|Ahead of print publication
Primary intraosseous squamous cell carcinoma ex-odontogenic cyst
Usha Hegde1, Sreeshyla Huchanahalli Sheshanna1, HP Jaishankar2, R Rajendra Prasad3
1 Department of Oral Pathology and Microbiology, JSS Dental College and Hospital, Mysore, Karnataka, India
2 Department of Oral Medicine and Radiology, JSS Dental College and Hospital, Mysore, Karnataka, India
3 Department of Oral and Maxillofacial Surgery, JSS Dental College and Hospital, Mysore, Karnataka, India
Department of Oral Pathology and Microbiology, JSS Dental College and Hospital (a Constituent College of JSSAHER), Mysore - 570 015, Karnataka
Source of Support: None, Conflict of Interest: None
Squamous cell carcinomas of the oral cavity are quite common, but primary intraosseous squamous cell carcinomas (PIOSCCs) are rare. Their origin from lining of different odontogenic cysts has been documented. More than 50% of such cases have been reported to occur in periapical inflammatory cysts, and less than 10 cases are reported to arise from odontogenic keratocyst (OKC). One such rare case of a PIOSCC, which presented as an OKC initially, is being reported.
Keywords: Aberrant keratinization, dysplasia, malignant transformation, odontogenic keratocyst, primary intraosseous squamous cell carcinoma
| > Introduction|| |
Primary intraosseous squamous cell carcinoma (PIOSCC) arising primarily in the bone is extremely rare and develops from the remnants of odontogenic epithelium within the jaw. It may also arise from the epithelial lining of a preexisting odontogenic cyst (periapical cyst, dentigerous cyst, or odontogenic keratocyst [OKC]), termed as PIOSCC ex-odontogenic cyst. OKC linings have the highest mitotic rate among these cysts and are also noted to have high potential for malignant transformation, although rare. A rare case of PIOSCC ex-odontogenic cyst is being presented here.
| > Case Report|| |
A 40-year-old male patient reported with the complaint of swelling. On examination, a diffuse, bony hard, nontender swelling was noted on the right lower third of the face [Figure 1]a. Intraoral examination revealed obliteration of the vestibule from 33 to 47 region, with expansion of both buccal and lingual cortical plates and an intact mucosal surface. Region 48 was partly erupted and grossly destructed [Figure 1]b. Orthopantomograph revealed a well-defined unilocular radiolucency extending from 33 crossing the midline to 47. Regions 33 and 43 were impacted [Figure 1]c. Lymph nodes were not palpable. An intrabony incisional biopsy was done in relation to 43 and 44.
|Figure 1: (a) Clinical photograph of the patient showing diffuse swelling on the right lower third of the face. (b) Intraoral photograph showing obliterated vestibule and an intact mucosa. (c) Orthopantomograph reveals a unilocular radiolucency with scalloped and sclerotic margins|
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Histopathologically, the hematoxylin and eosin-stained sections revealed a cystic lumen lined by epithelium and supported by connective tissue capsule. The lining epithelium was stratified squamous parakeratinized with basal cells showing palisading and polarized nuclei and few unusual findings such as dysplasia and abundant aberrant surface keratinization with an intact basement membrane [Figure 2]. On clinicopathologic correlation, a diagnosis of OKC with dysplastic changes was given. A thorough evaluation of the lesion was planned after the complete surgical removal. However, the patient was lost for treatment and follow-up.
|Figure 2: Hematoxylin and eosin-stained section showing epithelial lining of odontogenic keratocyst, with dysplasia and aberrant keratinization (×10)|
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The patient reported 6 months later with the complaint of swelling [Figure 3]a and growth in the right mandibular posterior region. Examination revealed an ulceroproliferative lesion extending from 43 distally [Figure 3]b. It was indurated, and the regional submandibular lymph nodes were palpable. Personal history was negative for smoking and drinking. Imaging showed an extensive lesion without clear margins, involving the right side of the mandible and extending onto the left side up to canine region [Figure 3]c. Incisional biopsy from this growth revealed connective tissue stroma with islands of dysplastic epithelial cells and keratin pearls, suggestive of well-differentiated squamous cell carcinoma [Figure 4]. A tiny biopsy bit also showed features of OKC. Considering the presentation of the lesion during the two short consecutive visits, wherein initially there was an intact mucosa with only a cystic well-defined unilocular lesion, to an ulceroproliferative growth on the mucosa with ill-defined radiolucent lesion in the next visit and correlating these with the histopathological findings of both the visits, a final diagnosis of well-differentiated squamous cell carcinoma arising from OKC was made. Clinically, the patient appeared healthy without any other obvious systemic symptoms. The patient was referred to a cancer center for further complete systemic evaluation to rule out secondaries, treatment, and follow-up.
