MINI-SYMPOSIUM: ORAL AND MAXILLOFACIAL PATHOLOGY

Odontogenic cysts: an was removed from the classification of cysts and called “kera-
tocystic odontogenic tumour” (KCOT) and the calcifying odon-

update togenic cyst was reclassified “calcifying cystic odontogenic

tumour”. The intention was to redefine these lesions as cystic
neoplasms, but the evidence for doing so was not clear and was
Lisette HC Martin controversial. The most striking and welcome change in the new
Paul M Speight 4th edition of the WHO classification is the return of the odon-
togenic cysts, thus restoring the book’s status as the only com-
plete classification of lesions of the odontogenic tissues.2
This review provides an update of our previous paper,1 clar-
Abstract
ifies terminology and explains the reasoning behind the new
The classification of odontogenic cysts has been widely debated and
there has been much debate and controversy about the true nature of
classification. For a detailed description of the clinical and
pathological features of these lesions, readers are referred to our
some of the lesions. Although cysts are common in the jaws, most are
original review article.1
radicular cysts of inflammatory origin or simple dentigerous cysts.
Others are less frequently encountered and may present diagnostic
difficulties because of their varied features. The previous WHO classi-
Update to the classification
fication, in 2005, redesignated a number of these lesions as true neo- The definition of jaw cysts remains the same6e‘a pathological
plasms, but this was controversial and was not based on sound cavity having fluid, semi-fluid or gaseous contents and which is
evidence. For the latest WHO classification (2017), an international not created by the accumulation of pus’. This definition does not
consensus group reappraised these lesions and agreed a terminology require the presence of an epithelial lining as essential for a
and new classification. This brief review presents this new classifica- diagnosis, and recognises that a number of lesions, which are not
tion, and explains the reasoning behind the agreed terminology. of epithelial origin are cystic and are commonly included in the
Keywords calcifying odontogenic cyst; collateral cysts; dentigerous classification of cysts. In the jaws all the odontogenic cysts are
cyst; gingival cysts; glandular odontogenic cyst; odontogenic cysts; epithelium lined, but a number of cystic lesions, which should be
odontogenic keratocyst; orthokeratinised odontogenic cyst; radicular included in the differential diagnosis, are not. These include, for
cyst example, solitary bone cyst and aneurysmal bone cyst, which are
included in the new classification as “bone cysts”.
The new classification of cysts of the jaws is very similar to
that used in the 2nd edition4 (Table 1). It is based first on the
Introduction origin of the epithelial lining and then according to their putative
Although the odontogenic cysts have been reviewed recently,1 pathogenesis. Those that derive their lining from remnants of the
the publication of the new WHO Classification of Head and tooth forming tissues are termed ‘odontogenic’ and are then
Neck Tumours2 has further clarified terminology and has intro- further subdivided into inflammatory or developmental. Cysts
duced new entities. The first two editions of the classification of whose epithelial lining is derived from sources other than tooth
odontogenic tumours3,4 were deliberately inclusive, and classi- forming tissues are classified as ‘non-odontogenic’ and are
fied all neoplasms and cysts of the odontogenic apparatus so that included, since they have similar clinical presentations and must
pathologists would appreciate and understand the commonly be considered in the differential diagnosis. In the 2nd edition4
shared features of these lesions and be able reach an informed two non-odontogenic cysts (nasopalatine duct cyst and nasola-
diagnosis. Inexplicably, the 3rd edition5 excluded the odonto- bial cyst) were included, but only the nasopalatine duct cyst is
genic cysts leading to uncertainty regarding the nature of these included in 20172 on the basis that the nasolabial cyst arises in
lesions and making it difficult to reach a correct diagnosis or plan soft tissues. The “bone cysts” are included and, ironically, given
appropriate management. The authors also ignored the fact that the exclusion of true cysts, were also included in the 5th edition.5
there was still ongoing debate regarding the true nature of a The classification of odontogenic cysts is shown in Table 1. It
number of lesions, which sat at the “cystetumour interface”. The is intended to be simple and is based on the current best evi-
most controversial change in the 3rd edition was to redefine a dence. The classification and terminology was vigorously
number of lesions, which had hitherto been regarded as devel- debated and agreed by an expert consensus group. The key ele-
opmental cysts, as neoplasms. Thus the odontogenic keratocyst ments to note are that it restores the odontogenic keratocyst and
calcifying odontogenic cyst as benign developmental cysts (see
below). The orthokeratinised odontogenic cyst is also recognised
as an entity rather than being regarded as a variant of the
Lisette H C Martin BSc BDS MFDS RCSEd is a Specialty Registrar in Oral odontogenic keratocyst. The lesions listed next to bullets are
and Maxillofacial Pathology, Academic Unit of Oral & Maxillofacial regarded as variants, or subsets of the main lesions.
Medicine, Pathology and Surgery, School of Clinical Dentistry,
Sheffield, UK. Conflicts of interest: none declared.
Odontogenic cysts of inflammatory origin
Paul M Speight BDS PhD FDSRCPS FDSRCS (Eng) FDSRCS (Edin) FRCPath is
This group of lesions result from the proliferation of epithelium
Professor in Oral and Maxillofacial Pathology and Honorary
Consultant Histopathologist, Academic Unit of Oral and Maxillofacial due to inflammation. The most common is the radicular cyst in
Medicine, Pathology and Surgery, School of Clinical Dentistry, which the source of inflammation is apical periodontitis
Sheffield, UK. Conflicts of interest: none declared. following the death of a tooth and necrosis of the pulp. The

