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                                                    PATHOLOGY



    Cysts and cystic lesions of the jaws




   P. R. Morgan



In this article, some recent findings on benign cysts and cystic neoplasms of odontogenic origin are
reviewed with special regard to their diagnostic relevance. Emphasis is given to less common lesions
and those which present diagnostic difficulty or which may involve more complex management.
Some recent applied research contributions in this area will also be included.


Introduction                                                        odontogenic cysts and tumours. Whilst all cysts lined
                                                                    by stratified epithelium contain the primary keratins of
The jaws are unique in the skeleton in the amount and
                                                                    keratinocytes, 5 and 14, keratocysts express keratins 1
variety of epithelial residues contained within them and
                                                                    and 10 (markers of cornification) as well as 4 and 13
in the range of cystic lesions to which they give rise.
                                                                    (markers of non-cornified epithelium). Dentigerous and
Management of such lesions is a significant proportion
                                                                    radicular cysts also express keratins 4 and 13. Keratin
of the work-load of oral and maxillofacial surgeons
                                                                    19 is expressed in odontogenic epithelia under all cir-
and relies on good pre-operative interpretation of radio-
                                                                    cumstances, normal development, adult vestiges, cysts
graphs and computerised tomography (CT) scans and
                                                                    and neoplasms (Fig. 1). Indeed, its presence is so con-
accurate histopathological diagnosis of biopsy and surgi-
                                                                    sistent that it could be considered an obligatory keratin
cal specimens. To some extent, it is artificial to separate
                                                                    of odontogenic epithelium and has the potential to be
the histopathological features from clinical and radio-
                                                                    of diagnostic value. 5 Keratins 8 and 18, found in abun-
logical appearances when considering these lesions, as in
                                                                    dance in simple epithelia, are expressed at low but vari-
other, longer reviews in this area 1,2and therefore descrip-
tions will not always be confined to histopathology.
For the purposes of this account, cysts will be divided
into benign cysts of odontogenic and non-odontogenic
origin and cystic neoplasms (benign and malignant).
Non-epithelial lined cysts will be mentioned briefly.


General characteristics of odontogenic epithelium
From the range and complexity of normal structures and
pathological lesions to which it gives rise, odontogenic
epithelium must be regarded as pluripotent? This is
borne out by the repertoire of keratin proteins which are
expressed in the developing normal tooth germ4 and in

                                                                    Fig. 1--A frozen section of an odontogenic keratocyst
P. R. Morgan, BSc, BDS, PhD, MRCPath, Departmentof Oral             stained with a monoclonal antibody to demonstrate keratin
Medicine & Pathology,UMDS, Floor 28, Guy's Tower, Guy's             19, present in all odontogenic epithelia. Streptavidin-biotin
Hospital, London SE1 9RT, UK                                        peroxidase reaction,

Current Diagnostic Pathology (1995) 2, 86-93
9 1995 Pearson Professional Ltd                                86
CYSTS AND CYSTIC LESIONSOF THE JAWS 87

                                                                     Table-~Simplified classification of jaw cysts
                                                                     ODONTOGENICCYSTS
                                                                     Developmental
                                                                     Dentigerous cyst
                                                                       Eruption cyst
                                                                     Odontogenic keratocyst
                                                                     Lateral periodontal cyst
                                                                     Botryoid odontogeniccyst
                                                                     Glandular odontogeniccyst
                                                                     Inflammatory
                                                                     Radicular cyst, lateral radicular cyst, residual cyst, paradental cyst
                                                                     NON-ODONTOGENICCYSTS
                                                                     Nasopalatine duct cyst
                                                                     'Fissural' cyst
                                                                     CYSTIC NEOPLASMS
                                                                     Ameloblastoma
Fig. 2 - - H y a l i n e bodies in the lining of a radicular cyst.   Unicystic ameloblastoma
These structures are probably a secretion product, unique            Calcifying odontogeniccyst
to o d o n t o g e n i c epithelia and similar to enamel cuticle,
which may be deposited concentrically on a 'template'
layer. H&E.
                                                                     completion of tooth development and eruption. A major
                                                                     division into developmental 13 and inflammatory catego-
able levels in keratinocytes of odontogenic cysts, apart             ries is usual.
from keratocysts, and of course in zones of mucous
metaplasia.
                                                                     Dentigerous cyst (follicular cyst)
   Hyaline bodies (Rushton bodies) are highly eosino-
philic, laminated, circular or folded elongate structures            This cyst is diagnosed by its precise relationship with the
(Fig. 2) which lie in the epithelium of about 10 per cent            crown of an unerupted tooth, commonly the lower third
of all forms of odontogenic cyst but do not occur in other           molar or upper permanent canine. Being derived from
cyst types. There is considerable evidence now that they             the reduced enamel epithelium, the remnant of the
represent a secretion product, probably similar to dental            enamel organ, it is attached to the tooth at the enamel-
cuticle which is deposited in variable amounts on tooth              cementum junction (Fig. 3A). It is therefore important
enamel at the completion of its formation. The available             for diagnosis that the tooth is supplied with the soft
histological, histochemical and ultrastructural evidence             tissue specimen, or at least that accurate clinical inlor-
supports the view that it is a product of odontogenic epi-           marion is supplied by the operator. Radiographically,
thelium secreted on to a template of endogenous or                   they are unitocular but the illusion of a dentigcrous
exogenous origin e.g. cholesterol crystal, root fragment             cyst on a radiograph can be given by other radiolucent
or root filling material)When present, hyaline bodies                lesions which may secondarily involve or displace an
may therefore be considered a marker of odontogenic                  unerupted looth, such as an ameloblastoma (see below).
cysts.                                                                  Histologically, the cyst lining is characterised by
                                                                     uniform, non-keratinised epithelium, either stratified
                                                                     squamous about 4 10 cells thick or with a cuboidal basal
Cyst growth
                                                                     layer, thus often resembling reduced enamel epithelium.
There is a considerable literature on possible mecha-                Mucous metaplasia is frequently encotmtered (Fig. 3B).
nisms of cyst initiation and subsequent enlargement. 7               In the young patient, the wall is myxoid and contains
Theories have ranged from the osmotic/hydrostatic                    clusters of odontogenic epithelial rests and in more
pressure concept of Toiler s to differential growth 9 and            mature follicles these often show cementicle-like miner-
inflammatory mediators such as prostaglandins m and,                 alisation. The immature, myxoid follicle has been vari-
more recently, interleukins. ~ There is little doubt that            ously misdiagnosed as odontogenic cyst, myxoma,
fluid-filled cysts are under positive hydrostatic pressure           odontogenic fibroma, odontome and even ameloblas-
but it may be doubtful whether this is transmitted as                toma.~4 Rests of odontogenic epithelium in the wall may
a resorptive force to the surrounding bone, especially               also form squamous pearls such as are found in greater
as the cell population of most cyst walls includes                   profusion in the squamous odontogenic tumour. In such
myofibroblasts which may serve to contain the pressure               pearls basal cells are inconspicuous and mitoses exceed-
generated. ~2                                                        ingly rare. It is not always possible to establish the point
   A simple classification of jaw cysts 1,2 groups them              at which an enlarged follicle becomes a dentigerous
broadly according to pathogenesis, with odontogenic                  cyst. Although there is rarely unanimity, a practical
cysts making up the largest proportion (Table).                      guide to the diagnosis of a cyst is a follicular space of
                                                                     5 mm or more on a radiograph and a lining of stratified
                                                                     squamous epithelium as well as, or instead of, reduced
Odontogenic cysts
                                                                     enamel epithelium.
These are derived from residues of odontogenic epithe-                  As developmental jaw cysts are usually symptomless,
lium which otherwise gradually involute following                    secondary inflammatory changes often provoke initial
88 CURRENTDIAGNOSTICPATHOLOGY




(A)                                                              (A)




