Senior Registrar of Oral Medicine, Basic Dental Science Department, College of Dentistry ,
Princess Nourah bint Abdulrahman University

Corresponding author email: aloyouas-j@hotmail.com

Article Publishing History

INTRODUCTION

Clear cell odontogenic carcinoma (CCOC) was first reported by Hensen et al. in 1985. The reported cases of CCOC are very few. Accordingly, the behavior and pathology pattern of this tumor is still considered mysterious and not fully understood. It is a rare, aggressive, odontogenic malignant tumor (L. S. Hansen, L. R. Eversole, T. L. Green, 1985). Approximately 74% of CCOC reported cases to affect the mandible with high incidence in females. Previously, CCOC was classified as a benign tumor, and it was also known as clear cell ameloblastoma.

CCOC owns aggressive features such as destructive growth patterns, regional lymphadenopathy, distant metastasis, and a high recurrence rate. Therefore, in 2005, the WHO reclassified it as a malignant odontogenic tumor. (F. P. S. Guastaldi, W. C. Faquin, 2019) An extensive review of literature in PubMed Medline revealed few similar cases of CCOC in the mandible. The reported case of CCOC in a 42-year-old, female patient with a swelling in the mandibular region. The work has been reported in line with the SCARE criteria”(Agha et al., 2018)

Case Presentation: Forty-two years old women presented with paresthesia of the lower lip and large swelling in the mandible for more than a year and a half ago. The patient reported no previous history of trauma and no abnormal discharges such as pus or blood coming out of the mass. However, paresthesia and slight mobility were noted.

She was diabetic and on medications for two years and she was allergic to pineapple which is associated with urticaria. Moreover, family medical history and genetic conditions were not remarkable. Moreover, the patient had a clean social record without smoking or abuse alcohol drinking. She had updated routine blood tests which were within normal limits.

Extraoral examination revealed a significant enlargement of the chin with intact, and normal colored skin. The examination illustrated no regional lymphadenopathy was noted. Remarkably, the extraoral examination confirmed the loss of sensation in the lower lip.

Intraoral examination showed a large, painless intra-bony swelling with a firm consistency and extending from the right lower first molar to the left lower first molar crossing the midline; area of teeth No. 20 to 30 (according to the universal numbering system). Notably, the patient had multiple missing teeth in the mandibular swelling area as follows tooth No.20, and No. 28.  Vitality testing of the involved non-carious mandibular teeth was performed which reflected no abnormal responses.

Radiographic analysis including orthopantomogram radiograph depicted an extensive, large, multilocular radiolucency associated with scalloping, non-sclerotic border lesion extending from the right lower first molar to the left lower first molar crossing the midline from tooth No. 19 to 30 without root resorption of the aforementioned teeth. Additionally, the radiographic film showed thinning of the inferior alveolar border in correspondence with the anterior mandible. Also, shifting of tooth No. 29 distally. (Figure 1a and 1b)

The patient medical history, the clinical and radiographic findings were all indicating the odontogenic tumors. The differential diagnosis of the mandibular mass included clear cell variant of ameloblastoma, clear cell odontogenic carcinoma, clear cell variant of a calcifying epithelial odontogenic tumor, mucoepidermoid carcinoma, acinic cell carcinoma, epithelial myoepithelial carcinoma, melanocytic tumors.

She was educated about the nature of the tumor, different treatment plan options, possible results, and prognosis. An incisional biopsy was considered as the first line of management to determine the type of the tumor. The biopsy was performed under local anesthesia, an incisional biopsy was obtained and sent for histopathology analysis.

Two different stains were used for histopathologic analysis to provide an accurate diagnosis. Hematoxylin and eosin (H&E) stain; an immunohistochemistry stain, and Alcian blue stain; a non-immunohistochemistry stain. Under the microscope, the lesion appeared to have notable stromal hyalinization with small multiple nests and strands. Also, it showed lobules of epithelial cells with clear to eosinophilic cytoplasm (H&E) (Figure 2a, and 2b).

Due to the overlapping and the similarity between odontogenic and salivary clear cell tumors, an Alcian blue stain was used to distinguish between them. The Alcian blue stain was negative for cellular mucin; therefore, salivary clear cell tumors and metastatic tumors were ruled out (Figure 2c).

The diagnosis was made based on the histopathologic features under the microscope which were strongly consistent with clear cell odontogenic carcinoma. Consequently, the patient was admitted to the hospital and surgical resection of the mandibular tumor with free margins was performed under general anesthesia (Figure 3a, 3b, and 3c). Then, the mandible was reconstructed to cope with the issues of functions and esthetic.

The diagnosis of CCOC was, also, confirmed by the histopathological analysis of the resected portion of the mandible. Surgical and post-surgical instructions were delivered verbally and in written form to the patient. Also, all patient’s concerns and inquiries were taking care of. The patient was monitored at the hospital for five days post-surgically. A two-week, one-month, and two-month, three-month, four-month, six-month, and one-year follow-up visits, she showed no recurrence or complications.

DISCUSSION

CCOC is a slow-growing, and locally invasive odontogenic tumor affecting the jaws. A rare tumor that mostly affects females more than males. It usually has confusing clinical characteristics, radiographical features and poses benign first glance histological features, making its identifications even more difficult. Clinically, most cases of CCOC show pain, however, in this case, the patient had paresthesia of the lower lip with no sign of pain. Moreover, swelling of the jaw, teeth loosening, displacement and mobility, thinning of the mandible are other signs of the tumor.

