Maxillary Ameloblastoma in an Asiatic Black Bear (Ursus thibetanus).

An approximately 30-year-old intact female Asiatic black bear (Ursus thibetanus) was presented for annual examination and a history of ptyalism. A large 9.5 cm × 5 cm × 5 cm, firm, round mass was identified attached to the hard palate on physical examination. A computed tomography scan was performed, and the heterogeneous, mineral-attenuating mass was seen arising from the right aspect of the palatine bone and extending rostrally to the level of the last maxillary molars, caudally into the oropharynx, and dorsally into the nasal choana. Surgical debulking was performed to remove the portion of the mass within the oral cavity. Histopathologic analysis was consistent with a keratinizing ameloblastoma. Nine months postoperatively, the patient was asymptomatic for the tumor. The patient was euthanized 23-months postoperatively, and severe diffuse pustular dermatitis, growth of the ameloblastoma on the hard palate, and various degenerative and aging changes were noted on necropsy at that time. This is the first report of an ameloblastoma in a member of the Ursidae family.

Odontogenic-like neoplasms of the rabbit cheek: pathological features and comparison to cutaneous trichoblastoma and jaw-associated ameloblastoma.

Odontogenic neoplasms demonstrate unique histopathological features and are thought to arise from the germinal tissues of the developing tooth germ, effectively restricting their anatomic origin to the tooth-bearing regions of the jaw and directly associated soft tissues of the oral cavity. Ectopic odontogenic-like neoplasms located in the skin of cats, rabbits, and human beings challenge these assumptions. Here we describe the clinical, pathological, and immunohistochemical features of 6 spontaneously occurring odontogenic-like neoplasms arising in the cutaneous tissue of the cheek in client-owned pet rabbits, including ameloblastoma-like (n = 3), ameloblastic fibroma-like (n = 2), and ameloblastic carcinoma-like neoplasms (n = 1). Microscopically, all the cheek tumors featured neoplastic epithelium exhibiting odontogenic architectural structures (plexiform ribbons, anastomosing trabeculae, follicles, cysts, and irregular structures with rounded botryoid protuberances) and 1 or more cardinal odontogenic epithelial features (basal palisading, antibasilar nuclei, and central stellate reticulum-like cells). The pancytokeratin, cytokeratin 5/6, cytokeratin 14, and vimentin immunohistochemical patterns of these odontogenic-like lesions were most similar to those of jaw-associated ameloblastoma and differed from those of cutaneous trichoblastoma. All neoplasms were narrowly excised, and for lesions with clinical follow-up information, none had evidence of recurrence 1-7 months after surgical removal. Although evidence suggests that these odontogenic-like tumors of the rabbit cheek may be derived from ectopic rests of transformed tooth germ, the histogenesis of these lesions remains unresolved.

Clinical, Radiographic and Histologic Evaluation of 40 Cystic Oral Lesions in 37 Cats.

Feline cystic oral lesions are uncommon and include odontogenic cysts and cystic odontogenic tumors. Accurate diagnosis requires close collaboration between the clinician's clinical and radiographic findings and the pathologist's histologic interpretations. The odontogenic cysts identified in this series include a periapical cyst, dentigerous cysts and a type of unclassified collateral cyst that appears to be a previously undefined, distinct entity in cats (UCC). Many of the cysts (52%) were unable to be classified due to insufficient diagnostic information, which often related to the associated tooth being unavailable for evaluation. Cystic odontogenic tumors included ameloblastomas, amyloid producing ameloblastomas (APA), and feline inductive odontogenic tumors (FIOT). The purpose of this case series was to assess correlations between clinical and radiographic findings, histopathologic interpretation and signalment to identify common characteristics and provide recommendations for clinicians and pathologists to optimize diagnostic efficiency and accuracy for cystic oral lesions in cats.

Immunohistochemical Characteristics of Spindle Cell Ameloblastic Carcinoma in a Horse.

A 2-year-old male Thoroughbred horse presented with a mass in the maxilla. The focally ulcerated mass, approximately 8 cm in diameter, covered the upper left intermediate and corner incisor teeth (nos. 602 and 603 according to the modified Triadan system) and radiographic examination revealed displacement and lysis of the incisors. Histologically, the tumour was composed of a dense proliferation of spindle-shaped cells and neoplastic odontogenic epithelial cells arranged in island, follicular, plexiform or sheetlike patterns. The spindle-shaped cells were immunopositive for cytokeratins AE1/AE3, 5/6, 14 and 19. The Ki-67 index was 32.6% in the spindle cell component. Based on the histological and immunohistochemical findings, the tumour was diagnosed as spindle cell ameloblastic carcinoma.

