Non-microbial etiology: periapical cysts sustain post-treatment apical periodontitis

18 Pages·2004·1.98 MB·English

EndodonticTopics2003,6,96–113 CopyrightrBlackwellMunksgaard
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ENDODONTICTOPICS2003
Non-microbial etiology: periapical
cysts sustain post-treatment apical
periodontitis
P.N. RAMACHANDRAN NAIR
INMICROSCOPY,ASINNATURE,ONERECOGNIZESONLYWHATONEALREADYKNOWS. Routine
histopathological diagnostic reports and publications based on retrospective reviewing of such, perpetuate the
notionthatnearlyhalfofallapicalperiodontitislesionsarecysts.Studiesbasedonmeticulousserialsectioningofapical
lesionsretrievedintotoshowthattheactualprevalenceofcystsisonlyabout15%ofallapicalperiodontitislesions.
Periapicalcystsexistintwostructurallydistinctclasses,namelythosecontainingcavitiescompletelyenclosedinepithelial
lining(periapicaltruecysts)andthosecontainingepithelium-linedcavitiesthatareopentotherootcanals(periapical
pocketcysts).Fromaclinicalpointofview,smallcysts,particularlythepocketcysts,canhealafternon-surgicalroot
canaltherapywhereaslargecysts,mainlytruecysts,arelesslikelytoberesolvedwithoutsurgicalintervention.
Introduction meaningsacorbladder.Therearediversecysticlesions
in the human body that are commonly categorized as
There isanevolvingconsensusthatthecauseofpost-
congenital, neoplastic, parasitic, retention, implanta-
treatment apical periodontitis associated with well-
tion and inflammatory types. Periapical cysts are
treatedroot-filledteethisthemicrobialinfection(1–4)
inflammatory jaw cysts at the apices of teeth with
persisting in the complex, apical root canal system (5,
infectedandnecroticpulps.
6).Theinfectioncannotbefullyeradicatedbyexisting
instruments, techniques and medicaments. Certain
Incidence
otheretiologicalfactorslocatedbeyondtherootcanal
system,withintheinflamedperiapicaltissue,alsocause The epidemiological prevalence and geographical
post-treatmentapicalperiodontitisbuttheirprevalence distributionofthediseasearenotyetknown.Periapical
is much lower than that of root canal infection. These cystsarethemostcommonofalljawcystsandcomprise
factors include extraradicular actinomycotic infections about 52% (14) to 68% (15) of all the cysts affecting
(7–10), foreign body reaction to exogenous materials the human jaws. Their prevalence is highest among
(11) or endogenous cholesterol crystals and a cystic patients in their third decade of life (14, 16, 17),
conditionofthelesion(12).Thesefactorsarereviewed and higher among men than women (14, 16).
in other articles in this issue. This article is meant to Anatomically,theapicalcystsoccurinalltooth-bearing
provideacomprehensiveoverviewofthepathobiology sitesofthejawsbutaremorefrequentinmaxillarythan
ofperiapicalcysts,theproblemofcystdiagnosisandthe mandibular teeth. In the maxilla, the anterior region
lingeringcontroversyregardingtheabilityofaperiapical appearstobemorepronetocystdevelopmentwhereas
cysttohealafternon-surgicalrootcanaltreatment. in the mandible the radicular cysts occur more
frequentlyinthepremolarregion(18).
Periapical cyst
Diagnosis of cysts
A cyst is a closed pathological cavity, lined by an
epitheliumthatcontainsaliquidorsemisolidmaterial Thedifferentialdiagnosisofcystsfromother formsof
(13). The term cyst is derived from the Greek Kystis apical periodontitis lesions has been extensively
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Non-microbial etiology:periapical cysts
debated over the years (19). Several radiographic thestratifiedsquamousepitheliumand(ii)differentia-
features have been proposed to support a diagnosis, tion of pluripotent cells within the jaw. Most of the
including size of the lesion and the presence of a reported ciliated cell-lined cysts were affecting max-
radioopaquerimdemarcatingthelesion.Althoughthe illary teeth. The close anatomical proximity of the
statisticalprobabilityofcystoccurrencemaybehigher inflammatorylesiontothemaxillarysinusmayresultin
among larger lesions (20), a definite relationship rarefaction of the sinus floor and perforation into the
between lesion size and cystic condition has not been sinuscavity(43,45).Suchperiapicalinflammationhas
supported by histology. Contrary to a claim (21), beenreportedtocausemaxillarysinusitis(52–54).The
periapical lesions cannot be differentially diagnosed lumen of a periapical cyst in the region may even
intocysticandnon-cysticlesionsbasedonconventional communicatewiththesinuscavityashasbeenconvin-
radiographs(16,22–26).Assumingthatcysticcavities cinglydemonstratedinphotomicrographsbyKronfeld
mayhavealowerdensitythanotherapicalperiodontitis (45). Once direct communication is established, a
lesions, computer tomography (27) and densitometry developingperiapicalcystmaybecomelinedpartiallyor
(21) have been used to differentiate these conditions, completelywithciliaryepitheliumofsinusorigin.