(B)                                                              (B)
Fig. 3--A dentigerous cyst on a lower third molar tooth. (A)     Fig. 4--Part of an odontogenic keratocyst which has formed
The cyst wall, attached at the enamel-cementum junction,         alongside an unerupted tooth. (A) The white, folded lining
has been partially removed after fixation to reveal the          reveals the presence of keratinising epithelium. Proximity
crown of the tooth. (B) Part of the vascular fibrous wall of a   to a tooth is an incidental but not uncommon feature and
dentigerous cyst lined by non-keratinised stratified             on a radiograph may simulate a dentigerous relationship.
squamous epithelium which shows a zone of mucous                 (B) Characteristic histological appearance of an
metaplasia. Such an appearance is characteristic in the          odontogenic keratocyst epithelium: uniform thickness and
absence of inflammation. H&E.                                    with a flat basal surface, elongate basal cells, a thin prickle
                                                                 cell zone and corrugated parakeratin surface layer. The
                                                                 fibrous wall is usually thin, delicate and vascular. H&E.

presentation and a high proportion of surgical specimens
of dentigerous cysts show lymphoplasmacytic infiltrates          folded inner surface (Fig. 4A) following discharge of
in the wall and neutrophils in the epithelial lining. Accu-      stacked keratin, as with an epidermoid cyst. In most
mulations of cholesterol clefts, foreign body giant cells        cases, there should be little difficulty in establishing the
and haemosiderin-laden macrophages may greatly en-               diagnosis histologically. Typically, the wall is thin and
large the wall and locally herniate into the cyst lumen.         rarely removed intact. It is lined by uniform, para-
Thus, at cut-up, disrupted cysts may glisten with                keratinised epithelium, some 10-12 cells thick, with a
discharging semi-fluid contents which are rich in                flat basal surface (Fig. 4B). Key features are a narrow,
cholesterol.                                                     folded (corrugated) zone of keratin, prickle cells which
                                                                 retain their long axes at right angles to the basement
                                                                 membrane until close to the keratinised layer and elon-
Odontogenic keratocyst (primordial cyst)
                                                                 gate, often palisaded, basal cells which show reversed
More has been written in recent years on the                     polarity in at least some areas. It was established many
odontogenic keratocyst than on any other jaw cyst.               years ago that keratocysts show a higher frequency
Radiographically it has a multilocular, or apparently            of mitoses than is found in other odontogenic cysts. 15
multilocular, appearance and is sometimes multiple,              Mitotic figures may be found in both basal and parabasal
especially when it represents a manifestation of the             layers. A study using PCNA as a marker of cell prolif-
naevoid basal cell carcinoma syndrome (Gorlin's syn-             eration has shown higher indices for keratocysts than for
drome). Rather than expanding the jaw, the cyst tends            other odontogenic cysts. 16 Odontogenic keratocysts have
to grow mesiodistally at the expense of the medullary            a higher recurrence rate too, due in part to their physical
bone and extends between the roots of the teeth.                 fragility leading to disruption during removal, the
   Macroscopically, the opened cyst reveals a white,             epithelium separating easily from the fibrous wall. A
CYSTS AND CYSTICLESIONSOF THE JAWS 89

further possible reason is the presence of daughter cysts       diagnosis in such cases, especially if the biopsy sample
in the wall which may remain after cyst enucleation.            is small.
   Differences in proliferation rates and in the frequency
of basal epithelial" cell budding between solitary, multi-
                                                                Lateral periodontal, botryoid, and glandular
ple and recurrent odontogenic keratocysts and those
                                                                odontogenic cysts
associated with naevoid basal cell carcinoma syndrome
have been the subject of a number of recent studies. 17         The lateral periodontal cyst is usually unilocular and lies
Significantly higher rates of mitosis occur in keratocysts      alongside a vital tooth and therefore, like the radicular
in patients with Gorlin's syndrome. Satellite cysts have        cyst, is presumed to originate from cell rests of Malassez
been detected in about 50% of syndrome patients and in          in the periodontal ligament or possibly from part of
the walls of 25% of multiple or recurrent cysts whereas         the developing follicle, z~ The stimulus to its formation is
they are found in less than 10% of solitary keratocysts.        unknown, and it is usually detected as a symptomless
In practical terms, the possible diagnosis of naevoid           radiolucency on routine radiography. Its epithelial lining
basal cell carcinoma syndrome should be investigated            is about 2-6 cells thick, non-keratinised, stratified
for all patients with odontogenic keratocysts. The syn-         squamous and with a flat basal surface. There may be
drome is an autosomal dominant condition with numer-            a narrow zone of subepithelial hyalinisation, a feature
ous defects, many involving the axial skeleton.                 occasionally encountered in other odontogenic cysts and
   It is important not to diagnose as a keratocyst every        neoplasms. The fibrous wall is usually uninflamed,
odontogenic cyst which shows some keratinisation. Parts         cellular and delicate, lacking daughter cysts. A charac-
of (probably) long-standing dentigerous or radicular            teristic feature is the presence of periodic, plaqueqike
cysts may show ortho- or parakeratinisation but without         thickenings in the epithelium (unrelated to inflamma-
the other features of odontogenic keratocysts. Also, soft       tion) which may bulge into the cyst lumen or wall or
tissue removed together with impacted, partially erupted        both (Fig. 6). These contain glycogen and may be
third molar teeth may include some keratinised gingival         composed predominantly of clear cells but there is no
mucosa which may unwittingly be mistaken for kera-              evidence that they represent centres of proliferation.
tocyst wall. It is of interest that, whilst all odontogenic     Indeed, mitotic figures, epithelial budding and daughter
keratocysts keratinise, only a minority are orthokera-          cyst formation are unusual in the lateral periodontal cyst.
tinised; moreover, these recur less frequently than             A proportion of cysts which radiographically suggest
parakeratinising cysts. 18,19                                   a diagnosis of lateral periodontal cyst turn out to be
   Although inflammatory infiltrates in odontogenic             odontogenic keratocysts on histological examination,
keratocysts are usually well-localised and mild, diagnos-       despite their unilocular profile.
tic problems may result from an ~xtensive inflammatory             Botryoid and glandular odontogenic cysts are rare
infiltrate which suppresses keratinisation (Fig. 5). This       entities with features in common with each other and
could give rise to misdiagnosis of a dentigerous or re-         with the lateral periodontal cyst. The former is so called
sidual cyst with the consequence that, in the absence           because the low magnification appearance or macro-
of follow-up, the patient may develop a recurrence              scopic cut surface sometimes resembles a bunch of
which is unrecognised until well advanced. If, in a simi-       grapes. Radiographically, most have been multilocular
lar context, the basal cells are markedly columnar the          and located in the mandible. In their more detailed fea-
keratocyst might be misdiagnosed as an ameloblastoma,           tures, botryoid cysts resemble lateral periodontal cysts,
particularly since the radiographic appearance of these         the thin, non-keratinised epithelial lining with thickened
two lesions are sinfilar. One should be wary of over-           plaques being a consistent feature. A number of recent




                                                                             4~




Fig. 5 - - A keratocyst which has become secondarily            Fig, 6--Wall of a lateral periodontal cyst with a Iocalised
inflamed. Note the loss of keratinisation in the zone           thickening of the uniform, non-keratinising epithelium.
showing an arcading pattern of epithelial hyperplasia. If the   Several such thickenings may be encountered in a given
biopsy is small or inflammatory change extensive, this may      plane of section. H&E.
lead to a mistaken diagnosis of an inflammatory cyst. H&E.
90 CURRENTDIAGNOSTICPATHOLOGY

