Odontogenic keratocyst (OKC, currently designated by the World Health Organization as a keratocysticodontogenic tumor) is a locally aggressive, cystic jaw lesion with a putative high-growth potential and apropensity for recurrence. Although it is generally agreed that some features of OKCs are those of a neo-plasia, notably the relatively high proliferative rate of epithelial cells, controversies over the behavior andmanagement of OKCs still exist. Although the question of whether the OKC is a cyst or a neoplasm is yetto be answered with certainty, recent advances in genetic and molecular research i.e. PTCH1 mutationsand involvement of the Hedgehog signaling pathway have a facilitated better understanding of its patho-genesis, hinting at potential novel treatment options. While some surgeons suggest a more conservativeapproach to treating OKCs, notably marsupialization and decompression, future treatment strategiesfocus on molecular approaches that may eventually reduce or eliminate the need for aggressive surgicalintervention. In addition to describing a case that was managed conservatively, we review the treatmentof odontogenic keratocyst, briefly discussing recent trends that help make diagnosis and therapy morespecific and effective.
Long after its first description in 1956 by Philipsen [1], it wasonly in 2005 that the WHO reclassified and renamed the odonto-genic keratocyst (OKC) as a keratocystic odontogenic tumor (KCOT)as it would better mirror its neoplastic behavior. Justifiably so, thisproved to be a major turning point that lead to the actual under-standing of the true pathogenesis of OKC. Hence, it has been definedas “a benign uni- or multicystic, intraosseous tumor of odontogenicorigin, with a characteristic lining of parakeratinized, stratifiedsquamous epithelium and a potential for aggressive, infiltrativebehavior” [2].
Accounting for 11% of all orofacial cysts, OKC could affect boththe jaws, with lesions commonly occurring in the mandible, mostfrequently in the posterior body and ascending ramus [3,4]. Itmay exist as a single lesion or display multiplicity, the latter often
� Asian AOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: AsianSociety of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathol-ogy; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: JapaneseSociety of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants.
being part of the Gorlin’s/Nevoid Basal Cell Carcinoma Syndrome(NBCCS). It has been recognized as the most aggressive of all odon-togenic cysts, owing to its relatively high recurrence rate and itstendency to invade adjacent tissue [3,5]. Thus, the treatment ofOKC has always been challenging. While, on the one hand, becauseOKC has a recurrence rate ranging from 25–62.5% [6], a more radi-cal form of therapy would usually be implemented [7]. On the otherhand, a more conservative strategy would sometimes be suggested.In both cases, however, it is essential that the epithelial compo-nent of the cyst be eliminated completely to reduce recurrence.Yet, complete enucleation of the cyst is difficult, owing to its thin,friable lining.
We describe a case managed conservatively that, in fact, wouldhave required more aggressive treatment. In addition, we reviewthe treatment of odontogenic keratocyst, briefly discussing noveltrends that help make diagnosis and therapy more specific andeffective.
2. Case report
A 35-year old female patient presented to the clinic on July9th 2008 with a swelling in the right lower face since twomonths. Extra-oral examination revealed a very diffuse, roughlyovoid, 3 cm × 4 cm swelling in the right lower third of face. The
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Fig. 1. (a) Clinical picture depicting the extraoral appearance of a swelling in the right lower face. (b) Intraoral picture showing an impacted lower right third molar associatedwith mild buccal and lingual cortical expansion, causing vestibular obliteration. The first and second molars also appear to be displaced superiorly.
