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PERIRADICULAR LESIONS
Mahmoud Torabinejad and Richard E. Walton
Other investigators examined the flora of previously macrophages, and lymphocytes,7 all of which have spe-
traumatized teeth with necrotic pulps with and with- cific roles in inflammatory responses.
out periradicular pathosis.3,4 Teeth without apical
lesions were aseptic, whereas those with periradicular Mediators of Periradicular Lesions
lesions had positive bacterial cultures. Korzen et al. The inflammatory process is not completely under-
demonstrated the importance of the amount of micro- stood, but a number of substances have been implicat-
bial inoculum in the pathogenesis of pulpal and peri- ed as mediators of inflammation. They include neu-
radicular lesions.5 They showed that higher levels of ropeptides, fibrinolytic peptides, kinins, complement
contamination lead to greater inflammatory responses. fragments, arachidonic acid metabolites, vasoactive
In addition to bacterial irritation, the periradicular amines, lysosomal enzymes, cytokines, and mediators
tissues can be mechanically irritated and inflamed. of immune reactions.
Physical irritation of periradicular tissues can also Neuropeptides. These are proteins generated from
occur during root canal therapy if the canals are instru- somatosensory and autonomic nerve fibers following
mented or filled beyond their anatomic boundaries. tissue injury. They include substance P (SP), calcitonin
Periradicular tissues can be irritated by impact trauma, gene–related peptide (CGRP), dopamine hydrolase,
hyperocclusion, endodontic procedures and accidents, neuropeptide Y originating from sympathetic nerve
pulp extirpation, overinstrumentation, root perfora- fibers, and vasoactive intestinal polypeptides generated
tion, and overextension of filling materials. from parasympathetic nerve fibers.8
Chemicals are used as adjuncts for better débride- Substance P is a neuropeptide present in both the
ment and disinfection of the root canal system. An in peripheral and central nervous systems. The release of
vitro study, however, has shown that many of these SP can cause vasodilation, increased vascular perme-
chemicals are highly concentrated and not biocompat- ability, and increased blood flow during inflammation.
ible.6 Irrigating solutions such as sodium hypochlorite In addition, it can cause the release of histamine from
and hydrogen peroxide, intracanal medications, and mast cells and potentiate inflammatory responses.
chelating agents such as ethylenediaminetetraacetic Calcitonin gene–related peptide has been localized
acid (EDTA) can also cause tissue injury and inflam- in small to medium sensory nerve fibers. Like SP, it is a
mation if inadvertently extruded into the periradicular potent vasodilator and may play a role in the regulation
tissues. Some components in obturation materials can of blood flow in bone, periosteum, and other sites.
irritate the periradicular tissues when extruded beyond Substance P and CGRP have been found in pulp and
the root canal system. periradicular tissues.9
Fibrinolytic Peptides. The fibrinolytic cascade is
Periradicular Reaction to Irritation triggered by the Hageman factor, which causes activa-
The periradicular tissues consist of apical root cemen- tion of circulating plasminogen, previously known as
tum, periodontal ligament, and alveolar bone. The apical fibrinolysin and digestion of blood clots. This results in
periodontium is also richly endowed with cellular and release of fibrinopeptides and fibrin degradation prod-
extracellular components containing blood and lymphat- ucts that cause increased vascular permeability and
ics, as well as sensory and motor nerve fibers supplying leukocyte chemotaxis.10
both pulp and periodontium. Other structural elements Kinins. Release of kinins causes many signs of
of the periodontal ligament include ground substance, inflammation.11 They include chemotaxis of inflam-
various fibers, fibroblasts, cementoblasts, osteoblasts, matory cells, contraction of smooth muscles, dilation
osteoclasts, histiocytes, undifferentiated mesenchymal of peripheral arterioles, increased vascular permeabili-
cells, and the epithelial cell rests of Malassez. ty, and pain. The kinins are produced by proteolytic
Irritation of periradicular tissues results in inflam- cleavage of kininogen by trypsin-like serine proteases,
matory changes taking place. The vascular response to the kallikreins. The kinins are subsequently inactivated
an injury includes vasodilation, vascular stasis, and by removal of the last one or two C-terminal amino
increased vascular permeability. The latter leads to acids by the action of peptidase.12 The kallikreins are
extravasation of fluid and soluble components into the also able to react with other systems, such as the com-
surrounding tissues. These vascular changes cause red- plement and coagulation systems, to generate other
ness, heat, swelling, and pain, which are the cardinal trypsin-like serine proteases.13 Elevated levels of kinins
signs of inflammation. The inflammatory cells involved have been detected in human periapical lesions.14
in various stages of tissue injury and repair include Complement System. The complement system con-
