Вы находитесь на странице: 1из 12

J Orat I'lilhot Meil tW4: 2,<: I It

I'rintrit in lienmurk . Att rif't)t,\

re.\crvcd

Review article

Developmental odontogenic cysts. An update^

Copyright

Mervyn Shear

J* Munksgaard

JOURNAL OF

ISSN

0904-2512

1994

Department of Oral Pathology, University of the Witwatersrand, Johannesburg, South Atrtca

Shear M; Developmental odontogenic cysts. An update, J Oral Pathol Med 1994; 23; I 11, ( Munksgaard, 1994,

This review paper reports recent advances in the subject of developmental odonto- genic cysts, essentially those of the past decade, starting with reference to the new WHO classification (1), On keratocysts, the latest reported recurrence rates are assessed as are their mode of growth, immunocytochetnistry, immunology, genetic studies, and work on specific keratocyst antigens. There is a critical account of the group of lesions which includes the gingival cyst of adults, lateral periodontal cysl, boUyoid odontogenic cyst and glandular odontogenic cyst, and ihcir possible relalioiiship to one another. On dentigerous cysts, reference is made to the relationship between them and deciduous teeth, as well as to their itnmuno- cytocheniistry and immunology. Recent work on the unicystic ameloblastomas, their classification and prognosis, is assessed, as is the calcifying odontogenic cyst and its relationship with solid odontogenic tumours.

Classification

The World Health Organization has re- cently ptiblished ihe second edition of Ilistological typing of odontogenic tu- nwtir,s (I) which includes ihe proposed cla,ssification of jaw cysts. The cpitheli- al-lincd cysts may be of dcxclopmcntal origin, either odontogenic or non-odon- togenic; or they may be of innammatory origin (Kig, I), It is the recent advances, essentially those in the past decade, which have been reported on the devel- opnicnlal odontogenic cysts that are dealt with in this review, albeit selective- ly. The calcifying odoniogenic cysl. which in the WHO classification is listed as a benign neoplasm, will be included ill this review. The order in which the different lesions are presenteil does not follow thai in the WHO classification,

Odontogenic keratocyst (primordial cyst)

There continues lo be considerable in- terest in the odontogenic keratocyst

' Based on a lecture delivered al the 6th Bien- nial Congress of the International Associa- tion of Oral Pathologisis, ,Iuly 1992, in Ham- burg, (iermany.

(primordial cyst), and numerous papers on the subject have been published since an earlier review (2), The frequency in our material has re- mained constant at about 11 per cent of jaw cysts but is lower in some reported series.

Recurrence rates

Reported recurrence rates continue to be high in most studies, although some reports indicate a declining frequency of recurrences with better understand- ing of the behaviour of this lesion and consequent modifications in their treat- ment. This view is borne out by the experience of VOORSMIT ct til, (3) who reported the results of a follow-up study of two groups of patients treated for keratocysts. In the ftrst group of 52 cases treated between 1959 and 1980. the cysts were treated conservatively by careful enuclealion of the entire wall, in the second group of 40 cases treated between 1970 and 1980. the cysts were removed by enucleation, along with ex- cision of the mucosa overlying any per- foration of the cortical bone which was determined at operation. Before remov- al, all cysts in this group were treated

Key words; cysts; odontogenic cysts

Mervyn Shear, Department of Oral Pathology,

University of the Western Cape, Private Bag

X08,

7785 Mitchells' Plain, South Africa

Accepted for publication July 23. 1993

with Carnoy's solution. The recurrence rate in their first group was 13,5 per cent in a I 21 year follow-up, while the recurrence rate in their second group has been 2,5 per cent in a i-10 year follow-up. Similarly. FORSSHLL ct al, (4) have pointed out that in their series of keratocytes treated before 1975. the re- currence rate was 50 per cent, whereas in the group treated duritig the period 1975 1980, the recurrence rate had dropped to 22 per cent, NII;MEYHR ct al, (5) reported that their experience of recurrences in a series of 62 patients with keratocysts was related to the operative procedure employed. Thirty-three of their patients were fol- lowed for at least 6 years. The highest frequency of recurrences occurred in their patients treated by cystostomy. On

the contrary. BRONDUM & Ji-NStN (6)

reported that in a 7 to i7 year follow- up, there were no recurrences in 12 of their cases treated by cystoslomy to re- duce the size of the lesions before cystec- toiny. whereas there were recurrences in 8 of their 32 cases treated by primary eysteciomy. The considerable variation in recur- rence rate reported by different workers may be ascribed partly to the variability

2

SHBA R

Fig.

/

World

Health Organizatio n

classification

of epithelial cysts of the jaw s (I) .

 

Rpithelial cysts

 

Developmental

 

I 'Gingival cysts" of infants (Hpstein's pearls)

26540*

.2.Odontogenic keratocyst (primordial cyst)

26530

.3 Dentigerous (follicular) cyst

26560

.4 Eruption cyst

26550

.5 Lateral periodontal cyst

26520

,6 Gingival cyst of adults

26540

.7 Glandular odontogenic cyst; sialo-odontogcnic cyst

26520

.2

Nnn-Oiiimtogenic

 

.2.1

Nasopalatine duct (inciisive canal) cyst

 

266(J0

.2.2 NasoJabial (nasoalveolar) cyst

26500

3.2

Inllammatory

 

3.2.

Radicular cyst

 

43X00

3.2.

. I Apical and lateral

 

3.2.

.2 Residual

 

3.2.2

Paradental (inflammatory collateral, mandibular infected buccal) cyst

26520

Morphology code of the International Classiftcation of Diseases lor Oncology (ICD-O) and the Systematized Nomenclature of Medicine (SNOMfiD).

in the follow-up period, VKDTOKTF; & PR/ETORIUS (7). FoR,s,sELL (8) and FOR.S- .SRI.I. ct al. (4) have shown quite clearly that in their own material the recurrence rate increased with extension ofthe fol- low-up period to 5 years or more. The latter authors (4) found that of 75 cases in 63 patients followed for periods rang- ing from 5 to 17 years (mean S.3). 32 (43"^) recurred. The cumulative recur- rence rate of 67 of these cysts in patients examined annually increased from T/n after the first year to'STA.after the third year. Thereafter, no new recurrences were noted.

Age

Further studies reported over the past few years confirm the bimodal age dis- tribution of patients with keratocysts (9 13), The explanation for this is prob- ably that some keratocysts remain un- diagnosed for many years, extending slowly either in the maxilla or along the mandible and into the a.scending ramus, rather than that there are two different varieties of the lesion, W(K)LC;AR et al. (14) have pointed out that the mean age of patients with multi- ple keratocysts. with or without the naevoid ba.sal cell carcinoma syndrome, is considerably lower than the mean age of patients with single non-recurrent keratocysts and that pooling patients Irom the three groups will account for differences in age distribution reported in different studies.

Mode of growth of the keratocyst

et al. (15) studied the pro- liferation patterns ofthe epithelium and

connective tissue of a keratocyst by means of autoradiography and DNA cytophotometry in serial sections sam- pled in numerous areas. These were compared with the proliferation pat- terns in a radicular cyst studied in the same way. The epithelium of the kerato- cyst showed a higher rate of prolifera- tion than the radicular cyst. The mean marking index was also substantially higher in the keratocyst than in the ra- dicular. The authors identified both slowly and rapidly proliferating areas in different parts ofthe keratocyst epitheli- um and in different planes of section. They also demonstrated that the con- nective tissue wall of the keratocyst showed both slowly and rapidly prolif- erating areas, whereas the connective tissue wall of the radicular cyst showed a low mean marking index. They con- cluded that exclusively passive expan- sion of the cyst connective tissue as a reaction to the growth ofthe keratocyst was unlikely. They thought that the in- vasive growth of keratocysts was likely to he the result of active growth of the connective tissue wall,

AiiLtoRS et al. (9) had postulated something along similar lines when in 1984 they proposed that the keratocyst should be regarded as a benign neo- plasm. They drew attention to the in- folding of the epithelial lining into the capsule and suggested that this was the result of active epithelial proliferation accompanied by collagenolytic activity within the fibrous capsule and resorp- tion of bone. SMrrii ('/ al. (16 18) have reported a series of three studies on the presence and role of glycosaminoglyeans in odontogenic cysts, including kerato-

cysts. In all cyst types, hyaluronic acid was the predominant glycosaminogly- ean present, as it was in the cyst fluids. Heparan and chondroitin-4-sulphate were present in substantial amounts, he- paran sulphate showing a higher inci- dence and abundance in the keratocyst than the other cysts, A considerable proportion of the glycosaminoglyeans appeared to be complexed with protein and was released only after proteolytic digestion. Mast cells were widespread in the connective tissue of all cyst types, particularly adjacent to the epithelium, and were probably the source of the heparin. Epithelial permeability, the au- thors suggested, would probably allow passage of smaller glycosaminoglycan chains into the luminal fiuid. The larger chains would probably pass through ep- ithelial discontinuities. They concluded from their series of studies that the re- lease of these molecules into the luminal lluid could be expected to contribute significantly to its osmotic and hydros- tatic pressures and hence to the expan- sile growth of odontogenie cysts.

