Benign odontogenic tumors versus histochemically related tissues: preliminary results from mid-infrared and solid-state nuclear magnetic resonance spectroscopy.

Three types of human odontogenic tumors histologically classified as compound composite odontoma, ossifying fibroma, and Pindborg tumor were characterized using mid-infrared spectroscopy (mid-IR) and solid-state nuclear magnetic resonance (ssNMR). For comparison, human jawbone and dental mineralized tissues such as dentin, enamel, and dental cement were also characterized. The studies focused on the structural properties and chemical composition of pathological tissues versus histochemically related tissues. All analyzed tumors were composed of organic and mineral parts and water. Apatite was found to be the main constituent of the mineral part. Various components (water, structural hydroxyl groups, carbonate ions (CO(3)(2-)), and hydrogen phosphate ions (HPO(4)(2-))) and physicochemical parameters (index of apatite maturity and crystallinity) were examined. The highest organic/mineral ratio was observed in fibrocementoma, a finding that can be explained by the fibrous character of the tumor. The lowest relative HPO(4)(2-) content was found in odontoma. This tumor is characterized by the highest mineral crystallinity index and content of structural hydroxyl groups. The Pindborg tumor mineral portion was found to be poorly crystalline and rich in HPO(4)(2-). The relative CO(3)(2-) content was similar in all samples studied. The results of spectroscopic studies of odontogenic tumors were consistent with the standard histochemical analysis. It was shown that the various techniques of ssNMR and elaborate analysis of the mid-IR spectra, applied together, provide valuable information about calcified benign odontogenic tumors.

Radiopacity in syndrome keratocystic odontogenic tumour.

Dystrophic calcification or radiopacity in syndromatic keratocystic odontogenic tumours is not uncommon although there have not been many reports. A case of dystrophic calcification in the cavity of the cyst of a patient with a syndromatic keratocystic odontogenic tumour was detected on panoramic radiograph and CT. The component of the calculus was analysed by Fourier transform infrared spectrum.

Expression of basement membrane components in odontogenic tumors.

OBJECTIVE: The objective was to characterize the expression of BMCs (laminins 1 and 5, collagen type IV, and fibronectin) in ameloblastomas, calcifying cystic odontogenic tumors (CCOTs), and adenomatoid odontogenic tumors (AOTs). STUDY DESIGN: BMCs were analyzed in 14 ameloblastomas, 7 CCOTs, and 7 AOTs using immunohistochemistry. RESULTS: In normal oral mucosa, linear deposits of these proteins were found at the epithelial-mesenchymal junction, but not in epithelial cytoplasm. In all tumors studied, linear deposits of all proteins were found at the epithelial-mesenchymal junction; laminin 1 was expressed in all tumor cells, regardless of cell types. For CCOTs, laminin 5 was found faintly in suprabasal cells, but expressed strongly in ghost cells. For AOTs, laminin 5 strongly decorated tumor cells adjacent to mineralization. CONCLUSIONS: Laminin 1 may be a marker for odontogenic epithelium. Additionally, laminin 5 may be involved in ghost cell formation and initiation of calcification.

Expressão imuno-histoquímica de proteínas da matriz extracelular em cistos odontogênicos calcificantes / Immunohistochemical expression of extracellular matrix proteins in calcifying odontogenic cyst

INTRODUÇAO: O cisto odontogênico calcificante (COC) é uma lesão odontogênica de natureza benigna considerada por alguns autores como uma lesão exclusivamente cística, enquanto outros admitem uma contraparte neoplásica benigna. Vários estudos têm pesquisado a natureza das células fantasmas características do COC, porém permanece obscuro o conhecimento sobre a expressão dos constituintes da matriz extracelular (MEC) nessa lesão. OBJETIVO: Realizar uma avaliação imuno-histoquímica da expressão de proteínas constituintes da MEC (fibronectina, tenascina e colágeno I) em espécimes de COCs, a fim de verificar se há diferenças significativas em tal expressão ou se esses padrões representam um espectro da mesma entidade. MATERIAL E MÉTODOS: Foram utilizados dez casos de COCs, representados por cinco do tipo unicístico simples, três do tipo produtor de odontoma e dois com proliferação ameloblastomatosa, que foram submetidos à técnica imuno-histoquímica da estreptoavidina-biotina com anticorpos monoclonais anti-fibronectina, anti-tenascina e anti-colágeno I. RESULTADOS: Verificou-se que houve uma expressão variável das proteínas pesquisadas, tanto entre as lesões do mesmo grupo, como entre os três grupos estudados, sendo notável a reatividade para os três anticorpos apresentada pelas células fantasmas. CONCLUSAO: Não foi possível observar um padrão de marcação que denotasse diferenças entre o tipo unicístico simples, o produtor de odontoma e o com proliferação ameloblastomatosa. Esse achado reforça a visão de que os vários tipos histológicos do COC podem, simplesmente, representar espectros histológicos diferentes de uma só entidade com comportamento biológico semelhante.

