Ninety-two cases of calcifying odontogenic cyst (COC) were reviewed with special consideration of their nature as cysts or neoplasms, the nature of ghost cells, and classification on the basis of clinicopathologic features. The cases were divided into 79 (85.9%) cysts and 13 (14.1%) neoplasms. The cysts occurred as four variants: (1) nonproliferative COC (35 cases), characterized by a simple
... [Show full abstract] unicystic structure; (2) proliferative COC (17 cases), characterized by a cystic structure with multiple daughter cysts, extensive ghost cell formations, and marked tendency for calcification; (3) ameloblastomatous COC (11 cases), characterized by ameloblastoma-like, cyst-lining epithelium with ghost cells and calcifications; and (4) COC associated with odontoma (16 cases), which combined features of COC and odontoma. The neoplasms occurred as three variants: (1) ameloblastoma ex COC (two cases), which showed unifocal and multifocal intraluminal and intramural ameloblastoma proliferating from the COC-lining epithelium; (2) peripheral epithelial odontogenic ghost cell tumor (eight cases), which occurred in the gingiva and resembled peripheral ameloblastoma except for clustered ghost cells in the central portion of epithelial islands and the presence of juxtaepithelial dentinoid; and (3) central epithelial odontogenic ghost cell tumor (three cases). The latter showed ameloblastomatous or adenomatoid odontogenic tumor-like epithelial clusters with ghost cell formation and juxtaepithelial dentinoid. The clinical features of cystic and neoplastic variants were tabulated and described. On the basis of histopathologic features and their immunohistochemical reaction to polyclonal antikeratin antibody, it is suggested that ghost cells might be the result of coagulative necrosis.