Journal of the Scientific Society

: 2020  |  Volume : 47  |  Issue : 1  |  Page : 3--7

Calcifying odontogenic cyst – A review

Bhupender Singh Negi1, Iftekhar Danish2, Preeti Gupta3, Robin Sabharwal4,  
1 Senior Resident, Department of Oral Medicine and Radiology, Government Dental College, Kottayam, Kerala, India
2 Tutor, Hi-Tech Dental College and Hospital, Odisha, India
3 Private Practitioner, New Delhi, India
4 Private Practitioner, Chandigarh, India

Correspondence Address:
Dr. Preeti Gupta
Private Practitioner, New Delhi


Calcifying odontogenic cyst (COC), also known as “Gorlin cyst,” is a rare developmental odontogenic lesion, introduced by Gorlin in 1962. COC exists either as a cystic or a solid variant. This lesion has been known by different names and classified into various subtypes. The World Health Organization classified (2005) COC as a neoplasm and used the term calcifying cystic odontogenic tumor for benign cystic type, the dentinogenic ghost cell tumor for the benign solid type lesions which occur centrally or peripherally, and the malignant one as ghost cell odontogenic carcinoma. COC mimics other odontogenic cysts clinically as well as radiologically, and a definitive diagnosis can be made only by histological means. The present article discusses the various terminologies, classification, histopathology, and immunohistochemistry of COC.

How to cite this article:
Negi BS, Danish I, Gupta P, Sabharwal R. Calcifying odontogenic cyst – A review.J Sci Soc 2020;47:3-7

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Negi BS, Danish I, Gupta P, Sabharwal R. Calcifying odontogenic cyst – A review. J Sci Soc [serial online] 2020 [cited 2020 Aug 12 ];47:3-7
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Several calcifying odontogenic cyst (COC) classifications have been suggested in literature, each trying to separate the cystic from solid variants, but none has been universally accepted. The solid variant of COC seems to represent the ultimate phase of the evolution of the COC and not necessarily a separate entity. There are two different concepts or schools of thought depending on the nature of COC: the monistic and the dualistic concept.[1],[2]

Classification based on the monistic concept: World Health Organization (WHO) Classification (1971, 1992)

The classification is based on the monistic concept that all COCs, both cystic and solid lesions, are neoplastic in nature, even though the majority appear to be nonneoplastic. In 1971, the WHO classified COC as a benign odontogenic tumor, though it described it as a nonneoplastic cystic lesion.[3]

In 1992, the WHO deleted the term “nonneoplastic” to resolve this contradiction, and it again classified the lesion with the benign odontogenic tumors. They cited the terms dentinogenic ghost cell tumor, Calcifying odontogenic cyst cell tumor (OGCT), especially for the solid lesion whose neoplastic nature is apparent. They however retained the term COC [Table 1].[2]{Table 1}

Classification based on dualistic concept

Buchner recognized the multicystic COC as a separate entity in an excellent review of 215 cases of central COCs and proposed a more detailed classification [Table 2]. Ninety-two cases of COC were reviewed by Hong et al., 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 cysts and neoplasms.[4]{Table 2}

The cysts occurred as four variants:

Nonproliferative COC, characterized by a simple unicystic structureProliferative COC, characterized by a cystic structure with multiple daughter cysts, extensive ghost cell formations, and marked tendency for calcificationAmeloblastomatous COC, characterized by ameloblastoma-like, cyst-lining epithelium with ghost cells and calcificationsCOC associated with odontoma, which combined features of COC and odontoma.

The neoplasms occurred as three variants:

Ameloblastoma, for example, COC, which showed unifocal and multifocal intraluminal and intramural ameloblastoma proliferating from the COC-lining epitheliumPeripheral epithelial OGCT, 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 dentinoidCentral epithelial OGCT. The latter showed ameloblastomatous or adenomatoid odontogenic tumor-like epithelial clusters with ghost cell formation and juxtaepithelial dentinoid.[4]

The new dualistic classification of the so-called COC by Toida was given in 1998.