Fig. 2. OPT depicting a large, well-defined, multilocular, corticated radioluscency inthe right body-ascending ramus of the mandible, extending to and partially erod-ing the inferior border, causing significant displacement and partial root resorptionof the molars. The inferior dental canal is also seen traversing through the lesionundisplaced.
skin over the swelling was normal (Fig. 1a). Upon palpation, theswelling was bony hard and non-tender. There was no evidenceof lymphadenopathy. Intraorally, partial buccolingual obliterationin the right mandibular posterior region was apparent, owing tocortical expansion (Fig. 1b). The associated soft tissues were how-ever normal. Paresthesia of the inferior alveolar nerve was alsoclinically evident. A panoramic view (Fig. 2) revealed the pres-ence of a large, multilocular, well-defined, corticated radioluscentlesion, about 6.4 cm × 2.6 cm in dimension and was located in theright body and ascending ramus of the mandible. Extending fromthe mandibular canine to third molar, the cyst caused superiordisplacement of the last two molars, simultaneously causing signif-
icant postero-inferior expansion of the lower border. The inferiordental canal did not appear to be displaced and root resorptionwas not evident. Vitality tests on the posterior teeth revealed noresponse.
Axial and coronal sections with 3D CT (Fig. 3a–c) were done. Sur-prisingly, two well-defined, expansile, cystic lesions were pickedup. The larger of the two, measuring 6.4 cm × 2.6 cm × 4.2 cm(Fig. 3a), was seen in the right hemi-mandible, involving the bodyand ascending ramus. Cortical erosion and destruction of bone atmultiple foci was seen, of bone at multiple foci, with compressionand displacement of the right submandibular gland and the over-lying mucosa into the oral cavity. The other was seen in the lefthemi-maxilla, measuring 3.6 cm × 2.7 cm × 3.5 cm (Fig. 4), and waslocated in the alveolus between the roots of 1st and 2nd premo-lars, causing sinus floor buckling, with invasion into infratemporalfossa, posterolaterally. The underlying teeth were displaced fromtheir gingival sockets with evidence of cortical thinning and expan-sion. Based on the signs and symptoms, a provisional diagnosis ofodontogenic cyst was made. Incision biopsy and microscopic exam-ination revealed an orthokeratinized, corrugated epithelium, 6–10layers in thickness, suggesting an orthokeratinized odontogenickeratocyst. Blood investigations and Chest X-ray were normal andthere were no other signs suggestive of NBCCS.
Under hypotensive anesthesia, via a transoral approach, enu-cleation of the mandibular cyst, followed by the applicationof Cornoy’s solution was carried out (Fig. 5a–c). The affectedteeth were extracted. The maxillary cyst was also treated ina similar manner (Fig. 6a and b). The larger of the two cavi-ties was left to heal by secondary intention. Periodic removal of
Fig. 3. (a, b) CT sections (axial, coronal and 3D) depicting a well-defined, expansile, cystic lesion measuring 6.4 cm × 2.6 cm × 4.2 cm seen in the right hemi-mandible,involving the body and ascending ramus. Cortical erosion and destruction at multiple foci seen resulted in compression and displacement of the right submandibular glandand overlying mucosa into the oral cavity. (c) Destruction and expansion of the lateral cortex, causing multiple perforations, are seen.
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Fig. 4. CT axial section (contrast) showing a well-defined, expansile, cystic lesionin the left hemi-maxilla, measuring 3.6 cm × 2.7 cm × 3.5 cm, located in the alveolusbetween the 1st and 2nd premolar roots, causing buckling of the sinus floor withinvasion into the infratemporal fossa, posterolaterally.
povidone-iodine-soaked paraffin ribbon gauze and saline irrigationof the cavity was done till healthy normal mucous membranecovered the floor and walls of the defect. The other was allowedto heal by primary intention. The final diagnosis suggested cameto be orthokeratinized OKC. The patient had been followed up
for thirty-one months and is relatively symptom-free. Serialfollow-up panoramic radiographs demonstrated complete resolu-tion of the lesion with new normal bone formation (Fig. 7a–d).The patient is still under periodic observation at our institutewith no apparent signs of recurrence, as supported by a 2year-10 month post-operative CT scan depicting good bicorti-cal integrity of the right mandible with no evidence of a lyticor sclerotic lesion (Fig. 8b). However, there was evidence of leftchronic maxillary sinusitis and a continuity defect was seen inthe antero-medial wall of the sinus. Nevertheless, clinically, therewere no signs or symptoms suggesting sinusitis (Fig. 9).
