Glandular odontogenic cyst
Other names	Sialo-Odontogenic cyst
Relative incidence of odontogenic cysts.[1] Glandular odontogenic cyst is labeled at bottom.
Symptoms	Jaw expansion, swelling, impairment to the tooth, root and cortical plate [2][3]
Causes	Cellular mutation, cyst maturation at glandular, BCL-2 protein [2][4]
Diagnostic method	Biopsy, CT scans, Panoramic x-rays [5][6]
Differential diagnosis	Central mucoepidermoid carcinoma, odontogenic keratocyst [7][6]
Prevention	Post-surgery follow-ups are commonly proposed to prevent the chances of recurrence [6]
Treatment	Enucleation, curettage, marginal or partial resection, marsupialization[6]
Frequency	0.12 to 0.13% of people [2]

A glandular odontogenic cyst (GOC) is a rare and usually benign odontogenic cyst developed at the odontogenic epithelium of the mandible or maxilla.^{[2][8][9][10]} Originally, the cyst was labeled as "sialo-odontogenic cyst" in 1987.^[7] However, the World Health Organization (WHO) decided to adopt the medical expression "glandular odontogenic cyst".^[9] Following the initial classification, only 60 medically documented cases were present in the population by 2003.^[6] GOC was established as its own biological growth after differentiation from other jaw cysts such as the "central mucoepidermoid carcinoma (MEC)", a popular type of neoplasm at the salivary glands.^[7][11] GOC is usually misdiagnosed with other lesions developed at the glandular and salivary gland due to the shared clinical signs.^[12] The presence of osteodentin supports the concept of an odontogenic pathway.^[10] This odontogenic cyst is commonly described to be a slow and aggressive development.^[13] The inclination of GOC to be large and multilocular is associated with a greater chance of remission.^[10][3] GOC is an infrequent manifestation with a 0.2% diagnosis in jaw lesion cases.^[14] Reported cases show that GOC mainly impacts the mandible and male individuals.^[3] The presentation of GOC at the maxilla has a very low rate of incidence.^[8] The GOC development is more common in adults in their fifth and sixth decades.^[1]

GOC has signs and symptoms of varying sensitivities, and dysfunction.^[13][14] In some cases, the GOC will present no classic abnormalities and remains undiagnosed until secondary complications arise.^[13] The proliferation of GOC requires insight into the foundations of its unique histochemistry and biology.^[7] The comparable characteristics of GOC with other jaw lesions require the close examination of its histology, morphology, and immunocytochemistry for a differential diagnosis.^[10] Treatment modes of the GOC follow a case-by-case approach due to the variable nature of the cyst.^[5] The selected treatment must be accompanied with an appropriate pre and post-operative plan.^[5]

Signs and Symptoms

The appearance of a protrusive growth will be present at their mandible or maxilla.^[2] The expansive nature of this cyst may destruct the quality of symmetry at the facial region and would be a clear physical sign of abnormality.^[2][7] The area of impact may likely be at the anterior region of mandible as described in a significant number of reported cases.^[8] At this region, GOC would eventually mediate expansion at the molars.^[7] A painful and swollen sensation at the jaw region caused by GOC may be reported.^[14] Detailing of a painless feeling or facial paraesthesia can be experienced.^[7][14] Alongside GOC, "root resorption, cortical bone thinning and perforation, and tooth displacement may occur".^[3] Experience of swelling at the buccal and lingual zones can occur.^[6] Usually, the smaller sized GOCs present no classical signs or symptoms to the case (i.e. "asymptomatic").^[4] GOC is filled with cystic a fluid that differs in viscosity and may appear as transparent, brownish-red, or creamy in colour.^[3]

Causes

The GOC can arise through a number of causes:^[7]

