Ⅰ. INTRODUCTION

Ameloblastoma is the most common epithelial odontogenic tumor, which can be classified into conventional, unicystic, and peripheral subtypes according to the clinicoradiographic presentation¹⁾. Among these subtypes, peripheral ameloblastoma is the soft tissue counterpart of intraosseous ameloblastoma that rarely occurs in the gingiva or alveolar mucosa²⁾. While stromal giant cell reaction has been noted in a few cases of intraosseous ameloblastoma^3-6), such distinctive microscopic finding has not been reported in peripheral ameloblastoma. Here, we report a novel case of peripheral ameloblastoma associated with peripheral giant cell granuloma (PGCG).

Ⅱ. CASE REPORT

A 65-year-old male presented with swelling in the right mandibular alveolar mucosa lasting 4 months. Intraoral examination revealed a 3.0-cm sized exophytic mass in the right retromolar region. Radiographic examination showed a soft tissue mass with superficial erosion of the underlying bone (Fig. 1). Incisional biopsy was performed, and histopathologically a proliferation of multinucleated giant cells was confirmed within a hemorrhagic background of mesenchymal cells, thus rendering a diagnosis of PGCG (Fig. 2A). Although focal histological alteration of the overlying mucosal epithelium was observed, it was thought to be a reactive epithelial change at the time of the initial histopathological examination (Fig. 2B).

Surgical excision was performed without ostectomy. Histopathological examination revealed that the mass consisted of two components: PGCG, which was the initial diagnosis of the lesion, and ameloblastoma. Islands of ameloblastic epithelium showing both follicular and plexiform patterns were found in association with stromal giant cell proliferation (Fig. 3A). In some areas, the connection between ameloblastic epithelium and the basal layer of the surface mucosal epithelium was noted (Fig. 3B). By immunohistochemistry for cytokeratin 19, the ameloblastic epithelium was distinguished from uninvolved surface epithelium (Fig. 3C). The PGCG component showed typical histopathologic findings characterized by multinucleated giant cells, plump mesenchymal cells, and hemorrhage (Fig. 3D). Multinucleated giant cells contained a few to dozens of nuclei and were positive for CD68, as were the background mesenchymal cells (Fig. 3E). CD34 immunohistochemistry highlighted newly formed blood vessels (Fig. 3F). The PGCG and ameloblastoma components were distributed in close proximity (Fig. 3G) but exhibited distinct immunostaining for CD68 (Fig. 3H) and cytokeratin 19 (Fig. 3I). Taken together, the final diagnosis of peripheral ameloblastoma associated with PGCG was made.

Uneventful healing was identified 1 month after surgery, after which the patient was lost to follow-up.

Ⅲ. DISCUSSION

It is widely recognized that giant cells can be observed in association with some types of odontogenic tumors. Concurrence of central odontogenic fibroma and giant cell granuloma has been well documented since the first report in 1992⁷⁾. Whether this phenomenon is the result of a reactive process, a unique microscopic presentation of the tumor, or a true hybrid lesion remains to be clarified; Eversole⁸⁾ and Neville et al.¹⁾ have postulated that odontogenic fibroma might induce a giant cell response. It has also been speculated that odontogenic mesenchymal tissue of the periodontium is a common origin of central odontogenic fibroma and giant cell lesion⁹⁾. Another odontogenic tumor that can exhibit giant cells is dentinogenic ghost cell tumor ¹⁰⁾. In cases where ghost cells come in contact with adjacent connective tissue, multinucleated giant cells representative of inflammatory foreign body reaction can be induced ²⁾.

In addition to the aforementioned odontogenic tumors– central odontogenic fibroma and dentinogenic ghost cell tumor, a few cases of ameloblastoma have been reported to be accompanied by stromal giant cells^3-6). A total of six cases including the present case are summarized in Table 1. The cases occurred in a wide age range (6–65 years; mean, 34.5 years), with a male-to-female ratio of 1:2. One case was found in the maxilla, and the others occurred in the mandible, which may reflect the mandibular predilection of ameloblastoma. Except the present peripheral case, five cases consisted of two conventional and three unicystic ameloblastomas. All the cases were surgically removed, and no recurrences were observed.

The nature and origin of giant cells were discussed in previous reports of intraosseous ameloblastoma with stromal giant cells^3-6). By identifying their immunoreactivity for CD68, α-1-antichymotrypsin, and HLA-DR, the authors have demonstrated that these multinucleated giant cells have a histiocytic origin (Table 1). While Kawakami et al.³⁾ stated that the giant cells are different from osteoclasts, Richard et al.⁴⁾ described that osteoclast-like giant cells coexist as a minority. In addition, Muni Sekhar et al.⁵⁾ suggested that the giant cells are probably of foreign-body type. Taken together, the nature of stromal giant cells that can rarely be observed in intraosseous ameloblastomas remains unclear, which warrants further analysis.

The present case is the first peripheral ameloblastoma reported to be associated with giant cells. PGCG is a well-established, tumorlike growth of the soft tissue, mostly occurring on the gingiva or alveolar ridge¹⁾. Since the present case had a giant cell-rich component with histologic features typical of PGCG, the diagnosis of “peripheral ameloblastoma associated with PGCG” could be made. Given that it is widely accepted that PGCG is a reactive process¹¹⁾, the present case can be explained as the result of local irritation by peripheral ameloblastoma, inducing reactive proliferation of mononuclear cells with multinucleated giant cells. Another possible scenario is that ameloblastoma occurred in the area already involved by PGCG, leading to the presentation of a collision lesion. The possibility that the present case is an example of histologic variants of ameloblastoma can be raised, although unlikely considering the scarcity of such cases.

In summary, this is the first report of peripheral ameloblastoma combined with PGCG, which may broaden our understanding of the association of reactive giant cell lesions with odontogenic tumors.