A Rare Case of a Concurrent Mandibular Odontogenic Keratocyst and Oral Rhabdomyosarcoma in a Young Cat

Introduction

Dentigerous cysts are developmental odontogenic cystic lesions that form in the region of unerupted, mainly permanent teeth. Failure of tooth eruption allows remnants of the enamel organ to accumulate fluid, forming an epithelial-lined cavity around the crown.^1,2 The cysts tend to be gradually expansive and invade into the surrounding tissues, provoking structural changes and may lead to pathological fractures.^2,3 Radiographic findings are almost pathognomonic, but histopathology is necessary to confirm the diagnosis.^2,4,5 Surgical extraction of the unerupted tooth and cyst enucleation is the preferred treatment. ⁶

Odontogenic keratocysts (OKC) are classified in the human literature as developmental cysts originating from remnants of the dental lamina and are considered common in the field of dentistry. One author suggested that the presence of parakeratosis, a palisaded basal cell layer, a corrugated surface and keratin in human OKCs are critical histological findings, there also may be separation of the epithelium from its underlying stroma.^7–9 OKCs are rarely reported in veterinary medicine. ⁸ The term Canine Odontogenic Parakeratinized Cyst (COPC) has been proposed to define these cysts in dogs. ⁸ These cysts exhibit aggressive behavior and a high recurrence rate, often being underdiagnosed due to their clinical and radiographic similarity to other odontogenic cysts. ⁹ While in humans they are frequently associated with unerupted teeth, no such correlation has been established in companion animals. ¹⁰

According to one report, odontogenic cysts in the feline are remarkably uncommon, comprising only 1.4% of oral biopsies. ¹¹ Like cysts, odontogenic neoplasms, which are generally benign, may occur in cats and they often have a cystic component. The most commonly reported odontogenic neoplasms include ameloblastomas and feline inductive odontogenic tumors (FIOT).^12–14

Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor of skeletal myoblast-like cells that in humans primarily affects pediatric patients, comprising approximately 7% of childhood malignancies but only 1% of adult cases, with oral involvement in 4–8%.^15,16 Reports of RMS in the feline oral cavity are extremely rare in the veterinary literature.

This case report describes an unusual presentation of a clinically diagnosed dentigerous cyst associated with an unerupted mandibular canine in a 3-year-old male cat. Histopathological evaluation identified the lesion as an odontogenic keratocyst, coexisting with a rhabdomyosarcoma in the left mandible.

Case Report

A 3-year-old neutered male domestic short-haired cat, weighing 4.9 kg, was referred to the Department of Dentistry and Maxillofacial Surgery at the Companion Animal Hospital of Aristotle University of Thessaloniki for evaluation and treatment of a mandibular fracture. The cat had no known medical conditions and was previously fed a standard dry-food diet. According to the medical history, the cat experienced pain while eating five days before presentation. Swelling developed in the left mandible, accompanied by hypersalivation, discomfort during mastication, audible crepitus, and pruritus in the affected area. The cat's food preferences changed, leading to avoidance of soft food.

During the physical examination, the findings were within normal limits, except for a mildly elevated temperature of 39.3°C. Oral cavity examination revealed the absence of the left mandibular canine tooth (304) and a soft, tender, and fluctuant swelling in the same area. Malalignment of the left mandible was observed (Figures 1A and B). Facial palpation detected a defect in the left mandible along with mild enlargement of the left mandibular lymph node. Subsequently, a complete blood count (CBC) and a serum biochemical profile were conducted, with no abnormal findings.

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Figure 1.

(A) and (B) Clinical appearance of the oral cavity at the time of presentation showing the absence of the left mandibular canine tooth (304), a soft, tender, and fluctuant swelling in the same area and malalignment of the left mandible.

