J Clin Exp Dent. 2020;12(8):e794-9. Therapeutic management of the odontogenic keratocyst Journal section: Oral Medicine and Pathology doi:10.4317/jced.56722 Publication Types: Case Report https://doi.org/10.4317/jced.56722 Therapeutic management of the odontogenic keratocyst. An energetic approach with a conservative perspective and review of the current therapeutic options Jordi Borrás-Ferreres 1, Alba Sánchez-Torres 2, Javier Alberdi-Navarro 3, José Manuel Aguirre-Urizar 4, Adal- berto Mosqueda-Taylor 5, Cosme Gay-Escoda 6 1 DDS. MS. Master’s Degree Program in Oral Surgery and Orofacial Implantology (EFHRE International University/FUCSO) 2 DDS, MS. Master of Oral Surgery and Orofacial Implantology. Associate Professor of the Oral Surgery Department, School of Dentistry, University of Barcelona, Spain 3 DDS, MS, PhD, Assistant Professor of the Oral Medicine and Oral and Maxillofacial Pathology Unit, Dental Clinic Service, Department of Stomatology II, University of the Basque Country (UPV/EHU), Leioa, Spain 4 MD, DDS, PhD. Chairman and Professor of the Oral Medicine and Oral and Maxillofacial Pathology Unit, Dental Clinic Service, Department of Stomatology II, University of the Basque Country (UPV/EHU), Leioa, Spain 5 MD, DDS, MSc. Health Care Department, Universidad Autónoma Metropolitana Xochimilco, Mexico City, Mexico 6 MD, DDS, MS, PhD, EBOS, OMFS. Chairman and Professor of the Oral and Maxillofacial Surgery Department, School of Dentistry, University of Barcelona. Director of Master’s Degree Program in Oral Surgery and Implantology (EFHRE International University/ FUCSO). Coordinator/Researcher of the IDIBELL Institute. Head of Oral and Maxillofacial Surgery and Implantology Department of the Teknon Medical Centre, Barcelona, Spain Correspondence: Clínica Dental Borrás Avda. Jacinto Benavente, nº2 (bajos) 12580 Benicarló; Castellón, España jborras@dentalborras.com Borrás-Ferreres J, Sánchez-Torres A, Alberdi-Navarro J, Aguirre-Urizar JM, Mosqueda-Taylor A, Gay-Escoda C. Therapeutic management of the odontogenic keratocyst. An energetic approach with a conservative per- Received: 26/12/2019 Accepted: 27/01/2020 spective and review of the current therapeutic options. J Clin Exp Dent. 2020;12(8):e794-9. Article Number: 56722 http://www.medicinaoral.com/odo/indice.htm © Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488 eMail: jced@jced.es Indexed in: Pubmed Pubmed Central® (PMC) Scopus DOI® System Abstract Background: Odontogenic keratocysts (OKC) are cystic lesions appearing in the jaws, usually asymptomatic with a progressive growth into the bone. Many of them are diagnosed by a routine radiological examination. Material and Methods: This study reports a 12-year-old girl that presented an asymptomatic large radiolucent uni- locular lesion associated to the crown of 3.8 that caused displacement of the molar and the inferior alveolar canal. Differential diagnosis included OKC, unicystic ameloblastoma, ameloblastic fibroma, dentigerous cyst and or- thokeratinized odontogenic cyst. Two surgical interventions were performed; first, a marsupialization, and 10 mon- ths after, the third molar extraction plus cyst enucleation, mucosa excision and the application of Carnoy’s solution. Results: The anatomopathological exam confirmed diagnosis of OKC. There was no evidence of recurrence after 2 years of follow-up. Conclusions: Marsupialization followed by surgical enucleation with mucosa excision and Carnoy’s solution can help manage treatment of OKC, a lesion characterized by an aggressive behavior. Key words: Odontogenic keratocyst, mucosa excision, carnoy solution, third molar, tooth extraction. e794 J Clin Exp Dent. 2020;12(8):e794-9. Therapeutic management of the odontogenic keratocyst Introduction followed by enucleation (3,7,16,17). Although adjuvants Odontogenic keratocysts (OKC) are cystic lesions to simple enucleation decrease the recurrence rate, they appearing in the jaws, classified as developmental still exceed 10% (11). Occasionally, in extensive or re- cysts arising from the dental lamina (1). They represent current cases, an aggressive surgical treatment based on approximately 11% of all odontogenic cysts and the age a radical “in block” resection with reconstruction with a of onset has two peaks of maximum frequency, one be- free or vascularized bone graft (5) would be indicated. tween the second and third decades of life and other, less Although amputation is the treatment modality with the intense, around the fifth decade (2). These cysts are more lowest recurrence rate, between 0% and 8.4% (10,11), frequent in men, with a ratio of 1:1.4, and they are more the subsequent reconstruction can produce important common in the mandible, with a predilection for the an- aesthetic and functional sequelae which can significant- gle and ramus (3). This lesion may occur in association ly alter the patient’s quality of life (5). with an impacted third molar (4-6). The main objective of this study was to show the clini- Radiographically, OKC appear as uni or multilocular ra- cal, radiographic and histological evolution of a pedia- diolucent lesions that can adopt a wide range of morpho- tric patient with a large OKC treated by a conservative logies, so radiological exam is not considered a pathog- surgical therapy that combined distinct therapeutic va- nomonic test for the definitive diagnosis of OKC since riants to minimize the risk of recurrence. several lesions may have similar characteristics (4,7,8). Generally, these lesions are asymptomatic and have a Case Report progressive growth into the bone, narrowing or bulging A 12-year-old girl came to the dental clinic for a com- the bone corticals and, ocasionally, provoking bony ero- plete dental check-up. No oral pathology was observed sion or resorption (9). Many of them are diagnosed by at clinical examination. However, the panoramic radio- a routine radiological examination, although some, spe- graph disclosed a radiolucent, unilocular lesion with cially if very large or inflammed can cause swelling and well-defined and corticated borders in the left man- pain (3,5,6,8). Histologically, OKC are characterized by dibular angle. The lesion measured 3x2x1.5 cm in the a very thin fibrous capsule whose epithelial lining has anteroposterior, coronoapical and mediolateral planes a parakeratinized corrugated surface and a basal layer respectively, associated to the crown of 3.8, which was of cylindrical cells in palisade that demonstrate inverted displaced towards the ascending ramus. Besides, the le- polarity, at least focally (3). sion displaced the inferior alveolar canal and reached Compared to other odontogenic cysts, OKC have an in- the roots of molar 3.7 (Fig. 1A). A cone-beam compu- filtrating growth pattern, an aggressive biological beha- ted tomography showed that the lesion had reabsorbed vior and a greater tendency to recur after its elimination, part of the alveolar ridge, involving internal and external which can reach up to 56% of cases after a simple enu- bone plates and expanding them (Fig. 1B). The differen- cleation (10). The delicate and fragile nature of its epithe- tial diagnosis of the radiological image included OKC, lial lining, weakly connected to the capsular connective unicystic ameloblastoma, ameloblastic fibroma, denti- tissue, makes these lesions prone to tearing, separating gerous cyst and orthokeratinized odontogenic cyst. and breaking during surgical excision, sparing some epi- Given the significant size of the lesion, a marsupializa- thelial remains which can lead to recurrence since they tion with an incisional biopsy was performed. The sur- have a high proliferative activity (11). Recurrence may gical intervention was done under local anesthesia (4% also be due to the persistence of satellite cysts that would articaine with epinephrine 1:200,000), using inferior al- remain during surgery, the presence of cystic debris in veolar and lingual nerve direct block technique. Subse- the adjacent bone or mucosa, or the existence of epi- quently, the buccal nerve was anesthetized by an infiltra- thelial islands in the lining mucosa (2,8,9,11). Moreo- tion on the vestibular mucosa of the retromolar trigone. ver, the fact that OKC arise from the inactivation of the The marsupialization consisted in a gingivectomy of the chromosome 9q patched gene (PTCH), a tumor suppres- tissue covering the bone fenestration caused by the le- sor gene, led in 2005 to be classified as a keratocystic sion. After the tissue excision, a large cavity lined by a odontogenic tumor (12). However, this denomination thin capsule was evidenced. A yellowish-white material has never reached great acceptance and currently, OKC that was herniated, appeared inside the cavity. A sample has again considered a type of developing cyst instead of the capsule was taken and sent for its anatomopatho- an unequivocal neoplasm (1). logical exam. Subsequently, the defect was filled with There are different surgical approaches to treat OKC. a sterile