publications point to a high recurrence rate for this
multicystic lesion.
   Greater difficulty attaches to the status of the glandular
(sialo- or mucoepidermoid-) odontogenic cyst. It is sur-
prising that this cyst has been recognised only recently
as a distinct entity 21,22 and less than 20 cases have been
reported in the world literature. It has an appearance of
multilocularity on radiographic examination. Its histo-
logical features include multiple thickened epithelial
plaques, like those of the lateral periodontal cyst, and
multicystic growth, like the botryoid cyst. Intriguing
additional features are present in the epithelium: papil-
lary 'outgrowths' into the cyst lumen with apocrine-like
'decapitation' secretion of surface cells, ductal struc-        Fig. 8--Radicular cyst: a frequent presentation with a
tures, mucin-producing goblet cells and occasionally            dense, mixed inflammatory infiltrate adjacent to variably
acini (Fig. 7). The nomenclature for this cyst has not yet      hyperplastic, non-keratinised epithelim. The upper part of
                                                                the field shows part of the wall apparently devoid of
been established and interpretations of the histological        epithelium, also a common finding. H&E.
features range widely. Mucous metaplasia may be
present in the lining of any odontogenic cyst and to some
commentators, the glandular odontogenic cyst is an ex-
                                                                pattern of hyperplasia (Fig. 5) can be so striking that the
treme example of this change. An opposing view is that
                                                                unwary may suspect the presence of an ameloblastoma. 23
the lesion is in fact a low-grade central mucoepidermoid
                                                                It is essential that the condition of the related tooth be
carcinoma. When more cases become available for study
                                                                known for the correct diagnosis to be made: the histo-
and when a wider range of markers of odontogenic
                                                                logical features of a radicular cyst may be identical
epithelium have been developed, the histogenesis of this
                                                                to those of a secondarily inflamed dentigerous cyst.
group of cysts should become clearer.
                                                                Similarly, a long-standing radicular cyst may come to
                                                                resemble a developmental cyst when the inflammatory
Inflammatory odontogenic cysts                                  infiltrate fades. A cyst which forms alongside a non-vital
                                                                tooth is termed a lateral radicular cyst and one which is
Radicular cyst
                                                                retained following removal of the offending tooth or root
By far the most common jaw cyst is the radicular cyst,          is referred to as a residual cyst, the histological features
an odontogenic cyst which forms from epithelial rests of        being identical to those just described.
Malassez in the periodontal ligament consequent upon
activation from the products of necrotic dental pulp in an
                                                                Paradental cyst
adjacent tooth. The wall is relatively thick and usually
contains a dense inflammatory infiltrate towards the            The paradental cyst is an inflammatory cyst which lies
inner aspect, consisting of plasma cells and lymphocytes.       on the disto-buccal aspect of fully or partially erupted
Neutrophils tend to accumulate in the epithelium which          third molar teeth, near the bifurcation of the roots
is of non-keratinised, stratified squamous type and varies      (Fig. 9). There is a male preponderance, a history of
greatly in thickness (Fig. 8). Sometimes the arcading           pericoronitis is common and sometimes a predisposing




Fig. 7--Parts of two Iocules of a glandular (sialo-)            Fig. 9--A paradental cyst attached to the enamel-cementum
odontogenic cyst with thickened epithelial plaques, similar     junction of a lower molar tooth on the disto-buccal aspect.
to those found in lateral periodontal and botryoid cysts but    Although slightly disrupted, it lies alongside the tooth and
also showing ductal structure, and extensive mucus-             does not enclose the crown.
secreting cells. H&E.
CYSTS AND CYSTICLESIONSOF THE JAWS 91

factor is an extension of enamel down to where the roots                 Differential diagnosis should include other odonto-
separate and a bilateral presentation is not u n u s u a l . 24 The   genic carcinomas: primary intra-osseous carcinomas,
associated tooth is therefore usually vital and such cysts            which are thought to arise from residues of odontogenic
are often removed still attached after extraction of the              epithelium in the jaws, and malignant variants of
erupting or partially erupted tooth due to impaction.                 ameloblastoma and other odontogenic tumours. Central
Whether the source of epithelium is the reduced enamel                mucoepidermoid carcinomas, in which the epidermoid
epithelium, periodontal pocket epithelium or cell rests               component may predominate, should also be considered.
of Malassez, the aetiological mechanism appears to be                 Any of these malignancies may be cystic, at least in
epithelial activation by inflammatory infiltrate which is             part. The mandible is also a well-recognised site for car-
induced by bacterial plaque.                                          cinomas metastatic to the jaws from such sites as lung,
   A related cyst, the mandibular infected buccal cyst,               breast, prostate, thyroid and kidney which may simulate
has a similar association with first or second lower per-             cysts radiographically.
manent molar teeth 25 but in younger patients than the                   Dysplastic change may be encountered in cyst epithe-
paradental cyst. As Shear 2 argues, the two entities are              lia and levels should be checked carefully for evidence
probably related but are worth while recognising as                   of frank invasion. This is particularly the case in those
distinct for reasons of management.                                   odontogenic keratocysts which show basal budding
   Both these cysts have the same histological appear-                (Fig. 11) and epithelial islands, since the presence of
ance as the radicular cyst: hyperplastic, non-cornified               dysplasia may give the impression of a wide field of
epithelium lining a fibrous wall containing a dense,                  invasion.
mixed inflammatory infiltrate. Clinical information is
therefore essential for an accurate diagnosis.
                                                                      AmelobIastoma and its unicystic variants
                                                                      Ameloblastomas are the most common odontogenic neo-
Malignant transformation in jaw cysts
                                                                      plasms. They present usually in the mandibular third
Although rare, malignant transformation does occur in                 molar region and least often in the anterior maxilla.
odontogenic cysts, about 60 cases having been reported                Their peak age prevalence is in the 4th or 5th decade.
in the world literature. Malignant transformation appears             Histological criteria for their diagnosis were set out by
to arise most frequently in residual cysts, reported cases            Vickers and Gorlin. 27 The epithelial cells comprise two
equalling those of dentigerous cysts and odontogenic                  distinct populations. Firstly, peripheral, or basal, cells
keratocysts combined; 80% of such malignancies occur                  which are columnar and often markedly elongate and
in the mandible (Fig. l()). 2r Not surprisingly, the age at           showing reversed polarity, with the nucleus occupying
presentation tends to be greater than that of patients with           the part of the cell away fi-om the basement membrane;
benign cysts; the 6th or 7th decade rather than the 4th or            this layer thus resembles the pre-ametoblast of the devel-
5th. As far as can be assessed with such small numbers                oping tooth germ. The second population consists of
of cases, the prognosis appears to be better than that of             polyhedral suprabasal cells with fewer intercellular con-
mucosal carcinomas which infiltrate the .jaws, and that               tacts than conventional prickle cells; this is the stellate
of primary intra-osseous carcinomas, nodal metastases                 reticulum-like layer, similar to the stellate reticulum of
being less common. This difference in prognosis might                 the bell stage in the developing tooth. Two principal
be expected when the carcinoma is removed while being                 arrangements of epithelium are recognised, follicular
retained within the confines of the fibrous cyst wall.                (Fig. 12A) and plexiform (Fig. 12B), although there is




Fig. 10--Squamous cell carcinoma which has arisen in an               Fig. 11--Odotogenic keratocyst showing extensive basal
odontogenic keratocyst. This mandibular t u m o u r was more          budding together with bulbous rete processes and some
solid than cystic but dysplastic keratocyst lining is still           cell disorganisation but minimal cytological features of
evident associated with islands of well-differentiated                malignancy. However, the presence of these features
carcinoma. A dense lymphocytic response is also present.              increase the likelihood of recurrence. H&E.
H&E.
92 CURRENTDIAGNOSTICPATHOLOGY

