Oral Maxillofacial Surg Clin N Am 16 (2004) 391 – 397
Calcifying odontogenic cyst and dentinogenic ghost
cell tumor
Charles E. Tomich, DDS, MSD
Dermatopathology Laboratory, 9292 North Meridian Street, Suite 210, Indianapolis, IN 46260, USA
The calcifying odontogenic cyst was first de-
scribed as a distinct clinicopathologic entity by Gor-
lin and his colleagues in 1962 [1]. Already in the
publication process but not yet in print was a report of
four cases by Gold [2]. Gold chose a similar, but not
identical, term for the lesion, namely ‘‘keratinizing
and calcifying odontogenic cyst.’’ Thus, by only a
short period of time the calcifying odontogenic cyst
commonly is termed eponymically the ‘‘Gorlin cyst’’
rather than the ‘‘Gold cyst.’’ Perhaps the Gorlin-Gold
cyst would be a fitting term for this interesting
odontogenic lesion. The first actual description of a
calcifying odontogenic cyst was published three dec-
ades earlier (1932) in the German literature by
Rywkind [3]. Rywkind believed the lesion to be a
variant of a cholesteatoma.
Other examples of the calcifying odontogenic cyst
were reported in the 30-year interval between Ryw-
kind’s report and the seminal paper by Gorlin and his
colleagues; however, none of the authors considered
the lesion to be a distinct clinicopathologic entity. For
example, Kurt Thoma and Henry Goldman [4]
reported three cases in 1940—one in an 8-year-old
and two in teenagers. They considered the lesions to
be odontogenic tumors of ectodermal and mesoder-
mal origin. They were not far from being correct.
Other single case reports described lesions as variants
of ameloblastoma or atypical adamantinoma; the
latter is an old term for ameloblastoma [5,6]. All of
the investigators noted the unusual ‘‘ghost cell’’
keratinization of the odontogenic epithelium. The
‘‘ghost cell’’ keratinization is the striking histologic
feature of the entity.
E-mail address: cjtomich@aol.com
1042-3699/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.coms.2004.03.006
Gorlin and his associates [1] suggested that the
calcifying odontogenic cyst might be the oral analog
of the ‘‘calcifying epithelioma of Malherbe’’ (now
preferably termed a ‘‘pilomatricoma’’). The piloma-
tricoma is a well-recognized lesion of skin. The lesions
have in common the peculiar abnormal keratinization
of odontogenic and metrical (hair) epithelial cells that
is termed ‘‘ghost cell’’ or ‘‘shadow cell’’ kera-
tinization. Actually, the calcifying odontogenic cyst
shares more histologic features with the rare, intracra-
nial neoplasm known as a ‘‘craniopharyngioma.’’ The
craniopharyngioma is considered to be related histo-
genetically to Rathke’s pouch, an invagination of the
superior aspect of the stomodeum (primitive oral
cavity) that gives rise to the anterior lobe of the
pituitary gland. Microscopically, the craniopharyn-
gioma is identical to the calcifying odontogenic cyst.
After the reports of Gorlin and his colleagues [1]
and Gold [2], the calcifying odontogenic cyst be-
came well-recognized by oral pathologists; subse-
quently, numerous single and series case reports
appeared in the literature. As more and more cases
were studied, it became apparent that the lesion was
not always a cyst; sometimes it was a solid lesion.
Furthermore, it became apparent that the lesion
could present centrally within the jaws or as an
extraosseous gingival lesion. This begged the ques-
tion: ‘‘Is the Gorlin cyst a cyst or is it a tumor that
is frequently cystic?’’
In view of these findings, investigators suggested
different names for this lesion. Fejerskov and Krogh
[7] suggested the term ‘‘calcifying ghost cell odonto-
genic tumor’’ and Freedman and his associates [8]
suggested the name ‘‘cystic calcifying odontogenic
tumor.’’ Neither of these terms met with approval,
possibility because of their similarity to the well-
392 C.E. Tomich / Oral Maxillofacial Surg Clin N Am 16 (2004) 391–397

recognized lesion called the ‘‘calcifying epithelial

odontogenic tumor’’ or Pindborg tumor.
The issue of ‘‘cyst versus tumor’’ or ‘‘cystic
versus solid’’ has not been resolved totally.

