|Year : 2012 | Volume
| Issue : 5 | Page : 118-121
Peripheral giant cell granuloma
Padam Narayan Tandon1, SK Gupta2, Durga Shanker Gupta1, Sunit Kumar Jurel3, Abhishek Saraswat1
1 Department of Oral and Maxillofacial Surgery, Teerthanker Mahaveer Dental College and Research Centre, Delhi Road, Moradabad, India
2 Department of Oral and Maxillofacial Surgery, Rama Dental College and Research Centre, Kanpur, Uttar Pradesh, India
3 Department of Prosthodontics, Faculty of Dental Sciences, Upgraded KGMC, Lucknow, India
|Date of Web Publication||17-Apr-2012|
Padam Narayan Tandon
Department of Oral and Maxillofacial Surgery, No. 1 Madhubani Duplex Kaanth Road, Moradabad, Uttar Pradesh
| Abstract|| |
Peripheral giant cell granuloma or the so-called "giant cell epulis" is the most common oral giant cell lesion. It normally presents as a soft tissue purplish-red nodule consisting of multinucleated giant cells in a background of mononuclear stromal cells and extravasated red blood cells. This lesion probably does not represent a true neoplasm, but rather may be reactive in nature, believed to be stimulated by local irritation or trauma, but the cause is not certainly known. This article reports a case of peripheral giant cell granuloma arising at the maxillary anterior region in a 22-year-old female patient. The lesion was completely excised to the periosteum level and there is no residual or recurrent swelling or bony defect apparent in the area of biopsy after a follow-up period of 6 months.
Keywords: Peripheral giant cell granuloma/giant cell epulis, Jaw, reactive
|How to cite this article:|
Tandon PN, Gupta S K, Gupta DS, Jurel SK, Saraswat A. Peripheral giant cell granuloma. Contemp Clin Dent 2012;3:118-21
| Introduction|| |
Peripheral giant cell granuloma (PGCG) is the most common oral giant cell lesion appearing as a soft tissue extra-osseous purplish-red nodule consisting of multinucleated giant cells in a background of mononuclear stromal cells and extravasated red blood cells.
This lesion is probably not present as a true neoplasm, but rather may be reactive in nature. The initiating stimulus has been believed to be due to local irritation or trauma, but the cause is not certainly known. It has been termed a peripheral giant cell "reparative" granuloma, but whether it is in fact reparative has not been established and its osteoclastic activity nature appears doubtful. Its membrane receptors for calcitonin demonstrated by immunohistochemistry and its osteoclastic activity when cultured in vitro are evidences that the lesions are osteoclasts, ,,,, whereas other authors have suggested that the lesion is formed by cells of the mononuclear phagocyte system.  The PGCG bears a close microscopic resemblance to the central giant cell granuloma, and some pathologists believe that it may represent a soft tissue counterpart of the central bony lesion. 
| Case Report|| |
A 22-year-old female patient reported to the Department of Oral and Maxillofacial Surgery with the complaint of swelling in the left upper jaw since 1 year. History revealed that the swelling started as a small one and progressively increased to the present size over a period of 1 year. It was associated with intermittent pain. There was no history of trauma, neurological deficit, fever, loss of appetite, loss of weight. There was no similar swelling present in any other part of the body. The patient was systemically healthy.
On extraoral examination, a single, diffuse swelling was seen on the left side of the face in the region of anterior maxilla. The swelling measured about 2 × 1.5 cm. The surface of the swelling was lobulated and present in relation to 11 21 22. The swelling was firm in consistency and bluish in color, and the overlying mucus membrane was intact [Figure 1]. Orthopantomogram, intraoral periapical radiographs, and maxillary occlusal radiograph showed no bone resorption. The fine needle aspiration cytology (FNAC) features showed numerous giant cells in a hemorrhagic background. Spindle cells/inflammatory cells were not seen.