Histopathologically, the name of the clear cells came from the special appearance of the cytoplasm under the microscope which shows a clear cytoplasm with H&E stain. The accumulation of intracellular components such as lipid, mucin, and glycogen resulted in the special appearance of the clear cell. The picture of the tumor cells under the microscope varies in each case and it is hard to standardize.

It includes different figures of stroma containing clusters and sheets of epithelial cells with color variations of cytoplasm, ranging from colorless to eosinophilic hue. In addition, in some cases, the epithelial cells could be arranged in a palisaded pattern which is similar to ameloblastoma. Alcian blue stain to rule out mucous cells containing tumors such as mucoepidermoid carcinoma and clear cell tumor of salivary glands. (Swain, Dhariwal and Ray, 2013)

Clear cells are, also, seen in odontogenic and non-odontogenic tumors. Clear cells of odontogenic origin such as odontogenic cysts, clear cell ameloblastoma, mucoepidermoid carcinoma, clear cell tumor of salivary glands, calcifying epithelial odontogenic tumor, acinic cell carcinoma, myoepithelial carcinoma, and squamous cell carcinoma. On the other hand, in patients with history of cancer, distant metastasis is possible. Therefore, undifferentiated clear cell tumors of non-odontogenic origin from kidneys, thyroid, breast, lungs, and colon could be metastasis to the mandible. (Swain, Dhariwal and Ray, 2013)

Consequently, a meticulous examination should be done for patients with a possible diagnosis of CCOC to rule out clear cell metastasis from distant organs.(Werle et al., 2009) Diagnosis of CCOC depends on the detailed medical history, thorough physical examination, radiographic imaging, and histological analysis of the provided incisional specimen.

CCOC ideal treatment is not clear yet due to the rarity of the documented and reported case. Most cases undergo radical surgical resection of the tumor with safe bone tissue margins. However, when palpable lymph nodes or extensive destruction of the bone with tissue invasion are involved, the management would be twisted and shifted to be more aggressive; to reduce the chance of recurrence. It would indicate lymph node removal, radiotherapy, or/and chemotherapy.

In our report, the patient did not show signs of lymphadenopathy or metastasis, and the resection of the mandibular tumor was performed with safety margins. Therefore, in this case, the patient did not go through lymph node removal, radiotherapy, or/and chemotherapy. Long-term follow-up of CCOC cases is highly recommended to exclude recurrence and metastasis of the tumor.

CONCLUSION

CCOC has confusing clinical features, radiographical patterns and poses benign first glance histological forms, making its recognition and diagnosis more difficult. A detailed investigation is essential to reach the definitive diagnosis and to manage the tumor properly.

Declarations List of abbreviations: Clear Cell Odontogenic Carcinoma (CCOC) Hematoxylin and Eosin (H&E)

Ethics approval and consent to participate: “The manuscript has been read and approved by all the authors, that the requirements for authorship as stated earlier in this document have been met, and that authors believe that the manuscript represents honest work”. Also, a copy of the written consent is available for review by the Editor-in-Chief of this journal on request”

Consent For Publication: Informed consent statement: Informed written consent was obtained from the patient for publication of this case report and accompanying images.

Competing Interests: The authors declare that they have no conflicts of interest.

Authors’ contributions

Conceptualization: Aloyouny, A; Data Curation: Aloyouny, A and Mahmoud Salem, H; Original draft preparation: Aloyouny, A; Review & editing: Aloyouny, A and Mahmoud Salem, H.

ACKNOWLEDGEMENTS

This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program.

Data Availability Statement: The database generated and /or analysed during the current study are not publicly available due to privacy, but are available from the corresponding author on reasonable request.

REFERENCES

Agha, R. A. et al. (2018) ‘The SCARE 2018 statement: Updating consensus Surgical CAse REport (SCARE) guidelines’, International Journal of Surgery, 60, pp. 132–136. doi: 10.1016/j.ijsu.2018.10.028.

F. P. S. Guastaldi, W. C. Faquin, F. G. et al. (2019) ‘Clear cell odontogenic carcinoma: a rare jaw tumor. A summary of 107 reported cases’, International Journal of Oral and Maxillofacial Surgery, 48(11), pp. 1405–1410.

L. S. Hansen, L. R. Eversole, T. L. Green, and N. B. P. (1985) ‘Clear cell odontogenic tumor–a new histologic variant with aggressive potential’, Head & Neck Surgery, 8, pp. 115–123.

Swain, N., Dhariwal, R. and Ray, J. G. (2013) ‘Clear cell odontogenic carcinoma of maxilla: A case report and mini review.’, Journal of oral and maxillofacial pathology : JOMFP, pp. 89–94. doi: 10.4103/0973-029X.110681.

Werle, H. et al. (2009) ‘Clear-Cell Odontogenic Carcinoma: A New Case and Long-Term Follow-Up of an Old Case, and Review of the Literature’, Journal of Oral and Maxillofacial Surgery. American Association of Oral and Maxillofacial Surgeons, 67(6), pp. 1342–1348. doi: 10.1016/j.joms.2008.06.020.