|Year : 2016 | Volume
| Issue : 2 | Page : 175-179
A silent transformation of keratocystic odontogenic tumour to squamous cell carcinoma: A case report and review of literature
Upendra Gurugubelli1, Ramesh Tatapudi1, Ravikanth Manyam2, Priyankesh Sinha1
1 Department of Oral Medicine and Radiology, Vishnu Dental College, Bhimavaram, Andhra Pradesh, India
2 Department of Oral and Maxillofacial Pathology, Vishnu Dental College, Bhimavaram, Andhra Pradesh, India
|Date of Submission||14-May-2015|
|Date of Acceptance||27-Aug-2016|
|Date of Web Publication||02-Dec-2016|
Dr. Upendra Gurugubelli
Department of Oral Medicine and Radiology, Vishnu Dental College, Vishnupur, Kovvada Village, Bhimavaram - 534 202, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Till date cases reported elsewhere in the world regarding keratocystic odontogenic tumor transformation to squamous cell carcinoma are very sparse. It has been usually noticed in adult males, with the predominant location being posterior mandibular area. We hereby report a case of squamous cell carcinoma involving anterior mandibular area to posterior mandibular region in a 65-year-old female patient with no evidence of any ulceration and growth intraorally, suggesting that the tumor had a bony origin. Therefore, thorough monitoring of such tumours is necessary to arrive at a proper diagnosis, followed by providing treatment at the earliest.
Keywords: Keratocystic odontogenic tumour, oral squamous cell carcinoma, primary intraosseous carcinoma
|How to cite this article:|
Gurugubelli U, Tatapudi R, Manyam R, Sinha P. A silent transformation of keratocystic odontogenic tumour to squamous cell carcinoma: A case report and review of literature. J Indian Acad Oral Med Radiol 2016;28:175-9
|How to cite this URL:|
Gurugubelli U, Tatapudi R, Manyam R, Sinha P. A silent transformation of keratocystic odontogenic tumour to squamous cell carcinoma: A case report and review of literature. J Indian Acad Oral Med Radiol [serial online] 2016 [cited 2021 Apr 13];28:175-9. Available from: https://www.jiaomr.in/text.asp?2016/28/2/175/195134
| Introduction|| |
Odontogenic keratocyst, first observed by Philipsen in 1956, is a cystic lesion of odontogenic origin, and is well studied for its high recurrent nature. The World Health Organization (WHO) renamed it as keratocystic odontogenic tumour (KCOT) in 2005 because it better reflects its neoplastic nature. WHO defined it as "a benign uni- or multicystic, intraosseous tumor of odontogenic origin, with a characteristic lining of a parakeratinized stratified squamous epithelium, with a potentially aggressive, infiltrative behaviour."  KCOT is usually noted in the second and third decade of life, and is rarely observed in individuals belonging to older age group. It has a slight male predilection. Its most common site is in the mandible followed by the maxilla; in the mandible, the majority of the cysts remain confined to the mandibular ramus and molar area.  Radiographically, KCOT appears as well-defined radiolucency which may be uni- or multilocular. Because KCOT has low potential to resorb the bone and it tends to involve the cancellous bone in early stages with the compact bone invaded much later, very little expansion is observed in KCOT. 
Oral squamous cell carcinoma (OSCC), which constitutes more than 90% of oral cancers, is used as a synonym for oral cancer according to the international classification of diseases. OSCC is usually known to arise from the epithelium, and may in some instances arise from the wall of an odontogenic cyst. It is a rare tumor that occurs exclusively in jaw bones. Because the source of this lesion is epithelium involved in the odontogenesis, WHO, in 1972, suggested the term primary intraosseous carcinoma, and has classified the lesion as an odontogenic carcinoma.  The most recent WHO classification of odontogenic tumors categorizes primary intraosseous carcinomas (PIOC) as solid type carcinomas, carcinomas originating from keratocystic odontogenic tumor (odontogenic keratocyst), and carcinomas arising from odontogenic cysts other than keratocystic odontogenic tumors. Various odontogenic cysts have been associated with odontogenic SCC which include residual cyst, dentigerous cyst, calcifying odontogenic cyst, and lateral periodontal cyst. The most common being residual cyst followed by dentigerous cyst.  In this article, we report one such rare case of SCC which originated from a KCOT in a 60-year-old female patient.
