Benign epithelial odontogenic tumors

Teeth are formed from a complex interaction of primitive ectoderm and ectomesenchymal tissues. Because humans develop 2 sets of teeth (deciduous and permanent), odontogenesis is a prolonged biologic process. Residues of odontogenic tissues are present in most humans- both during and after odontogenesis. These elements may be found in either bone or soft tissue of the jaws and may contribute to the formation of odontogenic tumors in these sites. Further, the mixture of epithelium and mesenchyme necessary for tooth formation allows for the development of tumors composed of either element or for mixed neoplasms. This article discusses 4 of the 5 benign odontogenic neoplasms that are of epithelial origin and offers an agreed on classification scheme, which includes important clinicopathological subtypes. Specifically discussed are ameloblastoma, calcifying epithelial odontogenic tumor (Pindborg tumor), adenomatoid odontogenic tumor, and squamous odontogenic tumor. A brief history of each tumor is given along with a discussion of demographic data, clinical findings, radiographic features, and gross features where useful. A thorough discussion is presented of diagnostic histopathology including histologic variants. Generally accepted modes of therapy and follow-up recommendations are discussed.     

Benign epithelial odontogenic tumors

The group of benign epithelial odontogenic tumors consists of the four member types of the ameloblastoma family (solid/multicystic, extraosseous/peripheral, desmoplastic, unicystic), squamous odontogenic tumors, calcifying odontogenic tumors, adenomatoid odontogenic tumors, and keratocystic odontogenic tumors, the former "keratocysts" that were recently reclassified by the World Health Organization and are now regarded as tumors. The latter are by far the most frequent tumors in this group, followed by solid/multicystic ameloblastoma. Although the etiology of these lesions is still unknown, a close relationship to normal tooth development is obvious, which is partially imitated by some tumors. Despite some similarities to each other, at least in part, the biological behavior of these lesions is quite different, as are treatment modalities. The diagnosis is essentially based on localization (intraosseous vs. extraosseous/peripheral) and histology, whereupon the correlation of histological findings with radiographic morphology may be of additional diagnostic value. Because of the range of variation, immunohistochemical investigations are not helpful in diagnosing a particular case.     

Odontogenic tumor with combined characteristics of adenomatoid odontogenic and calcifying epithelial odontogenic tumors

A very rare odontogenic epithelial tumor with the combined characteristics of an adenomatoid odontogenic tumor (AOT) and calcifying epithelial odontogenic tumor (CEOT) was found in a 27 year old female. The histopathology, immunohistochemistry of keratin, lectin-binding patterns and distribution of carbonic anhydrase were determined. The nature of the calcified bodies was also examined biophysically. The tumor consisted of cuboidal and columnar odontogenic epithelial cells in the cystic wall, and AOT and CEOT in the central cavity. Odontogenic epithelial cells forming the cyst wall in the CEOT were positive for TK- and KL1-keratins, while that detected with PKK1 antibody was absent in the tumorous epithelium. Lectin binding of tumor epithelial cells was examined with Concanavalin A (Con A), peanut agglutinin (PNA), soybean agglutinin (SBA), dolichos biflorus agglutinin (DBA), wheat germ agglutinin (WGA), ricinus communis agglutinin (RCA-I), and ulex europeus agglutinin I (UEA-I) lectins, and the tumor epithelium indicated existence of glucose, mannose, Gal, GalNAc, and GlcNAc residues. The lectin binding patterns of the calcified material showed an increased intensity by enzymatic pretreatments. With an electron probe X-ray microanalyser (EPMA), the calcified lesions gave a high peak for calcium ion and for phosphorus ion and a low one for magnesium ion, as obtained from line and surface analysis.     

Malignant epithelial tumors and hematologic malignancy

The aim of this study was to analyze the value of cytology in differentiation between malignant epithelial tumor metastases and hematologic malignancy. The follow-up of ten (10) patients who underwent diagnosis and treatment of two malignant diseases, i.e. carcinoma and hematologic malignancy, was performed in the 2000-2005 period. The median of age of our patients was 72 years (range: 49-79). Cytological examination included epithelial tumors, lymph nodes and bone marrow standard Pappenheim and immunocytochemically stained smears. Carcinoma was initially diagnosed in 40% (4/10) patients and hematologic malignancy in 50% (5/10) patients, while both diseases co-occurred in one patient (1/10). Most of hematologic malignancy cases (4/10) were diagnosed as lymphoma. Multiple myeloma was diagnosed in 3 out of 10 patients (30%). Individual cases of acute myeloblastic leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia were diagnosed in the remaining three patients. Most carcinomas were breast cancer (8/10), while prostate and thyroid gland cancer were diagnosed each in one patient, respectively.     