The cat was placed under general anesthesia to allow diagnostic procedures and imaging to be performed. Premedication was conducted with dexmedetomidine^a (10 μg/kg) and buprenorphine^b (15 μg/kg) intramuscularly (IM) and anesthesia was induced with propofol^c (2 mg/kg) intravenously (IV) to effect. Following intubation, maintenance was achieved with isoflurane^d in 100% oxygen. A computed tomography (CT) scan of the head was performed. A helical volume of data was acquired at 150 mAs and 120 kV, using a 16-row multidetector CT scanner^e. Images of 0.625 mm thick transverse overlapping slices of the cranium were reconstructed using a low spatial frequency algorithm and reformatted in sagittal and dorsal planes. Images were reviewed using a Picture Archiving and Communication System (PACS) workstation and with soft-tissue and bone window display settings. The CT scan revealed extensive bone loss in the body of the left mandible, with involvement of the surrounding soft tissues showing contrast enhancement after administration of iohexol^f (2 mI/kg) IV. Mild enlargement of the left mandibular lymph node was also noted. Additionally, an unerupted 304 was identified (Figure 2A–C).

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Figure 2.

Preoperative computed tomography reconstructed multiplanar reformation (MPR) images. (A) Sagittal, (B) Dorsal, and (C) Transverse views showing extensive bone loss in the body of the left mandible and impaction of 304 (red arrow).

A comprehensive examination of the oral cavity was conducted. Intraoral radiography^g revealed a large, circular, infiltrative, radiolucent, osteolytic lesion, with a well-defined thin radiopaque margin, extending proximally from the distal aspect of the left mandibular fourth premolar tooth (308) to the mandibular symphysis. A concurrent mandibular bone fracture was identified in the left third premolar tooth (307) area, along with an unerupted 304 tooth (Figure 3A and B). The cystic lesion was aspirated, yielding highly viscous serosanguinous fluid. Cytology revealed a pyogranulomatous inflammatory fluid pattern, characterized by neutrophils and macrophages. A fine-needle aspiration (FNA) of the mandibular lymph nodes was performed, revealing cytological features consistent with reactive lymphadenopathy.

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Figure 3.

Preoperative intraoral radiographs. (A) Lateral and (B) Dorsoventral views demonstrating an oval-shaped, infiltrative, radiolucent osteolytic lesion. The lesion exhibits a well-defined thin radiopaque margin rostro-laterally (yellow arrows) and an ill-defined border ventro-medially (blue arrows). It extends from the level of the left mandibular first molar (309) to the mandibular symphysis. Mandibular bone resorption is evident at the level of the mandibular third premolar (307) and first molar (309), with extensive bone loss involving the body of the left mandible. The unerupted left mandibular canine (304) is embedded within the lesion and shows evidence of tooth resorption (red arrow).

Based on the test results, a presumptive diagnosis of a dentigerous cyst was made. The therapeutic plan consisted of a unilateral left-sided segmental mandibulectomy ¹⁷ encompassing the region from mandibular symphysis to the left first molar tooth (309), due to the extended osteolytic lesion of the mandible (Figure 4A–D). Finally, tissue samples were submitted for histopathological examination.

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Figure 4.

Intraoperative images showing surgery to perform a unilateral left-sided segmental mandibulectomy encompassing the region from mandibular symphysis to the left first molar tooth (309), due to the extended osteolytic lesion of the mandible. (A) Prior to excision of mandible, (B) Post excision of mandible, (C) Post excision of soft tissue mass, and (D) Closure of surgery site.

The patient was hospitalized for two days and received amoxicillin-clavulanic acid^h (20 mg/kg) per os (PO) every 12 h, meloxicamⁱ (0.1 mg/kg) PO every 24 h, and morphine^j (0.2 mg/kg) IM every 8 h. Pain assessments were conducted every four hours to ensure adequate analgesia. The cat began eating soft food on the first postoperative day and exhibited hypersalivation and left tongue droop during this period. On the third day, the cat was discharged with a prescription for amoxicillin-clavulanic acid (20 mg/kg) PO every 12 h for 7 days and meloxicam (0.1 mg/kg) PO every 24 h for 3 days.