Radiology

While most keratocysts which appear to be dentigerious on radiographs are in fact envelopmental keratocysts, very oc- casionally the lining of a cyst in a true dentigerous relationship may be iden- tical to that of a keratocyst. This con- cept has been developed by Ai.riNi & C()III;N (19) who have introduced the term 'follicular primordial cyst" (follicu- lar keratocyst) for this. They postulated that follicular keratocysts might arise following eruption ofa tooth into a pre- existing keratocyst ciivity in the same way as a tooth erupts into the oral eavi- ty. In a later study (20), they were able to support their hypothesis in a series of animal experiments. It is noteworthy that in the rather extensive literature published on the subject of keratocysts over the past 10 years by authors with considerable ex- perience in the diagnosis and treatment of these lesions, very little reference has been made to the use of cotiiputerised tomography (CT) in their assessment, VooRSMiT (12) described two cases in which this techniqtie was used "to ob- tain accurate meastiremenl ofthe exient ofthe lesion, exaet localization of areas of perforation through the cortex and, particularly, assessment of soft tissue in- volvemenL" He described the important features of the technique as lack of image superimposition, preservation of

DcYclopnwntal odontogenic cysts

3

soft tissue detail, selective enlargement of areas of interest, a high degree of accuracy and the possibility of three- dimensional interpretation. On the other hand, tesolutioti of ftnc details is poorer than with conventional or xero- tomography. Ihe high expense of the procedure is referred to, but not the hazards of the radiation exposure,

MACKIN/II:

rt

al.

(21)

reported

the

use of computerized tomography in the diagnosis of a keratocyst and em- phasized the considerably higher ab- sorbed doses of radiation, particularly to the lens of the eye. In general, these authors stated, the absorbed radiation from CT studies is about 1000 titiies higher than those associated with a patioramic study. The associated risks, the cost of the examination, and the limits of the CT scan must be weighed against Ihe additional information which can be obtained from the proee- dure before it is used on an individual patient. A leport by a joint working party ofthe National Radiological Protection Hoard and the Royal College of Radiol- ogists in Britain, while stressing the ben- efits of X-rays in diagnositig di.sease. commented nevertheless that the avoid- able dose of radiatioti frotn tnedicine "outweighs the combined eontributioti of all other nian-niade sources of popu- hilion radiation exposure by a factor o\' three" (22). Data obtained by the Board indicated that CT scans now account lor at least 20'^ of the total effective dose of diagnostic radiation to the populatioti. and the secietary of ihe working party has suggested lliat radiol- ogists slioiikl be informed ofthe "high- dose implieations" of CT scans. When- ever possible, the report suggested, doc- tors should use the alternatives to X- ray. mainly ultrasotind and magnetic resonance imaging.

Histopathology

The histological features of the kerato- cyst ate vvell-doetnnented and reqtiiie little elaboration. Three recent studies have all shown that basal budding, odonlogenie rests in the eyst wall and satellite cysts apix'ar to be more coni- moti it) the eysts o\' patietits with the naevoiii basal cell carcinoma syndrome than in cyst patients without the syn- dtome (9. ly 25). SMr rii ct al. (26) foutul that tnast eells were ptesent in substantial ntinibets in keratocyst walls, as well as in the walls of dentigerotis and radieular eysts. The

highest eoticentration was in the sub- epithelial zotie where the count was 5,71 (SD±3,52) per tnicroscopie field, the latter being defined as the area encotii- passed by a 1 em- graticule. M;tst eells were also observed in the epithelial linings, whieh the authors suggested im- plies a chemotactic stimulus to mast cells in odontogenie cysts, attracting them to the epithelial lining or luminal fiuid contents. There has been eonsiderable interest recently in itntnunohistoehemical teeh- tiiques that ean be used to improve the aecuracy of histopathological diagnosis, Immunohistochemical staining with monoclonal antibodies was used (27) to study and compare the cytokeratin eon- tent of odontogenie eysts. normal gitigi- val epithelium and atiieloblastomas. Their results showed that keratocysts. radicular eysts and dentigerous cysts have distinet profiles of eytokeratin polypeptides and that, with the exeep- tion of some dentigerous eysts. they all laek large eytokeratins typieal of kera- tinizing squatnous epithelia. The au- thors cotieluded that epithelial eells in keratoeysts appear to undergo a gradual tnaturation as they tnigrate to the upper cell layers, whereas in tadicular and dentigerous cysts, no basal to apical dif- ferentiation was seen with these anti- bodies, A surprising finding in their sitidy was the absence of cytokeratin polypeptides typieal of keratinizing epi- thelia. namely numbers 1. 9 and 10/11. in all keratocyst epithelia. as judged by two monoclonal atitibodies whieh reaet with these eytokeratins: KA5. and K^ <S,60. These keratins are typical of tna- ture keratinoeytes and their absenee in- dieates, the authors suggested, that no true keratinization takes place in kera- toeysts. 1 hey eotieluded thetefote that the ptesence of true keratinization is not a distinguishing feature of keratoeysts. They suggested that a tnarker of the keratoeyst is the presenee of aceentuat- ed ba,sal eells together with the presenee of eytokeratins 8 and 19. eytokeratin IS being demonstrable in the basal and suprabasal eells.

L'sing tnonospeeifie antibodies on 50 odontogenie eysts with an enhanced in- diteet imniunopetoxidase tnethod. MArriiiAvs ct al. (28). as had HoRMtA et al. (27), detected keratin 19 in the epithelial linings of all eyst specitnens. This keratin was nortnally expiessed by the majority of epithelial eells, irrespec- tive of their level withiti the epithelium and/or dilTerentiation. In contrast to

the findings of HORMIA ct at. (27),

how-

ever, keratins assoeiated with eornified epithelia (keratins 10/11) were detected in the upper suprabasal layers in 17 of their sample of 18 keratocysts. They aseribed the eonllietitig results to difler- enees in the techniques used, and advo- cated the applieation of monoelonal an- tibodies to dry eryostat seetions. They suggested that the apparently kerato- eyst 'speeifie" profile (keratin 19. 10/

11 positivity) is dependent on eellular

ditTerentiation rather than histogenesis

or eyst type. Keratin profiles are there-

fore unlikely to distinguish between an

infiamed keratocyst which has lost its typical histological appearance, and other odontogenic cysts which have

keratinized epithelial linings as a results of metaplasia. They suggested that the consistent expression of both keratins

13 and 19 tnay provide a useful tnarker

of odontogenie epithelium in general.

The consistent histological appear-

ance of keratocyst epithelium suggested

to Sniui.KR & SnRivi R (29) that

eifie set of genetic events might be re- sponsible for its particular pattern of dif-

ferentiation. As the pattern of expression of keratin geties had beeti shown to be

elosely linked to the dilTerentiation of ep- ithelium, they exatnined the speeifie ker-

atin proteins in the lining epithelium of

keratoeysts by eleetrophoretie and im- munologie tnethods iti order to deter- mine whether the unique histologic ap- pearanee is retiected iti a reproducible pattern of keiatin proteins.

Their studies were done on three fresh keratoeyst speeimens, Polyaerylamide

ccl electrophoresis resolved identieal

patterns of proteins in the cytoskeletal estraets frotn the three eysts. whieh were in the keratin tnoleeular weight range (40 to 70 kilodaltons). The qualitative

and quantitative distribution of this

iiroup. whieh eonsisted of 7 proteins,

was identical for all three extraets, Iin- munoblot analysis of the proteins with

the antikeratin AEl and AE3 mono-

clonal antibodies detnonstrated that the previously identified pioteitis had kera- tin atitigenieity. A positive reaction was observed for all 7 proteins previously identified, but with variable intensity. These fitidings were consistent with other studies whieh had linked epithelial differentiation and keratin gene expres- sion, and suggested a eonnnon pattern of gene expression underlying the ehar- acteristie histologieal pattet n of the ker- atoeysl.

