periradicular lesions (chapter 5)

As a consequence of pathologic changes in the dentalpulp, the root canal system can harbor numerous irri-tants. Egress of these irritants from infected rootcanals into the periradicular tissues can initiate forma-tion and perpetuation of periradicular lesions.Depending on the nature and quantity of these irri-tants, as well as the duration of exposure of the peri-radicular tissues, a variety of tissue changes can occur.When the irritants are transient in nature, the inflam-matory process is short-lived and self-limiting.However, with an excessive amount of irritants or per-sistent exposure, the nonspecific and specificimmunologic reactions can cause destruction of peri-radicular tissues.1 Radiographically, these lesionsappear as radiolucent areas around the portal(s) ofexit of the main canal or lateral and/or accessorycanals. Histologically, depending on their stage ofdevelopment, the lesions contain numerous inflam-matory cells such as polymorphonuclear neutrophilleukocytes (PMNs), macrophages, lymphocytes, plas-ma cells, mast cells, basophils, and eosinophils. Theinteraction between the irritants and the host defen-sive mechanisms results in release of numerous medi-ators that curtail progression of infection and devel-opment of severe local infection (osteomyelitis) andsystemic complication such as septicemia. Numerousstudies, conducted within the past 30 years, elucidatethe reactions and mediators of pathogenesis of humanperiradicular lesions. This chapter contains informa-tion about the etiologic factors involved in the devel-opment of periradicular lesions, mediators that partic-ipate in the pathogenesis of the changes, a classifica-tion of periradicular pathosis with emphasis on theirclinical and histologic features, and repair of peri-radicular lesions following root canal therapy. In addi-tion, some nonendodontic lesions with clinical and/orradiographic signs and appearances similar toendodontic lesions of pulpal origin will be discussed.

PERIRADICULAR LESIONS OF PULPAL ORIGIN

Irritants

Irritation of pulpal or periradicular tissues results ininflammation. The major irritants of these tissues canbe divided into living and nonliving irritants. The liv-ing irritants are various microorganisms and viruses.The nonliving irritants include mechanical, thermal,and chemical irritants. Mild to moderate injuries ofshort duration cause reversible tissue damage andrecovery of these tissues. Persistent and/or severeinjuries usually cause irreversible changes in the pulpand development of periradicular lesions.

Microbial Irritants

Microbial irritants of pulp and periradicular tissuesinclude bacteria, bacterial toxins, bacterial fragments,and viruses. These irritants egress apically from theroot canal system into the periradicular tissues andinitiate inflammation and tissue alterations. A num-ber of studies have shown that pulpal and/or peri-radicular pathosis do not develop without the pres-ence of bacterial contamination. Kakehashi and asso-ciates created pulpal exposures in conventional andgerm-free rats.1 Pulpal necrosis and abscess formationoccurred by the eighth day in the conventional rats. Incontrast, the germ-free rats showed only minimalinflammation throughout the 72-day investigation.Möller and coworkers made pulpal exposures in mon-keys and lacerated the pulp tissue with endodonticinstruments.2 In one group, all procedures were car-ried out in a sterile environment and the access cavi-ties were sealed. In the other group, after pulp expo-sure the teeth were left open to intraoral contamina-tion. Six months later, only mild inflammation wasapparent in the periradicular tissues in the first group.In contrast, the periradicular tissues in the secondgroup were severely inflamed.

Chapter 5

PERIRADICULAR LESIONSMahmoud Torabinejad and Richard E. Walton

Other investigators examined the flora of previouslytraumatized teeth with necrotic pulps with and with-out periradicular pathosis.3,4 Teeth without apicallesions were aseptic, whereas those with periradicularlesions had positive bacterial cultures. Korzen et al.demonstrated the importance of the amount of micro-bial inoculum in the pathogenesis of pulpal and peri-radicular lesions.5 They showed that higher levels ofcontamination lead to greater inflammatory responses.

In addition to bacterial irritation, the periradiculartissues can be mechanically irritated and inflamed.Physical irritation of periradicular tissues can alsooccur during root canal therapy if the canals are instru-mented or filled beyond their anatomic boundaries.Periradicular tissues can be irritated by impact trauma,hyperocclusion, endodontic procedures and accidents,pulp extirpation, overinstrumentation, root perfora-tion, and overextension of filling materials.

Chemicals are used as adjuncts for better débride-ment and disinfection of the root canal system. An invitro study, however, has shown that many of thesechemicals are highly concentrated and not biocompat-ible.6 Irrigating solutions such as sodium hypochloriteand hydrogen peroxide, intracanal medications, andchelating agents such as ethylenediaminetetraaceticacid (EDTA) can also cause tissue injury and inflam-mation if inadvertently extruded into the periradiculartissues. Some components in obturation materials canirritate the periradicular tissues when extruded beyondthe root canal system.

Periradicular Reaction to Irritation

The periradicular tissues consist of apical root cemen-tum, periodontal ligament, and alveolar bone. The apicalperiodontium is also richly endowed with cellular andextracellular components containing blood and lymphat-ics, as well as sensory and motor nerve fibers supplyingboth pulp and periodontium. Other structural elementsof the periodontal ligament include ground substance,various fibers, fibroblasts, cementoblasts, osteoblasts,osteoclasts, histiocytes, undifferentiated mesenchymalcells, and the epithelial cell rests of Malassez.

Irritation of periradicular tissues results in inflam-matory changes taking place. The vascular response toan injury includes vasodilation, vascular stasis, andincreased vascular permeability. The latter leads toextravasation of fluid and soluble components into thesurrounding tissues. These vascular changes cause red-ness, heat, swelling, and pain, which are the cardinalsigns of inflammation. The inflammatory cells involvedin various stages of tissue injury and repair includeplatelets, PMNs, mast cells, basophils, eosinophils,

176 Endodontics

macrophages, and lymphocytes,7 all of which have spe-cific roles in inflammatory responses.

Mediators of Periradicular Lesions

The inflammatory process is not completely under-stood, but a number of substances have been implicat-ed as mediators of inflammation. They include neu-ropeptides, fibrinolytic peptides, kinins, complementfragments, arachidonic acid metabolites, vasoactiveamines, lysosomal enzymes, cytokines, and mediatorsof immune reactions.

Neuropeptides. These are proteins generated fromsomatosensory and autonomic nerve fibers followingtissue injury. They include substance P (SP), calcitoningene–related peptide (CGRP), dopamine hydrolase,neuropeptide Y originating from sympathetic nervefibers, and vasoactive intestinal polypeptides generatedfrom parasympathetic nerve fibers.8

Substance P is a neuropeptide present in both theperipheral and central nervous systems. The release ofSP can cause vasodilation, increased vascular perme-ability, and increased blood flow during inflammation.In addition, it can cause the release of histamine frommast cells and potentiate inflammatory responses.

Calcitonin gene–related peptide has been localizedin small to medium sensory nerve fibers. Like SP, it is apotent vasodilator and may play a role in the regulationof blood flow in bone, periosteum, and other sites.Substance P and CGRP have been found in pulp andperiradicular tissues.9

Fibrinolytic Peptides. The fibrinolytic cascade istriggered by the Hageman factor, which causes activa-tion of circulating plasminogen, previously known asfibrinolysin and digestion of blood clots. This results inrelease of fibrinopeptides and fibrin degradation prod-ucts that cause increased vascular permeability andleukocyte chemotaxis.10

Kinins. Release of kinins causes many signs ofinflammation.11 They include chemotaxis of inflam-matory cells, contraction of smooth muscles, dilationof peripheral arterioles, increased vascular permeabili-ty, and pain. The kinins are produced by proteolyticcleavage of kininogen by trypsin-like serine proteases,the kallikreins. The kinins are subsequently inactivatedby removal of the last one or two C-terminal aminoacids by the action of peptidase.12 The kallikreins arealso able to react with other systems, such as the com-plement and coagulation systems, to generate othertrypsin-like serine proteases.13 Elevated levels of kininshave been detected in human periapical lesions.14

Complement System. The complement system con-sists of a number of distinct plasma proteins capable of

Periradicular Lesions 177

interacting with each other and with other systems toproduce a variety of effects.15 Complement is able tocause cell lysis if activated on the cell membrane andalso to enhance phagocytosis through interaction withcomplement receptors on the surface of phagocyticcells. Complement can also increase vascular perme-ability and act as a chemotactic factor for granulocytesand macrophages. The complement system is a com-plex cascade that has two separate activation pathwaysthat converge to a single protein (C3) and complete thecascade in a final, common sequence. Complement canbe activated through the classic pathway by antigen-antibody complexes or through the alternative pathwayby directly interacting with complex carbohydrates onbacterial and fungal cell walls or with substances suchas plasmin.