The histopathological examination of tissue sections from the cyst wall stained with hematoxylin and eosin (HE) revealed the presence of stratified epithelium with orthokeratosis and underlying connective tissue, compatible with a dentigerous cyst. However, additional tissue samples from the cyst wall were examined and showed areas lined by stratified squamous epithelium consisting of approximately 10 cell layers, with parakeratosis, and an almost palisaded basal layer, features consistent with an odontogenic keratocyst (Figure 5A). Additional regions of the cyst wall showed a wavy appearance while small daughter cystic formations were detected within the underlying connective tissue (Figure 5B). In the deeper layers of the underlying connective tissue, a nonencapsulated solid mass was identified (Figure 5A). The mass was composed of dense aggregates of pleomorphic cells (Figure 5C and D). The latter were mostly round to polygonal and occasionally spindle-shaped, characterized by nuclear atypia and certain nuclei were 3 times larger than those of adjacent cells. One or two prominent nucleoli and numerous atypical mitotic figures were also evident (Figure 5D). Multiple necrotic foci as well as infiltration of the adjacent striated muscles by tumor accompanied by bone lysis were also observed (Figure 5C). The above features were consistent with a malignant mesenchymal tumor. Certain tumor cells showed characteristics of rhabdomyoblasts and to further evaluate the origin of the tumor, a phosphotungstic acid haematoxylin (PTAH) special stain was performed to visualize possible presence of striated muscle fibers. Aggregates of cells with a cytoplasmic basophilic striation pattern and a tadpole-like shape (rhabdomyoblasts) were observed and a diagnosis of pleomorphic embryonal rhabdomyosarcoma was made (Figure 5E and F).

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Figure 5.

Microhistographs showing stratified epithelium with parakeratosis and segmental palisading basal cell layer from the cyst wall. (A) Deeper in the well-developed connective tissue a large, nonencapsulated solid mass is visible. H&E stain. 40x. Bar: 250 μm. (B) Wavy cyst wall. The basal cell layer is focally detached by the proximal connective tissue and daughter cystic formations are also observed. H&E stain. 40x. Bar: 250 μm. (C) Area with numerous pleomorphic cells and two necrotic foci consisting of amorphous eosinophilic material and nuclear fragments. Large rhabdomyoblast-like formations with two or more nuclei and intensely eosinophilic cytoplasm, are sparsely distributed within the tumor. An infiltration of normal skeletal muscle fibers by tumor cells is shown (inset). H&E stain. 40x. Bar: 100 μm. Inset: 100x, Bar: 250 μm. (D) Same image as Figure 5C showing rhabdomyoblast-like formations and atypical mitotic figures. Nuclei are vesicular with prominent nucleoli. H&E stain. 400x. Bar: 25 μm. (E) PTAH stain reveals the presence of numerous anaplastic cells. Large strap or ribbon-like cells with multiple pleomorphic nuclei and cytoplasm of varying size with basophilic intracytoplasmic irregular, mostly cross, striation are also observed. The latter are described in embryonal RMSs. PTAH stain. 400x. Bar: 25 μm. F) Aggregates of tadpole or racket cells with PTAH positive cytoplasmic striation. PTAH stain. 400x. Bar: 25 μm.

Fifteen days postoperatively, the patient was presented for a scheduled recheck to assess surgical wound healing. Mild left tongue ptosis was observed. The owner reported normal jaw function, including yawning, grooming, food intake, chewing, licking, playing with toys, and biting. Transition to dry food was recommended. Five days later, the histopathological results were received and were discussed with the owner, who declined any adjuvant therapy.

