1 DEVELOPMENT OF THE JAWS
ODONTOGENESIS central to the process of mammalian tooth de- Similar to tumors of other organ systems, velopment in heterodonts (4). They are the only odontogenic neoplasms and cysts often recapitu- source of mesenchyme able to sustain tooth late the tissues seen in various stages of embryo- development, and give rise not only to most of genesis. A basic understanding of the embryology the dental tissues, but also to the periodontal of odontogenesis is essential for pathologists to tissues that hold teeth in position. understand the features of many lesions that occur in the jaws of children and adults. DEVELOPMENT OF THE TOOTH All ectodermal organs, including hair, teeth, AND SUPPORTING TISSUES and exocrine glands, develop as a result of At about 6 weeks’ gestation, tooth develop- complex interactions between the primitive ment begins as 20 separate invaginations of ecto- epithelium and mesenchyme (1). Tooth germs derm, termed buds, from the dental lamina. Sig- exhibit many features that are morphologically naling molecules secreted by the oral epithelium and molecularly similar to these other epithelial establish cellular fields which form specific teeth. appendages (2). The pharyngeal (branchial) ap- The critical information to model tooth shape paratus consists of a series of paired structures, resides in the neural crest–derived mesenchyme. including arches, pouches, grooves, and mem- Neural crest cells ultimately differentiate into branes, that are numbered in a cranial to caudal highly specialized cell types to produce mature direction. The first branchial arch forms the dental organs (5). The enamel organs that even- mandible and maxilla (3). The arch is surfaced tually form the crowns of each deciduous and by ectoderm that covers mesoderm and neural permanent tooth develop through three identifi- crest ectomesenchyme. Neural crest cells are able stages: bud, cap, and bell (fig. 1-1).
Figure 1-1 ODONTOGENESIS: CAP STAGE The early enamel organ is attached to the epithelial surface of the primitive stoma by the dental lamina.
Tumors and Cysts of the Jaws
Figure 1-2 Figure 1-3 ODONTOGENESIS: BELL STAGE ODONTOGENESIS The inner and outer enamel epithelium and induced Epithelial rests of Serres persist in the connective tissue dental papillae are no longer connected to the surface by following the degeneration of the dental lamina. the dental lamina.
Each dental lamina proliferates apically, point only a basement membrane separates the eventually taking on a bell shape (fig. 1-2). At ameloblasts from the odontoblasts. this time, the connection between the overlying With the apposition of predentin by the stomodeum and the forming enamel organ frag- odontoblasts, the enamel organ begins to show ments into small epithelial islands referred to as a fourth cell layer, termed the stratum interme- the epithelial rests of Serres (fig.1 -3). The enamel dium, directly adjacent to the ameloblasts (fig organ consists of three cell layers: inner enamel 1-4). Once the stratum intermedium forms, am- epithelium, stellate reticulum, and outer enamel eloblasts become more columnar and the nuclei epithelium, and forms a cap over the dental pa- move away from the basement membrane, a pillae. Together, the enamel organ and a dental process called reverse nuclear polarization (figs. papilla are referred to as the tooth germ. 1-5,1-6). Most other columnar secretory cells The bell stage is notable for cellular histo- have nuclei located near the basement mem- differentiation, morphologic alteration, and brane and secrete their product at the opposite early mineralization. Cells of the enamel organ end of the cell, usually into a duct lumen. The directly adjacent to the dental papillae, termed presence of nuclei that are polarized away from the inner enamel epithelium, transform into the basement membrane is a feature of a variety columnar ameloblasts. Through a subsequent of odontogenic tumors. process of induction, the ameloblasts cause cells The terminal differentiation of odontoblasts in the periphery of the dental papillae to dif- is controlled by the inner enamel epithelium ferentiate into columnar odontoblasts. At this and occurs according to a tooth-specific pattern.
Development of the Jaws
Figure 1-4 Figure 1-5 ODONTOGENESIS ODONTOGENESIS Early mineralization is seen at the interface of the inner Early tooth mineralization is characterized, from enamel epithelium and the dental papillae. bottom to top, by basophilic dental papillae, columnar odontoblasts, tall columnar ameloblasts with polarized nuclei and vesiculated cytoplasm, stratum intermedium, and stellate reticulum.
Figure 1-6 ODONTOGENESIS Columnar odontoblasts adjacent to the dental papillae at the bottom lay down predentin matrix and tall columnar ameloblasts at the top produce enamel matrix.
Tumors and Cysts of the Jaws
Figure 1-7 EPITHELIAL RESTS OF MALASSEZ Epithelial rests, remnants of the Hertwig epithelial root sheath, persist in the periodontal ligament which attaches the tooth root cementum to the surrounding cortical bone. Inset shows rest of Malassez at higher power.