gauze embedded in chlorhexidine to prevent One of the conservative surgical treatments consists in the oral mucosa from covering the lesion window. The the enucleation with or without the use of a complemen- characteristics of the capsule and the material inside tary procedure, such as the application of Carnoy’s so- constituted suggestive features of an OKC. The pieces lution or liquid nitrogen (4,9,13-15). Marsupialization is analyzed corresponded to a fibrocellular connective wall another conservative modality, as well as decompression lined by a well-defined polystratified epithelium with fo- e795 J Clin Exp Dent. 2020;12(8):e794-9. Therapeutic management of the odontogenic keratocyst Fig. 1: Radiological characteristics. A. Panoramic radiograph. B. Slides from cone-beam computed tomography. cally corrugated superficial parakeratosis, showing the and keeping it covered with a sterile gauze embedded basal cells in palisade. Focally, this epithelium appea- in 0.12% chlorhexidine digluconate. During follow-up red detached from the connective tissue showing several visits, the reduction of the lesion size was observed cli- fragments of epithelium alone (Fig. 2A,B). Thus, the fi- nically and radiographically, with the formation of bone nal diagnosis was OKC. Clinical and radiographic con- in its periphery and displacement of tooth 4.8 towards trols were performed every 3 months. The patient care the alveolar crest (Fig. 3A,B). throughout the process consisted in irrigating the cavi- Ten months after the onset of marsupialization, a com- ty with a syringe filled with salty water 3 times a day plete cystectomy of the residual lesion was performed. Fig. 2: Anatomopathological exam of the incisional biopsy (A,B) and enucleation (C,D). A. Squamous epithelium detached from capsular connective tissue (H&E 20x). B. Squamous epithelium with superfi- cial parakeratosis of corrugated aspect and palisade of basal cells. (H&E 40x). C. Squamous epithelium with loss of keratinization and lengthening of epithelial ridges. In the capsular connective tissue, a chronic inflammatory lymphoplasmocitary infiltrate is recognized. (H&E 40x). D. Squamous epithe- lium with focal parakeratosis, with areas of focal basal palisade. (H&E 40x). e796 J Clin Exp Dent. 2020;12(8):e794-9. Therapeutic management of the odontogenic keratocyst Fig. 3: Clinical and radiological follow-up. A. Three months after marsupialization. B. Six months after marsupialization. C. Six months after the cyst enucleation. At that time, the bone already covered the lower dental lisade, as well as the presence of a chronic inflammatory canal, a situation that prevented possible nerve damage infiltrate in the capsular connective tissue (Fig. 2C,D). during enucleation. The surgical intervention was per- Periodic check-ups to observe the filling of the cavity formed under local anesthesia using the same technique. and the complete bone regeneration at 6 months were Since the initially performed window now contained made (Fig. 3C). The last control visit at 2 years showed the epithelial transition between the cystic and oral ca- no signs of recurrence. vity, an elliptical incision was made 5 mm away from its edges, completely surrounding it until the healthy Discussion bone. This maneuver aimed to eliminate possible cystic Although OKC is a benign lesion, its biological charac- and epithelial remnants located in the adjacent mucosa. teristics make this cyst to be considered as an “aggressi- Subsequently, the cyst was removed from the edges of ve” entity (11). This lesion tends to recur and can reach the window, obtaining a complete enucleation of the le- large dimensions before being detected (8,10); therefo- sion and eliminating the included third molar. Then, a re, it is advisable to make a correct treatment with the chemical curettage of the bone cavity was carried out complete removal of the cystic lesion to reduce or elimi- with Carnoy’s solution for 5 minutes, with the aim of nate the possibility of recurrence (4,11). destroying the epithelial remnants. Finally, a buccal flap Enucleation has been the most used treatment modality was mobilized and sutured over the bony window. As for decades; however, applying this technique without the complete closure of the wound was not achieved, adjuvants contributes to high recurrence rates (11,13). healing by second intention was allowed, filling the ca- In a study by Zecha et al. (8) on 58 OKC treated by vity with a sterile gauze impregnated with chlorhexidine