| Case Report|| |
A 60-year-old female patient reported to the outpatient Department of Oral Medicine and Radiology with a chief complaint of pain and swelling in the lower chin region, which was noticed by the patient 20 days back. History revealed that the swelling gradually increased and attained the present size, which was followed by pain 10 days after its onset. Pain was noticed to be sudden in onset, intermittent, severe throbbing type, localized, aggravating on consuming food, and slowly subsiding on its own.
Extraoral examination revealed swelling in the anterior portion of mandible making it appear prognathic. Swelling was roughly oval in shape, measuring approximately 7 × 5 cm, superoinferiorly extending from the vermillion border of the lower lip to a point 3 cm below the inferior border of mandible onto the submental region, and confined to an area within 2 mid-pupillary lines drawn extending up to the lower border of the mandible. The surface over the swelling was smooth, shiny, and similar in color to the surrounding areas, with no associated secondary changes [Figure 1]a-c. Palpation revealed it to be hard in consistency, tender with localized rise in temperature, and no points of fluctuation were noticed. Skin over the swelling was non-pinchable and the swelling was not associated with paresthesia. Bilateral submandibular lymph nodes were palpable, 2 in number (one on each side), roughly oval in shape, measuring approximately 1 × 1 cm, soft in consistency, and mobile and tender on palpation. Intraoral examination revealed partial obliteration of lower labial and buccal vestibule bilaterally due to a swelling extending from incisors up to the molar area, with color over the swelling similar to the adjacent mucosa and no associated secondary changes. Palpation revealed it to be hard in consistency, tender with no points of fluctuation noticed [Figure 1]d.
|Figure 1: (a) Frontal view of swelling in the mandibular anterior region; (b) inferior view of swelling in the mandibular anterior region; (c) lateral view of swelling in the mandibular anterior region; (d) intraoral view with partial obliteration of labial and buccal vestibule|
Click here to view
Fine needle aspiration cytology revealed a blood-tinged fluid that was observed in the syringe following aspiration [Figure 2]a. Intraoral periapical radiograph of the lower left lateral incisor and canine tooth revealed partial loss of crown structure with an ill-defined radiolucency involving the periapical region, with loss in continuity of lamina dura and partial increase in the size of bony trabeculae [Figure 2]b. Orthopantomograph revealed a unilocular radiolucency with well-defined corticated borders toward the right extent and ill-defined jagged margins toward the left extent and inferior aspect of the lesion. It extended horizontally between the radicular portion of the lower right second molar and left second molar, crossing the midline and vertically extending from the alveolar margin up to the lower border of mandible, with complete thinning of cortical bone in the parasymphysis and symphysis region. It was not associated with any tooth displacement or root resorption [Figure 2]c. Anterior mandibular occlusal radiograph revealed an ill-defined radiolucency extending from the lower left second molar to canine region with complete erosion of the buccal cortical plate. Ill-defined ragged margins were observed in the lingual plate of symphysis region. A multilocular radiolucency with ill-defined borders extending from distal portion of lower right canine up to second molar region with expansion of buccal and lingual cortical plates with decreased cortical thickness was noted [Figure 2]d.