During the cap-bell transition, cells from the in- proliferation is responsible for the formation ner enamel epithelium segregate to form single and enlargement of cysts and neoplasms under or multiple cusps (6). When crown formation is certain physiologic conditions (7). completed, the enamel organ degenerates into a Dentin that is not covered by enamel is cov- thin layer of cuboidal or squamous cells, referred ered by cementum which is a form of modified to as the reduced enamel epithelium. Like the osteoid produced by cementoblasts that are rests of Serres, the reduced enamel epithelium indistinguishable from osteoblasts. The cemen- retains the potential to form odontogenic cysts tum is attached via Sharpey fibers through the and tumors. periodontal ligament to a thin layer of cortical Tooth root formation continues through bone termed the lamina dura. the apposition of dentin tubules, which are Because the mineralized tooth constitutes the eventually sheathed in cementum, necessary hardest substance in humans and is resistant to for attachment to bone via Sharpey fibers of the natural forces of decomposition after death, the periodontal ligament. For the apposition of the features of tooth development also play an root dentin to occur, the odontoblasts require instrumental role in forensic identification, an induction effect from cells of the enamel and in the evolutionary classification of our organ. The enamel epithelium forms a collar of hominid ancestors (8). cells known as Hertwig epithelial root sheath, While normal tooth development usually which proliferates apically and induces the dif- ends by about age 21, the potential for the ferentiation of odontoblasts. As it proliferates development of reactive, cystic, or neoplastic through the forming jaw bone, the root sheath lesions of the jaws persists in the remnants of apically leaves behind residual epithelial islands odontogenesis that are left behind. In addition known as rests of Malassez (fig.1 -7). These rests to the reduced enamel epithelium and un- persist in the periodontal ligament and provide named rests often found in the tooth follicle, an additional source of odontogenic epithelium as well as the rests of Serres or Malassez, the capable of forming cysts and tumors. Even original basal epithelium, which in the adult is though they appear inactive microscopically, represented by the gingiva and alveolar mucosa, experimental evidence has shown that the retains the capability to form odontogenic tis- rests of Malassez continue to have low levels sue. This capability is supported by the forma- of mitotic activity, indicating that cellular tion of peripheral odontogenic tumors, such as
Development of the Jaws
the ameloblastomas that appear to bud directly Nestin, one of the intermediate filaments from the basal cells of the gingiva. constituting the cytoskeleton, is a marker of neural stem cells or progenitor cells. Nestin is RECENT ADVANCES also involved in the differentiation of odon- While the process of odontogenesis has been togenic ectomesenchyme to odontoblasts and characterized for decades, recent research has in the formation of mesenchymal tissues in shed more light on this process at the molecular odontogenic tumors (14). level. More than 300 genes have so far been as- The genetic causes of most cases of abnormal sociated with tooth development. Most of these enamel development, such as amelogenesis genes are associated with signaling pathways imperfecta, are associated with mutations in mediating cellular communication between epi- enamel matrix specific genes. Recent evidence, thelial and mesenchymal tissues (9). Recently, however, has shown that mutations in genes micro-RNA pathways have emerged as impor- involved in pH regulation may affect enamel tant regulators of various aspects of embryonic structure as well (15). development including odontogenesis (10). New treatments for systemic disease also Restriction of the signaling peptide encoded effect tooth development. The use of oral and by the sonic hedgehog gene in localized thick- intravenous bisphosphonates in young children enings of oral epithelium has been shown with diseases such as osteogenesis imperfecta to play a crucial role during the initiation of inhibits tooth formation and eruption, and has odontogenesis (11). While the sonic hedgehog induced several types of dental abnormalities, gene helps regulate tooth growth and helps to which may be attributed to altered osteoclastic determine the shape of the tooth, signaling is activities (16). not essential for differentiation of ameloblasts By combining the knowledge of molecular or odontoblasts (12). regulation of tooth development with the re- Members of the Msx homeobox gene family cent breakthroughs in stem cell research, tooth are expressed at sites of epithelial-mesenchymal regeneration may someday be possible (17). The interaction during tooth formation. Msx1-defi- transfer of embryonic tooth primordia into the cient mice exhibit an arrest in tooth develop- adult jaw has resulted in the formation of tooth ment at the bud stage, while Msx2-deficient structures, indicating that embryonic primordia mice exhibit defects in later stages of tooth can continue to develop in an adult environ- development. (13). ment (18).
Tumors and Cysts of the Jaws
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