Recount of Clinicopathological Features of Squamous Odontogenic Tumor: A Case Report with Review

Abstract

Squamous odontogenic tumor (SOT), first described by Pullon et al. in 1975, is an exceptionally rare, locally infiltrative, and benign odontogenic epithelial neoplasm. To the best of our knowledge, English literature has reported only 50 cases till date, with central SOTs being more frequent than peripheral subtypes. A 25-year-old female patient reported with a persistent, asymptomatic, gingival growth with respect to mandibular incisor-canine region recurring for the third time. Surgeries were performed previously but no histopathological evaluation was done. Provisionally, a diagnosis of reactive jaw lesion was made based on the clinical and radiographic features, but on histopathological evaluation, the scenario changed. This case underscores the features of peripheral variant of SOT and the importance of considering it in the differential diagnosis of anterior jaw lesions, especially in atypical demographics such as young females. Early recognition through histopathology and other advanced diagnostic techniques are crucial to avoid the misdiagnosis and ensure the optimal outcomes.

Introduction

The World Health Organization (WHO) in 2024 has defined squamous odontogenic tumor (SOT) as “a benign epithelial odontogenic tumour with squamous differentiation.”[1] It is regarded as a rare condition, with around 170 cases documented in the English literature to date, and fewer than 50 acknowledged instances by the WHO.[2,3]

SOT is believed to develop from the epithelial cell rests of Malassez in the periodontal ligament (PDL) or remnants of dental lamina. Recently, the WHO has detected that the cytodifferentiation of SOT and mutations of Ameloblastin (AMBN) are related to NOTCH receptors and their ligands which indicates that this gene might be significant in the development of this neoplasm.[1,4]

SOT usually appears as solitary, slow-growing, asymptomatic, or painful intraosseous lesion with bony expansion mostly affecting the tooth-bearing parts of the jaws, characterized by tooth mobility. They have a predilection for anterior maxillary and posterior mandibular regions; the former exhibiting a more aggressive clinical presentation.[1,5] Clinically, there are two main categories: central SOT and peripheral SOT (Peripheral squamous odontogenic tumour [PSOT]), of which the latter is exceedingly scarce. From a clinicopathological perspective, there are three primary types of SOT: the intraosseous, mural, and extraosseous variants.[5,6]

Due to its indolent behavior and overlapping features with more common gingival lesions, peripheral SOT often go unrecognized or misdiagnosed, underlining the importance of awareness and accurate identification. This article documents the presentations of peripheral SOT and contributes a valuable insight into this obscure entity along with emphasizing the need for clinicians and pathologists to consider peripheral SOT in the differential diagnosis of other innocuous gingival swellings.

Case Report

A 25-year-old female patient reported to the outpatient department of our institute with a persistent, asymptomatic, gingival enlargement in the mandibular anterior region, in relation to 32 and 33, for the past 1 year. The patient had a history of similar lesion occurring in the same site which was excised, but no histopathological evaluation was done. The lesion recurred but was treated similarly. However, on the third recurrence, the patient reported to our institution. Her medical history was noncontributory.

Intraoral examination revealed a firm, lobulated, and soft-tissue growth of moderate size, localized to the gingiva in the region of teeth 32 and 33. The swelling was more pronounced on the lingual aspect than on the buccal aspect and measured about 35 mm × 20 mm × 32 mm. 33 was distobuccally displaced by the swelling creating a gap between 32 and 33. The overlying mucosa appeared pale, smooth, intact, and nonulcerated. The oral hygiene status of the patient was poor [Figure 1].

Figure 1.

Intra-oral photograph of the patient showing firm, lobulated, soft tissue growth of moderate size, localized to the gingiva in the region of teeth 32 and 33

Extraorally, no signs of facial asymmetry and no regional lymphadenopathy were noted.

Cone-beam computed tomography imaging of the mandibular anterior region showed a well-defined osseous defect corresponding to the 32 and 33 region characterized by thinning of the lingual cortical plate, with notable distobuccal tilting of tooth 33 [Figure 2].