platelets, PMNs, mast cells, basophils, eosinophils, sists of a number of distinct plasma proteins capable of
Periradicular Lesions 177
interacting with each other and with other systems to leukocytes and mast cells are the major sources for pro-
produce a variety of effects.15 Complement is able to duction of LTs.21 Leukotriene B4 is a powerful chemo-
cause cell lysis if activated on the cell membrane and tactic agent from PMNs. Increased levels of LTB4 have
also to enhance phagocytosis through interaction with been found in symptomatic human periapical
complement receptors on the surface of phagocytic lesions.22 Other leukotrienes such as LTC4, LTD4, and
cells. Complement can also increase vascular perme- LTE4 are chemotactic for eosinophil and macrophage,
ability and act as a chemotactic factor for granulocytes cause increased vascular permeability, and stimulate
and macrophages. The complement system is a com- lysozyme release from PMNs and macrophages.15
plex cascade that has two separate activation pathways Vasoactive Amines. Vasoactive amines are present
that converge to a single protein (C3) and complete the in mast cells, basophils, and platelets. Histamine, the
cascade in a final, common sequence. Complement can major one of these substances, is found in all three cell
be activated through the classic pathway by antigen- types, whereas serotonin is present only in platelets.21
antibody complexes or through the alternative pathway Release of these materials causes increased vascular
by directly interacting with complex carbohydrates on permeability, as well as muscle contraction of airways
bacterial and fungal cell walls or with substances such and gastrointestinal tracts. Numerous mast cells have
as plasmin. been detected in human periradicular lesions.23,24
Several investigators have found C3 complement Physical or chemical irritation of periradicular tissues
components in human periradicular lesions.10 during root canal therapy can cause mast cell de-
Activators of the classic and alternative pathways of the granulation. The discharged vasoactive amines can ini-
complement system include immunoglobulin (Ig) M, tiate an inflammatory response or aggravate an existing
IgG, bacteria and their by-products, lysosomal enzymes inflammatory process in the periradicular tissues.
from PMNs, and clotting factors. Most of these activa- Lysosomal Enzymes. Lysosomal enzymes are stored
tors are present in periradicular lesions. Activation of
preformed in membrane-bound bodies within inflam-
the complement system in these lesions can contribute
matory cell cytoplasm. Lysosomal bodies are found in
to bone resorption either by destruction of already
PMNs, macrophages, and platelets and contain acid as
existing bone or by inhibition of new bone formation
well as alkaline phosphatases, lysozyme, peroxidase,
via the production of prostaglandins (PGs).
cathepsins, and collagenase. They can be released via
Arachidonic Acid Metabolites. Arachidonic acid is
exocytotic type events during cell lysis or secreted dur-
formed from membrane phospholipid as a result of cell
ing phagocytosis. Release of these enzymes into the tis-
membrane injury and phospholipase A2 activity and is
further metabolized. sues causes increased vascular permeability, leukocyte
Prostaglandins are produced as a result of the acti- chemotaxis, generation of C5a from C5, and
vation of the cyclooxygenase pathway of the arachi- bradykinin formation.15 Aqrabawi and associates
donic acid metabolism. Their pathologic functions examined human periradicular lesions for the presence
include increased vascular permeability and pain. of lysosomal hydrolytic arylsulfatase A and B and
Torabinejad and associates demonstrated in an animal found higher levels of these substances in lesions of
model that periradicular bone resorption could be endodontic origin compared to the control tissues.25
inhibited by administration of indomethacin Cytokines. The major cytokines that have been
(Indocin), an antagonist of PGs.16 High levels of PGE2 implicated in bone resorption are various interleukins
were found in periradicular lesions of patients with (ILs) and tumor necrosis factors (TNFs).15
symptomatic apical periodontitis (SAP).17 Takayama Interleukin-1 is produced primarily by monocytes
et al.18 and Shimauchi and coworkers19 confirmed and macrophages.26,27 Human monocytes produce at
these findings by demonstrating lower levels of PGE2 least two IL-1 species, IL-1α and IL-1β.28 Interleukin-
associated with asymptomatic large lesions or cessation 1β is the major form secreted by human monocytes.
of symptoms subsequent to emergency cleaning and The chief component of osteoclast activating factor was
shaping of root canals. Miyauchi et al. used immuno- purified and found to be identical to IL-1β.29
histochemical staining and found PGE2, PGF2α, and Interleukin-1β is the most active of the cytokines in
6-keto-PGF1α in the experimentally induced periapi- stimulating bone resorption in vitro, 15-fold more
cal lesions in rats.20 potent than IL-1α and 1,000-fold more potent than
Leukotrienes (LTs) are produced as a result of the TNFs.30 Interleukin-1 has been associated with
activation of the lipoxygenase pathway of the arachi- increased bone resorption in vivo in several diseases.