These imtnunoeytoehemical studies

are interesting and it is itnportant that

they be puisued beeause they are pro-

a spe-

4

SHKAR

viding fundamental information about the tissues being investigated. Thus far. the diagnostic potential appears to be limited, and the variability ofthe results from different laboratories suggests that there needs to be further refinement and standardization of the methodology, KuusELA et al. (30) demonstrated an antigen in the fiuid of keratoeysts which was not present in the fiuids of other eyst types nor in plasma or saliva. A double-antibody fiuoresence technique localized the antigen to the epithelial cells of the keratocyst and they called it keratocyst antigen (KCA), A later study from the same laboratory (31) showed that KCA and keratin are related mole- cules and that the relationship of keratin and KCA would enable the use of eom- mereially available antikeratin antibod- ies in the detection of KCA in the cyst fiuids, thus making it possible to distin- guish keratocysts prior to surgery. Working along the same lines in the search for either a single protein, or group of proteins, that is eharacteristie of a particular cell type, DotJCit.AS & CRAIG (32) used immunologieal teeh- niques to search for eomponents of non- serum origin in cyst fiuids. Their investi- gation identified the presence ofa major antigen, which was not a keratin, in the fiuid aspirated from all the keratoeysts whieh they assayed. This antigen was identified in a later paper by them as lactoferrin. a secretory substance pres- ent in the azurophilic granules of poly- morphonuclear leukocytes and body se- eretions but not in serum (33). Although infiammation is rare in keratocysts they suggested that the polymorphonuclear leukocytes that infiltrate the cyst wall aet as the souree of the laetoferrin in the fiuid and, as it is unable to diffu.se away into the surrounding tissues be- cause of the relative impermeability of the keratocyst to proteins, its concentra- tion may increase with time. This view was reinforced in the third of their series of papers on the subject where they showed that the lactoferrin concentra- tion correlated very strongly with the numbers of neutrophils present in kera- tocyst fiuids, assessed in smears, but not with fiuids from dentigerous and radic- ular cysts (33a).

In a study of immunoglobulin-pro- ducing eells in human odontogenic cysts, SMiTit ct al. (34) found that igCi- containing plasma cells were the pre- dominant sjjecies in all eyst types with a much lower percentage of IgA- and few IgM-eontaining plasma cells. There were, however, significantly fewer IgG

and significantly more IgA plasma cells observed in the keratoeysts than in the radieular and dentigerous cysts. IgA plasma cells appear to represent a signi- fieantly higher proportion of the total plasma cell population in keratocysts than in radicular and dentigerous cysts, although IgG cells still predominate. Generally, IgG plasma cells predomi- nate in areas of diffuse chronic infiatn- mation and the rai.sed proportion of IgA plasma eells in the keratoeyst may, the authors speculated, refiect the focal nature of the infiammatory infiltrate. They also found intense extraeellular staining for IgG in the eapsule and this they thought would support the view that the IgGs in odontogenic cyst fiuids may be derived from local synthesis in the cyst capsules as well as from the infiammatory exudate,

Gingival cyst of adults, iaterai periodontai cyst, botryoid odontogenic cyst and gianduiar (siaio-odontogenic) cyst

This group of lesions also continues to excite interest and there has been some advance in thinking on their pathogene-

sis and their relationship to one another. WYSOCKI ct al. (35) postulated, on the basis of their clinical and morphological similarities, that the gingival eyst of adults and the lateral periodontal cyst have a comtnon histogenesis and that they represent the intra-osseous and ex- tra-osseous manifestations of the same lesion. In two recently eompleted stud- ies, we agreed (36, 37) that the two lesions probably share a common par-

entage, and

considered that they were probably of

the same epithelial origin.

BUCIINI:R

& HAN,SI:N

(38)

Frequency

There were 14 gingival eysts of adults

and 18 cases of lateral periodontal cyst registered in our department between

1958 and 1989. representing 0,5 and

O.TAi respectively of the 2616 eysts of the jaws seen during that period. Of some significance, however, is the fact that these lateral periodontal cysts were re-

corded during the 17-year period

1973 89. indicating that prior to this a

number of cases were probably going un- recognized.

Site

The most frequent location of adult gin- gival eysts and of lateral periodontal

eysts reported in the literature is the mandibular canine-premolar area, fol- lowed by the anterior region ofthe max- illa. In our material, surprisingly, the distribution was somewhat different. Although all otir cases occurred anlerior to the first permanent molars, 10 of 18 cases (56'^) were found in the maxilla, all of which were clustered anterior to the first premolar teeth.

Pathogenesis of the iaterai periodontai cyst

Although there can be little doubt that lateral periodontal eysts are of develop- tnental odontogenie origin, there is dis- pute about which odontogenic epitheli- um they arise from. There seem to be three possibilities: teduced enamel epi- thelium, remnants of dental lamina and cell rests of Malassez, As is well known, the cyst is lined for the most part by a narrow non-keratinized epitheliutn whieh resetnbles reduced enamel epithe- lium. As such, the proposal that it arises initially as a dentigerous eyst developing by expansion of the folliele along the lateral surfaee of the crown (39, 39a) is an attractive one. If tooth eruption is nortnal, the expanded follicle may fin- ally lie on the lateral aspect of the root. This hypothesis is supported by the faet that lateral periodontal eysts tend to oe- cur in areas where dentigerous cysts are likely to be assoeiated with vertieally impacted teeth sueh as mandibular pre- molars and maxillary incisors and ca- nines.

Further support lor origin of lateral periodontal cysts from reduced enamel epithelium eomes from immunoeyto- ehemical studies. HhiKiNiiMMO et al. (40) investigated the cytokeratin com- position ofthe eyst epithelium in a ea.se of a botryoid variety of lateral perio- dontal eyst and found that cytokeratin 18 was strongly expressed; HORMIA ct al. (27) have reported that this eytoker- atin is present in all the layers of some dentigerous eysts but not in other types of odontogenie eyst. WYS(KKI ct al. (35) have proposed that the lateral periodontal eyst, like the gingival eyst of adults, arises from elear eell rests of dental lamina. They suggest- ed that unicystic forms arise throtigh cystic ehange in a single dental latnina rest and polycystic lesions develop if concomitant changes oecur in several adjaeent eell rests. In support of their hypothesis, they placed a lot of empha- sis on the faet that glyeogen-eontaining elear-eell rests ofthe dental latnina may

Developmental odontogenic cysts

5

sometimes be demonstrated, and that similar cells also oecur in parts of the

lining of lateral periodontal eysls, as well

as in the epithelial plaques which are a

feature of their linitigs. They also pointed

to the occasional presenee of glyeogen-

rieh clear-cell rests of what they interpre-

ted as dental lamina in the wall of the cysts. It is important to note, however,

that the epithelial plaques do not coni- pri.se clear cells dc novo but start rather

as fusiform eells with seanty eytoplasm

arising by loealized proliferation of basal eells. We have suggested (37) that the strtietures deseribed as cell tests of the dental lamina adjaeent (o the eysts are more likely to be the "pitiehed off exten- sions ofthe epithelial plaques referred to above, a coneept originally postulated by Wi;ATm:Ks& WAI.DRON (41),

I share with WYSOCKI ct al. (35) the view that the lateral periodontal eyst and the gingival cyst of adults have a

comtnon ancestry; the lateral periodon-

tal cyst from redueed enamel epitheliutn

before eruption of the tooth and the gingival eyst of adults from redueed enamel epithelium after eruption of the tooth (36, 37, 39a).

The third po,ssibility is origin from the cell rests of Malassez, Other than

the faet that the rests of Malassez oecur

in the periodontiutn and that they are

well-positioned for a lateral periodontal cysL this is not a theory which has re- ceived very much support.

Histology of the iaterai periodontai cyst

A reeent study on a series of 20 lateral

periodotital eysts (37) has cotifirmed the presence of glyeogeti in abt)ut two-thirds

of

them, either in the lining epithelium or

in

the plaques, or both, II was not found

exelusively in the clear eells. niatiy of which showed no positivity. btit also oe- curred in the superfieial sqtiamous and cuboidal cells of the lining epithelium. In this study, two groups were reeognised; unieystie (9 eases. 45'^) and nniltieystie (11 eases. 55"/ii). Some ofthe inultieystie lesiotis (6 of our series) eonsisted of 2 or more cystic spaces eotUained within a single round or oval fibrous capsule; others (5 of our series) were larger and less regtilat, having a distinctly botryoid appearance, eonsisting of several cystic spaces ol' varying size separated by fi- brous tissue.

Most of the lesions were small, vary- ing frotn 5 15 tnni in dianielet. whereas the botryoid variety were substantially larger, one of the ea,ses having measuted 50 tnm.