|Figure 2: (a) Aspirated fluid; (b) intraoral periapical view reveals partial loss of crown structure with ill-defined radiolucency at root apex; (c) mandibular occlusal view showing bicortical expansion on right side with resorption of buccal cortical plate on left side; (d) orthopantomograph showing an ill-defined osteolytic lesion in the mandibular symphysis and body region|
Click here to view
In differential diagnosis of the present case, we considered central giant cell granuloma as it is the most common lesion with site of occurrence in the anterior mandibular area, which usually crosses the midline; however, commonly age at occurrence is young in patients and the borders in radiographs are ill-defined. On the contrary, in the present case, the borders were well-defined and the patient was a 60-year-old female. Further, dentigerous cyst, which is associated with crown of an unerupted or retained tooth and the swelling of which is fluctuant was considered. But the present case was not associated with crown of any unerupted or retained tooth and the swelling was not fluctuant. Most common tumor observed is ameloblastoma, which accounts for 10-20% cases noted anterior to the lower molar region usually with bicortical expansion along with resorption of adjacent roots; however, in the present case, expansion was observed to some extent but root resorption was not appreciated. Next, commonly encountered tumor is odontogenic myxoma which radiographically shows septae which are straight, few, thin and sharp, and less expansile than ameloblastoma; however, in our case, septae could not be clearly appreciated. Finally, in very rare circumstances, sialoodontogenic tumors are seen in the lower anterior mandibular region. Considering clinical features, history, and radiographic findings, we came to a tentative diagnosis of cyst/tumor of odontogenic origin. The cyst was sent for incisional biopsy and histopathological investigation.
Incisional biopsy and histopathological report
Incisional biopsy was performed and the specimen was sent for pathological evaluation [Figure 3]a and b. Microscopic examination in 4× magnification of Hematoxylin and eosin (H and E) stained section revealed parakeratinized epithelium with inflammatory cellular infiltrate of lymphocytes and hemorrhagic areas in the connective tissue [Figure 3]c. 10× magnification of H and E stained soft tissue section showed dysplasia of hyperplastic epithelium and islands exhibiting large area of necrosis with retepegs, and 40× magnification of H and E stained soft tissue section showed stratified squamous cystic epithelium with dysplastic features, such as nuclear hyperchromatism and hyperplasia, along with nuclear pleomorphism and mitotic figures. With these features, it was diagnosed as a moderately differentiated squamous cell carcinoma of keratocystic odontogenic origin [Figure 3]d]. We searched for a probable primary tumor by careful clinical examination, chest radiograph, and ultrasonography, and the possibility of metastasis was ruled out. The patient was referred to a cancer institute for further treatment and review.
|Figure 3: (a) Incisional biopsy; (b) specimen sample; (c) 10× magnification of hematoxylin and eosin (H and E) stained soft tissue section showing dysplasia of hyperplastic epithelium and islands exhibiting large area of necrosis with retepegs; (d) 40× magnification of H and E stained soft tissue section showing stratified squamous cystic epithelium with dysplastic features, such as nuclear hyperchromatism and hyperplasia, along with nuclear pleomorphism and mitotic figures|
Click here to view
| Discussion|| |
Odontogenic keratocyst, discovered by Philipsen in 1956, was previously described as cholesteatoma, which is a cystic lesion of odontogenic origin. ,, Pindborg and Hansen in 1963 described the essential features of this type of cyst, and it was named keratocyst because the cyst epithelium produced large amounts of keratin that filled the lumen of the cyst. In 1967, Toller suggested odontogenic keratocysts to be benign neoplasms rather than a cyst based on their clinical behavior.  Hence, it was termed as KCOT by WHO in 2005.  KCOT is considered to be a developmental cyst that arises from the dental lamina or its remnants. Ostrofsky found epithelial residues in the retromolar regions and explained their possible relationship to the formation of KCOTs. Their presence in KCOTs involving ascending ramus region may lead to a second thought about the origin of KCOT other than dental lamina. ,
WHO reclassified the tumor based on its
It represents approximately 10% of all jaw cysts. Although a considerable predilection for the mandibular third molar area and ascending ramus exists, KCOTs can also occur in the dentate area, both in the maxilla and mandible, presenting themselves as apparently ordinary odontogenic cysts. , KCOT affect patients of both young and old age groups with peak incidence in 2 nd and 3 rd decades of life. Men are affected more than females. In the maxillofacial region, mandible is more affected than maxilla. In the maxilla, canine region is mostly affected. In the mandible, most odontogenic keratocysts occur in the mandibular molar-ramus region (34.4%), 10.3% in premolar region, 10.3% in canine region, and 8.3% in 1 st and 2 nd molar area. 