3. Discussion
In recent years, a great deal of research into the nature andbehavior of OKC had been carried out. Consequently, it was lookedupon more as a locally aggressive, benign, cystic neoplasm, ratherthan just a cyst, of odontogenic origin. This led to the WHO revisingits nomenclature, thus, assigning the term Keratocystic Odonto-genic Tumor in lieu of Odontogenic Keratocyst in the Head andNeck Tumors’ Classification of 2005. Possessing two histologicalvariants, the parakeratinized variety is known to possess a higherrecurrence potential in comparison to the orthokeratinized type.Brannon, in 1976, suggested 3 mechanisms for its recurrence:incomplete removal of the cyst lining, growth of a new KCOT fromsatellite cysts (or odontogenic rests left behind after surgery) anddevelopment of a new KCOT in an adjacent area that is inter-preted as a recurrence [3]. Recurrence rates vary with follow-uptimes used by operators, the surgical technique employed, and thenumber of cases analyzed (Table 1). Although a few studies havereported recurrences more than 10 years following initial interven-tion, most take place within 5–7 years following treatment. Thus,
Fig. 5. (a) Intraoperative picture depicting the extent of cystic involvement in the left molar-ramus region of the lower jaw resulting in considerable ‘egg-shell’ corticalthinning. The involved teeth were extracted. (b) Seen is a large, deep cavity following piece-meal enucleation of the cyst lining and peripheral ostectomy. (c) Tissue specimenswhich include the enucleated cyst lining and extracted teeth (molars and premolars).
Fig. 6. (a) Intraoperative picture depicting the defect in the anterior wall of left maxillary sinus, resultant to erosive expansion by the cyst. (b) Tissue specimens followingpiecemeal enucleation of the cyst lining.
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Fig. 7. (a–d) Serial Orthopantomograms depicting progressive lesion resolution with normal new bone formation in the mandibular body and ascending ramus.
Fig. 8. (a) Pre-op 3D CT depicting considerable cotical expansion and perforation of the right mandible by the cyst. (b) Post-op 3D CT revealing complete reconstitution ofthe right body and ascending ramus of the mandible at 34 months post-op.
long-term follow-up is an essential aspect in the management ofsuch cysts.
A variety of treatment modalities, ranging from conservativeto radical, have been developed in an attempt to definitively treatKCOT. Most clinicians favor “conservative” therapy, while othersadvocate more “aggressive” forms of treatment. Meiselman et al.consider “enucleation, curettage and marsupialization” as conser-vative therapies [22]. Williams et al. defined aggressive treatmentas “that which is used in addition to enucleation and includescurettage (mechanical, and/or chemical) and/or resection with-out loss of jaw continuity” [23]. Morgan et al. also categorizetreatment methods for KCOT as conservative or aggressive, bothbeing forms of surgical intervention [17]. Aggressive treatmentaddresses the “neoplastic nature” of KCOT and includes periph-eral ostectomy, chemical curettage with Carnoy’s solution or enbloc/segmental resection. Excision of the mucosa overlying thelesion has been recommended, based on histological evidence thatclusters of epithelial islands and microcysts (presumably with thepotential to cause recurrence), found in the area where the lesionwas connected with the mucosa.
The terms decompression and marsupialization are usedinterchangeably; however, they are conceptually different. Firstdescribed by Partsch, in 1892, marsupialization is a means ofdecompressing a cyst. Proponents argue that as an adjunctiveprocedure, marsupialization allows for partial resolution (decreasein size) of the cyst that promotes new bone-fill so that teethor the inferior alveolar nerve may be spared. Furthermore,histological changes, leading to eventual replacement by oralepithelium, have been observed to occur in the lining [24]. In
fact, immunohistochemically, marsupialization not only promotesa reduction in the IL-1� levels in OKC but also results in thedemonstrable absence of cytokeratin 10 expression from the cystepithelium [25]. In addition, the expression of bcl-2 by OKC epithe-lium becomes negative, following decompression and epithelialtransition to normal oral mucosa. However, decompression ormarsupialization has not been recommended alone for the trea-ment of keratocyst, as such reports have documented recurrencerates between 0% and 100% [26].
