Cysts of Orofacial Region
The word ‘cyst’ is derived from Greek word kystitis meaning bladder. Kramer (1974) defined cyst as a pathological cavity having fluid, semifluid or gaseous contents and which is not created by the accumulation of pus. It is frequently, but not always, lined by the epithelium. Cysts may arise due to trauma, inflammation and degeneration or retention. They are called true cysts if lined by epithelium and, pseudocysts (false) if not lined by epithelium. During the initial stages, when the cysts are small they are usually asymptomatic. Secondary infection may result in the formation of abscess, cellulitis, osteomyelitis and subsequent sinus formation. As the cyst enlarges it may cause displacement of roots of teeth, resorption of roots, paresthesia, expansion of the cortical plates and eventually result in pathologic fracture of the jaw.
Malcolm Harris (1975) summarized various theories that explain cyst expansion. Mural growth theory, hydrostatic enlargement, and role of bone resorbing factors are the theories that have been proposed by various authors to explain enlargement of cysts.
1. Peripheral cell division: It is proposed that the cyst enlarges at the peripheries because of active division of the cells of the epithelium lining the cyst (Figure 1). It is believed that the division of these cells is a response to any irritating stimulus. The theory further suggests that once the stimulus is withdrawn the cyst regresses in size. This theory has not found many supporters as cyst regression will result in irregular inner surface of the cyst as the bone surrounding the cyst offers resistance. One should remember that the contents of the cyst will support the cystic lining and it can cause rapid resorption of surrounding bone to accommodate the enlarging cyst.
2. Accumulation of cellular contents: This theory was proposed by Kramer (1974) to explain the enlargement of OKCs. He proposed that as mural squames are shed off the lining epithelium they accumulate, thereby increasing the cyst volume. The sites of expansion and growth are represented by finger-like projections which are zones of active cell division or proliferation (Figure 2).
It is also believed that these finger-like extensions are formed because keratocysts have very poor bone resorbing properties. Hence, they proliferate along the cancellous bone which is less dense than the cortical bone. This explains the fact why keratocysts very rarely cause expansion or resorption of the cortical plates.
Kubota et al (2000) studied the role of interleukin-1 alpha (IL-α) and matrix metalloproteinase-9 (MMP-9) in the expansion of odontogenic cysts. They found that an active form of MMP-9 was present in OKC fluids more frequently than dentigerous cyst and radicular cyst fluids. However, proMMP-9 was present in all cyst fluids.
Oka et al (2005) studied the effects of positive intra-cystic fluid pressure in OKCs. They proposed that the positive intracystic pressure may play a crucial role in OKC growth via stimulating the expression of IL-1 in epithelial cells.
It has been proposed that accumulation of fluids within the cystic cavity will cause expansion of the cyst wall. The fluid accumulation can occur from secretion by the goblet cells that line the follicular cysts or by transudation or exudation from capsular capillaries in periodontal cysts as proposed by Main (1970) and hemorrhage in follicular and periodontal cysts as proposed by Harris and Pannell (1973).
James (1926) and Tratman (1939) proposed the osmotic theory or dialysis to explain hydrostatic enlargement of cysts. The cyst wall and the capillaries in the cystic capsule are made up of high molecular weight proteins like fibrin and α2-globulins which aid in increasing the permeability of the capsular capillaries and the cyst walls.
It was found that the mean osmolality of cystic fluid is 10 milliosmoles higher than that of serum. This gradient helps in the accumulation of all the shed degenerated cells from the lining of the cyst. As the cyst has inadequate lymphatic drainage, the fluid from the capsular capillaries enters and accumulates within the cyst thereby aiding its enlargement.
Harris et al (1973) proposed that cyst tissue (capsule) contains a combination of prostaglandins E2 and E3, which are considered very potent bone resorbing factors. It is believed that the leukocytic and bone resorbing factors aid in bone resorption. It is believed that the keratocyst secretes comparatively lesser amount of bone resorbing factors per unit surface area compared to other cysts (periodontal cyst, radicular cyst). This explains the burrowing nature or intramedullary growth of the keratocyst.
The odontogenic cysts are derived from epithelium associated with the development of dental apparatus. It is estimated that odontogenic cysts make up approximately 90% of the jaw cysts. These cysts are generally lined by stratified squamous epithelium. However, some developmental or fissural cysts in the maxilla will have respiratory epithelium as the lining.
