associated with odontogenic SCC, including residual cyst, dentigerous cyst, lateral periodontal cyst, and keratocystic odontogenic tumour (KCOT).2,3 However, ...
CASE REPORTS
Neuroendocrine Carcinoma Originating from a Keratocystic Odontogenic Tumour Kyu-Sup Cho, MD, PhD, Bit-Na Yoon, MD, PhD, Chang-Hun Lee, MD, PhD, and Hwan-Jung Roh, MD, PhD dontogenic cyst (OC) is a benign developmental tumour with many distinguishing clinical and histopathologic features. However, the epithelial lining of OCs may transform into mucoepidermoid carcinoma or squamous cell carcinoma (SCC).1,2 Various OCs have been associated with odontogenic SCC, including residual cyst, dentigerous cyst, lateral periodontal cyst, and keratocystic odontogenic tumour (KCOT).2,3 However, neuroendocrine carcinoma (NEC) in the maxillary sinus is extremely rare, and NEC originating from an OC in the maxillary sinus has not been reported previously. We describe a case of NEC originating from a KCOT of the maxillary sinus in a patient who presented with cheek pain and toothache. This study was approved by the Institutional Review Board of Pusan National University Hospital.
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Case Report A 36-year-old man presented with right-sided cheek pain and toothache in the upper jaw for 6 months. The endoscopic examination showed a mild deviated nasal septum to the left and medial bulging of the lateral nasal wall, narrowing and compressing the right middle and inferior meatus. A nonenhanced computed tomographic (CT) scan revealed a large expansile unilocular cystic mass with a thin bony septum in the right maxillary sinus. The cystic lesion that expanded the maxillary alveolus and lateral wall had scalloped margins (Figure 1A). On magnetic resonance imaging (MRI), the cystic mass had low to intermediate signal intensity on T1-weighted images (T1WIs) Kyu-Sup Cho, Bit-Na Yoon, and Hwan-Jung Roh: Department of Otorhinolaryngology, and Chang-Hun Lee: Department of Pathology, Pusan National University School of Medicine, Seo-gu Busan, Republic of Korea. Address reprint requests to: Kyu-Sup Cho, MD, PhD, Department of Otorhinolaryngology, Pusan National University School of Medicine, 110 Ami-dong, Seo-gu Busan 602-739, Republic of Korea; e-mail: choks@ pusan.ac.kr.
DOI 10.2310/7070.2011.100237 # 2011 The Canadian Society of Otolaryngology-Head & Neck Surgery
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and high signal intensity on T2-weighted images (T2WIs) without enhancement. Also, a small, well-demarcated mass with low signal intensity on both T1WIs and T2WIs without enhancement was detected in the alveolar process of the maxilla (Figure 1, B–D). At first, surgical access for removal of the cystic mass was gained via an intranasal endoscopic approach under general anesthesia. After the mass was perforated, a very distinct, bony, capsulated lesion with serous fluid was observed. The bony wall of the cyst was attached to the inferior and lateral maxillary sinus wall, and a Caldwell-Luc approach for complete removal of the cystic bony wall and mass originating from the alveolar process of the maxilla was added. During the operation, it was found that the cystic bony wall and mass originated from the root of the number 16 tooth. On histopathology, tumour cells showed hyperchromatic nuclei with finely dispersed chromatin and inconspicuous nucleoli. There were mild nuclear atypia and rare mitotic activity. Immunohistochemical staining revealed that tumour cells were strongly positive for neuron-specific enolase, cytokeratin, CD56, and synaptophysin. These findings were consistent with well-differentiated NEC. The NEC was arising from the dysplastic, stratified, squamous, keratinized epithelium lining the cyst wall. In focal areas, the cyst epithelium showed a uniform thickness of 8 to 10 cell layers, with basilar palisading, nuclear hyperchromasia, and parakeratinization. These findings were believed to be diagnostic of NEC originating from a KCOT (Figure 2). Since resection, the margins have been free of tumour, there has been no sign of regional or distant metastasis, and the patient has been followed closely without postoperative radiotherapy. An endoscopic examination, MRI, and positron emission tomography–CT performed 30 months postoperatively showed no evidence of recurrence.
Discussion The epithelial lining of OCs can undergo simple cystic expansion, keratinization, and malignant transformation.2 A carcinomatous transformation toward mucoepidermoid carcinoma or SCC occurs in 1% or less of all OCs.