Several investigators have found C3 complementcomponents in human periradicular lesions.10

Activators of the classic and alternative pathways of thecomplement system include immunoglobulin (Ig) M,IgG, bacteria and their by-products, lysosomal enzymesfrom PMNs, and clotting factors. Most of these activa-tors are present in periradicular lesions. Activation ofthe complement system in these lesions can contributeto bone resorption either by destruction of alreadyexisting bone or by inhibition of new bone formationvia the production of prostaglandins (PGs).

Arachidonic Acid Metabolites. Arachidonic acid isformed from membrane phospholipid as a result of cellmembrane injury and phospholipase A2 activity and isfurther metabolized.

Prostaglandins are produced as a result of the acti-vation of the cyclooxygenase pathway of the arachi-donic acid metabolism. Their pathologic functionsinclude increased vascular permeability and pain.Torabinejad and associates demonstrated in an animalmodel that periradicular bone resorption could beinhibited by administration of indomethacin(Indocin), an antagonist of PGs.16 High levels of PGE2were found in periradicular lesions of patients withsymptomatic apical periodontitis (SAP).17 Takayamaet al.18 and Shimauchi and coworkers19 confirmedthese findings by demonstrating lower levels of PGE2associated with asymptomatic large lesions or cessationof symptoms subsequent to emergency cleaning andshaping of root canals. Miyauchi et al. used immuno-histochemical staining and found PGE2, PGF2α, and6-keto-PGF1α in the experimentally induced periapi-cal lesions in rats.20

Leukotrienes (LTs) are produced as a result of theactivation of the lipoxygenase pathway of the arachi-donic acid metabolism. Polymorphonuclear neutrophil

leukocytes and mast cells are the major sources for pro-duction of LTs.21 Leukotriene B4 is a powerful chemo-tactic agent from PMNs. Increased levels of LTB4 havebeen found in symptomatic human periapicallesions.22 Other leukotrienes such as LTC4, LTD4, andLTE4 are chemotactic for eosinophil and macrophage,cause increased vascular permeability, and stimulatelysozyme release from PMNs and macrophages.15

Vasoactive Amines. Vasoactive amines are presentin mast cells, basophils, and platelets. Histamine, themajor one of these substances, is found in all three celltypes, whereas serotonin is present only in platelets.21

Release of these materials causes increased vascularpermeability, as well as muscle contraction of airwaysand gastrointestinal tracts. Numerous mast cells havebeen detected in human periradicular lesions.23,24

Physical or chemical irritation of periradicular tissuesduring root canal therapy can cause mast cell de-granulation. The discharged vasoactive amines can ini-tiate an inflammatory response or aggravate an existinginflammatory process in the periradicular tissues.

Lysosomal Enzymes. Lysosomal enzymes are storedpreformed in membrane-bound bodies within inflam-matory cell cytoplasm. Lysosomal bodies are found inPMNs, macrophages, and platelets and contain acid aswell as alkaline phosphatases, lysozyme, peroxidase,cathepsins, and collagenase. They can be released viaexocytotic type events during cell lysis or secreted dur-ing phagocytosis. Release of these enzymes into the tis-sues causes increased vascular permeability, leukocytechemotaxis, generation of C5a from C5, andbradykinin formation.15 Aqrabawi and associatesexamined human periradicular lesions for the presenceof lysosomal hydrolytic arylsulfatase A and B andfound higher levels of these substances in lesions ofendodontic origin compared to the control tissues.25

Cytokines. The major cytokines that have beenimplicated in bone resorption are various interleukins(ILs) and tumor necrosis factors (TNFs).15

Interleukin-1 is produced primarily by monocytesand macrophages.26,27 Human monocytes produce atleast two IL-1 species, IL-1α and IL-1β.28 Interleukin-1β is the major form secreted by human monocytes.The chief component of osteoclast activating factor waspurified and found to be identical to IL-1β.29

Interleukin-1β is the most active of the cytokines instimulating bone resorption in vitro, 15-fold morepotent than IL-1α and 1,000-fold more potent thanTNFs.30 Interleukin-1 has been associated withincreased bone resorption in vivo in several diseases.Interleukin-1 has been implicated in the bone resorp-

tion for periodontal disease and periradicularlesions.31–39

Interleukin-6 is produced by a number of cells witha wide range of cell targets.40 It is produced byosteoblasts, but in response to other bone resorptiveagents such as parathyroid hormone, IL-1, and 1,25-hydroxyvitamin D3.41 Interleukin-6 is produced dur-ing immune responses and may play a role in humanresorptive diseases such as adult periodontitis42 andrheumatoid arthritis.43 Recent studies have shown thatIL-6 may play a significant role in the pathogenesis ofhuman periradicular lesion.44,45

Tumor necrosis factor-α and TNF-β have boneresorption activities similar to that of IL-1. Their effectson osteoclasts are indirect and are mediated throughosteoblasts.46 The effect of TNF-α on bone resorptionis dependent on PG synthesis.47 Tumor necrosis factorshave been detected in periradicular lesions of experi-mental animals and humans.38,39,48,49

Immunologic Reactions. In addition to the non-specific mediators of inflammatory reactions, im-munologic reactions also participate in the formationand perpetuation of periradicular pathosis.10,15,35

These reactions can be divided into antibody- and cell-mediated responses. The major antibody-mediatedreactions include IgE mediated reactions and antigen-antibody (immune complex)–mediated reactions.

Immunoglobulin E–mediated reactions occur as aresult of an interaction between antigens (allergens)and basophils in the blood or mast cells in the tissues.Vasoactive amines such as histamine or serotonin arepresent in preformed granules in basophils and mastcells and are released by a number of stimuli includ-ing physical and chemical injuries, complement acti-vation products, activated T lymphocytes, and bridg-ing of membrane-bound IgE by allergens. Numerousmast cells have been detected in human periradicularlesions.23,24 IgE molecules have also been found inhuman periapical lesions.10 Presence of potentialantigens in the root canals, IgE immunoglobulin, andmast cells in pathologically involved pulp and peri-radicular lesions indicate that IgE-mediated reactionscan occur in periradicular tissues. Irritation ofperiradicular tissues during cleaning, shaping, orobturation of the root canal system with antigenicsubstances can cause mast cell degranulation. The dis-charged vasoactive amines can initiate an inflamma-tory response or aggravate an existing inflammatoryprocess in the periradicular tissues.15

Antigen-Antibody or Immune Complex Reactions.Antigen-antibody or immune complex reactions inperiradicular tissues can be formed when extrinsic anti-

178 Endodontics

gens such as bacteria or their by-products interact witheither IgG or IgM antibodies. The complexes can bindto the platelets and cause release of vasoactive amines,increased vascular permeability, and chemotaxis ofPMNs. The pathologic effects of immune complexes inperiradicular tissues have been demonstrated in experi-mental animals. Torabinejad and associates placed sim-ulated immune complexes in feline root canals andshowed a rapid formation of periradicular lesions andaccumulation of numerous PMNs and osteoclasts.16

These findings were confirmed when Torabinejad andKiger immunized cats with subcutaneous injections ofkeyhole-limpet hemocyanin and challenged the animalswith the same antigen via the root canals.50

Radiographic and histologic observations showed thedevelopment of periradicular lesions consistent withcharacteristics of an Arthus-type reaction.

Immune complexes in human periradicular lesionshave been found using the anticomplement immuno-fluorescence technique, localized immune complexesin human periradicular specimens.51 Torabinejad andassociates measured the serum concentrations of circu-lating immune complexes in patients with asympto-matic and symptomatic periradicular lesions. Theresults indicated that immune complexes formed inchronic periradicular lesions are confined within thelesions and do not enter into the systemic circulation.However, when the serum concentrations of circulatingimmune complexes in patients with acute abscesseswere compared with those of people without theselesions, they found that these complexes entered thecirculation in patients with symptomatic periradicularabscesses. The concentrations of these complexes cameback to normal levels after either root canal therapy orextraction of involved teeth.52,53

Cell-Mediated Immune Reactions. Numerous B andT lymphocytes have been found in human periradicularlesions by the indirect immunoperoxidase method,54

with the T cells outnumbering the B cells significantly.A number of investigators have found approximatelyequal numbers of T-cell subsets in chronic lesions (Thelper/T suppressor ratio < 1.0).55–58 Stashenko and Yudemonstrated in developing lesions in rats that T helpercells outnumber T suppressor cells during the acutephase of lesion expansion. In contrast, T suppressorcells predominate at later time periods when lesions arestabilized.58 Based on these results, it appears that Thelper cells may participate in the initiation of peri-radicular lesions, whereas T suppressor cells preventrapid expansion of these lesions.

