|Year : 2015 | Volume
| Issue : 2 | Page : 253-258
Keratocystic odontogenic tumor: A case report and review of literature
Keerthi K Nair, Ashok Lingappa, Poornima Rangaiah, Pramod Gujjar Vittobarao
Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davangere, Karnataka, India
|Date of Submission||28-Jan-2015|
|Date of Acceptance||14-Oct-2015|
|Date of Web Publication||21-Nov-2015|
Keerthi K Nair
House Number: 621/1, 1st Floor, 17th Cross, 2nd Main Indiranagar, Bangalore - 560 038, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Keratocystic odontogenic tumor (KCOT) has been identified as a "tumor" after observation of its biological behavior and genetic abnormalities consistent with neoplastic progression. In 2005, the World Health Organization (WHO) working group considered odontogenic keratocyst (OKC) to be a tumor and recommended the term KCOT, distinguishing the lesion from the orthokeratinizing variant, which is now considered an OKC or orthokeratinized odontogenic cyst. Very rarely, KCOTs can transform into more aggressive lesions such as ameloblastoma and primary intraosseous carcinoma (PIOSCC). In this paper, we present a case of KCOT involving the angle and ramus of the mandible, with histopathologic evidence of ameloblastomatous changes. We also discuss about the evolution of this lesion from a cyst to a tumor along with the latest updates of the entity.
Keywords: Ameloblastomatous changes, keratocystic odontogenic tumor, odontogenic keratocyst
|How to cite this article:|
Nair KK, Lingappa A, Rangaiah P, Vittobarao PG. Keratocystic odontogenic tumor: A case report and review of literature. J Indian Acad Oral Med Radiol 2015;27:253-8
|How to cite this URL:|
Nair KK, Lingappa A, Rangaiah P, Vittobarao PG. Keratocystic odontogenic tumor: A case report and review of literature. J Indian Acad Oral Med Radiol [serial online] 2015 [cited 2019 Sep 18];27:253-8. Available from: http://www.jiaomr.in/text.asp?2015/27/2/253/170148
| Introduction|| |
Keratocystic odontogenic tumor (KCOT) comprises a unique pathological entity characterized by aggressive or destructive behavior and propensity to recurrence. Usage of the term odontogenic keratocyst (OKC) had been under a lot of dispute from the time it was introduced in 1956. , The World Health Organization (WHO) reclassified this lesion in 2005 as a KCOT, , and defined it as "a benign uni- or multicystic intraosseous tumor of odontogenic origin, with a characteristic lining of parakeratinized stratified squamous epithelium and potentially aggressive, infiltrative behavior. It may be solitary or multiple. The latter is usually one of the stigmata of the inherited nevoid basal cell carcinoma syndrome (NBCCS)," ICD-O code 9270/0.  Longstanding KCOTs have been reported to transform into primary intraosseous carcinoma (PIOSCC) or an ameloblastoma. 
| Case Report|| |
A 40-year-old male patient was referred to our department from a private dental clinic with a panoramic radiograph revealing osteolytic lesion in the right side ramus of the mandible. Patient also complained of moderate to severe throbbing pain in his right lower back jaw region since 15 days. There was no associated history of swelling, fever, or pus discharge. Patient could not recollect any past history of trauma. His past dental history revealed that he had undergone extraction of the offending tooth in a private dental clinic 7 days back, following which the pain became severe and continuous. According to the patient, the extracted tooth had no decay. Subsequently, he had undergone panoramic imaging. Patient's past medical history was non-contributory.
On examination, no gross facial asymmetry or neurosensory deficit was elicited [Figure 1]a and b]. Right and left submandibular lymph nodes were palpable and his mouth opening was restricted to 1.5 cm. Patient's 47 and 3 rd molars of all quadrants were clinically missing. There was no obliteration of the buccal and lingual vestibule in 47 region and the mucosa appeared intact. On palpation, mild expansion of the buccal and lingual cortical plates were evident immediately distal to 47 and the area was tender [Figure 2]. There was no mobility of the adjacent teeth.
