Glandular Odontogenic Cyst: An Arduous Diagnostic Entity.

Introduction

Glandular odontogenic cyst (GOC) is an uncommon aggressive odontogenic cyst that is commonly seen in the mandibular anterior region.^1,2

It was first described as ‘sialo-odontogenic cyst’ in 1987 by Padayachee and Van Dyke based on the presence of mucous cells, mucous pools and its resemblance to salivary gland.^1,3,4

Shear was an advocate of the term ‘muco-epidermoid cyst’. However, it was not well accepted as the term had already been used to denote an odontogenic cyst with mucous metaplasia by Hodson in 1956.^5,3

Gardner proposed the term ‘glandular odontogenic cyst’ in 1988 reasoning that it is lined by odontogenic epithelium and contained mucous cells. It is also devoid of salivary tissue.^4,6 The absence of expression of sialogenic markers such as epithelial membrane antigen also supports the usage of this term.^3,7

Based on its clinical, radiological and histological characteristics, the World Health Organization admitted it as a separate entity in the year 1992.^3,8

High et al. in 1996 purported the term ‘polymorphous odontogenic cyst’ in lieu of the diverse histologic and radiological appearance.⁹ However, the term GOC is still widely used.

Clinically, GOC appears on the mandibular anterior region, commonly in persons above 30 years of age. It has a slight tendency to occur in males with about 70% of reported cases being in the mandible.^7,10

Radiologically, it appears as an intraosseous unilocular or multilocular lesion that may or may not cause root resorption.^10,11

Histologically, GOC resembles Lateral Periodontal Cyst (LPC), Botryoid Odontogenic Cyst (BOC), Low grade Mucoepidermoid Carcinoma (MEC), Surgical Ciliated Cysts (SCC), and therefore its diagnosis is challenging.¹⁰ We generally use the Kaplan’s major and minor criteria for the diagnosis of GOC.

The GOC cases presented in this series have been collected at our institution over an extensive period of eight years.

Case Presentation

Six patients, four males and two females presented to our institution complaining of facial swelling. The mean age at the time of presentation was 35.8 years. The youngest patient was 7 years and the oldest, 58 years.

The swelling was slow growing and not associated with pain. Patients’ medical history was not of any significance.

Case report 1

A 38-year-old male patient presented with a complaint of swelling in the left upper back tooth region for four years. Extra orally, a diffuse swelling was noticed over the left side of the face. Intraoral examination (IOE) revealed a well-defined swelling with vestibular obliteration, with respect to 26-27 region. Orthopantomography showed an ill-defined mixed radio-opaque radiolucent lesion at 27 region measuring approximately about 3 x 4 cm, extending antero-posteriorly from 26 to 28 region (Figure 1).

Case report 2

A 39-year-old female patient reported with a complaint of swelling on the right side of the face for 1.5 years. The swelling was initially small in size and gradually increased to a size of 2 x 2 cm with no pain associated. It was firm and non-tender. Patient gave history of a previous incisional biopsy, which was reported as calcifying odontogenic cyst. On orthopantomography, a well-defined unilocular radiolucency was noted in relation to apices of 12-15 (Figure 2).

Case report 3

A 34-year-old male, complained of a gradually increasing swelling on the left side of the face for three months without any pain. Intraorally, a 2 x 2 cm swelling was noted in buccal vestibular region of 23-26, which was seen as a well-defined, multilocular, radiolucent area on orthopantomograph (Figure 3).

Case report 4

A 58-year-old male patient reported with a pea sized swelling in the right lower back tooth region which was present since 15 years and had no other associated symptoms. Patient complained of a sudden increase in the size of the swelling and sensitivity with relation to right lower back tooth region. There was no history of tooth pain or discharge. The swelling was approximately 3 x 3.5 cm and was firm to hard in consistency, non-tender and was obliterating the buccal vestibule from 41- 46 region. On radiographic examination, multilocular, radiolucent lesion was noted in relation to 42-46 (Figure 4).

Case report 5

A 32-year-old female patient reported with a complaint of facial swelling near the right middle third of the face since eight months, which was associated with mild pain. The pain was intermittent and aggravated on eating food. Examination revealed a diffuse swelling of size approximately 2 x 2 cm. Skin over the swelling appeared stretched and on palpation, it was tender and firm in consistency. On CT scan, a lesion was noticed in right nasolabial fold in close relation to the roots of right central and lateral incisor (Figure 5)

Case report 6

A 7-year-old male patient was referred for assessing a painless swelling on the hard palate which was present since three and half months. The size of the swelling would reduce upon taking medication. On intraoral examination, a diffuse swelling was seen on the hard palate. Cone Beam Computed Tomography (CBCT) revealed a unilocular radiolucent lesion on the left side of the anterior maxilla involving 21, 63, developing 22 and a supernumerary tooth located palatal to 21.

