CENTRAL GIANT CELL GRANULOMA (CGCG)

Giant cell granuloma and its related lesions in the jaw are grouped under single umbrella but with varied clinical behaviour ranging from simple reactive to neoplasm sometimes even manifesting as aggressive malignant neoplasm. The ubiquitous presence of giant cells in many unrelated bone lesions further complicates differential diagnosis. The reactive secondary changes in the lesion, many a times give a pseudo picture of malignancy and it needs a great deal of expertise to recognize the basic nature of the lesion. That is why clinic pathological correlation taking into consideration of radiological findings and sometimes, the serum evaluation is of utmost importance before reaching the final diagnosis, especially into diverse group of histologically overlapping giant cell entities.

The central giant cell granuloma (CGCG) was once thought to represent reactive lesion, however the unpredictable and sometimes occasionally aggressive behavior and because of its possible relationship to tumors of long bone and some syndromes, it is best classified as benign neoplasm.

CLINICAL FEATURES

The CGCG has a wide age range in its manifestations; however, two-thirds of the cases occur below the age of 30 years with a predilection for females atleast twice as common than the males. Both the jaws are affected and 80% are involving the region anterior to the first premolar and rarely noticed in the posterior segment. In general, CGCG is asymptomatic in the beginning but later becomes expansile. Multiple cases of CGCG have been reported in patients with mutations of the RAS/MAPK pathway, especially in syndromal cases.

RADIOGRAPHIC FEATURES

Sharply demarcated radiolucency sometimes extends between the displaced tooth roots. Few cases exhibit sclerotic margin denoting the slow expansile nature. Sometimes, faint calcifications are noticed depicting the poorly mineralized osteoid trabeculae within the lesion and this helps to differentiate from giant cell tumors. The roots are not resorbed, but the tooth may be lost due to lack of bony support. Larger lesions may exhibit multilocularity. The cortex generally is intact, but in more aggressive lesions, it may be breached.

DIFFERENTIAL DIAGNOSIS

CGCG should be differentiated from the brown tumor of hyperparathyroidism, giant cell tumor, no ossifying fibroma and other osteolytic lesions of the jawbones associated with giant cells histologically like cherubim, aneurysmal bone cyst and so on.

The hyperparathyroidism can be differentiated on the basis of biochemical tests, where hypercalcemia, hypophosphatasia and increased PTH will point toward hyperparathyroidism.

The giant cell tumor of long bones virtually will be difficult to differentiate, especially when the CGCG is of the aggressive type. The giant cell tumor shows larger giant cells, more in number of nuclei and generalized distribution of giant cells and absence of osteoid formation. But for all practical purpose, the occurrence of giant cell tumor in the jawbones is very rare and cases have been reported where patients are already suffering from Paget's disease.

The no ossifying fibroma characteristically will show fibro histiocytic stroma with stipiform pattern and prominent xanthogranulomatous reaction. Other giant cells containing look alikes include aneurysmal bone cyst and cherubim, the former exhibit sinusoidal blood spaces within the tumor mass, while the cherubim is diagnosed on clinical grounds of bilateral involvement of the jaws with a family history and noticed in children.

TREATMENT

The first line of choice in treating CGCG is curettage and it is almost always curative. However, in large and aggressive lesions, especially in the growing facial skeleton where curettage is relatively mutilating in such cases, medical treatment with calcitonin and intralesional injection of steroids have been attempted. It has been reported that the size and number of giant cells are reduced and the stroma becomes collagenous to be replaced gradually by lamellar bone. Interferon-alpha-2A has been suggested as additional treatment of CGCG on the basis of anti-angiogenic action.

 CONCLUSION

There is a significant advancement in the quest of understanding this enigmatic group of lesions. However, the pathogenesis is yet to be defined with authenticity also therapeutic trials has to be worked out especially, the inhibitors of osteoclastic activity.