The odontogenic keratocyst (OKC) was first described by Philipsen in 1956 1. In 2005, the WHO redesignated OKC as keratocystic odontogenic tumor (KCOT) as it better reflects its neoplastic nature 2. Several factors, such as the cyst’s aggressive behavior, its high mitotic activity histologically, and evidence of associated genetic and chromosomal abnormalities (e.g. mutation of the PTCH gene) often seen in neoplasia, serve as the basis for this new classification 3–5. It also has unique tendency to recur after treatment. The recurrence rate varies from 0 to 62% in different studies 6. Today there is still much controversy with regard to the ideal treatment for KCOT. Therapeutic approaches vary from marsupialization to resection. Attempts have been made to reduce the recurrence rate through radical surgery.
In this study, we present a case of a large KCOT of the maxillary sinus treated with only enucleation and devitalization of the surrounding tissue using Carnoy’s solution, with no evidence of recurrence on 5 years of follow-up.
A 16-year-old girl with mild pain and swelling in the upper left side of her face since 6 months was referred to the Department of Oral and Maxillofacial Surgery. The patient also reported bad taste in the mouth for past 3 months.
Extraoral examination revealed slight swelling and tenderness over the left maxilla and obliteration of the nasolabial fold (Fig. 1). No anesthesia, paresthesia, visual disturbance, or nasal obstruction was reported or observed. There was no cervicofacial lymphadenopathy. A systemic physical examination was noncontributory. Intraoral examination showed fluctuant swelling obliterating the buccal sulcus, extending from the first premolar to tuberosity, and a discharging sinus in the first molar region. Examination of the teeth showed that all second molar were missing and all the third molars were unerupted. All the teeth gave negative results for percussion and mobility tests.
Aspiration showed a straw colored fluid mixed with the pus (Fig. 2). A panoramic radiograph revealed an opaque lesion occupying the entire maxillary sinus associated with an ectopic second molar seen at the infraorbital rim and an incompletely formed third molar tooth bud well above the tuberosity (Fig. 3). Subsequently, a computed tomography (CT) scan was performed. The CT scan revealed an enlarged left maxillary sinus with extensive mucosal thickening with air fluid level and an impacted tooth in the infraorbital region at the level of the infundibulum of the left maxillary sinus (Fig. 4). On the basis of above findings, a provisional diagnosis of a dentigerous cyst was made.
Under general anesthesia, complete enucleation along with removal of the impacted teeth was carried out through a vestibular incision lesion. On inspection, the maxillary sinus was enlarged and the anterior wall of the maxillary sinus was completely destructed (Fig. 5); however it had an intact roof and medial and lateral walls (Fig. 6). Chemical cauterization was performed using Carnoy’s solution. A medicated gauze pack was placed inside the bony defect, with one end out through the buccal sulcus, and sutured with 3-0 vicryl. The gauze pack was removed after 3 days. The enucleated specimen was sent for histopathological examination. The gross specimen showed a thick fibrous cyst (5×4×2 cm) that was brown with areas of hemorrhage, had a rough surface, and had an impact on second and third molars (Figs 7 and 8). Histopathological examination revealed that its wall was lined by parakeratinized stratified squamous epithelium admixed with granulation tissue and inflammatory cell infiltrate (Fig. 9). Histological findings established a diagnosis of infected parakeratinized KCOT. Healing was satisfactory, and the patient has been on regular follow-up since with no signs of recurrence in 5 years (Fig. 10).
KCOT has been one of the most controversial pathological entities in the maxillofacial region since it was first described by Philipsen in 1956 1. It is generally thought to be derived from remnants of the dental lamina (rests of serres) or as a result of traumatic implantation, down growth of the basal cell layer of the surface epithelium 7, or reduction of the enamel epithelium of the dental follicle 8. Studies have suggested a genetic cause, specifically a PTCH gene aberration, in the etiology of these cysts. This is the cause for about 3–11% of all odontogenic cysts of the jaws 9. These cysts mainly occur during the second and third decades of life with slight male predilection 10. Generally, KCOTs are solitary lesions unless they are associated with nevoid basal cell carcinoma syndrome 11. They may involve any part of the jaw, with ∼65% of the lesions occurring in the posterior body or ramus of the mandible 12. However, there is in consistency regarding the prominent location of KCOT in the maxilla. Involvement of the maxillary sinus is exceedingly rare. The literature suggests that less than 1% of all the cases of KCOT occur in the maxilla and exhibits sinus involvement 13. Frequently, KCOT is associated with an impacted tooth and may mimic a dentigerous cyst. In the present case, the lesion was occupying the entire maxillary sinus and was associated with the impacted ectopic second and third molar. Although there was obliteration of the buccal sulcus, the maxillary alveolus was not expanded clinically.