Epidemiology

The calcifying odontogenic cyst is not a common

lesion; the dentinogenic ghost cell tumor is even less
common and should be considered rare. During a
span of 23 years (1950 – 1973), 34 cases of calcify-
ing odontogenic cyst were found in 43,500 acces-
sions in the oral pathology diagnostic service at the
Fig. 2. This large calcifying odontogenic cyst was believed
Indiana University School of Dentistry [9]. Seven- to represent a residual inflammatory cyst. It produced buccal
teen more cases were diagnosed in the ensuing expansion but was not painful.
11 years (1974 – 1984). Thus, over a 34-year period,
only 51 cases of calcifying odontogenic cyst were
commonly seen to have the lesion [9 – 12]. Particu-
diagnosed—less than two cases per year! It follows
larly in the second decade of life, and to a lesser
that the average oral and maxillofacial surgeon is
extent in the third decade, the lesion is found in
likely to see only a case or two during his/her pro-
association with an odontoma or impacted tooth.
fessional career.
The cyst occurs in both genders with almost
Despite the uncommon occurrence of the calcify-
equal frequency. Buchner’s [10] extensive review of
ing odontogenic cyst and the rare dentinogenic ghost
cell tumor, the former has gained wide recognition
and a large series of cases have been reported in the
literature [8,10,11]. It is from these reports and
studies from academic institutions that the significant
clinicopathologic information is derived.

Age, gender, and anatomic location

Although the calcifying odontogenic cyst may

be seen in any decade of life, studies have shown
that persons in the second and third decades are most