The author concluded that if the monistic concept is true, the calcifying ghost cell odontogenic cyst (CGCOC) will be deleted from the below [Table 3] and the same classification can be used as the monistic one.{Table 3}

In this monistic classification scheme, it is unnecessary to differentiate cystic calcifying ghost cell odontogenic tumor from CGCOC. In the dualistic classification, it may be difficult to differentiate the two entities, especially when the intramural proliferation of the cyst lining epithelium is evident but not excessive.

Li and Yu (2003) on the basis of the likely differences in biologic behavior of the COC and its related lesions proposed a more concise terminology and classified the lesions into the following three groups:

CystsBenign tumorsMalignant tumors.

They suggested that the term COC should be used specifically for the unicystic lesions with or without an associated odontoma. Other suggested classifications of COCs were by Reichart et al., 2004, and Praetorius in 2006.

Gorlin et al.[5] described it as distinct pathological entity though the various classification systems and terminologies have been used in relation to COC.

The dualistic concept finds more favor among the researchers.

 Clinical Presentation

Swelling is the most frequent complaint. Only rarely has there been pain. Intraosseous lesions may produce a hard bony expansion and may be fairly extensive. Lingual expansion may sometimes be observed. Occasionally, the COC may perforate the cortical plate and extend into the soft tissues. In a few cases, displacement of the teeth has been described. Some cases have been completely symptomless and have been discovered fortuitously during routine radiological examination. Extraosseous lesions tend to be pink to red, circumscribed elevated masses measuring up to 4 cm in diameter.[6]

 Radiological Features

The COC that occurs as an intraosseous lesion appears as an essentially radiolucent area. Radiographically, these lesions appear to have well-demarcated margins, but in some cases, irregular poorly defined margins can be seen. They are usually unilocular, but a few have been multilocular. Irregular calcified bodies of varying size and opacity may be seen in the radiolucent lesion. Denser opacities are likely to be present if the cyst is associated with a complex odontome.

Displacement of teeth along with root resorption of adjacent teeth is a frequent finding, and is regarded as an important radiological feature. Local expansion sometimes occurs and perforation of the cortical plate, when present, may be radiologically demonstrable. The extraosseous lesions show localized superficial bone resorption, or saucer-shaped radiolucencies and sometimes displacement of adjacent teeth.[7],[8],[9]

 Pathogenesis and Pathology

The histological features of a classic COC are characteristic and present few diagnostic problems. As defined in the WHO classification of 1992, it is: “A cystic lesion in which the epithelial lining shows a well-defined basal layer of columnar cells, an overlying layer that is often many cells thick and that may resemble stellate reticulum, and masses of 'ghost' epithelial cell that may be in the epithelial lining or in the fibrous capsule. The 'ghost' epithelial cells may become calcified. Dysplastic dentine may be laid down adjacent to the basal layer of the epithelium, and in some instances the cyst is associated with an area of more extensive dental hard tissue formation resembling that of a complex or compound odontoma.”[10],[11],[12]

It was suggested that the COC was a unicystic process that developed from reduced enamel epithelium or remnants of odontogenic epithelium in the follicle, gingival tissue, or bone. Dentinoid alone, or an odontome, may be found in the cyst wall, induced by the lining epithelium.

The classic COC is most frequently a unilocular lesion, but multicystic lesions have been reported. Satellite cysts may develop from odontogenic epithelial islands in the wall, two-thirds were cystic, and one-third were solid. The epithelial lining has characteristic odontogenic features with a prominent basal layer consisting of palisaded columnar or cuboidal cells and hyperchromatic nuclei which are polarized away from the basement membrane.[10] The epithelium may be regular 6–8 cells thick over part of its length and be continuous with parts that may be very thin and others that are considerably thickened. Budding from the basal layer into the adjacent connective tissue and epithelial proliferations into the lumen are frequently seen. Melanin deposits are sometimes present in the epithelial linings. The most remarkable feature of the COC is the presence of ghost cells. The ghost cells are found in groups, particularly in the thicker areas of the epithelial lining.[13]

The spinous cells in such situations may be widely separated by intercellular edema, and the epithelium around the ghost cells is often convoluted. The ghost cells are enlarged, ballooned, ovoid, or elongated elliptoid epithelial cells [Figure 1].[14]{Figure 1}

