Differences in Inflammation and Bone Resorption between Apical Granulomas, Radicular Cysts, and Dentigerous Cysts.

INTRODUCTION: Dental cysts can be of inflammatory (radicular cysts) or noninflammatory (dentigerous cysts) origin. Apical periodontitis is a necrosis of the pulp and infection of the root canal causing the development of apical granulomas or radicular cysts. The immunology of granuloma and cyst formation is important because modern root filling materials are immunologically active and can contribute to the resolution of apical granulomas. In contrast, radicular cysts often require apicectomy. A better understanding of the pathophysiology of inflammation and bone resorption in apical periodontitis could be the basis for developing new root filling materials with superior immunomodulatory properties. METHODS: Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray of the 87 consecutive specimens was created, and human leukocyte antigen-DR isotype (HLA-DR)-, CD83-, receptor activator of nuclear factor kappa B ligand-, macrophage colony-stimulating factor (MCSF)-, galectin-3 (Gal3)-, CD4-, and CD8-positive cells were detected by immunohistochemistry. Tissue microarrays were digitized, and the expression of markers was quantitatively assessed. RESULTS: HLA-DR, CD83, MCSF, and Gal3 expression was significantly (P < .05) higher in radicular cysts compared with apical granulomas. HLA-DR, CD83, MCSF, receptor activator of nuclear factor kappa B ligand, and Gal3 expression in dentigerous cysts was significantly (P < .05) lower than in both periapical lesions (apical granulomas and radicular cysts). CD4 and CD8 infiltration was not statistically different between apical granulomas and radicular cysts. Dentigerous cysts showed a significantly (P < .05) lower T-cell infiltration than apical periodontitis. The CD4/CD8 ratio was not significantly different between the analyzed groups. CONCLUSIONS: The development of radicular cysts in apical periodontitis is associated with an increased expression of myeloid inflammatory markers and bone resorption parameters. Antigen-presenting cells and myeloid cells might be more relevant for the pathogenesis of apical periodontitis than T cells. Increased inflammation might promote the formation of radicular cysts and more pronounced bone resorption.

Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts.

OBJECTIVES: Apical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts. MATERIALS AND METHODS: Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed. RESULTS: Radicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions. CONCLUSIONS: The development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin. CLINICAL RELEVANCE: As M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst formation.

Immunoexpression of transforming growth factor beta and interferon gamma in radicular and dentigerous cysts.

INTRODUCTION: The aim of this study was to evaluate and compare the immunohistochemical expression of transforming growing factor beta (TGF-ß) and interferon gamma (IFN-γ) between radicular cysts (RCs) and dentigerous cysts (DCs). METHODS: Twenty RCs and DCs were selected for analysis of the immunoexpression of TGF-ß and IFN-γ in the epithelium and capsule. RESULTS: The cell reactivity of TGF-ß and IFN-γ in the lining epithelium and capsule of RCs showed no significant differences when compared with DCs (P > .05). There was a tendency of a higher expression of TGF-ß in the capsule of DCs. CONCLUSIONS: Our results showed the presence of TGF-ß and IFN-γ in RCs and DCs, supporting the hypothesis that both participate in the development of these lesions, where IFN-γ usually plays a role in bone resorption, which is counterbalanced by the osteoprotective activity performed by TGF-ß.

Does cytokine profiling of aspirate from jaw cysts and tumors have a role in diagnosis?

PURPOSE: The objective of the present study was twofold: first, to assess aspirates for use in cytokine profiling and second, to initiate pilot analyses to determine whether the cytokine profiling can serve as an aid in the diagnosis of jaw lesions. MATERIALS AND METHODS: The aspirates from 12 benign odontogenic cysts and tumors of the jaw were collected and randomized, and a formal incisional biopsy was performed to establish the tissue diagnosis. The biopsies revealed keratocystic odontogenic tumor, ameloblastoma, and dentigerous cyst. The cystic aspirate was analyzed using the Q-Plex Human Cytokine Screen to detect cytokine expression and determine the level of expression for each pathologic entity. An array of 16 cytokines was investigated, including interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IL-23, interferon-γ, tumor necrosis factor (TNF)-α, and TNF-ß. Tables were developed to determine the ratio of expression for the candidate cytokine pairs that were differentially expressed among the 3 pathologic entities encountered. One-way analysis of variance was used to search for significant differences in the ratio of expression of the candidate pairs among the 3 entities. RESULTS: Cytokines expressed by the 3 distinct jaw lesions were detected in the aspirate without the need for tissue biopsy. Cytokine profiling of these entities is possible owing to differential expression of the various cytokines studied. The ratio of expression was significant (P < .05) for 15 pairs of cytokines: IL-5/IL-1α, IL-4/IL-2, IL-8/IL-4, TNF-ß/IL-6, IL-23/IL-6, TNF-α/IL-23, TNF-α/TNF-ß, TNF-α/IL-8, TNF-ß/IL-5, TNF-ß/TNF-α, TNF-ß/IL-13, IL-12/IL-23, IL-13/IL-15, IL-15/IL-2, and IL-6/IL-2. A comparison of the mean values indicated a "high/low" expression value for each lesion type for the 15 cytokine pairs. CONCLUSIONS: Cytokines, expressed by the 3 groups of jaw lesions, can be detected in the cystic aspirate, and a comparison of the ratio of the expression of the aspirates demonstrated a differential expression pattern of cytokines among the 3 groups. These ratios could assist in establishing a prompt and accurate diagnosis of lesions that might be difficult to discern clinically and radiographically. The use of a simple, minimally invasive aspiration procedure can help to establish an accurate diagnosis.