Gingival cyst of infants or newborns is an odontogenic cyst which is developmental in nature. Like the name suggests these cysts are seen in infants. These cysts are seldom seen after 3 months of age. They arise from the epithelial remnants of dental lamina called cell rests of Serres. Clinically, the cyst is seen on the crest of the maxillary and mandibular dental ridges and appears creamish white. These cysts are usually minute in size and rarely exceed 3 mm in diameter and commonly occur on the maxillary alveolar ridge.
Histopathological evaluation reveals a keratin filled cyst lined by parakeratinized epithelium. Gingival cysts in infants need no treatment as they tend to undergo involution and disappear. Most cysts tend to rupture spontaneously.
The eruption cyst is a type of soft tissue cyst associated with erupting teeth. It surrounds the crown of a tooth that has already erupted through bone but impeded by the overlying soft tissue. Kuczek et al (2003) reported a case where a boy developed an eruption cyst who was administered cyclosporin A (potent immunomodulatory agent) subsequent to a cardiac transplantation. Cyclosporin A was replaced with tacrolimus and there was no new cyst formation. The authors proposed that the formation of an eruption cyst may be an adverse effect of cyclosporin A in children with erupting teeth.
Eruption cysts are usually seen in childhood. These cysts are commonly seen in the age groups of 5 and 9 years. However, Woldenberg (2004) published a case report of an eruption cyst in the maxilla of a 40-year-old female. Studies by Anderson (1990), Woldenberg (2004) and Aguiló (1998) show that these cysts are more prevalent in the maxillary arch. In a study of 24 cases of eruption cysts by Bodner et al (2004), it was found that eruption cysts were associated with natal teeth in two cases, with primary teeth in 10 cases and with permanent teeth in 12 cases. It was seen that males more commonly presented with eruption cysts than females (2:1). The primary mandibular central incisors and the permanent first molars were the most common site involved. Though most of the eruption cysts are reported as solitary entities, literature review reveals report of a patient presenting with multiple eruption cysts. Ramón Boj and García-Godoy (2000) described a case of a 15-month-old child who had six eruption cysts simultaneously.
On clinical examination, the cyst is visible as a soft fluctuant mass on the alveolar ridges and may vary in size from about 1 to 1.5 cm in diameter. It may have the same coloration of healthy oral mucosa or appear bluish or bluish black. Eruption cyst histologically mimics dentiger-ous cyst.
It is an odontogenic cyst formed by the accumulation of fluid between reduced enamel epithelium and enamel surface. It surrounds the crown of an impacted tooth and is attached to its neck. The crown of the involved tooth projects into the cyst lumen. It is estimated that 10% of impacted teeth are associated with dentigerous cysts. Dentigerous cysts may also be seen associated with supernumerary teeth and odontomas.
It occurs frequently in association with impacted mandibular (Figure 3), maxillary third molars (Figure 4), and maxillary canines (Figure 5). Dentigerous cyst is commonly seen in the 2nd and 3rd decades of life. Males are relatively more predisposed. It grows aggressively and produces facial asymmetry, bony expansion, displacement and resorption of teeth. Entire ramus might be hollowed if associated with mandibular third molar (Figure 6A, B). In case of maxillary canine, anterior maxilla is expanded. There will be no pain unless secondarily infected. On aspiration, yellow-colored fluid is obtained.
Figure 3 Orthopantomograph (OPG) showing dentigerous cyst (multilocular) associated with impacted right lower third molar and a supernumerary tooth displaced superiorly approximating the sigmoid notch. Courtesy: Dr NVS Sekhar Reddy
Radiographically, dentigerous cysts exhibit three different presentations, namely, the central, lateral and circumferential types. In central variety, the cyst symmetrically envelops crown. The cyst occurs on lateral aspect of the crown in lateral variety and envelops crown entirely in circumferential variety (Figure 7). Dentigerous cyst may appear as welldefined unilocular or multilocular radiolucency (Figure 8A, B). Occasionally these cysts may cause displacement and resorption of the adjacent teeth (Figure 9). Large cysts often cause expansion of the cortical plates.
It has no characteristic microscopic features. It has cyst lining and connective tissue wall. The connective tissue wall consists of very loose fibrous connective tissue and sparse collagenized myxomatous tissues. It has presence of odontogenic epithelium (Figure 10). The inflammation leads to presence of Rushton bodies of hematogeneous origin in the lining epithelium. Cholesterol clefts might be present.
The odontogenic cyst has following complications: the development of mural ameloblastoma (Figure 11), squamous cell carcinoma and mucoepidermoid carcinoma.