donic acid metabolism. Polymorphonuclear neutrophil Interleukin-1 has been implicated in the bone resorp-
178 Endodontics
tion for periodontal disease and periradicular gens such as bacteria or their by-products interact with
lesions.31–39 either IgG or IgM antibodies. The complexes can bind
Interleukin-6 is produced by a number of cells with to the platelets and cause release of vasoactive amines,
a wide range of cell targets.40 It is produced by increased vascular permeability, and chemotaxis of
osteoblasts, but in response to other bone resorptive PMNs. The pathologic effects of immune complexes in
agents such as parathyroid hormone, IL-1, and 1,25- periradicular tissues have been demonstrated in experi-
hydroxyvitamin D3.41 Interleukin-6 is produced dur- mental animals. Torabinejad and associates placed sim-
ing immune responses and may play a role in human ulated immune complexes in feline root canals and
resorptive diseases such as adult periodontitis42 and showed a rapid formation of periradicular lesions and
rheumatoid arthritis.43 Recent studies have shown that accumulation of numerous PMNs and osteoclasts.16
IL-6 may play a significant role in the pathogenesis of These findings were confirmed when Torabinejad and
human periradicular lesion.44,45 Kiger immunized cats with subcutaneous injections of
Tumor necrosis factor-α and TNF-β have bone keyhole-limpet hemocyanin and challenged the animals
resorption activities similar to that of IL-1. Their effects with the same antigen via the root canals.50
on osteoclasts are indirect and are mediated through Radiographic and histologic observations showed the
osteoblasts.46 The effect of TNF-α on bone resorption development of periradicular lesions consistent with
is dependent on PG synthesis.47 Tumor necrosis factors characteristics of an Arthus-type reaction.
have been detected in periradicular lesions of experi- Immune complexes in human periradicular lesions
mental animals and humans.38,39,48,49 have been found using the anticomplement immuno-
Immunologic Reactions. In addition to the non- fluorescence technique, localized immune complexes
specific mediators of inflammatory reactions, im- in human periradicular specimens.51 Torabinejad and
munologic reactions also participate in the formation associates measured the serum concentrations of circu-
and perpetuation of periradicular pathosis.10,15,35 lating immune complexes in patients with asympto-
These reactions can be divided into antibody- and cell- matic and symptomatic periradicular lesions. The
mediated responses. The major antibody-mediated results indicated that immune complexes formed in
reactions include IgE mediated reactions and antigen- chronic periradicular lesions are confined within the
antibody (immune complex)–mediated reactions. lesions and do not enter into the systemic circulation.
Immunoglobulin E–mediated reactions occur as a However, when the serum concentrations of circulating
result of an interaction between antigens (allergens) immune complexes in patients with acute abscesses
and basophils in the blood or mast cells in the tissues. were compared with those of people without these
Vasoactive amines such as histamine or serotonin are lesions, they found that these complexes entered the
present in preformed granules in basophils and mast circulation in patients with symptomatic periradicular
cells and are released by a number of stimuli includ- abscesses. The concentrations of these complexes came
ing physical and chemical injuries, complement acti- back to normal levels after either root canal therapy or
vation products, activated T lymphocytes, and bridg- extraction of involved teeth.52,53
ing of membrane-bound IgE by allergens. Numerous Cell-Mediated Immune Reactions. Numerous B and
mast cells have been detected in human periradicular T lymphocytes have been found in human periradicular
lesions.23,24 IgE molecules have also been found in lesions by the indirect immunoperoxidase method,54
human periapical lesions.10 Presence of potential with the T cells outnumbering the B cells significantly.
antigens in the root canals, IgE immunoglobulin, and A number of investigators have found approximately
mast cells in pathologically involved pulp and peri- equal numbers of T-cell subsets in chronic lesions (T
radicular lesions indicate that IgE-mediated reactions helper/T suppressor ratio < 1.0).55–58 Stashenko and Yu
can occur in periradicular tissues. Irritation of demonstrated in developing lesions in rats that T helper
periradicular tissues during cleaning, shaping, or cells outnumber T suppressor cells during the acute
obturation of the root canal system with antigenic phase of lesion expansion. In contrast, T suppressor
substances can cause mast cell degranulation. The dis- cells predominate at later time periods when lesions are
charged vasoactive amines can initiate an inflamma- stabilized.58 Based on these results, it appears that T
tory response or aggravate an existing inflammatory helper cells may participate in the initiation of peri-
process in the periradicular tissues.15 radicular lesions, whereas T suppressor cells prevent
Antigen-Antibody or Immune Complex Reactions. rapid expansion of these lesions.
Antigen-antibody or immune complex reactions in The specific role of T lymphocytes in the pathogen-
periradicular tissues can be formed when extrinsic anti- esis of periradicular lesions has been studied by several
Periradicular Lesions 179
investigators.39,59,60 Wallstrom and Torabinejad irritation of the periapical tissues can cause SAP.
exposed the pulps of mandibular molars of athymic Impact trauma can also cause SAP (see chapter 15).