The specific role of T lymphocytes in the pathogen-esis of periradicular lesions has been studied by several


investigators.39,59,60 Wallstrom and Torabinejadexposed the pulps of mandibular molars of athymicand conventional rats and left them open to the oralflora for 2, 4, or 8 weeks.59 Statistical analysis of the tis-sue reactions to this procedure showed no significantdifference between periradicular tissue responses of thetwo species of animals. Waterman and associates com-pared periradicular lesion formation in immunosup-pressed rats with that in normal rats and found no sig-nificant histologic differences between the twogroups.60 Fouad studied the progression of pulp necro-sis and the histomorphometric features of periapicallesions in mice with severe combined immunodeficien-cies.39 He found no significant differences between thereaction and progression of pulp and periapical tissuesbetween these animals and those in normal mice. Thesefindings suggest that the pathogenesis of periradicularlesions is a multifactorial phenomenon and is not total-ly dependent on the presence of a specific group of cellsor mediators.

CLINICAL CLASSIFICATION OF PERIRADICULAR LESIONS

Periradicular diseases of pulpal origin have beennamed and classified in many different ways. Theselesions do not occur as individual entities; there areclinical and histologic crossovers in the terminologyregarding periradicular lesions as the terminology isbased on clinical signs and symptoms as well as radi-ographic findings. In this chapter, periradicular lesionsare divided into three main clinical groups: sympto-matic (acute) apical periodontitis, asymptomatic(chronic) apical periodontitis, and apical abscess.Since there is no correlation between histologic find-ings and clinical signs, symptoms, and duration of thelesion,10,21 the terms acute and chronic, which are his-tologic terms, will not be used in this chapter. Instead,the terms symptomatic and asymptomatic, whichdescribe clinical conditions, will be used.

APICAL PERIODONTITIS

Depending on clinical and radiographic manifesta-tions, these lesions are classified as symptomatic orasymptomatic periodontitis.

Symptomatic Apical Periodontitis

Symptomatic apical periodontitis (SAP) is a localizedinflammation of the periodontal ligament in the apicalregion. The principal causes are irritants diffusing froman inflamed or necrotic pulp. Egress of irritants such asbacteria, bacterial toxins, disinfecting medications,debris pushed into the periradicular tissues, or physical

irritation of the periapical tissues can cause SAP.Impact trauma can also cause SAP (see chapter 15).

Sensitivity to percussion is the principal clinical fea-ture of SAP. Pain is pathognomonic and varies fromslight tenderness to excruciating pain on contact ofopposing teeth. Depending on the cause (pulpitis ornecrosis), the involved tooth may or may not respondto vitality tests. Regardless of the causative agents, SAPis associated with the exudation of plasma and emigra-tion of inflammatory cells from the blood vessels intothe periradicular tissues. The release of mediators ofinflammation causes breakdown of the periodontal lig-ament and resorption of the alveolar bone. A minorphysical injury, such as penetrating the periradiculartissues with an endodontic file, may cause a transientinflammatory response. However, a major injury, caus-ing extensive tissue destruction and cell death, canresult in massive inflammatory infiltration of the peri-radicular tissues. Although the dynamics of theseinflammatory lesions are poorly understood, the con-sequences depend on the type of irritant (bacterial ornonbacterial), degree of irritation, and host defensivemechanisms. The release of chemical mediators ofinflammation and their action on the nerve fibers inthe periradicular tissues partially explain the presenceof pain during SAP. Also, since there is little room forexpansion of the periodontal ligament, increased inter-stitial tissue pressure can also cause physical pressureon the nerve endings, causing an intense, throbbing,periradicular pain. Increased pressure may be moreimportant than the release of the inflammatory media-tors in causing periradicular pain. The effect of fluidpressure on pain is dramatically demonstrated onopening into an unanesthetized tooth with this condi-tion. The release of even a small amount of fluid pro-vides the patient with immediate and welcome relief.Radiographs show little variation, ranging from nor-mal to a “thickening” of the periodontal ligament space(Figure 5-1) in teeth associated with SAP.

Asymptomatic Apical Periodontitis

Asymptomatic apical periodontitis (AAP) may bepreceded by SAP or by an apical abscess. However,the lesion frequently develops and enlarges withoutany subjective signs and symptoms. Inadequate rootcanal treatment may also cause the development ofthese lesions. Generally, a necrotic pulp graduallyreleases noxious agents with low-grade pathogenicityor in low concentration that results in the develop-ment of AAP. This pathosis is a long-standing, “smol-dering” lesion and is usually accompanied by radi-ographically visible periradicular bone resorption.

This condition is almost invariably a sequela to pulpnecrosis.

The clinical features of AAP are unremarkable. Thepatient usually reports no significant pain, and testsreveal little or no pain on percussion. If AAP perforatesthe cortical plate of the bone, however, palpation ofsuperimposed tissues may cause discomfort. The asso-ciated tooth has a necrotic pulp and therefore shouldnot respond to electrical or thermal stimuli.

Radiographic findings are the diagnostic key.Asymptomatic apical periodontitis is usually associat-ed with periradicular radiolucent changes. Thesechanges range from thickening of the periodontal liga-ment and resorption of the lamina dura to destructionof apical bone resulting in a well-demarcated radiolu-cency (Figure 5-2).

Asymptomatic apical periodontitis has traditionallybeen classified histologically as either a periradiculargranuloma or a periradicular cyst. Various clinicalmethods have been used to attempt to differentiatethese two clinically similar lesions.61–66 The only accu-rate way to distinguish these two entitles is by histolog-ic examination.

Periradicular Granuloma. Nobuhara and del Rioshowed that 59.3% of the periradicular lesions weregranulomas, 22% cysts, 12% apical scars, and 6.7%other pathoses.67 Histologically, the periradicular gran-uloma consists predominantly of granulation inflam-matory tissue68 with many small capillaries, fibroblasts,numerous connective tissue fibers, inflammatory infil-trate, and usually a connective tissue capsule (Figure 5-3). This tissue, replacing the periodontal ligament,

180 Endodontics

apical bone, and sometimes the root cementum anddentin, is infiltrated by plasma cells, lymphocytes,mononuclear phagocytes, and occasional neutrophils.Occasionally, needle-like spaces (the remnants of cho-lesterol crystals), foam cells, and multinucleated for-eign body giant cells are seen in these lesions (Figure 5-4).69 Animal studies have shown that cholesterolcrystals can cause failure of some lesions to resolve fol-lowing nonsurgical root canal therapy.70 Nerve fibers

Figure 5-1 Radiographic features of symptomatic apical peri-odontitis. “High” amalgam restoration was placed on the occlusalsurface of a second mandibular molar. The periodontal ligamentspace is widened at the apex (arrows). Clinically, the tooth isextremely sensitive to percussion.

Figure 5-2 Radiographic appearance of asymptomatic apicalperiodontitis. Two distinct lesions are present at the periradicularregions of a mandibular first molar with necrotic pulp.

Figure 5-3 Apical periodontitis (granuloma) in its more classicform. The central zone is dense with round cells (plasma cells andsmall lymphocytes). Beyond is a circular layer of fibrous capsule.Limited bone regeneration (arrow) can be clearly seen at outermargin of capsule. Human tooth. Reproduced with permissionfrom Matsumiya S. Atlas of oral pathology. Tokyo: Tokyo DentalCollege Press; 1955.


have also been demonstrated in these lesions.71,72

Epithelium in varying degrees of proliferation can befound in a high percentage of periradicular granulo-mas (Figure 5-5).69

Periradicular Cyst. Histologic examination of aperiradicular cyst shows a central cavity lined by stratifiedsquamous epithelium (Figure 5-6). This lining is usuallyincomplete and ulcerated. The lumen of the periradicu-lar cyst contains a pale eosinophilic fluid and occasional-ly some cellular debris (Figure 5-7). The connective tissuesurrounding the epithelium contains the cellular andextracellular elements of the periradicular granuloma.Inflammatory cells are also present within the epitheliallining of this lesion. Histologic features of periradicularcysts are very similar to those of periradicular granulo-mas except for the presence of a central epithelium-linedcavity filled with fluid or semisolid material.

Local Effects of Asymptomatic Apical Periodontitis.Bone and periodontal ligament can be replaced byinflammatory tissue. This process is associated withformation of new vessels, fibroblasts, and sparse,immature connective tissue fibers. As long as egress ofirritants from the root canal system to the periradicu-lar tissues continues or macrophages fail to eliminatethe materials they have phagocytosed,73 destructive aswell as healing processes will occur simultaneously inasymptomatic apical lesions. The extent of the lesiondepends on the potency of the irritants within the rootcanal system and the activity level of defensive factorsin this region. If a balance between these forces is main-tained, the lesion continues in an asymptomatic man-ner indefinitely. On the other hand, if the causative fac-tors overcome the defensive elements, a symptomaticperiradicular lesion may be superimposed on the

Figure 5-4 Histopathologic examination of apical periodontitis (granuloma) reveals A, the presence of many plasma cells (white arrow)and lymphocytes (black arrow); B, cholesterol slits (black arrows); C, foam cells (black arrows); D, multinucleated giant cells (open arrows).All of these features may not be seen in one specimen of a chronic periradicular lesion.