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Please cite this article in press as: Martin LHC, Speight PM, Odontogenic cysts: an update, Diagnostic Histopathology (2017), http://dx.doi.org/
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 MINI-SYMPOSIUM: ORAL AND MAXILLOFACIAL PATHOLOGY

A classification of the odontogenic cysts

Odontogenic cysts of inflammatory origin
Radicular cyst
C Residual cyst
Inflammatory collateral cysts
C Paradental cyst
C Mandibular buccal bifurcation cyst
Odontogenic & non-odontogenic developmental cysts
Dentigerous cyst
C Eruption cyst
Odontogenic keratocyst
Lateral periodontal cyst
C Botryoid odontogenic cyst
Gingival cysts
C Gingival cysts of adults
C Gingival of infants (alveolar cyst)
Glandular odontogenic cyst
Calcifying odontogenic cyst
Orthokeratinised odontogenic cyst

Table 1

source of the epithelium in the collateral cysts remains a matter

of some debate.

Radicular and residual cyst Figure 1 Radicular cyst at the apex of a dead tooth with necrotic pulp.
Radicular cysts are the most common jaw cyst comprising about The cyst is attached to the apex and is composed of an inflamed wall
60% of all odontogenic cysts.7 Chronic inflammation in the lined by epithelium. The lumen is filled with necrotic cell debris.
peri-radicular tissues results in a periapical granuloma and
stimulates proliferation of the epithelial rests of Malassez. This is
stimulus is therefore pericoronitis, but the source of epithelium is
followed by central degeneration and necrosis to produce a
uncertain. Paradental cysts were first fully described by Craig in
cavity that becomes lined by epithelium. Cyst expansion then
19768 who postulated that the lining derived from proliferation of
occurs due to hydrostatic pressure as debris accumulates cen-
the reduced enamel epithelium. Although this is the most likely
trally. Radicular cysts are always associated with a non-vital
source, it is possible that rest cells of Malassez may be involved
tooth, and this is an important diagnostic criterion for radiolu-
and more recently an origin from sulcular or junctional epithe-
cent lesions at the apex of the teeth (Figure 1).
lium has been demonstrated.9
Inflammatory collateral cysts are divided into two main types.
Residual cysts are radicular cysts that remain in the jaws after
About 60% are associated with partially erupted lower third
extraction of the affected tooth. The histopathological features
molars and are called paradental cysts. Most of the remainder
are similar in both lesions (Figure 2). However, as the source of
(over 35%) occur in children, usually at the buccal aspect of an
inflammation has been removed, the wall of a residual cyst may
erupting first molar, and are now called mandibular buccal
mature and become relatively uninflamed and the epithelial
bifurcation cysts.2 Rarely, collateral cysts may arise in associa-
lining becomes thin and regular (Figure 2b). In these cases they
tion with partially erupted teeth at other sites, including the
may be mistaken for developmental odontogenic cysts, but
upper canines and lower premolars.
radiological examination and the clinical history can determine
that they are located at a site of a previous tooth extraction.
Developmental odontogenic cysts
Treatment of radicular and residual cysts is by simple
enucleation. Odontogenic cysts with a developmental aetiology occur with no
obvious clinical cause. Many of the developmental cysts show
Inflammatory collateral cysts overlapping histopathological features, and a diagnosis may only
Collateral cysts occur on the lateral, usually buccal, aspect of a be reached after careful consideration of clinical and radio-
partially erupted vital tooth and comprise about 5% of odonto- graphic evidence, particularly in the presence of secondary
genic cysts.1,7 The aetiopathogenesis of these lesions is uncertain inflammation.
and there is some controversy regarding their classification. They
most frequently occur in the posterior mandible associated with Dentigerous and eruption cyst
partially erupted mandibular third molars (wisdom teeth) where Dentigerous cysts embrace the crown of an unerupted tooth and
they are usually called paradental cysts. The inflammatory are lined by epithelium that derives from the reduced enamel

