Sine Qua Non: Dentigerous Cyst

Abstract

Dentigerous cysts, also known as follicular cysts, are among the most common developmental cysts of the gnathic bones. The majority of cases are clinically asymptomatic and discovered incidentally on panographic radiographs during routine dental care. The cyst appears as a radiolucency, classically unilocular, associated with the crown of an unerupted or impacted tooth. Usually diagnosed in the 2nd–3rd decade, third molars of the mandible are the most commonly affected teeth. Histologically, dentigerous cysts demonstrate a fibrous or fibromyxoid connective tissue wall lined by squamous epithelium, classically lacking rete ridges. Inflammation may introduce histologic changes, however. The differential diagnosis includes hyperplastic dental follicle, periapical or radicular cyst, unicystic ameloblastoma, odontogenic keratocyst, and other odontogenic cysts and tumors. While the findings are generally classic and pose no diagnostic dilemma, the diagnosis is best made in the context of the appropriate clinical and radiographic setting. Submitted tissue with a lack of history, to include a detailed relationship with the affected tooth, may result in misdiagnosis and subsequent confusion for the clinician. So, despite its simple features, dentigerous cysts are not uncommonly mischaracterized. Therefore a review of a classic case of dentigerous cyst is presented.

Case Presentation

A 21 year old man presented to the dentist for routine dental care and appropriate radiographs. He had no chief complaint and had no significant medical or dental history. A panographic radiograph revealed a unilocular radiolucency of the left mandible. The radiolucency was associated with the crown of an unerupted left mandibular third molar with apparent origins from the cemento-enamel junction. The lesion of interest was well-defined with a sclerotic border (Fig. 1). The adjacent molar appeared uninvolved and the remainder of the dentition was unremarkable.

Fig. 1.

A cropped image of the panographic radiograph shows a unilocular radiolucency associated with the unerupted left mandibular third molar

Diagnosis

The specimen was submitted in formalin and consisted of multiple free floating fragments of soft tissue and an intact molar tooth with tissue adherent near the cemento-enamel junction. The soft tissue was removed from the tooth and all the soft tissue was submitted for microscopic review. The tooth was examined and a gross diagnosis was rendered. Routine hematoxylin and eosin (H&E) stained sections of the soft tissue contained fragments of fibrous cyst wall, lined by non-keratinizing stratified squamous epithelium (Fig. 2). The epithelium was of variable thickness with most areas being two to three cell layers thick and focal areas with up to seven cells (Fig. 3). Scattered small odontogenic rests were seen in the fibrous connective tissue wall. (Fig. 4). The cyst wall exhibited focal areas of mild chronic inflammation consisting predominantly of lymphocytes and plasma cells with scattered neutrophils. The specimen was notable for a lack of other distinguishing features. Fragments of vital bone were present. The histologic findings in coordination with the clinical history and radiographic features, resulted in the diagnosis of dentigerous cyst.

Fig. 2.

Low power image shows the fibrous connective tissue wall lined by epithelium

Fig. 3.

High power image highlights the epithelium of the cyst, 2–3 cell layers thick

Fig. 4.

Cyst wall with scattered odontogenic rests

Discussion

Dentigerous cysts, also known as follicular cysts, are among the most common developmental cysts of the gnathic bones, accounting for 17–25% of jaw cysts [1, 2]. The cysts appear to arise due to accumulation of fluid between the reduced enamel epithelium and the dental follicle of an unerupted tooth [3]. The vast majority of dentigerous cysts are clinically asymptomatic and most are discovered on routine radiographs as part of regular dental care or as part of the evaluation for an unerupted tooth. Patients, however, may present with pain and swelling, usually the result of infection due to an oral communication.