and conventional rats and left them open to the oral Sensitivity to percussion is the principal clinical fea-
flora for 2, 4, or 8 weeks.59 Statistical analysis of the tis- ture of SAP. Pain is pathognomonic and varies from
sue reactions to this procedure showed no significant slight tenderness to excruciating pain on contact of
difference between periradicular tissue responses of the opposing teeth. Depending on the cause (pulpitis or
two species of animals. Waterman and associates com- necrosis), the involved tooth may or may not respond
pared periradicular lesion formation in immunosup- to vitality tests. Regardless of the causative agents, SAP
pressed rats with that in normal rats and found no sig- is associated with the exudation of plasma and emigra-
nificant histologic differences between the two tion of inflammatory cells from the blood vessels into
groups.60 Fouad studied the progression of pulp necro- the periradicular tissues. The release of mediators of
sis and the histomorphometric features of periapical inflammation causes breakdown of the periodontal lig-
lesions in mice with severe combined immunodeficien- ament and resorption of the alveolar bone. A minor
cies.39 He found no significant differences between the physical injury, such as penetrating the periradicular
reaction and progression of pulp and periapical tissues tissues with an endodontic file, may cause a transient
between these animals and those in normal mice. These inflammatory response. However, a major injury, caus-
findings suggest that the pathogenesis of periradicular ing extensive tissue destruction and cell death, can
lesions is a multifactorial phenomenon and is not total- result in massive inflammatory infiltration of the peri-
ly dependent on the presence of a specific group of cells radicular tissues. Although the dynamics of these
or mediators. inflammatory lesions are poorly understood, the con-
sequences depend on the type of irritant (bacterial or
CLINICAL CLASSIFICATION OF nonbacterial), degree of irritation, and host defensive
PERIRADICULAR LESIONS mechanisms. The release of chemical mediators of
Periradicular diseases of pulpal origin have been inflammation and their action on the nerve fibers in
named and classified in many different ways. These the periradicular tissues partially explain the presence
lesions do not occur as individual entities; there are of pain during SAP. Also, since there is little room for
clinical and histologic crossovers in the terminology expansion of the periodontal ligament, increased inter-
regarding periradicular lesions as the terminology is stitial tissue pressure can also cause physical pressure
based on clinical signs and symptoms as well as radi- on the nerve endings, causing an intense, throbbing,
ographic findings. In this chapter, periradicular lesions periradicular pain. Increased pressure may be more
are divided into three main clinical groups: sympto- important than the release of the inflammatory media-
matic (acute) apical periodontitis, asymptomatic tors in causing periradicular pain. The effect of fluid
(chronic) apical periodontitis, and apical abscess. pressure on pain is dramatically demonstrated on
Since there is no correlation between histologic find- opening into an unanesthetized tooth with this condi-
ings and clinical signs, symptoms, and duration of the tion. The release of even a small amount of fluid pro-
lesion,10,21 the terms acute and chronic, which are his- vides the patient with immediate and welcome relief.
tologic terms, will not be used in this chapter. Instead, Radiographs show little variation, ranging from nor-
the terms symptomatic and asymptomatic, which mal to a “thickening” of the periodontal ligament space
describe clinical conditions, will be used. (Figure 5-1) in teeth associated with SAP.
APICAL PERIODONTITIS Asymptomatic Apical Periodontitis
Depending on clinical and radiographic manifesta- Asymptomatic apical periodontitis (AAP) may be
tions, these lesions are classified as symptomatic or preceded by SAP or by an apical abscess. However,
asymptomatic periodontitis. the lesion frequently develops and enlarges without
any subjective signs and symptoms. Inadequate root
Symptomatic Apical Periodontitis canal treatment may also cause the development of
Symptomatic apical periodontitis (SAP) is a localized these lesions. Generally, a necrotic pulp gradually
inflammation of the periodontal ligament in the apical releases noxious agents with low-grade pathogenicity
region. The principal causes are irritants diffusing from or in low concentration that results in the develop-
an inflamed or necrotic pulp. Egress of irritants such as ment of AAP. This pathosis is a long-standing, “smol-
bacteria, bacterial toxins, disinfecting medications, dering” lesion and is usually accompanied by radi-
debris pushed into the periradicular tissues, or physical ographically visible periradicular bone resorption.
180 Endodontics
Figure 5-1 Radiographic features of symptomatic apical peri- Figure 5-2 Radiographic appearance of asymptomatic apical
odontitis. “High” amalgam restoration was placed on the occlusal periodontitis. Two distinct lesions are present at the periradicular
surface of a second mandibular molar. The periodontal ligament regions of a mandibular first molar with necrotic pulp.
space is widened at the apex (arrows). Clinically, the tooth is
extremely sensitive to percussion.
This condition is almost invariably a sequela to pulp apical bone, and sometimes the root cementum and
necrosis. dentin, is infiltrated by plasma cells, lymphocytes,
The clinical features of AAP are unremarkable. The mononuclear phagocytes, and occasional neutrophils.
patient usually reports no significant pain, and tests Occasionally, needle-like spaces (the remnants of cho-
reveal little or no pain on percussion. If AAP perforates lesterol crystals), foam cells, and multinucleated for-
the cortical plate of the bone, however, palpation of eign body giant cells are seen in these lesions (Figure
superimposed tissues may cause discomfort. The asso- 5-4).69 Animal studies have shown that cholesterol
ciated tooth has a necrotic pulp and therefore should crystals can cause failure of some lesions to resolve fol-
not respond to electrical or thermal stimuli. lowing nonsurgical root canal therapy.70 Nerve fibers
Radiographic findings are the diagnostic key.
Asymptomatic apical periodontitis is usually associat-
ed with periradicular radiolucent changes. These
changes range from thickening of the periodontal liga-
ment and resorption of the lamina dura to destruction
of apical bone resulting in a well-demarcated radiolu-
cency (Figure 5-2).