but without success. Ultrasonic imaging technique
(echography) has been recently introduced as a
periapical diagnostic method (28, 29). The technique
Prevalence among periapical lesions
seemstobeusefulindetectingfluid,softtissueandthe
real-timebloodflow.Inspiteofthesafetyofultrasound There have been many studies on the prevalence of
andtherelativeeaseofuse,thesonicwavesdonotpass periapical cysts among apical periodontitis lesions
through bone but are reflected back to the sensor, (Table 1). In this literature, the prevalence of cysts
therebyenablingonlydetectionoflesionsthatarenot variesfrom6%to55%.However,accuratehistopatho-
enclosed in bone. Currently, therefore, histological logical diagnosis of radicular cysts is possible only
serialsectioningofthelesionsintotoremainstobethe throughserialsectioningorstep-serialsectioningofthe
onlyreliablediagnosticmethodofperiapicalcysts(30, lesions removed in toto (30). There are only three
31). This, however, can only be applied after surgical studies (30, 36, 55) in which either one of those
removaloftheroottipandperiapicallesion;thus,itisa essentialtechniqueswasused,whilemostoftheothers
posthocdiagnosis. (Table 1) analyzed specimens obtained from wide
sources for routine histopathological reports. The
statistically impressive 2308 lesions in Bhaskar’s study
(16)hadbeenobtainedfrom314contributorsandthe
The cyst epithelium
800 biopsies of Lalonde and Luebke (26) originated
Apicalperiodontitislesionsoftencontainepithelialcells from 134 sources. Such histopathological diagnostic
(32–43) that are believed to be derived from the cell specimens, often derived through apical curettage, do
restsofMalassez(32).Theyproliferateinsomelesions not represent lesions in toto. In random sections from
and are presumed to serve as the major source of the fragmented and epithelialized lesions, part of the
stratified squamous epithelium (14, 31) that lines the specimenscangivetheappearanceofepithelium-lined
lumen of lesions that develop into cysts. Rarely, cavities that do not exist in reality. Indeed, other
however, periapical cysts have also been found to be authors (56) defined a typical radicular cyst as one in
linedpartiallyorpredominantlybyciliatedcolumnaror which ‘a real or imagined lumen was lined with
muco-secretory cells that have respiratory origin (43– stratifiedsquamousepithelium’.
51). In a recent investigation (51), three of the 256 Itshouldbepointedoutthatthephotomicrographic
apical periodontitis lesions examined were cysts lined illustrations (Fig. 3) in several studies (16, 26)
with ciliated columnar epithelium (Figs 1 and 2). represent only magnified views of selected small
However,theoriginofciliatedepitheliuminradicular segments of epithelialized lesions. They are not
cystshasnotyetbeensatisfactorilyclarified.Therehave supportedbyoverviewpicturesoflessermagnifications
beenthreeexplanations(48)forthepresenceofciliated of sequential sections derived from different axial
cells inradicular cysts:(i)migrationof suchcellsfrom planes of the lesions in question. The wide variation
themaxillarysinusorthenasalcavity,(ii)metaplasiaof in the reported incidence of periapical cysts is most
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Fig.1. Aphotomicrograph(a)ofacysticapicalperiodontitis(AP)oftheleftmaxillarysecondpremolarofa34-year-old
malepatient.Notethetwodiverticulaofasmallcysticlumenmagnifiedin(b)andpartoftheepithelialliningenlargedin
(c).Thelumen(LU)islinedwithcolumnarepithelialcells(CEP)withdistinctcilia(arrowheads).D,dentine.Original
magnifications:(a) (cid:1)19;(b) (cid:1)44;(c) (cid:1)500.From(51).Reproducedwithpermission.
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Non-microbial etiology:periapical cysts
Fig.2. Atransmissionelectronmicrographofciliatedcolumnarepithelialcells(CEP)liningofthecysticlumenofthe
lesionpresentedinFig.1.Notethedistinctcilia(CI)andtheneutrophilicgametocytes(NG).FI,fibroblasts.Original
magnification (cid:1)3690.From(51).Reproducedwithpermission.