Fig. 3. This calcifying odontogenic cyst produced soft tissue

Fig. 1. This is a (peripheral) calcifying odontogenic cyst that swelling that is evident radiographically. The crestal bone is
presented as a localized, exophytic lesion of the edentulous ‘‘cupped out,’’ which resulted in a radiographic image that
mandibular alveolar ridge in a male adult. was suggestive of a peripheral giant cell granuloma.
 C.E. Tomich / Oral Maxillofacial Surg Clin N Am 16 (2004) 391–397
Fig. 4. This calcifying odontogenic cyst is characterized by
a well-circumscribed radiolucency with a faint hint of
an opacity within. The superior margin of the lesion is
slightly corticated.
215 cases included 110 women and 105 men. The
lesion has been seen in many racial groups.
The mandible was affected most commonly in the
Indiana series of cases [9]. Forty-two of the 60 cases
(70%) were located there. Buchner [10] reported that
in Asians there was a predilection for the maxilla,
Fig. 5. This calcifying odontogenic cyst presented as a large
radiolucency of the anterior maxilla with a prominent
radiopacity. Note the divergence of the two incisor teeth.
393
whereas in whites there was a 62% disposition in
the mandible.
Clinical and radiographic features
The calcifying odontogenic cyst that occurs cen-
trally in the jaws may present as a painless expansile
lesion or it is discovered frequently on radiographic
examination in the dental office. The lesions that
occur peripherally (extraosseous) on the gingiva
present as painless swellings or nodules (Fig. 1).
There are no pathognomonic clinical features that
are diagnostic of the lesion.
It is by the radiographic presentation that most
intraosseous calcifying odontogenic cysts are de-
tected. The lesions may present as radiolucencies
(Figs. 2 and 3) or radiolucencies with foci of opaci-
fication (Figs. 4 and 5), particularly in the case of
those that are associated with odontomas (Fig. 6).
Expansion may be evident in some cases (Fig. 7). The
Fig. 6. This calcifying odontogenic cyst was associated with
an odontoma. There is a distinct follicular space around the
crown of the impacted canine tooth. The calcifying
odontogenic cyst was found in the soft tissue surrounding
the odontoma.
394 C.E. Tomich / Oral Maxillofacial Surg Clin N Am 16 (2004) 391–397
Fig. 7. This is a maxillary calcifying odontogenic cyst in a
young teenager. The lesion produced marked palatal and
buccal expansion.
dentinogenic ghost cell tumor is known to present as
an expansile radiopacity (Fig. 8).
Microscopic features
The main histopathologic criteria for the diagno-
sis of the calcifying odontogenic cyst are well-
established. The cyst lining should show proliferation
to the point that it resembles ameloblastoma (ie,
columnar cells over which are stellate and spindled
cells in an arrangement that suggest stellate reticu-
lum). Within this proliferation of epithelium, cells
undergo the characteristic ‘‘ghost cell’’ keratinization
(Figs. 9 – 11). The calcifying odontogenic cyst often
is encountered in association with an odontoma
(Fig. 12). At times, a ‘‘product’’ may be identified
in juxtaposition to the proliferative lining epithelium
or intermixed with the ghost cells (Fig. 12B). This
Fig. 8. Panoramic (A) and occlusal (B) radiographs of a mandibular dentinogenic ghost cell tumor. The asymptomatic tumor
produced marked labial and lingual expansion. The tumor is characterized by radiolucent and radiopaque zones.
has been called ‘‘dentinoid.’’ When this material is
formed in abundance and the lesion is ‘‘solid’’ rather
than ‘‘cystic,’’ the lesion may be termed a ‘‘dentino-
genic ghost cell tumor’’ (Fig. 13). Dystrophic calcifi-
cation of the ghost cells may be seen; however, it is
one of the less common and least important of the
histologic features.
The presence of ghost cells within the proliferative
odontogenic epithelium is the essential characteristic
for the diagnosis. The presence of ghost cell keratini-
zation alone is not sufficient enough for the diagnosis
nor is it pathognomonic. Ghost cell keratinization may
be observed in odontomas, ameloblastomas, amelo-
blastic fibro-odontomas, and in ameloblastic odonto-
mas to name a few. Thus, one must observe ghost cells
to make the diagnosis of the Gorlin cyst; however,
their presence alone is not sufficient enough to make
or dictate the diagnosis.
The ghost cells may be accentuated in routine
paraffin sections by the van Gieson, Goldner, or
Ayoub-Shklar histochemical stains [13]. This has
proven to be particularly helpful in the solid lesions
in which there is an abundance of dentinoid and the
ghost cells are less conspicuous (see Fig. 13C).
The ghost cells have been subjected to ultrastruc-
tural and immunologic studies. Chen and Miller [14]
found that the ghost cells contained numerous, thick
bundles of tonofilaments with intermingled remnants
of cell organelles. Sapp and Gardner [15] reported
similar findings. The ghost cells contained nuclear
remnants, remnants of cytoplasmic organelles, and
numerous tonofilaments. These findings are essen-
tially the same as those observed in the ghost cells in
pilomatricomas [16]. In normal keratinized skin and
oral mucose, similar findings are seen in the kerati-
nized squames in the cornified layer. The ghost cells
differ from normal keratotic squames in that they are
 C.E. Tomich / Oral Maxillofacial Surg Clin N Am 16 (2004) 391–397
Fig. 9. Calcifying odontogenic cyst (100). Note the thin
lining epithelium of the cyst in the upper portion of the
photomicrograph and the proliferation in the lower portion.
The orderly lining cells are seen immediately adjacent to the
capsule and the ghost cell keratinization in juxtaposition.
Hematoxylin & Eosin (H&E) stain.
larger, often vacuolated, and the remnants of the
nuclear membranes are more prominent. This may
be due to intracellular edema and the presence of
dilated degenerated membranous organelles.
The immunohistochemical studies that have been
performed on the ghost cells have been interesting.
Takata and coworkers [17] demonstrated that the
ghost cells express enamel-related proteins (ameloge-
nin, enamelin, sheathlin, and enamelysin). In con-
trast, the ghost or shadow cells in a pilomatricoma
were immunonegative for all of these proteins. A
study by Badger and Gardner [18] compared the
immunoprofile of the calcifying odontogenic cyst
with the craniopharyngioma. Both lesions demon-
strated similar immunoreactivity to low- and high-
molecular weight cytokeratins and involucrin—a
Fig. 10. This calcifying odontogenic cyst shows the pro-
liferation of the lining epithelium with palisaded, hyper-
chromatic columnar nuclei, stellate reticulum-like area, and
sheets of ghost cells (100; H&E stain).
395
Fig. 11. Aggregates of ghost cells are seen in association
with odontogenic epithelium. Low columnar cells (A) and
spindled cells (B) are seen in association with groups of
ghost cells (450; H&E stain).
protein that is characteristic of terminally-differenti-
ated keratinocytes. Although Gorlin and his cow-
orkers [1] suggested that the calcifying odontogenic
cyst is the oral counterpart of the cutaneous calcify-
ing epithelioma of Malherbe (pilomatricoma), it is
more likely to be the oral counterpart of the intracra-
nial craniopharyngioma.
Classification
Now that numerous cases of the Gorlin cyst have
been described, it has become obvious that it is not
one lesion but really two—a cystic lesion and a solid
neoplastic lesion. A third malignant counterpart of the
neoplasm lesion may be added. The calcifying odon-
togenic cyst may present as an intraosseous cystic
lesion or in association with an odontoma. On rare
occasions, it may present as a peripheral (gingival)
lesion. The neoplasm, more aptly termed a ‘‘dentino-
genic ghost cell tumor,’’ is a rare lesion that may
occur in bone or in the gingival soft tissue.
Earlier classifications by authorities such as Prae-
torius et al [19] and Buchner [10] have been invalu-
able in helping us to understand the various clinical
and microscopic expressions of these lesions; how-
ever, a more simple classification, such as that sug-
gested by Li and Yu [20], seems to be more practical.
Treatment and prognosis
The calcifying odontogenic cyst, with or without
an associated odontoma, can be treated successfully
by enucleation or thorough curettage. Peripheral
lesions should be treated by conservative excision.
396 C.E. Tomich / Oral Maxillofacial Surg Clin N Am 16 (2004) 391–397

