Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues.

The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.

Epithelioid cell granuloma with caseating necrosis possibly caused by periapical periodontitis: a case report.

BACKGROUND: Epithelioid cell granuloma with caseating necrosis is a typical pathological finding in tuberculosis. While specific inflammation, including that related to tuberculosis, can induce caseating granuloma formation, there have been very few reports on the induction of caseating granuloma by non-specific inflammation. Chronic periapical periodontitis is usually related to bacterial biofilm formation as well as fungal or viral infection in the periapical lesion. However, it is difficult to eliminate these extraradicular pathogenic microbes by normal endodontic therapy alone, and more invasive surgical removal is almost always required. CASE PRESENTATION: Here we describe the case of a 30-year-old Japanese woman who had suffered from dull pain related to periapical periodontitis for approximately 10 years. Although the causal tooth had been previously extracted at the Department of Oral Surgery of another hospital in 2015, inflammation of the surrounding tissue had not abated. She was referred to our hospital in May 2016 and underwent surgical debridement via an intra/extraoral approach under general anesthesia. A caseating granuloma accompanied by a small amount of fungi was histopathologically confirmed in the excised specimen. Her inflammation has not been exacerbated since the operation. CONCLUSIONS: This is the first report in which non-specific inflammation is shown to induce caseating granuloma arising in the jaw. Our report also highlights the importance of sufficient root canal treatment during the first stage of the procedure.

Traumatic ulcerative granuloma with stromal eosinophilia around mini dental implants without the protection of a denture base.

This is a report of a case of an unusual oral lesion after the placement of mini implants for the retention of a mandibular overdenture. A patient received four 2-mm-wide dental implants in the anterior mandible and had her mandibular denture relined with a soft material. After 3 months, she was not wearing her mandibular denture, and two nodular ulcerated lesions were observed near the mini implants. The lesions ceased following excision and regular denture wearing. Clinical and microscopic examination led to the diagnosis of traumatic ulcerative granuloma with stromal eosinophilia (TUGSE). TUGSE is rare lesion with a benign course that may occur following injury of the oral mucosa by mini implants under certain circumstances.

Role of matrix metalloproteinases in radicular cysts and periapical granulomas.

AIM: The aim of the present study was to evaluate the expression and distribution of different classes of matrix metalloproteinases (MMPs) in radicular cysts and periapical granulomas. METHODS: Twenty consecutive specimens of radicular cysts and 20 of periapical granulomas were selected. Expression of MMP-2, -9, -8, -13, -3 was immunohistochemically evaluated. The intensity of expression of the MMPs was evaluated using a semi-quantitative analysis: low = +; intermediate = ++; high = +++. RESULTS: Positive expression of MMPs was present with different distribution. MMP-9 expressed differently in the lesions. Indeed, in periapical granulomas low expression was found in endothelial cells and fibroblasts, whilst high intensities were only detected in inflammatory cells. On the contrary, in radicular cysts the high intensities were mainly present in keratinocytes and fibroblasts. MMP-8 was mainly expressed in inflammatory cells of periapical granulomas. MMP-2 and -3 presented a low intensity of expression in both groups. MMP-13 showed a variable pattern of distribution in the different cell types of the two different lesions. CONCLUSION: The present investigation supports the role of MMPs in the inflammatory process leading to the development of radicular cysts and periapical granulomas. The results of the present study suggested that the increased enlargement of radicular cysts, compared to periapical granulomas, might be related to a higher expression of MMP-9. On the other hands, the higher intensity of expression of MMP-8 in periapical granulomas could be related to an active inflammatory process. MMP-8 could play an important role in the inflammation processes during the development of periapical lesions.

Periapical granuloma associated with extracted teeth.

OBJECTIVE: This article aims to determine the incidence of periapical granuloma from extracted teeth and correlate the clinical diagnoses with the histopathological types of periapical granuloma. PATIENTS AND METHODS: Over a period of eight months, a prospective study designed as a routine biopsy of recoverable periapical tissues obtained from patients who had single tooth extraction was carried out. RESULTS: One hundred and thirty-six patients participated in the study, with 75 (55.1%) histopathologically diagnosed periradicular lesions. There were 23 (16.9%) cases of periapical granuloma, with a male to female ratio of 2: 1. The lesion presented mostly between the third and fourth decades of life (n=9, 6.6%). Clinically diagnosed acute apical periodontitis was significantly associated with periapical granuloma, with predominantly foamy macrophages and lymphocytes (P<0.05). CONCLUSION: Periapical granuloma appears to be a less common periapical lesion in this study compared to the previous reports. In contrast to reports that relate to an acute flare of the lesion with abundant neutrophilic infiltration, this study has shown marked foamy macrophages and lymphocytes at the acute phase, which are significantly associated with the clinical diagnosis of acute apical periodontitis. We recommend the classification of periapical granuloma into early, intermediate, and late stages of the lesion, based on the associated inflammatory cells.