Asymptomatic apical periodontitis has traditionally
been classified histologically as either a periradicular
granuloma or a periradicular cyst. Various clinical
methods have been used to attempt to differentiate
these 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 Rio
showed that 59.3% of the periradicular lesions were
granulomas, 22% cysts, 12% apical scars, and 6.7%
other pathoses.67 Histologically, the periradicular gran- Figure 5-3 Apical periodontitis (granuloma) in its more classic
uloma consists predominantly of granulation inflam- form. The central zone is dense with round cells (plasma cells and
matory tissue68 with many small capillaries, fibroblasts, small lymphocytes). Beyond is a circular layer of fibrous capsule.
Limited bone regeneration (arrow) can be clearly seen at outer
numerous connective tissue fibers, inflammatory infil- margin of capsule. Human tooth. Reproduced with permission
trate, and usually a connective tissue capsule (Figure from Matsumiya S. Atlas of oral pathology. Tokyo: Tokyo Dental
5-3). This tissue, replacing the periodontal ligament, College Press; 1955.
Periradicular Lesions 181
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.
have also been demonstrated in these lesions.71,72 Local Effects of Asymptomatic Apical Periodontitis.
Epithelium in varying degrees of proliferation can be Bone and periodontal ligament can be replaced by
found in a high percentage of periradicular granulo- inflammatory tissue. This process is associated with
mas (Figure 5-5).69 formation of new vessels, fibroblasts, and sparse,
Periradicular Cyst. Histologic examination of a immature connective tissue fibers. As long as egress of
periradicular cyst shows a central cavity lined by stratified irritants from the root canal system to the periradicu-
squamous epithelium (Figure 5-6). This lining is usually lar tissues continues or macrophages fail to eliminate
incomplete and ulcerated. The lumen of the periradicu- the materials they have phagocytosed,73 destructive as
lar cyst contains a pale eosinophilic fluid and occasional- well as healing processes will occur simultaneously in
ly some cellular debris (Figure 5-7). The connective tissue asymptomatic apical lesions. The extent of the lesion
surrounding the epithelium contains the cellular and depends on the potency of the irritants within the root
extracellular elements of the periradicular granuloma. canal system and the activity level of defensive factors
Inflammatory cells are also present within the epithelial in this region. If a balance between these forces is main-
lining of this lesion. Histologic features of periradicular tained, the lesion continues in an asymptomatic man-
cysts are very similar to those of periradicular granulo- ner indefinitely. On the other hand, if the causative fac-
mas except for the presence of a central epithelium-lined tors overcome the defensive elements, a symptomatic
cavity filled with fluid or semisolid material. periradicular lesion may be superimposed on the
182 Endodontics
B
in turn, produces more soft and hard tissue necrosis. Figure 5-11 A, Localized abscess resulting from an incomplete
The suppuration process finds lines of least resistance root canal treatment on a maxillary lateral incisor. B, Cellulitis
and eventually perforates the cortical plate. When it caused by a maxillary first molar with necrotic pulp. (Courtesy of
Dr. Mohammad Baghai.)
reaches the soft tissue, the pressure on the periosteum
is relieved, usually with an abatement of symptoms.
Once this drainage through bone and mucosa is
obtained, suppurative apical periodontitis or an
asymptomatic periradicular abscess is established.
The healing of periradicular tissues after root canal Do different types of endodontic periradicular
treatment is often associated with formation and lesions have different patterns of healing? Possibly
organization of a fibrin clot, granulation tissue forma- there are variations, but this has not been conclusively
tion and maturation, subsidence of inflammation, and, demonstrated. Of the three general lesion types—gran-
finally, restoration of normal architecture of the peri- uloma, cyst, and abscess—it is likely that the granulo-
odontal ligament. Since the inflammatory reactions are ma follows the pattern described above.99 The abscess
usually accompanied by microscopic and macroscopic may be slower; the exudates and bacteria must be
resorption of the hard tissues, bone and cementum cleared from the tissues before regeneration occurs. A
repair occurs as well. variation of the abscess, the sinus tract (intraoral and
Periradicular lesions repair from the periphery to extraoral) will heal following root canal treatment.100 It
the center. If the cortical plate is perforated by resorp- has been suggested that the periradicular cyst with a
tion, the healing process is partially periosteal in cavity that does not communicate with the root canal is
nature. Boyne and Harvey, after creating cortical plate less likely to resolve following root canal treatment101;
perforations in the jaws of humans, showed that labial this has yet to be proven.