Dentigerous cysts are first and foremost characterized by their relationship to the affected tooth. By definition, a dentigerous cyst is associated with the crown of an unerupted or impacted tooth. Classically these cysts show a central relationship, surrounding the crown of the tooth. A lateral relationship, with the cyst growing laterally along the root in addition to affecting the crown, is also seen. In very large dentigerous cysts, much of the root may be affected. Third molars of the mandible are the most commonly implicated teeth, followed by maxillary canines and less commonly mandibular premolars. Demographically, dentigerous cysts are diagnosed most often in young adults, usually in the 2nd–3rd decade, and are 1.5 times more common in men than in women [2].

Radiographically, dentigerous cysts classically present as unilocular radiolucent lesions. The lesion is generally well-defined and demonstrates a sclerotic border. The origins of the lesion often appears to emerge from the cemento-enamel junction, however, as stated earlier this is not always the case. Larger lesions may displace the affected tooth and or cause resorption of adjacent teeth. Cortical perforation is not usually seen. Occasionally, large cysts may appear multilocular. The presence of unusual findings does not exclude the very common dentigerous cyst but should elevate one’s index of suspicion for alternative diagnoses and also prompt extensive sampling or even complete submission of available tissue for microscopic examination.

The treatment of a dentigerous cyst is usually straight forward, with extraction of the affected tooth and thorough curettage of the associated soft tissue [4]. If it is possible to save the affected tooth, more commonly seen in sites other than third molars, the teeth may be maintained. Very large lesions may be treated with marsupialization. The treatment for most dentigerous cysts, curetting of the tissue during the extraction procedure, is generally rendered before confirmation of the diagnosis by microscopy and no further treatment is usually required. Recurrences are rare. Occasionally, recurrences or residual cystic epithelium has been implicated in the manifestation of odontogenic tumors, such as ameloblastoma or malignant transformation to squamous cell carcinoma [5, 6]. Likewise, central mucoepidermoid carcinoma is uncommonly reported in association with dentigerous cysts, either concurrently or as malignant transformation in the context of mucous metaplasia [7].

Histologically a dentigerous cyst typically demonstrates a fibrous or fibromyxoid connective tissue wall lined by nonkeratinizing stratified squamous epithelium usually only two to three cell layers thick [8]. Classically lacking rete, there is an abrupt transition with the underlying stroma, which may exhibit scattered odontogenic rests. Metaplastic differentiation of the epithelium may be seen and includes ciliated variants, mucous differentiation, and sebaceous differentiation [8], potentially expanding the differential diagnosis. The diagnosis is more complicated in cases of secondary inflammation, which is associated with epithelial thickening, hyperplastic rete ridges, and keratinization that when hyalinized may seldom form Rushton bodies [9]. Stromal cholesterol clefts may also be seen.

The differential diagnosis for dentigerous cyst is broad but is managed with the assistance of clinical and radiographic correlation. For example, an inflamed dentigerous cyst is essentially indistinguishable from an inflamed periapical cyst microscopically. Among the most common odontogenic jaw cysts, periapical cysts, also known as radicular cysts, are typically associated with non-vital teeth. These cysts appear as a radiolucencies of the jaw demonstrating clear relationship with the tooth root surface of the erupted teeth. As such, a radicular cyst may immediately be excluded based on the clinical history and radiology. Despite the importance of clinical history and reliable radiologic interpretation, this data may not be readily available to the pathologist at the time of microscopic interpretation and analysis, however. It has been reported that up to 8.4% of specimens are accompanied by no relevant clinical history [10], greatly increasing the risk of misdiagnosis. Therefore, when the necessary information is missing it is incumbent upon the pathologist to obtain the appropriate supporting clinical information to avoid a misdiagnosis.

Among the primary clinical and radiographic differential diagnoses for a dentigerous cyst is a hyperplastic dental follicle. A dental follicle may have the same intraoperative and radiographic relationship to the tooth as a dentigerous cyst. It has been suggested that a feature in distinguishing a small dentigerous cyst from a large dental follicle is the intraoperative finding of a clinically obvious cavity, containing fluid or semisolid contents, that is easily removed from the enamel surface of the underlying tooth [11]. Radiographically radiolucencies less than 4 mm [11] are more likely to be dental follicles, however only microscopic review of the tissues is definitive. Dental follicles lack a cystic lining, although cases exhibiting reduced enamel epithelium or, in the context of secondary inflammation, thin, nonkeratinizing squamous epithelium, are not uncommon.