Histopathology

Histologically, all the cases were lined by non-keratinized stratified squamous epithelium of 2-5 cell layers thick, showing varying thickness of the epithelium. The epithelial-connective tissue interface was flat and showed absence of basal palisading (Figure 6). The basal layer exhibited cuboidal to low columnar cells. At areas, the suprabasal layer exhibited cuboidal cells and at other areas, squamous cells were noted. Goblet cells were noted in cases 1, 2 and 5 in the basal and parabasal layers of the epithelium that contained mucous pools which stained with both mucicarmine and periodic acid-Schiff (PAS). Clear and vacuolated cells in the basal or spinous layer were seen in cases 2, 3, 4, 5, 6. Superficial layers showed eosinophilic cells presenting apically placed bulbous nuclei that gave a hobnail appearance in cases 2, 3, 4, 5, 6. Intrapeithelial microcysts were noticed in the superficial layers of the epithelium. Ciliated cells were seen in the superficial layers in the 4th and 5th cases.

Epithelial plaques were seen in cases 2, 3, 4, 5, and 6. Cases 1, 3, 4 were diagnosed as GOC on incisional biopsy itself, and later were confirmed with excisional biopsy.

Discussion

GOC is a benign, locally aggressive, odontogenic cyst usually seen in the middle aged adults.3 The clinical and radiological picture of GOC is not pathognomonic. The main symptom is that of a slow growing intraosseous swelling.⁴ It showcases characteristics of a benign tumour which can be aggressive in nature. On radiographs, it can present as a radiolucent lesion with scalloped borders and well-defined sclerotic rim. It can also appear as a unilocular or multilocular lesion which may or may not cause root resorption.⁴

There was slight male predominance among the individuals in the current case series (four males and two females). Only one had a patient who was 7 years old at the time of presentation; otherwise, all other patients were 30 years old at the time of presentation, which is consistent with the literature. A facial swelling was the main complaint reported, which is also consistent with the literature. Few of the individuals reported experiencing pain, while some did not.

The size of the lesion can suggest its aggressiveness and recurrence. If the lesion at the initial time of presentation is large (occupies bone area of two or more teeth), it might have a tendency for recurrence compared to those that are small in size (occupying a bone area of less than two teeth).⁷ All the cases that reported to us occupied a bone area of more than two teeth.

Approximately 20 years after the first description of GOC, Kaplan had listed a set of criteria in the year 2008 in an article titled, “Glandular odontogenic cyst: a challenge in diagnosis and treatment” which consisted of five major and four minor criteria which are generally followed while assigning the diagnosis of GOC.^3,7,12

A study was conducted by Fowler et al. in 2011 where he concluded that if in a case seven or more criteria as suggested by Kaplan are fulfilled, it strongly suggests the diagnosis of GOC. However, if only five or less features are present, then it may suggest some lesions that mimics GOC.¹³

In WHO 4th edition, ten histopathological criteria were put forward for the diagnosis of GOC. A diagnosis of GOC could be rendered by fulfilling seven of those criteria. Two of the criteria, i.e., the hobnail layer of cells and the variable thickness of the epithelium were believed to be seen in all cells.^4,14

However, in the updated version of 2022 (5th edition), the luminal layer of hobnail cells is considered the most characteristic of GOC. The other histological features are considered characteristic but none are considered essential to render a diagnosis of GOC.¹³

Additionally, in one case of GOC, MAML2 gene rearrangement was identified. This gene is considered to be seen exclusively in Central Mucoepidermoid Carcinoma (CMEC). This suggests that there is a hypothetical possibility of aggressive GOC converting into a CMEC if this particular gene arrangement is identified.¹⁴

The differential diagnosis that could be considered for GOC are LPC, BOC, Mucoepidermoid Carcinoma (MEC) and SCC. LPC and BOC exhibits varying epithelial thickness as well as epithelial plaques which project into the lumen. PAS positive clear cells which contain glycogen may also be present.^1,3 These features are similar to GOC. However, other features present in GOC like hobnail cells, goblet cells, mucous cells are absent. In MEC, mucous cells, multiple cyst like structures and clear cells may be found; however MEC additionally shows the presence of epidermoid and intermediate cell population. Apart from these hobnail cells, intraepithelial glandular or duct like structures are absent in MEC.^2,3 Surgical ciliated cysts are considered in the differential diagnosis of GOC as it exhibits clear or vacuolated cells, mucous cells and ciliated cells. However, other features pertaining to GOC like epithelial plaques, hobnail cells are absent. Radicular cyst showing mucous and ciliated cell metaplasia can also be considered as a differential diagnosis of GOC. However, it will be associated with the periapical area and non-vital tooth and intense inflammation can also be noticed. Histologically, other features like hobnail cells and epithelial plaques are absent.⁸

Precise diagnosis of GOC is of utmost importance because of the aggressive nature of the cyst as it has the capacity to cause perforation of the cortical plate and also has moderately high rate of recurrence.⁷

Table 2 shows the lesions considered in the differential diagnosis of GOC.

Conclusion

The GOC lesions are quite uncommon in the oral cavity with 0.012-1.3% frequency of all jaw cysts. It has aggressive potential and high recurrence rate which is attributed to the presence of microcysts and the thinness of the epithelium. Conservative approaches show higher recurrences compared to aggressive resection. It is necessary to increase the awareness of this cyst as the differential diagnosis includes even malignant lesions like central mucoepidermoid carcinoma.

Conflict of interest

None