Diverse Roles of Macrophages in Oral Inflammatory and Benign Lesions - A Narrative Review

Background: Macrophages are immune cells with diverse profiles and functions. Macrophages play significant roles in the repair and resolution of inflammatory and reactive lesions. They secrete cytokines and modulate the tissue microenvironment and surrounding cellular responses. Objectives: The present article reviews the histological presentation and role of macrophages in the pathogenesis of oral inflammatory and benign lesion. Materials and Methods: Data was collected by electronic search of databases including PubMed and Google Scholar for Mac- rophages, Periapical Granuloma, Mucocele, and Verruciform Xanthoma. Result: Distinct profiles of macrophages participate in regulation of pathogenesis, lesion size, and resolution of periapical lesions. In trauma-associated reactive or benign lesions, macrophages show phagocytosis and exhibit characteristic foamy his- tological appearance. The immunohistochemical profiles of macrophages aid in identifying the surface receptors and profiles of macrophages in oral lesions. Conclusion: Identifying and understanding macrophage-mediated pathogenesis can help diagnose and develop targeted therapies against various oral lesions.

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.

Detección y cuantificación de células plasmáticas (plasmocitos) en granulomas periapicales inducidos experimentalmente en ratas / Detection and quantification of plasma cells in experimentally induced rat periapical granulomas

Objetivo: En los granulomas periapicales, los plasmocitos (PL) participan activamente mediante la liberación de inmunoglobulinas. El propósito de este ensayo fue identificar y contar el número de PL en diferentes períodos de tiempo en lesiones periapicales experimentales en ratas. Materiales y métodos: Mediante la exposición al medio oral de la pulpa de los primeros molares inferiores izquierdos, se indujeron granulomas periapicales en ratas a las que previamente se les suministró anestesia. La pulpa de los primeros molares inferiores derechos no fue expuesta, y estos dientes se utilizaron como control. Los animales fueron eutanasiados a los 10, 30 y 60 días de la exposición. Los maxilares inferiores fueron removidos, y los primeros molares, junto con los tejidos circundantes, se procesaron para su estudio histológico. Se obtuvieron secciones semiseriadas, posteriormente coloreadas con verde de metilo-pironina (VMP). Cada tres secciones, las tres siguientes fueron coloreadas con hematoxilina y eosina (H-E). Los controles también fueron coloreados con H-E. Resultados: Todos los especímenes experimentales coloreados con H-E revelaron la presencia de granulomas periapicales. Luego de la exposición pulpar, el número de PL que reaccionó positivamente al VMP se incrementó de manera progresiva desde el día 10 hasta los días 30 y 60. A pesar de que a los 60 días el número de PL fue ligeramente menor que a los 30 días, no hubo diferencias estadísticamente significativas entre estos dos períodos. Los especímenes del grupo control coloreados con H-E mostraron que los tejidos periapicales se encontraban dentro de los parámetros normales en todos los períodos de observación. Conclusiones: Los resultados de este estudio revelaron que el número de plasmocitos VMP positivos se incrementa progresivamente en función del tiempo transcurrido pero se estabiliza al finalizar el experimento. También sugieren que el empleo de la coloración de VMP es un procedimiento adecuado para la identificación y la cuantificación de plasmocitos en los granulomas periapicales inducidos experimentalmente en ratas (AU)

Aim: Plasma cells (PL) release immunoglobulin in periapical lesions. The purpose of this assay was to identify and count the number of plasmocytes observed in periapical lesions in rats. Materials and methods: By exposing the pulp of the lower left first molars to the oral environment, periapical granulomas were induced in rats previously anesthetized. The pulp of right mandibular first molars was not exposed and these teeth were used as negative controls. The animals were euthanized at 10, 30 and 60 days after pup exposure. The mandibles were removed and specimens of the molar teeth along with the surrounding tissues were prepared for histology. Semi serial sections of the left first molar were stained with methyl green pyronine (MGP). Every three sections, the following three sections were stained with hematoxilyn and eosin (H-E). Negative control samples were stained with H-E. Results: All the H-E stained experimental samples revealed the presence of periapical granulomas. After pulp exposure, the number of PL increased from day 10 to 30 and 60. In the 60-day samples the number of PL was slightly less than that of the 30-day samples, with no statistically significant difference. The H-E stained control samples showed normal periapical tissues in all observation periods. Conclusions: The results of this study revealed that the number of VMP positive PL, increased progressively with time but it was stabilized at the end of the experiment. In addition, the results suggest that the use of VMP stain is a suitable procedure for the identification and counting of PL in experimentally induced periapical granulomas in rats (AU)

Chronic inflammatory periapical diseases: a Brazilian multicenter study of 10, 381 cases and literature review