Fig. 9. Post-op sagittal section depicting defect in antero-medial wall of the leftmaxillary sinus associated with sinus membrane thickening.
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Table 1A review of treatment modalities for KCOT done by various authors is presented as follows.
Sl. No. Author Year No. of cysts Treatment Follow-up period Recurrence
1 Pindborg and Hansen [8] 1963 16 Enucleation and marsupialization 62.5%2 Browne [9] 1970 12 Marsupialization >16 months 25%
72 Enucleation >16 months 23%3 Voorsmit et al. [10] 1981 52 Enucleation 1–21 years 50%
40 Enucleation + cornoy’s solution 1–10 years 3%4 Zachariades et al. [11] 1985 13 Enucleation >5 years 31%
1 Resection >5 years 0%1 Marsupialization >5 years 0%1 Decompression + enucleation >5 years 0%
5 Forssell et al. [6] 1988 28 Enucleation in 1 piece 5–17 years 18%41 Enucleation in > 1 piece 5–17 years 56%
5 Marsupialization 5–17 years 60%6 Brondum and Jensen [7] 1991 44 Marsupialization 7–19 years 18%7 Bataineh and Al Qudah [12] 1998 31 Resection 2–8 years 0%8 Meara et al. [13] 1998 49 Enucleation 1–15 years 35%9 Stoelinga [14] 2001 82 Enucleation, excision of overlying mucosa
and Carnoy’s solution1–25 years 11%
10 Schmidt and Pogrel [15] 2001 26 enucleation and liquid nitrogen cryotherapy 2–10 years 11.5%11 Pogrel and Jordan [16] 2004 10 Marsupialization followed by cystectomy 1.8–4.8 years 0%12 Morgan et al. [17] 2005 11 Enucleation only 5.3 years 54.5%
11 Peripheral ostectomy 18.2%13 Peripheral ostectomy with Carnoy’s solution 0%
2 Enucleation with Carnoy’s solution 50%3 En bloc Resection 0%
13 Maurette et al. [18] 2006 30 Marsupialization followed by Enucleation 2 years 14%14 Madras and Lapointe [19] 2008 16 Curettage 2 months–7
years37.5%
3 Marsupialization 0%2 Resection 0%
15 Martin Gosau [20] 2010 22 Enucleation 4.5 years 50%14 Enucleation with application of Carnoy’s
solution14.3%
16 Tonietto [21] 2011 9 Enucleation followed by liquid nitrogen 3–9 years 0%
Enucleation is another form of cyst treatment. Given the recur-rence rate to be as high as 62.5%, simple enucleation is no longeracceptable. Curettage and enucleation are considered by many asminimal requirement, therapeutically. Therefore, in order to makethese more effective, Stoelinga advocated excising the overlyingoral mucosa in continuity with the cystic lesion [27]. However,many authors have cited difficulty in enucleation and curettage ofOKC with or without cortical perforation, as adherence of the thinfriable lining to adjacent bone or soft tissue may preclude completeenucleation [28]. Thus, in such situations, several authors lend sup-port to Stoelinga’s advocacy [27]. We enucleated the cyst in totofollowing which Carnoy’s Solution (CS) was applied for 3 min. Thesurrounding mucosa was not excised; however, portions of perios-teum in areas of cortical perforation by the cyst were sacrificedduring enucleation.