Other differential diagnoses are primarily radiographic and in most cases ruled out by thorough histologic evaluation on routine H&E stained sections. Unicystic ameloblastoma may be associated with an unerupted tooth and is seen in a similar age demographic, occurring several decades earlier than classic ameloblastoma. The Vickers-Gorlin criteria, enthusiastically committed to memory by so many trainees, are not readily apparent in most examples of unicystic of ameloblastoma. Even so, these tumors remain sufficiently histologically distinct in comparison to the dentigerous cyst, demonstrating a variably plexiform architecture of the epithelium and foci of palisading basal cells [2]. Although unicystic ameloblastoma is less aggressive than usual ameloblastoma, misdiagnosis as a dentigerous cyst would nonetheless carry the risk of clinically relevant consequences, namely increased risk for local recurrence.

Odontogenic keratocyst (OKC), another radiographic mimic, is a relatively common odontogenic cyst. It accounts for approximately 10% of cysts of the jaws and its clinical presentation may be indistinguishable from a dentigerous cyst. Most commonly diagnosed in the 2nd–3rd decade and usually arising in the posterior mandible, either adjacent to or involving the third molar, the OKC is typically asymptomatic and identified incidentally on routine dental radiographs [2]. Grossly, the cyst may contain clear fluid, similar to dentigerous cyst, or may express yellow, keratinaceous debris. Histologically, the cyst is lined by somewhat thicker stratified squamous epithelium, usually up to 8 cell layers thick, while demonstrating a similar lack of rete ridges. The OKC is most reliably distinguished from the dentigerous cyst by the presence of parakeratosis with a characteristic undulating or “corrugated” architecture, as well as palisading basal cells [2].

The glandular odontogenic cyst (GOC), may also enter diagnostic consideration, particularly in cases of dentigerous cysts with mucous metaplasia. GOCs are rare, accounting for ~ 0.2% of all jaw cysts, and often exhibit goblet cells, hobnail cells, and focal “plaque-like” thickenings with whorled architecture. Radiographic correlation is helpful; although involvement of an unerupted tooth is not unheard of, GOCs typically arise periapically and involve multiple teeth with associated resorption, features largely absent in dentigerous cyst [12].

If epithelium is scant or poorly visualized on routine sections and robust myxomatous change of the fibrous stroma is present, then odontogenic myxoma may be considered. As a neoplasm that affects patients of a similar age demographic, clinical and radiographic correlation is key to avoiding misdiagnosis. Odontogenic myxomas usually demonstrate a “soap-bubble” multilocular appearance on imaging and may be associated with cortical perforation. Even though a significant subset (up to 50%) are associated with a displaced or unerupted tooth, presence of these other features should steer one away from the diagnosis of dentigerous cysts [13].

In conclusion, as the most common developmental cyst of the jaw, the dentigerous cyst is an entity general pathologists should expect to see routinely. Furthermore, as in other common entities, consistent accurate diagnosis depends not only on recognition of the classic histologic appearance but also on acknowledgement of the full spectrum of variation and awareness of histologic mimics. An appreciation for the value of radiologic and clinical findings in typical and atypical cases alike is paramount. Tissue submitted without adequate clinical history, to include a detailed relationship with the affected tooth, can result in misdiagnosis and subsequent confusion for the clinician.

Funding

This study has no funding.

Declarations

Conflict of interest

Both authors declare that there is no conflict of interest.

Disclaimer

The opinions and assertions expressed herein are those of the authors and are not to be construed as official or representing the views of the Department of the Navy, Department of Defense, or the U.S. Government. We are military service members of the United States government. This work was prepared as part of my official duties. Title 17 U.S.C. 105 provides that ‘copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. 101 defines a U.S. Government work as work prepared by a military service member or employee of the U.S. Government as part of that person's official duties.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.