defects measuring 5 to 8 mm in diameter healed com- There is some evidence that at least some lesions
pletely within 5 months.97 When they studied apical may heal with formation of scar tissue.102 Although the
defects measuring 9 to 12 mm, they found that these frequency of healing by scar tissue is unknown, it is
lesions had limited labial cortex formation and instead likely that it seldom occurs following root canal treat-
were filled with avascular fibrous connective tissue up ment, being much more common after periradicular
to 8 months following surgery. surgery on maxillary anterior teeth.103
If lesions have not involved the periosteum, the heal-
ing response will be endosteal, with formation of bony NONENDODONTIC PERIRADICULAR LESIONS
trabeculae extending inward from the walls of the lesion Bhaskar, in his textbook on radiographic interpreta-
toward the root surface. On the periphery, osteoblasts tion, listed 38 radiolucent lesions and other abnormal-
appear and elaborate bone matrix (osteoid), which grad- ities of the jaws.104 Three of these lesions, dental gran-
ually mineralizes as it matures. If cementum or dentin uloma, radicular cyst, and abscess, are categorized as
has been resorbed by the inflammation, remodeling and being related to necrotic pulps. In addition, Bhaskar
repair are by secondary cementum. identifies 16 radiopaque lesions of the jaws, 3 of which,
The last to form is likely the fibrous component inter- condensing osteitis, sclerosing osteomyelitis, and
posed between newly formed bone and the cemental root Garré’s osteomyelitis, are also related to pulpal patho-
surface. These fibers have basically two orientations. One sis. The dentist must therefore differentiate between the
is a true periodontal ligament arrangement, whereas the endodontic and the nonendodontic lesions, ruling out
other is an alignment of collagen parallel to the root sur- those that trace their origin from non–pulp-related
face. Both orientations represent complete healing. sources. Additional confusion in radiographic diagno-
The sequence of events post–endodontic treatment sis relates to normal radiolucent and radiopaque struc-
leading to complete repair of periradicular tissues, after tures that lie within or over apical regions.
inflammatory destruction of the periodontal ligament, Differential diagnosis of periradicular pathosis is
bone, or cementum, has not been validated. Most essential and, at times, confusing. There is a tendency
information is based on repair of extraction sites or for the clinician to assume that a radiolucency is an
healing of bone cavities following periradicular curet- endodontically related lesion and that root canal treat-
tage. These may or may not be accurate as to patterns ment is necessary without performing additional con-
of nonsurgical apical repair. A blood clot forms follow- firmatory tests. Avoid this pitfall!
ing extraction or apicoectomy, which becomes organ- The dentist must therefore be astute as well as
ized into recognizable granulation tissue. This tissue knowledgeable when diagnosing bony lesions. It is
contains endothelium-lined vascular spaces, vast num- important that teeth with sound pulps not be violated
bers of fibroblasts, and associated collagen fibers. The needlessly because of the mistaken notion that radiolu-
granulation tissue is infiltrated by neutrophils, lym- cencies in the apical region always represent endodon-
phocytes, and plasma cells. On the periphery of the tic pathema. The reverse is also true; endodontic
granulation tissue, osteoblasts and osteoclasts abound. lesions may mimic nonendodontic pathosis.
With maturation, the number of cells decreases, where- Significantly, most radiolucent lesions do indeed
as collagen increases. Ultimately, mature bone forms trace their origin to pulpal disease. Therefore, the den-
from the periphery toward the center.98 tist is likely to encounter many more endodontic
188 Endodontics
lesions, because of their sheer numbers, than other Routine periradicular or panographic films might
types of pathosis. However, many of the nonendodon- reveal its presence at the apex of adjacent teeth, some-
tic lesions mimic endodontic pathema, with similar times causing root resorption. An unusual variant is
symptoms and radiographic appearance.105 On the the circumferential dentigerous cyst (Figure 5-14). The
other hand, many of the nonendodontic lesions are tooth may erupt through the dentigerous cyst, with the
symptomless (as endodontic lesions frequently are) resulting radiolucency occurring periradicularly, thus
and are detected only on radiographs. To avoid errors, closely mimicking periradicular pathosis of pulp ori-
the dentist must approach all lesions with caution, gin.109 The dentigerous cyst occasionally may become
whether symptomatic or not. secondarily infected and inflamed, often via a pericoro-
This section will deal with lesions of the jaws cate- nal communication. The swelling and pain clinically
gorized as odontogenic or nonodontogenic in origin. resemble disease of pulpal origin.
Odontogenic lesions arise from remnants of odontoge- This cyst is readily differentiated from chronic apical
nesis (or the tooth-forming organ), either mesenchy- periodontitis or acute apical abscess in that the adjacent
mal or ectodermal in origin. Nonodontogenic lesions erupted tooth invariably demonstrates pulp vitality.
trace their origins to a variety of precursors and there- Lateral Periodontal Cyst. This uncommon cyst
fore are not as easily classified. arises at the lateral surface of a tooth, usually in the
Not all bony lesions that occur in the jaws will be mandibular premolar-canine area (Figure 5-15). This
discussed as many are extremely rare or do not ordi- lesion is currently thought to arise from remnants of
narily mimic endodontic pathosis. An oral pathology the dental lamina and probably represents the
text should be consulted for clinical features and intraosseous analog of the gingival cyst of the adult.110
histopathology of missing entities. Furthermore, the Clinically, the lesion is asymptomatic, and again the
lesions that are included are not discussed in detail. Of
primary concern are the clinical findings causing them
to resemble endodontic pathema, as well as those fac-
tors leading to accurate differential diagnosis.