182 Endodontics

asymptomatic one. This is one example of the so-calledphoenix abscess.

Systemic Effects of Asymptomatic ApicalPeriodontitis. When the serum concentrations of cir-culating immune complexes (immunoglobulins G, M,and E) and the C3 complement component of patientswith large periradicular lesions were measured and com-pared with those of patients with no lesions, investigatorsfound no statistical difference between the two groupsand concluded that asymptomatic periradicular lesionscannot act as a focus to cause systemic diseases viaimmune complexes.51 However, when the same compo-nents were measured in patients with symptomatic api-cal abscesses (SAAs), they found a statistically significantdifference between the levels of immune complexes, IgGand IgM, and the C3 complement component betweenthe two groups.52 In addition, significant differences werealso noted in the mean levels of concentration ofimmune complexes, IgG, IgM, and IgE, and the C3 com-plement component of these patients before and afterroot canal therapy or extraction of involved teeth. On the

Figure 5-5 Apical periodontitis (granuloma) with containedepithelium. Epithelial cells of periodontal ligament have proliferatedwithin new inflammatory tissue. The epithelium tends to ramify in areticular pattern (straight arrow) toward receding bone. It also may,as in this case, apply itself widely to the root surface (curved arrow).Infiltration of epithelium by round cells is everywhere apparent.Human tooth. Reproduced with permission from Matsumiya S. Atlasof oral pathology. Tokyo: Tokyo Dental College Press; 1955.

Figure 5-6 Apical cyst with marked inflammatory overlay. Roundcells permeate both the epithelium and the connective tissue imme-diately deep to it. Spaces indicate where crystalline cholesterol hasformed within the cyst. Bone formation is evident (arrow). Thismay reflect narrowing of the width of the connective tissue zone, asoccurs in some apical cysts. Human tooth. Reproduced with per-mission from Matsumiya S. Atlas of oral pathology. Tokyo: TokyoDental College Press; 1955.

Figure 5-7 Central cavity, epithelial lining, and some of the con-nective tissue wall of human apical cysts. Both epithelial cells andleukocytes are floating free within the cyst cavity (open arrow). Theepithelial lining is thin and penetrated by many round cells.Connective tissue shows moderate chronic inflammation.


basis of this study, it appears that symptomatic periradic-ular lesions may lead to measurable systemic immuno-logic reactions, but the clinical significance of thesechanges remains unclear.

Theories of Apical Cyst Formation. Histologicexamination of normal human periodontal ligamentshows remnants of Hertwig’s epithelial root sheath alongits length (the so-called epithelial cell rests of Malassez).Inflammation in the periradicular tissues, on the otherhand, is associated with proliferation of these normallyquiescent cells.74 This explains why proliferating epithe-lium has been found in a significant percentage of peri-radicular granulomas.75,76 The main difference betweenperiradicular granulomas and cysts is the presence of acavity lined by stratified squamous epithelium. The cystlining probably arises from offspring of the proliferatingepithelium present in apical granulomas.

The pathogenesis of apical cysts is not fully under-stood. The two prevailing theories for cavity formationin proliferating epithelium are the “breakdown” theo-ry69,77,78 and the “abscess cavity” theory.79,80 Thebreakdown theory postulates that a continuousgrowth of epithelium removes central cells from theirnutrition; consequently, the innermost cells die, and acyst cavity forms. Because there is no evidence for lackof blood supply and the proliferating epithelium isusually invaginated by connective tissue, this theory issomewhat unsatisfactory. The abscess cavity theorystates that a cyst results when an abscess cavity isformed in connective tissue and epithelial cells coverthe exposed connective tissue, as in an ordinarywound. Because of inherent differences between theepithelial cell rests of Malassez and the epithelial cellsof skin, and because of the numerous discontinuitiesin the linings of apical cysts, this theory does not fullyexplain cyst formation either.

Available evidence indicates that the development ofthese cavities in proliferating epithelium may be medi-ated by immunologic reaction. These reactions includethe presence of immunocompetent cells in the prolifer-ating epithelium of periradicular lesion,81–83 the pres-ence of Igs in cyst fluid,84 and the discontinuity in theepithelial linings of most apical cysts.85,86 Activatedepithelial cell rests of Malassez can obtain antigenicityor become recognized as antigens and consequentlyelicit immunologic reactions.87

Regardless of its pathogenesis, the apical cyst evident-ly carries its own seeds of destruction. It survives byvirtue of the irritants supplied to inflamed periradiculartissues and usually disintegrates spontaneously follow-ing elimination of those irritants.88 Its destruction maybe owing to the presence of antigenic epithelium.87

Condensing Osteitis

Inflammation of periradicular tissues of teeth usuallystimulates concurrent osteoclastic and osteoblastic activ-ities. Osteoclastic (resorptive) activities are usually moreprominent than osteoblastic (formative) activities, andperiradicular inflammation therefore is usually associat-ed with radiolucent changes. In contrast, condensingosteitis is associated with predominant osteoblasticactivity; the reason for this is unknown. Condensingosteitis is possibly attributable to a special balancebetween host tissues and the root canal irritants.

Condensing osteitis, or chronic focal sclerosingosteomyelitis, is a radiographic variation of AAP and ischaracterized as a localized overproduction of apicalbone. A low-grade inflammation of the periradiculartissues is usually related to condensing osteitis.Radiographically, this lesion is usually observed aroundthe apices of mandibular posterior teeth with pulpnecrosis or chronic pulpitis.

Condensing osteitis may manifest with varied signsand symptoms because it is associated with a variety ofpulpal and periradicular lesions. The tooth associatedwith condensing osteitis may be asymptomatic or sen-sitive to stimuli. Depending on the pulpal status, thetooth may or may not respond to electrical and thermalstimuli. The radiographic appearance of condensingosteitis, a well-circumscribed radiopaque area aroundone or all of the roots, is often indicative of chronicpulpitis (Figure 5-8). The radiopaque periradicularchanges return to normal after successful root canaltherapy (Figure 5-9).89

Figure 5-8 Apical condensing osteitis that developed in response tochronic pulpitis. Additional bony trabeculae have been formed andmarrow spaces have been reduced to a minimum. The periodontal lig-ament space is visible, despite increased radiopacity of nearby bone.

APICAL ABSCESSES

An abscess is a localized collection of pus in a cavityformed by the disintegration of tissues.90 Based on thedegree of exudate formation and its discharge, theseverity of pain, and the presence or absence of sys-temic signs and symptoms, apical abscesses can bedivided into symptomatic or asymptomatic conditions.

Symptomatic Apical Abscess

A sudden egress of bacterial irritants into the peri-radicular tissues can precipitate an SAA and its more

184 Endodontics

severe sequelae, acute osteitis and cellulitis. The clinicaland histopathologic features of these conditions appearto be related to either the concentration and toxicity ofthe irritant or the local proliferation of invading organ-isms with their destructive activities. Chemical or bac-terial irritation of the periradicular tissues throughimmunologic or nonimmunologic reactions can causerelease of biologic substances similar to those involvedin SAP and produce the same microvascular changes.

An SAA is an inflammatory process in the periradic-ular tissues of teeth, accompanied by exudate forma-tion within the lesion. A frequent cause of SAA is arapid influx of microorganisms, or their products,from the root canal system.

An SAA may occur without any obvious radi-ographic signs of pathosis. The lesions can also resultfrom infection and rapid tissue destruction arisingfrom within AAP, another example of the so-calledphoenix abscess.

The patient may or may not have swelling. Whenpresent, the swelling may be localized or diffuse.Clinical examination of a tooth with SAA shows vary-ing degrees of sensitivity to percussion and palpation.There is no pulp reaction to cold, heat, or electricalstimuli as the involved tooth has a necrotic pulp.Radiographic features of the SAA vary from a thicken-ing of the periodontal ligament space to the presence ofa frank periradicular lesion (Figure 5-10).

