SOT is classified as a benign, locally-infiltrative odontogenic epithelial neoplasm with three possible sources of origin depending on its location. Intraosseous SOT putatively originates from the cell rests of Malassez whereas its peripheral counterpart arises from the dental lamina remnants (glands of Serres) or the gingival surface epithelium . SOT must be distinguished from other intraosseous neoplasms notably ameloblastoma and primary intraosseous squamous cell carcinoma. Histopathologically, tumor islands in SOT consisted of well-differentiated squamous epithelium without peripheral palisading unlike those in the classic ameloblastoma which characteristically exhibits a peripheral layer of pre-ameloblasts and central stellate reticulum-like cells [3, 18]. Primary intraosseous squamous cell carcinoma can be ruled out on grounds of absence of cytological features of malignancy in the tumor islands of SOT [3, 7]. In the present case all these aspects were considered before arriving at a diagnosis of SOT.
The Notch family of receptors has been characterized as critical determinants of cell fate in a variety of organisms [8–10]. Notch receptors participate in cell fate decisions by the process of lateral inhibition or inductive signaling. In the developing tooth, Notch receptors and ligands have been found to be expressed in dental epithelium and/or ectomesenchyme, suggesting that Notch signaling may regulate odontogenesis . It is known that the morphological characteristics and inductive relationship between various parts of the developing tooth germ are reproduced to a greater or lesser extent in many of the tumors and tumor-like lesions of the odontogenic apparatus . In the light of this, the potential role of the Notch signaling pathway in the proliferation and cellular differentiation of some of these odontogenic neoplasms was examined. Notch1, 2 and 3, Jagged1 and Delta1 were detected in the central and peripheral cells of the follicular and plexiform ameloblastoma but were absent in areas exhibiting keratinization and granular cell differentiation, and in stromal cells (Table 2) . These findings led the authors to suggest that Notch signaling does not play an oncogenic role in the tumorigenesis of odontogenic epithelium but might contribute to the control of neoplastic cell differentiation and suppress neoplastic cell proliferation in odontogenic epithelium . In the ameloblastic carcinoma, Notch1 was expressed by most neoplastic epithelial cells including small numbers of mitoses, and these observations led to the suggestion that Notch1 plays some roles in the cytological differentiation or acquisition of tissue specific characteristics and may contribute to cell cycle arrest in these neoplastic cells [11, 16]. In the case of ameloblastic fibroma, Notch1 activity was detected in the peripheral and central cells of tumor nests and strands as well as in the dental papilla-like stromal cells, and these findings suggest that Notch signaling might be involved in the specific cell differentiation of the epithelial nests of this neoplasm . During odontogenesis, Notch1 transcriptions were seen in the dental mesenchyme after the cap stage . For the odontogenic myxoma, Notch signaling activity was absent and this was attributed to the fact that the mesenchymal tissue in this neoplasm is in a less advanced stage of differentiation than the dental papilla-like tissue in the ameloblastic fibroma .
In the current study, Notch1, 3 and 4, Jagged1 and Delta1 were expressed by the peripheral and central cells of the tumor islands in the SOT as well as in areas of keratinization, cystic degeneration, clear cell differentiation and dystrophic calcification foci. Notch2 and Jagged2 were consistently absent. These preliminary findings suggest that Notch signaling may be involved in the cellular differentiation of SOT. It is further observed that ameloblastoma and SOT are both benign neoplasms of odontogenic epithelium without odontogenic ectomesenchymal participation but their Notch expression patterns differ. We believed that these differences may be due to their different stages of cellular differentiation. In the ameloblastoma tumor epithelium, the peripheral cells resembled the pre-ameloblasts while the central cells resembled the stellate reticulum of the developing tooth germ after cap stage . In the SOT, the tumor epithelium has a squamous characteristic. These differences in Notch expression patterns may be related to the different functional activities of these cell signaling molecules during the cellular differentiation of the ameloblastoma and SOT.
In summary, a case of SOT is reported here and its Notch immunoexpression profile defined. As a wide range of neoplasms including odontogenic neoplasms occurs in the oral and craniofacial regions research on cell differentiation phenomenon and cell signaling factors is currently ongoing [11–17, 20–25]. Studies on larger series of SOT are also recommended to help refine the role of these signaling molecules in the development of this neoplasm.