[Histopathology and etiopathogenesis of chronic apical periodontitis--periapical granuloma]. / Histopatológia a etiopatogenéza chronickej apikálnej parodontitídy--periapikálnych granulómov.

Periapical lesions are among the most frequently diagnosed apical odontogenic pathologies in human teeth. The condition is generally described as apical periodontitis. Apical periodontitis is a sequel to endodontic infection and manifests itself as the host defense response to microbial challenge emanating from the root canal system to the periapical tissue. It is viewed as a dynamic encounter between microbial factors and host defenses at the interface between infected radicular pulp and periodontal ligament that results in local inflammation, resorption of hard tissues, destruction of other periapical tissues, and eventual formation of various histopathological categories of apical periodontitis, commonly referred to as periapical lesions. There are also factors located within the inflamed periapical tissue that can interfere with post-treatment healing of the lesion. The purpose of this article is to provide a comprehensive overview of the etiopathogenesis of apical periodontitis and causes of failed endodontic treatment. This study presents a histopathological analysis through optical microscopy of periapical lesions, commonly referred to as solid dental or periapical granuloma.

Pulse or hyaline ring granuloma. Review of the literature on etiopathogenesis of oral and extraoral lesions.

Since the late 1950s, reports on an unusual giant-cell granulomatous lesion affecting the jaws, lungs, stomach and intestines have been published. Histopathologically, the lesions showed the presence of structureless hyaline rings with multinucleated giant cells. The aim of this review was to summarize the literature on the etiopathogenesis of the so-called oral and extraoral pulse or hyaline ring granuloma. Literature was searched using PubMed and Medline. In addition, hand search was performed. Search words were oral and extraoral hyaline ring granuloma, giant-cell hyaline angiopathy, pulse granuloma and chronic periostitis. Numerous terms for hyaline ring granuloma have been introduced over time (1971-2008). One hundred seventy-three cases of oral hyaline ring granuloma have been retrieved from the literature. In the mandible, 72.3% occurred . Two theories for etiopathogenesis have been proposed: (1) the origin of the hyaline rings is due to a foreign material (pulse and legumes) having penetrated the oral mucosa or gastrointestinal tract and lungs (exogenous theory) and (2) the rings are due to hyaline degenerative changes in walls of blood vessels (endogenous theory). Experimental production of oral and extraoral hyaline ring granulomas is consistent with the exogenous origin. Particles or remains of leguminous cells having been implanted or aspirated into human tissues whether located to the oral cavity or throughout the entire digestive tract and respiratory system are thought to be causative. Pulse or hyaline ring granulomas are rare but are well-defined oral and extraoral lesions due to implantation of the cellulose moiety of plant foods in contrast to the starch components.

Tongue granulomatous lesion caused by mandibular primary incisors eruption.

The aim of this report was to present a case of granulomatous lesion on the ventral surface of the tongue in a 9-month-old, healthy, infant girl, caused by the habit of scraping the tongue on mandibular central incisors. Clinical treatment consisted of manual smoothing of the sharp edges of both incisors and excision of the 2-cm pediculate ulcerative granulomatous mass localized on the ventral surface of the tongue. After 3 weeks, the child could be properly fed and a complete healing of the lesion was observed.

Problems with dental implants that were placed on vertically distracted fibular free flaps after resection: a report of six cases.

We report the clinical outcome of dental implants placed on vertically distracted fibular free flaps that were used to reconstruct maxillary and mandibular defects after resection. Distraction osteogenesis (DO) of fibular free flaps was used for six patients (5 men, 1 woman) a mean of 19 months (range 11-38) after 5 mandibular and 1 maxillary reconstructions. A mean of 5 months (range 2-11) after removal of the distractor, 35 implants were inserted and loaded with implant-supported fixed prostheses. The mean (range) follow-up period was 39 (17-81) months. The course of the DO and the clinical and radiographic outcomes of the implants were assessed. Of six vertically distracted fibular free flaps, there was one case of vector lingual tipping during the consolidation phase and a fracture of the basal fibular cortex that necessitated additional grafting with iliac bone to stabilise the distracted area. The mean (range) vertical bone gain was 14 (12-15) mm. Four of 35 implants (11%) failed during the follow-up period. The mean peri-implant bone resorption was 2.5mm. Cumulative implant survival was 31/35 (89%) and survival after loading 31/33 (94%). Distraction osteogenesis of fibular free flaps caused a remarkable number of complications and pronounced resorption of bone around the implants, probably as a result of the formation of granulomatous tissue; a careful peri-implant follow-up and the maintenance of oral hygiene are essential.

