, necrosis y desmoplasia. El diagnóstico histológico del CA representa un raro desafío. El abordaje quirúrgico con ampliación de los márgenes de tejido duro y blando es esencial en la sobrevida del paciente. La descripción de nuevos casos puede revelar, mediante tratamiento y acompañamiento clínico, características que ayuden a comprender mejor el comportamiento del CA.

RESUMO O carcinoma ameloblástico (CA) é um tumor odontogênico raro que representa o equivalente maligno de um ameloblastoma. Existem poucos casos de CA na literatura em inglês: nos últimos 10 anos, foram relatados apenas 16 casos surgidos de ameloblastomas preexistentes. Múltiplas recorrências locais desse tumor precedem essa transformação. Neste relato, descrevemos um caso de CA em região posterior de maxila em uma mulher de 42 anos de idade, submetida à ressecção cirúrgica. Em um período de quatro anos, ocorreram três recidivas do ameloblastoma. Exames de imagem exibiram uma massa radiodensa com destruição da cortical óssea e invasão do seio maxilar. A análise histológica revelou ilhas e ninhos característicos de transformação maligna epitelial, atipias, pleomorfismo celular, hipercromatismo nuclear, necrose e desmoplasia. O CA representa um raro e desafiador diagnóstico histológico. O acesso cirúrgico com ampliação das margens de tecido duro e mole é essencial para o impacto na sobrevida do paciente. A descrição de novos casos pode revelar, por meio do tratamento e do acompanhamento clínico, características que ajudem a entender melhor o comportamento do CA.

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects.

The aim of this study was to evaluate macrophage M1 and M2 subpopulations in radicular cysts (RCs) and periapical granulomas (PGs) and relate them to clinical and morphological aspects. M1 macrophages were evaluated by the percentage of CD68 immunostaining associated with the inflammatory cytokine TNF-α, and M2 macrophages, by its specific CD163 antibody. The CD68+/CD163+ ratio was adopted to distinguish between the two macrophage subpopulations. Clinical, radiographic, symptomatology, treatment, and morphological parameters of lesions were collected and a significance level of p = 0.05 was adopted for statistical analysis. The results showed that the CD68+/CD163+ ratio was higher in the RCs (median = 1.22, p = 0.002), and the highest TNF-α immunostaining scores were found in RCs (p = 0.018); in PGs, the CD68+/CD163+ ratio was lower and associated with a greater CD163+ immunostaining (median = 1.02, p <0.001). The TNF-α in cyst epithelium had a score of 3 in 10 cases and predominance of M1 macrophages by CD68+/CD163+ (median = 2.23). In addition, CD68+ cells had higher percentage of immunostaining in smaller RCs (p = 0.034). Our findings suggest that increased CD68 immunostaining associated with TNF-α cytokine in RCs results in a greater differentiation of the M1 phenotype. The higher CD163 immunostaining in PGs results in greater differentiation of the M2 phenotype. Therefore, the inflammatory state promoted by M1 macrophages is related to growth and progression of RCs; on the other hand, the immunomodulatory state of M2 macrophages is related to maintenance of PGs.

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects

Abstract: The aim of this study was to evaluate macrophage M1 and M2 subpopulations in radicular cysts (RCs) and periapical granulomas (PGs) and relate them to clinical and morphological aspects. M1 macrophages were evaluated by the percentage of CD68 immunostaining associated with the inflammatory cytokine TNF-α, and M2 macrophages, by its specific CD163 antibody. The CD68+/CD163+ ratio was adopted to distinguish between the two macrophage subpopulations. Clinical, radiographic, symptomatology, treatment, and morphological parameters of lesions were collected and a significance level of p = 0.05 was adopted for statistical analysis. The results showed that the CD68+/CD163+ ratio was higher in the RCs (median = 1.22, p = 0.002), and the highest TNF-α immunostaining scores were found in RCs (p = 0.018); in PGs, the CD68+/CD163+ ratio was lower and associated with a greater CD163+ immunostaining (median = 1.02, p <0.001). The TNF-α in cyst epithelium had a score of 3 in 10 cases and predominance of M1 macrophages by CD68+/CD163+ (median = 2.23). In addition, CD68+ cells had higher percentage of immunostaining in smaller RCs (p = 0.034). Our findings suggest that increased CD68 immunostaining associated with TNF-α cytokine in RCs results in a greater differentiation of the M1 phenotype. The higher CD163 immunostaining in PGs results in greater differentiation of the M2 phenotype. Therefore, the inflammatory state promoted by M1 macrophages is related to growth and progression of RCs; on the other hand, the immunomodulatory state of M2 macrophages is related to maintenance of PGs.