                                                                be confused with an odontogenic keratocyst. 28 An addi-
                                                                tional but rare feature of ameloblastomas is the inclusion
                                                                of eosinophilic granular cells whose origin is obscure but
                                                                which are befieved to arise in the epithelial compartment.
                                                                   Other variants of ameloblastoma may also be pre-
                                                                dominantly cystic:
                                                                9 Desmoplastic, in which the stroma is more densely
                                                                  fibrous.
                                                                9 Basal cell, in which basaloid cells predominate.
                                                                9 Papilliferous keratoameloblastoma, a rare type in which
                                                                  cystic spaces may be filled with desquamated, kerati-
                                                                  nising squames.
                                                                   Some ameloblastomas are characteristically unilocular
(A)
                                                                on radiographs and prove to be unicystic (Fig. 13), and
                                                                sometimes in a dentigerous relation to a tooth, when
                                                                examined macroscopically. They also tend to present in
                                                                younger patients than do conventional ameloblastomas.
                                                                Levels should be taken through the excision specimen
                                                                to investigate the presence of a conventional amelo-
                                                                blastoma. Sometimes part of the lining expands into a
                                                                plexiform pattern of ameloblastoma. On occasion, strict
                                                                criteria for ameloblastoma can be hard to establish and
                                                                the diagnosis has to take account of the clinical presenta-
                                                                tion as well as 'suggestive' features in the epithelial lin-
                                                                ing. Unicystic ameloblastomas are generally considered
                                                                to have a lower recurrence rate than their conventional
                                                                counterparts. This is true of those with a continuous
                                                                epithelial lining and those with ameloblastomatous mural
(B)                                                             nodules which invaginate the lumen. They may be
Fig. 12--Examples of cyst formation in conventional             treated successfully by careful enucleation, but when
ameloblastomas. (A) Follicular ameloblastomas with cystic
                                                                the wall is found to be infiltrated by islands of amelo-
change in the stellate reticulum component of the
neoplasm. The cystic area on the right is lined by cells        blastomatous epithelium treatment should be as radical
showing 'acanthomatous' change. (B) Plexiform                   as for the conventional solid or multi-cystic types. 13
ameloblastomas with stromal cysts; surviving small blood
vessels indicate the location of the connective tissue
component. The lumen of the main cyst is shown at the top
of the figure and is composed of degenerate epithelial cells.
                                                                Calcifying odontogenic cyst
H&E.
                                                                This curious entity is usually classified with epithelial
                                                                odontogenic tumours since it is really a neoplasm which
                                                                sometimes may be as aggressive as an ameloblastoma.
no behavioural difference between the two. Although
usually slow growing and lacking in detectable mitoses,
both types tend to infiltrate the bone and to recur unless
removed by local resection. The follicular form consists
of round or irregular islands of tumour, the stroma being
composed of vascular, cellular fibrous tissue. As its de-
scriptive name suggests, in the plexiform ameloblastoma
the epithelial component takes the form of interlacing
strands which appear to entrap the stroma. Cystic change
is common in both types, microcysts forming in the
epithelial masses and stromal cysts in the connective
tissue. As the ameloblastoma enlarges, the cysts coalesce
and may form one or more cystic cavities containing
straw-coloured fluid. Biopsy of the stretched wall of
such a tumour may lead to the misdiagnosis of a non-
neoplastic cyst. Fortunately, the solid or invaginated          Fig. 13--Unicystic ameloblastoma. This lesion shows few
areas are likely to contain more representative amelo-          histological hallmarks of an ameloblastoma, Basal
blastoma. Another conmaon feature of ameloblastomas is          epithelial cells palisaded in places but with little evidence of
                                                                the reversed polarity characteristic of ameloblasts and
squamous metaplasia ('acanthomatous change') which              stellate reticulum cells are poorly developed. Epithelium in
only rarely consists of true keratinisation when it may         this field has a somewhat plexiform arrangement. H&E.
CYSTS AND CYSTIC LESIONS OF THE JAWS                    93

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                                                                                          15. Browne R. The odontogenic keratocyst histological features and
d o e s not calcify. Its basal cells and parabasal epithelial
                                                                                              their correlation with clinical behaviour. Br Dent J 197 I;
cells r e s e m b l e t h o s e o f the a m e l o b l a s t o m a but m o r e                  131 : 249-259.
superficial cells e x p a n d to f o r m lightly e o s i n o p h i l i c ,                16. Li T-J, Browne R, Matthews J. Quantification of PCNA+ ceils
                                                                                              within odontogenic jaw cyst epithelium. J Oral Pathol Med 1994;
partially keratinising and usually n u c l e a t e cells t e r m e d
                                                                                              23:184 189.
' g h o s t c e l l s ' (Fig. 14). T h e s e may b e c o m e c a l c i f i e d and        17. Woolgar J A, Rippin J W, Browne R M. A comparative
are not d i s s i m i l a r to cells o f the p i l o m a t r i x o m a wilh                   histological study of odontogcnic keratocysts in basal cell naevus
                                                                                              syndrome and control patients. J Oral Pathol 1987; 16: 75-80.
w h i c h this lesion has often been c o m p a r e d . G h o s t cells
                                                                                          18. Brannon R. The odontogcnic keratocyst. A clinicopathologic study
are not u n i q u e to the c a l c i f y i n g o d o n l o g e n i c cysl but                 {71312 cases. Part 11. Histoh}gical features. Oral Surg Oral Med
have been d e s c r i b e d in cases o f a m e l o b l a s t o m a , a m e l o -              Oral Pathol 1977: 43:233 255.
                                                                                          19. Wright J. The odontogenic kcratocyst: orthokcratinizcd w,'iant.
Mastic      fibroma        and     ameloblastic          fibroodonlome.            A
                                                                                              Oral Surg Oral McdOral Pathol 1981; 51: 609 618.
further feature seen in a proportion o f cases is the d e p o -                          20. Allini M, Shear M. The lateral periodontal cyst: an update. J Oral
sition     of    poorly       mineralised         dysplastic        dentine       or          Pathol Med 1992; 21:245 250.
                                                                                         21. Padayachee A, Van Wyk C W. Two cystic lesions with features of
'dentinoid" in the cyst wall. S o m e t i m e s typical dental
                                                                                              both the botyroid odontogeuic cyst and lhc central
hard tissues f o r m , in w h i c h case one has to c o n s i d e r                           mucoepidcrmoid turnout: sialo odontogenic cyst'? J Oral Pathol
w h e t h e r ' o d o n t o m e ' s h o u l d be the m o r e a p p r o p r i a t e            1987; 16: 499-504.
                                                                                         22. Gardner D G, Kessler H P, Morency R, Schaffner D L. The
d e s i g n a t i o n , a d e c i s i o n for w h i c h the age, site and radio-
                                                                                              glandular odontogenic cyst: an apparent entity. J Oral Pathol
graphic a p p e a r a n c e should be taken into account. As                                  1988; 17:359 366.
t h e s e turnouts are rather rare, this material has scarcely                           23. Lucas R. Pathology of Tumours of the Oral Tissues. 4th ed.
                                                                                              Edinburgh: Churchill Livingstone, 1984.
b e e n tested for its authenticity as dentine. A d i a g n o s i s
                                                                                         24. Craig G. The puradental cyst. A specific inflamnmtory
o f c a l c i f y i n g o d o n t o g e n i c cyst is not a clear p o i n t e r to a          odontogenic cyst. Br Dent J 1976; 141:9 14.
l e s i o n ' s likely behaviour. D e t a i l e d a n a l y s i s o f 92 c a s e s       25. Stoneman D, Worth H. The mandibular bucca] infected cyst -
                                                                                              molar area. Deut Radiol Photog 1983; 56:1 14.
e m p h a s i s e d the n e e d to s u b g r o u p t h e m into h a m a r t o -
                                                                                         26. Schwimmer A, Aydin F, Morrison S. Squamous ceil carcinoma
matous, cystic and n e o p l a s t i c variants. 29                                           arising in residual odontogenic cyst. Oral Surg Oral Med Oral
                                                                                              Pathol 1991; 72: 218--221.
                                                                                         27. Vickers R, Gorlin R. Ameloblastoma: delineation of early
References                                                                                    histopathologic features of neoplasia. Cancer 1970; 26:699 710.
                                                                                         28. Siar C, Ng K. 'Combined ameloblastoma and odontogenic
 1. Kramer 1, Pindborg J, Shear M. Histological typing of                                     keratocyst' or 'keratinising ameloblastoma'. Br J Oral Maxfac
    odontogenic tumours 2nd ed. Berlin Heidelberg: Spinger-Verlag,                            Surg1993; 31:183 186.
    1992.                                                                                29. Hong S, Ellis G, Hartman K. Calcifying odontogenic cyst. A
 2. Shear M. Cysts of the oral regions. 3rd ed. Oxford: Wright,                              review of 92 cases with reevaluation of their nature as cysts or
    Butterworth-Heinemann, 1992.                                                              neoplasms, the nature of ghost cells, and subclassification. Oral
 3. Smith A, Matthews J. Odontogenic epithelium and its residues. In:                         Surg Oral Med Oral Pathol 1991; 72:56 64.