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Table1. Theincidenceofradicularcystsamongapicalperiodontitislesions
Reference Cysts(%) Granuloma(%) Others(%) Totallesions(n)
Someretal.(82) 6 84 10 170
Blocketal.(83) 6 94 – 230
SonnabendandOh(36) 7 93 – 237
Winstock(84) 8 83 9 9804
Linenbergetal.(25) 9 80 11 110
Wais(24) 14 84 2 50
Pattersonetal.(85) 14 84 2 501
Nairetal.(30) 15 50 35 256
Simon(55) 17 77 6 35
StockdaleandChandler(86) 17 77 6 1108
Linetal.(87) 19 – 81 150
Nobuhara&DelRio(88) 22 59 19 150
Baumann&Rossman(23) 26 74 – 121
Mortensenetal.(17) 41 59 – 396
Bhaskar(16) 42 48 10 2308
Spataforeetal.(89) 42 52 6 1659
LalondeandLuebke(26) 44 45 11 800
Seltzeretal.(56) 51 45 4 87
Priebeetal.(22) 55 45 – 101
Adaptedfrom(31).
probablyduetothedifferenceinthehistopathological account in routine histopathological diagnosis. The
interpretationofthesections.Whenthehistopatholo- majorreasonforthishasbeenthenatureofthebiopsy
gical diagnosis is based on random or limited number itself. Apical specimens removed by curettage do not
of serial sections, most of epithelialized periapical contain the root tips of the diseased teeth, making
lesionswouldbewronglycategorizedasradicularcysts. structural reference to the root canals of the affected
Thisviewisstronglysupportedbytheresultsofastudy teethimpossible.In1980,Simon(55)pointedoutthat
(30) in which an overall 52% of the lesions (n5256) there are two distinct categories of radicular cysts,
were found to be epithelialized, but only 15% were namely those containing cavities completely enclosed in
actuallyperiapicalcysts. epithelialliningandthosecontainingepithelium-lined
cavities that are open to the root canals. The latter was
designated as ‘bay cysts’ (55) and later renamed as
Histopathogical categories of ‘pocket cysts’ (30). It seems that Simon (55) has
observed only the large type of such lesions with
radicular cysts
voluminous cavities, into which the root apices of the
Thestructureofaperiapicalcystinrelationtotheroot affectedteethappearedtoprotrude.Thephotomicro-
canal of the affected tooth has not been taken into graphs in the publication reveal severe damage of the
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Non-microbial etiology:periapical cysts
Fig.3. Roentgenogram (top) and photomicrograph
(bottom) of a ‘radicular cyst’. Note the small selected
segmentofanepithelializedlesion.Itisnotsupportedby
overview pictures of lesser magnification of sequential Fig.4. Root apices in cavities lined by epithelium (E in
sectionsderivedfromdifferentaxialplanesofthelesion. top). Note the severe damage of the micro-anatomical
From(16).ReproducedwithpermissionfromElsevier. relationshipbetweentherootapicesandthecystepithelia
thatmighthaveinfluencedcriticstowonderwhetherthe
‘baycysts’(55)arehistologicalartifacts.Originalmagni-
microanatomical relationship between the root apices fication (cid:1)25. From (55). Reproduced with permission
fromLippincott,Williams&Wilkins.
and the cyst epithelia (Fig. 4). This might have
influenced critics to wonder whether the ‘bay cysts’
(55) are histological artifacts. We (30) analyzed 256 Pathogenesis of true cysts
periapicallesionsobtainedintotowithextractedteeth.
The specimens were processed by a modern plastic- The periapical true cyst may be defined as a chronic
embedding technique, and meticulous serial or step- inflammatory lesion at the periapex that contains an
serial sections were prepared and evaluated based on epithelium-lined,closedpathologicalcavity(Fig.5).The
pre-defined histopathological criteria. Out of the 256 pathogenesisoftruecystshasbeendescribedbyvarious
specimens, 35% were found to be periapical abscesses, authors (30, 31, 33, 57–63). An apical cyst is a direct
50% were periapical granulomas, and only 15% were sequeltoapicalgranuloma,althoughagranulomaneed
periapicalcysts.Equallysignificantwasthefindingthat not always develop into a cyst. Due to still unknown
two distinct classes of radicular cysts – the apical true reasons only a small fraction (o10%) of the periapical
cysts, with cavities completely enclosed in epithelial lesions advance into true radicular cysts (16, 26). The
linings (Fig. 5) and the apical pocket cysts, with cyst- pathogenesis of the true cyst has been described in
lumina open to the root canals (Fig. 6) – could be three phases (14). During the first phase, the dormant
observed at the periapex when the lesions were cell rests of Malassez begin to proliferate as a direct
analyzed in relation to the root canals. An overall 9% effect of inflammation (61, 64), probably under the
of the 256 lesions were apical true cysts and 6% were influenceof bacterial antigens (65), epidermal growth
periapicalpocketcysts. factors(66–68),cellmediatorsandmetabolitesthatare
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Fig.5. Periapicaltruecyst.Photomicrograph(a)ofanaxialsectionpassingthroughtheapicalforamen(AF).Thelower
halfofthelesionandtheepithelium(EPinb)aremagnifiedin(b)and(c),respectively.Notethecysticlumen(LU)with
cholesterol clefts (CC) completely enclosed in epithelium(EP) havingno communication tothe root canal. Original
magnifications:(a) (cid:1)15;(b) (cid:1)30;(c) (cid:1)180.
