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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists


 
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CASE REPORT  
Year : 2021  |  Volume : 25  |  Issue : 4  |  Page : 11-17
 

Orthokeratinized odontogenic cyst: Report of eight cases and review of literature regarding its malignant transformation


1 Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Kashan, Iran
2 Department of Oral and Maxillofacial Pathology, School of Dentistry, Kashan University of Medical Sciences, Kashan, Iran
3 Department of Oral and Maxillofacial Surgery, School of Dentistry, Tehran University of Medical Sciences, Kashan, Iran

Date of Submission01-Jan-2020
Date of Decision28-Jul-2020
Date of Acceptance11-Aug-2020
Date of Web Publication19-Mar-2021

Correspondence Address:
Mona Zavarei
Department of Oral and Maxillofacial Pathology, School of Dentistry, Kashan University of Medical Sciences, Kashan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jomfp.JOMFP_1_20

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   Abstract 


Orthokeratinized odontogenic cyst (OOC) is an uncommon odontogenic cyst. It has been categorized as a subtype of odontogenic keratocyst (OKC). In 2005, it was classified as a distinct entity. OOC should be histopathologically differentiated from OKC, which has a higher recurrence rate and lower malignant potential. In addition, OOC should be examined for malignant transformation. The epithelium of odontogenic cysts may rarely show malignant transformation. However, malignant transformation has been reported in inflammatory cysts such as the residual cyst and periapical cyst. The number of carcinomas arising from an OOC is low. This paper describes eight cases of OOC; out of which, two showed the development of squamous cell carcinoma from their epithelial lining.


Keywords: Malignancy, malignant transformation, orthokeratinized odontogenic cyst, squamous cell carcinoma


How to cite this article:
Mahdavi N, Zavarei M, Derakhshan S, Nasab MH. Orthokeratinized odontogenic cyst: Report of eight cases and review of literature regarding its malignant transformation. J Oral Maxillofac Pathol 2021;25:11-7

How to cite this URL:
Mahdavi N, Zavarei M, Derakhshan S, Nasab MH. Orthokeratinized odontogenic cyst: Report of eight cases and review of literature regarding its malignant transformation. J Oral Maxillofac Pathol [serial online] 2021 [cited 2021 Apr 12];25:11-7. Available from: https://www.jomfp.in/text.asp?2021/25/4/11/311535





   Introduction Top


Orthokeratinized odontogenic cyst (OOC) is an uncommon developmental odontogenic cyst. The jaws are the most common site of involvement. OOC was first reported as a subtype of OKC by Wright in 1981. OOCs account for about 7%–17% of all keratinized cysts in the jaws and 10% of odontogenic keratocysts (OKCs).[1],[2] OOC is an odontogenic cyst that has an orthokeratinized epithelium in microscopic evaluation. It has been classified as a separate entity by the World Health Organization since OOC shows lower recurrence rate and higher malignant transformation than OKC.[1] The epithelium of odontogenic cysts can show keratinization or dysplasia.[3] Benign odontogenic tumors are the most common neoplasms arising from the epithelium of odontogenic cysts.[4] Nonetheless, mucoepidermoid carcinoma and squamous cell carcinoma (SCC) are two important malignancies that may arise from the epithelium of an OOC.[5] Malignant changes of the epithelium of odontogenic cysts are uncommon, and have a prevalence of 1–2/1000 cases.[6] Inflammatory cysts such as periapical or residual cysts (and not developmental cysts such as OOC) have the highest incidence of malignant transformation.[6] This paper describes eight cases of OOC; malignant transformation and development of SCC from the cyst lining occurred in two of them.


