Etiology and Pathogenesis

A periapical cyst develops from a preexisting periapical granuloma, which is a focus of chronically inflamed granulation tissue located at the apex of a nonvital tooth (Figures 10-1 and 10-2). Periapical granulomas are initiated and maintained by the degradation products of necrotic pulp tissue. Stimulation of the resident epithelial rests of Malassez occurs in response to the products of inflammation (Table 10-1). Cyst formation occurs as a result of epithelial proliferation, which helps to separate the inflammatory stimulus (necrotic pulp) from the surrounding bone (Figure 10-3).

Breakdown of cellular debris within the cyst lumen raises the protein concentration, increasing osmotic pressure and resulting in fluid transport across the epithelial lining into the lumen from the connective tissue side. Fluid ingress assists in outward growth of the cyst. With osteoclastic bone resorption, the cyst expands. Other bone-resorbing factors, such as prostaglandins, interleukins, and proteinases, from inflammatory cells and cells in the peripheral portion of the lesion permit additional cyst enlargement.

Clinical Features

Periapical cysts constitute approximately one half to three fourths of all cysts in the jaws (Box 10-1). The age distribution peaks in the third through sixth decades. Of note is the relative rarity of periapical cysts in the first decade, even though caries and nonvital teeth are rather common in this age group. Most cysts are located in the maxilla, especially the anterior region, followed by the maxillary posterior region, the mandibular posterior region, and finally the mandibular anterior region.

Periapical cysts usually are asymptomatic and often are discovered incidentally during routine dental radiographic examination (Figures 10-4 and 10-5). They cause bone resorption but generally do not produce bone expansion. By definition, a nonvital tooth is necessary for the diagnosis of a periapical cyst.

Radiographically, a periapical cyst cannot be differentiated from a periapical granuloma. Studies have shown that a provisional radiographic diagnosis was correct in 48% of cases for periapical granuloma and 36% for radicular cyst, with an incidence of cystic change in inflammatory periapical lesions of pulpal origin of approximately 30%. Use of more advanced radiographic techniques such as cone beam computed tomography (CBCT) has not been shown to increase the level of accuracy in distinguishing periapical granulomas from radicular cysts. The radiolucency associated with a periapical cyst is generally round to ovoid, with a narrow, opaque margin that is contiguous with the lamina dura of the involved tooth. This peripheral radiopaque component may not be apparent if the cyst is rapidly enlarging. Cysts range from a few millimeters to several centimeters in diameter, although most measure less than 1.5 cm. In long-standing cysts, root resorption of the offending tooth and occasionally of adjacent teeth may be seen.

Histopathology

The periapical cyst is lined by nonkeratinized stratified squamous epithelium of variable thickness (Figure 10-6). Transmigration of inflammatory cells through the epithelium is common, with large numbers of neutrophils (polymorphonuclear leukocytes [PMNs]) and fewer numbers of lymphocytes involved. The underlying supportive connective tissue may be focally or diffusely infiltrated with a mixed inflammatory cell population. The molecular signature of a periapical granuloma differs from that of the radicular cyst, with a high level of matrix metalloproteinase (MMP) activity compared with that within a radicular cyst. Plasma cell infiltrates and associated refractile and spherical intracellular Russell bodies, representing accumulated gamma globulin, are often found and sometimes dominate the microscopic picture. Foci of dystrophic calcification, cholesterol clefts, and multinucleated foreign body–type giant cells may be seen subsequent to hemorrhage in the cyst wall. A foreign body reaction to vegetable matter (Figure 10-7) (pulse or seed granuloma) is occasionally found in periapical cyst walls, indicating apical communication with the oral cavity through the root canal and carious lesion.

In a small percentage of periapical cysts (and dentigerous cysts), hyaline bodies, or Rushton bodies, may be found. Such bodies within the epithelial lining are characterized by a hairpin or slightly curved shape, concentric lamination, and occasional basophilic mineralization. Previous hemorrhage is believed to be related to the origin of these bodies, but their presence is of no clinical significance.

Differential Diagnosis

Radiographically, a differential diagnosis for periapical cyst must include periapical granuloma. In areas of previously treated apical pathology, a surgical defect or a periapical scar might also be considered. In the anterior mandible, periapical radiolucency should be distinguished from the earliest developmental phase of periapical cemento-osseous dysplasia. In the posterior quadrants, apical radiolucencies must be distinguished from a traumatic bone cyst. Occasionally, developmental odontogenic cysts, odontogenic tumors, giant cell lesions, metastatic disease, and primary osseous tumors may mimic a periapical cyst radiographically. In all of these considerations, associated teeth are vital.