With the additional application of CS, a recurrence rate between1% and 8.7% is observed [29]. But curettage or peripheral ostectomyafter enucleation does not lower recurrence rates, as compared toenucleation alone. Voorsmit reported a decreased recurrence ratewith enucleation plus CS (2.5%) as compared to enucleation (13.5%)[10]. Morgan, however, saw no association between reduced recur-rence rates and the use of Carnoy’s solution [17]. We had norecurrence for two and a half years, considering the size of thecyst and nature of treatment. But, in light of published literatureon orthokeratinized OKC, no mention, to our knowledge, of itsrecurrence has been made. Authors have advocated mechanicalcurettage techniques (hand and rotary) alone or in combinationwith a chemical solution (Carnoy’s) [27,30] or cryosurgical agents(liquid nitrogen) [30]. Although Voorsmit demonstrated the meandepth of bone penetration by CS with respect to time (1.54 mm after5 min) [27], yet it has been difficult to quantify depth of mechanicalcurettage.
Aggressive surgery/resection is indicated in multiple recurren-ces, in tumors that cannot be managed by other methods, and in
malignant transformation since cases of carcinoma arising fromOKC have been documented [31,32]. Conversely, cases have beensuccessfully treated by marsupialization alone, and this, in conse-quence, would deny OKC of its tumorigenic nature. In fact, a lesionhas also been reported to recur in a bone graft [33]. According to lit-erature, radical excision has no recurrence, i.e. 0%, but is associatedwith high morbidity and therefore should be reserved only afterinitial intervention has failed. In view of the cyst size and degree ofosteolysis, aggressive resection may well be indicated in our case,but conservative therapy seemed to generate an excellent response.
Madras and Lapointe have stated that a difference in recurrencerates between 2 modalities of ≥15% (arbitrarily chosen) is consid-ered the threshold for clinical significance [19]. Nevertheless, it ispossible to infer the following. Whereas enucleation with Carnoy’ssolution, with or without peripheral ostectomy, results in a signif-icantly lower rate of recurrence, than enucleation alone, the use ofcryotherapy with enucleation appears to have no significant effecton recurrence rates when compared with enucleation alone. Again,marsupialization, as a definitive treatment, is associated with asignificantly higher recurrence rate than when the cyst is subse-quently enucleated. Though resection offers a recurrence rate of 0%,it is associated with extreme morbidity. Conversely, to minimizeinvasiveness and recurrence, the most effective option appears tobe enucleation of the KCOT and subsequent application of Carnoy’ssolution.
4. Conventional tools in the diagnosis of odontogenickeratocyst
4.1. Protein analysis and exfoliative cytology
In principle, the finding that keratinizing cysts have lower sol-uble protein levels than those for non-keratinizing cysts suggests
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that protein levels less than 4.0 g per 100 ml would favor the diag-nosis of OKC, whereas values over 5.0 g would suggest other cysts[34]. Also, whenever an inflammatory process is incited in theOKC wall, the degree of keratinization over these areas is altered,thereby causing increased lining permeability, resulting in highersoluble-protein levels in the cyst fluid. Hence, it may be inferredthat the inflammatory process alone would influence the proteincontent of the fluid, and not merely the nature of the lining [35].
Exfoliative cytology, though a conventional tool, may still haverelevance in the preoperative diagnosis of OKC as the aspiratedemonstrates keratinized squames in a film stained by RhodamineB, producing fluorescence [36]. Also, exfoliative cytology and pro-tein estimations, when combined, could afford reasonable levelsof success in the diagnosis of such cysts [37]. Additionally, it ispresumed that protein analysis, qualitative protein electrophore-sis and smears are possible, using minute volumes of 100 �l (cystfluid), with diagnostic accuracy attained, in almost every case [38].
4.2. Keratocyst antigen
Employing specific techniques, an antigen, initially found in theOKC fluid, was later localized to the epithelial cells of its liningand thus was termed keratocyst antigen (KCA). It is not present inthe fluids of other cyst types or in plasma or saliva [39]. However,a subsequent analysis showed that KCA and keratin were relatedmolecules and that KCA might be a soluble component of the lat-ter in cyst fluid following proteolysis, presumably resulting froma structural (antigenic) alteration in keratin. Therefore, the rela-tionship of keratin and KCA facilitated the pre-operative diagnosisof the OKC, by way of agglutination reactions, using syntheticallyprepared anti-keratin [40].