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Cysts and cystic lesions

  • 1. 9 D][:Ir162 Ii[ I PATHOLOGY Cysts and cystic lesions of the jaws P. R. Morgan In this article, some recent findings on benign cysts and cystic neoplasms of odontogenic origin are reviewed with special regard to their diagnostic relevance. Emphasis is given to less common lesions and those which present diagnostic difficulty or which may involve more complex management. Some recent applied research contributions in this area will also be included. Introduction odontogenic cysts and tumours. Whilst all cysts lined by stratified epithelium contain the primary keratins of The jaws are unique in the skeleton in the amount and keratinocytes, 5 and 14, keratocysts express keratins 1 variety of epithelial residues contained within them and and 10 (markers of cornification) as well as 4 and 13 in the range of cystic lesions to which they give rise. (markers of non-cornified epithelium). Dentigerous and Management of such lesions is a significant proportion radicular cysts also express keratins 4 and 13. Keratin of the work-load of oral and maxillofacial surgeons 19 is expressed in odontogenic epithelia under all cir- and relies on good pre-operative interpretation of radio- cumstances, normal development, adult vestiges, cysts graphs and computerised tomography (CT) scans and and neoplasms (Fig. 1). Indeed, its presence is so con- accurate histopathological diagnosis of biopsy and surgi- sistent that it could be considered an obligatory keratin cal specimens. To some extent, it is artificial to separate of odontogenic epithelium and has the potential to be the histopathological features from clinical and radio- of diagnostic value. 5 Keratins 8 and 18, found in abun- logical appearances when considering these lesions, as in dance in simple epithelia, are expressed at low but vari- other, longer reviews in this area 1,2and therefore descrip- tions will not always be confined to histopathology. For the purposes of this account, cysts will be divided into benign cysts of odontogenic and non-odontogenic origin and cystic neoplasms (benign and malignant). Non-epithelial lined cysts will be mentioned briefly. General characteristics of odontogenic epithelium From the range and complexity of normal structures and pathological lesions to which it gives rise, odontogenic epithelium must be regarded as pluripotent? This is borne out by the repertoire of keratin proteins which are expressed in the developing normal tooth germ4 and in Fig. 1--A frozen section of an odontogenic keratocyst P. R. Morgan, BSc, BDS, PhD, MRCPath, Departmentof Oral stained with a monoclonal antibody to demonstrate keratin Medicine & Pathology,UMDS, Floor 28, Guy's Tower, Guy's 19, present in all odontogenic epithelia. Streptavidin-biotin Hospital, London SE1 9RT, UK peroxidase reaction, Current Diagnostic Pathology (1995) 2, 86-93 9 1995 Pearson Professional Ltd 86
  • 2. CYSTS AND CYSTIC LESIONSOF THE JAWS 87 Table-~Simplified classification of jaw cysts ODONTOGENICCYSTS Developmental Dentigerous cyst Eruption cyst Odontogenic keratocyst Lateral periodontal cyst Botryoid odontogeniccyst Glandular odontogeniccyst Inflammatory Radicular cyst, lateral radicular cyst, residual cyst, paradental cyst NON-ODONTOGENICCYSTS Nasopalatine duct cyst 'Fissural' cyst CYSTIC NEOPLASMS Ameloblastoma Fig. 2 - - H y a l i n e bodies in the lining of a radicular cyst. Unicystic ameloblastoma These structures are probably a secretion product, unique Calcifying odontogeniccyst to o d o n t o g e n i c epithelia and similar to enamel cuticle, which may be deposited concentrically on a 'template' layer. H&E. completion of tooth development and eruption. A major division into developmental 13 and inflammatory catego- able levels in keratinocytes of odontogenic cysts, apart ries is usual. from keratocysts, and of course in zones of mucous metaplasia. Dentigerous cyst (follicular cyst) Hyaline bodies (Rushton bodies) are highly eosino- philic, laminated, circular or folded elongate structures This cyst is diagnosed by its precise relationship with the (Fig. 2) which lie in the epithelium of about 10 per cent crown of an unerupted tooth, commonly the lower third of all forms of odontogenic cyst but do not occur in other molar or upper permanent canine. Being derived from cyst types. There is considerable evidence now that they the reduced enamel epithelium, the remnant of the represent a secretion product, probably similar to dental enamel organ, it is attached to the tooth at the enamel- cuticle which is deposited in variable amounts on tooth cementum junction (Fig. 3A). It is therefore important enamel at the completion of its formation. The available for diagnosis that the tooth is supplied with the soft histological, histochemical and ultrastructural evidence tissue specimen, or at least that accurate clinical inlor- supports the view that it is a product of odontogenic epi- marion is supplied by the operator. Radiographically, thelium secreted on to a template of endogenous or they are unitocular but the illusion of a dentigcrous exogenous origin e.g. cholesterol crystal, root fragment cyst on a radiograph can be given by other radiolucent or root filling material)When present, hyaline bodies lesions which may secondarily involve or displace an may therefore be considered a marker of odontogenic unerupted looth, such as an ameloblastoma (see below). cysts. Histologically, the cyst lining is characterised by uniform, non-keratinised epithelium, either stratified squamous about 4 10 cells thick or with a cuboidal basal Cyst growth layer, thus often resembling reduced enamel epithelium. There is a considerable literature on possible mecha- Mucous metaplasia is frequently encotmtered (Fig. 3B). nisms of cyst initiation and subsequent enlargement. 7 In the young patient, the wall is myxoid and contains Theories have ranged from the osmotic/hydrostatic clusters of odontogenic epithelial rests and in more pressure concept of Toiler s to differential growth 9 and mature follicles these often show cementicle-like miner- inflammatory mediators such as prostaglandins m and, alisation. The immature, myxoid follicle has been vari- more recently, interleukins. ~ There is little doubt that ously misdiagnosed as odontogenic cyst, myxoma, fluid-filled cysts are under positive hydrostatic pressure odontogenic fibroma, odontome and even ameloblas- but it may be doubtful whether this is transmitted as toma.~4 Rests of odontogenic epithelium in the wall may a resorptive force to the surrounding bone, especially also form squamous pearls such as are found in greater as the cell population of most cyst walls includes profusion in the squamous odontogenic tumour. In such myofibroblasts which may serve to contain the pressure pearls basal cells are inconspicuous and mitoses exceed- generated. ~2 ingly rare. It is not always possible to establish the point A simple classification of jaw cysts 1,2 groups them at which an enlarged follicle becomes a dentigerous broadly according to pathogenesis, with odontogenic cyst. Although there is rarely unanimity, a practical cysts making up the largest proportion (Table). guide to the diagnosis of a cyst is a follicular space of 5 mm or more on a radiograph and a lining of stratified squamous epithelium as well as, or instead of, reduced Odontogenic cysts enamel epithelium. These are derived from residues of odontogenic epithe- As developmental jaw cysts are usually symptomless, lium which otherwise gradually involute following secondary inflammatory changes often provoke initial
