Ⅰ. INTRODUCTION
Primary intraosseous carcinoma (PIOC) is a rare malignant odontogenic epithelial neoplasm that arises within the jawbone and develops from remnants of odontogenic epithelium [1,2]. By definition, it lacks any connection with the oral mucosa and any evidence of a pre-existing malignancy elsewhere [3,4].
Although some cases occur de novo, many develop from pre-existing odontogenic cysts, including dentigerous cysts, radicular cysts, and odontogenic keratocysts [3,5,6]. Therefore, its clinical and radiographic features often resemble those of the associated odontogenic cysts, making pre-operative differential diagnosis difficult and leading to delayed or inadequate treatment.
Here, we report a case of PIOC arising from an odontogenic cyst in the posterior mandible, emphasizing the importance of thorough evaluation of atypical features and routine histopathologic examination.
Ⅱ. CASE REPORT
A 61-year-old female patient visited to the Department of Oral and Maxillofacial Surgery with a chief complaint of a cystic lesion in the right mandible and a vague “floating” sensation around the third molar. Although the patient had a history of hypertension and hyperlipidemia, there were no systemic conditions considered relevant to the cystic lesion. The patient reported neither pain nor numbness, and intraoral examination revealed no mucosal abnormalities.
Panoramic radiography revealed a well-defined radiolucent lesion surrounding the crown of the completely impacted tooth, with no other remarkable findings (Fig. 1A). Based on these findings, a dentigerous cyst was provisionally diagnosed, and cone-beam computed tomography (CBCT) was performed for further evaluation and surgical planning. CBCT imaging demonstrated a circumscribed unilocular radiolucent lesion enveloping the crown of the impacted tooth (Fig. 1B). The lesion exhibited thinning of the lingual cortex with focal discontinuity but lacked overtly aggressive or infiltrative features (Fig. 1B). Small calcified foci were also observed internally, raising differential diagnostic considerations such as calcifying odontogenic cyst (COC), calcifying epithelial odontogenic tumor (CEOT), or a benign fibro-osseous lesion, in addition to a dentigerous cyst
Under local anesthesia, cyst enucleation and extraction of the impacted tooth were performed. During the procedure, the surgeon observed a cystic structure consistent with a cyst lining; however, instead of a typical fluid-filled cavity, the lesion contained mass-like solid components. The resected specimen was submitted in multiple fragments for histopathologic evaluation (Fig. 1C).
Microscopically, the lesion demonstrated a cystic structure lined by non-keratinized stratified squamous epithelium (Fig. 1D). However, some areas exhibited marked epithelial dysplasia, accompanied by invasive epithelial nests infiltrating the underlying connective tissue stroma (Fig. 1E-G). As communication with the adjacent mucosa was absent clinically, the lesion was diagnosed as PIOC arising from an odontogenic cyst (probably a dentigerous cyst).
Because the lesion was not removed en bloc, surgical margins could not be reliably assessed. Given the possibility of residual tumor, additional surgical intervention, including segmental mandibulectomy (Fig. 2A) and selective neck dissection (SND), was performed, followed by reconstruction using a fibular free flap (FFF).
Histopathologic examination of the resected mandible revealed residual tumor nests infiltrating the bone marrow spaces (Fig. 2B). All surgical margins were free of carcinoma, and no regional lymph node metastasis was identified. The patient has been followed for 4 years post-operatively, with no evidence of recurrence.