While the unieystie and tnultieystie va- rieties shared similar histologieal fea- tures, the botryoid type may oeeasional- ly show sotnewhat different charaeteris- ties. Two examples of the botryoid variety in our study were linked pre- dominantly by non-keratinizing strati- fied squamous epithelium with a lesser redueed enatnel epithelium-like cotnpo- nent. Clear eells were unusual both in the lining epithelium and in the plaques, the majority of which consisted only of stra- tified squamous epitheliutn. Moreover, iti two of our cases there was an increase in the nueleo-cytoplasmic ratio in tnuch ofthe epitheliutn, with resultant crowd- ing ofthe eells. The nuelei were pyknot- ie. One of our eases showed surfaee epi- thelial infolding with erypt formation and superfieial palisaded euboidal-eo- lutnnar eells. All varieties of lateral periodontal eyst may have small epithe- lial nests or follieles in the fibrotts wall and 1 have already referred to evidence whieh suggests that they arise frotn ex- tensions of the epithelial plaques. The fonnation of the epithelial plaques, their budding olT to form epi- thelial islands whieh in turn beeoine eys- tic. the repetition of this process through a number of generations, and the pre.senee of epithelial dysplasia in the botryoid varieties, are indicative of an active process of proliferation ofthe odontogenic epithelium involved in their genesis. Sinee their original description, bot- lyoid odontogenie eysts have been wide- ly regarded as variants of the lateral periodontal eyst, and generally publica- tions on the subjeets have not distin- guished them from the smaller multicys- tic lateral periodontal eysts. In tny opin- ion these two varieties are not entirely synonytnous. Some ofthe bottyoid vari- ety dilTer in inorphology and radio- graphie appeatanee, histology, behav- iour and prognosis, showing a distinet propetisity for recurretiee. It may be useful to distinguish between the clearly botryoid variety and other multieystie lateial periodontal cysts in prospective elinieopathological studies, as this will help to elueidate whether there is a dif- feretiee in biologieal behavior between the two. It tnust be regarded as a distinet possibility, however, that the multieystie variety can develop into a botryoid type by eontinued expansion of individual cysts . I n a ver y teeeti t papet \ VAN 1)I;R

WAAI (42) has argued th;\t the bottyoid

odontogenie eyst should tiot be tegard- ed as a variant ofthe lateial periodontal

eyst when it extends well beyond the lateral area ofa tooth. He suggested the terms "multieystie odontogenie lesions with features of a lateral periodontal eyst" or "lateral periodontal eystlike lesions" rather than botryoid odonto- genie eyst. Three of our cases of the botryoid variety also share some features of the glandular odontogenic cyst, in that they have epithelial erypts and supxirficial low columnar cells, although no mucous cells are demonstrable, a feature also deseribed in a ease reported by LINDH & LARSSON (42a), This raises the question

of whether the glandular odontogenie

cyst forms part of the clinieopathologi-

cal speetrum of the lateral periodontal eyst, a point which must be given seri- ous consideration.

Treatment

Provided that the lesion is unilocular

on radiological examination, the lateral

periodontal eyst is treated by surgical enucleation. Attempts should be made

to avoid sacrificing the associated tooth,

but this may not always be possible, A number of reports have been published

which indicate that the botryoid variety has a predileetion for reeurrenee (40, 43^5) and must be earefully exeised. It

is not yet elear from the literature

whether the encapsulated inultieystie

lateral periodontal eyst has the same tendeney to recur following simple enu- cleation. Eight of 10 recurrent cases re- ported by GRKER & JOHNSON (44) were unilocular radiologically but multilocu-

lar histologically. Lititil we have further

infonnation about the behaviour ofthe encapsulated inultiloeular variety, elini- eians are advised to follow these cases

for a nutnber of years.

Glandular odontogenic cyst (sialo- odontogenic cyst; mucoepidermoid odontogenic cyst)

A eyst with fairly typieal histologieal

features whieh has sotne eharaeteristies

in common with the lateral periodontal

cyst and the botryoid odontogenic eyst, has reeently been reported (46 47) and discussed at the tneeting of the Interna- tional Assoeiation of Oral Pathologists in 1984, WALDRON & Koii (48) have discussed it in eonnection with the cen- tral mticoepidemioid tumour of the jaws and Fu ARRA ct al. (49) reported a ease in which a diagnosis of low-grade mucoepidennoid eareinotna had been made.

6

SHEAR

The name of the cyst is not yet estab- lished. The term most descriptive ofthe lesion is probably 'mucoepidermoid odontogenie cyst" because of the pres- ence of both secretory elements and stratified squamous epithelium (50), The u,se of this name might, however, lead to confusion with the mueoepider- moid eareinoma, and is therefore un- likely to find favour,

PADAYACHEE & VAN WYK (46),

who

u.sed the term 'sialo-odontogenie cyst", reported two eases whieh resetnbled both the botryoid odontogenie eyst and the central mucoepidermoid tumour of the jaws, but after a careful analysis concluded that they differed suffieiently to warrant separation as an entity.

GARDNHR ('/ al. (47), who favoured

the

name 'glandular odontogenic cyst', sug- gested also that its histological features and biological behaviour are sufficiently distinct for it to be regarded as an entity.

PATRON ct al. (51)

reported

3 new

eases and summarized the data from 13 eases. The age range was 19 to 85 years. 9 of the 13 cases were in men and 10 oecurred in the mandible. Radiologieal- ly the lesions have been well-defined with a unilocular or multiloeular pattern but without specific diagnostic features, TTiree of 10 eases that have been followed up have recurred. Radiographs may show a unilocular radiolueent area with a smooth eortieat- ed margin or may be more extensive and multiloeular, T"he roots of adjaeent teeth may be displaced. The microscopie features are vari- able. The cyst may be lined in parts by

a non-keratinized stratified squamous

epithelium with a chronic inflammatory infiltration of the connective tissue wall, the same as is found in a radicular eyst.

The diagno.sis is made when the superfi- eial layer ofthe epithelial lining consists

of columnar or euboidal eells. occasion-

ally with cilia, and the epithelium has a glandular or pseudoglandular strueture. with intraepithelial crypts or mierocysts or pools lined by cells similar to those on the surface. In certain planes of sec- tion these mierocysts may be seen to open onto the surfaee of the epithelium through openings or crypts, giving the epithelium a papillary or corrugated surface. They are sometimes empty and sometimes contain a structureless eosin- ophilie material whieh gives a positive mucicarmine reaction. Numerous gob- let eells may be present, mainly in the superficial part ofthe epithelium. Occa- sionally the epithelium is thinner, sim- ilar to redueed enamel epithelium. Epi-

thelial thiekenings or plaques may be present in either this thin epithelium or in the stratified squamous epithelium. The plaques, whieh are idetitieal to those in the gingival cyst of adults, the lateral periodontal cyst and the botry- oid odontogenic cyst, may either pro- trude into the cyst cavity or extend into the connective tissue wall. Islands of odontogenic epithelium and even miero- cysts may be pre.sent in the connective ti,ssue wall of the cyst. Irregular calcifi- cations may be present in the connective tissue wall.

Treatment

Despite the paueity of documented ex- amples of this eyst. the available infor- mation suggests that, like the botryoid odontogenic cyst, it should be carefully excised rather than enucleated in order to obviate recurrence,

Dentigerous cyst

Frequency

In the 32-year period 1958-89. 433 of 2616 jaw cysts recorded in our depart- ment have been dentigerous eysts (16.6%). This means that we are seeing about 14 cases a year and, as our mate- rial is drawn from a number of sourees. individual surgeons and departments are apparently dealing with far fewer than this number eaeh year,

Pathogenesis

Some further work has been done re- cently to elucidate the pathogenesis of the dentigerous cyst but we are no eloser to knowing what triggers the process. Despite the faet that in mouse molar tooth transplant experiments (52 56) cysts fortn within the enamel organ of the developing tooth, it seems that in humans the cyst develops between the redueed enamel epithelium and the erown of an unerupted tooth in certain cyst-prone individuals; and it is likely that a genetie faetor contributes to the process, although this has yet to be dem- onstrated at a molecular level. Another tnode of origin which has been proposed is that the crown of a permanent tooth may erupt into a radic- ular cyst of its deciduous predecessor. This phenomenon probably does oecur, but only exceptionally rarely, beeause radieular cysts involving the deciduous dentition are so uncommon (57), In sueh a ease the erupting tooth may in- dent rather than penetrate the wall of

the radieular eyst and this sould be ap- parent histologically, if not macro,scopi- cally (58, 59),

A variation of this coneept is that

infiammation at the apex ofa deeiduous tooth can lead to the development of an infiammatory follicular cyst around the permanent sueees.sor (61, 62). BI:NN'S 1991 study (62) ineltided 15 patients ranging in age from 5 to 12 years. In 12 cases the infiammation arose from a non-vital deciduous predecessor, while two patients had Garre's osteomyelitis. The mandible was involved in 10 cases and the maxilla in 5, The premolar teeth were associated with the eysts in 9 eases, the eanines in 3 and the second molars in 2 cases, presumably in the patients with Garrc's osteomyelitis. Maeroseopi- cally, all the eysts were attached to the necks of teeth showing virttially no root formation, Histologieally. the most commonly occurring feature was the presence of non-keralinied stratified sqtiamous epithelium of varying thiek- ness with focal areas of arcading. All cases showed some degree of infiamma- tion.

There would appear thus to be some evidenee of an infiammatory etiology in the pathogenesis of some denligerous eysts. Nevertheless, individual cases need to be assessed critically. The eyst wall must surround the crown of the associated tooth and be attached to the neck; and microseopieally, the cyst lining should demonstrate a readily identifiable component of reduced enamel epitheliutn befote a diagnosis of dentigerous cyst is made. Most of the eases reported by SHAW ct at. (60) were resolved after extraction ofthe involved primary tooth and curellage of the socket.

