Lateral periodontal cysts (LPCs) are now considered to be an independent entity since the World Health Organization (WHO) classified them as such in the 1992 monograph on "The Histological Typing of Odontogenic Tumors."  Lateral periodontal cysts are defined as nonkeratinized and noninflammatory developmental cysts located adjacent or lateral to the root of a vital tooth.  These cysts arise along the lateral periodontium or within the bone between the roots of erupted vital teeth. 
The first well-documented case of a lateral periodontal cyst was reported by Standish and Shafer in 1958.  In the past, the term lateral periodontal cyst was used to describe any cyst that developed along the lateral root surface, including lateral radicular cysts and odontogenic keratocysts. The diagnosis of lateral periodontal cyst is primarily based on histopathologic features, as certain characteristic histologic features separate it from other odontogenic cysts.  Some authors have postulated that the lateral periodontal cyst is the intrabony counterpart of the gingival cyst in the adult. 
The Botryoid odontogenic cyst (BOC) is a polycystic variant of the lateral periodontal cyst.  In 1973, Weathers and Waldron reported the first case of a multilocular lesion of the jaws, which they called a Botryoid odontogenic cyst.  Clinically, the age group affected with Botryoid odontogenic cyst ranges from 23 to 85 years, with a mean age of 53.8 years. [7, 9] Most often Botryoid odontogenic cysts are multilocular, but unilocularity has also been reported.  Botryoid odontogenic cysts are larger than lateral periodontal cysts, ranging between 5 mm and 45 mm and often extending into the periapical region of involved teeth. [10, 11]
Clinical symptomatology of Botryoid odontogenic cysts can vary from lesions that are asymptomatic to lesions that are exceedingly painful. Paresthesia and tumefaction have also been reported.  Although the histopathologic features of Botryoid odontogenic cysts are similar to lateral periodontal cysts, the recurrence rate is higher, ranging from 15% to 33%.  It is estimated that over 67 cases of Botryoid odontogenic cysts have been reported in the literature. 
Some controversy exists about the relationship of Botryoid odontogenic cysts to lateral periodontal cysts, as some authors prefer to define a Botryoid odontogenic cyst as a "multicystic odontogenic lesion with histological characteristics of lateral periodontal cyst," or "cystic lesion similar to lateral periodontal cyst."  High et al proposed the term "polymorphic odontogenic cyst" to include lesions like Botryoid odontogenic cysts, glandular odontogenic cysts, and intraosseous mucoepidermoid carcinoma,  suggesting with this classification that careful histologic evaluation is necessary to confirm a diagnosis of Botryoid odontogenic cyst and separate it from any of these other possible lesions.
Lateral periodontal cysts do not typically show any racial predilection, although Carter et al reported in their study that lateral periodontal cysts affect white persons most often.  Men and women are equally affected, generally between the fifth to seventh decades of life,  although lateral periodontal cysts have been reported to occur between the ages 14 and 85 years. [7, 13] It has also been reported that there is a statistically significant difference between the mean age of the females affected (40.5 y) as opposed to males (58.2 y), and a hormonal association has been suggested as well.  The incidence of lateral periodontal cysts has been reported to be less than 1%,  and these cysts represent nearly 0.8% of all central cysts of the maxillary bone. 
The source of origin of lateral periodontal cysts remains controversial, with extensive debate in the literature over whether the lesion derives from the dental lamina, reduced enamel epithelium, or rests of Malassez.  Due to the morphologic similarity between the lateral periodontal cyst's epithelial lining, reduced enamel epithelium, and the presence of focal epithelial thickenings similar to that seen in the lining of dentigerous cysts, it has been hypothesized that the source of derivation is the reduced enamel epithelium of an erupting tooth. [4, 14]
The resemblance between dental lamina rests and the glycogen rich epithelial islands of the lateral periodontal cyst raises the possibility of a dental lamina source.  Wysocki et al noted that the majority of lateral periodontal cysts occur on the facial aspect of the alveolus, a distribution consistent with that of the rests of dental lamina but not the rests of Malassez.  The anatomic presence of rests of Malassez in the periodontal ligament supports the hypothesis that such rests are involved in the pathogenesis of lateral periodontal cyst. 