Co-expression of hepatocyte growth factor and c-met in epithelial odontogenic tumors

Hepatocyte growth factor (HGF) and its receptor, c-met, have been shown to regulate cell proliferation, motility and morphology in a variety of cell types. A significant role of the HGF/c-met pathway has been demonstrated in various tumors, however, little is known about the role of HGF/c-met pathway in odontogenic tumors. The aim of this study was to characterize the expression of HGF and c-met in 30 ameloblastomas, 7 unicystic ameloblastomas (luminal type), 10 calcifying cystic odontogenic tumors, 10 adenomatoid odontogenic tumors (AOTs), 30 keratocytic odontogenic tumors (KCOTs) and 6 ameloblastic carcinomas using an immunohistochemical method. HGF and c-met were generally immunolocalized in the cytoplasm of all epithelial tumor cells, except for keratinizing cells in acanthomatous ameloblastoma, in all the examined odontogenic tumors. These results, together with the expression of these two proteins in the epithelium of tooth germs, suggest that the HGF/c-met pathway is involved in the differentiation of odontogenic tumors. This pathway may also promote tumor proliferation in odontogenic tumors due to its potent mitogenic effect. The consistent and strong immunolocalization of HGF and c-met in squamous cells present in acanthomatous ameloblastomas, AOTs and ameloblastic carcinomas, and in the linings of KCOTs suggests that the HGF/c-met interaction may have an influence on squamous differentiation in these odontogenic tumors.     

Odontoblasts in odontogenic tumors

Odontoblasts are secretory cells displaying epithelial and mesenchymal features, which exist in a monolayer at the interface between the dentin and pulp of a tooth. During embryogenesis, these cells form a dentin shell and throughout life continue to produce dentin while, also acting as sensor cells helping to mediate tooth sensitivity. In this process, odontoblasts are forced to migrate inwards, resulting in an ongoing loss of pulp volume. Correspondingly, there is also a decrease in the surface area of the dentin which supports the odontoblast cell layer. As these events transpire, odontoblasts maintain a tightly controlled monolayer relationship to each other as well as to their dentin substrate. Stability is maintained laterally by epithelial attachment structures and transversely by complex cytoplasmic extensions into the supporting dentin. As a result, it is not possible for the layer to buckle to relieve the mechanical stresses, which develop during the inward migration. A theoretical consequence of this distinctive self-generated niche is the development of long term compressive stresses within the odontoblast population. We present a mechanobiology model, which causally relates the increase in cellular compressive stresses to contact inhibition of proliferation. We link this hypothesis to the observation that there are no reports of pulpal odontoblasts showing neoplasia or acquisition of changes suggestive of a pre-neoplastic phenotype.     

Benign mixed odontogenic tumors

As a group, the mixed odontogenic tumors histologically resemble various stages of tooth formation (odontogenesis). Because of this, confusion arises in diagnosis and nomenclature unless one is familiar with normal tooth development and its subsequent resemblance to the neoplasms and hamartomas which arise from the tooth-forming tissues of the jaws. This article reviews odontogenesis and relates it to the formation of the mixed odontogenic tumors-the ameloblastic fibroma, ameloblastic fibro-odontoma, and the odontomas. Correlation of clinical and radiographic features with the histologic features will generally result in correct diagnosis and proper treatment.     

Observations by G-banding in benign odontogenic tumors

The G-banding patterns in five cultured benign odontogenic tumors are described. Abnormal stem sideline karyotypes were observed in two tumors, whereas the remaining three tumors had a normal stemline. The latter cases, however, contained different types of variant cells, often showing deviations of nonrandom character. The results are discussed in relation to chromosomal findings in other benign tumor types and, briefly, in relation to oncogenes. A stepwise evolutionary pattern, which might be common to all benign tumor types, is suggested.     