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Please cite this article in press as: Martin LHC, Speight PM, Odontogenic cysts: an update, Diagnostic Histopathology (2017), http://dx.doi.org/
10.1016/j.mpdhp.2017.04.006
 MINI-SYMPOSIUM: ORAL AND MAXILLOFACIAL PATHOLOGY

(after radicular and dentigerous cysts) and comprises about 12%

of all cysts occurring in the maxillofacial region.7,11 In 2005
however, although cysts were not included, the odontogenic
keratocyst disappeared and was redesignated as a neoplasm and
was included as keratocystic odontogenic tumour within the
classification of odontogenic tumours.5 The authors argued that
the high recurrence rate, permeative growth pattern and the
presence of satellite cysts and budding, all indicate “aggressive”
behaviour and are consistent with a neoplasm (reviewed in11,12).
In addition, OKC are associated with mutations in the PTCH
tumour suppressor gene, which is also responsible for basal cell
carcinomas.13 This genetic change has been taken as indicative
of neoplasia, but although PTCH gene alterations may be found
in up to 85% of OKC associated with naevoid basal cell carci-
noma syndrome (NBCCS) they are only found in 30% of sporadic
cysts.13 In addition, changes in PTCH have been found in a range
of non-neoplastic lesions, including dentigerous cysts,14 indi-
cating that neoplasia cannot be simply defined on the basis of a
single genetic event. The name change and evidence for
neoplasia was controversial and was never fully accepted, as
evidenced by a study in 2012, which showed that over 80% of
authors still used the term ‘odontogenic keratocyst’.15 The 2017
WHO consensus group agreed that at the present time there is not
enough evidence to support a neoplastic origin for the keratocyst
and decided that the name of this lesion should revert back to
odontogenic keratocyst and it should be classified as a develop-
mental cyst.2 The OKC arises from remnants of the dental lamina
Figure 2 The epithelial lining of radicular cysts. (a) The lining is typically
hyperplastic with branching arcading rete pegs. Chronic inflammatory and has a distinctive appearance, so that a histological diagnosis
cells including numerous histocytes are seen in the wall. (b) Low power is rarely a problem. The connective tissue wall is uninflamed and
image of a residual cyst with uninflamed wall and thin epithelial lining. is lined by thin parakeratinised stratified squamous epithelium
with a characteristic corrugated surface. The basal epithelial
epithelium. Dentigerous cysts are the most common develop- layer is well defined, with palisaded basal cells with reversal of
mental odontogenic cyst comprising almost 20% of all odonto- nuclear polarity (Figure 3).
genic cysts and 60% of developmental odontogenic cysts.7 In
paediatric populations they account for 30% of the total num- Lateral periodontal cyst and botryoid odontogenic cyst
ber.10 Overall, dentigerous cysts are most frequently encountered Lateral periodontal cysts arise in association with the lateral
in association with impacted third molar (wisdom) teeth, but surface of a tooth root. They are usually asymptomatic and
their distribution is, not surprisingly, directly comparable to the found as incidental radiographic findings, where they appear
frequency of impacted teeth.1 The most common type of den- as a well demarcated corticated radiolucency usually about 5
tigerous cyst develops around the crown of an unerupted, mm in diameter. They account for just 0.4% of odontogenic
impacted tooth and attaches to it at the cementoenamel junction.
The second type overlies an erupting tooth and is called an
eruption cyst. These are most frequently found overlying de-
ciduous incisors or first permanent molars.
Dentigerous cysts are usually enucleated and the associated
tooth removed. Eruption cysts however can be treated conser-
vatively by simple marsupialisation, and the associated tooth
may then erupt normally.