4.3. Imaging features
The odontogenic keratocyst, on conventional radiographs, hasa varied appearance viz. a well-defined radiolucent lesion; a radi-olucent lesion associated with a tooth (not distinguishable from adentigerous cyst), or an expansive multilocular or unilocular lesion(similar to the ameloblastoma) and should therefore be always con-sidered in the differential diagnosis of cystic jaw lesions, owingto its frequent recurrence (13%-60%) following surgical treatment.Comparing the morphology of OKC with other non-keratinizingcysts on CT scans, it is seen that OKC and the dentigerous cyst havethe proclivity to develop more in a direction parallel to the longaxis of the mandible rather than perpendicular to it. Also, kerato-cysts tend to produce a discontinuity in the lingual cortex moreoften than radicular cysts. OKCs exhibit unilocular or multilocularpatterns, but dentigerous cysts are almost always unilocular andmay present with local cortical expansion. Radicular cysts, on theother hand, are mostly unilocular, and less often show a disconti-nuity toward the lingual mandibular cortex, producing an overallrounder shape, often being surrounded by a sclerotic rim [41].
5. Recent advances in the diagnosis and therapy of OKC
5.1. Enzyme histochemistry
Magnusson, in 1978, demonstrated oxidative enzymes NADH2-and NADPH2 diaphorase, glucose-6-phosphate dehydrogenase,glutamate dehydrogenase, as well as acid phosphatase, leucineaminopeptidase and ATPase in the OKC [42]. Also, unlike in othercysts, prominent acid phosphatase and leucine aminopeptidaseactivity is present in OKC. It was suggested that when residuesof OKC lining were left behind at operation, the apparently highmetabolic activity (i.e. glycolytic, citric acid pathways and pentose-phosphate shunt) in the epithelium was a factor that merited
greatest consideration, among reasons for high OKC recurrencerates. Also, as this enzyme has been implicated in the invasive-ness of malignant tumors, high leucine aminopeptidase activityreflects collagenolysis, thus, possibly having a role in the invasive-ness of these cysts. Mason and Matthews, in 1996, stated that highlevels of glucose-6-phosphate dehydrogenase in OKC linings wereconsistent with the clinical behavior of this cyst [43].
5.2. Immunohistochemistry
In 2002, Mervyn Shear immunohistochemically demonstratedPCNA, Ki67 and p53 protein expressivity in actively proliferat-ing cells, particularly in neoplasms. In general, positivity occurredmore frequently and more intensely in OKCs, and more in thesyndrome-related cysts than in solitary ones, when compared withnon-keratinizing cysts such as dentigerous or radicular [44]. Con-versely, in 2008, Gurgel et al. demonstrated no differences inimmunostaining for p53, Ki67 and p63 between primary and recur-rent OKCs or between syndrome-associated and sporadic OKCs[45].
Furthermore, it has been postulated that p63 may have a role inthe proliferative potential of epithelial cells due to its capabilityof blocking wild-type p53, thus, enhancing the biologic aggres-siveness of these cysts. Moreover, in 2005, Lo Muzio et al. havesuggested that p63 expression may be useful to identify cyst typeswith more aggressive and invasive phenotype, thus, corroborat-ing the hypothesis of a suprabasal, proliferative compartment inOKCs [46]. Additionally, in 2008, Cavalcante et al. suggested thatMMP-1 over-expression associated with OKC is thought to causedegradation of the organic bone matrix, favoring dissemination ofthese cysts through the trabecular spaces. MMP-2s have also beenobserved to reside in the basement membrane of odontogenic ker-atocysts and, therefore, have been implicated in the degradation ofthe extracellular matrix surrounding the cysts [47].