Figure 11 Orthopantomograph (OPG) showing multilocular radiolucency associated with the impacted mandibular third molar. The radiograph showing displacement of the third molar and the lesion extends to involve the entire ramus and apices of the second molar. The lesion was histopathologically diagnosed as mural ameloblastoma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore
Odontogenic keratocyst (OKC) was first described by Philipsen in 1956. WHO has recently designated OKC as keratocystic odontogenic tumor (KCOT) and is defined as ‘a benign uni- or multicystic, intraosseous tumor of odontogenic origin, with a characteristic lining of parakeratinized stratified squamous epithelium and potential for aggressive, infiltrative behavior’.
Philipsen in 1956, in his study of jaw cysts, described a distinct form of OKC which showed an orthokeratinized pattern. Wright et al (1981) reported 60 cases of orthokeratinized odontogenic cyst (OOC) and compared with OKC and found that the OOC appears to be a distinct clinicopathologic entity. It was suggested that this cyst be called OKC, orthokeratinized variant. Iamaroon et al (2004) compared the proliferation index of the epithelial cells between OKC, OOC, dentigerous cyst and ameloblastoma. He concluded that OKC should be considered a benign tumor rather than simply an odontogenic cyst and OOC as a non-aggressive cystic lesion.
Orthokeratinized odontogenic cyst usually presents as a solitary cyst in the posterior part of the mandible. It is usually seen in males commonly in the 2nd to 5th decade of life. In comparison to OKC it is less aggressive and has a very low recurrence rate (2.2%). Literature review reveals that almost two-thirds of the cases of OOC appear like dentigerous cyst on clinical and radiographic examination.
Orthokeratinized odontogenic cyst has a thin epithelial lining with a luminal surface of orthokeratin. The basal cell layer contains flattened squamous or cuboidal cells and a well-developed granular cell layer (Figure 13).
Orthokeratinized odontogenic cyst presents either as a well-defined unilocular or multilocular radiolucency. Radiographically, OOC may resemble a dentigerous cyst when it is unilocular and resembles ameloblastoma when it is multilocular. Occasionally, it may cause cortical plate expansion and thinning of the lower border of the mandible. Roots of teeth may be displaced (Figure 14). However, resorption of roots is seldom seen.
Figure 14 Orthopantomograph (OPG) showing a multilocular radiolucency in relation to the lower premolars, first and second molars causing displacement of the second molar in orthokeratinized odontogenic cyst. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore
Gingival cysts of adults are rare odontogenic cysts of developmental origin. The epithelial lining of these cysts are thin non-keratinized and are thought to arise from the rests of dental lamina. Some authors suggest that these cysts arise from the traumatic implantation of surface epithelium.
The common sites of involvement are the mandibular canine and premolar region. Occasionally, these may be seen in the lateral incisor, canine, premolar regions of the maxilla. The swelling is soft and fluctuant with a smooth surface and usually have the same coloration as that of the gingiva. Some authors have reported bluish and red color swellings. The teeth in relation to these cysts are vital.
Histologically, these cysts have a variety of presentations. The epithelium generally has three forms of presentation: (i) extremely thin epithelium, (ii) thicker stratified squamous epithelium and (iii) localized epithelial thickenings or plaque formation (similar to those evident in lateral periodontal cyst).
The thinner form of epithelium mimics the reduced enamel epithelium. It is generally composed of one to three layers of flat or cuboidal cells. The thicker variety may not show any rete pegs. The nuclei are pyknotic and show perinuclear cytoplasmic vacuolation. The localized thickening of epithelium or plaque may occasionally project into the cystic cavity. The cells in the localized thickenings have a whorled morphology. Rarely, these cells are swollen and clear and are referred to as water-clear cells.
It is a relatively uncommon cyst that is slow growing, non-expansile developmental odontogenic cyst derived from one or more rests of dental lamina, containing an embryonic lining of 1–3 squamous/cuboidal cell thickness and distinctive focal thickenings (plaques). These appear to have no gender predilection. According to Altini and Shear (1992), lateral periodontal cysts represent about 0.8% of all central cysts (intraosseous) of maxillary bones. These cysts are usually seen in adults between the 2nd and 8th decade of life.
These are usually seen by chance in routine radiographs. These are intraosseous forming beside vital tooth. These might even form near the crest of ridge. These cause no symptoms unless they erode through the bone to extend into the gingiva. Some patients may present with a swelling on the buccal aspect of the gingiva. The most common site of involvement is the mandibular premolar area followed by the anterior part of the maxilla.