Odontogenic keratocyst
The term ‘odontogenic keratocyst’ (OKC) was first used in the
1950s to describe any odontogenic cyst in which keratin had
formed (for a full review see11) Subsequently, however, it
became apparent that keratinisation was quite often seen in a
range of jaw cysts and the term keratocyst became reserved for a
specific cyst type with a range of features which distinguish it as
Figure 3 The characteristic lining of the odontogenic keratocyst shows
a distinctive entity. The odontogenic keratocyst thus appeared in parakeratinisation with a corrugated surface pattern with prominent
both the 1st (1971) and 2nd (1992) editions of the WHO classi- palisading of basal cells. Reversed nuclear polarity of the basal cells
fications.3,4 The OKC is the third most common odontogenic cyst can also be seen.

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Please cite this article in press as: Martin LHC, Speight PM, Odontogenic cysts: an update, Diagnostic Histopathology (2017), http://dx.doi.org/
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cysts,7 and are found predominantly in the mandibular pre- Glandular odontogenic cyst
molar area, followed by the anterior maxilla. The lateral peri- The glandular odontogenic cyst (GOC) is a rare lesion, account-
odontal cyst is lined by a simple stratified squamous ing for just 0.2% of all odontogenic cysts.7 The lesion is impor-
epithelium, but may also show characteristic epithelial plaques tant however, because it shares features with lateral periodontal
or thickenings with whorling of the epithelial cells, often with and botryoid odontogenic cyst, but may also resemble central
clear cell change. (intraosseous) mucoepidermoid carcinoma. Eighty percent occur
The botryoid odontogenic cyst (BOC) is a multilocular in the mandible, particularly in the anterior region, and they may
variant of the lateral periodontal cyst, which presents in similar reach a large size with erosion of the cortical plates. The GOC
sites, favouring the premolar mandibular region and anterior shows a variety of histological features, but is typically multi-
maxilla. The BOC differs somewhat from the lateral periodontal locular with an uninflamed fibrous wall lined by epithelium with
cyst due to its larger size and multicystic nature, often with a variable appearances.1,17 Microcysts or duct-like structures,
multilocular appearance on radiographs. Histologically BOC which often contain mucus are common and most lesions also
show multiple cystic spaces lined by thin non-keratinised strati- show plaque like thickenings or spheres, with whorling of the
fied squamous epithelium, with occasional plaque-like thicken- epithelial cells, similar to the lining of lateral periodontal or
ings (Figure 4). Lateral periodontal cysts rarely recur after simple botryoid cysts (Figure 5). A characteristic feature is the presence
enucleation, but the multicystic nature of BOC results in a ten- of superficial eosinophilc columnar cells, sometimes called “hob-
dency to recur, with a reported recurrence rate of 40%, likely due nail’ cells (Figure 5 arrows), which, although not specific are
to incomplete removal, and long term follow-up is recommended seen in all lesions and are considered necessary for the diag-
after surgical excision.16 nosis.17 Studies have shown that the GOC has a high recurrence
rate and multiple recurrences are not unusual. This behaviour
Gingival cysts and the histological features of a cystic lesion with squamous and
Gingival cysts are derived from remnants of the dental lamina mucous elements may lead to confusion with intraosseous
(rests of Serres) in the gingival or alveolar soft tissues. They may mucoepidermoid carcinoma and it has been suggested that GOC
arise in adults or in infants. Gingival cysts of adults are un- and mucoepidermoid carcinoma may be part of the same spec-
common and are frequently confused with the lateral periodontal trum or that mucoepidermoid carcinoma may arise from GOC.
cyst. Most are found on the mandibular attached gingivae as The specific criteria identified by Fowler et al.17 are not present in
small (<1 cm) pink or bluish sessile swellings. Histological ex- mucoepidermoid carcinoma and are useful in the differential
amination shows a thin lining of stratified squamous epithelium diagnosis. In addition, Bishop et al.18 have shown that GOC do
supported by an uninflamed wall of fibrous connective tissue. not show MAML2 rearrangements that are characteristic of
Gingival cysts of infants are common and may arise in as many mucoepidermoid carcinoma. Although it is possible that intra-
as 90% of neonates. They present as small yellow or cream osseous mucoepidermoid carcinoma (CMEC) may arise from
nodules on the edentulous alveolar mucosa and are often GOC, the current evidence suggests that they are separate
referred to as Bohn’s nodules. Similar small cysts also develop on entities.
the palate of neonates and are called Epstein’s pearls, but these
are not odontogenic. No treatment is required as these cysts Calcifying odontogenic cyst (COC)
naturally degenerate or fuse with the overlying surface epithe- Calcifying odontogenic cyst (COC) is a member of the “ghost cell
lium and expel their contents. family” of odontogenic lesions, the classification of which has
always received much debate. The 2nd edition of the WHO