enucleation, 20.7% of cases relapsed after a mean of 46 digluconate for one week. The sample obtained was sent months of follow-up. Previously, another similar study for histopathological analysis, which showed adaptive by Jensen et al. (13) showed that 33% of OKC treated changes in the cystic epithelium, hyperplastic in some by simple enucleation recurred in a period between 17 areas, mostly non-keratinized, with loss of the basal pa- and 58 months. One of the main reasons that would exp- e797 J Clin Exp Dent. 2020;12(8):e794-9. Therapeutic management of the odontogenic keratocyst lain these high recurrence rates could be the incomplete epithelial islands and daughter cysts. In addition, as the removal of the cyst, due to the well-known difficulties time from the onset of marsupialization increases, p53 for enucleating and perform the complete removal of expression and inflammatory changes increase, indica- the cyst, due to the thinness and friability of its capsu- ting a greater increase in recurrence rates (3). In line with le (8,9,13). Other reasons that would explain the recu- these findings, the retrospective study by Zecha et al. (8) rrences could be the presence of daughter cystic into the noted that, after an average follow-up of 49.5 months, adjacent bone or mucosa, or the presence of epithelial 20.7% of the OKC treated by simple enucleation and islands within the lining mucosa (6,8,9). Although the 40% of those treated by marsupialization recurred. The resective therapeutic modality obtains the lowest recu- meta-analysis performed by Al-Moraissi et al. (11) also rrence rates (5), this approach constitutes a severe muti- indicated an increase in recurrences with marsupializa- lation (10,11). Faced with these two opposite therapeutic tion (32.3%) compared to enucleation (23.1%). There- approaches, in this clinical case we tried to identify an fore, we consider that OKC cannot be treated only with intermediate treatment that would allow for an accepta- a decompression/marsupialization, but it is advisable to ble long-term success rate and a relatively low morbidity perform the complete enucleation of the residual lesion throughout the implementation of a close clinical control after reaching the objectives of the initial marsupializa- as well as careful radiographic evaluation. tion, as we have proceeded in our case. In recent years, the decompression or marsupialization The removal of the lining mucosa in contact with the of large odontogenic cysts have been widely used as cystic lesion has been recommended in order to reduce conservative treatments (3,7,16). These techniques are recurrence rates due to the permanence of cystic rem- intended to create a window in the cyst wall, exposing nants or epithelial islands (9). In addition to the above its content and maintaining its continuity with the oral mentioned, we consider essential to implement a cure- cavity. The only portion of the cystic capsule that is re- ttage of the bony bed to eliminate 1 to 2 mm of bone moved is the one that is eliminated to create the win- around the residual cystic cavity to diminish the risk of dow, leaving the remaining membrane. The difference recurrence (4,5,11,13). This behavior can be mechanical between them is that, in decompression, a smaller bone (2), chemical (4,15) or by cryosurgery (14). The most window is practiced, mantaining opened by a surgical conservative variant is the mechanical, which is perfor- drain sutured at its edges, which is shortened as the size med with a rotary bur practicing a peripheral ostectomy of the lesion decreases (3). On the contrary, marsupia- of the surrounding tissue (2). This treatment, in addition lization needs a larger window that is kept opened by to enucleation, provides better results than simple enu- means of surgical gauze (18). In our opinion, marsupia- cleation (11). Another option is cryosurgery, applying lization allows an easier cleaning of the cystic cavity and liquid nitrogen to the bone at -20°C. Which is associated avoids some complications that may occur with decom- to lower recurrence rates than those of simple enuclea- pression, such as the loss of drainage due to the decrease tion, as shown by Schmidt and Pogrel (14) in 26 cases in tensile strength of the suture (19). treated by enucleation and cryotherapy, with only 3 re- These two techniques produce changes in the histolo- currences (11.5%). The depth of bone penetration and gical structure of the cyst, thickening its capsule thanks cell