Histopathological profile of surgically removed persistent periapical radiolucent lesions of endodontic origin.

AIM: To determine the types of periapical lesions associated with root filled teeth with persistent periapical pathosis that required surgical treatment based on specific inclusion and exclusion criteria. METHODOLOGY: Periapical lesions from a consecutive clinical sample of 100 patients were examined histopathologically to determine a definitive diagnosis. RESULTS: Females were more represented (n = 56), the average age was 46.5 years and there were no age differences between gender or lesion type. A diagnosis of periapical granuloma was the most common finding with a similar number present in females (n = 40) and males (n = 37). A cyst was present in 18% of the cases with a majority of females (n = 12) represented in the sample. Evidence of foreign material, with an appearance consistent with endodontic sealer materials, was seen in 25 periapical granulomas, two cysts and one scar. Two periapical scars were seen, one had a history of apicectomy and amalgam root-end filling while the other was associated with extruded root filling material. CONCLUSIONS: By using defined clinical inclusion and exclusion criteria a predictable clinical diagnosis of a persistent periapical lesion due to endodontic origin can be reliably made. Periapical granulomas and cysts were the most common periapical lesions of endodontic origin associated with persistent periapical pathosis with the overall incidence of periapical cysts similar to previous studies. The presence of endodontic material in a high proportion of periapical lesions suggests a cause-effect association with the inference that clinicians should employ canal preparation techniques that limit apical extrusion of material.

Identificación de los restos epiteliales de Malassez en granulomas dentarios periapicales, determinantes del diagnóstico y evolución de los mismos / Identification of epithelial rests of Malassez in periapical granulomas, determining the diagnosis and evolution of such lesions

El objetivo del presente estudio fue determinar la presencia de las células epiteliales de Malassez en granulomas dentarios periapicales y una vez identificadas dichas células, comparar su grado de proliferación con la reacción inflamatoria adyacente. Las muestras fueron obtenidas de diferentes entidades de salud, consultorios privados, hospitales públicos y el Servicio de Emergencia de la Facultad de Odontología (UNNE). Se analizaron todas las muestras diagnosticadas clínicamente como proceso periapicales crónicos. Fueron procesadas con la técnica de rutina de inclusión en parafina y posterior tinción con hematoxilina y eosina. Se realizó el examen morfológico ytilizando microscopía óptica a 40X, 100X y 400X. Los resultados indicaron que del total de los casos estudiados, el 27 por ciento presentó proliferación de restos epiteliales de Malassez, los cuales mostraron diversos niveles de proliferación. Estos niveles de proliferación están en estrecha relación con el grado de intensidad del proceso inflamatorio, a mayor intensidad del proceso inflamatorio, mayor proliferación epitelial, con la consecuente interacción y potenciación mutua. También se observó que los granulomas periapicales epitelizados con altos niveles de proliferación e inflamación tienen mayor probabilidad de evolucionar a quistes radiculares.

Formación de los granulomas y quistes radiculares: una revisión de los aspectos inmunopatológicos / Formation of granulomas and radicular cysts: a review of the immunopathological aspects

Los granulomas y quistes radiculares representan lesiones crónicas que comprometen la región perirradicular, consideradas secuelas directas de la necrosis pulpar. El estudio de tales lesiones adquiere una importancia particular en la práctica odontológica debido a su alta frecuencia clínica. Este artículo presenta una revisión de la literatura sobre los principales eventos que llevan a la formación del granuloma periapical y la posterior formación de cavidades quísticas, dándole énfasis especial a los mecanismos inmunopatológicos relacionados con la patogénesis de tales lesiones.

Gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines interleukin-12 (IL-12) and IL-18 do not augment infection-stimulated bone resorption in vivo.

Periapical granulomas are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. In previous studies we have reported that the bone resorption in this model is primarily mediated by macrophage-expressed interleukin-1 (IL-1). The expression and activity of IL-1 is in turn modulated by a network of Th1 and Th2 regulatory cytokines. In the present study, the functional roles of the Th1 cytokine gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines IL-12 and IL-18 were determined in a murine model of periapical bone destruction. IL-12-/-, IL-18-/-, and IFN-gamma-/- mice were subjected to surgical pulp exposure and infection with a mixture of four endodontic pathogens, and bone destruction was determined by microcomputed tomography on day 21. The results indicated that all IL-12-/-, IL-18-/-, and IFN-gamma-/- mice had similar infection-stimulated bone resorption in vivo as wild-type control mice. Mice infused with recombinant IL-12 also had resorption similar to controls. IFN-gamma-/- mice exhibited significant elevations in IL-6, IL-10, IL-12, and tumor necrosis factor alpha in lesions compared to wild-type mice, but these modulations had no net effect on IL-1alpha levels. Recombinant IL-12, IL-18, and IFN-gamma individually failed to consistently modulate macrophage IL-1alpha production in vitro. We conclude that, at least individually, endogenous IL-12, IL-18, and IFN-gamma do not have a significant effect on the pathogenesis of infection-stimulated bone resorption in vivo, suggesting possible functional redundancy in proinflammatory pathways.