Cytologic features of an acanthomatous ameloblastoma in a dog.

An 8-year-old mixed breed male dog was presented with a mass on the rostral mandibular gingiva that quickly emerged 2-3 weeks prior to presentation. The mass was firm, smooth, well-circumscribed, and approximately 2 × 1 × 0.5 cm in size rostral to the left mandibular canine tooth (304). Clinical examination and radiographs were unremarkable. Cytology revealed two distinct cell populations, consisting of numerous uniform-appearing epithelial cell clusters and low numbers of individual spindle cells. Epithelial cells had mild anisocytosis and anisokaryosis, round nuclei with finely stippled chromatin, no prominent nucleoli, high N:C ratios, and low amounts of pale basophilic cytoplasm. Slender spindle cells observed had oval nuclei with no prominent nucleoli and wispy cytoplasm. On histopathologic examination, the lamina propria of the gingiva was dissected by numerous irregular and anastomosing trabeculae and islands of neoplastic epithelial cells. Neoplastic cells were focally in connection with the hyperplastic overlying epithelium. The trabeculae were surrounded and embedded by cell-rich fibrous stroma. Peripheral to the islands and trabeculae, cells were arranged in palisades, and the nuclei had an antibasilar location. The epithelial cells had prominent intercellular bridges, low amounts of cytoplasm, and one round to oval nucleus. Anisocytosis and anisokaryosis were mild to moderate, and six mitoses/10 HPF were present. Tumor cells reached the deep sample margins. Histopathologic evaluation was consistent with acanthomatous ameloblastoma. This locally aggressive neoplasm causes alveolar bone lysis and often extends beyond alveolar bone margins. Acanthomatous ameloblastoma is an important differential for rostral mandibular gingival masses containing numerous uniform epithelial cell clusters with rare slender spindle cells.

Ameloblastic carcinoma in horses: case report and literature review.

Ameloblastic carcinoma is a malignant odontogenic neoplasm that has been reported only rarely in veterinary species. A 16-y-old Arabian crossbred mare was presented for evaluation of a hard mass on the body of the mandible, with evidence of osteolysis on radiographs. Incisional biopsies revealed an invasive neoplasm comprised of spindloid epithelial cells with a high mitotic count and partial dual cytokeratin-vimentin immunoreactivity. The horse was euthanized because of rapid tumor progression 3 mo after presentation. Postmortem evaluation revealed partial obliteration of the mandible by a large, firm-to-hard, tan, locally destructive and invasive mass with no gross or histologic evidence of metastasis. Postmortem histology revealed a poorly differentiated epithelial neoplasm with variably prominent features suggestive of odontogenic histogenesis: a plexiform ribbon architecture, infrequent basilar palisading with antibasilar nuclei, rare basilar cytoplasmic clearing, subepithelial matrix hyalinization, and partial dual cytokeratin-vimentin immunoreactivity. Features of malignancy included regions of necrosis, pronounced cellular atypia, a high mitotic count, extensive tissue invasion and local tissue destruction, and extension of neoplastic cells beyond the margins of the mandibular bone. Collectively, these features are most consistent with mandibular ameloblastic carcinoma. Including our case described here, ameloblastic carcinoma has been reported in only 5 horses. The microscopic features reported most consistently are dual cytokeratin-vimentin immunoreactivity, a high mitotic count, and basilar palisading. Ameloblastic carcinoma should be considered as a differential diagnosis for rapidly growing, locally invasive masses arising from the dentate jaw of horses.

Odontoameloblastoma in the posterior maxilla of a -6-years-old Ardi goat (Capra aegagrus hircus).

A 6­year­old female Ardi goat was presented for evaluation of an expansile firm painless maxillary ovoid mass. Clinical and diagnostic imaging examination revealed a well­ demarcated extensive mass occupying the left posterior maxilla and altering its anatomical features. Surgical excision was not deemed feasible with this apparently extensive infiltrative features of the tumor and the owner elected to euthanize the goat. Gross examination of the mass showed a grayish­brown, multiloculated firm and gritty mass measuring 21 x 11 x 19 cm located on the left posterior maxilla. Histopathological examination revealed plexiform and follicular arranged, ameloblast ­like odontogenic epithelium. Follicular epithelium was disintegrated leaving spaces, identical to solid multicystic ameloblastoma, intermingled with primitive myxoid stroma resembling dental papilla, teeth like hard structure as enamel and dentine, and osteodentine matrix. Based on these findings, the tumor was diagnosed as odontoameloblastoma (OA) and to our knowledge this is the first report of OA in goats.

Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma.

Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. Because canine acanthomatous ameloblastomas (CAA) have clinicopathologic and molecular features in common with human ameloblastomas (AM), spontaneous CAA can serve as a useful translational model of disease. However, the molecular basis of CAA and how it compares to AM are incompletely understood. In this study, we compared the global genomic expression profile of CAA with AM and evaluated its dental origin by using a bulk RNA-seq approach. For these studies, healthy gingiva and canine oral squamous cell carcinoma served as controls. We found that aberrant RAS signaling, and activation of the epithelial-to-mesenchymal transition cellular program are involved in the pathogenesis of CAA, and that CAA is enriched with genes known to be upregulated in AM including those expressed during the early stages of tooth development, suggesting a high level of molecular homology. These results support the model that domestic dogs with spontaneous CAA have potential for pre-clinical assessment of targeted therapeutic modalities against AM.

CT features of malignant and benign oral tumors in 28 dogs.

An improved understanding of the computed tomographic (CT) features for malignant versus benign oral tumors would be helpful for guiding prognosis and treatment planning decisions in dogs. This retrospective, multi-center, observational study compared the CT features of malignant and benign tumors in 28 dogs with 31 oral masses. Malignant tumors were present in 20 dogs, including malignant melanoma (n = 14), squamous cell carcinoma (SCC, n = 4), adenocarcinoma (n = 1), and fibrosarcoma (n = 1). Eight dogs had benign tumors, including giant cell granuloma (n = 2), peripheral odontogenic fibroma (n = 2), acanthomatous ameloblastoma (n = 2), plasmacytoma (n = 1), and oncocytoma (n = 1). Common CT features of malignant tumors included heterogeneous enhancement, tumor invasion into the adjacent bone, tooth loss, and ipsilateral mandibular lymphadenopathy. Malignant tumors were significantly larger than benign tumors. Bone lysis was found in benign tumors (n = 4) such as acanthomatous ameloblastoma, giant cell granuloma, and plasmacytoma. The bone lysis was a well-defined geographic area regardless of malignancy and tumor type. In periosteal reactions, amorphous patterns were seen in both malignant (n = 2) and benign tumors (n = 2); the latter subgroup also showed solid patterns. Bone expansion (n = 2) was identified in malignant melanoma and acanthomatous ameloblastoma. Findings supported a diagnosis of possible malignancy for dogs with oral tumors having the following CT characteristics: large size, heterogeneous contrast enhancement pattern, bone lysis, tooth loss, and ipsilateral lymphadenopathy. However, there was a considerable overlap of CT findings among the different types of oral tumors and between benign and malignant tumors. Histological evaluation therefore remains necessary for definitive diagnosis.

Biological Behavior of Canine Acanthomatous Ameloblastoma Assessed With Computed Tomography and Histopathology: A Comparative Study.

Canine acanthomatous ameloblastoma (CAA) appears to have variable biological behavior with some tumors presenting with slow growth and minimal bone loss while others grow rapidly and cause severe cancellous and cortical bone destruction. The primary aim of the study is to elucidate if variations (grades) of CAA can be identified based on both histological and diagnostic imaging indices, and to compare markers of more aggressive behavior between these 2 commonly used diagnostic tools. This study evaluated 45 cases of CAA and confirmed that there is high degree of variability in tumor invasiveness as measured with computed tomography, with predominantly intraosseous tumors being significantly associated with more invasive behavior. However, the analysis also identified that there was very little correlation between computed tomographic and histological appearance of the tumor. CAA tends to have a highly uniform and predictable histological pattern, with tumors that aggressively invade bone (as seen on CT) not showing features of atypia that might be helpful in predicting the biological behavior of the neoplastic cells. Thus, reliance on diagnostic imaging as a measure of biological behavior is recommended for treatment planning as well as possible creation of a variant/grading scheme. Prospective studies are required to evaluate if differing variants of CAA as based on diagnostic imaging should be treated differently, and how this would affect long term clinical outcome.

Presentation, Diagnostic Imaging, and Clinical Outcome of Conventional Ameloblastoma in Dogs.