Abstract The aim of this study was to investigate the epidemiological and clinical characteristics of chronic inflammatory periapical diseases in different regions of Brazil and to compare with data from the literature. A multicenter study was carried out in four Brazilian referral centers in oral diagnosis. Histopathological records were reviewed, and all cases diagnosed microscopically as periapical granuloma, radicular cyst, and periapical abscess were included. Demographic and clinical data were collected. Descriptive statistics and Pearson's chi-square test were performed. A total of 10,381 cases of chronic inflammatory periapical diseases were found (13.8% of 74,931 archived specimens) over a period of 65 years. Radicular cysts were the most common lesion (59.9%). Women (56.1%) with a mean age of 37.01 years old (range 13 to 100 ± 14.42) and people of white skin color (59.2%) were the most affected individuals by chronic inflammatory periapical diseases. The lesions were generally asymptomatic (28.1%), located in the maxilla (60.1%), and posterior region (49.8%). The radicular cysts were larger when compared to periapical granulomas (p < 0.001). The disagreement between the clinical and histopathological diagnoses was higher when the final diagnosis was a periapical granuloma (p < 0.001). Chronic inflammatory periapical diseases continue to be common lesions affecting mainly adults. This should be a consequence of the burden of untreated caries in permanent teeth. Women are more affected and radicular cyst was the most common lesion.

Metaloproteinases da matriz: papel no desenvolvimento das lesões periapicais e modulação após tratamento endodôntico / Matrix metalloproteinases: role in the development of apical periodontitis and modulation after endodontic treatment

Introduction: Apical periodontitis represents a local immune response directed against the progression of microorganisms from the dental pulp to the apical foramen and periapical tissues, which results in bone and dental resorption. The aim of this review is to describe the expression of this group of proteases in apical periodontitis and its modulation during the periapical healing phase following root canal treatment. Literature review: The pathogenesis of apical periodontitis involves degradation of several extracellular matrix components. Matrix metalloproteinases (MMPs) are expressed in response to specific stimuli by resident cells of connective tissue during tissue remodeling and by inflammatory cells that arrive into the surrounding tissues during inflammatory events. MMPs have been reported in apical periodontitis, either experimentally induced or obtained from humans and there is evidence that these enzymes show diff erent expression patterns in granulomas and periapical cysts. Root canal therapy is important for the reduction of periapical inflammation as well as the synthesis of MMPs, especially when using a calcium hydroxide-based dressing. Conclusion: Apical periodontitis show high expression of matrix metalloproteinases and root canal treatment results in less expression of MMPs when compared to untreated apical periodontitis.

Introdução: A lesão periapical representa a resposta imunoinflamatória devido ao aumento do número e progressão de micro-organismos advindos dos canais radiculares contaminados em direção aos tecidos apicais e periapicais, resultando em reabsorção óssea. O objetivo desta revisão será abordar a importância das metaloproteinases da matriz no desenvolvimento das lesões periapicais e sua modulação durante a fase de reparação tecidual depois de instituído o tratamento endodôntico. Revisão da literatura: A patogênese da lesão periapical envolve a degradação progressiva de diversos componentes da matriz extracelular. Dentre as proteases responsáveis pela degradação destes componentes estão as metaloproteinases da matriz (MMPs). Estas proteinases são expressas em resposta a estímulos específicos pelas células residentes do tecido conjuntivo durante o processo de remodelação tecidual e por células inflamatórias que invadem os tecidos durante eventos inflamatórios. As MMPs foram descritas em lesões periapicais experimentais e em humanos e existem evidências de que estas enzimas apresentam padrões de expressões diferentes em granulomas e cistos periapicais. A terapia endodôntica é importante para a redução da inflamação periapical assim como da síntese das MMPs, principalmente quando utilizado um curativo de demora à base de hidróxido de cálcio. Conclusão: As lesões periapicais apresentam alta expressão de metaloproteinases da matriz e o tratamento endodôntico em dentes com lesão periapical resulta em menor expressão de MMPs quando comparado às lesões periapicais não tratadas.

Cirurgia do periápice para remoção de lesões granulomatosas: relato de caso / Periapical surgery to remove granulomatous lesion

Periapical granuloma is a histological term that refers to the formation of a mass of granulomatous tissue around the apex of a tooth resulting from inflammation and necrosis of the pulp tissue. It consists of an infiltrate of inflammatory cells such as macrophages, plasmocytes and lymphocytes, as well as fibroblasts, collagen fibers and capillaries. Periapical surgery is an alternative for preserving the tooth in the oral cavity in cases where periapical inflammation is persistent even after treatment of root canals. The objective of this study was to report a clinical case in which the surgical technique was used to remove granulomatous lesions from a patient, female, with a history of recurrent periapical abscess without painful symptomatology in the region of the anterior 11,12 and 13 teeth. The histopathological exam demonstrated the presence of a granulomatous tissue with intense inflammatory infiltrate mixed, permeated with lymphocytes and high number of plasmocytes, confirming the diagnosis of periapical granuloma. The treatment was considered successful since the patient remained asymptomatic and there was incorporation of the inorganic bovine bone graft and initiation of bone neoformation in the periapical region.