The experimental work of AI.TINI & COIII:N (19, 20) demonstrated that erupting teeth may penetrate epithelial lined-eysts and in (his way give rise to follicular keratoeysts. Reeent work has developed earlier studies whieh showed that vital eyst tissue in eulture releases a potent bone- re.sorbing faetor that is predominantly a mixture of prostaglandins B, and E, (63 66), The source of this resorbing factor was thought to be the capsule and its leucocyte content.

MA nuKA ('/ al. (bl) have made some

observations on dentigerous eysts. The two dentigerous cysts they investigated were the only two in their sample of 12 in which they found prostaglandin F,,,. Using radicular and dentigerous cysts. MiXiiiJi ('/ al. (68) demonstrated

Developmental odontogenic cysts

7

the synthesis in vitro ofa inaerotnolecu- lar faetor with osteolytic aetivity which has the eharaeteristies of interleukin I, They believed that the souree of the in- terleukin eoukl be the monoeyte/mae- rophage infiltrate, the strotnal fibro- blasts and the epithelial eyst linings; and that the interleukin 1 released by the cysts eould lead to a nutnber of osteolyt- ic cell reactions; the stimulation of os- teoelasts to tesorb botie. and the eon- neetive tissue cells to produee prosta- glandins which will be responsible for further osteoelast activation. It also stimulates eonneetive tissue cells to pro- duce collagenase whieh is involved in the destruelion of bone matrix.

Histoiogy

Iinnuinohistochemieal studies have been done on dentigerous eysts by a number of workers in the field, Undif- ferentiated epithelium lining dentiger- ous eysts. like redueed enamel epitheli- um of dental follicles, yielded eonsis- tently negative results for blood group antigens A and B in the hatids of

WRIGHT (69),

However, VHOTOI ii: ct al.

(70) were able to demonstrate the A. B and H type 2 antigens in dentigerous as well as in radicular and keratoeysts. They aseribed the variation between their findings and those of WRKiiir (69) to technical and sampling differences,

GARDNIR

&

O'Niiii

(71)

also

found

that 5 of 7 dentigerous eysts whieh they

studied were markedly positive lor blood group antigens A. B and H type 2. Two exhibited only a few positive cells.

MArriiivvs

HoKMiA Ct <d. (27) and

('/ al. (28) used iinnnrnohistoehernieal staining with monoclonal antibodies to study and eornpare the eytokeratin eon- tenl of odontogenic cysts. Results on dentigerous eysts in the two studies that coincided, were the demonstration of cytokeratin 19 in all speeimens and in cells at all levels; and cytokeratins 13 and 16 (although there was variation in staining intensity between samples). MAIHIIW S ct al. (28) found cytoker- atins 8 and 18 poorly expressed, where- as HORMIA ct al. (27) reported vari- ability in their staining reaetion. Both groups agreed on the absence of kera- lins 10 and II. MAIIHIAVS ct al. (28) detected careino-einbryonic antigen (CEA) and epithelial membrane antigen (EMA), partietrlarly the latter, in the majority of epithelial cells lining dentig- erous eysts; rat liver antigen (RLA) was expressed by the majority of suprabasal

cells in all linings and oeeasionally in all layers, HORMIA ct al. (27) pointed out that their results indicated that dentigerous eysts. but not other eyst types, may shate with sotne eases of atneloblastoma the expression of eytokeratin 18, The cytokeratin 18-positive eells eould have

a speeifie histogenetie origin and eould

eonsequently have distinet functional eharaeteristies. Another possibility, they suggested, is that the expression of eyto-

keratin 18 in dentigerous cysts is a sign of oncofetal transformation in these lesions. Further studies are required to determine whether the presenee of eyto- keratin 18 in dentigerotts eyst epitheli- um might be associated with aineloblas- toinatous ehanges in the eyst.

Unicystic ameiobiastoma

A nurnber of workers have referred to

the oecurrenee, in part ofa dentigerous eyst lining, ofa mural nodule of prolif- erating epithelium which elosely resem- bles a plexiform ameloblastoma (72 76), The nodule protrudes into the

eyst eavity and varies in size but gen- erally shows either no. or only limited, infiltration into the eonneetive tissue eapsule, GARDNIIR (74) regarded these lesions as ameloblastomas, although he suggested that they require only eon,ser- valivc trealineiit and propo,sed the term plexiform unicystic ameloblastoma. The use of this term has been regarded as unfortunate (39) because of its similari-

ty to the tenn 'plexiform ameloblasto-

ma' and beeause the eysts do not exhibit

the criteria in the epithelium deseribed

by

VicKr Rs & GoRi.rN (77) as itulieative

of

ameloblastoma, I have also been crit-

ical of the reference to this lesion as an ameloblastoma. as it was not infiltra- live. and suggested that it might be termed 'odontogenie papilloma" (2) and PHM IPSI-N (per s eornrn) refers t o it a s ameloblastoniatous hyperplasia. Never- theless the pathologist should examine numerous parts of sueh a eyst wall in order to exelude the possibility of infil- trating plexiform ameloblastoma else- where,

GARONI-R & CoRio (75. 76) have eotinter-ed this eritieisin by reporting cases of unieystie ameloblastoma that exhibit both patterns, namely a plexi-

form nodule and plexiform ameloblas- toma in the same lesion. In their 1984 study, they reported their findings in a .series of 35 ca,ses. Of 28 examples treat-

ed by enueleation or etirettage. only 3

which is a rntieh lower

reeurred (10,7"'

).

reeurrenee rate than that reported for typieal solid or tnultieystie ameloblasto- mas. They eautioned that cases should nevertheless be followed for at least 10 years after treatment beeause of the small proportion that do recur. They believed that the plexiform unieystie ameloblastoma should be regarded as a histologic variant of unieystie amel- oblastoma as its biologieal behaviour was no difierent frorn the others. Another point of interest in their se- eond paper (76) is that they identifed 4 eases of plexiform unieystie ameloblas- totna whieh were not in a dentigerous relationship with a tooth. We have undertaken a detailed study of the unicystic ameloblastomas in our department (78), In a series of 380 amel- oblastomas reeorded during the 30-year period 1958-1987. 57 (15%") were classi- fied as unieystie, Mieroseopieally, three distinet pat- terns eould be identified, on the basis of whieh the sample was divided into 3 groups. Group I eoinprises uniloeular eystic lesions whieh are lined to a greater or lesser extent by epithelium whieh shows eriteria defined by VKKI-.RS & GORLIN (77) for the diagnosis of ameloblasto- matous epitheliutn. These are eolurnnar basal eells with hyperehromatie nuclei, nuelear palisading with polarization, and cytoplasmic vacuoles with intercel- lular spaeing. Group 2 comprises uniloeular eystie lesions in which a mural nodule arises from the epithelial lining and projects into the lumen of the eyst. The nodule consists of odontogenic epithelium with a plexifortii pattern whieh elosely resetn- bles that seen in the plexiform amel- oblastoma. Part of the cyst lining may demonstrate the Viekers-Gorlin eriteria, but there is no evidence of infiltration of the fibrous eyst wall by odontogenie epithelium. Group S comprises unilocular cystic lesions in whieh invasive islands of ei- ther follieular or plexiform ameloblasto- ma. w hieh may or may not be eonnected to the epithelial lining of the eyst. are found in the fibrous wall. Substantial portions ofthe cyst lining in all 3 groups may laek the cytologieal features which are typieal of atneloblas- toma. and may instead be lined by a non-specifie epitheliutn ranging from one with only 1-2 cell layers to an acan- thotie stratified squamous epithelium, Stieh cases will pose problems in histo- logieal diagnosis and eognizance must be taken of clinical and radiological de-

8

SHEAR

tails. It is also essential to sample multi- ple areas from the specimen before mak-

ing a definitive diagnosis. SAKU et al.

(79) reported that staining for the lectins Ulex europaeus agglutinin I (UEA-l) and Bandeirea simplicifolia agglutinin I (BSA-I) assisted in the differentiation between eystic ameloblastoma and odontogenie cysts. Using a substantial sample of ameloblastomas, keratocysts, dentigerous cysts and radicular cysts, they found that in the simple cysts most of their specimens showed positive bind- ing with UEA-I and BSA-I in the epi- thelial linings. No positive reactions were obtained for these two lectins in the epithelium of the ameloblastomas, except for limited UEA-I binding to keratinized cells in 4 cases. With regard to the question of wheth- er these lesions develop dc novo or arise in existing odontogenic cysts, partic- ularly dentigerous cysts, ACKERMANN ct al. (78) pointed out that only a small number of their series were associated with the crowns of unerupted teeth in a true follicular relationship and there was no evidence at all that any other odontogenic eyst existed prior to the development of the lesions. As far as treatment is concerned, ACKERMANN ct al. proposed that Groups I and 2 may be treated conservatively, while Group 3 must be treated aggressively in the same manner as solid and multieystie ameloblastomas.