Clinically KCOT generally presents in association with swelling, pain, discharge, aggressive growth, invasion of adjacent structures, and recurrence 11,14. A localized asymptomatic swelling is the most common symptom; spontaneous drainage of the tumor into the oral cavity and mobility of the teeth are also common. The tumor classically grows within the medullary spaces of the bone in an anteroposterior direction, causing expansion that is minimal at first 15. Buccal expansion is noted in ∼30% of maxillary and 50% of mandibular lesions 8. It has been demonstrated that the collagenase activity in the cysts’ epithelium, with its resorptive properties, regulates the ability of the lesion to grow expansively in the bone 16. Nasal obstruction, paresthesia, and root erosion are rare symptoms. Some reports emphasize that KCOTs can undergo malignant transformation at a frequency of 5–62.5% 13,17. It is important to note that KCOTs can be confused with inflammatory lesions, as patients with this type of cystic neoplasm usually have inflammatory symptoms such as pain, swelling, and discharge 18. In the present case, the patient also had intermittent pain and swelling of the left cheek, which could easily be confused with inflammatory lesions such as sinusitis.
Radiographically, KCOT usually presents as a unilocular or a multilocular radiolucency with scalloped and well-defined margins 11. As KCOT in the maxillary sinus is rare, its radiographic appearance in this situation may be misinterpreted. CT can provide information on the extent of these lesions, contributing to diagnosis and preoperative preparation. KCOT is difficult to diagnose clinically because of a relative lack of specific clinical and radiographic characteristics 19. As KCOT can be associated with the crown of an involved tooth 11, the lesion must be distinguished from a dentigerous cyst (on radiography). Therefore, even if both radiology and clinical features indicate KCOT, a definitive diagnosis cannot be made without histological examination, and ideally, examination of a biopsy specimen and accurate clinical, radiographic, and intraoperative observations are essential to determine the most effective treatment in order to avoid recurrence 20.
According to the histological typing of odontogenic cysts by the WHO, dentigerous cysts have a stratified squamous epithelium that is three to four cells in thickness with no basal palisading; they may be mucous or ciliated cells; keratinization may also occur; cell vacuolation is rare, but when present, it is usually keratinizing; these cysts may have a fibrous stroma 21.
In 1962, Pindborg, Phillipsen and Henriksen established strict histological criteria for the diagnosis of KCOT. These criteria include an epithelial lining that is usually thin and uniform in thickness, with little or no evidence of rete ridges; a well-defined basal cell layer, the component cells of which are cuboidal or columnar in shape and often fashioned in a palisaded arrangement; a thin spinous cell layer that often shows a direct transition from the basal cell layer; spinous cell layer intracellular edema; surface keratinization that is corrugated and predominantly parakeratotic; and a fibrous connective tissue cyst wall that is thin and usually uninflamed 22. In addition, satellite cysts, solid epithelial proliferations, odontogenic rests, and basal layer budding have been described in association with the KCOT 23. The incidence of daughter cysts in the cyst wall is reported to range from 7 to 30.1%. Mineralization of the fibrous connective tissue wall may occur, along with inclusion of cholesterol crystals and Rushton bodies 23. The parakeratotic type is the most frequent (80%) and has a more aggressive clinical presentation than the orthokeratotic variant 24,25. The lesion reported in this case is a parakeratotic KCOT, and because of the presence of secondary infection there was fibrosis of the lining, which facilitated easy enucleation.