|Figure 2: Intraoral view revealing clinically missing 47 and 48 with extraction socket of 47|
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Panoramic radiograph (OPG) revealed a well-defined multilocular radiolucency involving the right angle and ramus regions of the mandible. The radiolucency measured approximately 6 cm × 3 cm in its largest dimensions and was irregular in shape with well-corticated scalloped borders. Antero-posteriorly, it extended from the mesial aspect of 46 to 1 cm below the sigmoid notch. Supero-inferiorly, it extended from the anterior border of the ramus of the mandible to the inferior border of the mandible. Within the radiolucency, some evidence of internal septa and impacted 48 were present. Inferior alveolar nerve was not traceable [Figure 3]. Intraoral periapical (IOPA) radiograph revealed evidence of loss of lamina dura in relation to the distal root of 46 [Figure 4]. Fine-needle aspiration cytology (FNAC) of the lesion yielded few drops of blood, which on cytological examination revealed inflammatory cells. Computed tomography (CT) was performed which demonstrated expansion of the buccal and lingual cortical plates. The inferior alveolar nerve was intact. Varying values of Hounsfield units were noted within the osteolytic area [Figure 5]a and b]. Radiographic differential diagnoses of KCOT and ameloblastoma were considered. Later, an incisional biopsy was performed for the osteolytic lesion. The histopathologic features were suggestive of KCOT. But a small portion of tissue showed ameloblastomatous change [Figure 6]. Hence, a diagnosis of KCOT showing ameloblastomatous changes was made. Later, the lesion was completely excised with marginal resection of the mandible and disarticulation of the condyle on the left side. Specimen radiograph was taken to confirm the margins [Figure 7]. The resected specimen histopathologically revealed features of KCOT [Figure 8]. The patient was advised intermaxillary fixation with transosseous screws and reconstruction has been planned at a later date. Currently, he is kept under regular follow-up [Figure 9].
|Figure 3: OPG radiograph showing multilocular radiolucency in the right angle and ramus of the mandible with impacted 48 within the radiolucency|
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|Figure 4: IOPA radiograph showing impacted 48 within the radiolucency with evidence of loss of lamina dura in the distal root of 46|
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|Figure 5: (a) Axial section showing buccolingual expansion (arrows) of the right side body and ramus of the mandible. There is evidence of impacted tooth (black arrow) within the osteolytic area. The cortical plates are intact. Internal structure had 20-30 HU in most of the areas. (b) Coronal section revealing thinning of the lingual cortical plate (arrow)|
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|Figure 6: Photomicrograph showing (a) epithelium and connective tissue, with epithelial lift from the connective tissue showing cleft formation (H&E, 10× magnifi cation) and (b) Stellate reticulum-like cells suggestive of ameloblastomatous change (H&E, original magnifi cation 40×)|
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|Figure 7: (a) Resected specimen of the mandible. (b) Specimen's radiograph showing marginal clearance from the lesion|
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|Figure 8: Photomicrograph showing corrugated parakeratinized epithelium and few areas of epithelial budding into the connective tissue stroma (H&E, original magnifi cation 10×). Inset: Palisade layer of low columnar basal cells with few cells showing hyperchromatic nuclei (H&E, original magnifi cation 40×)|
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|Figure 9: 1 month postoperative (a) clinical photograph and (b) radiograph|
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| Discussion|| |
The first description of OKC was published by Philipsen in 1956 for all the cysts that showed keratinization histologically.  Pindborg and Hansen (1963) suggested the histological criteria, which were confirmed by Browne in 1970 and 1971. , Toller (1967) suggested that the OKC should best be regarded as a benign cystic neoplasm, rather than an odontogenic cyst.  In 1992, WHO reported that OKC was the preferred terminology for cysts with keratinized lining.  In 2005, WHO reclassified intraosseous parakeratinized variant as a tumor.  Cystic jaw lesions that are lined by orthokeratinized epithelium, therefore, do not form part of spectrum of KCOT, which remains a subject of controversy  and is now recognized as an entirely different group of lesions termed orthokeratinized odontogenic cyst (OOC).  Keratocystic odontogenic tumors are of great interest in clinical practice and require special attention due to their specific histopathologic features, aggressive and infiltrative behavior, and tendency to recur. 
There are few factors which led to re-characterization of the keratocyst as KCOT. 
The KCOT is believed to arise from cell rests of the dental lamina. ,, The human homolog of the Drosophila segment polarity gene PTCH1 has been identified as the gene responsible for NBCCS as well as in sporadic KCOTs. PTCH1 has been mapped to 9q22.3-31.  Markers of proliferation found to be associated with KCOT are proliferating cell nuclear antigen (PCNA), Ki67, p53, Bcl 2 sequencing of the enzyme dihydrolipoyl acetyl transferase, matrix metalloproteinase 2 and 9. ,, Higher proliferative activity in NBCCS-associated lesions reflects the underlying genetic abnormalities.  Human papilloma virus (HPV) has been suggested as a possible etiology due to the presence of koilocytosis in the tumor. 
- The KCOT exhibits locally destructive and highly recurrent behavior. 
- KCOTs are characterized by parakeratinized epithelium, in contrast to the orthokeratinized variant seen in OOC.  KCOT reveals budding of the basal layer into the connective tissue and frequent mitotic figures. 
- KCOTs are associated with inactivation of PTCH, the tumor suppressor gene. ,,
- Multiple KCOTs may present as one of the stigmata of the inherited NBCCS. It is also known as Gorlin syndrome. 