Treatment and Prognosis

A periapical lesion (cyst/granuloma) may be successfully managed by extraction of the associated nonvital tooth and curettage of the apical zone. Alternatively, a root canal filling may be performed in association with an apicoectomy and direct curettage of the lesion. The third, and most often used, option involves performing a root canal filling only, because most periapical lesions are granulomas and resolve after removal of the inflammatory stimulus (necrotic pulp). Surgery (apicoectomy and curettage) is performed for lesions that are persistent, indicating the presence of a cyst or inadequate root canal treatment. The presence of endodontic filling material within a significant proportion of persistent apical radiolucencies following endodontic treatment suggests a possible causal relationship, with emphasis directed toward proper treatment to restrict extrusion of filling material beyond the periapex.

When the necrotic tooth is extracted but the cyst lining is incompletely removed, a residual cyst may develop months to years after the initial extirpation (Figure 10-8). If a residual cyst or the original periapical cyst remains untreated, continued growth can cause significant bone resorption and weakening of the mandible or maxilla. Complete bone repair is usually seen in adequately treated periapical and residual cysts.

Lateral Periodontal Cyst

A lateral periodontal cyst is a nonkeratinized developmental cyst occurring adjacent or lateral to the root of a tooth. Gingival cysts of the adult are histogenetically and pathologically similar and are also discussed here.

Clinical Features

Most lateral periodontal cysts and gingival cysts of the adult occur in the mandibular premolar and cuspid regions and occasionally in the incisor area (Figure 10-9; Box 10-2). In the maxilla, lesions are noted primarily in the lateral incisor region. A distinct male predilection has been noted for lateral periodontal cysts, with a greater than 2 : 1 distribution. Gingival cysts show a nearly equal gender predilection. The median age for both types of cysts is between the fifth and sixth decades of life, with a range of 20 to 85 years for lateral periodontal cysts, and 40 to 75 years for gingival cysts of the adult.

Box 10-2   Lateral Periodontal Cyst

Origin from rests of the dental lamina in bone

Occurs along lateral surface of tooth root

Associated with a vital tooth

Most found in mandibular canine-premolar area

Males affected more than females

Treated by cystectomy; multilocular variant has recurrence potential

Dental lamina rests in soft tissue give rise to gingival cysts of adult.

Clinically, a gingival cyst appears as a small soft tissue swelling within or slightly inferior to the interdental papilla (Figure 10-10). It may assume a slightly bluish discoloration when it is relatively large. Most cysts are less than 1 cm in diameter. Radiography reveals no findings.

A lateral periodontal cyst presents as an asymptomatic, well-delineated, round or teardrop-shaped unilocular (and occasionally multilocular) radiolucency with an opaque margin along the lateral surface of a vital tooth root. Root divergence is rarely seen. The term botryoid odontogenic cyst is sometimes used when the lesion is multilocular.

Histopathology

Both the lateral periodontal cyst (Figure 10-11) and the gingival cyst of the adult (Figure 10-12) are lined by a thin, nonkeratinized epithelium. Clusters of glycogen-rich, clear epithelial cells may be noted in nodular thickenings of the cyst lining.

Gingival Cyst of the Newborn

Gingival cysts of the newborn are also known as dental lamina cysts of the newborn, or Bohn’s nodules. These cysts typically appear as multiple nodules along the alveolar ridge in neonates. It is believed that fragments of the dental lamina that remain within the alveolar ridge mucosa after tooth formation proliferate to form these small, keratinized cysts. In the vast majority of cases, these cysts are self-limiting and degenerate, and they involute or rupture into the oral cavity within a few weeks to a few months.

Histologically, this cyst is lined by a bland stratified squamous epithelium (Figure 10-13). Treatment is not necessary because nearly all involute spontaneously or rupture before the patient is 3 months of age.

Similar epithelial inclusion cysts may occur along the midline of the palate (palatine cysts of the newborn, or Epstein’s pearls). These cysts are of developmental origin and are derived from epithelium that is included in the fusion line between the palatal shelves and the nasal processes. No treatment is necessary because they fuse with the overlying oral epithelium, discharge their contents, and resolve spontaneously.