Immunolocalisation of laminin-1 in keratocystic odontogenic tumors

Keratocystic odontogenic tumors (KOTs) are distinct odontogenic lesions frequently affecting the jawbones. They may be associated with nevoid basal cell carcinoma syndrome (NBCCS), and may exhibit disorders involving the extracellular matrix. The aim of this study was to investigate the immunolocalisation of laminin-1 in 20 cases of KOTs in order to contribute to the characterization of this protein, which is little studied in odontogenic tumors. Our results showed laminin-1 in all 20 KOTs studied; its labelling intensity was weak in three cases (15%), moderate in five (25%) and strong in 12 cases (60%). Laminin-1 immunolocalisation was predominantly continuous in 18 (90%) KOTs, including areas of acanthosis, subepithelial split and epithelial buds. Weak immunolabelling was observed in regions exhibiting an inflammatory process, especially in the case of intense inflammation. These findings suggest that laminin-1 does not participate in biological processes such as cystic epithelium-cystic wall separation or the formation of epithelial islands in KOTs. Furthermore, the discontinuous and weak labelling of this protein in the basement membrane of these tumors is probably a consequence of the inflammatory process in the tumor stroma.     

Calcifying epithelial odontogenic tumor: report of two cases

Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign odontogenic tumor. It constitutes 0.4-3% of all odontogenic tumors. There is only a single case, which has been reported in the Indian literature that too in cytology. Microscopically, these are composed of large sheets of epithelial cells, amorphous amyloid-like material and calcification. Although these lesions are benign, they can be locally aggressive, but malignant transformation and metastasis is rare. Considering its locally aggressive nature, appropriate management and long-term follow-up is recommended. We describe two cases of CEOT involving the hard palate and leading to facial alterations.     

Expression of p21RAS in odontogenic tumors.

Using an immunohistochemical assay 10 benign odontogenic tumors were evaluated for expression of the HRAS- and KRAS-encoded gene products p21RAS. Overexpression of p21RAS was found in ameloblastomas, ameloblastic fibromas and odontogenic myxomas compared with normal human developing teeth. The highest expression was noted in a recurrent plexiform ameloblastoma in which almost 100% of the tumor cells were brightly reactive. In general, p21RAS was preferentially expressed in ectodermal cells of odontogenic tumors, consistent with the findings in the tooth germs. The significance of p21RAS expression is considered in relation to the biological behavior of ameloblastomas.     

Immunohistochemical expression of amelogenins in odontogenic epithelial tumours and cysts

Summary Amelogenins, enamel proteins in odontogenic tumours, were detected immunohistochemically using a monoclonal antibody. They were strongly expressed in amyloid-like material, ghost cells, and the cells surrounding ghost cells of calcifying epithelial odontogenic tumours and cysts, whereas calcified bodies within the tumours and cysts showed negative staining. The expression of amelogenins was also positive in tumour cells of ameloblastoma, adenomatoid odontogenic tumour, squamous odontogenic tumour and ameloblastic fibroma. Peripheral tumour cells of the follicular ameloblastoma were positive with relatively intense staining. Undifferentiated or flattened tumour cells of adenomatoid odontogenic tumour and non-keratinized tumour cells of the squamous odontogenic tumour showed marked staining. Reduced ameloblasts in the odontoma displayed the strongest staining for amelogenins. The study suggests that biosynthesis of amelogenins may occur in the homogeneous materials of calcifying epithelial odontogenic tumours and cysts.     

Aggressive (malignant) epithelial odontogenic ghost cell tumor.

A 57-year-old man had an expanding cystic lesion of the anterior maxilla that demonstrated destruction and disruption of local structures. A cystic odontogenic neoplasm as well as various forms of odontogenic carcinoma was suspected. Incisional biopsy and microscopic examination revealed an aggressive epithelial odontogenic tumor with histologic features suggesting malignant transformation from an odontogenic cyst. The patient continues to refuse further treatment despite remaining tumor. This case further documents the malignant potential of a calcifying odontogenic cyst and the existence of at least an aggressive or possibly malignant form of epithelial odontogenic ghost cell tumor. To date, metastatic work-up has not been performed.     

Calcifying epithelial odontogenic tumours in three cats and a dog

Neoplasms histologically similar to calcifying epithelial odontogenic tumour (CEOT) of man are described in three cats and a dog. The diagnostic features of these neoplasms are their occurrence in the jaw and the histological appearance of cords of epithelial cells, amyloid spherules and foci of calcification. The histogenesis and behaviour of the tumour are discussed.