Abstract
Clear cell odontogenic carcinoma (CCOC) is a rare, malignant tumor primarily affecting the mandible in middle-aged women, known to be highly recurrent post-surgery. A 56-year-old female, with an initial diagnosis of ameloblastoma based on radiological findings, had her diagnosis revised to CCOC at Ghent University Hospital after histopathological analysis and EWSR1::CREB1 gene fusion confirmation. Despite undergoing a Brown-Shah IID maxillectomy, radical neck dissection, and fibula flap reconstruction, she faced a recurrence within a year, complicated by an Aspergillus fumigatus infection requiring antifungal treatments and debridements. Diagnosis relies on immunohistochemical markers p40, p63, CK5, SMA, Calponin, and S-100. Additionally, over 80 % of CCOC cases show EWSR1 gene rearrangements. Treatment includes surgical resection and fibula free flap reconstruction. Adjuvant radiotherapy may be beneficial in cases with compromised margins or positive lymph nodes. Prophylactic antifungal treatment is recommended for at-risk patients. The complex nature of CCOC requires thorough follow-up and potentially adjuvant therapies.
Highlights
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EWSR1::CREB1 fusion distinguishes Clear Cell Odontogenic Carcinoma from Ameloblastoma.
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p40 positivity excludes RCC; SMA, S-100 negativity exclude salivary tumors.
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Adjuvant radiotherapy may benefit CCOC cases with positive surgical margins.
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Prophylactic antifungal therapy may prevent superinfection in at risk patients with necrotic flap tissue.
1
Introduction
Clear cell odontogenic carcinoma (CCOC), first described by Hansen et al., in 1985, was initially classified as benign. However, due to its aggressive behavior, marked by local recurrence and distant metastasis, the World Health Organization reclassified it as a malignant tumor in 2005, acknowledging its potential for significant morbidity and mortality [ ].
CCOC primarily affects women, with an average age of 54.4 years, and is more common in the mandible than the maxilla (3:1 ratio). Clinical presentations typically include pain, swelling, and tooth mobility, reflecting the tumor’s expansive growth [ , ].
Histologically, CCOC features polygonal clear cells, often resembling other clear cell (odontogenic) tumors. EWSR1 gene rearrangements are present in 83.3 % of cases, aiding in the differentiation from similar pathologies [ , ].
The treatment primarily involves surgical resection with clear margins due to the high rate of local recurrence, metastases to cervical lymph nodes, and the possibility of distant metastasis, most notably to the lungs and bones [ , ].
This article will examine a case of CCOC in a 56-year-old patient, illustrating the diagnostic and treatment challenges for this rare malignancy. By exploring the surgical, histopathological, and reconstructive aspects of managing CCOC, we aim to contribute to the current understanding of this pathology.
2
Case presentation
A 56-year-old female patient initially presented at another institution in March 2023, with complaints of a loose tooth, a symptom persisting for approximately two years. Recently, this was accompanied by swelling around her left eye, leading to noticeable facial asymmetry. Following clinical and radiographic evaluation, she was diagnosed with ameloblastoma and was recommended for a maxillectomy with fibula free flap reconstruction.
The patient was previously treated for triple-negative breast cancer in 2018 and is in remission. BRCA testing was negative. She had no other relevant medical or dental history.
In May 2023, upon presentation at Ghent University Hospital, clinical examination revealed a hard, non-fluctuating, palpable swelling in the left maxilla, involving both the vestibular and paranasal regions. This swelling was associated with the mobility of teeth 21–25 and a noticeable asymmetry of the nose. The teeth did not respond to CO2 cold tests due to previous endodontic treatments. There were no signs of infection, and the affected teeth were not percussion-sensitive. The patient also reported frequent nasal congestion without epistaxis. No lymphadenopathy or cranial nerve involvement was detected.
Initial imaging, including radiographs, CT, and MRI, revealed a large radiolucent mass in the left maxilla extending to the midline with anterior cortical breakthrough. The lesion demonstrated invasion of the paranasal skin and the medial wall of the sinus ( Figs. 1 and 2 ). Lymphadenopathies were observed ipsilaterally in the occipital and left neck regions (IIa, IIb, V).
A revision biopsy revealed nests and trabeculae of monomorphic polygonal clear cells embedded in a hyalinized stroma ( Fig. 3 ). This led to a revision of the initial diagnosis of ameloblastoma to CCOC. Additionally, RNA Next-Generation Sequencing (NGS) and Fluorescence in Situ Hybridization (FISH) identified an EWSR1::CREB1 gene fusion, further confirming the diagnosis [ ]. Following the 2022 TNM classification for sinonasal tumors, the tumor was staged as cT4aN2bM0.
On October 4, 2023, the patient underwent a Brown-Shah IID maxillectomy with 1.5cm margin, modified radical neck dissection, and occipital dissection, followed by a reconstruction using a fibula free flap of the left leg. During the same procedure, four dental implants were placed in the neo-maxilla. The skin defect was reconstructed with a local cervicofacial Mustardé flap.
Histopathological analysis of the resected specimen confirmed the diagnosis of a 2.7cm × 2.5cm x 2.5cm CCOC, with perineural invasion but no lymphovascular involvement, extending to the cranial infraorbital margin ( Figs. 3 and 4 ). Immunohistochemistry showed strong CK5, p63, and p40 expression, with a variable Ki67 proliferation index. Myoepithelial markers (SMA, Calponin, S100) were negative. The clear cells were negative for mucin, but they were PAS-positive and diastase-sensitive, indicating glycogen ( Fig. 3 ). Positive margins were noted on the left side cranially.
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