**2. Radicular cysts**

#### **2.1 Radicular and residual cysts**

Radicular cysts are inflammatory cyst of jaw bones developing as a result of proliferation of the epithelium on the site of inflammation. They are the types of inflammatory lesions, which develop from epithelial residues of Hertwig lining in the process of periapical periodontitis after pulp necrosis. Cysts, which develop like this, are predominantly located around root apex and/or on the lateral side of the root, and in that case, they are called lateral radicular cysts. It often happens that radicular cyst remains in jaw bones after removal of the offending tooth, and in that case, it is called as residual cyst [1].

Radicular and residual cysts are by far the most common cystic lesions in the jaws, comprising 30% of all odontogenic cysts over a 30-year period according to results published by Jones et al. [3]. According to the age distribution of radicular cysts, most occur in patients who are in the third decade of life [3, 4]. There are many cases of patients who are between 40 and 60 years old, and after that, the number of cases decreases. Only few cases are seen in children even though dental caries commonly occurs in children.

Numerous studies have shown that radicular cysts occur more often in men than in women. The lower frequency in women may be because they take more care about mouth hygiene, especially the maxillary anterior incisors, where occurrence of cysts is very common. However, trauma to maxillary anterior teeth usually occurs to men [3].

Generally, radicular cysts show no symptoms and are discovered only after taking periapical radiographs of teeth with non-vital pulps. However, radicular cyst is the most common cause of swelling of the jaws, which patients often complain for. In the beginning, the enlargement is bony hard but as the cyst grows, the covering bone becomes very thin, and the swelling exhibits "egg shell crackling" or "springiness." The lesion becomes fluctuant only when the cyst has completely eroded the bone. In the mandible there is labial or buccal enlargement, rarely lingual, whereas in the maxilla, it is usually buccal or palatal [1].

Among other symptoms, pain and infection are very common in radicular cysts. Unless there is an infection, patients with radicular cyst usually feel no pain. But, it seems like there is no correlation between symptoms and infection. In the study done by Vier and Figueiredo, 21 out of 24 cysts were described as cavities which are filled with pus [5]. Authors did not correlate this finding and clinical symptoms, but it is unlikely that there is a relationship because most cysts are symptomless. In some cases patients complain of pain even though there is no evidence of infection and no

**61**

*Oral Pathology: Gene Expression in Odontogenic Cysts DOI: http://dx.doi.org/10.5772/intechopen.80555*

**2.2 Pathogenesis of radicular cysts**

endotoxins in radicular than in the other cysts [13].

pro-inflammatory molecules as well [14, 15].

*2.2.2 Phase of cyst formation*

three phases.

*2.2.1 The phase of initiation*

evidence of acute inflammation is present histologically after the cyst is removed [5]. On the other hand, some patients have histologically inflamed and clinically infected cysts, but they feel no pain [6]. A number of authors believe that there are cyst-prone individuals who are susceptible to developing radicular cysts because it often happens that more than one cyst is seen in one patient [7]. This can be supported and explained by the fact that occurrence of cysts is rare in relation to the large numbers of carious teeth which have dead pulps. Possibly, an immune mechanism inhibits formation of the cyst in most individuals, and patients who are prone to cyst development have a defect in suppression mechanism and immunological surveillance [8]. There is a possibility that some individuals are genetically susceptible to radicular cyst development. Residual radicular cysts are cysts which remain after the non-vital offending tooth is removed. Studies have shown that they represent approximately 10% of all odontogenic cysts [9, 10]. In the study, Nair et al. considered that the type of cyst was important because of its persistence after treatment [11]. His findings confirmed the work of Simon [12] who stated that there were two types of radicular cyst: true radicular cyst, which contains a closed cavity lined by the epithelium, and the periapical pocket cyst in which the epithelium is attached to the margins of the apical foramen, so that the cyst lumen stays open to the root canal which is affected. Pocket cyst heals after treatment and tooth extraction, but true cyst, which is completely enclosed, is self-sustaining and persists even if there is no cause present [12].