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Case Reports
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Odontogenic carcinomas may theoretically arise from the epithelial lining of OCs or de novo from presumed odontogenic cell rests.4 The KCOT was previously known as the the odontogenic keratocyst. The name was changed to reflect its neoplastic nature.5 Although a malignant change in a KCOT has infrequently been reported, there has been no report on NEC arising from a KCOT. The present case displayed foci of NEC associated with a dysplastic change in adjacent epithelium of a KCOT. Tumour cells showed positivity for neuron-specific enolase, CD56, and synaptophysin, implying neuroendocrine differentiation. Although most NECs are found in the lung and alimentary tract and its appendages, they have also been found in almost every organ of the body.6 NECs are classified into three subtypes: typical carcinoid tumour (well-differentiated NEC), atypical carcinoid tumour (moderately differentiated NEC), and small cell carcinoma (poorly differentiated NEC).7 The clinical behavior of these tumours correlates with their histologic characteristics. Although the typical carcinoid tumours have, for the most part, a favourable course, the atypical carcinoid and small
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Figure 1. Preoperative computed tomographic (A) and magnetic resonance (B–D) images show a large, expansile, unilocular cystic mass with a scalloped margin in the right maxillary sinus. A small mural nodular lesion (arrow) was detected on T1 (B), T2 (C), and postcontrast T1 (D) magnetic resonance images.
cell NECs can metastasize by lymphatic and hematogenous routes. Small cell NECs are the most aggressive of the three types and frequently manifest metastases at the time of tumour discovery.8 Carcinomas arising from all types of OCs occur more frequently in men, and most patients are older adults, with a mean age of 57 to 61 years.4,9 The mandible is affected more frequently than the maxilla, and the most common symptoms are pain and swelling.4,9 Although the diagnosis of odontogenic carcinomas can be established only by histopathologic examination, showing a transition area from benign cystic epithelial lining to invasive carcinoma,1,2 it has been reported that a malignant change in OCs should be considered if the CT scans show bony destruction, accumulation of contrast medium within the lesion,10 or a small mural nodule.11 In our case, we discovered bony destruction of the lateral wall and alveolar process on a CT scan and small budding of the cyst wall on an MRI. These findings could suggest the possibility of malignant changes in a KCOT, although a KCOT without a malignant change can also show cortical destruction owing to its potential for locally destructive behaviour.
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Figure 2. A, Histopathologic finding shows the transition from keratinized squamous epithelium (hematoxylineosin stain; 3200). B, Tumour cells show uniform hyperchromatic nuclei with small nucleoli (hematoxylin-eosin stain; 3400). C, Immunohistochemical stain for neuron-specific enolase shows diffuse strong positivity (3400).
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The treatment for odontogenic carcinomas is determined by the extent of the carcinoma, although the gold standard treatment consists of surgery and/or radiotherapy.4,9 If the carcinoma is well differentiated, further surgical intervention could be deferred and the patient followed up closely. If the margins of the tumour were positive or there was carcinoma in the adjacent bone, additional therapy is indicated. Our patient underwent surgery without radiotherapy, based on the favourable histopathologic type and complete resection with a sufficient safe margin. Although malignant transformation of a KCOT to an NEC is very rare, it is important for otolaryngologists to be aware of this disease process. When a KCOT in the maxillary sinus shows bony destruction and small budding or a nodule of the cyst wall on a radiologic image, the malignant potential of the KCOT should be considered.
Acknowledgement Financial disclosure of authors and reviewers: None reported.
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3. Yasuoka T, Yonemoto K, Kato Y, et al. Squamous cell carcinoma arising in a dentigerous cyst. J Oral Maxillofac Surg 2000;58:900–5, doi:10.1053/joms.2000.8219. 4. Suei Y, Tanimoto K, Taguchi A, et al. Primary intraosseous carcinoma: review of the literature and diagnostic criteria. J Oral Maxillofac Surg 1994;52:580–3, doi:10.1016/0278-2391 (94)90094-9. 5. Press SG. Odontogenic tumors of the maxillary sinus. Curr Opin Otolaryngol Head Neck Surg 2008;16:47–54, doi:10.1097/ MOO.0b013e3282f419da. 6. Erlandson RA, Nesland JM. Tumors of the endocrine/neuroendocrine system: an overview. Ultrastruct Pathol 1994;18:149–70, doi:10.3109/01913129409016286. 7. Wenig BM, Hyams VJ, Heffner DK. Moderately differentiated neuroendocrine carcinoma of the larynx. A clinicopathologic study of 54 cases. Cancer 1988;62:2658–76, doi:10.1002/10970142(19881215)62:12,2658::AID-CNCR2820621235.3.0.CO;2-M. 8. Woodruff JM, Senie RT. Atypical carcinoid tumor of the larynx. A critical review of the literature. ORL J Otorhinolaryngol Relat Spec 1991;53:194–209. 9. Chaisuparat R, Coletti D, Kolokythas A, et al. Primary intraosseous odontogenic carcinoma arising in an odontogenic cyst or de novo: a clinicopathologic study of six new cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:194–200, doi:10.1016/ j.tripleo.2005.03.037. 10. Cavalcanti MG, Ruprecht A, Quets J. Progression of maxillofacial squamous cell carcinoma evaluated using computer graphics with spiral computed tomography. Dentomaxillofac Radiol 1999;28: 238–44, doi:10.1038/sj.dmfr.4600447. 11. Han MH, Chang KH, Lee CH, et al. Cystic expansile masses of the maxilla: differential diagnosis with CT and MR. AJNR Am J Neuroradiol 1995;16:333–8.
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