- Behavior: As described earlier, KCOT is locally aggressive and highly recurrent
- Histopathology: Shows the basal layer of the KCOT budding into connective tissue. In addition, frequent appearance of mitotic figures in the suprabasal layers is noted
- Genetics: PTCH ("patched"), a tumor suppressor gene involved in both NBCCS (nevoid basal cell carcinoma syndrome) and sporadic KCOTs, is seen on chromosome 9q22.3-q31. Normally, PTCH forms a receptor complex with the oncogene SMO ("smoothened") for the SHH ("sonic hedgehog") ligand. This binding of PTCH to SMO inhibits growth-signal transduction. SHH bound to PTCH releases this inhibition. If the normal functioning of PTCH is lost, the proliferation-stimulating effects of SMO are permitted to predominate. Thus, these features denote the neoplastic nature of KCOT. ,
Clinical symptoms may be pain, soft tissue swelling, expansion of bone, drainage, and various neurological manifestations such as paraesthesia of the lip or teeth.  However, half of all the lesions are described as incidental findings because KCOTs are often asymptomatic until the bone is expanded or if the cyst becomes infected.  Radiologically, there are four variants of the KCOT. They are envelopmental, replacement, extraneous, and collateral.  Radiographically, KCOT appears as well-defined radiolucency which may be unilocular or multilocular. Approximately 20-40% of KCOTs are associated with an unerupted tooth and can be identical in appearance to that of a dentigerous cyst. Root resorption is relatively uncommon.  KCOT have poor bone resorption and involve the cancellous bone in early stages of its development. The compact bone is invaded later in the course and thus exhibits very little expansion.  Cystic lesion which have been reported for long periods of time showed scalloped margins due to the regional resorption of the surrounding bone. 
KCOTs usually occur as a single lesion either unilateral or bilateral. If multiple KCOTs were observed it may be suspected as a case of nevoid basal cell carcinoma syndrome or Gorlin-Goltz syndrome, with characteristic features of nevoid basal cell carcinoma syndrome such as the presence of bifid ribs, calcification of the falx cerebri, frontal bossing, multiple epidermoid cyst, and medulloblastoma. , Recurrence associated with resection is 0% and with simple enucleation combined with adjunctive therapy is 1-8.7%, whereas enucleation alone has shown to have a recurrence rate of 17-56%. This high recurrence rate of KCOTs drives the attention of oral physicians to take utmost interest to diagnose and treat these lesions. Reason for their recurrence are considered to be thin fragile epithelial lining and satellite cysts seen along the basement layer, which are often left out after the surgery. ,
OSCC constitutes 95% of oral cancer cases recorded, and is thus considered a synonym for oral cancer according to the international classification of diseases. They usually arise from the epithelial lining of soft tissues, and very few cases were found to be arising from the epithelial lining of odontogenic cysts. Cases reported to be arising from radicular cyst and dentigerous cyst were common and those from KCOT were recorded to be very sparse. To diagnose SCC derived from odontogenic cysts, Gardner in 1975 proposed criteria that included:
To this, Waldron added a 4 th criterion stating that the lesion representing a metastasis from a distant tumor must be ruled out by physical and radiological examination and the subsequent clinical course. 
- A microscopic transition area from benign cystic epithelial lining to invasive SCC
- No carcinomatous changes in the overlying epithelium
- No source of carcinoma in the adjacent structures.
Schwimmer et al. conducted a literature review and noted 56 cases that strictly adhere to Gardner's criteria. The mean age was 57 years with a 2:1 male to female ratio. The mandible was observed to be involved four times more frequently compared to the maxilla.  The site of lesion was usually seen in the posterior mandible, which may be unilateral or bilateral and less often tended to cross the midline. In some studies, squamous cell carcinoma derived from KCOT cases were also reported to be involving maxilla, which could extend so as to involve maxillary antrum. In our case, the patient's age was within the range of common age of occurrence, i.e. 60-year-old, but we observed a female patient with site of the lesion involving the anterior portion of the mandible crossing the midline, which is contrary to the usual scenario.
