Ⅰ. INTRODUCTION

Ameloblastic carcinoma (AC) is rare odontogenic malignant neoplasm. In the World Health Organization (WHO) classification of odontogenic tumors published in 2017, it was summarized that, AC can be histologically classified as odontogenic carcinoma, with primary intraosseous carcinoma, sclerosing odontogenic carcinoma, clear cell odontogenic carcinoma, ghost cell odontogenic carcinoma and odontogenic carcinosarcoma.[1] ACs can be classified either as a primary type when they develop de novo or as a secondary type when they dedifferentiate from a pre-existing ameloblastoma. A majority of ACs appear to be of the primary type, and little is known about secondary type ACs.[2] The incidence of ACs is 1.79 cases per 10 million population, however, only approximately 138 cases have been reported.[2,3] Males are at a higher risk of developing ACs than females (1.75:1), and the average age at onset is 44 years.[4]

Here, we report a case of a patient in whom acanthomatous ameloblastoma malignantly transformed into AC after receiving, surgical interventions for a total of five times for tumor removal.

Ⅱ. CASE REPORT

A 55-year-old male patient with swelling in the buccal mucosa of the right maxillary anterior region was referred by a local dental clinic to the Oral and Maxillofacial Surgery Department of Kyungpook National University Dental Hospital in August 2015. In 1995, the patient had been diagnosed with ameloblastoma in a local medical center, and had undergone surgery. During the patient’s initial visit, panoramic radiography and computed tomography scans showed extensive bone destruction of the right maxillary sinus (Fig. 1). Based on the patient’s history, clinical features, and findings from imaging examination, a provisional diagnosis of ameloblastoma was made. In August 2015, the first operation, curettage, was performed under general anesthesia. The excised mass was sent for histopathological examination to confirm diagnosis. Histopathological features included formation of columnar ameloblast-like cells arranged in a single layer lining the periphery of the follicle. Many solid epithelial nests also showed squamous differentiation with well-formed keratin pearls. These histopathologic features were suggestive of acanthomatous ameloblastoma (Fig. 2-A).

Two months after the first surgery, an oroantral fistula formation was observed on the right maxillary buccal mucosa. During the first year after the initial surgery, bone destruction throughout the entire maxillary sinus was sustained; 1 year later, acanthomatous ameloblastoma recurred and re-curettage was planned. The specimen was sent for histopathological examination, and the final diagnosis was recurrent acanthomatous ameloblastoma (Fig. 2-B).

Three months after the second surgery, pus was continuously discharged, and the third surgery, right total maxillectomy, was performed using Weber-Ferguson incision approach. The right orbital area was also removed and reconstructed using a titanium mesh. The mass was also diagnosed as a recurrent acanthomatous ameloblastoma (Fig. 2-C). Surgery was performed two more times under general anesthesia after the patient’s condition did not improve even after the third surgery. First, titanium mesh was removed during the fourth surgery. Despite titanium plate removal, healing was not achieved because pus discharge persisted; consequently, surgical intervention was performed for the fifth time. During the fifth surgery, proliferation of the mass occurred within the right infraorbital and the right posterior orbital walls. On performing histopathological examination, keratin formation and squamous cell dysplasia, which are features of ameloblastoma and carcinoma, respectively, were observed, and thus, a definitive diagnosis of AC was made (Fig. 2-D). Although a clear margin was not obtained during surgery, no further surgical intervention was carried out, and radiotherapy was established as the subsequent treatment method. After 1-year radiotherapy, no clinical or radiological signs of recurrence were noted.

Ⅲ. DISCUSSION

Ameloblastoma is a rare, benign neoplasm of the odontogenic epithelium. The histopathologic pattern variants of ameloblastoma include follicular, plexiform, acanthomatous, granular, desmoplastic, and basal cell types.[5] Acanthomatous ameloblastoma is classified as ameloblastoma, but it is locally aggressive and frequently invades or recurs after surgical excision.[6] The mean age of the patients affected by acanthomatous ameloblastoma is 70 years. Unlike the finding in our case, the most prevalent site of occurrence was the mandible (accounting for 80% of ameloblastoma cases).[7] Most lesions are accidentally discovered on radiographic studies and remain asymptomatic; however, a few symptomatic cases of acanthomatous ameloblastoma, presenting as malocclusion or loose teeth or more uncommonly, as paresthesia and pain. The mass proliferates slowly but if left untreated, it can resorb the cortical bone and extend into the adjacent anatomical structures.[6] The recurrence rates reported in the literature are 13%–15% after surgical resection and 90%–100% after curettage. Some reporters believe that acanthomatous ameloblastoma can develop into an invading squamous cell carcinoma.[7]