Eruption cyst

There have been no new papers on the subject of eruption cyst in recent years,

Caicifying odontogenic cyst

There have been some noteworthy pub- lications on this subject during the past decade (80-88).

Frequency

Despite the fact that the calcifying odon- togenic cyst is now a well-recognized lesion, it is not very commonly encoun- tered. We see only one or two ca.ses a year in our department and regard the lesion as extremely rare. During the 32-year period 1958 89. 25 examples were re- corded in our archives, representing V'Ai of 2616 jaw cysts doeumented during that period. In his literature review of 215 cases, Bw HNER (86) pointed out that there have been about five times as many central lesions reported in the literature as peripheral lesions.

Age

The observation that there is a distinct peak in the second decade has been eon- firtned in the extensive literature review of 215 lesions reported by BUC"HNI:R (86), PR/ETORIUS et al. (80) have drawn attention to the bimodal age distribu- tion in support of their contention that two different entities may be involved, SHAMA.SKIN ct al. (82) found that of 5 extraosseous lesions, 4 were in patients over 50 years, while in their literature review of 29 extraosseous eases, KAIJG- ARS ct al. (88) found that 16 patients were in their sixth decade or older. However, in their study of the peripher- al calcifying odontogenic cyst, BUCHNER et al. (85) observed a bimodal age distri- bution with peaks in the second and sixth decades.

Site

Again referring mainly to the peripheral lesions of the .series of 29 extraosseous ca,ses documented by KAUCJARS ct al. (88), about one-half developed between the canines and none was posterior to the first molar; in the study of BUCHNER ct al. (85), most ofthe peripheral lesions were located in the maxillary or man- dibular gingiva or alveolar mucosa an- terior to the first molar.

Pathogenesis and pathology

The histologieal features of a classic calcifying odontogenic cyst are eharac- teristic and present few diagnostic prob- lems. Elueidation ofthe pathogenesis is, however, considerably complicated by the fact that the epithelial lining of a calcifying odontogenie eyst appears to have the ability to induce the formation of dental tissues in the adjacent connec- tive tissue wall; and that other odonto- genic tumours sueh as the ameloblasto- ma, the odontoameloblastoma. the ameloblastie fibroma and the amelo- blastie fibro-odontome may sometimes be associated with it. It is widely accept- ed that those calcifying odontogenie cysts which have other features of odon- togenic tumours develop these second- arily, rather than that they are them- selves secondary phenomena in pre-ex- isting odontogenic tumours (80. 83). pR/T'TORius ct al. (80) suggested that the calcifying odontogenic cyst is a unicystic process which develops from reduced enamel epithelium or remnants of odon- togenie epithelium in the follicle, gingi- val tissue or bone. Dentinoid alone, or

an odontome, may be found in the cyst wall, induced by the lining epithelium. They classified these as Type I, whieh may have 3 different patterns; Type I A, the simple unieystie type; Type 1 B, the odontome-producing type; and Type IC, the ameloblastomatous proliferat- ing type. The neoplasm which pos,sesses some of the histological features of the calcifying odontogenic cyst should, in the opinion of PR/f;T()RitJS ct al. be re- garded as a .separate entity, and they have classified it as Type 2. It occurs in older patients and consists of amel- obla,stomatous epithelium in whieh the development of cysts is a secondary fea- ture. Areas of ghost cell formation and varying amounts of dentinoid are in- dueed by the odontogenie epithelium. They have suggested the term 'dentino- genie ghost cell tumour' for this neo- plasm, I have seen a ease of this type in which enamel as well as dentine was found. HiR.snBER(; ct ai (89) reviewed the literature and identified 6 eases reported as calcifying odontogenie cysts which were solid masses with or without amel- oblastomatous proliferation and with- out any association with other odonto- genic tumours. In their review of'odon- togenic ghost cell tumours'. COI,MI:NI:RO ct al. (90) observed two different enti- ties; one with infiltrating odontogenic epithelium and ghost cells which was locally aggressive like the ameloblasto- ma; and the other which was malignant with potential to metastasize. The latter entity is best deseribed as an 'odonto- genic ghost cell carcinoma' (91). S(OIT & WooiJ (92) reported a case with ameloblastomatous and basaloid fea- tures which behaved aggressively, and believed that as sueh a tumour has rnore in eommon with an ameloblastoma than a caleifying odontogenie eyst, its diagnostie designation should adequate- ly refiect this. They propo.sed the term 'dentinogenic ghost-eell ameloblasto- ma,' I concur with this view and would suggest that the rare cases with enamel deposition as well as dentine, should be termed 'odontogenic ghost eell amel- oblastoma' in keeping with the pattern used in the World health Organization classification of odontogenic tumours

(1).

The caleifying odontogenic cyst is most frequently a uniloeular lesion but multieystie lesions have been reported (86. 87), Satellite cysts may develop from odontogenie epithelial islands in the wall (83), In the sttidy of the periph- eral lesions by BUCHNER et al. (85), two-

Developmental odontogenic cysts

9

thirds were eystie and one-third were solid. The satellite cyst described by TAKI-PA ('/ al. (83) could be grouped into the same 3 histologieal types deseribed by PR/ITORKIS ct at. (1981), but these did not always eoineide with the typing of the mother cyst.

Treatment

The calcifying odontogenic eyst is treat- ed by surgical enucleation unless it is assoeiated with another odontogenie tu- mour such as an ameloblastic fibrotna, in which case wider excision will be re- quired. In the presenee of a complex odontome, conservative removal will still be adequate. An ameloblastoma or one of its variants with foei of ghost cells must be treated radieally. Although classic uncomplicated cases of calcifying odontogenic cyst may grow to a large size, reported recurrences are rare,

Acknowledgement I am most grateful to DR J. J. Hir.i.i:, Head ofthe Department of Oral Pathology. University of ihe Western Cape, who kindly tiiadc available the facilities of his department.

References

1.

KRAMIiR

IRH . PlNDDORti

J.I . SlllAR M ,

tumor'.' J Oral Ma.xiltofae 5«r? 1984; 42,- 10 9.

carcinoma syndrome, J Oral Pathoi

1988;

17: 39

42 ,

10. DoNATii K . Odontogene un d

nicht-

26 .

SivirTH G. SMirir AJ. BASU MK Mast cells

odontogene Kicferzysten. Otseli Zalin- iirtzl 7. 1985; 40: 502 9.

in human odontogeriic cysts. J Orai Pa- thol Med 1989: 18: 274^8,

11. PARiRiiKii; M . TowriRs Ji-. Th e primor-

Br J Oral Maxillofae Surg 1987; 25:

27 ,

HORMIA

M . YUPAAVAI.NIEMI

P. NAOLE

dial cyst (odontogenic keratocyst); its tu- mour-like characteristics and behaviour.

RB. ViRTANKN I, Expression of cytoker- atins in odontogenic jaw cysts: mono- clonal antibodies reveal distinct varia-

271 9,

12. VcxjRSMtr RACA, The ineredibie kerato-

tion between different cyst types, J Oral Pathol 1987; 17: 338 46.

cyst. M,D, Thesis. Naarden: Los Print-

28.

MATTHEWS

JB .

MA.SON

GI .

BROWNE

ers. University of Nijmegen. 1984, 1,1. W(X)ixiAR JA. Rrr-PiN JW. BROWNE RM, The odontogenic keratocyst and its oc- currence in the nevoid basal cell carcino- 29, ma syndrome. Oral Surg Orai Med Oral Pathol 1987; 64: 727 30.

14. WoorxfAR JA , RirMMN

JW, BROWNK RM ,

A comparative study of the elinical and

histological

non-recurrent odontogenic keratocysts,

J

features

of recurrent

and

Orai Pathot

1987; 16: 124 8.

30,

15.

SciiARriKTriiR

LAHRANCit; W. Koni:Rii W . MinERMAYUR

CH, Proliferation kinetics-study of the 31, growth of keratocysts, J Cran-Max-Fac Surg 1989: 17: 226 33,

K.

BAI.Z-HKRRMANN

C .

16. SMirir Ci. SMITH AJ. BROWNE RM . Gly-

cosaminoglyeans in fluid aspirates from 32, odontogenic cysts. J Oral Patiioi 1984;

13: 61 4

21 .

17. SMirir G . SMITH AJ . BROWNE RM . His-

tochemical studies on glycosaminogly- 33, cans of odontogenie eysts. J Oral Pathot

18.

1988:

17: 55 9.

SMITH

G ,

SMITH

AJ,

BROWNE

RM ,

Quantification and analysis ofthe glyco- ,saminoglyeans in human odontogenie cyst linings. Arch Orat Biol 1988; 33:

33a

623

6,

34.

Al itNi M . COHEN M . Th e follicular pri-

mordial cyst (odontogenic keratocyst), //(/./ Oral Surg 1982; 11; 17.5 82.

At ttNi M . CoritN M . Experitncntal ex-

tra-follicular histogenesis of follicular

cysts, J Oral Pattiot 1987: 16: 49 52 .