Ki-67 expression in dentigerous cysts, unicystic ameloblastomas, and ameloblastomas arising from dental cysts.

This study investigated whether or not an ameloblastoma developing in the wall of a dentigerous cyst is a distinct lesion from the unicystic ameloblastoma. An immunohistochemical evaluation of Ki-67 in dentigerous cysts, unicystic ameloblastomas, and ameloblastomas arising in dentigerous cysts was done. The values of Ki-67 positivity were 3.14 for the dentigerous cyst, between 5.32 and 16.56 for unicystic ameloblastoma, and 11.77 for ameloblastoma arising in a dentigerous cyst. Statistically significant differences were found between the dentigerous cyst and the unicystic ameloblastoma and between the dentigerous cyst and the ameloblastoma arising from a dentigerous cyst. No statistically significant difference was present between unicystic ameloblastoma and ameloblastoma arising from dentigerous cyst. These immunohistochemical data confirm the hypothesis that an ameloblastoma arising from a dentigerous cyst has a similar biological behavior to the unicystic ameloblastoma and should be considered as merely a histologic variant.

Expresión de la proteína p53 en quistes dentígeros y queratoquistes odontogénicos / p53 protein expression in dentigerous cysts and odontogenic keratocysts

Objetivo: Se realizó un estudio descriptivo comparativo para valorar la expresión de la proteína p53 en los quistes dentígeros (QD) y queratoquistes odontogénicos (QQO), con sus variantes ortoqueratósica (QQO-O) y paraqueratósica (QQO-P), con el propósito de relacionar el grado de expresión de la proteína p53 con el potencial de agresividad de las patologías mencionadas. Método: La proteína p53 fue identificada, empleando el anticuerpo monoclonal M7001 junto con técnica de inmunoperoxidasa estándar. Se emplearon un total de 25 muestras de tejido, fijadas en formalina neutra y embebidas en parafina, correspondientes a 13 quistes dentígeros y 12 queratoquistes odontogénicos, previamente diagnosticados histológicamente. Estas fueron obtenidas de los archivos de Patología Oral de la Facultad de Odontología de la Pontificia Universidad Javeriana. La expresión de la proteína p53 fue medida observando el número de células con núcleos teñidos de color café en el epitelio quístico y que fueron identificadas con el miroscopio óptico de luz. Resultados: Grado de expresión nulo (72 por ciento) distribuidos así: QD 52 por ciento, QQO-O 16 por ciento y QQO-P 4 por ciento; grado de expresión leve (8 por ciento distribuidos así: QQO-O 4 por ciento y QQO-P 4 por ciento; grado de expresión moderado (20 por ciento) se presentó únicamente en los QQO-P. Ninguna patología presentó grado de expresión alto. La variable localización también fue estudiada relacionándola con el grado de expresión; no mostró significancia clínica. Conclusiones: La proteína p53 marcó más en los queratoquistes odontogénicos comparada con los quistes dentígeros, posiblemente por los cambios de queratinización que se presentan en su epitelio, siendo ésta una característica histológica importante en lesiones con potencial de transformación neoplásica o carcinomaS propiamente dichos

Estudo imunocitoquímico comparativo dos folículos pericoronários, cistos dentígeros e queratocistos odontogênicos / Immunohistochemical comparative study of the dental follicles with dentigerous cysts and odontogenic keratocysts