Spread of inflammatory response into the cancellousbone results in apical bone resorption. Since inflamma-tion is not confined to the periodontal ligament but hasspread to the bone, the patient now has an acuteosteitis. These patients are in pain and may have sys-temic symptoms such as fever and increased whiteblood cell count. Because of the pressure from theaccumulation of exudate within the confining tissues,the pain can be severe. Spread of the lesion toward asurface, erosion of cortical bone, and extension of theabscess through the periosteum and into the soft tis-sues is ordinarily accompanied by swelling and somerelief. Commonly, the swelling remains localized, but italso may become diffuse and spread widely (cellulitis)(Figure 5-11). The extent of swelling reflects theamount and nature of the irritant egressing from theroot canal system, the virulence and incubation periodof the involved bacteria, and the host’s resistance. Thelocation of the swelling is determined by the relation ofthe apex of the involved tooth to adjacent muscleattachments.91

Immunologic or nonimmunologic inflammatoryresponses contribute to the breakdown of the alveolarbone and cause disruption of the blood supply, which,

Figure 5-9 A, Apical condensing osteitis associated with chronicpulpitis. Endodontic treatment has just been completed. Obviouscondensation of alveolar bone (black arrow) is noticeable aroundthe mesial root of the first molar. Radiolucent area is evident at theapex of the distal root of the same tooth. The retained primarymolar root tip (open arrow) lies within the alveolar septum mesialto the molar. B, Resolution (arrow) of apical condensing osteitisshown in A, 1 year after endodontic treatment. From a radiograph-ic standpoint, complete repair of both periradicular lesions hasbeen obtained. Reversal of apical condensing osteitis and disap-pearance of radiopaque area are possible.

A

B


in turn, produces more soft and hard tissue necrosis.The suppuration process finds lines of least resistanceand eventually perforates the cortical plate. When itreaches the soft tissue, the pressure on the periosteumis relieved, usually with an abatement of symptoms.Once this drainage through bone and mucosa isobtained, suppurative apical periodontitis or anasymptomatic periradicular abscess is established.

Asymptomatic Apical Abscess

Asymptomatic apical abscess (AAA), also referred to assuppurative apical periodontitis, is associated with agradual egress of irritants from the root canal systeminto the periradicular tissues and formation of an exu-date. The quantity of irritants, their potency, and theirhost resistance are all important factors in determiningthe quantity of exudate formation and the clinical signsand symptoms of the lesion. Asymptomatic apicalabscess is associated with either a continuously orintermittently draining sinus tract. This is visually evi-dent as a stoma on the oral mucosa (Figure 5-12) oroccasionally as a fistula on the skin of the face (Figure5-13). The exudate can also drain through the gingivalsulcus of the involved tooth, mimicking a periodontallesion with a “pocket.” This is not a true periodontal

Figure 5-10 Radiographic features of symptomatic apical abscess.The patient developed sudden symptoms of pain and facialswelling. Radiographically, a lesion is apparent apically to the max-illary left lateral incisor, that did not respond to vitality tests, con-firming pulpal diagnosis of necrosis.

Figure 5-11 A, Localized abscess resulting from an incompleteroot canal treatment on a maxillary lateral incisor. B, Cellulitiscaused by a maxillary first molar with necrotic pulp. (Courtesy ofDr. Mohammad Baghai.)

Figure 5-12 Apical abscess and its stoma. Initially, the abscess wasasymptomatic, but when the opening of the sinus tract from themaxillary left central incisor became blocked, the accumulation ofdrainage caused pain.

A

B

pocket as there is not a complete detachment of con-nective tissue from the root surface.92 If left untreated,however, it can be covered with an epithelial lining andbecomes a true periodontal pocket.

An AAA is usually associated with little discomfort.If the sinus tract drainage becomes blocked, however,varying levels of pain and swelling will be experienced.Correspondingly, clinical examination of a tooth withthis type of lesion reveals a range of sensitivity to per-cussion and palpation, depending on whether the tractis open, draining, or closed.

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Vitality tests are negative on teeth with AAA becauseof the presence of necrotic pulps. Radiographic exami-nation of these lesions shows the presence of bone lossat the apexes of the involved teeth (Figure 5-13, B).

The sinus tract that leads away from this suppurativecore to the surface may be partially lined with epitheli-um or the inner surface composed of inflamed connec-tive tissue.93 The sinus tract, like the periradicular cyst,arises and persists because of irritants from the pulp.Similarly, these sinus tracts, whether lined or not,resolve following root canal treatment removing theetiology.

REPAIR OF PERIRADICULAR LESIONS

Removal of irritants from the root canal system and itstotal obturation result in repair of inflamed periradicu-lar tissue.94 Depending on the extent of tissue damage,repair varies from a simple reduction and resolution ofinflammation to a more complex regeneration, involv-ing remodeling of bone, periodontal ligament, andcementum. Repair of the lesion, therefore, may takedays to years. Periradicular inflammatory lesions usual-ly arise from irritants of a necrotic pulp. Endodontictreatment may initiate or amplify the inflammation byextruded debris, overextended instruments, or fillingmaterials extended into the periradicular tissues. As aresult, the periodontal ligament and its surrounding tis-sues are replaced by chronic inflammatory tissue. Aslong as irritation continues, simultaneous destructionand repair of these periradicular tissues continue.

This pattern of breakdown/repair was demonstratedby Fish,95 who produced infected lesions in guinea pigsby drilling holes in the bone and packing wool fiberssaturated with microorganisms. He described four reac-tive zones to the bacteria: infection, contamination,irritation, and stimulation. The central infection zonehad microorganisms and neutrophils. Contaminationwas a zone of round-cell infiltrate. The zone of irrita-tion was characterized by the presence of macrophagesand osteoclasts. The outermost area was the zone ofstimulation, containing fibroblasts and forming colla-gen and bone.

Extrapolations of Fish’s findings to the tooth with anecrotic pulp have been made. Egress of microorgan-isms and the other irritants from the root canal systeminto the periradicular tissues causes the central zones oftissue destruction near the zone of infection. As thetoxicity of irritants is reduced in the central zones, thenumber of reparative cells increases peripherally.96

Removal of the irritants and their source by root canaldébridement and proper obturation permits thereparative zone to move inward.

Figure 5-13 A, Apical abscesses occasionally drain extraorally(white arrows). After several years of treatment for “skin infection”with no results from topical application of numerous antibiotics,the problem was traced to the central incisor with previous rootcanal treatment. B, The tooth was retreated nonsurgically and thechin lesion healed within a few weeks with some scarring.(Courtesy of Dr. Leif K. Bakland.)

A

B


The healing of periradicular tissues after root canaltreatment is often associated with formation andorganization of a fibrin clot, granulation tissue forma-tion and maturation, subsidence of inflammation, and,finally, restoration of normal architecture of the peri-odontal ligament. Since the inflammatory reactions areusually accompanied by microscopic and macroscopicresorption of the hard tissues, bone and cementumrepair occurs as well.

Periradicular lesions repair from the periphery tothe center. If the cortical plate is perforated by resorp-tion, the healing process is partially periosteal innature. Boyne and Harvey, after creating cortical plateperforations in the jaws of humans, showed that labialdefects measuring 5 to 8 mm in diameter healed com-pletely within 5 months.97 When they studied apicaldefects measuring 9 to 12 mm, they found that theselesions had limited labial cortex formation and insteadwere filled with avascular fibrous connective tissue upto 8 months following surgery.

If lesions have not involved the periosteum, the heal-ing response will be endosteal, with formation of bonytrabeculae extending inward from the walls of the lesiontoward the root surface. On the periphery, osteoblastsappear and elaborate bone matrix (osteoid), which grad-ually mineralizes as it matures. If cementum or dentinhas been resorbed by the inflammation, remodeling andrepair are by secondary cementum.

The last to form is likely the fibrous component inter-posed between newly formed bone and the cemental rootsurface. These fibers have basically two orientations. Oneis a true periodontal ligament arrangement, whereas theother is an alignment of collagen parallel to the root sur-face. Both orientations represent complete healing.

The sequence of events post–endodontic treatmentleading to complete repair of periradicular tissues, afterinflammatory destruction of the periodontal ligament,bone, or cementum, has not been validated. Mostinformation is based on repair of extraction sites orhealing of bone cavities following periradicular curet-tage. These may or may not be accurate as to patternsof nonsurgical apical repair. A blood clot forms follow-ing extraction or apicoectomy, which becomes organ-ized into recognizable granulation tissue. This tissuecontains endothelium-lined vascular spaces, vast num-bers of fibroblasts, and associated collagen fibers. Thegranulation tissue is infiltrated by neutrophils, lym-phocytes, and plasma cells. On the periphery of thegranulation tissue, osteoblasts and osteoclasts abound.With maturation, the number of cells decreases, where-as collagen increases. Ultimately, mature bone formsfrom the periphery toward the center.98

Do different types of endodontic periradicularlesions have different patterns of healing? Possiblythere are variations, but this has not been conclusivelydemonstrated. Of the three general lesion types—gran-uloma, cyst, and abscess—it is likely that the granulo-ma follows the pattern described above.99 The abscessmay be slower; the exudates and bacteria must becleared from the tissues before regeneration occurs. Avariation of the abscess, the sinus tract (intraoral andextraoral) will heal following root canal treatment.100 Ithas been suggested that the periradicular cyst with acavity that does not communicate with the root canal isless likely to resolve following root canal treatment101;this has yet to be proven.