Granuloma periapical é um termo histológico que refere-se à formação de uma massa de tecido granulomatoso ao redor do ápice de um dente, decorrente da inflamação e necrose do tecido pulpar. É constituído por um infiltrado de células inflamatórias como macrófagos, plasmócitos e linfócitos, além de fibroblastos, fibras colágenas e capilares. A cirurgia do periápice é uma alternativa para preservação do dente na cavidade bucal nos casos em que a inflamação periapical é persistente mesmo após tratamento dos canais radiculares. O objetivo desse trabalho é relatar um caso clínico no qual a técnica cirúrgica do periápice foi utilizada para remoção de lesões granulomatosas de uma paciente, do sexo feminino, com histórico de abscesso periapical recidivante sem sintomatologia dolorosa na região dos dentes anteriores superiores 11, 12 e 13. O exame histopatológico demonstrou a presença de um tecido granulomatoso com intenso infiltrado inflamatório misto, permeado com linfócitos e elevado número de plasmócitos, confirmando o diagnóstico de granuloma periapical. O tratamento foi considerado exitoso, visto que a paciente se manteve asintomática e houve incorporação do enxerto ósseo bovino inorgânico e início da neoformação óssea na região periapical.

Periapicopatias inflamatórias de origem endodôntica: estudo multicêntrico na população brasileira / Endodontic periapical lesions: A multicenter study in the Brazilian population

Introdução: as periapicopatias inflamatórias de origem endodôntica são as doenças mais frequentes dos ossos maxilares e ocorrem principalmente como consequência da disseminação da infecção endodôntica. Apesar de vários estudos, não existem dados recentes sobre as características epidemiológicas e clínicas dessas lesões envolvendo uma amostra tão grande da população. Objetivo: Investigar as características epidemiológicas e clínicas das periapicopatias inflamatórias de origem endodôntica, incluindo o granuloma periapical, o cisto radicular e o abscesso periapical. Metodologia: foi realizado um estudo retrospectivo e multicêntrico em quatro instituições com centros de referência em diagnóstico oral no Brasil. Todos os registros histopatológicos foram revisados e foram incluídos todos os casos diagnosticados microscopicamente como granuloma periapical, cisto radicular e abscesso periapical. Foram coletados os seguintes dados demográficos e clínicos: sexo, idade e cor da pele dos pacientes, sintomas, duração, tamanho e localização das lesões e concordância entre o diagnóstico clínico e histopatológico. Análises estatísticas descritivas e bivariadas, utilizando o teste Qui-quadrado de Pearson, foram realizadas. Em casos de variáveis com mais de duas categorias, utilizou-se o teste Z para comparação das proporções de colunas e a correção de Bonferroni. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: foram encontrados 10.381 casos de lesões periapicais entre 74.931 espécimes arquivados (13,8%) em 65 anos. Os cistos radiculares foram as lesões mais comuns (59,9%). As lesões periapicais acometeram principalmente mulheres (56,1%), com média de idade de 37,01 anos (13 a 100 ± 14,42 anos) e cor de pele branca (59,2%). As lesões eram geralmente assintomáticas (28,1%), persistindo por mais de um ano (13,3%), com tamanho de até 10 mm (25,2%) e localizadas na maxila (60,1%) e região posterior (49,8%). Os cistos radiculares foram maiores (p < 0,001), com maior ocorrência de sintomatologia (p < 0,027) e maior frequência na região posterior (p < 0,001) em relação aos granulomas periapicais. A possibilidade de discordância entre o diagnóstico clínico e histopatológico foi maior nos granulomas periapicais (p < 0,001). Conclusões: as periapicopatias inflamatórias de origem endodôntica foram comuns em serviços de Patologia Bucomaxilofacial, acometendo principalmente adultos. Isso deve ser uma consequência da carga de cáries não tratadas em dentes permanentes. As mulheres são mais afetadas e o cisto radicular é a lesão mais comum.

Introduction: Inflammatory periapical lesions are the most frequent diseases of maxillary bones and occur mainly as a consequence of the dissemination of endodontic infection. Despite several studies, there are no recent data on the epidemiological and clinical characteristics of these lesions involving such a large sample. Objective: To investigate the epidemiological and clinical characteristics of periapical lesions, including periapical granuloma, radicular cyst and periapical abscess. Methodology: A multicenter retrospective study was realized in four institutional reference centers in oral diagnosis in Brazil. Histopathological records were reviewed and included all cases diagnosed microscopically as periapical granuloma, radicular cyst and periapical abscess. Data on patient sex, age, skin color, symptoms, lesion duration, lesion size, lesion location and concordance between clinical and histopathological diagnosis were collected. Descriptive statistics and bivariate analyses using Pearson's Chi-square test were done. A z-test, to compare the column proportions, and Bonferroni correction were used, in the case of variables with more than two categories. P values < 0.05 were considered statistically significant. Results: Were found 10,381 cases of periapical lesions among 74,931 archived specimens (13.8%) in 65 years. Radicular cysts were the most common lesions (59.9%). Periapical lesions affected mainly women (56.1%), with a mean age of 37,01 years (range 13 to 100 ± 14,42) and white-skinned (59.2%). The lesions were generally asymptomatic (28.1%), persisting for more than one year (13.3%), size up to 10 mm (25.2%) and located in the maxilla (60.1%) and posterior region (49.8%). The radicular cysts were larger (p < 0.001), with a higher occurrence of symptomatology (p < 0.027) and higher frequency in the posterior region (p < 0.001) compared to periapical granulomas. The possibility of disagreement between clinical and histopathological diagnosis was higher in periapical granulomas (p < 0.001) than radicular cyst. Conclusions: Endodontic periapical lesions were common in the Bucomaxillofacial Pathology services affecting mainly adults. This should be a consequence of the burden of untreated caries in permanent teeth. Women are more affected and radicular cyst is the most common lesion.