A noninductive tumor of odontogenic epithelium occurs within the tooth bearing regions of the jaw in dogs and fits the conventional definition of ameloblastoma, which is distinct from, and less common than, canine acanthomatous ameloblastoma. In order to clarify the clinical and radiological features of this uncommon odontogenic tumor in dogs, we performed a retrospective study of 20 dogs that were diagnosed between 2007 and 2015. Follow-up information was obtained for 17 of 20 dogs. The study group of dogs showed no apparent age, breed, or gender predilection. Conventional ameloblastoma is typically slow growing, well demarcated, and locally destructive. Tumors most commonly occurred as a mass or focal bony swelling within the maxilla (13/20) or mandible (7/20). Based on cases with available diagnostic imaging, as either dental radiographs or computed tomographic images, the tumors were usually intraosseous and caused mixed lytic/proliferative bone changes. Nevertheless, conventional ameloblastomas did not aggressively infiltrate adjacent tissues and recurrence was not observed within the study group, even in patients with narrow surgical margins or treatment by cyst enucleation.

Ki67 Labelling Index of Neoplastic Epithelial Cells Differentiates Canine Acanthomatous Ameloblastoma from Oral Squamous Cell Carcinoma.

Canine acanthomatous ameloblastoma (CAA) and oral squamous cell carcinoma (OSCC) are the most common oral tumours of epithelial origin in dogs. Overlapping clinical, radiographical and histological features can make distinction between CAA and OSCC difficult. The ability to distinguish tumour identity is critical due to their different biological behaviour and recommended treatment modalities, as well as respective comparative and translational applications as potential models of human disease. Based on marked differences in biological behaviour (i.e. benign versus malignant), it is reasonable to predict that the tumour cell proliferation activity is lower in CAA than in OSCC. However, to our knowledge, the epithelial cell proliferation activity of CAA has not been studied or compared with that of OSCC. Therefore, the aims of this study were to (1) compare the neoplastic epithelial cell proliferation activity of CAA and OSCC based on conventional mitotic index (MI) and Ki67 labelling index (LI), and (2) correlate these findings with clinical parameters including patient signalment, anatomical tumour location and degree of local invasion at the time of diagnosis as determined by computed tomography. We found that (1) the Ki67 LI of OSSC (n = 14) was significantly higher than that of CAA (n = 25), (2) the Ki67 LI correlated with a more aggressive locally invasive behaviour, and (3) the MI was not associated with tumour type. We conclude that the Ki67 LI, but not the MI, is a useful differential marker of CAA from OSCC, and that the epithelial cell proliferation activities of OSCC and CAA correlate with their known differences in biological behaviour.

Ultra-frequent HRAS p.Q61R somatic mutation in canine acanthomatous ameloblastoma reveals pathogenic similarities with human ameloblastoma.

Ameloblastoma is a locally aggressive odontogenic tumour that occurs in humans and dogs. Most ameloblastomas (AM) in humans harbour mutually-exclusive driving mutations in BRAF, HRAS, KRAS, NRAS or FGFR2 that activate MAPK signalling, and in SMO that activates Hedgehog signalling. The remarkable clinical and histological similarities between canine acanthomatous ameloblastoma (CAA) and AM suggest they may harbour similar driving mutations. In this study, aimed at characterizing the mutational status of SMO, BRAF, HRAS, KRAS, NRAS and FGFR2 in CAA, we used RNA sequencing, Sanger sequencing and restriction fragment length polymorphism assays to demonstrate that 94% of CAA (n = 16) harbour a somatic HRAS p.Q61R mutation. The similarities in MAPK-activating mutational profiles between CAA and AM implicate conserved molecular mechanisms of tumorigenesis, thus, qualifying the dog as a potentially useful model of disease. Given the relevance of RAS mutations in the pathogenesis of odontogenic tumours and other types of cancer, the results of this study are of comparative, translational, and veterinary value.

Immunohistochemical Profile of Ameloblastic Carcinoma Arising from an Amyloid-Producing Odontogenic Tumour in a Miniature Dachshund.

A 13-year-old female miniature dachshund was presented with a centrally-located sublingual mass in the rostral mandibular region. The focally ulcerated growth completely covered the left (305) and right (405) premolar teeth and partially covered the right canine teeth (404). A punch biopsy sample revealed neoplastic proliferation of odontogenic epithelium arranged in irregular cords with frequent comedo-like necrosis. Following the initial diagnosis of ameloblastic carcinoma, a bilateral rostral hemimandibulectomy was performed. Although the detailed examination of the resected mass was consistent with the initial diagnosis, it also contained birefringent congophilic, amelogenin-labelled amyloid deposits similar to an amyloid-producing odontogenic tumour (APOT) in 30-40% of the mass, in continuity with the ameloblastic carcinoma. All neoplastic cells had diffuse moderate expression of cytokeratin (CK) AE1/AE3 and CK5, diffuse mild expression of CK14 and multifocal moderate expression of CK19. Because the APOT-like growth in the mass was histologically benign, the tumour was diagnosed as an ameloblastic carcinoma arising from an APOT.