They are eosinophilic and although the cell outlines are usually well defined, they may sometimes be blurred so that groups of them appear fused. A few ghost cells may contain nuclear remnants, but these are in various stages of degeneration, and in the majority, all traces of chromatin have disappeared leaving only a faint outline of the original nucleus. The ghost cells represent an abnormal type of keratinization and have an affinity for calcification. They have the same histological reactions as keratin, giving a yellow fluorescence with rhodamine B.[15],[16]

Hong et al.[4] showed that in formalin-fixed tissue, the ghost cells expressed little or no cytokeratin (CK) reactivity and suggested that this, in association with their histological features, may represent the product of coagulative necrosis of odontogenic epithelium. Sapp and Gardner[12] found that calcification may occur in some of the ghost cells, initially as fine powdery or coarse basophilic granules and later as small spherical bodies that ultrastructural studies have shown to represent dystrophic calcification. The ghost cells may be in contact with the connective tissue wall of the cyst where they may then evoke a foreign body reaction with the formation of multinucleate giant cells. In the fibrous wall, there are usually strands and islands of odontogenic epithelium, either in direct contact with the epithelium or separately in the connective tissue.[17]

These vary from a few strands to extensive proliferations. An atubular dentinoid is often found in the wall close to the epithelial lining and often in relation to the epithelial proliferations. It is frequently described as being found particularly in contact with masses of ghost cells. As pointed out in the classification of Pretorius, there are many variations of odontogenic lesions characterized by the presence of these “ghost cells”. A number of these are solid tumors and not cysts at all. Others are cysts but are associated with odontogenic hamartomas or benign neoplasms, for which the term “calcifying cystic odontogenic tumor” is thought to be more appropriate than “calcifying odontogenic cyst”.


Recent immunohistochemical studies on the COC have been published by Kumamoto et al.[18] and Takata et al.[19]

The Takata group was interested in determining the nature of the ghost cells by examining their immunoreactivity with antibodies against amelogenin, enamelin, enamelysin (MMP-20), and sheathlin (prism sheath protein). They showed that the cytoplasm of the ghost cells in COCs demonstrated distinct immunolocalization of the enamel-related proteins, but was negative in the ghost cells of the calcifying epitheliomas (Malherbe) in the skin. Monoclonal antibody 203-IC7 was found to be useful as an enamel-specific marker in the late stage of enamel matrix development and calcification, including the immature enamel matrix of ameloblastic fibro-odontomas and odontomas. Enamelysin was detected in a portion of the ghost cells in COCs tested. Kusama et al. (2005) investigated the immunoreactivity of the ghost cells in 14 COCs to three kinds of antibodies raised against human hair proteins. These antibodies reacted only with ghost cells, not with other epithelial cells. The authors speculated that the ghost cells might represent differentiation into the hair. Immunoreactivity for phosphothreonine, detected in hard alpha-keratins, was also found in the ghost cells.

In an immunohistochemical study to determine the localization of amelogenin in human odontogenic tumors, Abiko et al. (2001) confirmed that some ghost cells in the linings of COCs were strongly stained. In a range of ghost cell odontogenic lesions, Yoshida et al. confirmed the presence of amelogenin protein in the cytoplasm of the ghost cells in all 16 of their cases and also the epithelial linings of five of these specimens. CK 19 protein was expressed in the epithelial lining cells in all cases, whereas ghost cells were devoid of staining. Bcl-2 protein was expressed in the epithelial linings of 12 cases, but ghost cells in only two. They found that the epithelial lining cells showed only sporadic Ki-67-positive reactions in nuclei. While their material included lesions exhibiting various histological features including “proliferative type lining epithelium, ameloblastomatous appearance, and combined odontoma,” they also observed transitional features. However, they found no difference in amelogenin or CK 19 expression among the lesions with various histological features and only a slight difference in Bcl-2 and Ki-67 expression. They concluded that COCs with varying histological features have neoplastic potential and may not be separate entities.[18]


The COC is treated by surgical enucleation unless it is associated with another odontogenic tumor; in that case, an excision wider than the lesion may be required. In case of association with complex odontome, conservative removal will still be adequate. A variant of ameloblastoma with foci of ghost cells must be treated as would be an ameloblastoma without ghost cells. Although classic uncomplicated cases of COCs may grow to a large size, reported recurrences are rare.

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