Differentiating between lesions of endodontic and
nonendodontic origin is usually not difficult. Pulp
vitality 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 pulp
necrosis, giving negative vitality responses. Except by
coincidence, nonendodontic lesions are rarely associat-
ed with pulpless teeth. Other significant radiographic
and 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 reduced
enamel epithelium of an impacted or embedded tooth.
Therefore, they are most often associated with the
crowns either of impacted third molars, maxillary
canines, or mandibular second premolars. The majori-
ty are found in the mandible.106,107 Although most
remain small and asymptomatic, dentigerous cysts
have the potential to become aggressive lesions.
Continued enlargement may involve large areas of the
jaws, particularly the mandible, with displacement of Figure 5-14 Circumferential dentigerous cyst developed around
the crown of an unerupted canine. The cyst may be enucleated (care
teeth and expansion of cortices.108 must be taken to avoid the incisor) and the canine brought into
Dentigerous cysts may be confused with endodontic position with an orthodontic appliance. (Courtesy of Dr. Russell
lesions by either radiographic or other clinical findings. Christensen.)
Periradicular Lesions 189
demonstrates lesions that are often multiple, usually induces resorption of the medullary bone surrounding
involve the mandibular incisors, and occur most often the apex, resulting in a radiolucent lesion closely mim-
in middle-aged African American women. However, icking a lesion of pulpal origin (Figure 5-17). During
they can and do occur elsewhere in the jaws and in any this stage of radiolucency, errors are frequently
race and at other ages. Their etiology is unknown. made,122 emphasizing the necessity of pulp testing.
Periradicular cemental dysplasia has an interesting Unlike apical periodontitis or an apical cyst, this new
evolution.121 The progression is from normal alveolar growth is free of inflammation. Furthermore, nerves
bone to bone resorption and fibrosis and finally to and vessels are unimpeded as they make their passage
dense, atypical reossification. The initial stage (oste- to and from the root canal.
olytic stage) is characterized histologically by a prolif- In time, cementoblasts differentiate within the soft
eration of fibroblasts and collagen fibers in the apical tissue, and a central focus of calcification appears
region of the periodontal ligament. The resultant mass (intermediate stage) (Figure 5-18). This deposition of
A B
C
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 the
Walter Reed Army Institute of Research. US Army photograph.)
Periradicular Lesions 191
A B
Figure 5-18 A, Periradicular cemental dysplasia, intermediate stage, central incisor and canine. Slight calcification of the fibrotic lesion is
now 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.)
hard tissue may be continued over the years until near- ly a mandibular first molar.124 The tumor mass is often
ly all of the fibrous tissue is reossified. When this surrounded by a thin, radiolucent zone that is continu-
occurs, the evolution has reached its third and final ous with the periodontal ligament space. Histologically,
stage (mature stage) (Figure 5-19). The reossification the tumor shows fusion with the root cementum.
is characterized radiographically by increasing Differentiation between cementoblastoma and con-
radiopacity. densing osteitis is based on differences in radiographic
Problems of differential diagnosis arise in conjunc- appearance; condensing osteitis is diffuse, shows no
tion with the initial radiolucent stage of periradicular well-defined borders, and is associated with chronic
cemental dysplasia (see Figure 5-17). Clinically, the pulpal disease. Furthermore, the lamina dura and nor-
lesions are always asymptomatic, and the adjacent mal periodontal ligament space may remain intact in
teeth respond to vitality testing. Radiographically, an condensing osteitis.
intact lamina dura is usually (but not always) visible Cementifying and Ossifying Fibroma. The central
around the apices if carefully looking “through” the ossifying fibroma is a benign, neoplastic, fibro-osseous
radiolucency. lesion. Circumstantial evidence indicates that central
Osteoblastoma and Cementoblastoma. These are ossifying fibromas originate from elements of the peri-
apparent benign neoplasms and are closely related odontal ligament.120 Most of these lesions arise in the
lesions. Some believe that a cementoblastoma is, in periradicular region and therefore can be easily con-
reality, an osteoblastoma with an intimate relationship fused radiographically with endodontic periradicular
with the root (Figure 5-20). The benign cementoblas- lesions (Figure 5-21). They tend to occur in younger
toma (or true cementoma) is an uncommon neoplasm patients and in the premolar-molar region of the
thought to represent a neoplasm of cementoblasts.123 mandible. Because they are asymptomatic, the lesions
Radiographically, the lesion is characteristically associ- are frequently undetected. They attain a large size, often
ated and continuous with the roots of the teeth, usual- with visible expansion of the overlying cortex.
192 Endodontics
A B
Figure 5-19 A, Periradicular cemental dysplasia, mature stage, canine. Osseous calcification associated with vital pulp. Fibrotic stage is seen
at 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.)
The central ossifying fibroma has a characteristic The lesion may manifest endodontic-like clinical
progression of radiologic findings. During the early symptoms. An ameloblastoma may cause expansion of
stage, which is osteolytic, bone is resorbed and the jaws or erode the cortical bone and invade adjacent
replaced by fibrous tissue. Ossifying fibromas usually soft tissue. It is then visible and detectable on palpa-
appear as solitary radiolucencies that may or may not tion. Some lesions are solid, whereas others are soft and
be in contact with the apices of adjacent teeth (Figure fluctuant. If the lesion has undergone cystic degenera-
5-22). 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 appears
radiopaque (see Figure 5-22).