Calcifying epithelial odontogenic (Pindborg) tumor-associated amyloid consists of a novel human protein.

Calcifying epithelial odontogenic tumors (CEOTs), also known as Pindborg tumors, are characterized by the presence of squamous-cell proliferation, calcification, and, notably, amyloid deposits. On the basis of immunohistochemical analyses, the amyloidogenic component had heretofore been deemed to consist of cytokeratin-related or other molecules; however, its chemical composition had never been elucidated. We have used our microanalytic techniques to characterize the protein nature of CEOT-associated amyloid isolated from specimens obtained from 3 patients. As evidenced by the results of amino-acid sequencing and mass spectrometry, the fibrils were found to be composed of a polypeptide of approximately 46 mer. This component was identical in sequence to the N-terminal portion of a hypothetical 153-residue protein encoded by the FLJ20513 gene cloned from the human KATO III cell line. That the amyloid protein was derived from this larger molecule was demonstrated by reverse transcription-polymerase chain reaction amplification of tumor-cell RNA where a full-length FLJ20513 transcript was found. Furthermore, immunohistochemical analyses revealed that the amyloid within the CEOTs immunostained with antibodies prepared against a synthetic FLJ20513-related dodecapeptide. Our studies provide unequivocal evidence that CEOT-associated amyloid consists of a unique and previously undescribed protein that we provisionally designate APin.

beta-Catenin is expressed aberrantly in tumors expressing shadow cells. Pilomatricoma, craniopharyngioma, and calcifying odontogenic cyst.

We studied the beta-catenin immunohistochemical profile in tumors expressing shadow cells: pilomatricoma, 10 cases; calcifying odontogenic cyst, 6 cases; and craniopharyngioma, 9 cases. There was strong membranous, cytoplasmic, and nuclear staining of the immature basaloid cells in all of these tumors. Shadow cells were negative in all tumors. It has been documented that rising levels of free beta-catenin drive the formation of complexes with T-cell factor/lymphoid enhancer factor (TCF-Lef) and up-regulate the wingless-Wnt cell-cell signals. The end result is an abnormality of beta-catenin degradation and, thus, a buildup of free beta-catenin in the cytoplasm and/or nucleus, resulting in the stimulation of cellular proliferation and/or inhibition of cell death. beta-Catenin seems to have an important role in the oncogenesis of these tumors. The similar pattern of keratinization in these tumors and the similar pattern of beta-catenin immunoreactivity in the cytoplasm and the nucleus are important findings. It seems that the activation of a common cellular pathway, namely Wnt-beta-catenin-TCF-Lef, has a role in the pathogenesis of these tumors. The latter could be related to their shared method of keratinization or shared dysfunction of the cellular adhesion complex leading to tumorigenesis.

Peripheral clear cell variant of calcifying epithelial odontogenic tumor: Report of a case and immunohistochemical investigation.

A case of peripheral calcifying epithelial odontogenic tumor, clear cell variant, located on the right gingival maxilla of a 48-year-old woman, presenting as a 2.0-cm solitary, firm nodule was studied. Microscopically, it was composed of polyhedral and clear epithelial cells associated with amyloid-like deposition. The clear epithelial cells exhibited granules that were positive for periodic acid-Schiff, and the amyloid-like deposit stained with Congo red showed a green birefringence in the polarized light. Polyhedral and clear epithelial cells were immunopositive for AE1/AE3 and cytokeratin 14. Immunoexpression of fibronectin and types I and III collagen were different between the amyloid-like deposits and the connective tissue stroma. Tenascin surrounded epithelial cells located inside the amyloid-like deposits. Laminin and type IV collagen were immunodetectable around the strands, cords, and nests of epithelial cells. This report represents the seventh case of peripheral calcifying epithelial odontogenic tumor, clear cell variant.