The pathogenesis of radicular cysts can be separated into three phases: the phase

Scientists agree that the epithelial cell rests of Malassez found in the periodontal ligament in periapical granulomas which are connected to necrotic and inflamed pulps are, in fact, the source of cyst linings [13]. The epithelial cell rests begin to multiply by inflammation which results from bacteria and debris discharged from the dead pulp. Bacterial endotoxins released from the necrotic pulp may be the key factor which initiates the inflammation and immune response and cause epithelial proliferation [1]. Meghji et al. investigated cyst fluids and grew cyst explants from radicular cysts and other cyst types and revealed that there are higher levels of

Immunological studies are crucial in further understanding of granulomas and cysts, and they indicate that humoral and cell-mediated processes are involved in the pathogenesis of these lesions. Immunological studies have also demonstrated that inflammatory cytokines have an important role in the proliferation of epithelial cell rests. Stern et al. demonstrated that T lymphocyte infiltrates are involved in the development of periapical granulomas [1]. After a large number of studies, it became clear that endotoxins and inflammatory cytokines are highly involved in stimulation of the epithelial proliferation and they function as chemotactic and

Pathogenesis of a radicular cyst is the next phase of cyst development, and it involves the process of cavity being lined by odontogenic epithelium. Two theories have been proposed, and both of them are reasonable and may function

of initiation, the phase of cyst formation, and the phase of enlargement. Many studies have been done to investigate the mechanisms which are involved into these

#### *Oral Pathology: Gene Expression in Odontogenic Cysts DOI: http://dx.doi.org/10.5772/intechopen.80555*

*Gene Expression and Control*

**2. Radicular cysts**

**Figure 1.**

**2.1 Radicular and residual cysts**

*Modified classification of cysts found in oral and maxillofacial regions [1].*

case, it is called as residual cyst [1].

caries commonly occurs in children.

in the maxilla, it is usually buccal or palatal [1].

Radicular cysts are inflammatory cyst of jaw bones developing as a result of proliferation of the epithelium on the site of inflammation. They are the types of inflammatory lesions, which develop from epithelial residues of Hertwig lining in the process of periapical periodontitis after pulp necrosis. Cysts, which develop like this, are predominantly located around root apex and/or on the lateral side of the root, and in that case, they are called lateral radicular cysts. It often happens that radicular cyst remains in jaw bones after removal of the offending tooth, and in that

Radicular and residual cysts are by far the most common cystic lesions in the jaws, comprising 30% of all odontogenic cysts over a 30-year period according to results published by Jones et al. [3]. According to the age distribution of radicular cysts, most occur in patients who are in the third decade of life [3, 4]. There are many cases of patients who are between 40 and 60 years old, and after that, the number of cases decreases. Only few cases are seen in children even though dental

Numerous studies have shown that radicular cysts occur more often in men than in women. The lower frequency in women may be because they take more care about mouth hygiene, especially the maxillary anterior incisors, where occurrence of cysts is very common. However, trauma to maxillary anterior teeth usually occurs to men [3]. Generally, radicular cysts show no symptoms and are discovered only after taking periapical radiographs of teeth with non-vital pulps. However, radicular cyst is the most common cause of swelling of the jaws, which patients often complain for. In the beginning, the enlargement is bony hard but as the cyst grows, the covering bone becomes very thin, and the swelling exhibits "egg shell crackling" or "springiness." The lesion becomes fluctuant only when the cyst has completely eroded the bone. In the mandible there is labial or buccal enlargement, rarely lingual, whereas

Among other symptoms, pain and infection are very common in radicular cysts. Unless there is an infection, patients with radicular cyst usually feel no pain. But, it seems like there is no correlation between symptoms and infection. In the study done by Vier and Figueiredo, 21 out of 24 cysts were described as cavities which are filled with pus [5]. Authors did not correlate this finding and clinical symptoms, but it is unlikely that there is a relationship because most cysts are symptomless. In some cases patients complain of pain even though there is no evidence of infection and no

**60**

evidence of acute inflammation is present histologically after the cyst is removed [5]. On the other hand, some patients have histologically inflamed and clinically infected cysts, but they feel no pain [6]. A number of authors believe that there are cyst-prone individuals who are susceptible to developing radicular cysts because it often happens that more than one cyst is seen in one patient [7]. This can be supported and explained by the fact that occurrence of cysts is rare in relation to the large numbers of carious teeth which have dead pulps. Possibly, an immune mechanism inhibits formation of the cyst in most individuals, and patients who are prone to cyst development have a defect in suppression mechanism and immunological surveillance [8]. There is a possibility that some individuals are genetically susceptible to radicular cyst development.