Figure 2.

(a-d) Cone-beam computed tomography imaging of the mandibular anterior region revealed a well-defined osseous defect corresponding to the 32 and 33 region characterized by thinning of the lingual cortical plate, with notable distobuccal tilting of tooth 33

Considering the clinical and radiological features, a list of differential diagnosis was made which consists of pyogenic granuloma, peripheral ossifying fibroma, peripheral giant cell granuloma, or peripheral ameloblastoma.

All the parameters of hematological investigations were within the normal limits and informed consent was acquired from the patient before surgery. Under general anesthesia, the entire lesion was surgically excised along with the extraction of teeth 32 and 33, and thorough curettage was performed [Figure 3]. The excised specimen was submitted for H/P evaluation.

Figure 3.

Peroperative photograph

Microscopic examination of hematoxylin and eosin–stained sections [Figure 4] revealed the presence of stratified squamous epithelium backed by mature fibrous connective tissue stroma. The notable characteristic feature is the existence of many discrete islands of varying sizes comprising of neoplastic odontogenic epithelial cells. These islands were peripherally lined by cuboidal epithelial cells enclosing polygonal epithelial cells of uniform size with abundant eosinophilic cytoplasm and exhibited prominent intercellular bridges with no features of cytologic or nuclear atypia. Anastomoses of some islands were also observed. Focal areas of keratinization and occasional microcyst formation were also noted.

Figure 4.

Photomicrograph of hematoxylin and eosin–stained sections showing the presence of stratified squamous epithelium backed by mature fibrous connective tissue stroma characterized by multiple islands, cord and strands of neoplastic epithelial cells of varying sizes. (a): ×4 magnification, (b) ×10 magnification

An immunohistochemical staining with p63 was done to assess the aggressiveness of the tumor. The section showed diffuse nuclear immunopositivity with p63 [Figure 5].

Figure 5.

Photomicrograph of the section showed diffuse nuclear immunopositivity with p63 (a and b: ×10 magnification)

The clinical, radiographic, and histopathological findings were suggestive of squamous odontogenic tumor. The patient was placed on a periodic follow-up schedule at the 3-month intervals. Over 3 years, no sign of recurrence was observed and showed good healing of the operated site [Figure 6]. The patient expressed satisfaction with the overall result of the treatment.

Figure 6.

Postoperative photograph

Discussion

The SOT is a benign odontogenic neoplasm with local infiltration.[7] The tumor has a wide range of age from the 1^st to 8^th decades of life, with a noticeable peak occurring during the third decade. Both genders are affected equally. The lesion typically appears as a painless swelling in the alveolar bone, commonly found in the premolar-canine area of the maxilla and the molar area of the mandible, although it can manifest in any part of the jaws.[1,5,7,8] The present case is about a 25-year-old female patient whose the anterior region of the mandible was affected, which was not a frequent finding according to the literature.

SOT usually develops intraosseously, in proximity to PDL and typically manifests as a painless, slow-growing swelling. The movement of the affected tooth/teeth has been noted, along with sensitivity when percussed.[1,4,7] Consensus on the clinical signs of SOT is very limited in the literature. However, the case under discussion presents a unique feature that is not very likely of the tumor.

SOT usually appears as a unilocular, triangular, or semicircular radiolucency, featuring well-defined edges adjacent to one or more tooth roots. The degree of cortication of the margins can vary. While root displacement frequently occurs, root resorption is uncommon. In less frequent multilocular and aggressive cases, perforation of the cortical bone may be observed. The radiological characteristics observed in this case align with those described in the literature.

Histologically, SOT lacks true capsule and is characterized by numerous well-differentiated, round or ovoid, squamous epithelial islands distributed relatively uniformly within a fibrous connective tissue stroma which is moderately cellular and containing plump, ovoid to spindle-shaped fibroblasts with occasionally scattered inflammatory infiltrates. The epithelial cells exhibit uniformity in size and cytoplasmic staining, demonstrating abundant eosinophilic cytoplasm with prominent desmosomal connections. Each epithelial island is bounded peripherally by a single layer of flattened basal cells.[1,4,7] In this case too, we observed similar histopathological features.