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.

Residual cyst with semisolid content, a clinical case / Quiste residual con contenido semisólido, a propósito de un caso clínico

Abstract Objective: To present a clinical case of a residual cyst in the right maxillary region with semi-solid content. Main data of the case: 61-year-old patient who comes to consultation for the realization of upper jaw dentures, during the clinical examination a slight facial asymmetry of the right side is observed; radiographic and tomographic examination revealed a radiolucent lesion in the right premolar region. It is diagnosed as a residual cyst and an enucleation is decided; during the surgical procedure a viscous content of yellowish coloration and semi-solid content is observed. Main comments: It is very rare to find residual cysts with semi-solid content, since they generally have purulent or serosanguinous contents.

Resumen Objetivo: Presentar un caso clínico de un quiste residual en la región maxilar derecha, con contenido semisólido. Datos principales del caso: Paciente de 61 años, que acude a consulta para la realización de una prótesis en el maxilar superior, al examen clínico se observa leve asimetría facial del lado derecho; al examen radiográfico y tomográfico se observa lesión radiolúcida en región premolar derecha. Se diagnostica como quiste residual y se decide enucleación, en el procedimiento quirúrgico se observa un contenido viscoso de coloración amarillenta y contenido semisólido. Principales comentarios: Es muy poco común encontrar quistes residuales con contenido semisólido, generalmente son de contenido purulento o serosanguinoso.

Apical Surgery: Therapeutic Option for Endodontic Failure / Cirurgia Parendodôntica: Opção Terapêutica para o Insucesso Endodôntico

The aim of this study is present a surgical solution of the case of endodontic root canal failure caused by overfilling, with a history of endodontic retreatment and aesthetic rehabilitation with porcelain veneers. Patient C.F.P.L, 50 years old, female, was looking for treatment complaining of pain. Previous endodontic treatment was reported on tooth 11, and root canal retreatment after 6 months due to the persistence of painful symptomatology. Later, the patient carried out aesthetic rehabilitation with porcelain veneers, and approximately 6 months later the vitro pain related to the tooth 11 occurred again. Radiographic and tomographic images showed obturation of the root canal of the tooth 11 associated with diffuse hypodense area in the periapical region, with overextended endodontic material. The probable clinical diagnosis was symptomatic traumatic apical periodontitis, and apical surgery was proposed as treatment plan. After infiltrative anesthesia, a Newmann incision and split flap were performed, followed by osteotomy with micro-chisel and curettage of the lesion. An apicectomy was performed with Zecrya drill, followed by retro cavity with diamond ultrasonic tip and retrograde obturation with white MTA. After 2 years of follow-up bone neoformation and absence of symptomatology were observed, tooth in function and preservation of aesthetic rehabilitation harmony. Apical surgery is a therapeutic alternative with favorable prognosis for the treatment of endodontic failure, provided that it is correctly indicated and with a wellexecuted surgical protocol. (AU).

O objetivo deste estudo é apresentar a resolução cirúrgica de um caso de insucesso endodôntico ocasionado pela sobre obturação do canal radicular, com histórico de retratamento endodôntico e reabilitação estética com facetas cerâmicas. Paciente C.F.P.L, 50 anos, gênero feminino, procurou atendimento odontológico queixando-se de dor. Foi relatado tratamento endodôntico prévio no dente 11, e retratamento do canal radicular após 6 meses devido à persistência de sintomatologia dolorosa. Posteriormente, a paciente passou por reabilitação estética com facetas cerâmicas e, aproximadamente 6 meses após, houve o reaparecimento de dor espontânea relacionada ao dente 11. As imagens radiográficas e tomográficas revelaram obturação do canal radicular do dente 11 associado à área hipodensa difusa na região periapical, com extravasamento de material obturador. O diagnóstico clínico provável foi de periodontite apical sintomática traumática, e plano de tratamento proposto uma cirurgia parendodôntica. Posterior a anestesia infiltrativa, realizou-se incisão do tipo Newmann e retalho dividido, seguido de osteotomia com micro cinzel e curetagen da lesão. A apicectomia foi realizada com broca Zecrya, seguida da confecção da retrocavidade com ponta ultrassônica diamantada e obturação retrógrada com MTA branco. Após 2 anos de proservação foi observada neoformação óssea e ausência de sintomatologia, dente em função e preservação da harmonia da reabilitação estética. A cirurgia parendodôntica é uma alternativa terapêutica com prognóstico favorável para o tratamento do insucesso endodôntico, desde que corretamente indicada e com protocolo cirúrgico bem executado. (AU).