Differentiating the ossifying fibroma from periradic-
ular lesions is not difficult unless the dentist depends on
radiographic findings alone. Characteristically, the
pulps in the teeth in the region of the lesion are vital.
Final diagnosis is by excision and biopsy, which show
elements of calcified structures within the stroma.125
Odontogenic Tumors
Ameloblastoma. The ameloblastoma is a rare but
destructive lesion. It is a locally invasive and sometimes A
dangerous lesion classified as an odontogenic tumor. It is
usually painless and grows slowly. Clinically, it may
resemble a periradicular lesion, demonstrating similar
signs. As the lesion expands, it can cause displacement
and increased mobility of teeth (Figure 5-23).
Radiographically, it is usually multilocular but may
appear as a solitary lesion, frequently associated with the
apices of teeth, particularly in the mandibular posterior
region. Often there is associated root resorption.126
B
Figure 5-22 Central ossifying fibroma gradually calcifying with Figure 5-23 Two examples of ameloblastoma. A, Surgical specimen
time. The asymptomatic lesion discovered in a radiographic survey of infiltrating ameloblastoma of mandible. B, “Unicystic” ameloblas-
initially resembled endodontic pathosis. (Courtesy of Dr. Raymond toma. This solitary lesion has displaced teeth much as an apical cyst
J. Melrose.) would do. The teeth are vital. (Courtesy of Dr. Raymond J. Melrose.)
194 Endodontics
tion, straw-colored fluid may be aspirated, which gives lar radiolucency in the anterior-premolar region of the
the appearance of an apical cyst. mandible. Clinically, the lesion is usually asympto-
Again, the differential diagnosis depends on a more matic, but the involved region may be painful and
careful examination than radiographs alone. show bony expansion.123 Radiographically, it often
Radiographically and clinically, the ameloblastoma surrounds apices and occasionally may produce root
may resemble many other types of bony lesions, resorption or tooth displacement (Figure 5-24).
including periradicular lesions. The critical test is the Histologically, the stroma is characterized by fibroblas-
vitality of pulps of adjacent teeth. Unless the tic tissue with foci of hemorrhage, many vascular
ameloblastoma has caused significant damage by spaces, and concentrations of multinucleated giant
invading and disrupting sensory nerves (which is sel- cells (Figure 5-25). Significantly and diagnostically, the
dom), the teeth will respond to pulp testing. pulps are usually vital, although the teeth are occasion-
ally nonresponsive, apparently because of sensory
Nonodontogenic Lesions nerve damage.
Central Giant Cell Granuloma. Of unknown eti- Because the pulps of adjacent teeth often have their
ology, the central giant cell granuloma is an expansile blood supply interrupted during curettage of the
destructive lesion of the bone.127 It most commonly lesion, root canal treatment is often necessary before or
occurs in children and young adult females and after surgical removal.
appears radiographically as a unilocular or multilocu- Nasopalatine Duct Cyst. Also known as the inci-
sive canal cyst and median anterior maxillary cyst, the
nasopalatine duct cyst is one of the more common
pathologic entities arising in the anterior region of the
maxilla. Because of its location, radiographic appear-
ance, and symptoms, it is easily confused with a peri-
radicular lesion (Figure 5-26). It arises from remnants
of the embryologic nasopalatine duct and so is consid-
ered a developmental cyst.
Clinically, the lesion is usually asymptomatic but may
show swelling or, if secondarily infected, discharge of pus
in the incisive papilla region.128 Radiographically, a
well-defined radiolucent area is seen interradicularly or
apically to the maxillary central incisors. It is often heart
shaped owing to superimposition of the anterior nasal
Figure 5-24 Central giant cell granuloma. A relatively smooth Figure 5-25 Central giant cell granuloma—relatively loose con-
radiolucent lesion in the anterior region of the mandible. No nective tissue with numerous fibroblasts and a few giant cells (white
resorption or displacement of teeth is noted. The teeth responded arrows).
to vitality tests. (Courtesy of the Department of Oral Pathology,
Loma Linda University.)
Periradicular Lesions 195
A B
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.
196 Endodontics
A B
Figure 5-29 Two examples of a so-called “globulomaxillary” cyst. A, Although having every appearance of a true apical cyst, this lesion is
associated with vital anterior teeth. This may be a true globulomaxillary cyst. (Courtesy of Dr. Richard E. Walton.) B, Necrotic pulp in the
lateral 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.)
Periradicular Lesions 197
Figure 5-32 Metastatic breast cancer. All three teeth are nonre-
sponsive to pulp testing. Unusual chisel edge and moth-eaten
Figure 5-31 Vestibular-buccal swelling from metastatic breast resorption are not typical of inflammatory osseous lesion. A biopsy
cancer. Appearance and symptoms can be confused with apical proved lesion malignant. (Courtesy of Drs. Raymond J. Melrose and
abscess. (Courtesy of Drs. Raymond J. Melrose and Albert Abrams.) Albert Abrams.)
198 Endodontics
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