5.3. Genetics
PTCH (“patched”), a tumor-suppressor gene, involved in bothNBCCS and sporadic KCOTs, occurs at chromosome locus 9q22.3-q31 [48,49]. Under normal circumstances, the PTCH forms areceptor-complex with the proto oncogene SMO (“smoothened”)for the SHH (“sonic hedgehog”) ligand. Binding of PTCH to SMOinhibits growth-signal transduction, but the binding of SHH to PTCHreverses this inhibition [50]. However, in the event of loss of nor-mal functioning of PTCH, the proliferation-stimulating effects ofSMO predominate.
Data has shown that the pathogenesis of NBCCS and sporadicKCOTs involves a “2-hit hypothesis,” with allelic loss at 9q22, lead-ing to tumor-suppressor gene inactivation. In KCOTs, this leads tothe dysregulation of oncoproteins, cyclin D1 and p53 [51]. Lenchet al. indicated that LOH in the 9q22.3-q31 region has been similarlyreported for many epithelial tumors, including basal cell carcino-mas, squamous cell carcinomas and transitional cell carcinomasand, hence, concluded through such elucidation that LOH is, “bydefinition a feature of tumorigenic tissue” [52].
Recent research has hinted at possible novel techniques forthe treatment of KCOT. In 2000, Taipale et al., through scientificresearch, proved that cyclopamine, a plant-derived, steroidal alka-loid/teratogen, can block cellular proliferative responses to theSHH growth-signal transduction via the activated SHH pathway,caused by oncogenic mutation of proto oncogene Smoothenedand tumor-suppressor Patched (PTCH). Thus, a “mechanism-based”therapeutic strategy emerged for the treatment of human tumorsassociated with both types of oncogenic mutation [53]. Further-more, in 2003, Williams et al. discovered another compoundCUR622414, an Hh small-molecule inhibitor, for the SHH pathway.
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Its binding to the Smoothened oncogene consequently inhibitsSHH-pathway activity, resulting from oncogenic mutations inPatched1. This agent is known to suppress proliferation and induceapoptosis of basaloid cell nests in the BCC, whereas having no effecton normal skin cells. Hence, Hh inhibitors would serve as a validtherapeutic tool for NBCCS-associated OKCs [54].
More recently, however, in 2006, Zhang et al. postulated that anystrategy to develop antagonists of active receptors-transcriptionalfactors of SHH signaling pathway would prove therapeuticallyeffective for the OKC. These include the reintroduction of a ‘wild-type’ form of PTCH, inhibition of the SMO molecule by synthetic,small antagonists and suppression of the downstream transcriptionfactors of the SHH signaling pathway. The inhibition of the SMOoncogene by intra-cystic injection of an SMO protein-antagonistwould thus serve as the most potential treatment alternative forsuch cysts [55].
6. Conclusion
Much of the medical literature pertaining to Odontogenic Ker-atocyst deals with its incidence, nature and clinical behavior,therapeutic approaches and recurrence rates. However, with recentresearch and understanding of its fascinating histochemistry,immunology and molecular genetics, the pathogenetic mecha-nism of OKC, though currently postulated, would yet requirefurther elucidation. However, with regard to treatment protocolsdesigned specifically for the management of this benign cys-tic neoplasm, nothing substantially seems to have changed overthe years. The conventional approaches to treating such cystsmay well influence recurrent rates; however, in the event ofrepeated failure from initial intervention, aggressive (resective –en bloc/segmental/disarticulation) treatment is usually indicatedas the last resort. Although, it may result in effective cure rates, thedegree of physical, psychological and social impairment is signif-icant. The risk-to-benefit ratio, therefore, needs appraisal in eachcase. Long term follow-up constitutes an integral part in the man-agement of these cysts as they are known to recur after severalyears following initial intervention.
Thus far, molecular genetics, having emerged as a versatile toolin the diagnosis of Odontogenic Keratocyst, has revolutionizedour understanding of its nature and behavior. Such precise under-standing may therefore, from the therapeutic standpoint, generateseveral potential alternatives for its better management in future.
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