Periapical Diseases

Periapical Diseases: Spectrum and Differentiating Features

There are a variety of lesions besides the typical granulomas and cysts that can appear at the apices of teeth. These other lesions must receive consideration in the diagnosis of periapical disease because of their potential impact on patient treatment and outcome. This paper will review the spectrum of diseases that may present in periapical tissues, the pathogenesis of periapical inflammatory disease, and the signs and symptoms that separate periapical inflammatory disease from neoplastic disease.

In addition to the commonly encountered periapical granulomas and cysts of the jaws, there are many other lesions that may appear at the apices of teeth. These other lesions, which range from nonodontogenic cysts to malignancies, must receive due consideration in the diagnosis of periapical disease because of their potential impact on patient treatment and outcome. In distinguishing between periapical inflammatory disease and periapical neoplastic disease, a definitive diagnosis based on clinical and radiographic parameters can never be absolute because of the many overlapping signs and symptoms. This makes differential diagnosis for a periapical lesion as important as it is for any other lesion of bone or soft tissue. Unless the clinician is thinking in broad rather than narrow terms, serious conditions may go undiagnosed and untreated for an inappropriate period of time.

The purpose of this paper is to review:

* The spectrum of diseases that may present in periapical tissues;

* The pathogenesis of periapical inflammatory disease; and

* The signs and symptoms that may be useful in separating periapical inflammatory disease from neoplastic disease.

Diseases That Appear as Periapical Radiolucencies

Inflammatory tooth-associated diseases, non-odontogenic cysts, dysplastic bone disease, benign neoplasms, and malignancies can all appear as radiolucencies at the apices of teeth (Figures 1 through 4). In Table 1, periapical diseases are classified according to biologic behavior. This is not an exhaustive list, but it is representative of the more commonly reported diseases found in periapical tissues of the jaws.1-5 Only 10 percent of periapical lesions turn out to be something other than a granuloma or cyst.

Pathogenesis of Periapical Inflammatory Disease

All periapical inflammatory conditions have a common etiology and represent variations of the inflammation-repair theme. All are associated with nonvital teeth whose necrotic pulps stimulate an inflammatory response in the periodontal ligament and bone at the tooth apex. Chemical mediators of inflammation (cytokines and chemokines) released from the dead and dying tissue affect the recruitment of white blood cells into the area. Here they phagocytose necrotic tissue and release additional mediators to sustain the inflammatory response and initiate the repair process. Specific diagnosis is dependent upon the stage of the inflammatory process, i.e., whether the process is acute, chronic, or chronic with acute exacerbation. Once the inflammatory stimulus is removed (through tooth extraction or endodontic filling), the repair process continues, ultimately resulting in healing with regenerated bone in the area.

Figure 1. A periapical cyst showing radiographic continuity with the periodontal ligament space. The biopsy specimen (right) shows nonspecific hyperplastic epithelium supported by inflamed connective tissue. A cyst lumen is evident, top left. Figure 2. A lateral jaw radiogram showing lucency at apices of vital canine and premolar teeth. The biopsy specimen (right) is a classic odontogenic keratocyst. Figure 3. A periapical radiolucency at the apex of a mandibular canine with equivocal vitality. The biopsy specimen (right) shows fibroblasts and multinucleated giant cells, which are characteristic of central giant cell granuloma. Figure 4. Periapical radiolucencies associated with mandibular incisors. Note that the lucency extends coronally along lateral periodontal ligament spaces and that the lamina dura is ill-defined. The biopsy (right), which shows atypical cells making tumor bone, was diagnosed as osteosarcoma. Figure 5. The microscopic appearance of a biopsy of a periapical lucency associated with a nonvital tooth shows a colony of actinomycosis. A gram stain (right) of tissue section shows characteristic gram-positive filamentous structures at the colony periphery. Figure 6. A persistent periapical radiolucency that upon biopsy (right) proved to be a calcifying odontogenic cyst. Note the typical keratinization (light globules) and calcification (dar globules) in the epithelial lining (courtesty of Dr. Timothy A. Wong, Sacramento, Calif.). Figure 7. A persistent periapical radiolucency that upon biopsy (right) was found to be a nasopalatine duct cyst. Lobules of anterior palatal salivary gland can be seen to the left of the cystic lesion. Figure 8. A persistent periapical radiolucency that was diagnosed as periapical cemento-osseous dysplasia after biopsy (right). Figure 9. Poorly defined persistent periapical radiolucencies associate with apices of maillary incisors. The biopsy (right) was diagnosed as lymphoma.