Surgery (excisional biopsy) was planned under local anesthesia (LA). The overlying mucosa was incised and undermined. Lesion was separated from the adjacent tissue by blunt dissection and removed in one piece [Figure 2]. Primary closure was done with 3-0 silk suture [Figure 3]. The specimen was sent for histopathologic examination. Sutures were removed after 1 week. There was no evidence of recurrence till 5 months of follow-up [Figure 4].
Histopathologic examination of biopsied specimen revealed it to be whitish in color, oval in shape, firm in consistency and measuring about 2 × 1 cm in dimension [Figure 5]. The connective tissue stroma was highly cellular, consisting of proliferating plump fibroblasts. Numerous giant cells of various shapes and sizes, containing 8-15 nuclei, were seen with proliferating and dilated endothelial lined blood capillaries with extravasated red blood cells (RBCs). Few giant cells were also seen inside the vascular spaces. Numerous ossifications were also seen in the stroma [Figure 6].
| Discussion|| |
The etiology and nature of PGCG (giant cell epulides) still remains undecided. In the past, several hypotheses had been proposed to explain the nature of multinucleated giant cells, including the explanation that they were osteoclasts left from physiological resorption of teeth or reaction to injury to periosteum. There is strong evidence that these cells are osteoclasts as they have been shown to possess receptors for calcitonin and were able to excavate bone in vitro.
The PGCG occurs throughout life, with peaks in incidence during the mixed dentitional years  and in the age group of 30-40 years. , It is more common among females (60%). , The mandible is affected slightly more often than the maxilla. , Lesions can become large, some attaining 2 cm in size. The clinical appearance is similar to that of the more common pyogenic granuloma, although the PGCG often is more bluish-purple compared with the bright red color of a typical pyogenic granuloma. Recently, the PGCG associated with dental implants has also been reported. 
Although the PGCG develops within soft tissue, "cupping" superficial resorption of the underlying alveolar bony crest is sometimes seen. At times, it may be difficult to determine whether the mass is a peripheral lesion or a central giant cell granuloma eroding through the cortical plate into the gingival soft tissues. ,,
The extra-osseous lesions of cherubism involving the gingiva appear very similar to giant cell epulides. However, the other distinctive clinical and radiographic features of cherubism will indicate the correct diagnosis. 
Histologically, PGCG is composed of nodules of multinucleated giant cells in a background of plump ovoid and spindle-shaped mesenchymal cells and extravasated RBCs. The giant cells may contain only a few nuclei or up to several dozen of them. Some of them are large, vesicular nuclei; others demonstrate small, pyknotic nuclei. The origin of the giant cell is unknown. Ultrastructural and immunological studies ,,,, have shown that the giant cells are derived from osteoclasts. 
There is also a growing body of opinion that giant cells may simply represent a reactionary component of the lesion and are derived via blood stream from bone marrow mononuclear cells and may be present only in response to an as yet unknown stimulus from the stroma. This concept is based on the results of some more recent studies using cell culture and transplantation, , in which the giant cells have been found to be short lived and to disappear early in culture in contrast to the active proliferation of the stromal cells.
A study by Willing et al. revealed that the stromal cells secrete a variety of cytokines and differentiation factors, including monocyte chemoattractant protein-1 (MCP1), osteoclast differentiation factor (ODF), and macrophage-colony stimulating factor (M-CSF). These molecules are monocyte chemoattractants and are essential for osteoclast differentiation, suggesting that the stromal cell stimulates blood monocyte immigration into tumor tissue and enhances their fusion into osteoclast-like, multinucleated giant cells. Furthermore, the recently identified membrane-bound protein family, a disintegrin and metalloprotease (ADAM), is considered to play a role in the multinucleation of osteoclasts and macrophage-derived giant cells from mononuclear precursor cells. 