|Figure 3: (a) Clinical photograph of the second visit of the patient. (b) Intraoral photograph revealing a proliferative growth on the buccal, lingual, and distal aspects of 44. (c) Computed tomography image reveals an extensive lesion without clear margins|
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|Figure 4: Hematoxylin and eosin sections showing islands of dysplastic squamous epithelial cells in a connective tissue stroma (a: ×4; b: ×10)|
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| > Discussion|| |
The WHO (2005) classification of odontogenic cysts and tumors designates OKCs as keratocystic odontogenic tumors. However, the recent WHO classification (2017) has recategorized it as a cyst, and hence, OKC remains the preferred terminology to be used for such lesions. PIOSSC arising within the jaw bones from the wall of an OKC is quite rare. A retrospective study has showed that there have been only 16 known cases of PIOSCC arising from an OKC. A literature review has shown that mandible is more predominantly affected than maxilla, with a male predilection and wide age range of occurrence. In the present case too, the lesion occurred in the mandible, in a male patient aged 40 years.
The pathogenesis of PIOSCC arising from an OKC is not known. Varying assumptions have been proposed. According to one view, keratin metaplasia followed by epithelial hyperplasia and then epithelial dysplasia of the cyst lining could be the cause of neoplastic changes. Long-standing chronic inflammation may induce carcinogenesis by the formation of reactive oxygen metabolites. These metabolites cause damage to DNA, protein, and cell membranes that eventually results in compensatory proliferative response of neoplastic cells against the normal apoptotic mechanism. Further, it has been said that the presence of keratinization in the cyst lining results in a greater risk for malignant changes. The long-standing inflammation associated with the grossly destructed third molar in this case could have been the main causative factor for the malignant transformation.
Correlating the initial clinical presentation of a bony hard swelling showing cortical plate expansion without any mucosal lesion or pain or lymphadenopathy, with that of the unilocular well-defined radiolucency, a provisional diagnosis of an odontogenic cyst was given. The histopathology also confirmed it as OKC. Even though odontogenic lesions are quite well established, many a times the overlapping and varying histopathological findings continue to tickle our thoughts. Hence, in the present case, in view of the dysplastic nature and aberrant keratinization associated with the cystic lining, a thorough evaluation and follow-up was planned after the complete surgical treatment of the cyst.
The criteria proposed to identify a lesion as PIOSCC ex-odontogenic cyst are microscopic transition area from benign cystic epithelial lining to squamous cell carcinoma, an intact overlying oral mucosa, absence of carcinoma in the adjacent structures, and absence of metastatic carcinoma from a distant tumor. In the present case, initially, the overlying mucosa was intact with no carcinomatous lesion in any of the adjacent structures. The presence of distant carcinoma was also ruled out. Only after he presented to us 6 months later, the histopathology revealed features of well-differentiated squamous cell carcinoma, and hence, the case was diagnosed as PIOSCC ex-odontogenic cyst. Since it was an only incisional biopsy, we could not establish the continuity of the cystic lining to the tumor transition.
Usually, PIOSCC ex-odontogenic cyst is treated surgically with wide local resection, and in most cases, en bloc excision or radical resection is advised. Our patient was referred to a cancer hospital for further treatment.
| > Conclusion|| |
Malignant transformation of the epithelial lining of an odontogenic cyst is rare. However, the presence of a diffuse radiolucency crossing the midline and the histopathology showing dysplastic features and aberrant keratinization should alert the practitioner to evaluate the case thoroughly. A regular follow-up of the patient has to be done for better prognosis and detection of any changes at the earlier stage.
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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