Transformation of a Glandular Odontogenic Cyst into an Ameloblastoma: A Uncommon Phenomenon with a Review of Documented Cases

Abstract

Glandular odontogenic cysts(GOC) are among the rarest odontogenic cysts defined by the presence of glandular epithelium in the epithelial lining posing some diagnostic difficulties. GOC associated with ameloblastoma is extremely rare with only 5 cases reported. This report deals with this rare occurrence of GOC along with unicystic ameloblastoma.

Introduction

The odontogenic apparatus and its remnants give rise to a diverse range of lesions known as odontogenic cysts and tumors. [1] With a 0.12–0.2% incidence rate, glandular odontogenic cysts (GOCs) are a rare type of odontogenic cysts. [2] The lining epithelium including glandular-type tissue distinguishes it. WHO (2017) indicates that ten distinct criteria have been presented for diagnosing GOC; the most recent update from 2022 lists the presence of hobnail cells, at least focally, in the luminal surface together with changing epithelial thickness [3]. The histological features of GOC may resemble those of low-grade mucoepidermoid carcinoma, dentigerous cyst, and botryoid odontogenic cyst, but not ameloblastoma. [2] One common kind that arises in a cystic structure is called unicystic ameloblastoma (UA). It has a significant preference for the mandible and is most frequently detected in the second decade of life. A unicystic ameloblastoma resembles a dentigerous cyst and typically manifests as an unilocular radiolucency with a corticated border of 50–80% related to impacted third molars. [4] The association between GOC and unicystic ameloblastoma has not been explored because of this entity’s scarcity. Here, we present a case of GOC along with histological features of unicystic ameloblastoma (luminal subtype) along with a review of the literature (Table 1).

Table 1.

Review of literature on the reported cases

Cases	Age/sex	Location	Size of the lesion	Clinical finding	Radiographic finding	Initial diagnosis	Predominant histopathological features	Special investigation done	Type/pattern of ameloblastoma seen	Treatment	Resolution and follow-up
Gardner et al. [5]	19 year/M	Left Mandibular region crossing the midline	5.2 cm in diameter	Swelling	Unilocular radiolucency	-	Pseudoglandular lining epithelium without mucous pools, and with odontogenic nests and islands in the CT stroma	-	Mural growth in the cystic CT stroma	Enucleation	1 year follow up, No recurrence
M Hisatomi et al. [6]	45 year/F	Right mandibular premolar region	3 cm in diameter	Swelling, pain, paresthesia of right lower lip, and tooth mobility	Unilocular radiolucency with bone perforation and tooth resorption	-	Pseudoglandular lining epithelium with mucous cells and with dispersed odontogenic islands resembling ameloblastoma	Mucicarmine- Highlighting mucous cells of the lining epithelium (weakly stained)	Mixed plexiform and follicular ameloblastoma	-	-
I. Ponniah et al. [7]	65 year/M	Right maxillary region	2.7 cm in diameter	Swelling, pain, and exfoliation of tooth	Multilocular radiolucency with a soap bubble appearance	Ameloblastoma	Pseudoglandular lining epithelium with odontogenic islands associated with peripheral nerve fibers and encroachment of salivary gland	Masson Trichrome	Unicystic ameloblastoma (Mural subtype)	Surgical Resection	2 year and 9 months follow up, no local or distance recurrence
Naik et al. [8]	14 year/M	Right posterior mandibular region	7.2 cm in diameter	Swelling, pain, and non-vital tooth	Unilocular radiolucency with root resorption	Dentigerous cyst	Pseudoglandular ciliated epithelial lining with the proliferation of odontogenic follicles into a fibrous capsule	PAS, Congo Red and Mucicarmine - Negative	Unicystic ameloblastoma (Mural subtype)	-	1 year follow up, no recurrence
Cousin T et al. [2]	58 year/M	Left mandibular region	4.2 cm in diameter	Swelling	Multilocular radiolucency	-	Pseudoglandular epithelial lining with ameloblatomatous islands showing follicular and acanthomatous changes in the CT wall	Mucicarmine- Mucous cells of lining epithelium (positive)	Unicystic ameloblastoma (Mural subtype)	-	-
Present case	12 year/M	Left maxillary region	3.2 cm in diameter	Swelling	Unilocular radiolucency	Radicular cyst Dentigerous cyst Adenomatoid odontogenic tumor	Pseudoglandular epithelial lining with ameloblastomatous changes on the lining epithelium	-	Unicystic ameloblastoma (Luminal subtype)	Enucleation	1 year follow up, no recurrence with good osseous regeneration

