A Comparative Immunohistochemical Analysis of Central and Peripheral Giant Cell Granulomas Microenvironment Using KI-67, Fibronectin, α-SMA, Cathepsin D, CD163, and CSF-1R

BACKGROUND: Central and peripheral giant cell granulomas are pathologic lesions of the jaws with similar histopathologic features but with different biological behaviors. Clinically, peripheral giant cell granuloma has a low recurrence rate and mainly originated as a benign lesion, which is possibly related to a local irritant factor, while central giant cell granuloma is an expansile osteolytic lesion, which is more aggressive and variable, ranging from an asymptomatic, slow-growing lesion to a painful, rapidly growing, and highly recurrence lesion. METHODS: This retrospective study included 30 cases of central giant cell granuloma and 35 cases of peripheral giant cell granuloma to compare the expressions of KI-67, fibronectin, α-SMA, cathepsin D, CD163, and CSF-1R in multinucleated giant cells and mononuclear stromal cells. This study further evaluates immunohistochemical differences between recurrent and nonrecurrent groups of the studied cases, which had been followed up during the period (2018-2024). RESULTS: This study exhibited significantly higher expressions of all studied markers in central lesions than in peripheral lesions and there were strong correlations among them. In addition, recurrent lesions revealed significantly higher expressions of the studied markers than nonrecurrent lesions. CONCLUSION: CGCG displays a distinct immunophenotypic profile characterized by enhanced proliferation potential, ECM remodeling, activated stromal myofibroblasts, increased osteoclastic activity and M2 macrophage polarization, compared with PGCG. Strong correlations among the studied markers suggest that CGCG's aggressive clinical behavior and recurrence tendency are driven by a combined macrophage-osteoclast-stroma-ECM network. In addition, recurrent lesions showed significantly higher expressions than nonrecurrent lesions, indicating that changes in the lesion microenvironment, rather than specific molecular events.