Fig. 12. (A,B) The calcifying odontogenic cyst is associated with an odontoma in a significant percentage of cases. ES, enamel
space; GC, sheets of ghost cells; O, odontoma (A 40; B 450; H&E stain).

The central (intraosseous) dentinogenic ghost cell
tumor is treated by surgical excision. The removal of
the tumor may require block excision or segmental
resection, depending upon its size or anatomic extent.
Although too few cases have been reported to predict
prognosis based upon a specific type of treatment (eg,
curettage, block excision, segmental resection), re-
currence following conservative treatment has been
reported [21] and is known by personal experience.
Peripheral lesions can be treated by conservative
surgical excision.
A rare malignant counterpart is recognized. Al-
though first reported in the Spanish language litera-
ture in 1965 by Astacio and Martinez [22], it was not

Fig. 13. (A,B) The dentinogenic ghost cell tumor is characterized by sheets of ghost cells with intermixed dentinoid. (C) The
Ayoub-Shklar stain is helpful in delineating the ghost cells (GC) and the dentinoid (D) (A,B 100, H&E stain; C 450, Ayoub-
Shklar stain).
 C.E. Tomich / Oral Maxillofacial Surg Clin N Am 16 (2004) 391–397
recognized until it was discussed in the first edition of
the famous World Health Organization ‘‘small blue
book’’ on the histologic typing of odontogenic cysts
and tumors [23]. This tumor has been known by a
variety of terms, including ‘‘malignant calcifying
odontogenic cyst’’ [5], ‘‘odontogenic ghost cell car-
cinoma’’ [24], and ‘‘aggressive epithelial ghost cell
odontogenic tumor’’ [25], to name a few. The terms
seem to be cumbersome but the designation ‘‘odon-
togenic ghost cell carcinoma’’ [24,26] seems to be
descriptive and specific.
Although less than two dozen cases have been
reported in the literature, small series of cases [25,26]
and reviews of the literature [24] have provided valu-
able information on these unusual and rare lesions.
The lesions have arisen in previously diagnosed cal-
cifying odontogenic cysts and as de novo tumors.
They are capable of locally aggressive behavior as
well as distant metastasis.
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