Ⅰ. INTRODUCTION
Orthokeratinized odontogenic cysts (OOCs) represent approximately 7%–17% of all keratinized cysts within the jaw1,2,3). Initially regarded as a subtype of odontogenic keratocysts (OKCs), the World Health Organization has since recognized OOC as a distinct entity2,4). Histologically, OOCs are characterized by a thin, uniform epithelial lining containing luminal orthokeratin, a well-defined granular layer, and a basal layer composed of cuboidal or flattened squamous cells displaying minimal polarization5). In contrast, OKCs feature epithelia of uniform thicknesses with corrugated parakeratinized surfaces and basal columnar cell polarization6). Despite being less aggressive than OKCs, OOCs are more likely to undergo malignant transformation2). While benign tumors are the predominant neoplasms arising from odontogenic cysts, mucoepidermoid carcinoma and squamous cell carcinoma (SCC) are significant malignancies associated with them.5,7). Malignant transformations of odontogenic cysts are rare, with a prevalence of 0.1%–0.2%6). Among these transformations to malignancies, more than 50% have developed in inflammatory cysts such as periapical or residual cysts8-11). However, several cases of dysplastic changes in the lining of orthokeratinized epithelia have been reported 1,4,6,12). This report presents a case of SCC arising in an OOC in an 89-year-old female, highlighting the potential for malignant progression in these cysts.
Ⅱ. CASE REPORT
An 89-year-old female presented to the periodontal department of another hospital with inflammation of the maxillary anterior right palate. Subsequently, she was referred to the Department of Oral and Maxillofacial Surgery due to persistent inflammation following extractions of the maxillary right central incisor, left central incisor, and lateral incisor. Despite antibiotic therapy, her condition did not improve, leading to curettage of the maxillary anterior area and extraction of the maxillary right lateral incisor under a diagnosis of osteomyelitis of the anterior maxilla. Histological examination revealed inflammatory granulation tissue and a periodontal abscess.
Because of persistent pain and residential concerns, the patient was referred to our department at Kyungpook National University Dental Hospital in Korea. Radiographic examinations, including panoramic x-ray and cone-beam computed tomography (CBCT), indicated osteolysis throughout the maxillary anterior portion, concomitant with the discharge of pus from the maxillary anterior gingiva (Fig. 1A–C). Consequently, surgical curettage of the lesion and extraction of the maxillary right canine, left canine, and first premolar were performed under general anesthesia (Fig. 1E).
Postoperatively, histopathological analysis disclosed a well-differentiated SCC originating from an orthokeratinized odontogenic cyst. Notably, keratohyaline granules were prominent, and orthokeratin was evident on the luminal surface (Fig. 2A, B). Additionally, keratin pearls were observed within focal inflammatory fibrous tissue, accompanied by cells with variable sizes of nuclei (Fig. 2C, D).
During subsequent follow-up appointments, the patient reported discomfort in the bilateral ala of the nose area. Enhanced computed tomography (CT) imaging revealed swelling in this region with a mass-like lesion, corroborating clinical findings of swelling on the left ala of the nose area (Fig. 3A, B). An intraoral incisional biopsy confirmed the diagnosis of well-differentiated SCC. Histopathological findings showed cystic lining surrounding inflammatory fibrous walls (Fig. 3C), whereas other portions showed features of a well-differentiated SCC producing large amount of keratin (Fig. 3D).
Given the patient's advanced age and general condition, chemotherapy and radiation therapy were recommended over additional surgical interventions. The patient was referred to the radio-oncology department for initiation of radiotherapy treatment. Over the course of 35 radiotherapy sessions, the patient was administered a cumulative dose of 7,000 grays. The patient undergoes regular follow-ups in the outpatient department, and there have been no signs of recurrence.
Ⅲ. DISCUSSION
Initially described as dermoid cysts by Shultz in 1927, orthokeratinized odontogenic cysts are rare developmental cysts occurring in the jaws. In 1981, Wright categorized them as orthokeratinized variants of odontogenic keratocysts (OKCs)13). However, the classification was revised in 2005 by the World Health Organization, recognizing OOC as a distinct entity from OKC due to its clinicopathological features.14,15). Unlike OKCs, which exhibit aggressive behavior and high recurrence rates, OOCs are characterized by milder behavior and more favorable prognoses. Nonetheless, while malignant transformation is infrequent in OOCs, several authors have reported these occurrences1,4,6). Some evidence suggests that the orthokeratinized epithelial linings of OOCs may contribute to higher risks of malignant transformation, although further research is needed to substantiate this claim6).
Of the rare transformations to malignancy in odontogenic cysts, more than 50% are associated with inflammatory cysts, such as periapical or residual cysts1-3). Moreover, reports have suggested that chronic inflammation may contribute to malignant changes16). In the case presented here, the patient exhibited clinical inflammatory features, such as pus discharge, which warrants further investigation into the correlation between inflammatory states and the transformation to a malignant state. Histopathological diagnosis after surgery also revealed inflammatory features (Fig. 2C)
Ward and Cohen identified three possible mechanisms for malignant changes in cystic lesions17,18): 1) a pre-existing cyst becomes secondarily involved in a carcinoma of unrelated origin arising either from an adjacent epithelial structure or as a distant primary tumor; 2) the lesion is a carcinoma from the outset, of which a portion has undergone cystic transformation; or 3) the initial lesion is a cyst, and malignant changes have subsequently taken place in the epithelial lining. It is likely that the third mechanism is applicable in this case because the histopathological findings indicated SCC arising within the epithelial lining surrounded by a lumen (Fig. 2).
The diagnosis of SCC was unexpected in this case because the initial diagnosis was osteomyelitis due to the broad osteolysis observed in the radiographic findings and clinical features such as pus discharge. Treatment decisions following diagnosis must consider the extent of the carcinoma 7). While an immediate hemimaxillectomy could be contemplated, the potential complications and the patient's overall condition, including advanced age, led to the recommendation of chemotherapy and radiation therapy. Further studies are warranted to enhance the understanding and determine management strategies for SCC arising in OOCs.
This case underscores the importance of considering malignant transformation in the differential diagnosis of odontogenic cysts, particularly OOCs. Despite their historically recognized benign nature, OOCs can give rise to SCC, as evidenced by the unexpected diagnosis in our patient. This highlights the necessity for vigilance and thorough investigation, especially when confronted with atypical clinical presentations or radiographic findings.
Furthermore, this case emphasizes the need for continued research into the pathogenesis, risk factors, and optimal management strategies for SCCs arising in OOCs. Enhanced understanding in these areas will facilitate earlier detection, more accurate risk stratification, and tailored treatment approaches, ultimately improving outcomes for affected patients.