death caused by liquid nitrogen is close to 0.82 mm to the fibrosis that induces inflammation secondary to and the advantage of its use is that it maintains the bone oral exposure, which facilitates a possible subsequent architecture and facilitates its regeneration (14). On the removal (3). Since the capsule of OKC is extremely other hand, some disadvantages are the poor availability thin and friable, these changes will be advantageous. of this equipment and the facility to produce nerve da- In addition, by decreasing its osmotic pressure together mage or soft tissue necrosis if it is not correctly applied with the appearance of inflammation, the formation of (14, 20). Finally, and as we use in our case, a chemi- interleukin-1α, responsible for bone resorption and the cal curettage can be performed using Carnoy’s solution expansion of the lesion, is inhibited (16). With all this, it (15). This fixing liquid is a caustic mixture of ferric is possible to reduce the size of the lesion, enabling bone chloride in alcohol, chloroform and concentrated acetic growth from its periphery and decreasing the extent of acid, which fixes and denatures the tissues to a depth of posterior enucleation (6,7,17,18). approximately 1.54 mm, enough to destroy the neces- It is interesting to note that recurrence rates do not de- sary bone wall (9,15). However, unlike liquid nitrogen, crease despite the histopathological changes that take it does not favor bone regeneration and the inclusion of place (7). In fact, Nakamura et al. (17) showed high chloroform in its formula represents a great disadvanta- frequency in satellite cysts and epithelial remnants even ge since this product has been classified as carcinoge- after marsupialization, ranging from 21.4% to 43.5%. In nic (20). Despite this, with the use of Carnoy’s solution, the study of Awni et al. (3), similar results were found. recurrence rates of less than 10% have been published These findings indicate that cell proliferative activity (5,10,15). persists during and after marsupialization in pre-existing The combination of the cystectomy, performed after a e798 J Clin Exp Dent. 2020;12(8):e794-9. Therapeutic management of the odontogenic keratocyst previous decompression/marsupialization, with adju- of treatment of keratocysts by enucleation or enucleation combined vant treatments in the management of OKC entails an with cryotherapy. A preliminary report. J Craniomaxillofac Surg. 1988;16:362-5. energetic approach for these lesions. In our opinion, the 14. Schmidt BL, Pogrel MA. The use of enucleation and liquid nitro- combination of these complementary maneuvers to enu- gen cryotherapy in the management of odontogenic keratocysts. J Oral cleation might minimize the risk of recurrence. Maxillofac Surg. 2001;59:720-5; discussion 726-7. 15. Díaz-Belenguer Á, Sánchez-Torres A, Gay-Escoda C. Role of Car- noy’s solution in the treatment of keratocystic odontogenic tumor: A Conclusions systematic review. Med Oral Patol Oral Cir Bucal. 2016;21:689-95. This case report reviews the current therapeutic options 16. Ninomiya T, Kubota Y, Koji T, Shirasuna K. Marsupialization in- for OKC and shows the treatment of a large OKC in a hibits interleukin-1alpha expression and epithelial cell proliferation in pediatric patient by an energetic approach with a con- odontogenic keratocysts. J Oral Pathol Med. 2002;31:526-33. 17. Nakamura N, Mitsuyasu T, Mitsuyasu Y, Taketomi T, Higuchi Y, servative perspective. Marsupialization followed by Ohishi M. Marsupialization for odontogenic keratocysts: long-term fo- surgical enucleation with mucosa excision and Carnoy’s llow-up analysis of the effects and changes in growth characteristics. solution can help manage treatment of OKC, lesions Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;94:543-53. characterized by an aggressive behavior. There was no 18. Pogrel MA. Treatment of keratocysts: the case for decompression and marsupialization. J Oral Maxillofac Surg. 2005;63:1667-73. evidence of recurrence after 2 years of follow-up. It is 19. Swantek JJ, Reyes MI, Grannum RI, Ogle OE. A technique for mandatory to perform clinical and radiographic monito- long term decompression of large mandibular cysts. J Oral Maxillofac ring for years after surgery, since recurrences can appear Surg. 2012;70:856-9. after several years later. 20. Pogrel MA. The use of liquid nitrogen cryotherapy in the mana- gement of locally aggressive bone lesions. 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