Figure 5 Glandular odontogenic cyst. Medium power image showing

Figure 4 Botryoid odontogenic cyst is multicystic and lined mostly by short papillary projections and epithelial thickenings with a spherical
simple non-keratinised stratified epithelium, but with areas of plaque- whorling pattern. The arrows highlight the superficial eosinophilic
like thickening. cuboidal or “hob-nail” cells.

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 MINI-SYMPOSIUM: ORAL AND MAXILLOFACIAL PATHOLOGY

classification4 regarded these cystic lesions as non-neoplastic, Conclusions

but also described a solid variant with ameloblastomatous pro-
Odontogenic cysts are common lesions of the jaws, which all derive
liferations, which they regarded as a true neoplasm and called
their lining from residues of epithelium involved in tooth devel-
dentinogenic ghost cell tumour. In the 2005 WHO classification5
opment. They are classified into cysts of inflammatory or devel-
these two lesions were described as separate entities, and the
opmental origin. However, some cysts have a reputation for
calcifying odontogenic cyst was redesignated as a neoplasm and
recurrence, or unusual features, which have resulted in much
was renamed calcifying cystic odontogenic tumour (CCOT).
debate and some speculation about their nature. In 2005 the WHO
However no evidence for a neoplastic origin has ever been pre-
redesignated some of these lesions as neoplasms with potentially
sented, and in a detailed multi-centre review of ghost cell lesions
serious consequences for patients and resultant confusion over the
and their terminology Ledesma-Montes et al.19 showed that over
most appropriate management. The evidence for these changes
85% of “CCOTs” are simple cysts either alone (65%) or associ-
was not strong, and in 2016 the WHO consensus group agreed that
ated with odontomes. Very few showed ameloblastomatous
there was, at present, insufficient evidence for a neoplastic origin
proliferations and only 5% of lesions were solid and could be
for these lesions and the change in name had not been justified. The
described as true neoplastic dentinogenic ghost cell tumours.
reinstatement of the odontogenic cysts, as well as the reclassifica-
These findings agree with a previous study by Hong et al.20 and
tion of odontogenic keratocyst and calcifying odontogenic cyst in
both authors show that simple cystic lesions rarely recur and
the new WHO classification is a positive reflection of the current
have a completely benign course.
evidence of the behaviour of these entities. Efficient utilisation of
There seems, therefore, to be good evidence that simple cystic
the new terminology is encouraged by the authors in order for
lesions should be regarded as developmental cysts, which arise
appropriate management of these lesions to be introduced. A
alone or in association with other developmental lesions, espe-
cially odontomes. The new WHO classification2 reverts back to
the view that these lesions are benign developmental cysts and
has restored the term calcifying odontogenic cyst. The solid REFERENCES
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Please cite this article in press as: Martin LHC, Speight PM, Odontogenic cysts: an update, Diagnostic Histopathology (2017), http://dx.doi.org/
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 MINI-SYMPOSIUM: ORAL AND MAXILLOFACIAL PATHOLOGY

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Please cite this article in press as: Martin LHC, Speight PM, Odontogenic cysts: an update, Diagnostic Histopathology (2017), http://dx.doi.org/
10.1016/j.mpdhp.2017.04.006