Histopathological and immunohistochemical analysis of calcifying odontogenic cysts.

METHOD AND RESULTS: Calcifying odontogenic cysts (COCs) were examined histopathologically and immunohistochemically to characterize the histological and cytological properties of these lesions. Histopathologically, COCs showed thin or thick lining epithelium with ghost cells. COCs were classified according to proliferative type or nonproliferative type lining epithelium, the presence or absence of ameloblastomatous appearance, and the presence or absence of odontoma in the cyst walls. Immunohistochemically, amelogenin protein was expressed chiefly in ghost cells, whereas cytokeratin 19 (CK19) and bcl-2 proteins were expressed chiefly in lining epithelial cells. The proportion of cases positive for bcl-2 protein was slightly higher in COCs with odontoma than in those without odontoma. Lining epithelial cells sporadically showed positive reactions for Ki-67 antigen. Mean Ki-67 labeling index was slightly greater in COCs with proliferative type lining epithelium, COCs with ameloblastomatous appearance of the cyst walls, and COCs with odontoma of the cyst walls than in COCs without these histological features. Our results suggest that ghost cells or lining epithelial cells show ameloblastic cytodifferentiation or odontogenic epithelial characteristics, that bcl-2 protein is associated with survival of lining epithelial cells in COCs, and that high proliferation potential is associated with ameloblastomatous proliferation or combined odontoma. COCs exhibited various histological features with several transitional forms, and immunohistochemical examinations revealed little or no difference in cytodifferentiation and cellular activity among COCs. CONCLUSION: We conclude that COCs with various histological features have neoplastic potential and may not be separate entities within the same histological spectrum.

CK13 in craniopharyngioma versus related odontogenic neoplasms and human enamel organ.

The monoclonal antibody NCL-CK13 was studied in specimens of craniopharyngioma, ameloblastoma and calcifying odontogenic cyst neoplasms and the mandible and maxillae of normal human fetuses. There was a decrease in NCL-CK13 as the dental lamina developed, with a complete loss in the enamel organ. The neoplastic epithelia of the neoplasms revealed a clear phenotypic and immunohistochemical reactive relationship to the stratified embroyonic mucosa, away from the enamel organ. This suggests that these neoplasms might have their histogenesis from early stage epithelium, the oral part of the dental lamina or its remnants.

Proliferative activity of calcifying odontogenic cysts as evaluated by proliferating cell nuclear antigen labeling index.

The calcifying odontogenic cyst (COC) presents with diverse histological features; thus, several subclassifications have been proposed. To evaluate the significance of the various histological features and subtypes of COC from the perspective of proliferative activity, the proliferating cell nuclear antigen (PCNA) labeling index (LI; the percentage of positive nuclei) was assessed immunohistochemically in 25 cases of COC (21 benign and four malignant). All of the benign cases were of the cystic variety and further subclassified into non-proliferative subtype (NPS; four cases); proliferative subtype (PS; eight cases); and COC associated with odontoma (COCaO, nine cases). The PCNA LI of the malignant COC (65.2+/-5.6) was significantly higher than that of the benign COC (11.6+/-9.0; P = 0.002). Non-proliferative subtype (6.8+/-2.8) showed the lowest PCNA LI and PS (17.2+/-11.2) the highest of among the three subtypes of benign cystic COC (P = 0.028). In nine cases of COCaO, six showed epithelial lining of the non-proliferative type as NPS and the other three had lining with proliferative features as PS. The PCNA LI of the latter COCaO group (14.3+/-6.6) was significantly higher than that of the former (6.1+/-4.3; P = 0.05), as seen between PS and NPS. These results demonstrate that PCNA LI is a possible parameter for differentiating malignant COC from benign COC and, whatever the subtypes, the proliferative features in the lining are the main factor influencing the proliferating activity of COC.