Recurrence of KCOT is usual 10,13,19, occurring principally during the first 5 years after operation 13,19,20; however, recurrence may occur after much longer time intervals as well. Recurrence rate was found to vary from 0 to about 62%, depending on the kind of treatment and follow-up period 6,10,19. The recurrence of KCOT is thought to be based on the high rate of mitotic activity and the growth potential found in the epithelium rather than on other sources such as remnants of dental lamina and epithelial islands. These findings led to recommendation of surgery for eradication of epithelial components of these tumors and for excision of the mucosa at regions where KCOT adheres 26.
Treatment of KCOT is controversial 27. KCOTs are observed to have a high mitotic rate, a high level of proliferating cell nuclear antigen, as well as to overexpress p53 protein, cell-surface gp38 glycoprotein, and Ki-67 antigen 28. It has been established that the majority of KCOTs have chromosomal abnormalities and harbor an allele loss at the same loci as squamous cell carcinomas. This further supports the current view that a KCOT resembles a neoplasm 29. It is not known how the biologic behavior of the KCOT changes after marsupialization, but some believe it to be related to inflammation of the cyst lining 30. The overall effect on the KCOT seems to be less aggressive behavior when left open to the oral cavity for several months. If the lesions are left untreated, they can become quite large and locally destructive. Various surgical approaches have been suggested, such as marsupialization, enucleation, enucleation with Carnoy’s solution, enucleation with cryotherapy, curettage, and resection 10,19,27. Surgeons have long recognized the aggressive features of KCOT. The choice of treatment must take into account the patient’s age, the size of lesion, previous recurrence history, soft-tissue involvement, and histological type 31. Large KCOTs associated with resorption of the surrounding bone may warrant radical therapy such as resection. However, in the present case, although the lesion was huge, involving the entire maxillary sinus associated with bone resorption, and was histologically confirmed to be a parakeratinized variant of KCOT, the decision was made against radical resection considering the age of the patient. Only enucleation and chemical cauterization with Carnoy’s solution were performed. The patient was motivated to attend regular follow-up sessions and was reported to be disease free even after 5 years of follow-up.
The reclassification of OKC as KCOT by the WHO stresses on its aggressive nature and motivates the clinician to manage the lesion in an aggressive manner. However, treatment should be carefully tailored to obtain the best prognosis, especially among younger patients. All forms of treatment for KCOT have been associated with propensity for recurrence. Complete enucleation with chemical cauterization may offer good prognosis in selected cases.
Conflicts of interest
There are no conflicts of interest.
1. Philipsen HP. On keratocysts in the jaws. Tandlaebladet. 1956;60:963–980
2. Philipsen HPBarnes L, Eveson JW, Reichart P, Sidransky D. Keratocystic odontogenic tumour. World Health Organization classification of tumours. Pathology and genetics of head and neck tumors. 2005 Lyon IARC Press:306–307
3. González-Alva P, Tanaka A, Oku Y, Yoshizawa D, Itoh S, Sakashita H, et al. Keratocystic odontogenic tumor: a retrospective study of 183 cases. J Oral Sci. 2008;50:205–212
4. Madras J, Lapointe H. Keratocystic odontogenic tumour: reclassification of the odontogenic keratocyst from cyst to tumour. J Can Dent Assoc (Tor). 2008;74:165–165h
5. Cavalcante RB, Pereira KMA, Nonaka CFW, Maia Nogueira RL, de Souza LB. Immunohistochemical expression of MMPs 1, 7, and 26 in syndrome and nonsyndrome odontogenic keratocysts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106:923–929
6. Maurette PE, Jorge J, De Moraes M. Conservative treatment protocol of odontogenic keratocyst: a preliminary study. J Oral Maxillofac Surg. 2006;64:379–383