MAiKENzrE GO , OATrs GW . MuttriN MP. GRISU'S RJ . Computed loniography

in the diagnosis of an odontogenic kera-

tocyst. Oral Surg Orai Med Oral Puihoi 1985; 59: M)2 5.

BROWN

for cancer deaths.' New .Scientist 1990;

127, No. 1733. 27. Coninicnt on the re-

P. 'Unneces.sary

X-rays blamed

35.

36.

37,

port Patient Dose Reduction in Diagnos- tic Radiology. National Radiological Protection Board, HMSO. 1990,

W<X)HiAR JA, RiPiMN JW. BROWNt: RM.

A comparative

odontogenic keratocysts in basal cell

/

naevus syndrotnc and control Oral Paihol 1987; 16: 75 80.

W(H)i (JAR JA . Rri'PiN JW. BROWNE RM .

A comparative study of the clinical and

histological

non-recurrent odontogenic keratocytsts. ./ Orat Patiiot 1987; 16: 124 8.

DoMlNdiiEZ FV. KrszriR A . Compara- tive study of keratocysts. associated and non-associated with nevoid basal cell 41 ,

40.

histological

39,

38.

study

of

patients

and

39a.

features

of recurrent

RM. Epithelial cell markers and prolifer- ating cells in odontogenie jaw cysts. J Pathoi 1988; 156: 283 90,

SHULER

CF . SHRIVER

BJ,

Identification

of intermediate filament keratin proteins in parakeratinized odontogenic kerato- cysts, Orai Surg Orai Med Orai Patiioi 1987; 64: 439 44,

KuustiLA p. HORMIA M . TIIOMIV H . YM -

PAAVALNiEMi P, Demon.stration and par- tial characterization of a novel soluble antigen present in keratocysts, Oncodev Bioi Med 1982; 3: 283 90, '

THES-

KUUSKLA

u-EEE I, Th e relationship between the keratocy,st antigen (KCA) and keratin. J

Orai Patiioi 1986; 15; 287

DoLJCiLAS CWI. CRAIG GT . Recognition

of protein apparently specific to odonto- genic keratocyst fluids. J Ciin Patiiot

P.

YtJPAAVALNIKMI

91 .

P.

1986; 39: 1108

15.

Douca.AS CWI. CRAIC; GT. Evidence for the presence of laetoferrin in odontogen- ic keratocyst lluids, J Clin Pathol 1987; 40; 914 21, . Doucr.AS CWI. CRAK; GT. Quantitation

of laetoferrin in odontogenic eyst fluids.

J ctin

SMITH

BROWNE RM .

ing cells in human odontogenic cysts. J Oral Pathol 1987; 16; 45 8.

Imniunoglobulin-produc-

Pathol 1989; 42: 180 3.

G .

MAITHEWS

JB .

SMITH

AJ.

WYSCKKI

GP . BRANNON

RB . GARDNER

DG. SAI'P P. Histogenesis of the lateral periodontal cyst an d the gingival cyst of the adult. Oral Surg Oral Med Orat Pa-

thol 1980; 50: 327 34 .

NxuMALO TN . SHEAR M . Th e gingival cyst of adults, J Orai Pathol Med 1992; 21: 309-13.

ALTiNr M . SHEAR M , Th e lateral perio-

dontal

Med 1992; 21: 24S .50. Buc HNER A . HANSEN LS. Th e histomor- phologic spectrum of the gingival cyst in the adult. Oral Surg Orat Med Oral Pa- thot 1979: 4S: 532 9. SHAIER WG. HiNE MK . Livv BM . ,4 textbook of oral pntiiology. 4th cd. Phila- delphia and London: Saunders, 1983.

SHEAR M . Cysts of the orcil regions. 3rd cd. Oxford: Wright Butterworth-Heine- tiiann, 1992.

HErKiNHirMO

cyst: an update.

./ Oral

Pathol

K,

Ki'usriFHT O

HAPPONKN

R-P . FORS-

SEi r

K .

A . VIRTANE N I . A

botryoid odontogenic cyst with multiple recurrences. Int .1 Oral .^taxiltotac Surg

1989:

18: 10

3.

WEATHERS DR ,

WAIIIRON

CA , Unusual

///.•itotiiginil ty/'ini; of oilontogcnie tu- mours ik-rliti: Spritiger Vcrlag. 1^92.

2.

Sill

AR M . Cysts of the

jaws: recent ad-

19.

vances. J (hat Pathot ms,*;; 14: 4,^ 59 .

3.

VooRSMir RAC'A. Sioi i iN(iA PJW. VAN

ilAi i.si U,ICiM. Tin; matiitgetnent ol'ker-

20.

atocysts.

./

Maxillofac .'iwg 1981; 9:

22X Ml.

4.

loRSSi I I K . I-oR,s,si;i I H. KAiiNtu RI; K -

21.

i;. Rccirrrcncc of keralocysts, A long- term follow-tip study, /lit J Ma.xitloftic Ora/,S"i»x 1981; «7: i s 8.

5.

NttMi.viR

K . ScHt.iKN H-P, HAHI:I, G ,

Ml

Ni l i.R C \ Bchandlungscrgcbtiiss c iiti d

22.

I,angzcilbeobaclitttiigen bei 62 I'atictuen tiiit Kerato/ysrcti. Dtscti /.uhniirtzt '/. 198,5; 40: 6,^7 40.

6.

BRONDtiM N , JiNsiN VJ. Recurrence ol' kcrati'cysts and decompression treat- ment. A long-term follow-up of lorly- finir cases. Oral Surg Orat Med Oral /'<;- Ihot 1991; 72: 265 9.

23.

1.

Vl rrroi ri P. i»R/i loRriis I . Rcctirrencc

of

the

odontogenic keratocyst in relation to

 

clinical and histological features. A 20-

24.

ycar lollow-up sttidy of 72 patients. Int

J

Oral Surg 1979; 8: 412 20.

 

8.

H)Rs.si 11 K. The primordial cyst. A clin- ical and radiographic study. I'roc Finn Denl .Soc 1980; 76: 129 74.

25.

9.

Am loRS !•;. LAR.SSON A. SKXiKPN S. Phc odontogenic keralocyst: a benign cystic

10

SHEAR

multiloeular eysts of the jaws (botryoid odontogenic cysts). Orai Surg Orat Med Orai Pathol 1973; 36: 235 41 .

42. VAN DER WAAI. I. Lateral periodontal

eystlike lesion a discussion of the so- called botryoid odontogenic cyst. J Dent A.s.-iS Afr 1992; 47: 231 3. 42a. LrNDH C. LAR.SSON A. Unusual jaw-bone eysts. J Oral Maxillofac Surg 1990; 48:

258-63.

43. KAUGARS GE . Botryoid odontogenic cyst. Oral Surg Oral Med Oral Pathol 1986; 62: 555 9.

44.

GREER

RO .

JOHNSON

M .

Botryoid

mental dentigerous cysts and enamel hypoplasia: Iheir possible significance in explaining the pathogenesis of human dentigerous cysts. J Oral Pathol

1980;

9: 82

91,

57. LiisTMANN J. SHEAR M . Radicular cysts arising from deciduous teeth. Review of the literature and report of 23 cases, Int J Oral .Surg 1985: 14: 153-61.

58.

GEHHARDT

P, LENZ

W , Zur

Frage

der

follikularer Zysten im Wech-

sclgebiss durch Wurzelbehandlung von Milch/ahnen, Dt.sch Zaimiirtzl /. 1985:

40:

Induktion

541 3,

 

odontogenic cyst: clinicopathologic analysis of ten ca.ses with three recur- rences. J Oral Maxiihfac Surg 1988; 46: 574 9.

59. Wofji) RE . NoRTjfe CJ . PADAYACHEE A . GROTEI'ASS F . Radicular cysts of pri- mary teeth mimicking premolar dentig- erous cysts: report of three cases. J

45. MACHADO

D E SOU.SA SO . CAMKW

AC .

Dent Child 1988; 55: 288 90.

 

SATIACiO

JL . jAKCiKR

RG . CAVA U ANTI

60.

SHAW

W , SMITH

M . Hir.i.

F.

Inflamma-

DE ARAOJO V, Botryoid odontogenic

tory follicular

cysts.

./ Dent Child 1980;

cyst: report of a ca.se with clinical and hi.stogenetic considerations, Br J Orai Maxillofac Surg 1990; 28: 275 6,

47: 97 101.

61. MAIN DMG . Epithelial jaw cysts: 10 years of the WHO classification. J Oral

46 .

PAIMVAf flEE

A ,

VAN

WvK

CW . Tw o

Pathol 1985; 14: 1 7.

cystic lesions with features of both the botryoid odontogenic cyst and the cen- tral mucoepidermoid tumour: sialo- odontogenic cyst? J Orai Pathol 1987; 16: 499 504.

