Pathology of Ghost Cells and Calcifying Odontogenic Cyst (Calcifying Ghost Cell Odontogenic Cyst )


Dr Sampurna Roy MD   








(1) The most striking microscopic feature of this tumour are the so-called  "Ghost" epithelial cells present either in the epithelial lining or connective tissue. 

Ghost cells are large pale anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas instead of a basophilic nucleus. 

Individual ghost cells may fuse together to form large sheets of amorphous eosinophilic structure on which calcification may occur.

Confocal laser scanning microscopy observations have disclosed that Calcifying odontogenic cyst  ghost cells autofluoresce. However, autofluorescence intensities are variable, possibly due to hard keratin presence .

(2)  Anucleated ghost cells have been referred to in the English literature using a variety of terms, including "degenerated epithelium" , "epithelial pearls" , "enamel organ" , "concentric homogenous bodies" , "calcified globules resembling keratin" , "hyaline-like bodies"  , and "keratinized squamae", to name a few.

In the German literature, Rywkind and Shiltzow introduced the name "rote Zellen" (red cells) for ghost cells in 1931.

(3)  Dr RJ Gorlin et al, was the first person to describe calcifying ghost cell odontogenic cyst (CGCOC) under the term calcifying odontogenic cyst (COC) in 1962.

Although Gorlin et al. coined the term "calcifying odontogenic cyst" (COC) in 1962, this type of cyst was initially reported three decades earlier by Dr AW Rywkind in Russia, and almost concurrently by Dr JC Bloodgood in the United States and Dr S Sato in Japan.

(4)  The term "calcifying epithelioma of Malherbe" first appeared in a 1931 French report.

Highman and Ogden (1944)  first described ghost cell in pilomatrixomas. They described ghost cells as dyskeratotic cells, which are similar to viable cells, but have a distinct outline.

According to some authors the term "ghost cells" had its origin in two American seminal articles by Thoma and Goldman in 1946.

As the number of cases increased, Gorlin et al. began to call calcifying odontogenic cyst as "oral Malherbe" by the 1950s.

(5)  Dr L Gold  also reported on COC in 1963. Dr RJ Gorlin's study stressed the histological resemblance of COC to cutaneous calcifying epithelioma of Malherbe and Dr L Gold  focused on the relationship between COC and calcifying epithelial odontogenic tumour.

In consideration of Dr Gold’s suggestion , Dr Gorlin in 1968 also used a similar compound name "calcifying and keratinizing odontogenic cyst" only once.

(6)  Although Thoma in 1946 came to the conclusion that ghost cell keratinization is caused by necrobiosis of the odontogenic epithelium preceding calcification, there is no mention of ghost cells in the 3rd (1950), 4th (1954) , or 5th (1960) editions of his textbooks.

(7) This fascinating tumour has been reported under a variety of other names including  keratinizing cyst ; keratinizing cyst and calcifying odontogenic cyst (KCOC) ; calcifying ghost cell odontogenic tumor; dentinogenic ghost cell odontogenic tumour ; epithelial odontogenic ghost cell tumour; ghost cell cyst ; calcifying ghost cell odontogenic tumour, and dentino-ameloblastoma by various authors.

(8) From the year of description, disagreements exist regarding the nature, terminology and classification of CGCOC.

These controversies and confusion about the lesion are due to existence of two variants of the lesion: cystic and the neoplastic forms.

In 1971, the WHO described CGOC as a "non-neoplastic" cystic lesion; nevertheless, it decided that the lesion should be classified as a benign odontogenic tumour.

In 1992, the World Health Organization (WHO) classified CGOC as a neoplasm rather than a cyst but confirmed most of the cases are nonneoplastic. 

(9) The unified term "odontogenic ghost cell lesions (OGCL)"  or "ghost cell odontogenic tumors", which refers to the origin and nature of these lesions and also defines their most characteristic microscopic feature, was proposed under the 2005 WHO guidelines. 

World Health Organization (2005) updated its classification of odontogenic tumors , and reclassified the calcifying odontogenic cyst subdividing it into three distinct entities:

- calcifying cystic odontogenic tumor (CCOT),

- dentinogenic ghost cell tumor (DGCT) and

- ghost cell odontogenic carcinoma (GCOC)

(10) Calcifying ghost cell odontogenic cyst is a very rare tumour. Average oral and maxillofacial surgeon is likely to see only one case or two during his/her professional career.

(11)  In Asians, it showed a higher incidence in younger age group; almost 70% occurred in the second and third decades, whereas in Caucasians, this tumour was reported in only about 53% of patients in this age group.

(12) In the Asians, the lesions showed a predilection for the maxilla (65%), whereas in Caucasians, the mandible (62%) was more commonly involved. The most common site of occurrence has been the anterior part of the jaws. In the mandible, several cases have crossed the midline, but this is not a prominent feature in the maxilla

(13)  Although characteristic of calcifying cystic odontogenic tumors , "Ghost cells" are also found in other odontogenic lesions namely ameloblastoma  odontoma  and ameloblastic fibro-odontoma , and in nonodontogenic tumours such as pilomatrixoma  and craniopharyngioma.

The World Health Organization Classification of Head and Neck Tumours considered ghost cells as transitory squamous cells at various stages of development. However to date the true nature of these ghost cells is not known. The calcifying process of ghost cells also remains ill-understood.






Lee SK, Kim YS. Current Concepts and Occurrence of Epithelial Odontogenic Tumors: II. Calcifying Epithelial Odontogenic Tumor Versus Ghost Cell Odontogenic Tumors Derived from Calcifying Odontogenic Cyst. Korean Journal of Pathology. 2014;48(3):175-187.


Sonone A, Sabane VS, Desai R. Calcifying Ghost Cell Odontogenic Cyst: Report of a Case and Review of Literature. Case Reports in Dentistry. 2011;2011:328743. 


The Early History of Odontogenic Ghost Cell Lesions: From Thoma to Gorlin


Odontogenic Tumors, WHO 2005: Where Do We Go from Here?


Calcifying ghost cell odontogenic cyst: A review on terminologies and classifications


Notch signaling and ghost cell fate in the calcifying cystig odontogenic tumor










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