There is some evidence that at least some lesionsmay heal with formation of scar tissue.102 Although thefrequency of healing by scar tissue is unknown, it islikely that it seldom occurs following root canal treat-ment, being much more common after periradicularsurgery on maxillary anterior teeth.103

NONENDODONTIC PERIRADICULAR LESIONS

Bhaskar, in his textbook on radiographic interpreta-tion, listed 38 radiolucent lesions and other abnormal-ities of the jaws.104 Three of these lesions, dental gran-uloma, radicular cyst, and abscess, are categorized asbeing related to necrotic pulps. In addition, Bhaskaridentifies 16 radiopaque lesions of the jaws, 3 of which,condensing osteitis, sclerosing osteomyelitis, andGarré’s osteomyelitis, are also related to pulpal patho-sis. The dentist must therefore differentiate between theendodontic and the nonendodontic lesions, ruling outthose that trace their origin from non–pulp-relatedsources. Additional confusion in radiographic diagno-sis relates to normal radiolucent and radiopaque struc-tures that lie within or over apical regions.

Differential diagnosis of periradicular pathosis isessential and, at times, confusing. There is a tendencyfor the clinician to assume that a radiolucency is anendodontically related lesion and that root canal treat-ment is necessary without performing additional con-firmatory tests. Avoid this pitfall!

The dentist must therefore be astute as well asknowledgeable when diagnosing bony lesions. It isimportant that teeth with sound pulps not be violatedneedlessly because of the mistaken notion that radiolu-cencies in the apical region always represent endodon-tic pathema. The reverse is also true; endodonticlesions may mimic nonendodontic pathosis.

Significantly, most radiolucent lesions do indeedtrace their origin to pulpal disease. Therefore, the den-tist is likely to encounter many more endodontic

lesions, because of their sheer numbers, than othertypes of pathosis. However, many of the nonendodon-tic lesions mimic endodontic pathema, with similarsymptoms and radiographic appearance.105 On theother hand, many of the nonendodontic lesions aresymptomless (as endodontic lesions frequently are)and are detected only on radiographs. To avoid errors,the dentist must approach all lesions with caution,whether symptomatic or not.

This section will deal with lesions of the jaws cate-gorized as odontogenic or nonodontogenic in origin.Odontogenic lesions arise from remnants of odontoge-nesis (or the tooth-forming organ), either mesenchy-mal or ectodermal in origin. Nonodontogenic lesionstrace their origins to a variety of precursors and there-fore are not as easily classified.

Not all bony lesions that occur in the jaws will bediscussed as many are extremely rare or do not ordi-narily mimic endodontic pathosis. An oral pathologytext should be consulted for clinical features andhistopathology of missing entities. Furthermore, thelesions that are included are not discussed in detail. Ofprimary concern are the clinical findings causing themto resemble endodontic pathema, as well as those fac-tors leading to accurate differential diagnosis.

Differentiating between lesions of endodontic andnonendodontic origin is usually not difficult. Pulpvitality testing, when done with accuracy, is the pri-mary method of determination; nearly all nonen-dodontic lesions are in the region of vital teeth, where-as endodontic lesions are usually associated with pulpnecrosis, giving negative vitality responses. Except bycoincidence, nonendodontic lesions are rarely associat-ed with pulpless teeth. Other significant radiographicand clinical signs and symptoms, however, aid in dif-ferential diagnosis.

Odontogenic Cysts

Dentigerous Cyst. Also called follicular cysts, dentiger-ous cysts are derived histogenetically from the reducedenamel epithelium of an impacted or embedded tooth.Therefore, they are most often associated with thecrowns either of impacted third molars, maxillarycanines, or mandibular second premolars. The majori-ty are found in the mandible.106,107 Although mostremain small and asymptomatic, dentigerous cystshave the potential to become aggressive lesions.Continued enlargement may involve large areas of thejaws, particularly the mandible, with displacement ofteeth and expansion of cortices.108

Dentigerous cysts may be confused with endodonticlesions by either radiographic or other clinical findings.

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Routine periradicular or panographic films mightreveal its presence at the apex of adjacent teeth, some-times causing root resorption. An unusual variant isthe circumferential dentigerous cyst (Figure 5-14). Thetooth may erupt through the dentigerous cyst, with theresulting radiolucency occurring periradicularly, thusclosely mimicking periradicular pathosis of pulp ori-gin.109 The dentigerous cyst occasionally may becomesecondarily infected and inflamed, often via a pericoro-nal communication. The swelling and pain clinicallyresemble disease of pulpal origin.

This cyst is readily differentiated from chronic apicalperiodontitis or acute apical abscess in that the adjacenterupted tooth invariably demonstrates pulp vitality.

Lateral Periodontal Cyst. This uncommon cystarises at the lateral surface of a tooth, usually in themandibular premolar-canine area (Figure 5-15). Thislesion is currently thought to arise from remnants ofthe dental lamina and probably represents theintraosseous analog of the gingival cyst of the adult.110

Clinically, the lesion is asymptomatic, and again the

Figure 5-14 Circumferential dentigerous cyst developed aroundthe crown of an unerupted canine. The cyst may be enucleated (caremust be taken to avoid the incisor) and the canine brought intoposition with an orthodontic appliance. (Courtesy of Dr. RussellChristensen.)


pulp of the involved tooth is vital. Radiographically, thelesion is usually less than 1 cm in diameter and may ormay not have a surrounding rim of dense bone. Itresembles the lateral radicular cyst, which is anendodontic inflammatory lesion related to a necroticpulp.111 Differentiation is made on the basis of pulpvitality testing.

Odontogenic Keratocyst. The odontogenic kera-tocyst is a relatively common lesion, probably arisingfrom remnants of the dental lamina.112 Clinically andradiographically, this lesion may resemble a periradic-ular lesion.113 The keratocyst may confuse the clinicianby manifesting pain, soft tissue swelling, or expansionof bone. Radiographically, the lesion may appear as aunilocular or multilocular radiolucency in the lateralor apical region of teeth, usually in the mandible114

(Figure 5-16). However, other keratocysts mimic (andmay have their origins in) dentigerous and lateral peri-odontal cysts in their radiographic appearance.

Differentially, the adjacent teeth respond to vitalitytesting. The keratocyst is easily differentiated fromlesions of pulp origin on the basis of its pathognomon-ic histologic features. The lesion has a marked tenden-cy to recur following surgical removal,115 indicatingthat the keratinized epithelium has a greater growthpotential than does ordinary cyst epithelium.116

Residual Apical Cyst. The residual apical cyst orresidual dentigerous cyst reportedly represents a per-sistent apical cyst that was associated with an extractedpulpless tooth. It has been theorized that an apical cysthas the potential to develop from epithelial remnantsafter extraction and to be a self-perpetuating lesion.108

Contradicting this theory is the evidence that apicalcysts usually resolve spontaneously following nonsur-gical root canal treatment.117 The cyst wall may, in fact,carry the seeds of its own destruction. Toller118 andTorabinejad87 have presented evidence that the epithe-lium may be antigenic and speculate that it wouldtherefore be eliminated by the immune mechanism.

Consequently, only a few specimens of residual cysthave been carefully described. Kronfeld noted the basicepithelium, cavity, and capsule.119 He stressed theabsence of inflammatory cells in both the epithelial lin-ing and the connective tissue zone, which further castsdoubt that this would truly be a “residual” apical cyst.Very uncommon (if it exists at all) and uncomplicated,the lesion offers few problems.

Bone Pathology: Fibro-osseous Lesions

In a comprehensive publication, Waldron and Giansanticlassified and reviewed fibro-osseous lesions of thejaws.120 These represent a phenomenon in which nor-mal bone is replaced by a tissue compound of fibroblastsand collagen, containing varying amounts of a bony orcementum-like calcification. The radiographic appear-ance varies according to size and relative amounts andmixtures of fibrous tissue/hard tissue. Because of theseradiographic appearances and their location over andaround apices, some types of fibro-osseous lesions areoften confused with endodontic lesions. These will bediscussed further.

Periradicular Cemental Dysplasia. Also termedperiradicular osteofibrosis or, more commonly, peri-apical cementoma, periradicular cemental dysplasia

Figure 5-15 Lateral periodontal cyst. Well-circumscribed radiolu-cent area in apposition to the lateral surfaces of the lower premolars(black arrows demarcate the extent of lesions). No clinical signs orsymptoms were noted. Pulps tested vital.