62. BENN AML . Th e role of deciduous teeth in the pathogenesis of odontogen- ic cysts. MSc (Dent) re.search report. University of the Witwatersrand, Jo- hannesburg. 1991.

47.

GARDNER

DG .

KESSI.ER

HP,

MORENCY

63. HARRIS M . GOEDHAHI:R

P, The

produc-

R, ScHAfTNER DL . The glandular odontogenic cyst: an apparent entity, J Oral Pathol 1988; 17: 359 66.

 

tion of a bone resorbing factor by den- tal cysts in vitro, Br J Oral Surg 1973; 10: 334- 8.

48.

WALIJRON

CA .

KoH

ML .

Central

mu-

64. HARRIS

M ,

JENKINS

MV,

BENNETT

A.

coepidermoid carcinoma of the jaws:

 

WriLs MR . Prostaglandin production

report of four ca,ses with analysis of the

and bone resorption by dental cysts.

literature and discussion of the rela-

Nature 1973; 245: 213 5.

65. HARRIS M . TOILER

P. The

pathogenesis

tionship to mucoepidermoid, sialodon- togenie, and glandular odontogenic

of dental cysts. Br Med Bull 1975; 31 :

cysts. J Oral Maxillofac Surg 1990; 4«:

159 63.

871 7.

66.

HARRIS M . Odontogenic cyst growth

49.

FifARRA

G .

CHOU

L ,

PANZONI

I;.

and prostaglanding-induced bone re-

Glandular odontogenic cyst (sialo-

 

sorption, .inn R Coll Surg Engt 1978;

odontogenic eyst). Int ,/ Oral Maxillo-

60: 85 91.

fac

.Surg 1990; 19: 331 3.

 

67. MATI.JKA M , PORTEDER H , KI.KINERI

50.

SAOKGHI

EM . WEIJX)N

LL .

KWDN

PH .

SAMPSON E , Mucoepidermoid odonto- genic cyst, /nt J Orat anil Maxittofac .Surg 1991; 20: 142 3.

51 PATRON M . COLMENERO C . LARRAURI J.

Glandular odontogenic cyst: clinieo- pathological analysis of throe cases. Oral .Surg Oral MetJ Oral Pathol 1991 72: 71 4 .

52. ATKINSON ME , A hi.stological study o f tooth grafts in an inbred strain of mice. J Oral Pathol 1972; 1: 115 24.

53. ATKINSON MB. A histological study of odontogenic cysts Tormed following mouse molar tooth transplantation. J Oral Pathol 1976; 5: 347 57.

54.

ATKINSON

ME .

An

autoradiographic

study of experimental odontogenic cyst

formation

in the mouse. J Oral Pathol

1977;

6: 382 6.

55.

56.

RIVIERE

GR ,

SABET

TY . Experimental

histologic

study. Oral Surg Oral Med Oral Pathol

in mice

follicular

cysts

a

1973;

36: 205

AL-TAI,ABAM

13.

NG .

SMITM

CJ.

Experi-

W. Ul.RK M W. WAT/EK G , SrNZrNGER

H. Evidenee that PGl,-generation in

human dental cysts is stimulated by leukolrienes C , and D,. J Maxillofac

Surg 1985; 1.1: 93 6.

In-

68. MixiiiM

S,

HARVEY

W

HARRIS

M.

terleukin I-like activity in cystic lesions of the jaw. Br .1 Oral Maxillojac Surg

19H9;

27:

1

II .

69. WRK;HT JM . The A an d B blood group

substances on odontogenic epithelium.

70.

71.

J

Dent

Res 1979: 58: 624 8.

VEDTOITE

P .

PiNDBORCi

JJ.

HAKOMORI

SI. Relation of blood group carbohy-

drates to differentiation patterns of normal and pathological odontogenic epithelium, APMIS Sect A 1985; 93 :

25 34,

GARDNER

DG ,

O'NEILI

PA.

Inability

to distinguish ameloblastomas from

odontogenic cysts based on expression of blood cell carbohydrates. Oral Surg Oral Med Oral Pathol 1988; 66; 480

2.

72. RoRiNSON L. MARTINIZ MG . Unicystic

ameloblastoma.

A

prognoslically dis-

tinet

entity.

Cancer

\911\ 40: 2278-

85,

73.

SHTEYER

A .

LUSTMANN

J.

Li:wi.s-Ki'-

STEIN J, The mural ameloblastoma: a

Surg

review

of the literature.

./ Oral

1978;

36: 866 72.

74. GARDNiiR DG . Plexiform unicystic ameloblastoma: a diagnostic problem in dentigerous cysts. Cancer 1981: 47:

1358 63,

75. GARDNER

DG .

CORIO

RL.

The

rela-

tionship of plexiform unicystic amel- oblastoma to conventional amelobla.s- toma. Oral .Surg Oral Med Oral Pathol

76.

1983;

56: 54 60,

GARDNER

DG .

CORIO

RL.

Plexiform

unicystic ameloblastoma: a variant of ameloblastoma with a low-recurrence rate after enucleation. Ciiiner 1984; 53; 1730 5,

77. VicKERS RA . GoRMN RJ . Ameloblasto- ma: delineation of early hislopathologic features of neoplasia. Cancer 1970; 26:

699 710.

78. AcKiRMANN GL , At rrNi M . SHEAR M . The unicystic amelohlastoma: A clini-

eopathological study of 57 Pathol 1988; 17: f>4\ 6.

cases.

./ Or<il

79.

SAKtJ T. SiriHATA Y. KOYAMA Z . CHINC;

J, OKAIH: H . YEH Y. Lcclin histochcmis- Iry of cystic jaw lesions: an aid for dif- ferential diagnosis belwccn cystic amel- oblastoma and odontogenic cysts, J Oral Pathol Med 1991; 20: 108 13.

80.

PR;1 lORlUS

F.

HjORTIN<i-HAN,SEN

E .

CioRiiN RJ . VuKERS RA , Calcifying odontogenic cyst. Range, variations and neoplastie potential. Acta Odontol .Scant! 1981: .19: 227 40.

81. NA(iAO Y. NAKAJIMA T . FlJKliSHlMA M . isHiKi T. Calcifying odontogenic cyst: a survey of 23 cases in the Japanese liter-

 

ature ,

J

Maxilto-fac

 

Surg

1983 ;

II :

174 9.

82.

SllAMA,SKIN

RG . SVIR.SKY JA , KAIHiARS

Gi;. Inlraosscous and extraosseous

calcifying odontogenic

cyst.

./ Oral

Maxiltofac Surg 1989; 47: 562 5.

 

83.

TAKEDA

Y . SUZUKI

A,

YAMAMOTO

H .

Hislopathdiogic study of epithelial components in the connective tissue

wall of unilobular type of calcifying

odontogenic

cysl.

./ Oral Pathot Med

1990;

19: 108

13.

84.

BtKiiNER

A,

MERREI I

i'W . CARPENTER

WM, LiiDiR AS. Central (inlraosscous) calcifying odonlogenie cyst. //;/ ./ Oral Ma.xillofac Surg 1990: 19: 260 2.

85.

BUCHNER A,

MERREI.I. PW. HANSI N LS,

86.

LiiiDER AS, Peripheral (extraosseous) calcifying odontogenic cyst. A review of forty-live cases. Oral Surg Oral Med Oral Pathot 1991; 72: 65 70.

A . Th e centra l (intraosseous )

calcifying odonlogenie cyst: an analysis

of

Surg 1991; 49: 3,30 9.

./ O/Y;/ and Maxiltofac

Bu< HNi R

215 ca.scs.

87. HoNCJ SP. hiir s CiL, HARTMAN KS . Calcifying odonlogenie cyst. A review of ninety-two cases with rccvaluation of

Developmental odonlogenie cysts 11

their nature as cysts or neoplasms, the nature of ghost cells, and subclassifica- tion. Oral Surg Oral Med Orat Pathol 1991; 72: 56-64.

88.

KAUGARS CC.

KAUGARS GE.

DEBIASA

GF, Extraossecius calcifying odontogen- ic cyst: report of case and review of lit- erature, JADA 1989; 119: 715-8,

89.

HiRSHBERG A,

DAYAN

D .

HOROWITZ

I.

Dentinogenic ghost eell tumor, Int J Orat Maxillofae Surg 1987; 16; 620-5.

90.

COLMENERO C,

PATRON

M .

COLMENERO

B, Odontogenic ghost eell tumors, J Cran-Max-Fac Surg 1990; 18; 215-8.

91. GRODJEST JE, DOLINSKY HB , SCHNEI-

DliR

LC.

DoLINSKY

EH.

DoYLE

JL.

Odontogenic ghost celi carcinoma. Oral Surg Oral Med Orat Pathot 1987; 63;

576-8L

92, ScxjTT J, Wcx)D GD, Aggressive calcify- ing odontogenic cyst - a possible vari- ant of ameloblastoma. Br J Oral Maxi- llofae Surg 1989; 27: 53-9,