STAT3 is a key pathway in primary intraosseous squamous cell carcinoma arising from an odontogenic keratocyst

Primary intraosseous squamous cell carcinoma (PIOSCC) arising within an odontogenic keratocyst (OKC) is rare malignancy, entailing a poor prognosis for delayed diagnosis. The number of reports concerning this entity is extremely small. The aim of this study is to present the clinical and pathologic characteristics of PIOSCC and investigate its pathogenesis.

This study describes three patients with mandibular PIOSCC derived from an OKC over a seven-year period, each of which suffering from decompression in mandible. Important diagnostic criteria included the absence of overlying oral mucosal ulceration, the absence of a distant potential primary tumor, and the presence of a completely intraosseus lesion. The malignant transformation of OKC to PIOSCC was confirmed by pathologic evaluation of surgical resection specimens. Immunohistochemistry (IHC) was used to evaluating expression of Ki-67, p65, EGFR, phospho-AKT, and STAT3 in each of the three tumors and adjacent cyst walls.

Analysis by IHC indicated that Ki67, P65, EGFR and STAT3 were substantially elevated in PIOSCC. There was an obvious positive correlation between Ki67, P65, EGFR and STAT3 expression in adjacent benign epithelium. Each tumor exhibited long-standing chronic inflammation in the benign odontogenic cyst, suggesting that a sustained immune response may be partially responsible for malignant transformation of the benign cystic lining cells.

These findings indicate that inflammation may be the principal mediator in PIOSCC ex-OKC, and the STAT3 signaling pathway is an important contributor to this process. Combined detection of Ki67, P65, and EGFR in the lesional epithelium can support the diagnosis of PIOSCC.