Histologically, differential diagnosis of SOTs includes two histological subtypes of ameloblastoma, i.e. acanthomatous and desmoplastic, and squamous cell carcinoma. The differential diagnosis is given in Table 1.

Table 1.

Histopathological differential diagnosis of squamous odontogenic tumor

Histopathological differentials	Most common site of involvement	Clinical features	Radiological features	Histopathological features	Pathogenesis
SOT[1,7]	Anterior maxillary and posterior mandibular regions	Solitary, slow-growing, asymptomatic intraosseous lesion or as a painful bony expansion affecting the tooth-bearing parts of the jaws, characterized by tooth mobility	Unilocular, triangular or semicircular radiolucency, featuring well-defined edges adjacent to one or more tooth roots and root displacement. The degree of cortication varies In our case, CBCT imaging of the mandibular anterior region showed a well-defined osseous defect corresponding to the 32 and 33 region characterised by thinning of the lingual cortical plate, with notable distobuccal tilting of tooth 33	Composed of islands of well-differentiated squamous epithelium, rounded or oval in shape, but they may also reveal irregular and cord-like structures. Tumor islands are surrounded by mature connective tissue with little or no inflammatory reaction Each epithelial island is bounded peripherally by a single layer of flattened basal cells enclosing polygonal epithelial cells of uniform size with abundant eosinophilic cytoplasm and exhibited prominent intercellular bridges No stellate reticulum like cell noted	NOTCH receptors AMBN
Acanthomatous ameloblastoma[7]	Ramus area of the mandible	Large, slow-growing mass, causing significant facial asymmetry, malocclusion, loosening of teeth	Multilocular radiolucency showing soap-bubble or honey-comb pattern and well-corticated margins. Expansion of the both the cortical plates with frequent occurrence of perforation Root resorption of adjacent teeth is a common finding	Composed of islands of odontogenic epithelial nests having central portions comprising of squamous cell differentiation with keratin formation The peripheral cells may be more cuboidal and resemble basal cells Cyst formation is common and may vary from microcysts to large macroscopic cysts within the epithelial islands	Increased reactivity of BMP-7
Desmoplastic ameloblastoma[7]	Maxillary anterior region	Benign, locally infiltrative painless swelling	Mixed radiolucent -radiopaque appearance producing a fine honey-comb pattern with ill-defined border Resorption of tooth roots is a common finding	Composed of thin strands, cords or whipcord-like offshoots of epithelium surrounded by dense collagenous stroma that may appear hyalinized and hypocellular Epithelial Island comprises of stellate reticulum-like cells enclosed by short columnar or cuboidal cells showing reverse polarity	TGF-β immunoreactivity
Intraosseous squamous cell carcinoma[7,9]	Posterior body and the ramus of mandible	Rapidly growing swelling of the jaw with persistent pain	Osteolytic bone changes are characteristic. The margins are poorly defined, diffuse, and irregular Root resorption may or may not occur	Composed of islands and small nests of pleomorphic squamous epithelium with or without keratin formation Foci of central necrosis or degeneration within the epithelial islands The connective tissue stroma is fibrovascular with abundant inflammatory infiltrates	Unknown
Peripheral ossifying fibroma[10,11]	Gingiva	Painless pink-red, nodular mass, either pedunculated or sessile, not exceeding 3 cm in diameter	There is no obvious evidence of bone involvement seen on the radiograph. On rare occasions, there can be superficial bone erosion present	Composed of highly cellular mass of connective tissue comprising numerous plump proliferating fibroblasts intermingled with fibrillar stroma Calcification may be in the form of single or multiple interconnecting trabeculae of bone or osteoid (either mature lamellar bone or immature cellular bone)	POF may initially develop as pyogenic granuloma that undergoes subsequent fibrous maturation and calcification Metaplasia of the connective tissue leads to dystrophic calcification and bone formation
Peripheral giant cell granuloma[11,12]	Gingiva or edentulous alveolar ridge The mandible is affected slightly more often than the maxilla	Painless, soft tissue purplish-red nodule which can be sessile or pedunculated	Sometimes “cupping” resorption of the underlying alveolar bone is seen	Composed of a delicate reticular and fibrillar connective tissue stroma containing large numbers of multinucleated giant cells Abundant hemorrhage is characteristically found throughout the mass	Stromal cells secrete a variety of cytokines and differentiation factors, like MCP1, ODF, and M-CSF which are monocyte chemoattractants essential for osteoclast differentiation, suggesting that the stromal cell stimulates blood monocyte immigration into tumor tissue and enhances their fusion into osteoclast-like, multinucleated giant cells
Pyogenic granuloma[11,13]	Gingiva	Painless, solitary, smooth or lobulated, pedunculated or sessile, pink to red to purple mass Often bleeds easily on provocation	There is no obvious evidence of bone involvement seen on the radiograph. Long-standing cases may show superficial erosion of bone	Shows a highly vascular proliferation that resembles granulation tissue Numerous small and larger endothelium-lined channels are formed that are engorged with red blood cells A mixed inflammatory cell infiltrate of neutrophils, plasma cells, and lymphocytes is evident	Proposed mechanisms emphasize the importance of insults resulting in an imbalance of pro-angiogenic and anti-angiogenic factors, which lead to a rapid proliferation of capillaries of a neovascular, friable, and lobulated character

