# Peripheral Giant Cell Granuloma in Pregnancy: A Case Report
## 3 Discussion  
Peripheral giant cell granuloma (PGCG) is an exophytic, extra-osseous, and non-neoplastic pathology that originates in the periosteum or periodontal ligament [1]. The etiology of PGCG is unknown; however, hormones have been considered as contributing factors, although this association is controversial. Few clinical cases of pregnancy-associated  
Figure 4: Excised tissue samples for histopathological examination. Figure 5: Histopathological examination of the excised specimen showing proliferation of multi-nucleated giant cells in the cell matrix. Magnification: (**A**) \(\times\)10. Vascular and lymphatic spaces of different calibers (white arrow), deposits of eosinophil material compatible with fibrin (black arrow); (**B**) \(\times\)20. Multi-nucleated osteoclast-type giant cells (yellow arrow). PGCG have been described [10; 11; 12]. This study presents a case of pregnancy-associated PGCG in the upper jaw. The complexity of the etiology of GPCG involves several hypotheses of reactive processes, the nature of multinucleated giant cells, and the influence of cytokines and differentiation factors [1; 4; 13; 14; 15]. GPCG is generally considered a reactive lesion, which means that it is probably triggered by external factors such as the presence of local irritants such as dental biofilm, dental calculus, overflowing restorations, indiscriminate use of toothpicks, chronic infections, food, and tooth impaction [1; 4; 13; 14; 15]. One theory of the nature of the multinucleated giant cells in GPCG proposes that they are osteoclasts, possibly residual from physiological tooth resorption or in reaction to injury to the periosteum; evidence supporting this includes the presence of receptors for calcitonin in these cells and their ability to excavate bone in vitro [4]. On the other hand, studies suggest that the giant cells in the GPCG could represent a reactive component derived from bone marrow mononuclear cells in response to an unknown stimulus from the stromal tissue [4]. Recently, research has shown that stromal cells in GPCG secrete various cytokines and differentiation factors. These factors are believed to stimulate the migration of monocytes into the tumor tissue and promote the fusion of these cells into multinucleated osteoclast-like giant cells [4; 13]. The imbalance in the Receptor Activator of Nuclear Factor xB Ligand (RANKL)/Receptor Activator of Nuclear Factor xB (RANK)/osteoproteger (OPG) system could be a contributing factor in the development of GPCG. Alteration in the balance between RANKL and OPG, either by an increase in RANKL or a decrease in OPG, could lead to increased differentiation and activity of osteoclasts and potentially to the formation of multinucleated giant cells [4]. However, it is important to recognize that the etiology of GPCG is multifactorial, and this last mechanism is only one of the possible factors involved. The roles played by sex hormones in pregnancy in relation to the initiation, development, and progression of PGCG are controversial. During pregnancy, hormonal changes, particularly those involving estrogen and progesterone, promote alterations in the oral cavity. These alterations encompass physiological, vascular, microbiological, and cellular changes, creating a favorable environment for the initiation and development of various pathologies [16; 17; 18; 19; 20; 21; 22; 23]. Among the physiological changes that significantly contribute to the prevalence of oral lesions, especially in gingival tissue, are an approximate 1500 mL increase in blood volume (normal volume in women being 4 to 4.5 L), establishing a framework clinical diagnosis for physiological anemia, which can stimulate gingival bleeding and the possible increase in blood glucose levels due to the decrease in sensitivity to insulin by pregnancy hormones, potentially generating a decrease in the elasticity and increase in the permeability of blood capillaries [16; 22].