Incidental Discovery of Acinic Cell Carcinoma of the Oral Mucosa with Metachronous Adenoid Cystic Carcinoma of the Upper Lip / Hallazgo Incidental de Carcinoma de Células Acinares de la Mucosa Oral con Carcinoma Adenoide Quístico Metacrónico del Labio Superior

ABSTRACT: Multiple salivary gland tumors represent an unusual event characterized by the development of composite lesions originated from minor or major salivary glands. These neoplasms can be categorized into three perspectives: Histologic type, time of appearance and topographic distribution. We report an unusual case of a 73-year-old black man with an acinic cell carcinoma (ACC) of the oral mucosa discovered incidentally during surgical removal of an adjacent mucocele. Approximately one year after the first consultation, the patient was seen at the local cancer reference center with a third lesion that was diagnosed as an adenoid cystic carcinoma (AdCC) of the upper lip. The patient underwent surgical reconstruction of the treated areas and has been free of the disease for the past year. To our knowledge, the combination of ACC and AdCC in intraoral sites has not been reported in the literature.

RESUMEN: Los tumores de glándulas salivales múltiples representan un evento inusual caracterizado por el desarrollo de lesiones compuestas, originadas en glándulas salivales menores o mayores. Estos neoplasmas se pueden categorizar en tres perspectivas: tipo histológico, tiempo de aparición y distribución topográfica. Reportamos un caso inusual de un hombre negro de 73 años con un carcinoma de célula acínica (ACC) de la mucosa oral descubierta incidentalmente durante la extirpación quirúrgica de un mucocele adyacente. Aproximadamente un año después de la primera consulta, el paciente se presentó en el centro de referencia del cáncer local con una tercera lesión que fue diagnosticada como carcinoma adenoide quístico (AdCC) del labio superior. El paciente se sometió a la reconstrucción quirúrgica de las áreas tratadas y durante el último año no ha presentado recurrencia de la enfermedad. De acuerdo a nuestro conocimiento la combinación de ACC y AdCC en sitios intraorales no se ha informado en la literatura.

Avaliação imunoistoquímica de CD34 e triptase em cistos odontogênicos radiculares e cistos dentígeros inflamados / Immunohistochemical evaluation of CD34 and tryptase in root odontogenic cysts and inflamed dentigerous cysts

Dentre os cistos odontogênicos comumente encontrados na prática clínica odontológica, os cistos radiculares (CRs) e os cistos dentígeros (CDs) representam conjuntamente os mais frequentes cistos dos ossos gnáticos. Os cistos odontogênicos possuem origem inflamatória ou de desenvolvimento. No entanto, alterações inflamatórias secundárias podem ser vistas nos últimos. Alguns estudos têm identificado os mastócitos nessas lesões císticas e sua possível relação com a angiogênese. Nesta perspectiva, a presente pesquisa objetivou avaliar e comparar a expressão imunoistoquímica do CD34 e da triptase em CDs inflamados e CRs e verificar se os mastócitos influenciam na angiogênese destas lesões. Para tanto, foram selecionados 20 casos de CDs inflamados e 20 casos de CRs para serem submetidos à análise morfológica e imunoistoquímica. A imunomarcação de cada caso foi avaliada de forma quantitativa. Após a identificação das áreas de maior imunorreatividade, foram analisadas a densidade microvascular (DMV), a área microvascular (AMV) e o perímetro microvascular (PMV) mensurados através da imunoexpressão do CD34 e a densidade dos mastócitos (DMC) mensurada por meio da imunoexpressão da triptase, realizadas nas mesmas áreas dos consecutivos campos representativos de cada caso.

A análise estatística foi realizada através dos testes de Mann-Whitney, Qui-quadrado de Pearson, Exato de Fisher e Correlação de Spearman (r), com nível de significância estabelecido em 5% (p < 0,05). Os resultados demonstram diferenças estatisticamente significativas entre as lesões císticas supracitadas em relação à avaliação da DMC (p < 0,001). Além disso, a análise da DMV revelou diferenças estatisticamente significativas entre as lesões císticas (p = 0,007) e também no que se refere à intensidade do infiltrado inflamatório (p = 0,021). Por fim, observou-se nos casos de CDs inflamados, moderada correlação positiva entre a DMC e a AMV (r = 0,660; p = 0,002), assim como moderada correlação positiva entre a DMC e o PMV (r = 0,634; p = 0,003). Face ao exposto, pode-se concluir que os mastócitos participam em diferentes etapas da angiogênese associada à inflamação dos CRs e CDs. (AU)