SOT: Squamous odontogenic tumor; M-CSF: Macrophage-colony stimulating factor; ODF: Osteoclast differentiation factor; MCP1: Monocyte chemoattractant protein-1; CBCT: Cone-beam computed tomography; AMBN: Ameloblastin

Recent immunohistochemical investigations have detected the presence of transmembrane receptors like Notch 1, Notch 3, and Notch 4, and their ligands Jagged 1 and Delta 1, in the epithelial component of SOT, implicating the Notch signaling pathway in epithelial cytodifferentiation. Notch pathway is also expressed in odontogenic neoplasms such as ameloblastoma, ameloblastic carcinoma, and ameloblastic fibroma, although the expression is markedly significant in SOT. In a pivotal study, Perdigão and co-workers detected unique AMBN gene mutations in the pathogenesis of various epithelial odontogenic tumors, including SOT, underscoring a potential role for AMBN in their oncogenesis. Moreover, SOTs exhibit strong, diffuse immunoreactivity for p63 and p40, paralleling findings in other benign odontogenic neoplasms.[14] The present case showed diffused immunopositivity for p63, highlighting the locally aggressive nature of the tumor.

Conservative management includes enucleation and curettage for cystic odontogenic tumors, and local excision for cases of PSOT. Tumors found in the maxilla necessitate more extensive treatment due to their aggressive biological behavior. Recurrences have been reported, but they appear to be uncommon and likely result from inadequate removal of the tumor.[4,7] In the literature review performed by Mohr et al., 4 out of 46 cases in a cohort study showed recurrence, leading to an estimated recurrence rate of around 9%. In a similar manner, Upadhyay et al. and his team reported a recurrence rate of about 19.4% in their review.[14,15] The case under discussion, underwent surgical removal of the lesion along with the complete resection of the surrounding area, which also included the extraction of teeth 32 and 33, and has been monitored for 3 years without any recurrence.

Conclusion

Long-standing untreated or recurrent cases of SOT have shown malignant transformation. Since the number of reported cases of SOTs is limited, the biologic profile of this entity is still not clear, especially its association with squamous cell carcinoma.[9] A study conducted by Alonso-Juarranz et al. even demonstrated mutations in the RET, POLE, ALK, CDKN1B, and MAP2K1 genes which can result in aggressiveness of this disease.[2] This highlights the importance of early detection and timely intervention crucial to prevent potential complications, including extensive tissue destruction and the rare but possible malignant transformation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.