   Report of Cases Top


Case 1

A 31-year-old pregnant woman presented to dental clinic of Tehran University with a chief complaint of swelling of the anterior maxilla. Radiographic examination revealed a radiolucent, unilocular lesion in the anterior maxilla with corticated borders at the site of right canine tooth [Figure 1]. Radiographic and excisional biopsy findings were suggestive of a cystic lesion. Microscopic examination confirmed a cystic lesion as well. The cyst had orthokeratinized stratified squamous epithelium. Elongated bulbous rete ridges, nuclear pleomorphism, prominent nucleoli, and dyskeratotic cells with focal areas of invasion to the underlying connective tissue were noted in some areas of the epithelium. According to the histopathological findings, the diagnosis of SCC was made [Figure 2]. Another surgical procedure was suggested to the patient to obtain adequate safe margins but the patient refused to undergo another surgical procedure. After 10 months, the patient presented to another medical center complaining of an expansile lesion at the same area. The lesion was completely excised and sent for histopathological analysis, and the diagnosis of acanthotic ameloblastoma was made. The surgeon sent the paraffin blocks of the lesion to our center and asked for consultation. Microscopic examination revealed a tumor consisting of epithelial nests and islands of squamous cells with prominent acantholysis in a myxomatous stroma. Keratin pearls and necrosis were also seen in some foci. The tumor cells showed hyperchromatic nuclei, increased nuclear-cytoplasmic ratio, nuclear and cellular polymorphisms and increased mitotic activity [Figure 3]. Immunohistochemical staining for calretinin was performed to rule out acanthomatous ameloblastoma, which revealed no expression in the tumor cells [Figure 4]. Ki-67 immunostaining showed high proliferative activity of tumor cells [Figure 5]. The diagnosis of SCC was confirmed. The patient underwent en bloc resection, chemotherapy and radiotherapy, and showed no recurrence or metastasis after 1 year of follow-up.
Figure 1: A unilocular radiolucent lesion with corticated borders in the anterior maxilla

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Figure 2: Nuclear pleomorphism, prominent nucleoli, and dyskeratotic cells with focal areas of invasion to the underlying connective tissue

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Figure 3: Squamous cell carcinoma with extensive necrosis

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Figure 4: Immunohistochemical staining for calretinin was performed to rule out acanthomatous ameloblastoma, which revealed no expression in the tumor cells

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Figure 5: Ki-67 immunostaining showed high proliferative activity of tumor cells

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Case 2

A 50-year-old male patient presented to dental clinic of Tehran University with a chief complaint of pain in the right maxilla for some time. Radiographic examination revealed a radiolucent unilocular lesion with corticated borders in the pericoronal area of maxillary right impacted third molar. Afterexcisional biopsy, gross evaluation showed several pieces of sheet-like tissue. Microscopic examination revealed a cystic lesion. The cyst had parakeratinized and orthokeratinized stratified squamous epithelium with elongated rete ridges that showed severe dysplasia. Verrucous hyperplasia was also present in some areas. Islands of dysplastic cells had invaded the connective tissue [Figure 6]. Atypical mitotic figures and keratin pearls were also seen. The cyst wall revealed mild, diffuse infiltration of chronic inflammatory cells and hemorrhage. The diagnosis of SCC arising from OOC was made. The patient died 2 years later.
Figure 6: Verrucous hyperplasia seen in some areas. Islands of dysplastic cells invading the connective tissue are also seen

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Case 3

A 26-year-old female patient presented to dental clinic of Tehran University with a chief complaint of expansion and pain in the left mandible for 1 year. The covering mucosa was normal without any tenderness. Radiographic examination revealed a radiolucent lesion that was unilocular with corticated borders extending from the mandibular left second molar to the left impacted third molar [Figure 7]. After excisional biopsy, gross examination of biopsy specimen showed 2 pieces of cystic tissues, with a keratinized material inside their lumen. Microscopic evaluation showed a cystic lesion. The cyst had orthokeratinized stratified squamous epithelium with a prominent granular cell layer subjacent to the orthokeratinized layer. The cyst wall revealed mild diffuse infiltration of chronic inflammatory cells and hemorrhage. Orthokeratinized strands were seen within the cyst lumen [Figure 8]. The diagnosis of OOC was made.
Figure 7: A unilocular radiolucent lesion with corticated borders extending from the mandibular left second molar to the mandibular left impacted third molar

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Figure 8: Orthokeratinized stratified squamous epithelial lining with prominent granular cell layer (H and E) and elongated rete ridges

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Case 4

A 58-year-old female patient was referred to our department with a lesion that was accidentally detected in radiographic examination. The covering mucosa was normal without any tenderness. Radiographic examination revealed a radiolucent lesion that was unilocular with corticated borders extending from the pericoronal area of the right mandibular third molar to the mid-portion of the mandibular ramus [Figure 9]. Microscopic examination showed a cystic lesion. The cyst had orthokeratinized stratified squamous epithelium with varying thickness and prominent granular cell layer. The underlying connective tissue revealed diffuse mild infiltration of chronic inflammatory cells and sections of blood vessels. Orthokeratinized strands were seen within the cyst lumen. The diagnosis of OOC was made
Figure 9: Panoramic radiograph showing a unilocular radiolucent lesion with corticated borders extending from the pericoronal area of the mandibular right impacted third molar to the mid-portion of the mandibular ramus

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Case 5

A 34-year-old male patient was referred to Tehran University with a chief complaint of swelling in the left posterior mandible. The covering mucosa was normal without any tenderness. Radiographic examination revealed an expansile unilocular radiolucent lesion with corticated borders extending from the mandibular left first molar to the left third molar. There was no impacted tooth [Figure 10]. Lingual expansion and perforation of the cortical plate were detected on cone-beam computed tomography scans [Figure 11]. Afterexcisional biopsy, gross examination of biopsy specimen revealed a cystic lesion that was elastic and creamy brown in color, measuring 2 cm × 1.5 cm × 0.2 cm. The microscopic examination showed a cystic lesion. The cyst had orthokeratinized stratified squamous epithelium with a prominent granular cell layer. Keratin strings were seen within the cyst lumen. The diagnosis of OOC was made.
Figure 10: A unilocular radiolucent lesion with corticated borders extending from the left mandibular first molar to the left mandibular third molar

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Figure 11: Cone-beam computed tomography scans showing lingual expansion and perforation of the cortical plate

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Case 6

A 28-year-old female patient presented to Tehran University with a chief complaint of rapid expansion of the maxilla in the past month. The covering mucosa was normal without any tenderness. After excisional biopsy, gross examination of the biopsy specimen showed multiple pieces of irregular creamy tissues with fragile consistency totally measuring 2.8 cm × 2.2 cm × 1 cm, and two pieces of sheet-liked tissue totally measuring 2.5 cm × 0.5 cm × 0.4 cm. Microscopic examination showed a cyst. The cyst had orthokeratinized stratified squamous epithelium with a prominent granular cell layer. The underlying connective tissue revealed severe mixed inflammatory cell infiltration, collagen fibers, scattered fibroblasts, dystrophic calcification, extravasated red blood cells and bacterial colonies. The diagnosis of OOC was made.

Case 7

A 38-year-old male patient presented to the dental clinic of Tehran University. His chief complaint was expansion of the right side of the maxilla for 4 years. The covering mucosa was normal without any tenderness. After excisional biopsy, gross examination of the biopsy specimen showed multiple irregular pieces of soft tan brown tissue totally measuring 3 cm × 2.5 cm × 0.7 cm. Microscopic evaluation showed a cyst. The cyst had orthokeratinized stratified squamous epithelium with a prominent granular cell layer. The underlying connective tissue revealed diffuse severe chronic inflammatory cell infiltration. The diagnosis of OOC was made.

Case 8

A 53-year-old male patient presented to dental clinic of Tehran University. His chief complaint was swelling of the anterior maxilla. The covering mucosa was normal without any tenderness. Radiographic examination revealed a unilocular radiolucent lesion with corticated borders in the anterior right side of the maxilla with no associated impacted tooth. After excisional biopsy, gross examination showed one piece of gray, brown, cystic lesion measuring 3.2 cm × 2 cm × 1.2 cm. Microscopic examination showed a cystic lesion. The cyst had orthokeratinized stratified squamous epithelium with nodular thickening toward the lumen in some areas. A prominent granular cell layer was evident in the epithelial lining [Figure 12]. The diagnosis of OOC was made.
Figure 12: A cystic lesion lined by orthokeratinized stratified squamous epithelium with nodular thickening toward the lumen in some areas

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   Discussion Top


OOC is an uncommon developmental odontogenic cyst, and 5.2%–16.8% of the cases of OKC are re-categorized as OOC.[1] OOC accounts for approximately 11% of all the jaw cysts.[7] MacDonald and Li,[7] and Li et al.[8] reported that OOC was more common in males. However, in our case series, 5 out of 8 cases were female and only 3 were male.

[Table 1] presents the OOC cases. Evidence shows that OOC more commonly occurs in the third and fourth decades of life,[1],[7],[8] which was the case for 6 out of 8 cases reported in this study; however, two of them were in their sixth decade of life. Moreover, MacDonald and Li[7] reported a preponderance for females in the second decade of life. The most common areas of involvement are the posterior mandible and the mandibular ramus region[8],[9],[12] but in our patients, maxilla and mandible were equally involved. OOCs are usually asymptomatic and the most frequent symptom is a slow-growing swelling, which is occasionally associated with pain.[12] In our study, one patient complained of pain and seven patients had swelling.OOC is a cystic lesion. The cyst has orthokeratinized stratified squamous epithelium with a very prominent granular cell layer. OKC must be considered as a differential entity. The epithelial surface of OKC is corrugated and the basal cell layer is palisaded.[9],[13],[14] The difference between OKC and OOC in keratin expression explains the difference in the characteristics of these two lesions.[15]
Table 1: Orthokeratinized odontogenic cysts reported in the literature

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Malignancy has been rarely reported in OOC or OKC.[16] Evidence shows that the cysts with orthokeratinized surface have a higher risk of malignancy, but evidence is inconclusive on this topic.[2] However, OKCs have a more aggressive behavior than other types of odontogenic cysts.[17] A review study reported 15 cases of SCC developing from OCC or other types of odontogenic cysts.[3] A review on primary intraosseous SCCs arising from odontogenic cysts showed that 60% of cases were related to inflammatory odontogenic cysts such as residual and radicular cysts, and 14% (16 cases) were related to OKC or OOC.[18]

[Table 2] shows malignancies such as SCC arising from OOC and OKC. In our study, two of eight cases showed malignant changes in the cyst lining. Carcinomas developing from an odontogenic cyst are scarce. However, SCC is the most common type of malignancy arising from odontogenic cysts.[6] In our study, two patients had SCC. The most important etiologies for carcinomas include genetics, smoking and alcohol consumption.[17] Malignant changes of odontogenic cyst epithelium often require 30–40 years.[18] Malignant transformation occurs faster in inflammatory cysts.[18] In contrast, in our report, both cases of OOC with malignant transformation occurred in young women (26 and 31-year-old). This may suggest that the nature of the lesion in cases in whom, the malignancy develops at a younger age within a shorter period of time is different from SCC that develops in odontogenic cysts after a long period of time. The lesion may be a primary intraosseous carcinoma with a cystic growth pattern in cases in whom, the malignant lesion develops within a short period of time; whereas, in patients who have a history of a preexisting cystic lesion for many years, malignant transformation occurs in the epithelium of the cyst after a long period of time.
Table 2: Cases of squamous cell carcinoma arising from Orthokeratinized odontogenic cyst and odontogenic keratocyst reported in the English literature from 2006 to 2016

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   Conclusion Top


OOCs are scarce developmental cysts that require careful consideration. They should be differentiated from the more common OKCs, which have a higher recurrence rate and lower malignant potential. OOCs should be carefully examined to rule out any malignant transformation.

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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[30]



 
   References Top

1.
Dong Q, Pan S, Sun LS, Li TJ. Orthokeratinized odontogenic cyst: A clinicopathologic study of 61 cases. Arch Pathol Lab Med 2010;134:271-5.  Back to cited text no. 1
    
2.
Neville B, Douglas D, Allen C, Bouquot J. Oral and Maxillofacial Pathology. 3rd ed.. Philadelphia: W.B. Saunders; 2002.  Back to cited text no. 2
    
3.
Makowski GJ, McGuff S, van Sickels JE. Squamous cell carcinoma in a maxillary odontogenic keratocyst. J Oral Maxillofac Surg 2001;59:76-80.  Back to cited text no. 3
    
4.
Siar CH, Ng KH. Squamous cell carcinoma in an orthokeratinised odontogenic keratocyst. Int J Oral Maxillofac Surg 1987;16:95-8.  Back to cited text no. 4
    
5.
MacLeod RI, Soames JV. Squamous cell carcinoma arising in an odontogenic keratocyst. Br J Oral Maxillofac Surg 1988;26:52-7.  Back to cited text no. 5
    
6.
Bereket C, Bekçioğlu B, Koyuncu M, Şener I, Kandemir B, Türer A. Intraosseous carcinoma arising from an odontogenic cyst: A case report. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:e445-9.  Back to cited text no. 6
    
7.
Macdonald DS, Li TK. Orthokeratinized odontogenic cyst in Hong Kong community: The clinical and Radiographic features. Dentomaxillofac Radiol 2010;39:240-5.  Back to cited text no. 7
    
8.
Li TJ, Kitano M, Chen XM, Itoh T, Kawashima K, Sugihara K, et al. Orthokeratinized odontogenic cyst: A clinicopathological and immunocytochemical study of 15 cases. Histopathology 1998;32:242-51.  Back to cited text no. 8
    
9.
González Galván Mdel C, García-García A, Anitua-Aldecoa E, Martinez-Conde Llamosas R, Aguirre-Urizar JM. Orthokeratinized odontogenic cyst: A report of three clinical cases. Case Rep Dent 2013;2013:672383.  Back to cited text no. 9
    
10.
Manickam S, Andamuthu Y, Praveen S. Prevalence and clinicopathological comparison of kerotocystic odontogenic tumor and orthokeratinized odontogenic cyst in South Indian sample population: A retrospective study over 13 years. J Pharm Bioallied Sci 2014;6 Suppl 1:S127-30.  Back to cited text no. 10
    
11.
Vera-Sirera B, Forner-Navarro L, Vera-Sempere F. Immunohistochemical expression of glucose transporter 1 in keratin-producing odontogenic cysts. BMC Oral Health 2016;16:32.  Back to cited text no. 11
    
12.
Mahdavi N, Taghavi N. Orthokeratinized odontogenic cyst of the maxilla: Report of a case and review of the literature. Turk Patoloji Derg 2017;33:81-5.  Back to cited text no. 12
    
13.
Deyhimi P, Hashemzade Z. Comparative study of TGF-alpha and P53 markers expression in odontogenic keratocyst and orthokeratinized odontogenic cyst. Dent Res J 2012;9:S39-44.  Back to cited text no. 13
    
14.
Rangiani A, Motahhary P. Evaluation of bax and bcl-2 expression in odontogenic keratocysts and orthokeratinized odontogenic cysts: A comparison of two cysts. Oral Oncol 2009;45:e41-4.  Back to cited text no. 14
    
15.
Aragaki T, Michi Y, Katsube K, Uzawa N, Okada N, Akashi T, et al. Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenic tumor and orthokeratinized odontogenic cyst. Hum Pathol 2010;41:1718-25.  Back to cited text no. 15
    
16.
Foley WL, Terry BC, Jacoway JR. Malignant transformation of an odontogenic keratocyst: Report of a case. J Oral Maxillofac Surg 1991;49:768-71.  Back to cited text no. 16
    
17.
Yoshida H, Onizawa K, Yusa H. Squamous cell carcinoma arising in association with an orthokeratinised odontogenic keratocyst. J Oral Maxillo fac Surg 1996;54:647-51.  Back to cited text no. 17
    
18.
Saito T, Okada H, Akimoto Y, Yamamoto H. Primary intraosseous carcinoma arising from an odontogenic cyst: A case report and review of the Japanese cases. J Oral Sci 2002;44:49-53.  Back to cited text no. 18
    
19.
Falaki F, Delvarian 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.  Back to cited text no. 19
    
20.
Chaisuparat R, Coletti D, Kolokythas A, Ord RA, Nikitakis NG. Primary intraosseous odontogenic carcinoma arising in an odontogenic cyst or de novo: A clinicopathologic study of six new cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:194-200.  Back to cited text no. 20
    
21.
Sato T, Kamiya Y, Tochihara S, Toyoda N, Asada K, Ishibashi K. Primary intraosseous squamous cell carcinoma of the mandible: Report of a case and review of the recent literature. Oral Med Pathol. 2006; 11:83-8.  Back to cited text no. 21
    
22.
Mitchell O, Cameron M, Coghill S. Squamous cell carcinoma arising from an odontogenic keratocyst associated with an impacted upper canine. Br J Oral Maxillofac Surg 2010;48:S25-55.  Back to cited text no. 22
    
23.
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.  Back to cited text no. 23
[PUBMED]  [Full text]  
24.
Lee JW, Gates R, Wignall A. Squamous cell carcinoma arising from a keratocystic odontogenic tumor. Otolaryngol Head Neck Surg 2011;145:356-7.  Back to cited text no. 24
    
25.
Acharyaa S, Tayaara AS, Hallkeria K, Adirajaiahb S, Gopalkrishnanb K. Squamous cell carcinoma emerging in an orthokeratinized odontogenic cyst: A case report and brief review. JOMSMP 2014;26:563-8.  Back to cited text no. 25
    
26.
Tamgadge S, Tamgadge A, Modak N, Bhalerao S. Primary intraosseous squamous cell carcinoma arising from an odontogenic keratocyst: A case report and literature review. Ecancermedicalscience 2013;7:316.  Back to cited text no. 26
    
27.
Jain M, Mittal S, Gupta DK. Primary intraosseous squamous cellcarcinoma arising in odontogenic cysts: An insight in pathogenesis. Jh J Oral Maxillofac Surg 2013;71:E7-14.  Back to cited text no. 27
    
28.
Akheel M, Hussain J, Chablani D. Keratinizing squamous cell carcinoma A rare case report. J Oncol Res Med 2014;1:1-4.  Back to cited text no. 28
    
29.
Saxen C, Aggarwal P, Wadhwan V, Bansal V. Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity 2015;19:406.  Back to cited text no. 29
    
30.
Martínez-Martínez M, Mosqueda-Taylor A, Delgado-Azañero W, Rumayor-Piña A, de Almeida OP. Primary intraosseous squamous cell carcinoma arising in an odontogenic keratocyst previously treated with marsupialization: Case report and immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;121:e87-95.  Back to cited text no. 30
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]
 
 
    Tables

  [Table 1], [Table 2]



 

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