The origin of the GOC can be understood through its biological and histochemistry foundations.^[4] It has been suggested that GOC can be a result of a traumatic event.^[12] The occurrence of GOC may be from a mutated cell from "the oral mucosa and the dental follicle" origin.^[15] Another probable cause is from pre-existing cysts or cancerous constituents.^[12] A potential biological origin of GOC is a cyst developed at a salivary gland or simple epithelium, which undergoes maturation at the glandular.^[4] Another origin is a primordial cyst that infiltrates the glandular epithelial tissue through a highly organised cellular differentiation.^[4] Pathologists discovered a BCL-2 protein, commonly present in neoplasms, to exist in the tissue layers of the GOC.^[4][15] The protein is capable of disrupting normal cell death function at the odontogenic region.^[4][15] The analysis of PTCH, a gene that specialises in neoplasm inhibition, was carried out to determine if any existing mutations played a role in the initiation of the GOC.^[7] It is confirmed that the gene had no assistance in triggering cystic advancement.^[7]

Diagnosis

Radiology

The performance of radiographic imaging i.e. computed tomography, at the affected area is considered essential.^[13] Radiographic imaging of the GOC can display a defined unilocular or multilocular appearance that may be "rounded or oval" shaped upon clinical observation.^[5][4] Scans may present a distribution of the GOC at the upper jaw as it presents a 71.8% prevalence in cases.^[2] The margin surrounding the GOC is usually occupied with a scalloped definition.^[2] A bilateral presentation of the GOC is possible but is not common at either the maxilla or mandible sites.^[13] The GOC has an average size of 4.9 cm that can develop over the midline when positioned at the mandible or maxilla region.^[3][14] Analysis of scans allow for the differentiation of GOC from other parallel lesions, i.e. "ameloblastoma, odontogenic myxoma, or dentigerous cyst" in order to minimise the chance of a misdiagnosis.^[5] These scans can display the severity of cortical plate, root, and tooth complications, which is observed to determine the necessary action for reconstruction.^[5]

Histology

Histological features related to the GOC differ in each scenario; however, there is a general criterion to identify the cyst.^[14] The GOC usually features a "stratified squamous epithelium" attached to connective tissue that is filled with active immune cells.^[2][7] The lining of the epithelium features a very small diameter that is usually non-keratinised.^[8][13] In contrast, the lining of the GOC has rather an inconsistent diameter.^[2] The basal cells of the GOC usually has no association to a cancerous origin.^[12] Tissue cells can be faced with an abnormal increase in the concentration of calcium, which can cause the region to calcify.^[7] The transformation of the epithelium is associated with a focal luminal development.^[2] Eosinophilic organelles such as columnar and cuboidal cells can be observed during microscopy.^[11] Intra-epithelial crypts may be identified in the internal framework of the epithelium or at the external space where it presents itself as papillae protrusions.^[8][13] Mucin is observable after the application of "alcian blue dye" on the tissue specimen.^[8] The histological observation of goblet cells is a common feature with the "odontogenic dentigerous cyst".^[11] In some circumstances, the epithelium can have variable plaque structures that appear as swirls in the tissue layers.^[8] Interestingly, histologists were able to identify hyaline bodies within the tissue framework of the GOC.^[7] It is encouraged that the histological identification of at least seven of these biological characteristics is required to accurately distinguish the presence of the GOC.^[11]

Intraepithelial Hemosiderin

Pathologists have identified hemosiderin pigments that are considered unique to the GOC.^[12] The discovery of this pigment can be pivotal to the differentiation of the GOC from other lesions.^[12] The staining at the epithelium is due to the haemorrhaging of the lining.^[12] The cause of the haemorrhaging can be triggered by the type of treatment, cellular degradation, or structural deformation inflicted during GOC expansion.^[12] Examination of the GOC tissue section indicated that red blood cells from the intraluminal space had combined with the extracellular constituents.^[12] This process is carried out through transepithelial elimination.^[12] This clinical procedure is beneficial to confirm the benign or malignant nature of the GOC.^[12]

Immunocytochemistry

The examination of cytokeratin profiles is deemed useful when observing the differences between the GOC and the central MEC.^[14] These two lesions show individualised expression for cytokeratin 18 and 19.^[7] Past studies observed Ki-67, p53, and PCNA expression in common jaw cysts that shared similar characteristics.^[7] There was a lack of p53 expression found in radicular cysts.^[7] Similarly, Ki-67 was seen less in the central MEC compared to the other lesions, though this discovery is not essential to the process of differential diagnosis.^[7][14] Proliferating cell nuclear antigen readings were established to have no role in the differentiation process.^[14] The TGF-beta marker is present in the GOC and can explain the limited concentration of normal functioning cells.^[15]

