Giant cell Granuloma are of two forms; Peripheral giant cell granuloma (PGCG) and central giant cell granuloma [6, 7, 8, 9]. These two different groups of pathological entities of giant cell granuloma has similar histological features but pathogeneses of both are still not clear. PGCG are also reactive and exophytic lesion arising from extraosseous tissues (soft gum tissues). It is not a true neoplasm but thought to be as a result of chronic irritation to the area due to local irritation or trauma. Whereas, CGCG are intraosseous and non-proliferative lesions and non- neoplastic lesions. It is less common than PGCG and are commonly manifested in mandible and maxillary bones. Histologically, PGCG and CGCG both are similar. However, they differ in terms of aggressiveness as CGCG are more aggressive and higher recurrence tendency than PGCG [6, 8, 9].
CGCG can display variable clinical presentation, including slow asymptomatic growth without recurrence to fast painful growth with perforation of cortical bone plate and ulceration to the mucosal surface. It can be present in patients from age of 2 years above. But most cases are seen between 20 to 40 years of age [1, 5]. Females are affected slightly more than males, the reason for this is thought to be because of hormonal factors despite the fact that lesions rarely express estrogen receptors [6, 10].
CGCG are more commonly located in the anterior portion of mandible and often crosses the midline. But the literatures have reported its occurrence in different locations like hard palate, orbital region, para nasal sinus, nasal cavity and septum, metacarpal bones and phalanges etc. which indicates that it can occur anywhere in the body [6, 11, 12].
The etiology of CGCG is still not certain and has many theories for its pathogenesis [12, 13]. Previously it was considered to be a hyperplastic reparative reaction to the intraosseous hemorrhage induced by trauma. However, a definite history of trauma may not be reliably elicited. Other theories on pathogenesis of CGCG including infectious and repair process, developmental disturbance, or even inflammatory causes had been proposed, but no single theory has been widely accepted . It has also been hypothesized as genetic etiology but lacks the convincing evidence to support the hypothesis [5, 6].
The most common clinical manifestations of CGCG include pain, swelling and palpable bone lesions and symptoms can vary according to the site of the lesion. In our study, apart from pain and swelling, patients had presented with headache, nausea and vomiting, visual disturbance, protrusion of eyes etc as per the location of the lesion.
Histological examination of CGCG suggests the lesions are composed of hypercellular fibrous stroma containing numerous multinucleated giant cells within the background of mononuclear stromal cells and spindle shaped fibroblasts along with areas of hemorrhages or foci of cystic degeneration and osteoid production [5, 6, 7, 10, 11, 12]. The histologic findings of CGCG, Giant Cell Tumor (GCT) and brown tumor of hyperparathyroidism have virtually identical histologic features and closely resembles granulomas. Immunohistochemical studies have reported CGCG positive for CD 68 [5, 6]. In our study also, 4 cases of Immunohistochemistry were positive for CD 68.
Radiographically, CGCG appearance ranges from unilocular to multilocular radiolucent well defined to ill-defined margins. The lesion bony defects size and nature varies according to the aggressiveness of the lesion. Moreover, the lesions may cause damage to adjacent structures like, displacement of teeth, tooth root resorption, cortical bone perforation [6, 8, 12]. Chuong et al  and Ficarra et al  has classified CGCG into aggressive and non-aggressive types on the basis of 6 criteria like pain, growth rate, swelling, tooth root resorption, cortical perforation and recurrences. Aggressive lesions exhibit pain and rapid growth and usually more than 5 cm in size with the features of swelling and cortical bone perforation and teeth displacement and root resorption [4, 6, 9, 16]. And this type of lesion has high chances of recurrence. Whereas, non-aggressive lesions are low growing and have no or less symptoms and may be without associated features.
CT scan can reveal well circumscribed lytic lesion and expansile mass with the presence of subtle granular bone pattern at the periphery [Fig. 1C] of the expanded bone with some internal septa . MRI reveals a soft tissue area of low signal intensities on both T1 and T2 weighted images along with variable intensities within lesion if there is presence of fibrosis, osteoid, hemorrhage or hemosiderin deposits. The lesion mass can show enhancement but the degree of enhancement can vary . These features may be indistinguishable from GCT, ABCs and brown tumor of hyperparathyroidism.
The differential diagnosis of CGCG includes aneurysmal bone cyst, benign chondroblastoma, brown tumor of hyperparathyroidism, cherubism, fibrous dysplasia, non-osteogenic fibroma, osteosarcoma and true giant cell tumor [5, 7, 12].
Fibrous dysplasia and other odontogenic tumors and non-odontogenic tumors can be easily ruling out on the basis of their clinical and radiological features and histopathology .
Brown cell tumor of hyperthyroidism usually occurs later in the life and is characterized by multiple lesions. Parathyroid hormone, serum and urinary levels of calcium, phosphate and bone or serum alkaline phosphatase are used in the diagnosis of brown cell tumors [7, 8, 11, 12].
ABCs are non-neoplastic lesions in the bone containing giant cells. Radiographs show multiple cystic cavities filled with blood within thin walls. MRI reveals a heterogeneous high signal intensity lesion but histologically, they are characterized by thin-walled blood-filled sinuses lined by fibroblasts and giant cells [6, 8, 17].
Chondroblastoma of the temporal bone is a locally aggressive tumor and histologically it is characterized by presence of hemosiderin pigment, chondroid differentiation, scattered giant cells and calcification and can appear as high-density mass on CT scan [8, 12].
While differentiation between GCT and CGCG is often difficult and confusing. GCTs are benign and locally aggressive true neoplasm. They have an incidence of 3–7%. And among them only 2% of GCTs occur in skull . It occurs in 3rd to 4th decade of life while symptoms vary according to the site of the lesion. These tumors can go into malignant transformation [5, 8, 10, 12, 18]. CGCG and GCT origin are different. CGCG origins from periosteal connective tissue while GCT originates from bone marrow connective tissue. But both the lesions are composed of multinucleated giant cells and small oval or spindle shaped fibroblasts [6, 17]. CGCG can be differentiated from GCT on the basis of histopathological features as; CGCG have relatively fewer multinucleated giant cells than GCT with increased incidence of osteoid, fresh hemorrhages and hemosiderin deposits. In contrast, the giant cells are more evenly distributed in GCT. Other features of CGGC include increased fibrosis, increased spindle shaped fibroblasts and absence of necrosis [5, 11, 12, 17]. However, considerable overlap of characteristics can occur between these two lesions.
The definitive treatment for CGCG is surgical management. Unfortunately, medical management are found to be ineffective in treating CGCG. Different medical approaches including alpha interferon, calcitonin and intra-lesional corticosteroid injections have been described in literatures but surgical management is the most common treatment modality employed. It can be done by 2 different procedures: curettage ± adjunctive treatment (e.g. cryotherapy, osteotomy etc) and resection. All patients in this study had underwent surgical resection and no recurrence cases were observed till now on regular follow up. Literatures have reported the higher recurrence rate of curettage (33–75%) so, total surgical resection is considered to be the best one for CGCG with lesser recurrence rate (10–20%) [7, 19, 20]. Radiotherapy can also be used for CGCG cases where surgery is difficult to perform, but literatures have reported the higher chances of malignant transformation post radiotherapy [8, 9]. Newer studies are being conducted on use of drugs like calcitonin, phosphate and corticosteroid injections which are focused on inhibition of osteoclast differentiation and activation leading to reduce in recurrence of CGCG rates [7, 20]. For the close monitoring of recurrence of CGCG after surgical treatment, CT and MRI should be done on follow up regularly.