  • 3. 88 CURRENTDIAGNOSTICPATHOLOGY (A) (A) (B) (B) Fig. 3--A dentigerous cyst on a lower third molar tooth. (A) Fig. 4--Part of an odontogenic keratocyst which has formed The cyst wall, attached at the enamel-cementum junction, alongside an unerupted tooth. (A) The white, folded lining has been partially removed after fixation to reveal the reveals the presence of keratinising epithelium. Proximity crown of the tooth. (B) Part of the vascular fibrous wall of a to a tooth is an incidental but not uncommon feature and dentigerous cyst lined by non-keratinised stratified on a radiograph may simulate a dentigerous relationship. squamous epithelium which shows a zone of mucous (B) Characteristic histological appearance of an metaplasia. Such an appearance is characteristic in the odontogenic keratocyst epithelium: uniform thickness and absence of inflammation. H&E. with a flat basal surface, elongate basal cells, a thin prickle cell zone and corrugated parakeratin surface layer. The fibrous wall is usually thin, delicate and vascular. H&E. presentation and a high proportion of surgical specimens of dentigerous cysts show lymphoplasmacytic infiltrates folded inner surface (Fig. 4A) following discharge of in the wall and neutrophils in the epithelial lining. Accu- stacked keratin, as with an epidermoid cyst. In most mulations of cholesterol clefts, foreign body giant cells cases, there should be little difficulty in establishing the and haemosiderin-laden macrophages may greatly en- diagnosis histologically. Typically, the wall is thin and large the wall and locally herniate into the cyst lumen. rarely removed intact. It is lined by uniform, para- Thus, at cut-up, disrupted cysts may glisten with keratinised epithelium, some 10-12 cells thick, with a discharging semi-fluid contents which are rich in flat basal surface (Fig. 4B). Key features are a narrow, cholesterol. folded (corrugated) zone of keratin, prickle cells which retain their long axes at right angles to the basement membrane until close to the keratinised layer and elon- Odontogenic keratocyst (primordial cyst) gate, often palisaded, basal cells which show reversed More has been written in recent years on the polarity in at least some areas. It was established many odontogenic keratocyst than on any other jaw cyst. years ago that keratocysts show a higher frequency Radiographically it has a multilocular, or apparently of mitoses than is found in other odontogenic cysts. 15 multilocular, appearance and is sometimes multiple, Mitotic figures may be found in both basal and parabasal especially when it represents a manifestation of the layers. A study using PCNA as a marker of cell prolif- naevoid basal cell carcinoma syndrome (Gorlin's syn- eration has shown higher indices for keratocysts than for drome). Rather than expanding the jaw, the cyst tends other odontogenic cysts. 16 Odontogenic keratocysts have to grow mesiodistally at the expense of the medullary a higher recurrence rate too, due in part to their physical bone and extends between the roots of the teeth. fragility leading to disruption during removal, the Macroscopically, the opened cyst reveals a white, epithelium separating easily from the fibrous wall. A
  • 4. CYSTS AND CYSTICLESIONSOF THE JAWS 89 further possible reason is the presence of daughter cysts diagnosis in such cases, especially if the biopsy sample in the wall which may remain after cyst enucleation. is small. Differences in proliferation rates and in the frequency of basal epithelial" cell budding between solitary, multi- Lateral periodontal, botryoid, and glandular ple and recurrent odontogenic keratocysts and those odontogenic cysts associated with naevoid basal cell carcinoma syndrome have been the subject of a number of recent studies. 17 The lateral periodontal cyst is usually unilocular and lies Significantly higher rates of mitosis occur in keratocysts alongside a vital tooth and therefore, like the radicular in patients with Gorlin's syndrome. Satellite cysts have cyst, is presumed to originate from cell rests of Malassez been detected in about 50% of syndrome patients and in in the periodontal ligament or possibly from part of the walls of 25% of multiple or recurrent cysts whereas the developing follicle, z~ The stimulus to its formation is they are found in less than 10% of solitary keratocysts. unknown, and it is usually detected as a symptomless In practical terms, the possible diagnosis of naevoid radiolucency on routine radiography. Its epithelial lining basal cell carcinoma syndrome should be investigated is about 2-6 cells thick, non-keratinised, stratified for all patients with odontogenic keratocysts. The syn- squamous and with a flat basal surface. There may be drome is an autosomal dominant condition with numer- a narrow zone of subepithelial hyalinisation, a feature ous defects, many involving the axial skeleton. occasionally encountered in other odontogenic cysts and It is important not to diagnose as a keratocyst every neoplasms. The fibrous wall is usually uninflamed, odontogenic cyst which shows some keratinisation. Parts cellular and delicate, lacking daughter cysts. A charac- of (probably) long-standing dentigerous or radicular teristic feature is the presence of periodic, plaqueqike cysts may show ortho- or parakeratinisation but without thickenings in the epithelium (unrelated to inflamma- the other features of odontogenic keratocysts. Also, soft tion) which may bulge into the cyst lumen or wall or tissue removed together with impacted, partially erupted both (Fig. 6). These contain glycogen and may be third molar teeth may include some keratinised gingival composed predominantly of clear cells but there is no mucosa which may unwittingly be mistaken for kera- evidence that they represent centres of proliferation. tocyst wall. It is of interest that, whilst all odontogenic Indeed, mitotic figures, epithelial budding and daughter keratocysts keratinise, only a minority are orthokera- cyst formation are unusual in the lateral periodontal cyst. tinised; moreover, these recur less frequently than A proportion of cysts which radiographically suggest parakeratinising cysts. 18,19 a diagnosis of lateral periodontal cyst turn out to be Although inflammatory infiltrates in odontogenic odontogenic keratocysts on histological examination, keratocysts are usually well-localised and mild, diagnos- despite their unilocular profile. tic problems may result from an ~xtensive inflammatory Botryoid and glandular odontogenic cysts are rare infiltrate which suppresses keratinisation (Fig. 5). This entities with features in common with each other and could give rise to misdiagnosis of a dentigerous or re- with the lateral periodontal cyst. The former is so called sidual cyst with the consequence that, in the absence because the low magnification appearance or macro- of follow-up, the patient may develop a recurrence scopic cut surface sometimes resembles a bunch of which is unrecognised until well advanced. If, in a simi- grapes. Radiographically, most have been multilocular lar context, the basal cells are markedly columnar the and located in the mandible. In their more detailed fea- keratocyst might be misdiagnosed as an ameloblastoma, tures, botryoid cysts resemble lateral periodontal cysts, particularly since the radiographic appearance of these the thin, non-keratinised epithelial lining with thickened two lesions are sinfilar. One should be wary of over- plaques being a consistent feature. A number of recent 4~ Fig. 5 - - A keratocyst which has become secondarily Fig, 6--Wall of a lateral periodontal cyst with a Iocalised inflamed. Note the loss of keratinisation in the zone thickening of the uniform, non-keratinising epithelium. showing an arcading pattern of epithelial hyperplasia. If the Several such thickenings may be encountered in a given biopsy is small or inflammatory change extensive, this may plane of section. H&E. lead to a mistaken diagnosis of an inflammatory cyst. H&E.
  • 5. 90 CURRENTDIAGNOSTICPATHOLOGY publications point to a high recurrence rate for this multicystic lesion. Greater difficulty attaches to the status of the glandular (sialo- or mucoepidermoid-) odontogenic cyst. It is sur- prising that this cyst has been recognised only recently as a distinct entity 21,22 and less than 20 cases have been reported in the world literature. It has an appearance of multilocularity on radiographic examination. Its histo- logical features include multiple thickened epithelial plaques, like those of the lateral periodontal cyst, and multicystic growth, like the botryoid cyst. Intriguing additional features are present in the epithelium: papil- lary 'outgrowths' into the cyst lumen with apocrine-like 'decapitation' secretion of surface cells, ductal struc- Fig. 8--Radicular cyst: a frequent presentation with a tures, mucin-producing goblet cells and occasionally dense, mixed inflammatory infiltrate adjacent to variably acini (Fig. 7). The nomenclature for this cyst has not yet hyperplastic, non-keratinised epithelim. The upper part of the field shows part of the wall apparently devoid of been established and interpretations of the histological epithelium, also a common finding. H&E. features range widely. Mucous metaplasia may be present in the lining of any odontogenic cyst and to some commentators, the glandular odontogenic cyst is an ex- pattern of hyperplasia (Fig. 5) can be so striking that the treme example of this change. An opposing view is that unwary may suspect the presence of an ameloblastoma. 