Background:  The nature and the mechanism involved in the formation of the multinucleated giant cells (MGCs) in various giant cell‐containing lesions of the jaws are not fully understood. The aim of this study is to clarify the osteoclastic features of the MGCs in central giant cell granuloma (CGCG), peripheral giant cell granuloma (PGCG), cherubism, and aneurysmal bone cyst (ABC), and the mechanism underlying the interrelations between cellular components in the formation of the MGCs.

Methods:  Immunohistochemical study with a panel of antibodies including vacuolar H⁺‐ATPase (V‐ATPase), carbonic anhydrase II (CA II), Cathepsin K, matrix metalloproteinases‐9 (MMP‐9), CD68, and proliferating cell nuclear antigen (PCNA), and enzyme histochemical staining for tartarate‐resistant acid phosphatase (TRAP) were applied on a total number of 53 cases of giant cell‐containing lesions including CGCG (n = 34), PGCG (n = 6), cherubism (n = 7), and ABC (n = 6). In situ hybridization was also carried out to detect the mRNA expression of the receptor activator of NF‐kappaB ligand (RANKL), a newly identified cytokine that is shown to be essential in the osteoclastogenesis, its receptor RANK (receptor activator of NF‐kappaB ligand), and its decoy receptor OPG (osteoprotegerin) in these four types of lesions.

Results:  Immunohistochemical and enzyme histochemical studies showed that both the MGCs and a fraction of mononuclear cells in these lesions were strongly positive for TRAP, V‐ATPase, CA II, Cathepsin K, MMP‐9, and CD68, while the spindle‐shaped mononuclear cells were positive for PCNA. The results with in situ hybridization indicated that RANKL mRNA was mainly expressed in the spindle mononuclear cells while OPG was extensively distributed in both the MGCs and the mononuclear cells. RANK mRNA was expressed in the MGCs and some round mononuclear cells.

Conclusions:  These results suggest that MGCs in the four types of giant cell‐containing lesions of the jaws show characteristics of the osteoclast phenotype. The mononuclear stromal cells, which show TRAP positively, may be the precursors of the MGCs. RANKL, OPG, and RANK expressed in these lesions may play important roles in the formation of the MGCs. The similar characteristics and mechanisms in the differentiation of MGCs in these lesions also suggest that there might be a similar kind of pathogenesis involved in the formation of the MGCs in these lesions