Clinical examination revealed no signs of any ulcerations or growth intraorally, which is in contrast to the observation by Falaki et al. and similar to the observation by Maria et al. Lymph nodes are palpable in only 20% of cases according to the available data. In the present case, bilateral submandibular lymph nodes were appreciable and were soft in consistency, mobile, and tender on examination. , Radiographically, a unilocular or multilocular lesion presenting with ill-defined or well-defined border is observed in odontogenic SCC. If the radiolucent area has jagged or irregular margins with indentations and indistinct borders, it can be depicted as malignancy.  In the present case, ill-defined radiolucency was noted associated with bicortical expansion in the fourth quadrant in premolar-molar region and resorbed buccal cortical plate with respect to the third quadrant in premolar-molar region. Few reports reveal SCC derived from odontogenic cyst termed as primary intraosseous carcinoma because they mimic similar clinical and radiological features, which should be ruled out by histopathological examination.
| Conclusion|| |
Although similar type of cases are noted elsewhere in different geographical locations, SCC arising from KCOT are rare and those confined to the old age group and belonging to female sex are very sparse, as exemplified in our present case report. Therefore, thorough monitoring of diagnosed KCOT cases should be conducted not only to check their recurrence but also to keep a third eye on their transformation potential to a devastating malignant form.
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Koppula SK, Kumar A, Nandi D, Choudhary A. Large keratocystic odontogenic tumor of the mandible. J Indian Acad Oral Med Radiol 2015;27:259-63.
Gupta A, Rai B, Nair MA, Bhut MK. Keratocystic odontogenic tumor with impacted maxillary third molar involving the right maxillary antrum: An unusual case report. Indian J Dent Res 2011;22:157-60.
Falaki F, Delavarian Z, Salehinejad J, Saghafi S. Squamous cell carcinoma arising from an odontogenic keratocyst: A case report. Med Oral Patol Oral Cir Bucal 2009;14:E171-4.
Nagraja A, Anigol PS, Kamath VV, Setlur KP. Keratocystic odontogenic tumor of the maxilla: Report of a rare case and review of literature. World J Dent 2012;3:100-8.
Hauer A. Ein Cholesteatom im linken Unterkiefer unter einem retinierten Weisheitszahn. Z Stomatol 1926;24:40-59.
Kostecvka F. Ein Cholesteatom im Unterkiefer. Z Stomatol (Wien) 1929;27:1102-8.
Levy SH. Cyst and tumors of odontogenic origin. In: Rajendran R, editor. Shafer's Textbook of Oral Pathology, Vol. 6. Noida: Elsevier; 2009; p. 254-62.
Motwani MB, Mishra SS, Anand RM, Degwekar SS, Bhawate RR. Keratocystic Odontogenic Tumour: Case Reports and Review of Literature. J Indian Acad Oral Med Radiol 2011;23:150-4.
Stoelinga PJ. Long-term follow-up on keratocysts treated according to a defined protocol. Int J Oral Maxillofac Surg 2001;30:14-25.
Shear M, Speight P. Odontogenic keratocyst. In: Shear M, Speight P, editors. Cysts of the Oral and Maxillofacial Regions. 4 th
Ed. Oxford: Blackwell Munksgaard; 2007. p. 6-58.
Ali M, Ronald AB. The odontogenic keratocyst: Clinical, radiological, and histopathological study. J Am Dent Assoc 2003:134:877-83.
Boffano P, Ruga E, Gallesio C. Keratocystic odontogenic tumor (odontogenic keratocyst): Preliminary retrospective review of epidemiologic, clinical, and radiologic features of 261 lesions from University of Turin. J Oral Maxillofac Surg 2010;68:2994-9.
Madras J, Lapointe H. Keratocystic odontogenic tumour: Reclassification of the odontogenic keratocyst from cyst to tumour. J Can Dent Assoc 2008;74:165-165h.
Maria A, Sharma Y, Chhabria A. Squamous cell carcinoma in a maxillary odontogenic keratocyst: A rare entity. Natl J Maxillofac Surg 2011;2:214-8.
[Figure 1], [Figure 2], [Figure 3]