Discussion

COC is a developmental odontogenic cyst characterised by an epithelial lining containing ghost cells, which frequently calcify. Calcifying cystic odontogenic tumour and Gorlin cyst are acceptable alternative terms. Although several histological patterns have been described, the current WHO classification recognises no formal subtypes. 

Clinical features and distribution

COC is rare, accounting for less than 1% of odontogenic cysts. It has no sex predilection and occurs most often in the second and third decades. Most lesions arise in tooth-bearing jaw segments, with approximately equal involvement of the maxilla and mandible. Maxillary lesions favour the anterior region, whereas mandibular lesions are more evenly distributed. Approximately 10% are extraosseous, with a predilection for the anterior mandibular gingiva. 

Patients are usually asymptomatic. Intraosseous lesions commonly produce cortical expansion; extraosseous lesions present as submucosal or gingival swellings. A gingival presentation alone does not establish peripheral origin, because an intraosseous lesion may extend into the overlying soft tissue. Dental imaging is therefore important for localisation. 

Imaging and gross appearance

Imaging usually shows a well-defined, unilocular lesion. Approximately one third are uniformly radiolucent, while the remainder have mixed radiolucency reflecting variable mineralisation. The lesion may be associated with an unerupted tooth or an odontoma. Grossly, COC has a cystic cavity, although curettage and fragmentation may obscure this architecture. 

Histopathological features

A fibrous cyst wall is lined by stratified odontogenic epithelium of variable thickness. The basal cells are often cuboidal to columnar, palisaded and hyperchromatic, with ameloblast-like features. The overlying cells may be loosely arranged and resemble stellate reticulum. The lining can form prominent intraluminal nodules or mural epithelial proliferations with an ameloblastoma-like appearance. 

Ghost cells are rounded or flattened eosinophilic cells that retain distinct outlines despite nuclear loss. They occur singly, in clusters, or as large confluent masses and commonly undergo dystrophic calcification. Ghost cells extending into the cyst wall may elicit a foreign body giant cell reaction. Adjacent dentinoid is a dentine-like matrix or mineralised tissue without tubular architecture. COC may coexist with an odontoma or another mixed odontogenic tumour. Calcification is frequent but is not an essential criterion. Dentinoid is likewise not required. Recognition of the architecture and ghost cells is more important than the amount of calcified material. 

Pathogenesis and ancillary studies

COC is associated with CTNNB1 alterations involving the WNT/β-catenin pathway. Similar alterations occur in pilomatrixoma and adamantinomatous craniopharyngioma. Diagnosis rests on morphology; routine diagnostic molecular testing is not clinically required. 

Interpretation of the EQA case

This lesion shows conspicuous cystic architecture, ameloblastoma-like epithelial proliferation, stellate-reticulum-like areas, and abundant ghost cells with focal calcification. These findings favour COC with prominent intraluminal proliferation. Large eosinophilic aggregates include confluent ghost cells with retained cellular outlines. The proliferative appearance explains the diagnostic overlap with DGCT. 

Diagnostic pitfalls

Proliferative COC may contain thick epithelial nodules, satellite cysts, and epithelial extensions into the cyst wall. These features can give parts of the lesion a solid appearance. The textbook describes this as a cystic proliferative or ameloblastomatous pattern; it is a descriptive pattern, not a formal current WHO subtype. Assessment at low power helps establish the relationship of epithelial proliferations to the cystic spaces. 

COC may be mistaken for ameloblastoma if ghost cells are overlooked. Conversely, ghost cells also occur in other odontogenic lesions, including odontomas, and are insufficient on their own to diagnose COC. An associated odontoma or mixed odontogenic tumour should be recognised from its additional tissue components. Ghost cell odontogenic carcinoma is an additional differential when malignant epithelial features are present. 

Brief distinction from DGCT

DGCT is a benign but locally infiltrative solid odontogenic tumour composed of conventional ameloblastoma-like epithelium, ghost cells, and stromal dentinoid; all are essential diagnostic components. Focal cystic degeneration may occur. The distinction from COC depends chiefly on the overall solid versus cystic architecture. Central DGCT has a greater recurrence risk and warrants long-term follow-up, whereas peripheral DGCT is generally indolent and rarely recurs after conservative excision. 

Treatment and prognosis of COC

COC is generally treated by conservative surgical removal, enucleation, and/or curettage. Prognosis is favourable. A systematic review cited by WHO reported an approximately 8% recurrence rate, supporting follow-up after treatment. The textbook likewise describes good outcomes after conservative management. COCs can occur with odontomas or other mixed odontogenic tumours. An associated odontogenic tumour should be identified because the complete pathological diagnosis informs clinical management. 

References

1. WHO Classification of Tumours Online. Calcifying odontogenic cyst; Dentinogenic ghost cell tumour. International Agency for Research on Cancer. tumourclassification.iarc.who.int.

2. Neville BW, Damm DD, Allen CM. Odontogenic cysts and tumors. In: Gnepp DR, ed. Diagnostic Surgical Pathology of the Head and Neck. 2nd ed. Saunders Elsevier; 2009:822–825.