Differential diagnosis of Giant Cell Lesions of the Jaw

Giant cell lesions of the jaw (GCLJ) include a diverse group of lesions that affect the mandible and maxilla which characterized histopathologically by presence of multinucleated osteoclast-like giant cells, these lesions range from reactive processes to true neoplastic lesions, and can also manifest as part of systemic disorders or genetic syndromes. The overlap in their clinical features, radiological, and histopathological features presents significant diagnostic complexities. This report provides a comprehensive review of the major GCLJ, including Central Giant Cell Granuloma (CGCG), Peripheral Giant Cell Granuloma (PGCG), Syndromic Central Giant Cell Granulomas associated with RASopathies, Cherubism, Brown Tumor of Hyperparathyroidism, Aneurysmal Bone Cyst (ABC), Giant Cell Tumor of Bone (GCT), Giant Cell Reparative Granuloma (GCRG), and Tenosynovial Giant Cell Tumor (TGCT). It highlights the critical importance of an integrated diagnostic approach, including clinical evaluation, advanced imaging, histopathology, immunohistochemistry, and molecular testing to achieve accurate diagnoses and guide effective, multidisciplinary management strategies.