23 the lesion is in fact a low-grade central mucoepidermoid It is essential that the condition of the related tooth be carcinoma. When more cases become available for study known for the correct diagnosis to be made: the histo- and when a wider range of markers of odontogenic logical features of a radicular cyst may be identical epithelium have been developed, the histogenesis of this to those of a secondarily inflamed dentigerous cyst. group of cysts should become clearer. Similarly, a long-standing radicular cyst may come to resemble a developmental cyst when the inflammatory Inflammatory odontogenic cysts infiltrate fades. A cyst which forms alongside a non-vital tooth is termed a lateral radicular cyst and one which is Radicular cyst retained following removal of the offending tooth or root By far the most common jaw cyst is the radicular cyst, is referred to as a residual cyst, the histological features an odontogenic cyst which forms from epithelial rests of being identical to those just described. Malassez in the periodontal ligament consequent upon activation from the products of necrotic dental pulp in an Paradental cyst adjacent tooth. The wall is relatively thick and usually contains a dense inflammatory infiltrate towards the The paradental cyst is an inflammatory cyst which lies inner aspect, consisting of plasma cells and lymphocytes. on the disto-buccal aspect of fully or partially erupted Neutrophils tend to accumulate in the epithelium which third molar teeth, near the bifurcation of the roots is of non-keratinised, stratified squamous type and varies (Fig. 9). There is a male preponderance, a history of greatly in thickness (Fig. 8). Sometimes the arcading pericoronitis is common and sometimes a predisposing Fig. 7--Parts of two Iocules of a glandular (sialo-) Fig. 9--A paradental cyst attached to the enamel-cementum odontogenic cyst with thickened epithelial plaques, similar junction of a lower molar tooth on the disto-buccal aspect. to those found in lateral periodontal and botryoid cysts but Although slightly disrupted, it lies alongside the tooth and also showing ductal structure, and extensive mucus- does not enclose the crown. secreting cells. H&E.
  • 6. CYSTS AND CYSTICLESIONSOF THE JAWS 91 factor is an extension of enamel down to where the roots Differential diagnosis should include other odonto- separate and a bilateral presentation is not u n u s u a l . 24 The genic carcinomas: primary intra-osseous carcinomas, associated tooth is therefore usually vital and such cysts which are thought to arise from residues of odontogenic are often removed still attached after extraction of the epithelium in the jaws, and malignant variants of erupting or partially erupted tooth due to impaction. ameloblastoma and other odontogenic tumours. Central Whether the source of epithelium is the reduced enamel mucoepidermoid carcinomas, in which the epidermoid epithelium, periodontal pocket epithelium or cell rests component may predominate, should also be considered. of Malassez, the aetiological mechanism appears to be Any of these malignancies may be cystic, at least in epithelial activation by inflammatory infiltrate which is part. The mandible is also a well-recognised site for car- induced by bacterial plaque. cinomas metastatic to the jaws from such sites as lung, A related cyst, the mandibular infected buccal cyst, breast, prostate, thyroid and kidney which may simulate has a similar association with first or second lower per- cysts radiographically. manent molar teeth 25 but in younger patients than the Dysplastic change may be encountered in cyst epithe- paradental cyst. As Shear 2 argues, the two entities are lia and levels should be checked carefully for evidence probably related but are worth while recognising as of frank invasion. This is particularly the case in those distinct for reasons of management. odontogenic keratocysts which show basal budding Both these cysts have the same histological appear- (Fig. 11) and epithelial islands, since the presence of ance as the radicular cyst: hyperplastic, non-cornified dysplasia may give the impression of a wide field of epithelium lining a fibrous wall containing a dense, invasion. mixed inflammatory infiltrate. Clinical information is therefore essential for an accurate diagnosis. AmelobIastoma and its unicystic variants Ameloblastomas are the most common odontogenic neo- Malignant transformation in jaw cysts plasms. They present usually in the mandibular third Although rare, malignant transformation does occur in molar region and least often in the anterior maxilla. odontogenic cysts, about 60 cases having been reported Their peak age prevalence is in the 4th or 5th decade. in the world literature. Malignant transformation appears Histological criteria for their diagnosis were set out by to arise most frequently in residual cysts, reported cases Vickers and Gorlin. 27 The epithelial cells comprise two equalling those of dentigerous cysts and odontogenic distinct populations. Firstly, peripheral, or basal, cells keratocysts combined; 80% of such malignancies occur which are columnar and often markedly elongate and in the mandible (Fig. l()). 2r Not surprisingly, the age at showing reversed polarity, with the nucleus occupying presentation tends to be greater than that of patients with the part of the cell away fi-om the basement membrane; benign cysts; the 6th or 7th decade rather than the 4th or this layer thus resembles the pre-ametoblast of the devel- 5th. As far as can be assessed with such small numbers oping tooth germ. The second population consists of of cases, the prognosis appears to be better than that of polyhedral suprabasal cells with fewer intercellular con- mucosal carcinomas which infiltrate the .jaws, and that tacts than conventional prickle cells; this is the stellate of primary intra-osseous carcinomas, nodal metastases reticulum-like layer, similar to the stellate reticulum of being less common. This difference in prognosis might the bell stage in the developing tooth. Two principal be expected when the carcinoma is removed while being arrangements of epithelium are recognised, follicular retained within the confines of the fibrous cyst wall. (Fig. 12A) and plexiform (Fig. 12B), although there is Fig. 10--Squamous cell carcinoma which has arisen in an Fig. 11--Odotogenic keratocyst showing extensive basal odontogenic keratocyst. This mandibular t u m o u r was more budding together with bulbous rete processes and some solid than cystic but dysplastic keratocyst lining is still cell disorganisation but minimal cytological features of evident associated with islands of well-differentiated malignancy. However, the presence of these features carcinoma. A dense lymphocytic response is also present. increase the likelihood of recurrence. H&E. H&E.
  • 7. 92 CURRENTDIAGNOSTICPATHOLOGY be confused with an odontogenic keratocyst. 28 An addi- tional but rare feature of ameloblastomas is the inclusion of eosinophilic granular cells whose origin is obscure but which are befieved to arise in the epithelial compartment. Other variants of ameloblastoma may also be pre- dominantly cystic: 9 Desmoplastic, in which the stroma is more densely fibrous. 9 Basal cell, in which basaloid cells predominate. 9 Papilliferous keratoameloblastoma, a rare type in which cystic spaces may be filled with desquamated, kerati- nising squames. Some ameloblastomas are characteristically unilocular (A) on radiographs and prove to be unicystic (Fig. 13), and sometimes in a dentigerous relation to a tooth, when examined macroscopically. They also tend to present in younger patients than do conventional ameloblastomas. Levels should be taken through the excision specimen to investigate the presence of a conventional amelo- blastoma. Sometimes part of the lining expands into a plexiform pattern of ameloblastoma. On occasion, strict criteria for ameloblastoma can be hard to establish and the diagnosis has to take account of the clinical presenta- tion as well as 'suggestive' features in the epithelial lin- ing. Unicystic ameloblastomas are generally considered to have a lower recurrence rate than their conventional counterparts. This is true of those with a continuous epithelial lining and those with ameloblastomatous mural (B) nodules which invaginate the lumen. They may be Fig. 12--Examples of cyst formation in conventional treated successfully by careful enucleation, but when ameloblastomas. (A) Follicular ameloblastomas with cystic the wall is found to be infiltrated by islands of amelo- change in the stellate reticulum component of the neoplasm. The cystic area on the right is lined by cells blastomatous epithelium treatment should be as radical showing 'acanthomatous' change. (B) Plexiform as for the conventional solid or multi-cystic types. 