Three months postoperatively, the patient presented with localized oral dysphagia and occasional blood-stained ptyalism. The owners reported intermittent difficulty with drinking. On clinical examination, the animal displayed mildly pale mucous membranes and mild swelling of the left mandibular lymph node. Additionally, the cat's weight had decreased by 1.5 kg. Bloodwork revealed a decreased hematocrit (Hct) (19.5%; normal range 30.3%–50.3%) and hemoglobin (Hb) (6.2 g/dL; normal range 9.8–16.2 g/dL), consistent with non-regenerative anemia. Serum biochemical analysis showed a marginal increase in globulin levels (5.2 g/dL; normal range 2.8–5.1 g/dL), with a normal albumin-to-globulin ratio. Chest radiographs were negative for metastatic disease, and the extraoral skull radiograph revealed no additional bone lesions. General anesthesia was performed as previously described, and a large, soft mass was observed, firmly adherent to the base of the tongue and surrounding soft tissues (Figure 6A and B).

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Figure 6.

Three-month postoperative. (A) Clinical presentation and (B) Lateral plain radiographic view showing soft tissue swelling (red arrows), without bone resorption.

Further diagnostic investigation was recommended, but the owner declined additional tests. Consequently, a treatment plan was initiated, including gabapentin^k (15 mg/kg) PO every 12 h, meloxicam (1 mg/kg) PO every 24 h, and chlorhexidine gel^l (12%) applied PO every 12 h. Fifteen days later, the owner elected humane euthanasia for the cat.

Discussion

To the best of the authors’ knowledge, this is the first reported case of an odontogenic keratocyst in a cat in the mandibular region associated with an embedded tooth and concurrently occurring with an oral rhabdomyosarcoma. Odontogenic cysts and odontogenic tumors with cystic components are considered rare pathological entities in the feline oral cavity, and the available literature on these conditions is currently extremely limited.^1,6,18–21

In a recent study, 40 cystic oral lesions in feline patients were assessed. Four were classified as dentigerous cysts, one was a periapical cyst and 18 were nonspecific odontogenic cysts. Of the documented cystic tumors, 5/15 were classified as ameloblastomas, 5/15 as amyloid producing ameloblastomas (APA) and FIOT, while two remained undiagnosed. ¹ A case in a feline patient with an unerupted tooth and ameloblastoma has also been reported. ⁶ Veterinary studies suggest cysts may undergo malignant transformation.^4,22 This study reports a case of a keratocyst in the mandible of a cat, which was associated with an unerupted left mandibular canine. Based on the current literature, this is the first reported instance of such a case in the feline. In human dentistry, embedded teeth have been recognized as potential contributing factors in the formation of odontogenic keratocysts in 27% of cases; however, such an association has not previously been described in the veterinary literature. ²³

Odontogenic keratocysts have been extensively studied in humans due to their propensity for recurrence. As a result, the World Health Organization (WHO) Classification of Head and Neck Tumors classified them as odontogenic tumors between 2005 and 2017. Nevertheless, due to insufficient evidence supporting true neoplastic behavior, the term was revised to “odontogenic keratocyst.”^9,24 This reclassification aligns with the clinical progression observed in the present case, where the lesion caused rapid and significant bone destruction, ultimately resulting in a pathological fracture of the left mandibular body.

In human medicine, there have been proposals that some odontogenic tumors may arise from pre-existing odontogenic cysts, although the underlying pathogenesis remains unclear.^25–28 One hypothesized mechanism involves the malignant transformation of cystic epithelium following chronic inflammation.^25,29,30 The link between chronic inflammation and tumor development in the oral cavity has been supported in both the human and veterinary literature.^31–34

Chronic, unresolved inflammation has been implicated in tumorigenesis through multiple molecular pathways. These include the activation of oncogenic signaling cascades, suppression of tumor suppressor genes, and induction of genomic instability. ³⁵ Additionally, persistent inflammatory cell infiltration contributes to the sustained release of pro-tumorigenic mediators such as cytokines and growth factors, which promote neoplastic cell proliferation, survival, and progression.^36,37