Aspectos radiográficos de imágenes periapicales asociadas a incisivos primarios traumatizados / Aspectos radiográficos de imagens periapicais associadas a incisivos decíduos traumatizados / Radiographic aspects of periapical images associated with traumatized primary incisors

Las imágenes radiolúcidas periapicales que involucran dientes primarios traumatizados se pueden confundir entre sí y dar lugar a diagnósticos erróneos y tratamiento. Por lo tanto, es importante identi-ficar las características radiográficas de las imágenes radiolúcidas periapicales en los incisivos prima-rios traumatizados, principalmente debido al hecho de que la superposición de imágenes se produce en esta región. Además, es frecuente observar la expansión del folículo haciendo que el diagnóstico radiográfico sea aún más difícil. El objetivo de este estudio fue describir, a través de una revisión de la literatura, las características radiográficas de las imágenes periapicales asociadas con los incisivos primarios traumatizados.

Periapical radiolucencies involving traumatized primary teeth can be confused with each other and lead to misdiagnosis and treatment. Therefore, it is important to identify radiographic characteristics of periapical radiolucent images in traumatized primary incisors, mainly due to the fact that overla-pping of images occurs in this region. Besides, it is frequent to observe follicle expansion making the radiographic diagnosis even more difficult. The objective of this study was to describe, through a literature review, the radiographic characteristics of periapical images associated with traumatized primary incisors.

As radioluscências periapicais envolvendo dentes decíduos traumatizados podem ser confundidas entre si e levar a um erro de diagnóstico e tratamento. Por isso, é importante identificar características radiográficas de imagens radiolúcidas periapicais em incisivos decíduos traumatizados, principalmente pelo fato que nesta região ocorre sobreposição de imagens e, é frequente observar expansão do folículo, dificultando ainda mais o diagnóstico radiográfico. O objetivo deste trabalho foi descrever através de uma revisão de literatura as características radiográficas de imagens periapicais associadas a incisivos decíduos traumatizados.

Pro-inflammatory and anti-inflammatory cytokine expression in post-treatment apical periodontitis

Abstract Objective: This study evaluated the expression of pro-inflammatory (IL-1β, IL-6, IFN-γ and TNF-α) and anti-inflammatory (IL-4 and TGF-β) cytokines in apical periodontitis lesions. Correlations between these cytokines and clinical and cone-beam computed tomographic (CBCT) data were also assessed. Material and Methods: Apical periodontitis lesions' data were obtained from 27 patients subjected to periradicular surgery. Specimens were processed for histopathologic and immunohistochemical analysis. Sections were evaluated according to the amount of positive staining for each antibody. Expression levels of the target mediators were compared with clinical and CBCT data. Results: Twenty lesions were diagnosed as granuloma and 7 as cyst. In granulomas, IL-4 expression was significantly higher than IL-6 (p=0.001) and TNF-α (p=0.001). There was a significant relationship between high levels of TNF-α and lesions <5 mm (p=0.017). In cysts, IL-6 expression was significant lower than IL-4 (p=0.001) and IFN-γ (p=0.004). There was a significant relationship between high levels of TGF-β and endodontic treatment performed ≤4 years before (p=0.045). In general, IL-4 was the most expressed mediator in both cysts and granulomas. Conclusions: There was a balance between the expression of pro-inflammatory and anti-inflammatory cytokines associated with the chronic periradicular inflammatory process. TNF-α and TGF-β were related to some clinical and CBCT data.

Correlación en el diagnóstico clínico, radiográfico e histológico de lesiones apicales dentales / Correlation of clinical, radiographic and histological diagnoses of apical dental lesions

Objetivo: Establecer la correlación entre las características clínicas, radiográficas e histológicas de lesiones apicales dentales al momento de su diagnóstico. Material y métodos: Estudio descriptivo en el que se realizó la comparación de las características clínico-radiográficas con el estudio histopatológico de las lesiones. Se incluyeron muestras de individuos que fueron diagnosticados con procesos de patología periapical, obtenidas a través de apicectomías y extracciones dentales. Los cortes fueron procesados rutinariamente y evaluados por patólogo para su diagnóstico histológico. Resultados: El 50% de las muestras fue diagnosticado como periodontitis apical, seguido por quistes periapicales (28.5%). Al correlacionar entre sí características clínicas como sensibilidad a la percusión y dolor espontáneo hubo asociación (p = 0.01). Igualmente, al relacionar la pérdida ósea vertical con movilidad dental (p = 0.023) y ésta con el órgano dentario afectado (p = 0.036). Sin embargo, no mostró asociación, la correlación entre el estado sintomático del paciente como dolor espontáneo y el tipo de infiltrado inflamatorio predominante en las lesiones (p = 1.4); pero sí la hubo, con el tipo de infiltrado secundario que existía en ellas (p = 0.057). La movilidad dental se mostró como un marcador diagnóstico para granuloma y quiste periapical (p = 0.025). Conclusiones: Se hallaron ciertos marcadores clínicos capaces de predecir la presentación histológica de las lesiones, como la movilidad dental para granuloma y quiste periapical. Sin embargo, la predicción exacta de cada una de las patologías aún se hace difícil, debido a la misma dinámica de las lesiones y a la poca correlación que existe entre las características clínico-radiográficas con la descripción histológica de las lesiones.