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Non-microbial etiology:periapical cysts
Fig.6. Periapicalpocketcyst.Axialsectionspassingperipheraltotherootcanal(a,b)givethefalseimpressionofthe
presenceofacystlumen(LU)completelyenclosedintheepithelium.Sequentialsection(c)passingthroughaxialplaneof
therootcanalclearlyrevealsthecontinuityofthecysticlumen(LU)withtherootcanal(RCind).Theapicalforamen
withthecystlumen(LU)ofthesection(c)ismagnifiedin(d).Notethepouch-likelumen(LU)ofthepocketcystwith
the epithelium (EP) forming a collar at the root apex. Original magnifications: (a)–(c) (cid:1)15; (d) (cid:1)50. D, dentine.
Adaptedfrom(90).Reproducedwithpermission.
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releasedbyvariouscellsresidingintheperiapicallesion.
During the second phase, an epithelium-lined cavity
comes into existence. There are two main theories
regarding the formation of the cyst cavity: (i) the
‘nutritionaldeficiencytheory’isbasedontheassump-
tion that the central cells of the epithelial strands
become removed from their source of nutrition and
undergo necrosis and liquefactive degeneration (61,
69–71). The accumulating products in turn attract
neutrophilic granulocytes into the necrotic area. Such
microcavities containing degenerating epithelial cells,
infiltratingmobilecellsandtissuefluidcoalescetoform
the cyst cavity lined by stratified epithelium, (ii) the
‘abscess theory’ postulates that the proliferating
epithelium lines an abscess cavity formed by tissue
necrosis and lysis because of the innate nature of the
epithelial cells to cover exposed connective tissue
surfaces (34, 38). During the third phase the cyst
grows,butwhoseexactmechanismisstillunknown.It
isgenerallybelievedtobebyosmosis.Thepresenceof
necrotic tissue in the cyst lumen attracts neutrophilic
granulocytes, which extravasate and transmigrate
through the epithelial lining (Figs 7 and 8) into the
cystcavitywheretheyperish.Thelyticproductsofthe
dyingcellsinthecystlumenreleaseagreaternumberof
molecules.Asaresult,theosmoticpressureofthecyst
fluidrisestoalevelhigher thanthatofthetissuefluid
(72).Thelatterdiffusesintothecystcavitysoastoraise
the intraluminal hydrostatic pressure well above the
capillarypressure.Theincreasedintracystpressuremay
lead to bone resorption and expansion of the cyst.
However,thefactthatanapicalpocketcystwithlumen
opentothenecroticrootcanalcanbecomelarger(30,
63) suggests against osmotic pressure as a potential
factor in the development of radicular cysts. Further,
there is increasing evidence in support of a molecular
mechanismforcystexpansion(63).TheT-lymphocytes
(73) and macrophages in the cyst wall may provide a
continuoussourceofboneresorptivemetabolites(74)
andcytokines.Thepresenceofeffectormoleculessuch
as matrix metalloproteinase-1 and -2 have also been
reportedinthecystwalls(75).
Fig.7. Composite transmission electron micrograph
showing neutrophils (NG, arrowheads) apparently in
theprocessoftransmigrationthroughtheepithelialwall
ofacyst(EP)intothecystlumen(LU).ST,subepithelial
tissue; PC, plasma cells; MA, macrophages. Original
magnification (cid:1)1600.Adaptedfrom(63).
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Non-microbial etiology:periapical cysts
Fig.8. An intramural scanning electron microscopic view of a cyst luminal wall (LU, in a) enlarged in stages (b–d).
Note the flat epithelial cells (EP) and the globular neutrophilic granulocytes (NG). The latter emerge through
the interepithelial-cell-spaces into the cyst lumen. Original magnifications: (a) (cid:1)20; (b) (cid:1)230; (c) (cid:1)670;
(d) (cid:1)1300.
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