Figure 5-16 Odontogenic keratocyst. A multilocular radiolucencywith sclerotic border (arrows) in the mandible. All of the molars inthis case responded to a vitality test. (Courtesy of the Departmentof Oral Pathology, Loma Linda University.)

demonstrates lesions that are often multiple, usuallyinvolve the mandibular incisors, and occur most oftenin middle-aged African American women. However,they can and do occur elsewhere in the jaws and in anyrace and at other ages. Their etiology is unknown.

Periradicular cemental dysplasia has an interestingevolution.121 The progression is from normal alveolarbone to bone resorption and fibrosis and finally todense, atypical reossification. The initial stage (oste-olytic stage) is characterized histologically by a prolif-eration of fibroblasts and collagen fibers in the apicalregion of the periodontal ligament. The resultant mass

190 Endodontics

induces resorption of the medullary bone surroundingthe apex, resulting in a radiolucent lesion closely mim-icking a lesion of pulpal origin (Figure 5-17). Duringthis stage of radiolucency, errors are frequentlymade,122 emphasizing the necessity of pulp testing.

Unlike apical periodontitis or an apical cyst, this newgrowth is free of inflammation. Furthermore, nervesand vessels are unimpeded as they make their passageto and from the root canal.

In time, cementoblasts differentiate within the softtissue, and a central focus of calcification appears(intermediate stage) (Figure 5-18). This deposition of

Figure 5-17 A, Periradicular cemental dysplasia (osteofibrosis), initial stage. Pulps in both teeth are vital. B,Transition to the second stage is developing. C, Biopsy of periradicular osteofibrosis, initial stage. Fibrous con-nective tissue lesion has replaced cancellous bone. (Photomicrograph courtesy of Dr. S. N. Bhaskar and theWalter Reed Army Institute of Research. US Army photograph.)

A B

C


hard tissue may be continued over the years until near-ly all of the fibrous tissue is reossified. When thisoccurs, the evolution has reached its third and finalstage (mature stage) (Figure 5-19). The reossificationis characterized radiographically by increasingradiopacity.

Problems of differential diagnosis arise in conjunc-tion with the initial radiolucent stage of periradicularcemental dysplasia (see Figure 5-17). Clinically, thelesions are always asymptomatic, and the adjacentteeth respond to vitality testing. Radiographically, anintact lamina dura is usually (but not always) visiblearound the apices if carefully looking “through” theradiolucency.

Osteoblastoma and Cementoblastoma. These areapparent benign neoplasms and are closely relatedlesions. Some believe that a cementoblastoma is, inreality, an osteoblastoma with an intimate relationshipwith the root (Figure 5-20). The benign cementoblas-toma (or true cementoma) is an uncommon neoplasmthought to represent a neoplasm of cementoblasts.123

Radiographically, the lesion is characteristically associ-ated and continuous with the roots of the teeth, usual-

ly a mandibular first molar.124 The tumor mass is oftensurrounded by a thin, radiolucent zone that is continu-ous with the periodontal ligament space. Histologically,the tumor shows fusion with the root cementum.

Differentiation between cementoblastoma and con-densing osteitis is based on differences in radiographicappearance; condensing osteitis is diffuse, shows nowell-defined borders, and is associated with chronicpulpal disease. Furthermore, the lamina dura and nor-mal periodontal ligament space may remain intact incondensing osteitis.

Cementifying and Ossifying Fibroma. The centralossifying fibroma is a benign, neoplastic, fibro-osseouslesion. Circumstantial evidence indicates that centralossifying fibromas originate from elements of the peri-odontal ligament.120 Most of these lesions arise in theperiradicular region and therefore can be easily con-fused radiographically with endodontic periradicularlesions (Figure 5-21). They tend to occur in youngerpatients and in the premolar-molar region of themandible. Because they are asymptomatic, the lesionsare frequently undetected. They attain a large size, oftenwith visible expansion of the overlying cortex.

Figure 5-18 A, Periradicular cemental dysplasia, intermediate stage, central incisor and canine. Slight calcification of the fibrotic lesion isnow developing. The pulps are vital. B, Biopsy of the intermediate stage with foci (arrows) of calcification appearing throughout the lesion.(Photomicrograph courtesy of Dr. S. N. Bhaskar and the Walter Reed Army Institute of Research, US Army photograph.)

A B

192 Endodontics

Figure 5-19 A, Periradicular cemental dysplasia, mature stage, canine. Osseous calcification associated with vital pulp. Fibrotic stage is seenat the periapex of the first premolar. B, Biopsy of the final stage with advanced, dense calcification. (Photomicrograph courtesy of Dr. S. N.Bhaskar and the Walter Reed Army Institute of Research. US Army photograph.)

Figure 5-20 Cementoblastoma. The lesion is a fairly well-definedradiopaque mass surrounded by a thin radiolucent line. It has alsoreplaced the apical portions of the distal root of the first molar.

Figure 5-21 Ossifying fibroma. The patient presented with pain.The pulp was vital, indicating that this was not an endodonticpathosis. Root canal treatment was followed by root end removaland excision of the lesion. Biopsy confirmed the diagnosis.

A B


The central ossifying fibroma has a characteristicprogression of radiologic findings. During the earlystage, which is osteolytic, bone is resorbed andreplaced by fibrous tissue. Ossifying fibromas usuallyappear as solitary radiolucencies that may or may notbe in contact with the apices of adjacent teeth (Figure5-22). Because the lesion is ossifying (or cementifying),the lesion, with time, demonstrates calcified compo-nents in its center. These components enlarge and coa-lesce, until eventually most of the lesion appearsradiopaque (see Figure 5-22).

Differentiating the ossifying fibroma from periradic-ular lesions is not difficult unless the dentist depends onradiographic findings alone. Characteristically, thepulps in the teeth in the region of the lesion are vital.Final diagnosis is by excision and biopsy, which showelements of calcified structures within the stroma.125

Odontogenic Tumors

Ameloblastoma. The ameloblastoma is a rare butdestructive lesion. It is a locally invasive and sometimesdangerous lesion classified as an odontogenic tumor. It isusually painless and grows slowly. Clinically, it mayresemble a periradicular lesion, demonstrating similarsigns. As the lesion expands, it can cause displacementand increased mobility of teeth (Figure 5-23).Radiographically, it is usually multilocular but mayappear as a solitary lesion, frequently associated with theapices of teeth, particularly in the mandibular posteriorregion. Often there is associated root resorption.126

The lesion may manifest endodontic-like clinicalsymptoms. An ameloblastoma may cause expansion ofthe jaws or erode the cortical bone and invade adjacentsoft tissue. It is then visible and detectable on palpa-tion. Some lesions are solid, whereas others are soft andfluctuant. If the lesion has undergone cystic degenera-

Figure 5-22 Central ossifying fibroma gradually calcifying withtime. The asymptomatic lesion discovered in a radiographic surveyinitially resembled endodontic pathosis. (Courtesy of Dr. RaymondJ. Melrose.)

Figure 5-23 Two examples of ameloblastoma. A, Surgical specimenof infiltrating ameloblastoma of mandible. B, “Unicystic” ameloblas-toma. This solitary lesion has displaced teeth much as an apical cystwould do. The teeth are vital. (Courtesy of Dr. Raymond J. Melrose.)

A

B

tion, straw-colored fluid may be aspirated, which givesthe appearance of an apical cyst.

Again, the differential diagnosis depends on a morecareful examination than radiographs alone.Radiographically and clinically, the ameloblastomamay resemble many other types of bony lesions,including periradicular lesions. The critical test is thevitality of pulps of adjacent teeth. Unless theameloblastoma has caused significant damage byinvading and disrupting sensory nerves (which is sel-dom), the teeth will respond to pulp testing.

Nonodontogenic Lesions

Central Giant Cell Granuloma. Of unknown eti-ology, the central giant cell granuloma is an expansiledestructive lesion of the bone.127 It most commonlyoccurs in children and young adult females andappears radiographically as a unilocular or multilocu-

194 Endodontics

lar radiolucency in the anterior-premolar region of themandible. Clinically, the lesion is usually asympto-matic, but the involved region may be painful andshow bony expansion.123 Radiographically, it oftensurrounds apices and occasionally may produce rootresorption or tooth displacement (Figure 5-24).Histologically, the stroma is characterized by fibroblas-tic tissue with foci of hemorrhage, many vascularspaces, and concentrations of multinucleated giantcells (Figure 5-25). Significantly and diagnostically, thepulps are usually vital, although the teeth are occasion-ally nonresponsive, apparently because of sensorynerve damage.

Because the pulps of adjacent teeth often have theirblood supply interrupted during curettage of thelesion, root canal treatment is often necessary before orafter surgical removal.