Among the odontogenic cysts commonly found in dental clinical practice, radicular cysts (RCs) and dentigerous cysts (DCs) together represent the most common cysts of gnathic bones. Odontogenic cysts feature inflammatory or developmental origin. However, secondary inflammatory changes can be seen in the latest. Some studies have identified mast cells in these cystic lesions and its possible relation to angiogenesis. From this perspective, the present study aimed to evaluate and compare the immunohistochemical expression of CD34 and tryptase in inflamed RCs and DCs and to verify if mast cells influence the angiogenesis of these lesions. For this purpose, we selected 20 cases of inflamed DCs and 20 cases of RCs to undergo morphological and immunohistochemical analysis. Immunostaining of each case was evaluated quantitatively. After identifying the areas of greatest immunoreactivity, we analyzed microvessel density (MVD), microvessel area (MVA) and microvascular perimeter (MVP), measured by CD34 immunostaining, and the density of mast cells (DMC), measured by tryptase immunostaining, which were held in the same representative areas of consecutive fields for each case. Statistical analysis was performed using the Mann-Whitney, Chi-square and Fisher's exact tests, and Spearman's correlation (r). Significance level was set at 5% (p < 0.05). The results showed statistically significant differences between the abovementioned cystic lesions regarding DMC evaluation, being higher in CR (p < 0.001). Furthermore, MVD analysis revealed statistically significant differences between cystic lesions (p = 0.007) being greater in CR and also in regard to intensity of the inflammatory infiltrate with a predominance of lesions classified as intense infiltration (p = 0.021). Finally, we observed in cases of inflamed DCs, moderate positive correlation between DMC and MVA (r = 0.660; p = 0.002) and moderate positive correlation between DMC and MVP (r = 0.634; p = 0.003). Given the above, it can be concluded that mast cells participate in different stages of inflammation-associated angiogenesis in RCs and DCs. (AU)

Granular cell tumor in two oral anatomic sites.

Granular cell tumor (GCT) is an uncommon benign soft tissue neoplasm, which usually presents as a solitary nodule, appearing especially in the tongue. There are few cases of multiple oral GCT in the English-language literature, with only three cases reported in the last 20 years. This report describes a case of two oral GCT in a young patient and provides a literature review from 1995 to 2015. Clinical characteristics of the reviewed cases were retrieved and compared with the present case. Exceptionally, the current case was the only one that occurred in an adolescent and solely affected the oral cavity. Besides the oral cavity, the other cases also observed GCT lesions in the skin. Although rare, it is important to know multiple oral GCT clinical and histopathological characteristics so they can be correctly diagnosed, treated and followed up.

Perfil de acadêmicos de Odontologia sobre biossegurança / Profile of dental students about biosafety

Objetivo: A formação do profissional da Odontologia requer preparo e esclarecimento quanto ao uso das medidas universais de biossegurança em virtude da exposição a agentes infectocontagiosos. Este estudo descritivo teve como objetivo avaliar o nível de conhecimento de uma população de acadêmicos de Odontologia a respeito de biossegurança, além de identificar as dúvidas mais frequentes sobre medidas preventivas no ambiente odontológico e avaliar o interesse desses acadêmicos em relação ao tema biossegurança. Materiais e métodos: A amostra foi constituída por 358 alunos de três universidades. Foi aplicado um questionário contendo perguntas objetivas e subjetivas em alunos dos 1º, 5º e últimos períodos. Resultados: Observou-se que 92.6% dos alunos conheciam o significado de biossegurança e 92.3% relatou o uso de EPI pelo seu CD e para o paciente. Frente a um atendimento na clínica, 291 (82.7%) alunos responderam que saberiam se cuidar e 59 (16.8%) que não, sendo 94.9% destes últimos, alunos do primeiro período. Entre os alunos do primeiro período, 38.4% responderam não ser importante considerar o paciente como potencial portador de doença. Conclusões: Conclui-se que, é importante ministrar conteúdos básicos sobre biossegurança nos períodos pré-clínicos, visando a entrada dos alunos às atividades clínicas com maior segurança. Ressalta-se ainda a importância da fiscalização e atualização periódicas de práticas, e conhecimentos das medidas preventivas adequadas que permitam o exercício de atividades acadêmicas em segurança em todos os períodos do curso.

Aim: The professional formation in Dentistry requires preparation andknowledge regarding the use of universal biosafety measures againstexposure to infectious agents. This descriptive study aimed to evaluate the level of knowledge of dentistry students about biosafety, and identify the most frequent doubt about preventive measures in dental care environment, also assess the student’s interest bybiosafety. Material and methods:The sample consisted of 358 students from three universities. A questionnaire with subjective and objective questionswas applied to students at 1st, 5th and last periods. Results: It was observed that 92.6% of students knew themeaning of biosafety and 92.3% reported the use of PPE for their dentist and for the patient. When as ked if theywould know to take care in clinicalenvironment, 291 (82.7%) students answered that they would know how to care and 59 (16.8%) not, 94.9% of the latter were students of the first period, in this group, 38.4% of students responded not be important to consider the patient as a potential transmitter ofdisease. In the total sample, 98.6% considered to be important the topic of the research. Conclusions: It was concluded that it is important introduce basic content on biosafety in the pre-clinical periods, aimin g at the entry of students to the clinical activities moresafely. It is emphasized the importance of supervision and periodic update of practices and knowledge about preventive measures facilitating the exercise of academic activities in safety at all course periods.