A periapical abscess is an acute phenomenon characterized by rapid focal fluid exudation and neutrophil emigration from resident vessels, resulting in pus formation and intense pain. A periapical or dental granuloma represents a focus of granulation tissue and inflammatory cells that have replaced apical bone. Periapical granuloma is not the same as granulomatous inflammation, which is defined as a type of chronic inflammation that features a predominance of macrophages (e.g., tuberculosis, sarcoidosis). A periapical granuloma may develop from low-grade sustained chronic inflammation or from an abscess left untreated. Variable amounts of scarring are seen in periapical granulomas, and they represent advanced repair. Occasionally, when there is cortical perforation by the inflammatory process, osteogenesis may not occur, and the lesion remains as a fibrous scar even in the presence of an adequate root canal filling. Also, if there is open communication between the tooth apex and oral cavity (e.g., through a carious lesion), the microaerophilic bacterium actinomyces, found in the oral flora, can colonize in the inflamed periapical tissues (Figure 5). This variation of periapical granuloma can result in an actinomycotic infection of the jaw. Diagnosis of these various inflammatory conditions is usually obvious microscopically; but because chronic abscess, periapical granuloma, and periapical scar share many microscopic features, separation can be somewhat subjective.

A periapical cyst can be defined simply as a pathologic space lined by epithelium at the apex of a nonvital tooth. The epithelium, derived from the ubiquitous epithelial rests of Malassez in the apical periodontal ligament, proliferates due to inflammatory stimulation in a pre-existing periapical granuloma. The epithelial proliferation can be regarded as a defense mechanism that protects surrounding bone from the irritants of the necrotic dental pulp. Microscopic examination of this dynamic process shows a variable picture ranging from partial to complete epithelization of the periapex. Again, diagnosis is subjective and dependent upon when in this process the lesion is biopsied and how the pathologist defines periapical cyst. The subjectivity associated with microscopic diagnosis in all likelihood accounts for the wide range of periapical cyst incidences (10 percent to 50 percent) reported in the literature.⁶

It is generally agreed that once a periapical granuloma becomes well-epithelialized, complete bony healing is unlikely with root canal therapy alone. Whether a partially epithelialized periapical granuloma can heal following root canal therapy is still unknown, although it is likely that some can. Probably most of the endodontically treated teeth in which the periapical lesions persist (approximately 10 percent to 20 percent of cases) will be related to cystic change of a periapical granuloma. Also, persistent lesions may be associated with incompletely filled canals and/or apical foreign material.⁷ Although large lesions are more likely to be cysts, there is no way to distinguish radiographically a periapical granuloma from a periapical cyst.

A small but important number of persistent periapical lucencies will be noninflammatory (Figures 6 through 9). These lesions, which range from dysplastic to malignant, should be considered whenever a periapical radiolucency is unusual or refractory to endodontic therapy. The benign aggressive and malignant lesions are of particular importance because of their prognostic implications. Delayed diagnosis of one of these lesions could have profound consequences for the patient. Occasionally, signs and symptoms can give some early signals that the lesion in question is not inflammatory. It should be remembered that these other lesions not only can mimic chronic inflammatory periapical disease, but also can occur concomitantly with an inflammatory lesion. The reader is referred to a current oral pathology text for the clinical-pathologic details of these other lesions.⁸

In the vast majority of cases, it is neither practical nor desirable before performing root canal therapy to biopsy all periapical lesions to eliminate the risk of overlooking a malignancy or a benign aggressive condition. While a biopsy ensures the certainty of a diagnosis, it is invasive and may have some associated morbidity. When there are no inexplicable signs or symptoms associated with the lesion in question, it is most likely a periapical granuloma or cyst. This rationale would support endodontic therapy without microscopic diagnosis. If, however, a presenting sign or symptom suggests that malignancy or benign aggressive disease should be included in the differential diagnosis, a tissue biopsy would be well-advised. Also, if after "conservative" endodontic therapy, the lesion does not heal as expected or the patient continues to have symptoms, then a biopsy of the periapical region is warranted.