Nasopalatine Duct Cyst. Also known as the inci-sive canal cyst and median anterior maxillary cyst, thenasopalatine duct cyst is one of the more commonpathologic entities arising in the anterior region of themaxilla. Because of its location, radiographic appear-ance, and symptoms, it is easily confused with a peri-radicular lesion (Figure 5-26). It arises from remnantsof the embryologic nasopalatine duct and so is consid-ered a developmental cyst.

Clinically, the lesion is usually asymptomatic but mayshow swelling or, if secondarily infected, discharge of pusin the incisive papilla region.128 Radiographically, awell-defined radiolucent area is seen interradicularly orapically to the maxillary central incisors. It is often heartshaped owing to superimposition of the anterior nasal

Figure 5-24 Central giant cell granuloma. A relatively smoothradiolucent lesion in the anterior region of the mandible. Noresorption or displacement of teeth is noted. The teeth respondedto vitality tests. (Courtesy of the Department of Oral Pathology,Loma Linda University.)

Figure 5-25 Central giant cell granuloma—relatively loose con-nective tissue with numerous fibroblasts and a few giant cells (whitearrows).


spine (see Figure 5-26). Growth of the cyst may causedivergence of roots.

As with other periradicular radiolucencies, pulptesting is the critical diagnostic determinant. A radi-olucency associated with vital teeth indicates anasopalatine duct cyst. A radiolucency associated witha nonvital pulp, although it resembles a nasopalatineduct cyst, is likely to be an endodontic lesion. In addi-tion to pulp testing, exposing radiographs from differ-ent horizontal angles can help in differentiation. If theradiolucency is caused by a necrotic pulp, it will not beseparated from the apex by the change in angles.However, if the radiolucency is caused by a large nor-mal or a cystic nasopalatine duct, it will be moved fromthe apices with different horizontal angles of the cone(Figure 5-27).

Simple Bone Cyst. Also referred to as the solitary,traumatic, or hemorrhagic bone cyst or idiopathicbone cavity,106 the simple bone cyst is most frequentlyfound in the posterior mandible of young people, withfewer in older age groups. There is no sex predilec-tion.129 The etiology is unknown.

Simple bone cysts usually present a well-definedradiolucency but may also manifest radiopacities.130

They may have characteristically scalloped superficial

Figure 5-26 Nasopalatine duct cyst. This could be confused withendodontic pathosis. There was a history of trauma, with calcificmetamorphisis of the right central incisor. Note the heart-shapedappearance of the lesion. (Courtesy of Dr. Richard Walton).

Figure 5-27 Nasopalatine duct cyst. A, A radiolucent lesion was noted near the apex of the vital maxillary central incisor (open arrows).B, By change of angulation, the radiolucent area “moves” between the two central incisors (white arrows). The lesion was asymptomatic.

A B

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borders as the lesions extend between the roots of theteeth. Superimposed over the root apices, they closelyresemble periradicular lesions (Figure 5-28). The dif-ferentiation is not easily made on radiographs alone. Inthe case of the traumatic bone cyst, the lamina duraoften remains intact, and the associated teeth respondto pulp testing.

An empty or fluid-filled cavity with a scanty granu-lation tissue lining is encountered at surgery. Treatmentconsists of establishing hemorrhage into the defect.These lesions should not be curetted in their entiretybecause this may sever the blood supply to the pulps inthe overlying teeth and result in pulp necrosis.

Globulomaxillary Cyst. Although the globulo-maxillary cyst has been classically regarded as a fissuralcyst,131 histologic and clinical evidence seemed to indi-cate that this lesion does not, in fact, exist as a separateentity.132,133 Recently, D’Silva and Anderson ques-tioned this assumption, stating that “the globulomaxil-lary cyst should again be considered an identifiableclinicopathologic entity.”134 The radiograph in Figure5-29, A, may well represent an example of the so-called“true” lesion.

Figure 5-28 Simple bone cyst. Radiolucency superimposed over themesial root apex of the first molar demonstrates the typical scallopedappearance. The teeth respond to pulp testing. Characteristically, thebony cavity is empty on surgical exposure.

Figure 5-29 Two examples of a so-called “globulomaxillary” cyst. A, Although having every appearance of a true apical cyst, this lesion isassociated with vital anterior teeth. This may be a true globulomaxillary cyst. (Courtesy of Dr. Richard E. Walton.) B, Necrotic pulp in thelateral incisor with dens en dente. The resultant lesion simulates a globulomaxillary cyst and is a frequent occurrence with anomalous inci-sors. (Courtesy of Dr. Raymond J. Melrose.)

A B


Contrary to this classic assumption, Wysocki andGoldblatt have countercharged that D’Silva andAnderson are wrong, that the “so-called globulomaxil-lary cyst is extinct” and is, in all reality, related tonecrotic pulps in maxillary lateral incisors135 (Figure5-29, B).

Careful diagnosis, in particular pulp vitality testing,should always be performed on teeth in the region ofthe globulomaxillary cyst.

Enostosis. The general group of radiopacities seenunder the classification of enostosis must be differenti-

ated from the common condensing osteitis frequentlyfound in association with necrotic or inflamed pulps.There is confusion in the literature concerning thenature and classification of these lesions. Some authorsconsider them to be an osteoma or osteosclerosis,136

whereas others refer to them as enostosis.137 The term“enostosis” is preferable as these radiopacities probablyrepresent developmental entities analogous to exosto-sis. They are not malignant neoplasms, as would beimplied by the term “teoma.”

Clinically and radiographically, enostoses usuallycan be readily differentiated from condensing osteitis.Enostoses are not pathosis; therefore, they are asymp-tomatic and cause no outward manifestations of jawenlargement or soft tissue swelling. The growth is cen-tral and therefore on the endosteal surface and resideswithin the trabecular space. Radiographically, these areusually better defined (Figure 5-30) and less diffusethan condensing osteitis, which tends to have a concen-tric radiopaque appearance around the apices ofinvolved teeth. Because condensing osteitis is aninflammatory endodontic lesion, it may be associatedwith the signs and symptoms that accompany pulpal orperiradicular pathosis and may repair following rootcanal treatment (see Figure 5-9).

Malignancies

Carcinomas or sarcomas of various types are found inthe jaws, rarely as primary but usually as metastaticlesions (Figures 5-31 and 5-32). Since they may mani-fest a variety of clinical and radiographic findings, this

Figure 5-30 Enostosis. Also known as sclerotic bone. Theradiopaque mass (arrows) probably represents an outgrowth ofcortical bone on the endosteal surface. It is associated with neitherpulpal nor periradicular pathosis and can be differentiated radi-ographically from condensing osteitis (see Figure 5-9) by itswell-defined borders and homogeneous opacity.

Figure 5-31 Vestibular-buccal swelling from metastatic breastcancer. Appearance and symptoms can be confused with apicalabscess. (Courtesy of Drs. Raymond J. Melrose and Albert Abrams.)

Figure 5-32 Metastatic breast cancer. All three teeth are nonre-sponsive to pulp testing. Unusual chisel edge and moth-eatenresorption are not typical of inflammatory osseous lesion. A biopsyproved lesion malignant. (Courtesy of Drs. Raymond J. Melrose andAlbert Abrams.)

discussion will be limited to a few of the more impor-tant aspects.123

Sarcoma. When seen in the jaws, these usually rep-resent metastasis from other sites, although occasional-ly a primary lesion will arise in the mandible or maxil-la. The osteosarcoma may have an appearance thatresembles a periradicular lesion. It is frequentlyaccompanied by pain and swelling and may causeextensive bone loss and mobility of teeth in areas of its

198 Endodontics

growth. A common early manifestation is the symmet-ric widening of the periodontal ligament space, whichclosely resembles acute apical periodontitis.138 Therapidly growing lesion may cause extensive rootresorption and loss of pulp vitality in the associatedteeth.

Carcinoma. Generally found in older patients,involvement of the jaws (usually the mandible) is bymetastasis from a primary lesion elsewhere. Occasionally,the diagnosis of a jaw metastasis is the initial indication ofa primary lesion at another site.139 Therefore, the dentistmust be alert to this possibility. These jaw lesions are usu-ally radiolucent but may be mixed with radiopacities. Theprognosis for these patients is poor; most do not survivemore than a year.

Carcinoma lesions of the jaw may also manifest painand swelling, loosening of teeth, or paresthesia, similarto endodontic pathosis.140 Overall, however, metastaticcarcinoma of the jaws usually has enough dissimilari-ties to endodontic periradicular pathosis to make thedentist suspicious. But because of similarities, differen-tial diagnosis of the malignant lesions from periradicu-lar pathosis is not always simple (Figure 5-33).Radiolucent jaw malignancies have been mistaken forperiradicular lesions.141

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periradicular lesions (chapter 5)

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