7. Eryilmaz T, Ozmen S, Findikcioglu K, Kandal S, Aral M. Odontogenic keratocyst: an unusual location and review of the literature. Ann Plast Surg. 2009;62:210–212
8. Hyun HK, Hong SD, Kim JW. Recurrent keratocystic odontogenic tumor in the mandible: a case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108:e7–e10
9. Chuong R, Donoff RB, Guralnick W. The odontogenic keratocyst. J Oral Maxillofac Surg. 1982;40:797–802
10. Chirapathomsakul D, Sastravaha P, Jansisyanont P. A review of odontogenic keratocysts and the behavior of recurrences. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:5–9
11. Gustafson G, Lindahl B, Dahl E, Svensson A. The nevoid basal cell carcinoma syndrome – Gorlin’s syndrome. Multiple jaw cysts and skin cancer. Swed Dent J. 1989;13:131–139
12. Neville BW, Damm DD, Brock T. Odontogenic keratocysts of the midline maxillary region. J Oral Maxillofac Surg. 1997;55:340–344
13. Brannon RB. The odontogenic keratocyst: a clinicopathologic study of 312 cases. I. Clinical features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1976;42:54–72
14. Macdonald-Jankowski DS. The involvement of the maxillary antrum by odontogenic keratocysts. Clin Radiol. 1992;45:31–33
15. Preston RD, Narayana N. Peripheral odontogenic keratocyst. J Periodontol. 2005;76:2312–2315
16. Donoff RB, Harper E, Guralnick WC. Collagenolytic activity in keratocysts. J Oral Surg. 1972;30:879–884
17. Absi EG, Sim RL. Odontogenic keratocyst involving the maxillary sinus: report of two cases. Dentomaxillofacial Radiol. 1994;23:226–229
18. Tsukamoto G, Sasaki A, Akiyama T, Ishikawa T, Kishimoto K, Nishiyama A, Matsumura T. A radiologic analysis of dentigerous cysts and odontogenic keratocysts associated with a mandibular third molar. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:743–747
19. Stoelinga PJW. Long-term follow-up on keratocysts treated according to a defined protocol. Int J Oral Maxillofac Surg. 2001;30:14–25
20. Chapelle KAOM, Stoelinga PJW, de Wilde PCM, Brouns JJA, Voorsmit RACA. Rational approach to diagnosis and treatment of ameloblastomas and odontogenic keratocysts. Br J Oral Maxillofac Surg. 2004;42:381–390
21. Pindberg JJ, Kramer IRH, Torloni H. Histological typing of odontogenic tumors, jaw cysts and allied lesions. International Histological Classification of Tumors. No 5. 1971 Geneva WHO
22. Pindborg JJ, Philipsen HP, Henriksen JSognnaes RF. Studies on odontogenic cyst epithelium. Fundamentals of keratinisation. 1962 Washington, DC American Association of the Advancement of Science:151–160
23. Sciubba JJ, Fantasia JE, Kahn LB Odontogenic keratocyst. Atlas of tumor pathology: tumors and cysts of the jaw. 19993rd ed. Washington, DC Armed Forces Institute of Pathology:34–40
24. Verbin RS, Barnes LBarnes L. Cysts and cystlike lesions of the oral cavity, jaws, and neck. Surgical Pathology of the head and neck, vol. 2. 1985 New York Marcel Dekker:1257–1263
25. Brannon RB. The odontogenic keratocyst. A clinicopathologic study of 312 cases. II. Histologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1977;43:233–255
26. Ahlfors E, Larsson A, Sjogren S. The odontogenic keratocyst: A benign cystic tumor? J Oral Maxillofac Surg. 1984;42:10–19
27. Morgan TA, Burton CC, Qian F. A retrospective review of treatment of the odontogenic keratocyst. J Oral Maxillofac Surg. 2005;63:635–639
28. Giuliani M, Grossi GB, Lajolo C, Bisceglia M, Herb KE. Conservative management of a large odontogenic keratocyst: Report of a case and review of the literature. J Oral Maxillofac Surg. 2006;64:308–316
29. Henley J, Summerlin DJ, Tomich C, Zhang S, Cheng L. Molecular evidence supporting the neoplastic nature of odontogenic keratocyst: a laser capture microdissection study of 15 cases. Histopathology. 2005;47:582–586
30. Rodu B, Tate AL, Martinez MG Jr. The implications of inflammation in odontogenic keratocysts. J Oral Pathol. 1987;16:518–521
31. Kolokythas A, Fernandes RP, Pazoki A, Ord RA. Odontogenic keratocyst: to decompress or not to decompress? A comparative study of decompression and enucleation versus resection/peripheral ostectomy. J Oral Maxillofac Surg. 2007;65:640–644