Peripheral giant cell granuloma (PGCL) is a proliferative lesion in response to chronic trauma. It is more common between the fourth and sixth decades of life with a female predilection [6]. The most common location is the mandibular incisor and canine region [15]. Clinically, it may be sessile or pedunculated, reddish-blue in color with spontaneous or provoked bleeding. Bone resorption adjacent to the lesion may be noted [16]. The clinical aspects of the present case were similar to previous literature. Here, the trauma caused by the maxillary prosthesis was certainly associated with the development of PGCL.The origin and etiopathogenesis of PGCL are still uncertain. Some authors have suggested that PGCL results from the proliferation of periodontal and periosteal cells [8].
PGCL is characterized by multinucleated giant cells and ovoid or spindle-shaped mononuclear cells interspersed with hemorrhagic areas and hemosiderin deposits [2]. In the present case, vascular transmigration and intravascular multinucleated giant cells were also detected in H&E analysis. Some authors have reported multinucleated giant cells near and within blood vessels [13, 15]. This phenomenon is known in giant cell tumor of bone [12]. However, the role of vascular transmigration and intravascular multinucleated giant cells in GCL is unclear. This finding is consistent with Adkins [14, 17] and they suggest active invasion of vessels by multinucleated giant cells. Thus, gaps created by transmigrated MGCs allow extravasation of red blood cells and plasma. These data may clarify part of the etiopathogenesis and explain the hemorrhagic areas as a typical feature of PCGL.
Multinucleated giant cell transmigration is a peculiar finding. Immunohistochemical analysis was performed to verify the mechanisms of this phenomenon. In this case, both cell components and blood vessels were CD44 positive. CD44 is a cell surface marker involved in cell interaction, adhesion, and migration [18]. This result may suggest an interaction between multinucleated giant cells and endothelial cells to facilitate vascular transmigration. MMP-2 expression was not detected here; in comparison, giant cell tumor of bone shows positivity for MMP-2 [19], which may be a differential marker for neoplastic giant cell lesions; further studies are needed for this suggestion. On the other hand, MMP-9 positivity was found in the cytoplasm of multinucleated giant cells and some mononuclear and endothelial cells. Matrix metalloproteinases can cleave extracellular matrix components involved in signal transduction, vascularization, and metastasis regulation [20]. These findings are consistent with Matos study [21], which linked MMP-9 expression in PGCL to angiogenic activity and bone resorption through its proteolytic role in the bone matrix. In the present case, MMP-9 may be involved in the degradation of the basement membrane of blood vessels and indicate a "step" of multinucleated giant cell transmigration. Angiogenic activity is also associated with CD34. In the present case, there were microvessels within the lesion that were CD34 positive, similar to the study by Sadri [22]. This marker is expressed by mesenchymal stem cells, endothelial progenitor cells and newly formed blood vessels [23]. On the other hand, large peripheral vessels were labeled with von Willebrand. This result is consistent with the study of Sargolzaei [24], suggesting that the involvement of von Willebrand represents an inflammatory response in PGCG and the production of pro-angiogenic factors.
The origin of multinucleated giant cells in the GCL remains unclear. Here, the expression of vimentin in all PGCG components suggests a mesenchymal origin, which is consistent with the study of Kujan [25]. Macrophage fusion and proliferation in response to hemorrhagic areas [9] and fibroblast proliferation [10] are some theories of MGC origin. The in vitro study of Itonaga [11] showed that MGC are formed from monocyte/macrophage precursors. Further studies are needed to clarify all the findings of this case report and to investigate other giant cell-rich lesions in the oral cavity.