Com o objetivo de estabelecer as características imunocitoquímicas de folículos pericoronários, cistos dentígeros e queratocistos odontogênicos, foram selecionados dos arquivos do Laboratório de Anatomia Patológica do Departamento de Patologia da Faculdade de Odontologia de Bauru USP, dez casos de folículos pericoronários com epitélio reduzido do orgäo do esmalte, dez casos de folículos pericoronários com metaplasia escamosa, dez casos de cistos dentígeros e dez casos de queratocistos odontogênicos, submetidos a evidenciaçäo imunocitoquímica de um painel constituído dos seguintes marcadores: citoqueratina de alto peso molecular, citoqueratina de baixo peso molecular, laminina, fibronectina, colágeno IV, vimentina e proteína S100. A partir dos resultados obtidos pudemos concluir que o padräo imunocitoquímico das 4 condiçöes estudadas permite uma diferenciaçäo diagnóstica entre folículos pericoronários, cistos dentígeros e queratocistos odontogênicos, utilizando-se a marcaçäo da proteína S100. A diferenciaçäo pela marcaçäo com a proteína S100 pode ser complementada pela evidenciaçäo das células de Langerhans, que caracteristicamente estäo presentes nos revestimentos epiteliais dos cistos dentígeros

[Expression of certain cytokeratins in the epithelium of dentigerous and primordial cysts]. / L'expression de certaines cytokératines par l'épithélium de kystes dentigères et primordiaux.

The histopathologic diagnosis of odontogenic cysts is based mainly on the morphological nature of the epithelial lining of the cyst. A standard immunocytochemical method based on anticytokeratin monoclonal antibodies was used for the diagnosis of dentigerous and primordial cysts: 12 odontogenic cysts were diagnosed on clinical, radiological and pathological criteria in 9 dentigerous cysts and 3 primordial cysts. The anticytokeratin antibodies used in this study were KL1 (Immunotech, France) and AE1, AE2, AE3 and AE8 (ICN-Miles, France). The anticytokeratin antibodies used stained only the epithelial cells confirming their accuracy. The KL1 antibodies stained homogeneously the various epithelial cells. This positive reaction was not modified by the various fixation methods used. Some reactions observed with AE antibodies seemed to be modified by Bouin's fixative. The staining homogeneity of the primordial cysts and the staining heterogeneity of the dentigerous cysts seemed to be related to morphological aspects of their respective epithelia. The epithelial reactions in these 2 types of cysts towards inflammation were different.

Distribution of type 1 and 2 blood group chains in normal and pathological odontogenic epithelium defined by monoclonal antibodies specific for Lea and H type 2.

This study describes the distribution of type 1 and type 2 blood group carbohydrate chains in human normal and pathological odontogenic epithelia and in epithelia of human oral mucosa. Odontogenic epithelium was examined from 12 fetal tooth germs, 25 ameloblastomas, 13 odontogenic keratocysts, 13 follicular cysts and 13 radicular cysts. Oral mucosal epithelia was studied from 12 fetuses and 10 adults. Cell surface carbohydrates were detected using antibodies with reactivity for the blood group antigens A, B, type 1 chain Lea and type 2 chain H by an immunofluorescence technique. The expression of Lea and H type 2 chain in fetal palatal epithelium and only H type 2 chain in adult palatal epithelium suggests that a change in synthesis of blood group chains occurs during development. Type 2 blood group chains (antigen H) were found in fetal tooth germs, type 1 (Lea) in ameloblastomas and both type 1 and type 2 in odontogenic cysts. These results indicate that a modulation in synthesis of blood group carbohydrates has occurred in ameloblastomas and odontogenic cysts as compared with the cells from which the lesions presumably are developed. It is suggested that ameloblastomas may be distinguished from odontogenic cysts by the inability of ameloblastomas to synthesize type 2 blood group chains and antigens A and B.

The pathogenesis of odontogenic cysts: a review.

The pathogenesis of the three common forms of odontogenic cyst is discussed. It is concluded that the dental cyst arises from proliferation of the epithelial rests of Malassez in a focus of inflammation stimulated by pulpal necrosis of the associated tooth. It enlarges by unicentric expansion from the hydrostatis pressure of its contents. The dentigerous cyst arises from pooling of inflammatory exudate, which is derived from the obstructed follicular veins of an unerupted tooth and accumulates between the reduced enamel epithelium and the crown of the tooth. It enlarges by unicentric expansion from the hydrostatic pressure of its contents. The odontogenic keratocyst arises by proliferation of the residues of the dental lamina, possibly as a hamartomatous abnormality. It enlarges by both multicentric expansion due to the proliferation of localized groups of epithelial cells in the lining and by unicentric expansion from the hydrostatic pressure of its contents.