13 ameloblastomas with stromal cysts; surviving small blood vessels indicate the location of the connective tissue component. The lumen of the main cyst is shown at the top of the figure and is composed of degenerate epithelial cells. Calcifying odontogenic cyst H&E. This curious entity is usually classified with epithelial odontogenic tumours since it is really a neoplasm which sometimes may be as aggressive as an ameloblastoma. no behavioural difference between the two. Although usually slow growing and lacking in detectable mitoses, both types tend to infiltrate the bone and to recur unless removed by local resection. The follicular form consists of round or irregular islands of tumour, the stroma being composed of vascular, cellular fibrous tissue. As its de- scriptive name suggests, in the plexiform ameloblastoma the epithelial component takes the form of interlacing strands which appear to entrap the stroma. Cystic change is common in both types, microcysts forming in the epithelial masses and stromal cysts in the connective tissue. As the ameloblastoma enlarges, the cysts coalesce and may form one or more cystic cavities containing straw-coloured fluid. Biopsy of the stretched wall of such a tumour may lead to the misdiagnosis of a non- neoplastic cyst. Fortunately, the solid or invaginated Fig. 13--Unicystic ameloblastoma. This lesion shows few areas are likely to contain more representative amelo- histological hallmarks of an ameloblastoma, Basal blastoma. Another conmaon feature of ameloblastomas is epithelial cells palisaded in places but with little evidence of the reversed polarity characteristic of ameloblasts and squamous metaplasia ('acanthomatous change') which stellate reticulum cells are poorly developed. Epithelium in only rarely consists of true keratinisation when it may this field has a somewhat plexiform arrangement. H&E.
  • 8. CYSTS AND CYSTIC LESIONS OF THE JAWS 93 Browne R, ed. Investigative pathology of odontogenic cysts. CRC Press, 1991:53 85. 4. Heikinheimo K, Sandberg M, Happonen R-P, Virtanen I, Bosch F. Cytoskeletal gene expression in normal and neoplastic human odontogenic epithelia. Lab Invest 1991; 65: 688-701. 5. Morgan P R, Shirlaw P J, Johnson N W, Leigh I M, Lane E B. Potential applications of anti-keratin antibodies in oral diagnosis. J Oral Pathol 1987; 16: 212-222. 6. Morgan P, Johnson N. Histological, histochemical and ultrastructural studies on the nature of hyalin bodies in odontogenic cysts. J Oral Pathol 1974; 3: 127-147. 7. Browne R, Smith A. Pathogenesis of odontogenic cysts. In: Browne R, ed. Investigative pathology of odontogenic cysts. CRC Press, 1991: 87-109. 8. Toiler P. The osinolality of fluids from cysts of the jaws. Brit Dent J 1970; 129: 275-278. 9. Kramer I R H. Changing views on oral disease. Proc Roy Soc Med 1974; 67: 271-276. Fig. 14--Calcifying odontogenic cyst with characteristic 10. Harris M, Toller P. The pathogenesis of dental cysts. Brit Med ghost cells suprabasally. Basal and parabasal layers Bull 1975; 31: 159-163. resemble eqivalent cells in ameloblastomas. Groups of 11. Meghji S, Henderson B, Bando Y, Harris M. Interleukin-1: the ghost cells may find their way into the connective tissue principal osteolytic cytokine produced by keratocysts. Archs oral and stimulate a foreign body reaction. H&E. Biol 1992; 37: 935-943. 12. Lombardi T, Morgan P R. hnmunohistochemical characterisation of odontogenic cysts with mesenchymal and myofilament markers. J Oral Pathoi Med 1995; 24:170 176. 13. Shear M. Developmental odontogenic cysts. An update. J Oral It s h o w s a w i d e site and age variation 29 but is c o n f i n e d PatholMed 1994; 23:1 11. to the t o o t h - b e a r i n g r e g i o n s o f the j a w s . S o m e t i m e s the 14. Kim J, Ellis G. Dental follicular tissue: misinterpretation as c a l c i f y i n g o d o n t o g e n i c cyst is not cystic and often it odontogenic tumors. J Oral Maxillofacial Surg 1993; 51: 762-767. 15. Browne R. The odontogenic keratocyst histological features and d o e s not calcify. Its basal cells and parabasal epithelial their correlation with clinical behaviour. Br Dent J 197 I; cells r e s e m b l e t h o s e o f the a m e l o b l a s t o m a but m o r e 131 : 249-259. superficial cells e x p a n d to f o r m lightly e o s i n o p h i l i c , 16. Li T-J, Browne R, Matthews J. Quantification of PCNA+ ceils within odontogenic jaw cyst epithelium. J Oral Pathol Med 1994; partially keratinising and usually n u c l e a t e cells t e r m e d 23:184 189. ' g h o s t c e l l s ' (Fig. 14). T h e s e may b e c o m e c a l c i f i e d and 17. Woolgar J A, Rippin J W, Browne R M. A comparative are not d i s s i m i l a r to cells o f the p i l o m a t r i x o m a wilh histological study of odontogcnic keratocysts in basal cell naevus syndrome and control patients. J Oral Pathol 1987; 16: 75-80. w h i c h this lesion has often been c o m p a r e d . G h o s t cells 18. Brannon R. The odontogcnic keratocyst. A clinicopathologic study are not u n i q u e to the c a l c i f y i n g o d o n l o g e n i c cysl but {71312 cases. Part 11. Histoh}gical features. Oral Surg Oral Med have been d e s c r i b e d in cases o f a m e l o b l a s t o m a , a m e l o - Oral Pathol 1977: 43:233 255. 19. Wright J. The odontogenic kcratocyst: orthokcratinizcd w,'iant. Mastic fibroma and ameloblastic fibroodonlome. A Oral Surg Oral McdOral Pathol 1981; 51: 609 618. further feature seen in a proportion o f cases is the d e p o - 20. Allini M, Shear M. The lateral periodontal cyst: an update. J Oral sition of poorly mineralised dysplastic dentine or Pathol Med 1992; 21:245 250. 21. Padayachee A, Van Wyk C W. Two cystic lesions with features of 'dentinoid" in the cyst wall. S o m e t i m e s typical dental both the botyroid odontogeuic cyst and lhc central hard tissues f o r m , in w h i c h case one has to c o n s i d e r mucoepidcrmoid turnout: sialo odontogenic cyst'? J Oral Pathol w h e t h e r ' o d o n t o m e ' s h o u l d be the m o r e a p p r o p r i a t e 1987; 16: 499-504. 22. Gardner D G, Kessler H P, Morency R, Schaffner D L. The d e s i g n a t i o n , a d e c i s i o n for w h i c h the age, site and radio- glandular odontogenic cyst: an apparent entity. J Oral Pathol graphic a p p e a r a n c e should be taken into account. As 1988; 17:359 366. t h e s e turnouts are rather rare, this material has scarcely 23. Lucas R. Pathology of Tumours of the Oral Tissues. 4th ed. Edinburgh: Churchill Livingstone, 1984. b e e n tested for its authenticity as dentine. A d i a g n o s i s 24. Craig G. The puradental cyst. A specific inflamnmtory o f c a l c i f y i n g o d o n t o g e n i c cyst is not a clear p o i n t e r to a odontogenic cyst. Br Dent J 1976; 141:9 14. l e s i o n ' s likely behaviour. D e t a i l e d a n a l y s i s o f 92 c a s e s 25. Stoneman D, Worth H. The mandibular bucca] infected cyst - molar area. Deut Radiol Photog 1983; 56:1 14. e m p h a s i s e d the n e e d to s u b g r o u p t h e m into h a m a r t o - 26. Schwimmer A, Aydin F, Morrison S. Squamous ceil carcinoma matous, cystic and n e o p l a s t i c variants. 29 arising in residual odontogenic cyst. Oral Surg Oral Med Oral Pathol 1991; 72: 218--221. 27. Vickers R, Gorlin R. Ameloblastoma: delineation of early References histopathologic features of neoplasia. Cancer 1970; 26:699 710. 28. Siar C, Ng K. 'Combined ameloblastoma and odontogenic 1. Kramer 1, Pindborg J, Shear M. Histological typing of keratocyst' or 'keratinising ameloblastoma'. Br J Oral Maxfac odontogenic tumours 2nd ed. Berlin Heidelberg: Spinger-Verlag, Surg1993; 31:183 186. 1992. 29. Hong S, Ellis G, Hartman K. Calcifying odontogenic cyst. A 2. Shear M. Cysts of the oral regions. 3rd ed. Oxford: Wright, review of 92 cases with reevaluation of their nature as cysts or Butterworth-Heinemann, 1992. neoplasms, the nature of ghost cells, and subclassification. Oral 3. Smith A, Matthews J. Odontogenic epithelium and its residues. In: Surg Oral Med Oral Pathol 1991; 72:56 64.