Objective: To establish a correlation amongst clinical, radiographic and histological characteristics of dental apical lesions at the time of diagnosis. Material and methods: A descriptive study which undertook to establish comparison of clinical and radiographic characteristics with histopathological study of lesions. Included in the study were samples of individuals which had been previously diagnosed with periapical disease processes; samples were harvested from apicoectomies and dental extractions. In order to achieve histological diagnosis, a pathologist routinely processed and assessed all specimens. Results: 50% of all samples were diagnosed as apical periodontitis, followed by periapical cysts (28.5%). An association of (p = 0.01) was found when correlating clinical characteristics such as sensitivity to percussion and spontaneous pain. The same situation arose when relating vertical bone loss to dental mobility (p = 0.023), and dental mobility with affected tooth (p = 0.036), nevertheless, no association was found with correlation of patient's symptomatic status, such as spontaneous pain, and type of predominant inflammatory infiltrate in the lesions (p = 1.4), nevertheless, association was found with the secondary infiltrate type existing in them (p = 0.057). Dental mobility was taken as diagnostic marker for granuloma and periapical cyst (p = 0.025). Conclusions: Certain clinical markers were found with the ability to predict histological manifestation of the lesions, such as dental mobility for granuloma and periapical cyst cases. Nevertheless, exact prediction of each one of the diseases is still dificult to obtain, this is due to the lesion's dynamics and the scarce correlation existing among clinical and radiographic characteristics with the histological description of the lesions.

Immunohistochemical expression of TGF-ß1 and MMP-9 in periapical lesions

Abstract The objective of this study was to evaluate the expression of matrix metalloproteinase 9 (MMP-9) and transforming growth factor beta (TGF-β1) in periapical lesion samples correlated with the intensity of the inflammatory infiltrate and thickness of the epithelial lining. Forty-five cases of periapical lesions (23 periapical granulomas and 22 radicular cysts) were subjected to morphological and immunohistochemical analyses using anti-MMP-9 and anti-TGF-β1 antibodies. The data were analyzed using the following tests: non-parametric Mann-Whitney, chi-square, Fisher's exact test and Spearman's correlation test (P<0.05). Analysis of inflammatory infiltrate revealed that 78% of periapical granulomas presented infiltrate grade III, in contrast with 32% of radicular cysts (P<0.001). Morphological evaluation of the epithelial thickness in radicular cysts revealed the presence of atrophic epithelium in 86% of the cysts. The immunostaining of MMP-9 was score 2 in 67% of the granulomas and 77% of the cysts. Both lesions were predominantly score 1 for TGF-β1. Significant differences were confirmed between the expression scores of TGF-β1 and MMP-9 in periapical granulomas (p = 0.004) and in radicular cysts (p < 0.001). Expression of TGF-β1 was different for periapical granulomas and radicular cysts. This immunoregulatory cytokine seems more representative in asymptomatic lesions. The extracellular matrix remodeling process dependent on MMP-9 seems to be similar for both periapical granulomas and radicular cysts. TGF-β1 and MMP-9 may play an important role in the maintenance of periapical lesions.

Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts

Abstract: The aim of this study was to compare the number of CD57+ natural killer (NK) cells and CD8+ T lymphocytes between periapical granulomas (PGs) and radicular cysts (RCs). Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification) and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8+ T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57+ NK cells and CD8+ T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively). Comparison of the number of CD57+ NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042). A larger number of CD57+ NK cells and CD8+ T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively). CD8+ T lymphocytes were more prevalent than CD57+ NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001). CD57+ NK cells and CD8+ T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8+ T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.

Analysis of the presence and location of mast cells in periapical cysts and periapical granulomas / Análise da presença e localização de mastócitos nos cistos periapicais e granulomas periapicais

ABSTRACT Objective: The aim of the present study was to locate mast cells in chronic periapical lesions (granulomas and cysts) by using histochemical techniques and toluidine blue staining. Methods: A quantitative, descriptive, cross-sectional and retrospective research was performed. The sample was obtained from histopathological reports in the archives of the laboratory of surgical pathology of the University of Pernambuco between November 2014 and May 2015. Results: Sixteen cases of granuloma and 21 cases of periapical cysts were selected. The stained slides were analyzed by two examiners at different times, in a double-blind study. Mast cells were found in 13 (61.9%) of the periapical cyst cases, located in the capsule of the lesion. In the periapical granuloma cases, mast cells were found in eight cases (50%), located in the granulation tissue. Conclusion: Mast cells were detected in both cysts and periapical granuloma, located in the capsule and granulation tissue, respectively. Mast cells were more prevalent in periapical cysts than in periapical granuloma.