Case Report

A 12-year-old child reported to our department with mild facial swelling over the left side of his face involving the anterior maxillary region for the past 8 months. Clinically the swelling was evident from 21 to 25(Fig. 1- A). The patient denied having paresthesia or discomfort. On palpation, the lesion was firm in consistency. A provisional diagnosis of radicular cyst and adenomatoid odontogenic tumor was made due to the site prevalence and age of the patient. The teeth involved in the lesion were vital on thermal tests which ruled out a radicular cyst. Radiographic examination revealed a unilocular, well-circumscribed lesion extending from the left central incisor to the mesial surface of the left first molar region (Fig. 1- B). Fine needle aspiration of the cystic fluid yielded chronic inflammatory cells and few extravasated RBCs. Based on the FNAC finding, complete enucleation of the cystic cavity was planned and executed under local anesthesia. On histopathological examination, stratified squamous epithelium of varying thicknesses showed clear cells, mucous cells, microcystic spaces, areas of papillary tufting pattern, and hobnailing of cells in the lining epithelium (Fig. 1-C & D) which fulfilled seven diagnostic criteria of GOC from WHO 4th edition which made us rule out central mucoepidermoid carcinoma(CMEC). Through the course of the lining epithelium, there was a gradual transition in the characteristics of the epithelium where basal cells of the lining epithelium showed a reversal of the polarity, peripheral palisading with overlying loosely arranged epithelial cells resembling stellate reticulum (Fig. 1- E & F). GOC converting into unicystic ameloblastoma was diagnosed based on the histopathological feature. Careful examination of the entire lesion was done to rule out the mural growth pattern of the lesion, which needs an extensive course of treatment. Owing to the timely intervention of the cystic lesion and histopathological examination resulted in a disease-free 1-year follow-up with good osseous regeneration.

Fig. 1.

(A) Surgical exploration of the lesion showing mild swelling, (B) Well-defined unilocular radiolucent lesion involving 21, 22, 23, 24, 25 and 26, (C) Papillary tufting of the lining epithelium, (D) Presence of clear cells, microcystic spaces and mucous cells in the lining epithelium of varying thickness, (E) Subtle transition of the epithelium exhibiting mucous cells and basal cells showing reversal of polarity and, (F) Transitioned epithelium showing peripheral palisading, basal reversal of polarity and loosely arranged cells that resemble stellate reticulum

Discussion

GOC poses some diagnostic difficulties due to certain similarities with CMEC which can be ruled out with the help of MAML2 gene rearrangements. The current update of odontogenic cysts and odontogenic tumors WHO 5th edition mentioned a GOC exhibiting MAML2 which is hypothetically believed to be an aggressive variant of GOC converted to CMEC [3]. The potential of odontogenic cysts to convert into odontogenic tumors is a common phenomenon with many cases reported but the occurrence of GOC is rare and its conversion to unicystic ameloblastoma is scarce with only five reported cases so far. [2, 5–8] This makes us wonder about the potential of the odontogenic epithelium and its metaplastic and tumorigenic factors. The novel molecular discoveries may have practical applications and herald a new era of therapeutic techniques distinct from those that have been conventionally accepted up until now. [3] Some cysts and tumors may share similar molecular rearrangements like odontogenic keratocyst and ameloblastoma [1], which answers the conversion from the cyst to tumor under certain conditions. Lesions like GOC and ameloblastoma have very vast and varying histopathological features and treatment outcomes making us realize the complex mechanism yet to be explored. The molecular mechanism involved in ameloblastoma is found to be BRAF, RAS family, FGFR2, and SMO mutations, though these mutations are prevalent, sporadic cases do occur. [9] The molecular findings of these transition lesions from cysts to neoplasms pose the same molecular mutation or they come under the sporadic cases that are yet to be analyzed. Histologically, the present case shows a distinct transition from cyst to tumor in the lining epithelium, four of the instances that have been published also show this distinct transition [2, 5–7]. The prognosis and recurrence rate were discussed in 3 out of 5 cases that were described, nor were there any remarks made regarding the clinical behavior of such histologic abnormalities within GOC. Treatment, prognosis, and recurrence cannot be predicted from such a restricted population at this time. Therefore, it is not appropriate to extrapolate findings from ameloblastoma emerging in dentigerous cysts to ameloblastoma associated with GOC. The clinical, radiological, and histologic appearances of these two cysts vary greatly, and their behavior, prognosis, and recurrence rates are even more likely to differ.

Conclusion

To conclude, GOC converting to ameloblastoma is a scarce occurrence with limited knowledge about the clinical behavior, recurrence rate, and molecular mechanism to be discovered. Oral pathologists should be aware of such lesions which might require extensive treatment at times instead of simple enucleation.

Author Contributions

All the authors contributed significantly to this manuscript.

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The authors declare that they have no known conflict of interest.