Peripheral giant cell granuloma – case report

Abstract Peripheral giant cell granuloma (PGCG) or “Epulis gigantocelularis” is the most common oral lesion that originates from giant cells. It typically manifests in the form of soft tissue tumor purple-red or red-watery color consisting of multinuclear giant cells in the mononuclear stroma and extravascular erythrocytes. This lesion is not considered true neoplasm, rather reactive lesion stimulated by local irritation and trauma. However, the cause is not known with certainty. This paper presents a 13-year-old boy with a large lesion in the region of right maxillary canine that was retained in jaw despite favorable vertical position and available space to accommodate in the dental arch. The lesion was completely removed under local anesthesia and histopathological findings confirmed the diagnosis of PGCG. Postoperative period went without complications. After four months additional surgical procedure was needed due to the recurrence, which after tooth naturally erupted and positioned in the dental arch.


INTRODUCTION
Epulis name originates from the Greek epi -on and Oulon -gums, and, in general, considers any growth on gingiva regardless of etiology [1]. Clinically, most epulis lesions look similar and it is difficult to differentiate these from other tumor-like masses. Since large number of gingival lesions macroscopically looks similar to epulis, the literature has not yet determined the official classification of such lesions.
The most common epulis located on gingiva is made up of connective tissue and covered with stratified squamous epithelium -epulus gigantocellularis. It can be found in the literature under different names such as: peripheral giant cell tumor or peripheral giant cell granuloma. It is most commonly found in the intercanine sector on interdental papilla [2], more often on buccal side in the lower jaw [3]. It is five times more common than central giant cell granuloma that develops in bone [4].
Peripheral giant cell granuloma (PGCG) is of unknown etiology and has slow growth [2]. According to most authors, the cause may be permanent irritation or trauma [5]. In some patients diagnosed with PGCG cytomegalovirus has been isolated [6]. However, it has not been confirmed whether it is the cause or just contributes to the development of the disease.
Initially, mucosa shows unchanged color and looks thickened but PGCG eventually grows to an impressive mass, red or dark red in color and soft consistency that can destroy bone [2]. Also, ulcerations may be present on the surface. PGCG usually does not exceed the size of 5 cm in diameter, but can be bigger. Due to its volume it can push away adjacent teeth [4]. Its base is narrower than its entire volume and impressions of adjacent structures of the oral cavity (teeth, cheeks, language) can be seen on its surface.
It the early stage of its development x-ray does not show any change however after some time changes become noticeable. At this point differential diagnosis should include the central giant cell granuloma.
Treatment is surgical and sometimes requires removing the tooth from the affected area. Recurrent lesions are quite common but they are usually interpreted as the result of inadequate surgery.
The aim of this case report was to present PGCG in 13-year-old boy that was removed by simple surgical procedure that enabled normal eruption of canine and its placement in the dental arch.

CASE REPORT
A 13 -year-old boy presented at the Clinic for Oral Surgery, Faculty of Medicine Foca, with evident tumefaction on the alveolar ridge of maxilla in the region of the right canine. Lesion was 3.5×2.5cm in size, kidney-shaped, redpurple in color and localized in the space of mesial surface of the first right premolar up to the mid part of upper right central incisor, both on vestibular and palatal sides, fulfilling almost the entire vestibule (Figures 1 and 2). X ray revealed right canine present in the bone that could not erupt due to this lesion on ginigiva ( Figure 3). The patient underwent fine aspiration biopsy, which after histopathologic examination confirmed the presence of mul-tinucleate giant cells with hemorrhage around. Spindle / inflammatory cells were not detected.
Surgical removal of the lesion was performed under local anesthesia when it was completely removed in one piece and sent for histopathological analysis (Figure 4). Histopathology revealed the presence of numerous multinuclear cells of different shapes and sizes, containing 8-15 nuclei in fibroblast stroma. Expanded endothelial cells with extravasal erythrocytes were also detected. Moreover, the presence of several giant cells within the vascular space, as well as signs of ossification within the stroma was observed ( Figure 5). Based on found histopathological changes it was evident that it is a peripheral giant cell lesion. After surgical procedure was done packaged bandage was placed in the defect, which was removed seven days after the procedure.
After four months, the patient came back with the reccurence of the lesion in the form of blue-purple nodule 5 mm in size ( Figure 6), which was again completely re-

DISCUSSION
Etiology and nature of PGCG remains undefined. In the past there have been several proposed hypotheses that tried to explain the nature of multinuclear giant cells. These include the hypothesis that they are remnants of osteoclasts that perform natural resorption of primary dentition or that have arisen in response to violations of the periosteum.
PGCG can occur any time in life, but the most common incidence is in the mixed dentition [4]. The lesions are more common in the lower jaw [3,7] while its size can reach over 2 cm in diameter. Clinically it is similar to pyogenic granuloma, but PGCG typically have bluepurple color compared to red pyogenic granuloma. Recently, there was published case of PGCG associated with dental implants [8]. Although PGCG develops in the soft tissue, local bone resorption of the alveolar ridge can be observed as well. Sometimes it is difficult to assess whether the tumor mass is peripheral lesion or central giant cell granuloma (CGCG) that originate in bone tissue of the alveolar ridge and spreads into gingiva [9,10,11].
Histologically, PGCG consists of islands of multinuclear giant cells in the stroma filled with oval and spindle mesenchymal cells and extravasal erythrocytes. Giant cells can contain several to several tens of nuclei. Some of them are large vesicular nuclei, while others are small, pyknotic nuclei. The origin of giant cells is unknown. Ultrastructural and immunological studies [12][13][14][15][16] have shown that they, in fact, originate from osteoclasts [17]. Some researchers believe that they represent reactive component of the lesion, in fact, mononuclear cells from bone marrow that mature through the bloodstream and their sequential extravasation in response to an unknown stimulus from the stroma. This concept is based on the results of recent studies using cell culture and transplantation [18,19], where giant cells with short life were found and disappeared in culture, in comparison with active proliferation of stromal cells.
According to the findings of Willing et al. [20] it was revealed that stromal cells secrete cytokines and other factors of cell differentiation, including monocyte chemo attractant protein-1 (MCP1), osteoclasts differentiating factor (ODF), and macrophage-stimulating factor (M-CSF). MCP1 is essential for osteoclast differentiation, indicating that stromal cells stimulate migration of monocytes into the tumor tissue fusing in multinucleated giant cells that resemble osteoclasts.