Dentigerous Cyst

Dentigerous or follicular cysts are the second most common type of odontogenic cyst, and the most common developmental cyst of the jaws. In children from 2 to 14 years of age, dentigerous cysts account for 49% of intraosseous cystic lesions, with eruption cysts, odontogenic keratocysts, and radicular cysts accounting for more than 10% each. By definition, a dentigerous cyst is attached to the tooth cervix at the enamel-cementum junction, and it encloses the crown of the unerupted tooth.

Clinical Features

Dentigerous cysts are most commonly seen in association with third molars and maxillary canines, which are the most commonly impacted teeth (Box 10-3; Figure 10-14). The highest incidence of dentigerous cysts occurs during the second and third decades. A greater incidence in males has been noted, with a ratio of 1.6 : 1 reported.

Box 10-3   Dentigerous Cyst

Clinical

Second most common odontogenic cyst after periapical cyst

Third molars and canine teeth most commonly affected

Stimulus unknown

Radiographic Features

Lucency associated with crown of impacted tooth

Histopathology

Lined by nonkeratinized stratified squamous epithelium

Proliferation of reduced enamel epithelium

Possible Complications

Extensive bone destruction with growth

Resorption of adjacent tooth roots

Displacement of teeth

Neoplastic transformation of lining (rare)—ameloblastoma formation; carcinoma very rarely

Symptoms generally are absent, and delayed eruption is the most common indication of dentigerous cyst formation. This cyst is capable of achieving significant size, occasionally with associated cortical bone expansion, but rarely does it reach a size that predisposes the patient to a pathologic fracture.

Radiographically, a dentigerous cyst presents as a well-defined, unilocular radiolucency with corticated margins in association with the crown of an unerupted tooth. The unerupted tooth is often displaced (Figure 10-15). These cysts range in size from several millimeters to several centimeters, where they may compromise jawbone integrity and produce facial asymmetry. In the mandible, associated radiolucency may extend superiorly from the third molar site into the ramus or anteriorly and inferiorly along the body of the mandible. In maxillary dentigerous cysts involving the canine region, extension into the maxillary sinus or to the orbital floor may be noted. Resorption of roots of adjacent erupted teeth may occasionally be seen.

A variant of the dentigerous cyst arising at the bifurcation of molar teeth is the paradental cyst or buccal bifurcation cyst (Figure 10-16). Originally, this cyst was described along the buccal root surface of partially erupted mandibular third molar teeth, but later, involvement of other mandibular molar teeth was recognized. Often in these latter circumstances, the molar teeth are fully erupted. Radiographically, paradental cysts are characterized as well-circumscribed radiolucencies in the buccal bifurcation region. Often buccal tipping of the crown can be demonstrated by occlusal radiography.

Histopathology

Microscopically, the dentigerous cyst is formed by a fibrous connective tissue wall and is lined by stratified squamous epithelium (Figures 10-17 to 10-19). In an uninflamed dentigerous cyst, the epithelial lining is nonkeratinized and tends to be approximately four to six cell layers thick. On occasion, numerous mucous cells, ciliated cells, and, rarely, sebaceous cells may be found in the lining of the epithelium. The epithelium–connective tissue junction is generally flat, although in cases of secondary inflammation, epithelial hyperplasia may be noted.

Eruption Cyst

An eruption cyst results from fluid accumulation within the follicular space of an erupting tooth (Figure 10-20). The epithelium lining this space is simply reduced enamel epithelium. With trauma, blood may appear within the tissue space, forming an eruption hematoma. No treatment is needed because the tooth erupts through the lesion. Subsequent to eruption, the cyst disappears spontaneously without complication.

Glandular Odontogenic Cyst

The rare glandular odontogenic cyst, or sialo-odontogenic cyst, was first described in 1987 and has some histologic features that suggest a mucus-producing salivary gland tumor (low-grade mucoepidermoid carcinoma).

Clinical Features

A strong predilection is seen for the mandible (80%), especially the anterior mandible (Box 10-4; Figure 10-21). Maxillary lesions tend to be localized to the anterior segment. A slow growth rate is characteristic and symptoms are absent. Jaw expansion is not uncommon, particularly in association with mandibular lesions. The gender ratio is approximately 1 : 1. The mean age is 50 years, with a wide age range from the second through ninth decades.

Box 10-4   Glandular Odontogenic Cyst (Sialo-odontogenic Cyst)

Rare developmental cyst

Clinical Features

Adults

Either jaw (anterior > posterior)

Histopathology

Focal mucous cells, pseudoducts

Resembles low-grade mucoepidermoid carcinoma

Behavior

Locally aggressive; recurrence potential

>, More frequently affected than.

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