Residual radicular cysts are cysts which remain after the non-vital offending tooth is removed. Studies have shown that they represent approximately 10% of all odontogenic cysts [9, 10]. In the study, Nair et al. considered that the type of cyst was important because of its persistence after treatment [11]. His findings confirmed the work of Simon [12] who stated that there were two types of radicular cyst: true radicular cyst, which contains a closed cavity lined by the epithelium, and the periapical pocket cyst in which the epithelium is attached to the margins of the apical foramen, so that the cyst lumen stays open to the root canal which is affected. Pocket cyst heals after treatment and tooth extraction, but true cyst, which is completely enclosed, is self-sustaining and persists even if there is no cause present [12].

#### **2.2 Pathogenesis of radicular cysts**

The pathogenesis of radicular cysts can be separated into three phases: the phase of initiation, the phase of cyst formation, and the phase of enlargement. Many studies have been done to investigate the mechanisms which are involved into these three phases.

#### *2.2.1 The phase of initiation*

Scientists agree that the epithelial cell rests of Malassez found in the periodontal ligament in periapical granulomas which are connected to necrotic and inflamed pulps are, in fact, the source of cyst linings [13]. The epithelial cell rests begin to multiply by inflammation which results from bacteria and debris discharged from the dead pulp. Bacterial endotoxins released from the necrotic pulp may be the key factor which initiates the inflammation and immune response and cause epithelial proliferation [1]. Meghji et al. investigated cyst fluids and grew cyst explants from radicular cysts and other cyst types and revealed that there are higher levels of endotoxins in radicular than in the other cysts [13].

Immunological studies are crucial in further understanding of granulomas and cysts, and they indicate that humoral and cell-mediated processes are involved in the pathogenesis of these lesions. Immunological studies have also demonstrated that inflammatory cytokines have an important role in the proliferation of epithelial cell rests. Stern et al. demonstrated that T lymphocyte infiltrates are involved in the development of periapical granulomas [1]. After a large number of studies, it became clear that endotoxins and inflammatory cytokines are highly involved in stimulation of the epithelial proliferation and they function as chemotactic and pro-inflammatory molecules as well [14, 15].

#### *2.2.2 Phase of cyst formation*

Pathogenesis of a radicular cyst is the next phase of cyst development, and it involves the process of cavity being lined by odontogenic epithelium. Two theories have been proposed, and both of them are reasonable and may function

#### **Figure 2.**

*Schematic representation of the development of radicular cyst. Starting from the left, superficial caries forms first, followed by medium and deep caries. Untreated deep caries leads to total pulp inflammation. Subsequently, necrosis of the pulp appears, which becomes infected. The resulting infection of the root canal initiates the epithelial remnants of Hertwig sheath (Malassez epithelial rests) to proliferate. Once the cells proliferate, the epithelial nest is formed. When the epithelial nest reaches the size of 1 cm, the center becomes necrotic leading to the formation of future cystic cavity, which becomes lined with the epithelium. For unknown reasons, this epithelium starts secreting fluid, which is called cystic fluid. These steps lead to the formation of radicular cyst, a round cavity filled with fluid and lined with the epithelium and fibrous connective tissue. This description of the radicular cyst development is the prevailing theory.*

independently. The primarily accepted theory proposes that epithelial cells multiply and enclose the surface of connective tissue of an abscess cavity or cavity, which resulted from the breakdown of connective tissue by activity of proteolytic enzymes [16]. The secondary one, which is supported more, states that radicular cyst forms inside of the multiplying epithelial mass in periapical granuloma by cell death in the center (**Figure 2**) [16].
