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ISSN : 1225-1577(Print)
ISSN : 2384-0900(Online)
The Korean Journal of Oral and Maxillofacial Pathology Vol.46 No.3 pp.41-45

Peripheral Ameloblastoma Associated with Peripheral Giant Cell Granuloma in the Mandibular Alveolar Mucosa

Kyu-Young Oh, Hye-Jung Yoon, Sung-Dae Cho, Seong-Doo Hong, Jae-Il Lee*
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic
of Korea
* Correspondence: Jae-Il Lee, Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea. Tel: +82-2-2072-3621 Email:
May 30, 2022 June 3, 2022 June 10, 2022


It is well documented that giant cells can be observed in some types of odontogenic tumors such as central odontogenic tumor and dentinogenic ghost cell tumor. However, the presence of stromal giant cells has only rarely been reported in ameloblastoma, although being the most common epithelial odontogenic tumor. In this study, we present a novel case of peripheral ameloblastoma associated with peripheral giant cell granuloma arising in the mandibular alveolar mucosa of a 65-year-old male patient. The possible pathogenesis of this combined lesion will be discussed, in addition to the review of previous reports of ameloblastoma accompanied by stromal giant cells.

하악 치조점막에 발생한 주변성 거대세포육아종과 동반된 주변성 법랑모세포종

오 규영, 윤 혜정, 조 성대, 홍 성두, 이 재일*
서울대학교 치의학대학원 구강병리학교실



    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 ameloblastoma3-6), 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).


    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.


    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 cells3-6). 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 cells3-6). 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.


    This study was presented in part at the 82nd annual meeting of the Korean Academy of Oral and Maxillofacial Pathology held on May 30–31, 2015.



    Radiographic findings of peripheral ameloblastoma associated with peripheral giant cell granuloma. Panoramic radiograph (A) and computed tomography (B) show a soft tissue mass in the right retromolar region (arrowheads). Superficial erosion of the underlying bone is noted.


    Histopathological findings of the biopsied specimen in the present case (original magnification ×100). (A) Multinucleated giant cells and stromal mononuclear cells within a hemorrhagic background suggest the diagnosis of peripheral giant cell granuloma. (B) Focal change of the overlying mucosal epithelium is noted.


    Histopathological and immunohistochemical findings of the excised mass in the present case. (A) A low-power view shows a combination of peripheral ameloblastoma (right) and peripheral giant cell granuloma (left). Pan-cytokeratin immunohistochemistry highlights the ameloblastoma component (inset). (B) The connection between peripheral ameloblastoma and the surface epithelium is identified. (C) Cytokeratin 19 immunohistochemistry highlights the ameloblastoma component indicated by the box in Figure 3B. (D–F) The giant cell-rich component is histologically identical to peripheral giant cell granuloma, showing CD68 immunoreactivity (E) and CD34-positive small blood vessels (F). (G–I) Although the ameloblastoma (left) and giant cell granuloma (right) components are located in close proximity, their immunoreactivities for CD68 (H) and cytokeratin 19 (I) are distinct from each other. Original magnification ×12.5 (A); ×40 (B); ×100 (C, G–I); ×200 (D–F).


    Summary of cases of ameloblastoma with stromal giant cells


    1. Neville BW, Damm DD, Allen CM, Chi AC: Oral and maxillofacial pathology. St. Louis, Elsevie, 2016.
    2. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ: WHO classification of head and neck tumours, 4th ed. Lyon, France, IARC, 2017.
    3. Kawakami T, Antoh M, Minemura T: Giant cell reaction to ameloblastoma: an immunohistochemical and ultrastructural study of a case. J Oral Maxillofac Surg 1989;47:737-741.
    4. Richard BM, Thyveetil M, Sharif H, Athanasou NA: Ameloblastoma with stromal multinucleated giant cells. Histopathology 1994;25:497-499.
    5. Muni Sekhar MS, Kiran G, Reddy KR, Krishna A, Suri C: Multinucleated giant cells in unicystic ameloblastoma: a very rare case report and review of the literature. Adv Hum Biol 2015;5:56-59.
    6. Robinson L, Fonseca FP, Lacerda JCT, van Heerden WFP: Unicystic ameloblastoma with stromal giant cells: A case series of a rare entity. Oral Surg Oral Med Oral Pathol Oral Radiol 2022;133:e20-e25.
    7. Allen CM, Hammond HL, Stimson PG: Central odontogenic fibroma, WHO type. A report of three cases with an unusual associated giant cell reaction. Oral Surg Oral Med Oral Pathol 1992;73:62-66.
    8. Eversole LR: Odontogenic fibroma, including amyloid and ossifying variants. Head Neck Pathol 2011;5:335-343.
    9. Roza A, Sousa EM, Leite AA, Amaral-Silva GK, Morais TML, Wagner VP, et al: Central odontogenic fibroma: an international multicentric study of 62 cases. Oral Surg Oral Med Oral Pathol Oral Radiol 2021;131:549-557.
    10. Soares CD, Carlos R, de Lima Morais TM, de Almeida OP: Giant dentinogenic ghost cell tumor: A case report. Oral Surg Oral Med Oral Pathol Oral Radiol 2018;126:e215-e219.
    11. Morais TM, Soares CD, Aguirre Urizar JM, Alberdi-Navarro J, Almeida OP, Pires FR: Peri-implant peripheral giant cell lesions: report of 13 new cases and comparative histological and immunohistochemical analysis with peripheral and central giant cell lesions. Med Oral Patol Oral Cir Bucal 2019;24:e739-e745.
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