Following are the signs and symptoms that suggest the possibility of noninflammatory periapical disease:

* Paresthesia or atypical pain;

* A lesion that appears to have no radiographic relationship to the apical periodontal ligament and lamina dura;

* Large lesions and lesions with ill-defined margins; and

* A lesion-associated tooth that is intact and of positive or equivocal vitality.

If paresthesia is present, malignancy should be given serious consideration and placed at the top of the differential listing. Approximately half of the patients presenting with a numb lip have an intrabony malignancy. Because acute inflammation can also cause paresthesia, abscess should be placed high in the differential diagnosis. In the absence of paresthesia and in the presence of a long history of intermittent low-grade pain, an inflammatory process would receive top consideration. If the associated tooth also tests nonvital, the lesion is most likely a periapical granuloma/cyst/chronic abscess.

Focal widening of the periodontal ligament space and relative thinning of the lamina dura may be helpful in separating inflammatory lesions from others. The spatial relationship of "true" periapical inflammatory disease to tooth apex may be different than with other nondental lesions. Superimposition of a neoplasm on the tooth apex (so-called false periapical lucencies) can sometimes be detected by changing the radiograph angulation, thereby causing a shift of the pathologic image.

Generally, the larger the lesion, the greater the likelihood that it is a periapical cyst rather than a granuloma.⁹ Other cysts and neoplasms will likewise be more likely. Because age and location are highly characteristic of many of the noninflammatory lesions, these two factors will have considerable influence on the differential ranking of these lesions. Slow-growing lesions such as periapical granulomas and cysts will typically be well-defined and surrounded by reactive sclerotic bone. These signs are not often associated with faster growing benign aggressive and malignant lesions.

If the tooth in question is deemed nonvital after pulp testing with one or, preferably, two vitality tests, inflammatory periapical disease should be strongly favored. The well-known vagaries of vitality testing and the occasional association of neoplasms with nonvitality deem it necessary, however, to be inclusive in building a differential diagnosis.¹⁰ Further, a patient could have two lesions: a neoplasm superimposed upon a periapical granuloma/cyst.

When reviewing the health history of a patient with a periapical lesion, any previous treatment for a jaw tumor would be significant, as recurrence could potentially appear near the apices of teeth. Also, a history of a previously treated malignancy of another organ, including lymphoma and multiple myeloma, would be important.¹¹ Of particular importance would be a history of breast, lung, gastrointestinal, thyroid, or kidney cancer, as these commonly metastasize to the jaws, especially the mandible.¹² It should be remembered that with adenocarcinoma of the breast, metastatic disease may occur as late as 10 to 15 years after treatment of the primary lesion. Paresthesia and pain are typically associated with jaw metastases.

Summary

The diseases that may present as periapical radiolucencies have been listed and some examples have been illustrated. Signs and symptoms that should be considered when evaluating a periapical lesion have also been discussed. The following points were emphasized:

* Neoplasms, while infrequently encountered, can clinically and radiographically mimic periapical granulomas and cysts.

* Atypical lesions (especially those associated with paresthesia) and large periapical lesions should be biopsied.

* If, following endodontic therapy, there is no relief of symptoms and/or the periapical lesion does not resolve, a biopsy should be considered.

* Definitive microscopic diagnosis should be made for all excised periapical lesions.

Author

Joseph A. Regezi, DDS, MS, is a professor of oral pathology in the Division of Oral Medicine, Pathology, and Radiology at the University of California at San Francisco School of Dentistry.

References

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To request a printed copy of this article, please contact: Joseph A. Regezi, DDS, MS, 513 Parnassus, S-512, San Francisco, CA 94143-0424