In the most recent study by Bo Liu et al.,  in situ hybridization was carried out to detect the mRNA expression of the newly identified receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) that is shown to be essential in the osteoclastogenesis, its receptor, receptor activator of NF-kappaB (RANK), and its decoy receptor, osteoprotegerin (OPG). They concluded that RANKL, OPG and RANK expressed in these lesions may play important roles in the formation of multinucleated giant cells.
| References|| |
|1.||Bonetti F, Pelosi G, Martignoni G, Mombello A, Zamboni G, Pea M, et al. Peripheral giant cell granuloma: evidence for osteoclastic differentiation. Oral Surg Oral Med Oral Pathol 1990;70:471-5. |
|2.||Lim L, Gibbins JR. Immunohistochemical and structural evidence of a modified microvasculature in the giant cell granuloma of the jaws. Oral Surg Oral Med Oral Pathol 1995;79:190-8. |
|3.||Mighell AJ, Robinson PA, Hume WJ. PCNA and Ki-67 immunoreactivity in multinucleated cells of giant cell fibroma and peripheral giant cell granuloma. J Oral Pathol Med 1996;25:193-9. |
|4.||Souza PE, Mesquita RA, Gomez RS. Evaluation of p53, PCNA, Ki-67, MDM2 and AgNOR in oral peripheral and central giant cell lesions. Oral Dis 2000;6:35-9. |
|5.||Bo Liu, Shi-Feng Yu, Tie-Jun Li. Multinucleated giant cells in various forms of giant cell containing lesions of the jaws express features of osteoclasts. J Oral Pathol Med 2003;32:367. |
|6.||Carvalho YR, Loyola AM, Gomez RS, Araujo VC. Peripheral giant cell granuloma.An immuno-histochemical and ultrastructural study. Oral Dis 1995;1:20-5. |
|7.||Katsikeris N, Kakarantza-Angelopoulou E, Angelopoulos AP. Peripheral giant cell granuloma. Clinicopathologic study of 224 new cases and review of 956 reported cases. Int J Oral Maxillofac Surg 1988;17:94-9. |
|8.||Chadwick BL, Crawford PJ, Aldred MJ. Massive giant cell epulis in a child with familial cyclic neutropenia. Br Dent J 1989;167:279-81. |
|9.||Giansanti JS, Waldron CA. Peripheral giant cell granuloma: review of 720 cases. J Oral Surg 1969;27:787-91. |
|10.||Hirshberg A, Kozlovsky A, Schwartz-Arad D, Mardinger O, Kaplan I. Peripheral giant cell granuloma associated with dental implants. J periodontol 2003;74:1381-4. |
|11.||Dayan D, Buchner A, Spirer S. Bone formation in peripheral giant cell granuloma. J Periodontol 1990;61:444-6. |
|12.||Smith BR, Fowler CB, Svane TJ. Primary hyperparathyroidism presenting as a "peripheral" giant cell granuloma. J Oral Maxillofac Surg 1988;46:65-9. |
|13.||Burkes EJ, White RP. A peripheral giant-cell granuloma manifestation of primary hyperparathyroidism: report of case. J Am Dent Assoc 1989;118:62-4. |
|14.||Odell EW, Morgan PR. Biopsy Pathology of the Oral Tissues. London: Chapman Hall Medical; 1998. p. 111. |
|15.||Flanagan AM, Tinkler SMB, Horton MA, Williams MD, Chambers DJ. The multinucleated giant cell granulomas of the jaws are osteoclasts. Cancer 1988;62:1139-45. |
|16.||El-Mofty SK, Osdoby P. Growth behaviour and lineage of isolated and cultured cells derived from giant cell granuloma of the mandible. J Oral Pathol 1985;14:539-52. |
|17.||Cohen MA, Grossman ES, Thompson SH. Features of central giant cell granuloma of the jaws xenografted in nude mice. Oral Surg Oral Med Oral Pathol 1988;66:209 |
|18.||Willing M, Engels C, Jesse N, Werner M, Delling G, Kaiser E. The nature of giant cell tumor of bone. J Cancer Res Clin Oncol 2001;127:467-74. |
|19.||Abe E, Mocharla H, Yamate T, Taguchi Y. Monolages SC. Meltrinalpha, a fusion protein involved in multinucleated giant cell and osteoclast formation. Calcif Tissue 1999;64:508-15. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]