Primary Intraosseous Carcinoma in the Pediatric Mandible

Background: Primary intraosseous carcinoma (PIOC) is a rare malignant odontogenic tumor that predominantly occurs in males older than 50 years. PIOC can be misdiagnosed as odontogenic cyst because it occasionally shows well-dened border on radiography. In this study, a case of a 14-year-old female with PIOC who was misdiagnosed with odontogenic cyst clinically is reported along with a literature review of pediatric PIOC cases. Case Presentation: A 14-year-old female patient presented with painful swelling on the mandibular right premolar area. There was a radiolucent lesion with a well-dened border in panoramic view. She was diagnosed with odontogenic cyst, and the cystic mass was enucleated with extraction. However, the biopsy result was consistent with PIOC. After cancer work-up, she underwent partial mandibulectomy, selective neck dissection, and reconstruction with a bular free ap. Although the surgical resection margins were clear, local recurrence and lung metastasis occurred four months after surgery. She underwent concurrent chemo-radiation therapy, but the prognosis was poor. Conclusions: PIOC should be diagnosed differentially from odontogenic cyst even in pediatric populations.

as a unilocular radiolucent lesion. In our review of pediatric cases, six of 10 cases showed unilocular radiolucency. Radiologic borders that were de ned but non-corticated were reported to occur in 57% of the PIOC cases and the remaining 43% had diffuse borders. In cases with poorly de ned borders, such as those with diffuse margins, the lesions could be unambiguously distinguished from odontogenic cyst. However, since cases with well-de ned borders can be misdiagnosed as odontogenic cyst, a differential diagnosis should be thoroughly considered. According to Kaffe et al. [21], a de ned but non-corticated border could be a useful feature for differential diagnosis. A well-de ned but non-corticated border was observed in ve of the 10 pediatric PIOC patients (Table 1). Moreover, tooth displacement and root resorption should be considered as other radiologic features as PIOC tends to grow too rapidly to produce such features [7,19,21,25]. However, four of the pediatric cases in our review showed tooth displacement and ve showed root resorption. It was peculiar that these features occurred in the pediatric patients. Although tooth displacement and root resorption are features for slowly growing lesions such as odontogenic cysts, these features should be considered for differential diagnosis of PIOC in pediatric populations. As a rare nding, radiopaque foci were observed in this case and in Punnya et al.'s pediatric case [15]. Although PIOC usually presents as an osteolytic lesion, small radiopaque foci due to calci cation or periosteal reaction can be observed, albeit rarely [10,[26][27][28].
Among the 10 pediatric cases we reviewed, the initial diagnosis for ve was odontogenic cyst. Huang et al. [7] reported that this diagnostic delay did not show any statistically signi cant prognostic difference. However, Naruse et al. [25] reported that preoperative dental procedures might be potential prognostic factors and suggested that no intervention before de nitive diagnosis could achieve a better prognosis. Therefore, incisional biopsy with obtaining multiple specimens is necessary to rule out an underlying carcinoma [8,9,14,17]. Regardless of patient age, biopsy should be considered for any lesion with any of the unusual radiographic presentations mentioned above. The pediatric patient reported by Charles et al. [17] was accurately diagnosed by biopsy and had the longest follow-up period without recurrence. A biopsy was not considered for de nitive diagnosis in the present case although there were atypical radiographic ndings. Local recurrence occurred ve months after the initial operation, that is, four months after the de nitive surgery.
The primary treatment for PIOC is surgical resection [3,8,11,29]. In the present case, because simultaneous reconstruction was necessary, hand-wrist radiography was analyzed for assessment of growth potential. Her skeletal age was assessed as 15-16 years old. Previous research has concluded that the face matures between 12 and 15 years in males and two years earlier in females [30,31]. The vascularized bular free ap is a reliable option for mandibular reconstruction, even in pediatric patients [32,33]. Therefore, the bular free ap was employed for this 14-year-old female patient.
Recent reviews reported the rate of cervical lymph node metastasis to be 12.8% [3] and 70.1% [11]. In our case review, three of the 10 pediatric cases showed cervical metastasis. Wenguang et al. [11] reported nodal status to be a signi cantly poor prognostic factor for survival. However, de Morais et al. [3] reported that lymph node metastasis was not statistically associated with survival. Although these outcomes con ict, it seems reasonable that neck dissection be considered among the surgical procedures for PIOC. In the present case, there were no metastatic lymph nodes on enhanced CT or MRI. However, because there were borderline-sized lymph nodes at the right level IB, selective neck dissection was performed.
In recent literature, de Morais et al. [3] reported a local recurrence rate of 22.1% and Ye et al. [4] reported a local recurrence rate of 24.1%. In this study, local recurrence occurred in three pediatric patients, including the present case, a rate of 30% although the total cases were only 10. In one report, a four-year-old female patient suffered recurrence ve months after excision and underwent additional radical excision [3]. However, 10 months later, recurrence recurred, the lesion was removed, and the area was irradiated. She was alive after one year of follow-up. In another case, a 16-year-old male patient suffered recurrence two months after excision and underwent total mandibulectomy after one month. However, he died two months after the surgery [13]. The 14-year-old female patient in the present study suffered recurrence four months after de nitive surgery. She underwent CCRT for one months, but the recurred lesion did not decrease. According to de Morais et al. [3] and Ye et al. [4], local recurrence is a signi cant prognostic factor for survival. Likewise, pediatric PIOC cases with local recurrence showed poor prognosis. The ve-year survival rate has been reported as 44.6% [3] and 53.2% [4]. However, the ve-year survival rate of the pediatric patients could not be evaluated because of the rarity of the cases and relatively short follow-up periods.
Because PIOC has a poor prognosis, accurate diagnosis and adequate surgical procedures are important. Continuous updates are required to analyze the pathophysiologic mechanism of PIOC, and a recent approach such as genetic analysis [34] could contribute to understanding the pathophysiology of PIOC.

Conclusion
PIOC is a rare malignant odontogenic tumor that can be misdiagnosed as odontogenic cyst because it occasionally presents with a well-de ned border on radiography. According to the literature review, 10 pediatric PIOC cases have been reported, ve of which were initially diagnosed as odontogenic cyst. PIOC with a well-de ned border usually has non-corticated margin. Atypically, tooth displacement and root resorption were observed in approximately half of the pediatric cases. Incisional biopsy with multiple specimens is necessary to rule out PIOC in cases with atypical radiographic ndings. PIOC should be differentially diagnosed from odontogenic cyst even in pediatric populations.

Consent for publication
Written informed consent was obtained from the patient for publication of this manuscript and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
Not applicable.

Authors' contributions
All authors read and approved the nal manuscript. HJO read and wrote the manuscript, DHS collected the literature data, HM designed the article, HJY prepared the histopathologic data, and SMK prepared the gures and wrote the manuscript.