The cyst wall and the lining usually show no signs of inflammation. The lateral periodontal cyst presents two important histologic features, namely, the presence of epithelial thickenings or ‘plaques’ and the presence of glycogenrich clear cells either in ‘plaques’ or in the superficial layers of the lining epithelium.
The cyst may appear as a round, oval or teardrop-like well-circumscribed interradicular radiolucent area, usually with a sclerotic margin, lying usually between the apex and the cervical margin of the teeth. Resorption of adjacent teeth though uncommon, has been reported. Occasionally, loss of lamina dura and widening of the periodontal ligament space may be present.
Botryoid odontogenic cyst (BOC) is considered as a variant of the lateral periodontal cyst. Weathers and Waldron in 1973 first used this term to describe a multilocular cystic lesion of the jaw that on gross morphology resembled a bunch of grapes.
The exact nature of this cyst is still not understood. Some authors consider the BOC as a multilocular variant of lateral periodontal cyst. Others consider BOC and lateral periodontal cyst as two distinct unrelated entities. They consider BOC as a multicystic odontogenic lesion with the histologic characteristics of lateral periodontal cysts.
However, histopathologically the BOC resembles lateral periodontal cyst. Another striking difference between BOC and lateral periodontal cyst is its rate of recurrence. It is estimated that the recurrence rate of BOC is between 15 and 33%, which is much higher than lateral periodontal cyst.
High et al (1996) proposed the term ‘polymorphic odontogenic cyst’. This term included GOC, mucoepidermoid intraosseous carcinoma and botryoid odontogenic cyst. Greer Jr and Johnson (1998) studied the clinicopathologic features of 10 botryoid odontogenic cysts. In their study the radiographic size of the cysts varied between 5 and 45 mm radiographically.
It is believed that the size and multilocular pattern could be the main factors responsible to the high recurrence rates of botryoid odontogenic cyst. The high recurrence rates warrant the need for a more aggressive treatment. Some authors suggest the systematic use of Carnoy solution along with enucleation and curettage.
It was thoroughly described by Gorlin and coworkers in 1962 and in 1963. Gold introduced the terms ‘keratinizing’ and ‘calcifying odontogenic cyst’. It reportedly accounts for about 2% of all odontogenic pathologies affecting the maxilla and mandible. It may be found along with other odontogenic tumors. However, in 24% of the cases it is associated with odontomas.
The calcifying odontogenic cyst can either occur as an intraosseous (central) or extraosseous (peripheral) lesion. The peripheral form is very rare. The incisor and canine regions are the most common sites of involvement. The maxilla is more commonly affected. It can occur at any age. However, most cases are seen in the 2nd decade of life.
Type 2: Monocystic odontoma creative type, with all the characteristics of the previous type, except that the hard tissue was complex or compound odontoma, and a presence of ameloblastic fibroma tissue in the cystic wall extending into the surrounding tissue.
Type 3: Monocystic ameloblastomatous proliferating type which was marked by ameloblastomatous proliferation both in the walls and in the lumen, and hard dental tissue which consisted of dentinoid formation in connection with islets of epithelia in the connective wall.
It was described as an odontogenic tumor with ghost cells. The epithelial elements consist of numerous ameloblastomatous proliferations of tissue in the connective tissue of the stroma. Varying amounts of ghost cells are present within the epithelial islets. The hard tissue is composed of different amounts of dentinoid in direct contact with the epithelium.
It produces slow growing painless non-tender swelling of jaws (Figures 16 and 17). It occurs more in 2nd decade of life. It is commonly seen in the anterior part of the jaws. In the maxilla, the canine region is the most commonly affected site. In the mandible, the cyst is rarely found posterior to the first molar. Occasionally the cyst may be seen crossing the midline. On aspiration, it yields viscous granular yellow fluid. According to Wood et al, 68% of cases occur in mandibular molar area. At least 52% cases are associated with unerupted tooth, occasionally associated with pain.
Figure 16 Intraoral photograph showing swelling in relation to the attached gingiva of the right maxillary incisor and canine region. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore
The radiographic features are quite variable. The central lesion may be radiolucent with a variable margin that is smooth and well-defined or, irregular and poorly defined. It might contain small foci of calcified material. It is usually present as a unilocular radiolucency. However, in about 5–13% of the cases, it may present as multilocular radiolucency. Intraosseous lesions may produce expansion of the lingual cortical plate. Resorption of the roots of adjacent teeth is frequently seen (Figure 18).
Figure 18 Maxillary occlusal radiograph showing a well-defined unilocular radiolucency in the incisor-canine region containing radiopaque foci of calcification. Resorption of the apex of the right central incisor can be appreciated. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore