|Year : 2015 | Volume
| Issue : 4 | Page : 275-279
Primary intraosseous squamous cell carcinoma arising from keratocystic odontogenic tumor: CK 17 evaluation
Rashmi Metgud1, Bhagwandas A Rai2, Bipin A Bulgannawar2, Kanupriya Gupta3
1 Department of Oral and Maxillofacial Pathology, Pacific Dental College and Hospital, Udaipur, Rajasthan, India
2 Department of Oral and Maxillofacial Surgery, Pacific Dental College and Hospital, Udaipur, Rajasthan, India
3 Department of Oral and Maxillofacial Pathology, Mithila Minority Dental College and Hospital, Darbhanga, Bihar, India
|Date of Web Publication||14-Dec-2015|
Professor and Head of Department, Department of Oral and Maxillofacial Pathology, Pacific Dental College and Hospital, Paher University, Udaipur - 313 001, Rajasthan
Source of Support: None, Conflict of Interest: None
Primary intraosseous squamous cell carcinoma (PIOSCC) derived from an odontogenic keratocyst (OKC) is a rare malignant neoplasm of the jaws, which is locally aggressive, with predominantly poor prognosis. The number of well-documented cases of PIOSCC ex OKC is extremely small; thus sufficient incidence data are not available in the literature. Overall and disease-free survival is poor, with almost 50% patients failing to survive within the first 2 years of follow-up, and this can be attributed to the delayed diagnosis. Knowledge of the clinical, radiographic, and histopathologic features of primary intraosseous squamous cell carcinoma (PIOSCC) allows accurate diagnosis and appropriate treatment of this rare malignancy.
Keywords: Cytokeratin, immunohistochemistry, malignant transformation, keratocystic odontogenic tumor (KCOT), primary intraosseous squamous cell carcinoma (PIOSCC)
|How to cite this article:|
Metgud R, Rai BA, Bulgannawar BA, Gupta K. Primary intraosseous squamous cell carcinoma arising from keratocystic odontogenic tumor: CK 17 evaluation. J NTR Univ Health Sci 2015;4:275-9
|How to cite this URL:|
Metgud R, Rai BA, Bulgannawar BA, Gupta K. Primary intraosseous squamous cell carcinoma arising from keratocystic odontogenic tumor: CK 17 evaluation. J NTR Univ Health Sci [serial online] 2015 [cited 2020 Apr 4];4:275-9. Available from: http://www.jdrntruhs.org/text.asp?2015/4/4/275/171749
| Introduction|| |
The World Health Organization (WHO) defines primary intraosseous carcinoma (PIOC) of the jaw as a "squamous cell carcinoma arising within the jaw, having no initial connection with the oral mucosa and presumably developing from residues of the odontogenic epithelium."  Most arise in odontogenic cysts such as residual periapical cysts, dentigerous cysts, and odontogenic keratocysts (OKCs), and such lesions are called primary intraosseous squamous cell carcinoma (PIOSCC) ex odontogenic cyst. Of these cysts, OKC linings seem to have higher mitotic activity than those of other odontogenic cysts, with a great potential to evolve into squamous cell carcinoma (SCC), and although rare, this has been reported. 
According to the new histological classification of tumors from the WHO, KCOT is currently considered a specific odontogenic tumor and the PIOSCC derived from it is considered as a specific entity that is different from other PIOSCC derived from odontogenic cysts.  Even though PIOSCC has been clearly deﬁned by the WHO, the diagnostic criteria remain obscure.
| Case Report|| |
A 35-year-old male patient reported with a chief complaint of reduced mouth opening since 2 months and a history of swelling on left side of the face, which was followed by pain since 15 days. In addition there was history of heaviness with altered sensation on the same region for the same duration. On extraoral examination, diffuse, firm swelling was evident on the left lower third of the face involving the left body of the mandible, the angle of the mandible extending anteriorly to the left parasymphysis region, posteriorly to the ramus and preauricular region, superiorly to the line drawn from the left corner of the mouth to the pinna region, and inferiorly to the submandibular region. The overlying skin was normal and not associated with raised temperature. Swelling was tender on palpation. The left submandibular lymph nodes and upper cervical chain of lymph nodes were tender and palpable. With reduced mouth opening, intraoral examination revealed an intact overlying mucosa [Figure 1].
Computed tomography (CT) scan revealed an expansile cystic mass along the body and ramus of the mandible, with cortical thickening and focal breaches [Figure 2].
On panoramic radiograph, the posteroanterior view of the mandible and the cross-sectional occlusal view of the mandible demonstrated multilocular, well-defined radiolucency showing knife-edge borders with multiple septae from #33 extending posteriorly to the angle, ramus, and coronoid region of the left mandible with impacted #38 at the midway of the left ramus with a discontinuity in the lower border of the mandible. At the angle region, pathological fracture with resorption of roots was observed [Figure 3],[Figure 4] and [Figure 5].
|Figure 3: Panoramic radiograph of mandible revealing multilocular radiolucency|
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Incisional biopsy was performed, which on microscopic examination revealed cystic lumen lined by an epithelium and connective tissue stroma. Cystic epithelial lining was of varied thickness, a few areas showing 6-8 cell layers along with tall columnar basal cells and separation from the connective tissue. Epithelial lining was dysplastic and showed invasion into the stroma in the form of nests and islands. Dysplastic features such as mitotic figures, nuclear hyperchromatism, pleomorphism, and individual cell keratinization were evident, and in some islands squamous metaplasia was seen. Connective tissue stroma was composed of collagen fibers interspersed with fibroblasts, moderate and diffuse chronic inflammatory cell infiltrate, endothelial-lined vascular spaces, and extravasated red blood cells (RBCs) [Figure 6]a and b.
|Figure 6: (a) Sections revealing cystic epithelial lining invading into the stroma (b) Sections revealing tumor epithelial islands with inflammatory cells (Hematoxylin and eosin 10×, 40×)|
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Immunohistochemical staining with cytokeratin 17 (CK 17) was performed, which confirmed the histopathological findings [Figure 7]a and b. Thus, on clinicopathological correlation a final diagnosis of PIOSCC arising in keratocystic odontogenic tumor (KCOT) was rendered.
|Figure 7: (a) CK 17 expression in epithelial islands (10×) (b) CK 17 expression in cystic lining (40×)|
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| Discussion|| |
Primary intraosseous squamous cell carcinoma occurs only in the jaw bones and predominantly in the posterior mandible. It affects men more than women, at a ratio of about 2.2:1, and mostly occurs in patients aged above 60 years. 
Odontogenic carcinomas are extremely rare tumors, first described by Loos in 1913 as a "Central Epidermoid Carcinoma" of the jaw. It is difficult to determine the total number of reported cases because of insufficient data about published cases and different classifications suggested for these tumors, although there appear to be about 82 cases reported in the world literature. 
According to the new WHO classification of odontogenic cysts and tumours (2005), OKCs were designated as KCOTs. A PIOSSC arising from the wall of KCOT is a rare tumor occurring within the jaw bones. Bodner et al. conducted a retrospective study of 116 cases of PIOSCC between 1938 and 2010. The results of the study showed that there have been only 16 known cases of PIOSCC arising from an OKC. 
The pathogenesis of PIOSCC arising from an KCOT is largely unknown. According to Browne and Gouch,  keratin metaplasia followed by epithelial hyperplasia and then epithelial dysplasia of cyst epithelia were the significant events in the development of SCC in OKCs. In this context, van der Wal et al.  mentioned that the presence of keratinization in the cyst lining results in a greater risk of malignant changes. According to Gardner and Yu et al., , long-standing chronic inflammation has also been suggested as a possible predisposing factor. The main mechanism of the inflammation-induced carcinogenesis includes the formation of reactive oxygen metabolites, causing damage to DNA, protein, and cell membranes, and eventually showing the compensatory proliferative response of neoplastic cells against the normal apoptotic mechanism.  In the present case inflammation may have possibly led to the development of PIOSCC.
Gardner (1969) proposed definitive criteria to identify a lesion as PIOSCC ex odontogenic cyst:
- A microscopic transition from benign cystic epithelial lining to SCC,
- An intact overlying oral mucosa,
- absence of carcinoma in the adjacent structures, and
- Absence of metastatic carcinoma from a distinct tumor.
The histopathologic criterion employed to document malignant transformation of the cyst lining is the identification of a transition from the normal lining epithelium to dysplasia and to carcinoma.  This transition was observed in the present case.
The neoplasms associated with the epithelial lining of an odontogenic cyst include ameloblastoma, ameloblastic fibroma, calcifying epithelial odontogenic tumor, adenomatoid odontogenic tumor, odontoma, SCC, and mucoepidermoid carcinoma. Among the odontogenic cysts, neoplastic transformation is considered to be highest in keratocysts and dentigerous cysts. 
Differential diagnoses of odontogenic cysts and malignant tumors arising in a cyst may be difﬁcult owing to their nonspeciﬁc clinical and radiological presentation. Although dentigerous cysts and OKCs both arise from odontogenic epithelium and may have similar radiographic and histologic appearances, their behavior in terms of recurrence is sufficiently different to warrant distinct treatment and follow-up.  Differences in expression of cytokeratins may allow a given epithelium to be characterized by a speciﬁc pattern of its cytokeratin components.
In the present case, immunohistochemistry was performed using CK 17 as an adjunct to histopathological staining in order to confirm histopathologic findings. CK 17 is a member of the acidic type subfamily. CK 17 is a cytokeratin generated in basal cells and myoepithelial cells with CK 727. According to Meara et al. (2000)  and Stoll et al. (2005),  CK 17 was evident in the epithelial layer of all OKCs for patients with nevoid basal-cell carcinoma syndrome, but not in dentigerous cysts. Therefore, CK 17 can be a useful indicator in distinguishing OKC and other cysts.
Kim et al. (2012)  evaluated the immunoreactivities of CK 10, CK 16, and CK 17 in OKCs and dentigerous cysts. OKCs showed maximum immunohistochemical expression of CK 17 (38 out of 43 cases), and basal and suprabasal cells were strongly positive, whereas in dentigerous cysts only 6 out of 38 cases showed positivity, with CK 17 leaving the basal layer blank. Thus, it may be concluded that higher expression of CK 17 can be a valuable additional parameter for distinguishing OKCs and dentigerous cysts when distinguishing them is difficult, and it can also be useful in determining clinical treatment methods.
In addition, among cytokeratins CK17 should be focused on as a diagnostic marker of oral squamous cell carcinoma (OSCC) as several studies have reported that the expression of CK17 could be detected in malignant tissues compared to normal tissues in SCC. Moreover, CK17 is markedly expressed in well-differentiated SCC. 
We found intense staining with CK 17, which was predominantly expressed in the cellular cytoplasm of the cystic epithelial lining, including the basal layer. The islands and nests of epithelial cells displaying dysplastic features showed strong positivity with CK 17 in the inner cells as compared to that of the outer cells. This finding along with histopathological findings confirmed the diagnosis of PIOSCC arising in KCOT.
As only 1% of all odontogenic cysts undergo carcinomatous change, these carcinomas present with clinical features similar to a benign expansile lesion of the jaws not associated with pain or paresthesia. On plain radiographs they appear similar to the cystic lesions from which they arise. Cavalcanti et al.  have stated that a CT scan would be a more sensitive tool for detecting a carcinomatous change in the lesion due to better appreciation of the destruction to surrounding structures.
Metastases from these lesions are not common (<20%), and most are moderate- to well-differentiated carcinomas. A malignant change in KCOTs has been rarely reported. Most of these cases were treated in two phases, with enucleation or incisional biopsy as phase 1. When carcinoma was found unexpectedly, further treatment included radical resection (in most of the cases), neck dissection and radiation, or chemotherapy (in one-third of the cases).  Our approach toward this case was in accordance with the previous cases.
This case report clearly demonstrates the importance of the clinician's awareness of the malignant potential of apparently innocuous cystic lesions, and adds to the existing database about this rare tumor, which will eventually yield better information on the theories about the origin, biological behavior, management, and prognosis of these truly uncommon neoplasms.
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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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]