A male predominance has been reported in KCOT. ,,, On the contrary, few studies have reported a predilection for females. , KCOT has been reported in a wide age range, with a peak incidence found in the second and third decades. The mandible is involved more frequently than the maxilla: About 65-83% of KCOTs occur in the mandible. Both in maxilla and mandible, it has a predilection for the posterior part of the jaw. ,,, A noticeable number of cases are diagnosed incidentally during routine dental examination. Most frequently occurring signs and symptoms include swelling, pain, and paresthesia. If secondarily infected, discharge, abscess and trismus, and cellulitis can be present. ,, It almost always occurs within bone, although a small number of cases of peripheral KCOT have been reported. ,, FNAC can be non-productive in case of KCOT or may produce a yellowish white keratin material. 
Characteristic radiographic features of KCOT are listed below: ,,,
In 25-40% of cases, there is an unerupted tooth involved in the lesion. , In the maxilla, they can invaginate and occupy the entire maxillary antrum.  Computed tomography (CT) scans and contrast-enhanced magnetic resonance imaging (MRI) may be useful in assessment of cortical perforation and soft tissue involvement.  On a plain CT study, high attenuation within an expansile benign lesion, with no enhancement after contrast material injection indicates KCOT. Involvement of the adjacent vital structures can be better studied on CT.  The relatively high isotropic spatial resolution of osseous structures with a reduced radiation dose, low cost, and easy accessibility are advantages of cone beam computed tomography (CBCT) over CT.  On MRI, KCOT usually shows heterogeneous signal intensity on T1- or T2-weighted images, or in both. ,
- Unilocular or multilocular radiolucency with distinctly corticated, often scalloped, borders.
- Minimal expansion, especially toward the lingual (medial) side and growth along the length of the mandible.
- A radiolucent lumen is seen which can have a hazy appearance in conventional radiography. This hazy appearance or high attenuation is suggestive of a dense proteinaceous material such as keratin.
- Displacement of developing teeth and/or separation or rarely resorption of the roots of erupted teeth and extrusion of erupted teeth.
KCOT may need to be differentiated from dentigerous cysts, ameloblastomas, radicular cysts, simple bone cysts, and central giant cell granulomas.  It is found that a distinctive epithelial cell proliferation in KCOT may determine its unique growth and behaviour, and its imaging features. The growth pattern of KCOT epithelium is characterized by heterogeneity, and explains the infiltrative growth in KCOTs in contrast to the expansive growth in other cysts.  On histopathology, the epithelium is distinctive with uniformly thin epithelial lining of six to eight cell layers and does not demonstrate rete ridges. This results in epithelial lifting from the fibrous connective tissue and cleft formation, which are considered as artifactual but are characteristic of KCOT.  The superficial luminal surface of the epithelium demonstrates wavy parakeratotic epithelial cells; hence, the epithelium is usually described as corrugated parakeratinized epithelium. , A prominent palisaded basal layer of hyperchromatic columnar to cuboidal cells are often described as having "picket fence" or "tomb-stone" appearance  with keratinaceous material in the cystic cavity. , Epithelial islands, daughter cysts, hyaline bodies, epithelial budding of the basal layer, and dystrophic calcification have been reported in OKC and KCOT. 
Morgan and colleagues categorize the surgical treatment methods for KCOT as conservative and aggressive. Conservative treatment includes enucleation, with or without curettage, or marsupialization. Conservative treatments preserve the anatomical structures, but have a risk of higher recurrence rate.  Aggressive treatment is usually recommended which includes peripheral ostectomy, chemical curettage with Carnoy's solution, or en bloc resection.  Treatment of cysts with Carnoy's solution before enucleation tends to damage the epithelial lining to such an extent that proper histological diagnosis may be difficult.  Recent studies have shown possible treatment modalities for KCOT, such as cyclopamine, a plant-based steroidal alkaloid, which inhibits the cellular response to the sonic hedgehog (SHH) signal activity. Zhang et al. postulate that antagonists of SHH signaling factors could effectively treat KCOTs. They suggest that intracystic injection of a smoothened (SMO) protein antagonist has the greatest potential as a future treatment option. 
The average reported recurrence rate ranges from 30 to 62%. The presence of residual epithelium or an epithelial remnant after the treatment is one of the suspected contributing factors for the high recurrence rate or presence of satellite cysts in the cyst wall.  A higher recurrence rate in young patients and maxillary lesions and intermediate rate in mixed lesion of OKC and KCOT have been reported. ,, A long-term follow-up of 5-10 years is recommended.  Some KCOT linings may have the characteristics of epithelial dysplasia or show features of ameloblastoma. Tumors with such characteristics rarely evolve into squamous cell carcinoma or ameloblastoma. 
| Conclusion|| |
Definite diagnosis of KCOT on a clinical and radiographic basis is not possible. But with appropriate and advanced imaging modalities, we can strongly suspect this entity, and they help us in selecting the necessary treatment protocol as it is an aggressive tumor. Very rarely, KCOT may show features which could possess the potential to evolve into PIOSCC or ameloblastoma, similar to the present case.
Declaration of Patient Consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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