In this clinical case, a keratocyst coexisted with a neoplastic lesion, suggesting that the chronic inflammatory environment may have contributed to tumor development. ³⁰

Given the similar clinical presentation of odontogenic cysts and tumors, it is crucial to obtain tissue samples during cyst excision and submit them for histopathological examination to rule out an underlying neoplastic process. RMS is composed of striated muscle progenitor and mature, well-differentiated cells. It can arise anywhere in the body and is considered rare. It can be regionally infiltrative and metastasize depending on the variant.^38,39 In human medicine, RMS is classified as parameningeal and non-parameningeal and is considered one of the most frequent malignant neoplasms in children and adolescents.^40–44 Despite its predilection for the head and neck, oral cavity RMS accounts for only 10–12% of head and neck RMS cases in humans.^40–42,44 Its presence in the oral cavity of small animal patients is considered uncommon, with few reported cases in dogs.^31,38 In a recent study on malignant tumor prevalence in dogs, only 1/408 cases was diagnosed with RMS ³¹ while no published reports of oral RMS in cats exist. The only relevant report is a case of an 11-year-old British Shorthair cat with laryngeal RMS affecting the left arytenoid and the thyroid cartilage, treated with partial laryngectomy and it remained disease-free at the one-year follow-up. ⁴⁵ In the present study an infiltrative embryonal pleomorphic RMS was identified. Although it is difficult to distinguish this from adult pleomorphic RMS, the presence of large rhabdomyoblasts, large nuclei and evidence of cross-striations is highly suggestive of the embryonal nature of the tumor.

According to the human medical literature, the optimal therapeutic protocol for RMS involves a combination of surgical excision and adjuvant chemotherapy and/or radiotherapy. ³⁸

In the present case, a unilateral left-sided segmental mandibulectomy was performed, extending from the mandibular symphysis to mesial aspect of tooth 309, in an attempt to remove a lesion that had developed as a result of an odontogenic keratocyst. However, due to the lack of awareness of the concurrent neoplastic process at the time of surgery, complete excision and determination of clean surgical margins were not achieved.

Following the histopathological diagnosis of RMS, the owner declined further adjuvant treatment. Three months postoperatively, local recurrence of the neoplasm was observed, a finding consistent with the existing literature, which reports a recurrence rate of 50% within 1 year and 87% within 2 years. ⁴⁶

After the reappearance of local swelling, the owner declined further diagnostic evaluation to confirm RMS recurrence. Following a short period of conservative treatment without improvement, humane euthanasia was elected. This study has limitations. At initial presentation, no chest CT scan was performed to rule out pulmonary metastases. Additionally, no follow-up head CT, cytology, or histopathology was conducted to confirm regional recurrence.

Conclusion

To the authors’ knowledge this report describes the first case of an odontogenic keratocyst accompanied by oral RMS and highlights the importance of histopathological examination when an oral cystic lesion is being treated, to diagnose potential concurrent benign or malignant tumors, even in young patients.

Materials

a. Dextomidor 0.5 mg/ml, Orion Corporation Orion Pharma, Finland

b. Bupredine, Dechra Pharmaceuticals, United Kingdom

c. Propofol 10 mg/ml, Fresenius Kabi AG, Germany

d. Iso-Vet 1000 mg/g, Piramal Enterprises limited, Ireland

e. Optima CT520; GE Hangwei Medical Systems, China

f. Omnipaque 300 mg I/mL (iohexol), GE Healthcare A.E., Greece

g. Progeny, Midmark Corporation, USA

h. Synulox Palatable Tablets 250 mg, Zoetis Animal Health, UK

i. Metacam 1 mg, Boehringer Ingelheim Animal Health, Canada

j. Morphine Sulfate 10 mg/mL Injection, Pfizer, USA

k. Neurodin 300 mg (Gabapentin), Medochemie Ltd, Greece

l. Dentihex Oral Gel (Chlorhexidine), Dechra Veterinary Products, UK