RESUMO Objetivo: Localizar mastócitos em lesões periapicais (granulomas e cistos) através de técnicas histoquímicas e corante azul de toluidina. Métodos: Uma pesquisa quantitativa, descritiva, transversal e retrospectiva foi realizada. As amostras foram obtidas de documentos histopatológicos nos arquivos do laboratório de patologia cirúrgica da Universidade de Pernambuco entre Novembro de 2014 e Março de 2015. Resultados: Dezesseis casos de granuloma e 21 casos de cistos periapicales foram selecionados. As lâminas coradas foram analisadas por dois examinadores em tempos diferentes, em um estudo duplo-cego. Mastócitos foram encontrados em 13 (61,9%) dos casos de cistos periapicales, localizados na cápsula da lesão. Nos granulomas periapicais, mastócitos foram encontrados em oito casos (50%), localizados no tecido de granulação. Conclusão: Mastócitos foram detectados tanto em cistos quanto em granulomas periapicais, localizados na cápsula e no tecido de granulação respectivamente. Os mastócitos estavam mais presentes nos cistos do que nos granulomas periapicais.

Apicoectomy and retrograde filling as periapical granuloma treatment: a case report / Apicectomía y obturación retrógrada como tratamiento de un granuloma periapical: informe de caso

ABSTRACT Periapical granulomas are chronic inflammatory processes appearing as a lesion around the apex of the tooth, which increase in size due to a proliferation of granulomatous tissue formed by lymphocytes, plasmocytes, some polymorphonuclears, macrophages, eosinophils, multinucleated giant cells, fibroblasts, and neoformation of capillaries. Etiologically, they occur due to deep caries affecting the pulp, infected root canals or endodontic failures. The objective of the present article is to report the finding of a periapical granuloma in a previously treated tooth, by means of excisional biopsy, curettage, and apical surgery with retrograde filling using mineral trioxide aggregate (MTA) as filling material on tooth # 11 in a 65-year old male patient, with subsequent histopathological study of the lesion. The clinical and radiographic follow-up showed the effectiveness of MTA as a retrograde filling material and apicoectomy as surgical procedure for the treatment of periapical granuloma.

RESUMEN. Los granulomas periapicales son procesos inflamatorios crónicos que se presentan como una lesión rodeando el ápice del diente, la cual aumenta de tamaño debido a una proliferación de tejido granulomatoso conformado por linfocitos, plasmocitos, algunos polimorfonucleares, macrófagos, eosinófilos, células gigantes multinucleadas, fibroblastos y capilares de neoformación. Etiológicamente, su aparición obedece a caries profundas que afectan la pulpa, conductos radiculares infectados o fracasos endodónticos. El objetivo del presente artículo es informar el hallazgo de un granuloma periapical en un diente previamente tratado. Se realizó biopsia excisional, curetaje y cirugía apical con obturación retrógrada usando compuesto de minerales trióxido (MTA) como material de obturación a nivel del órgano dentario 11 en un paciente masculino de 65 años de edad, con posterior estudio histopatológico de la lesión. El seguimiento clínico y radiográfico demostró la efectividad del uso de MTA como material de obturación retrógrada y la apicectomía como procedimiento quirúrgico para el tratamiento del granuloma periapical.

MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements

ABSTRACT Increased matrix metalloproteinases (MMPs) activity is a hallmark of periapical granulomas. However, the factors underlying the MMPs expression modulation in healthy and diseased periapical tissues remains to be determined. Objective In this study, we evaluated the association between the MMP1-1607 polymorphism (rs1799750) and pro-inflammatory milieu elements with MMP-1 mRNA levels in vivo. Material and Methods MMP1-1607 SNP and the mRNA levels of MMP-1, TNF-a, IFN-g, IL-17A, IL-21, IL-10, IL-4, IL-9, and FOXp3 were determined via RealTimePCR in DNA/RNA samples from patients presenting periapical granulomas (N=111, for both genotyping and expression analysis) and control subjects (N=214 for genotyping and N=26 for expression analysis). The Shapiro-Wilk, Fisher, Pearson, Chi-square ordinal least squares regression tests were used for data analysis (p<0.05 was considered statistically significant). Results The MMP1-1607 1G/2G and 1G/2G+2G/2G genotypes were significantly more prevalent in the patients than in controls, comprising a risk factor for periapical lesions development. MMP-1 mRNA levels were higher in periapical lesions than in healthy periodontal ligament samples, as well as higher in active than in inactive lesions. The polymorphic allele 2G carriers presented a significantly higher MMP-1 mRNA expression when compared with the 1G/1G genotype group. The ordered logistic regression demonstrated a significant correlation between the genetic polymorphism and the expression levels of MMP-1. Additionally, the pro- and anti-inflammatory cytokines IL-17A, IFN-g, TNF-a, IL-21, IL-10, IL-9, and IL-4 were significant as complementary explanatory variables of MMP-1 expression. Conclusion The MMP1-1607 SNP was identified as a risk factor for periapical lesions development, possibly due to its association with increased MMP-1 mRNA levels in periapical lesions. The MMP-1 expression is also under the control of the inflammatory milieu elements, being the cytokines TNF-a, IL-21, IL-17A, and IFN-g associated with increased MMP-1 levels in periapical lesions, while IL-10, IL-9, or IL-4 presented an inverse association.