Exarticulation and reimplantation utilizing guided tissue regeneration: a case report.

The extraction and reimplantation of teeth is a technique that has been practiced for many years, resulting in successful retention of teeth for up to 30 years. Although evidence confirming the advantages of this technique is limited, clinical observations and histologic examinations have revealed some important factors that are prerequisites for success: limitation of the time the tooth is exposed to the extraoral environment and preservation of vital periodontal tissue attachments on root surfaces. The latter goal can be achieved by gentle, atraumatic removal of the tooth from its socket, and hence the term exarticulation and reimplantation is more representative of the technique. In the present case report, a maxillary lateral incisor with a developmental defect was treated by exarticulation and reimplantation and application of calcium sulfate. Exarticulation and reimplantation seems to be a useful clinical procedure, but controlled studies are required to confirm its efficacy.

The periapical space--a dynamic interface.

The ultimate aim of endodontic treatment is to encourage the healing of apical periodontitis, or to prevent it from occurring if it was not present prior to treatment. Apical periodontitis is a general term used to describe an inflammatory response to irritation caused by the contents of a root canal system and it has several distinct forms. The most common is a granuloma but this can develop into other disease entities such as an abscess, a periapical pocket cyst or a true cyst, all of which present as radiolucencies. However, periapical radiolucencies may also be caused by extra-radicular infections, foreign body reactions and periapical scars, or they may be due to other tumours and cysts that have not originated from pulp disease. Practitioners must recognise and understand the different pathological entities and the dynamic interactions that occur in the periapical tissues in order to correctly diagnose and treat these conditions.

Tuberculous osteomyelitis of the mandible: a case report.

Osteomyelitis of jaws caused by infection with Mycobacterium tuberculosis is uncommon, especially in children. We present a case of tuberculous osteomyelitis in a young child. Its clinical presentation, with features similar to a dento-alveolar abscess, underline the importance of considering it in the differential diagnosis of jaw lesions. We discuss of the diagnostic techniques, management and preventive measures, and stress the importance of history taking during clinical examination.

Development and treatment of retrograde peri-implantitis involving a site with a history of failed endodontic and apicoectomy procedures: a series of reports.

Osseointegrated implants provide predictable restorative support for crowns, restorations, prosthesis abutments, and removable dentures. Their widespread use in recent years has produced different types of complications. Retrograde peri-implantitis, a lesion occurring at the periapical area of an osseointegrated implant, has recently been described. This paper presents a series of reports describing the occurrence and management of retrograde peri-implantitis involving implants replacing teeth with histories of failed endodontic and apicoectomy procedures.

Effect of interleukin-6 deficiency on the formation of periapical lesions after pulp exposure in mice.

OBJECTIVE: The multifunctional cytokine interleukin-6 (IL-6) has actions on multiple cell types, including promotion of the development of immune cells and osteoclasts. Periapical inflammation as the result of root canal infection is characterized by the accumulation of inflammatory cells and bone resorption. The effect of IL-6 on periapical lesion formation after pulpal infection is unknown. We sought to determine whether deletion of IL-6 affects periapical lesion formation after pulp exposure. METHODS: Molar pulps of homozygous IL-6 knock-out mice (IL-6(-/-), strain B6, 129-Il6tm1Koe ) and wild-type mice (IL-6(+/+)) were exposed, and the mice were killed at 1, 2, 3, 5, and 8 weeks after the exposure. Mouse jaws were decalcified and prepared for histologic examination of periapical lesions. RESULTS: The IL-6(-/-) mice developed larger periapical lesions more rapidly than did the IL-6(+/+) mice. CONCLUSIONS: IL-6 deletion promoted periapical lesion development.

The periapical space--a dynamic interface.

The ultimate aim of endodontic treatment is to encourage the healing of apical periodontitis, or to prevent it from occurring if it was not present prior to treatment. Apical periodontitis is a general term used to describe an inflammatory response to irritation caused by the contents of a root canal system and it has several distinct forms. The most common is a granuloma but this can develop into other disease entities such as an abscess, a periapical pocket cyst or a true cyst, all of which present as radiolucencies. However, periapical radiolucencies may also be caused by extra-radicular infections, foreign body reactions and periapical scars, or they may be due to other tumours and cysts that have not originated from pulp disease. Practitioners must recognize and understand the different pathological entities and the dynamic interactions that occur in the periapical tissues in order to correctly diagnose and treat these conditions.