In the past, the terms malignant ameloblastoma and AC were distinguished and classified separately. The term malignant ameloblastoma was used for a metastatic tumor, and both primary and metastatic lesions were diagnosed as ameloblastoma, which was histopathologically a benign tumor. Contrastingly, the term AC itself implies a histologically malignant feature of the primary tumor, recurrent tumor, or any metastatic deposit, but metastasis does not necessarily occur.[5] The 1st and 2nd editions of WHO classification of odontogenic tumors did not include AC separately in the classification system, whereas, malignant ameloblastoma was classified as a single entity in both 1st and 2nd editions.[8] In 2005, AC was included as a separate entity and divided into three subtypes : (a) primary, (b) secondary (dedifferentiated), intra-osseous, and (c) secondary (dedifferentiated), extraosseous.[ 9] There was little justification for classifying such a rare tumor into three subtypes; therefore, an update from the 4th edition of WHO classification of head and neck tumors published in 2017 continued to consider odontogenic tumors as a single entity after histological typing.[1]

The clinical features or symptoms of AC are more aggressive than those of ameloblastoma. AC can also manifest as swelling with rapid growth, perforation of the cortex, pain, tooth mobility, a nonhealing surgical wound, ulcer or fistula, facial asymmetry, trismus, and paresthesia.[10]

AC is defined by a combination of cytological features of malignancy and the histological pattern of an ameloblastoma. These include an increased nuclear-to-cytoplasmic ratio, nuclear hyperchromatism, and the presence of mitoses. Dystrophic calcification and necrotic area in islands may also be observed.[5] AC is composed of islands of ameloblastomatous odontogenic epithelium with an infiltrative pattern. The epithelium may possess a single layer of columnar or cuboid-shaped ameloblastic cells, which may or may not exhibit palisading tendency and reverse nuclear polarity. Hypercellularity of the stellate reticulum could also be observed. The characteristic features of AC are nuclear enlargement with granular stippled nucleus, nuclear hyperchromatism, mild pleomorphism, and increased mitotic activity with abnormal forms of mitosis. Dyskeratosis, keratin pearl formation, necrosis and dystrophic calcification may be observed in some cases. Different histopathologic patterns such as highly differentiated squamous cells or a more basaloid and poorly differentiated variety may be noted in the malignant counterparts.[11] Therefore, AC may have features that are histopathologically similar to those of malignant tumors including intraosseous squamous cell carcinoma, squamous odontogenic tumor, clear cell odontogenic carcinoma, metastatic clear cell carcinoma, and even ameloblastoma which may occasionally show the presence of some mitotic figures.[2] It may be difficult to distinguish AC from ameloblastoma, particularly AC in which there were only focal areas showing malignancy. Therefore, pathologists should examine many sections of the excised tumor. In this report, when histological examination was performed until the fourth surgery, certain characteristic features such as an outer lining around the follicle formed by a single layer of columnar ameloblast-like cells and keratin formation were observed, which led to the diagnosis being acanthomatous ameloblastoma. After the fifth surgery, biopsy was also performed, and malignancy features such as an infiltrative pattern of ameloblastomatous odontogenic epithelium, and hypercellularity as well as some other cytological features of malignancy were observed than facilitated a definitive diagnosis of AC.

Because AC is a rare tumor, the treatment of AC still remains controversial. However, surgical resection is the most widely used treatment modality. Yoon et al.[12] reported a recurrence rate of 92.3% after curettage alone and 28.3 % after partial resection, therefore, a wide surgical resection, with clear margins free of tumor, is recommended. Radiotherapy is used in cases with positive surgical margins, perineural infiltration or soft-tissue invasion.[13] The patient who has been described in this case report experienced recurrence up to five times. One of the important factors that contribute to its recurrence is the maxillary location. Because there several important structures such as the orbit, cranial base and pterygomaxillary fossa are present in this location, it is difficult to perform surgical resection with clear surgical margins.

Ⅳ. CONCLUSION

In our report, the patient underwent five surgical interventions for approximately 3 years after the initial diagnosis, and was ultimately diagnosed with AC. In acanthomatous ameloblastoma cases, it is important to distinguish malignancy from the initial histological diagnosis because its characteristic histological pattern includes squamous cell differentiation similar to that seen during squamous cell carcinoma. In addition, because of a higher metastasis rate of the malignant type than that of other subtypes, careful monitoring of the patient during the follow up period is warranted. Moreover, AC is not well documented with regard to its clinical features and long-term prognosis, and further analysis and studies are needed.