Ⅲ. DISCUSSION
Odontogenic carcinoma is a rare group of malignant epithelial neoplasms originating from odontogenic epithelium. According to the World Health Organization (WHO) Classification of Odontogenic Maxillofacial Bone Tumours in both the 2017(4th edition) and the 2024 (5th edition), this group includes PIOC, ameloblastic carcinoma, sclerosing odontogenic carcinoma, clear cell odontogenic, and ghost cell odontogenic carcinoma [1,2]. Among them, PIOC, accounting for only 1-2% of all oral cancers [3,4,7], is defined as a squamous cell carcinoma arising within the jawbone and developing from remnants of odontogenic epithelium [1,2]. By definition, it is an exclusive diagnosis: there must be no connection with the oral mucosa and no evidence of a pre-existing malignancy elsewhere [3,4]. Historically, it had been divided to three subtypes based its presumed origin and histologic features [8-10]: solid type, ex odontogenic cyst, and ex benign odontogenic tumor, particularly keartocystic odontogenic tumor (KCOT), a former term for odontogenic keratocyst (OKC). This subclassification was widely accepted and reflected in the earlier WHO classification (2005, 3rd edition) [11]. However, it is no longer considered relevant in the recent WHO classification [1,2], as the solid type might represent the late stage of the other two types during tumor progression [12].
PIOC commonly affects patients in their fifth to seventh decade of life [3-5]. It occurs approximately twice as often in male as in female [3,5], and most frequently arises in the posterior mandible, though a few cases in the anterior maxilla have also been reported [4,5]. This striking predilection for sex and location may relate to the underlying distribution of pre-existing occurrence odontogenic cysts. Several case series have described its development either from a pre-existing odontogenic cyst, especially OKC, or de novo, and have proposed mechanisms for malignant transformation including long-standing chronic inflammation, accumulation of genetic alterations, and evasion of immunological surveillance within the jawbone (so-called osteomimicry) [3,5,6,13]. In our case, given the patient’s old age, the pre-existing odontogenic cyst (most likely a dentigerous cyst) may have persisted for a prolonged period in the jaw bone, creating a chronic inflammatory and immunocompromised micro-environment conducive to malignant transformation.
Many researchers have attempted to identify clinical and radiographic clues that distinguish PIOC from other cystic lesions, but these efforts have not been successful. Clinical features such as pain, swelling, perforation of cortical plates, adherence of the cyst lining to the bone cavity, and continuous sinus tract formation are not specific to PIOC but rather common to cystic lesions with secondary infection [4]. Hopefully, sensory disturbance such as parethesia and numbness may be helpful, as it suggests neural invasion by malignancy [5,6]. Moreover, although radiographic features vary and sometimes appear innocuous, ‘defined but non-corticated’ borders may be informative, as it suggests rapid tumor development [14]. In our case, the patient did not report numbness, but CBCT imaging revealed cortical thinning with focal perforation, not a typical finding for a dentigerous cyst. In addition, the presence of internal calcified foci were notable, because a few studies have reported microscopic calcified structures in PIOC, which may correspond radiographically to such findings [15]. Though it is not yet regarded as a reliable pre-operative criterion, it would have diagnostic value in the future.
Intra-operatively, the surgeon encountered a mass-like solid components rather than the expected fluid-filled cavity and therefore submitted the specimen for histopathologic evaluation. If these atypical findings had been overlooked and histopathologic examination had not been requested, the residual tumor within the bone marrow could have continued to grow over time. This highlights the critical importance of (routine) histopathologic evaluation whenever unexpected findings are encountered.
Due to its rarity, the prognostic factors of PIOC have not been investigated sufficiently [4]. Even though parameters such N staging in the TNM system, nodal status, and histologic grade have been suggested, their prognostic significance remains questionable [16,17]. For the same reason, a specific staging system or standardized treatment guideline has not yet been established. According to Naruse et al. [18], the overall survival of patients with PIOC is comparable to that of stage-Ⅳ oral squamous cell carcinoma, and the treatment of PIOC should be compatible with that of T3N0 oral cancer.
In our case, several findings retrospectively pointed toward malignant transformation. Although malignant transformation from odontogenic cysts is rare, the consequences of un-recognition or mis-recognition are significant. Therefore, careful assessment of subtle clinical, radiographic or intra-operative abnormalities is essential, as these may serve as early flag signs. Routine histopathologic examination of all odontogenic cysts, even when imaging appears benign lesion, is likewise necessary.
