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[8
] and in the age group of 30–40 years.[7
] It is more common among females (60%).[7
] The mandible is affected slightly more often than the maxilla.[7
] 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.[10
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.[11
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.[14
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[2
] have shown that the giant cells are derived from osteoclasts.[15
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,[16
] 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.[19
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.