Correlação clínica e histopatológica de cistos e granulomas periapicais / A Clinical and Histopathological Correlation of Periapical Cysts and Granulomas

Cistos e granulomas periapicais estão entre as lesões radiolúcidas mais prevalentes. Porém, há situações em que os padrões clínicos e radiográficos se misturam e, portanto, o estudo histopatológico faz-se necessário para o diagnóstico definitivo. O objetivo deste estudo foi avaliar a correlação clínica e histopatológica no diagnóstico de cistos e granulomas periapicais. Para isso, foram selecionadas amostras obtidas no Laboratório de Patologia Cirúrgica da Faculdade de Odontologia de Pernambuco, FOP/UPE, no período de 11/2005 a 05/2008. Um total de 37 lesões, distribuídas entre cistos e granulomas periapicais, foram incluídas no estudo. Baseadas nos aspectos clínico-radiográfico e transoperatório, cirurgiões-dentistas forneceram hipóteses diagnósticas, as quais foram comparadas aos exames histopatológicos. Achados clínicos revelaram 28 casos (75,7%) de cistos, 4 casos (10,8%) de granulomas, 4 casos (10,8%) com características de ambas lesões, e 1 caso (2,7%) no qual o dentista não forneceu o diagnóstico. Entretanto, os achados histopatológicos revelaram 21 (56,8%) e 16 (43,2%) casos de cistos e granulomas, respectivamente. Os resultados mostraram uma correlação de 45,9% entre os achados para os cistos e de 8,1% para os granulomas. Diante do exposto, a discrepância observada dos achados clínicos quando comparados aos histopatológicos deve ser discutida quanto aos critérios diagnósticos que vêm sendo utilizados atualmente... (AU)

Cysts and periapical granulomas are among the most prevalent radiolucent lesions. However, there are situations where the clinical and radiographic patterns are mixed and therefore the histopathological study is necessary for definitive diagnosis. The aim of this study was to evaluate the clinical and histopathological correlation in the diagnosis of periapical cysts and granulomas. For this, samples were selected obtained from histopathological reports of Pathology Laboratory, Faculty of Dentistry of Pernambuco, FOP / UPE, during the period from 11/2005 to 05/2008. A total of 37 lesions distributed among periapical cysts and granulomas, were included in the study. Based on clinical, radiographic and intraoperative lesions, dentists provided diagnostic hypotheses, which were compared to histopathological diagnostic. Clinical findings revealed 28 cases (75.7%) of radicular cysts, 4 cases (10.8%) of granulomas alone, 4 cases (10.8%) with characteristics of both lesions, and 1 case (2.7 %) in which the dentist has not provided the diagnosis. However, the histopathological findings revealed 21 (56.8%) and 16 (43.2%) cysts and granulomas images, respectively. The results showed a 45.9% correlation between the findings for periapical cysts and 8.1% for periapical granulomas. Given the above, the discrepancy observed clinical findings compared to histopathology should be discussed as to the diagnostic criteria that have been used nowadays... (AU)

Analysis of Interleukin 17A in periapical abscess and granuloma lesions

Abstract Interleukin 17A (IL-17A) is a proinflammatory cytokine responsible for the initiation and propagation of inflammation. One of its actions is the recruitment of neutrophils to the site of infection. The aim of this study was to investigate whether there is association between IL-17A expression and neutrophil infiltration in periapical abscesses and periapical granulomas, as well as to find which type of T lymphocyte effector (CD4+ or CD8+) expresses IL-17A in these lesions. Elastase, CD4, CD8, and IL-17A were analyzed by immunohistochemistry and immunofluorescence, in the biopsies of periapical lesions. Abscess lesions exhibited the highest labeling area for IL-17A (p = 0.011). During double immunofluorescence staining, there were significantly more CD4+/IL-17A+ cells compared to CD8+/IL-17A+ cells, both in the abscesses (p = 0.025) and granulomas (p = 0.011). In conclusion, IL-17A was intensively expressed in periapical abscesses rich in neutrophils. The high percentage of IL-17A in these cases suggests the participation of this cytokine particularly in the acute stages of the inflammatory process of the periapical lesions.