Immunohistochemical analysis of a dentinogenic ghost cell tumour.

A dentinogenic ghost cell tumour in an 80-year-old male patient is presented. It is an extremely rare tumour and only 10 cases have been reported in the English literature. The lesion showed odontogenic epithelium, ghost cells, dentinoid, giant cells. The immunohistochemical analysis for Mib-1 and bel-2 showed a strong positivity of the cells of the odontogenic epithelium, while with p53 only a rare positivity was observed. Completely negative were the ghost cells, giant cells and dentinoid material. In this tumour the cells expressing Mib-1 and bcl-2 could be the cells that proliferate, and that could undergo malignant transformation.

Calcifying odontogenic cyst: a clinicopathologic study of 57 cases with immunohistochemical evaluation for cytokeratin.

PURPOSE: A clinicopathologic study of all cases accessioned as calcifying odontogenic cyst (COC) from 1971 to 1996 from the files of the Oral Pathology Laboratory at Temple University School of Medicine was undertaken. MATERIALS AND METHODS: Microscopic slides and clinical histories of cases diagnosed as calcifying odontogenic cyst were reviewed and analyzed. Ten cases were processed for cytokeratin immunohistochemical staining. RESULTS: Fifty-seven cases were reviewed, 28 males and 29 females. Patients' ages ranged from 7 to 83 years, with a mean age of 49.8 years. Thirty-four cases involved the mandible and 23 were from the maxilla. Seventeen were reported in peripheral locations, and 38 occurred centrally within the jaws. Two were found both centrally and peripherally. The most common clinical sign for central lesions was a radiolucency sometimes associated with a jaw expansion. The most common clinical complaint for peripheral lesions was a nodular growth on the gingiva. Although lining epithelial cells were strongly positive for cytokeratin, full-brown ghost cells and disintegrating ghost cells were nonreactive. CONCLUSION: Calcifying odontogenic cyst can occur in any age-group, intraosseously or extraosseously, and as a solid lesion. No recurrences were found after surgical removal in the current series.

A clinicopathological and immunohistochemical study of the calcifying epithelial odontogenic tumour (Pindborg tumour) in Malaysians.

We reviewed the clinicopathological characteristics of 13 cases of calcifying epithelial odontogenic tumour (CEOT) (Pindborg tumour) diagnosed in the Division on Stomatology, Institute for Medical Research, Kuala Lumpur, over a 29-year period. There were eight female and five male patients. These consisted of eight (61.5 per cent) Malays, three (23.1 per cent) Chinese, one (7.7 per cent) Indian and one (7.7 per cent) Melanau. Their ages at presentation ranged from 19-61 years (mean age, 31.8 years). There were 12 central and one peripheral CEOT. Of these, 76.9 per cent of cases were located in the maxilla, the remaining in the mandible. The commonest clinical diagnosis was a dentigerous cyst (66.7 per cent). Enucleation was the main mode of treatment. Histologically, sheets and strands of polyhedral epithelial cells containing eosinophilic, homogeneous globules with Liesegang rings were observed. One case also showed extensive calcification and clear cell differentiation. Immunohistochemistry revealed a variable keratin staining of the CEOT epithelium, confirming its heterogeneity.

The so-called calcifying epithelial odontogenic tumour in dogs and cats (amyloid-producing odontogenic tumour).

This paper describes the microscopical features of a rare odontogenic tumour that occurs in dogs and cats and which has been referred to as the calcifying epithelial odontogenic tumour (CEOT), although it is not the counterpart of the human tumour of that name. We have proposed amyloid-producing odontogenic tumour (APOT) as an appropriate alternative term. The tumour is composed of irregularly shaped strands of squamous epithelium, which in some areas exhibit palisading of the basal cells, similar to that seen in ameloblastomas. Stellate reticulum occurs focally in some examples. The second prominent feature is the presence of amyloid which tends to calcify. Finally, in some examples, a collagenous matrix, which is apparently a form of dentine, is present focally, adjacent to the epithelium. These histological features are compared with those of the canine keratinizing ameloblastoma and the human CEOT. To date, to few examples have been reported to determine accurately the biological behaviour of APOTs, but some have recurred after excision; none has metastasized.