MAML2 rearrangement

The observation of a MAML2 rearrangement is described as a procedure useful in the differential diagnosis of the GOC and its closely related lesion, the central MEC.^[11] A second cystic development displayed the presence of CRTC3-MAML2 fusion after an in-vitro application.^[11] The MAML2 rearrangement represents the developmental growth of the central MEC from the GOC.^[11] The use of fusion-gene transcript may be helpful towards the differentiation of the GOC from the central MEC of the jaw and salivary glands.^[11]

Treatment

Pre-treatment protocols

A computed tomography and panoramic x-ray must be undertaken in order to observe the severity of internal complications.^[5] These scans allow for the observation of the GOC size, radiolucency, cortical bone, dentition, root, and vestibular zone.^[5] In some cases, the dentition may be embedded into the cavity walls of the lesion, depending on the position of expansion at the odontogenic tissue.^[13] The diagnosis of a smaller sized GOC is related to the attachment of only two teeth.^[6] While, a greater sized GOC develops over two teeth.^[6] Presentation of a greater sized lesion usually requires a biopsy for a differential diagnosis and a precise treatment plan.^[6]

Treatment process

The unilocular and multilocular nature is imperative to the determination of treatment style.^[6] Local anesthesia is regularly provided as the GOC is embedded within the tissue structure of the jaw and requires an invasive procedure for a safe and accurate extraction.^[2] For unilocular GOCs with minimal tissue deterioration, "enucleation, curettage, and marsupialization" is a suitable treatment plan.^[6] Notably, the performance of enucleation or curettage as the primary action is linked to an incomplete extraction of the GOC and is only recommended to the less invasive lesions.^[6] Multilocular GOCs require a more invasive procedure such as "peripheral ostectomy, marginal resection, or partial jaw resection".^[6] GOCs associated with a more severe structural damage are encouraged to undergo marsupialization as either an initial or supplementary surgery.^[6] The frequency of reappearance is likely due to the lingering cystic tissue structures that remain after the performance of curettage.^[13] The incorporation of a "dredging method i.e. repetition of enucleation and curettage" is also suggested until the remnants of the GOC diminishes for certain.^[9] The treatment ensures scar tissue is removed to promote the successful reconstruction of osseous material for jaw preservation.^[9] Alongside the main treatments, bone allograft application, cryosurgery, and apicoectomy are available but have not been consistently recommended.^[9][13][5] Though Carnoy's solution, the chloroform-free version, is recommended with the treatment as it degenerates the majority of the damaged dental lamina.^[13] The most effective type of treatment remains unknown due to the lack of detailed data from reported cases.^[3]

Post-treatment protocols

Follow-up appointments are necessary after the removal of the GOC as there is a high chance of remission, which may be exacerbated in cases dealing with "cortical plate perforation".^[13][5] The GOC has a significant remission rate of 21 to 55% that can potentially develop during the period of 0.5 to 7 years post-surgery.^[7][6] Cases occupied with a lower risk lesion are expected to continue appointments with physicians for up to 3 years post-surgery.^[6] A higher risk lesion is encouraged to consistently consult with physicians during a 7-year period after treatment.^[13] Remission events require immediate attention and appropriate procedures such as enucleation or curettage.^[6] In more damaging cases of remission, tissue resection, and marsupialization may have to be performed.^[7]

Epidemiology

The clinical presentation of the GOC is very low in the population as noted by the 0.12 to 0.13% occurrence rate, extrapolated from a sample size of the 181 individuals.^[2] The GOC mainly affects older individuals in the population, especially those that are in their 40 to 60s.^[8] However, the GOC can affect younger individuals i.e. 11, and more older individuals i.e. 82 in the population.^[2] The age distribution starts at a much lower number for people living in Asia and Africa.^[2] Those in their first 10 years of life have not been diagnosed with the GOC.^[14] The GOC does present a tendency to proliferate in more males than females.^[3] There is no definitive conclusion towards the relevance of gender and its influence on the rate of incidence.^[7]