Several additional theories had been proposed regarding the origin of lateral periodontal cysts, including the possibility that the lesions may arise as a result of pulpal infection manifesting itself in a lateral position or chronic periodontal disease activating the rests of Malassez. 
An estimated 50-75% of lateral periodontal cysts occur in the mandible.  These cysts most often affect the mandibular region extending from the lateral incisor to the premolar.  In one report, the majority of cases documented affected the left side of the jaw as opposed to the right. 
Clinical Features and Imaging
Lateral periodontal cysts are most often identified during routine radiography, and the majority of patients are asymptomatic.  Rarely, these cysts can present with expansion of the mandibular or maxillary bone or with perforation of the bone and communication with the overlying gingiva.  The clinical course of a lateral periodontal cyst is slow and insidious, with a growth rate of 0.7 mm per year. [11, 18] The vitality of the adjacent teeth is of significant importance in arriving at a presurgical working diagnosis of lateral periodontal cyst. However, if adjacent teeth are missing or have been treated endodontically, the differential diagnosis can be confusing.
Radiographically, lateral periodontal cysts present as a well-delineated unicystic radiolucency, typically round, teardrop, or oval in shape, and usually less than 1 cm in size (see the image below). The lesions are usually located between the lateral surface of the tooth root between the alveolar crest and the root apex. [2, 3, 5] The cyst most often demonstrates a prominent cortical boundary.  Root divergence of the associated teeth and root resorption can occasionally be seen, [3, 19] with possible loss of the lamina dura and periodontal ligament space. 
The Botryoid lateral periodontal cyst variant typically presents as a multilocular radiolucency between teeth with a pattern that has some semblance to a cluster of grapes.  These loculated clusters represent lobulations and thickened nodules of epithelium when viewed microscopically.
The most common gross finding in a lateral periodontal cyst is that of a thin-walled, soft-tissue sac that has nodular excrescences in the sac wall.
The lateral periodontal cyst is composed of a cystic cavity with a connective tissue wall.  The cyst lining of the lateral periodontal cyst is generally composed of 1-5 cell layers of cuboidal to stratified, nonkeratinized, squamous epithelium, with focal plaquelike thickenings that appear as whorls and mural protrusions (see the following image).  Shear and Pindborg suggested that these thickenings represented an example of the odontogenic epithelium establishing original morphology under pathologic conditions, akin to the thickening of stomatodeal ectoderm in the formation of dental lamina during early odontogenesis. 
Glycogen-rich, clear cells have been observed in lateral periodontal cyst epithelium, which are periodic acid-Schiff (PAS) positive. The epithelium of the cyst is supported by connective tissue without significant inflammation, and artifactual separation of the lining epithelium from the underlying connective tissue can be seen.  Occasional melanin pigment in the cyst lining has been reported. There may be hyalinized areas subjacent to the cystic epithelium. 
The Botryoid odontogenic cyst has a similar histology to that of the lateral periodontal cyst, except for more pronounced plaquelike thickenings, mural protrusions, and a multilocular pattern histologically (see the images below).  The thickened areas are usually separated by thin, fibrous septa. Microscopic assessment is necessary to distinguish lateral periodontal cyst from other odontogenic cysts and pathologic processes. 
Fibroblast growth factors FGF-1 and FGF-2 and receptors FGFR2 and FGFR3 have been identified in the cytoplasm and occasionally the nuclei of the epithelium of lateral periodontal cysts when they were evaluated immunohistochemically. 
Prognosis and Predictive Factors
Lateral periodontal cysts and Botryoid odontogenic cysts should be removed surgically by conservative enucleation or excision, and the patient should be followed radiographically for several years thereafter to monitor for recurrence.  The bone will likely regenerate in the bony defect over 6 months to 1 year. [20, 24] Recurrences are uncommon but have been reported in the literature. [25, 26]
Root divergence caused by lateral periodontal cysts are reduced, or they become normalized after removal of the cyst without the need for orthodontic intervention.  Development of ameloblastoma and squamous cell carcinoma has been reported to occur in lateral periodontal cysts. [27, 28]