Amyloid-producing Odontoameloblastoma in a Black-tailed Prairie Dog (Cynomys ludovicianus).

A 6-year-old female black-tailed prairie dog (Cynomys ludovicianus) was presented with a space-occupying lesion in the left submandibular region. On computed tomography, a low attenuating, poorly circumscribed mass infiltrated the left mandibular bone, with osteolytic change. Microscopically, the lesion was composed of odontogenic epithelium proliferating in nests and embedded in abundant dental papilla-like ectomesenchyme, including dentine and enamel. Multifocal amyloid deposition was observed. Immunohistochemically, the neoplastic epithelial cells were positive for cytokeratin (CK) AE1/AE3, CK14 and p63. Some epithelial cells were positive for amelogenin and some adjacent to the amyloid deposits co-expressed S100. The ectomesenchymal cells expressed vimentin and strong S100 immunoreactivity was observed in odontoblast-like cells. The amyloid was immunolabelled with amelogenin. The tumour was diagnosed as amyloid-producing odontoameloblastoma.

Clinical Characterization of Canine Acanthomatous Ameloblastoma (CAA) in 263 dogs and the Influence of Postsurgical Histopathological Margin on Local Recurrence.

Canine acanthomatous ameloblastoma (CAA) has been reported to be the most common odontogenic tumor in dogs. This retrospective study evaluated 263 dogs with histopathologically confirmed CAA. Within this data set, CAA presents most commonly in the rostral mandible in adult large breed dogs, with golden retriever dogs being overrepresented. Patients with appropriate follow-up after curative intent surgery were evaluated to assess the effect of histopathological margin on local tumor recurrence. No local recurrence was noted in any patient. This study raises questions about what the recommended surgical margin should be for treatment of CAA. It also serves as a stimulus for discussion as to whether further treatment for CAA is required when inadequate surgical margins are obtained, or if medical surveillance would be an appropriate management recommendation. Prospective studies are necessary to answer these questions.

Ameloblastoma of the Jaw in Three Species of Rodent: a Domestic Brown Rat (Rattus norvegicus), Syrian Hamster (Mesocricetus auratus) and Amargosa Vole (Microtus californicus scirpensis).

Ameloblastoma is a locally aggressive tumour derived from the odontogenic epithelium of the developing tooth germ. This uncommon odontogenic tumour is generally considered benign, but rarely, both distant metastasis and cytological atypia occur and this malignant version is referred to as malignant ameloblastic carcinoma. Here we document a spontaneous malignant ameloblastic carcinoma in a rat (Rattus norvegicus) with metastasis to the submandibular lymph node. We also describe ameloblastomas in two other muroid rodents, an Amaragosa vole (Microtus californicus scirpensis) and a Syrian hamster (Mesocricetus auratus). To our knowledge, this is the first report of a malignant ameloblastic carcinoma in any animal and the first report of ameloblastoma in a vole and hamster.

Maxillary unicystic ameloblastoma in a 6-week-old filly evaluated with computed tomography.

CASE REPORT: A 6-week-old Thoroughbred filly was presented for evaluation of an expansile mass overlying the right nasal passage and causing respiratory stertor. On skull radiographs, there was a loculated, soft tissue-opaque mass identified dorsal to the right upper premolars and effacing the right nasal cavity. Computed tomography (CT) revealed a locally extensive mass with relatively benign characteristics located centrally on the tooth root apices of the deciduous second premolar (506). The mass extended axially into the right nasal cavity, occluding the meatuses and causing displacement of the nasal septum to the left. CLINICAL OUTCOME & SIGNIFICANCE: Surgical excision was not deemed feasible with an athletic future in mind and the owners elected to euthanase the filly. Histopathologically, the mass was consistent with unicystic ameloblastoma and was lined intermittently with palisading, columnar basal cells (ameloblast-like cells) overlying a zone containing stellate cells in loose stroma. To the authors' knowledge this is the first report of a CT scan of an equine ameloblastoma. Although histopathology was essential for definitive diagnosis, CT clearly defined the origin of the mass and identified its locally extensive, cystic nature, which enabled informed decisions to be made.

Suspected Lateral Periodontal Cyst Presenting Concurrently with Canine Acanthomatous Ameloblastoma in a 2-Year-Old Standard Poodle.

Lateral periodontal cysts (LPCs) are odontogenic epithelial cysts composed of nonkeratinized epithelial cells that are in the category of developmental cysts, rather than inflammatory cysts. Lateral periodontal cysts are rare both in people and domestic animals; they are associated with vital teeth and located lateral to a tooth root. Lateral periodontal cysts are typically asymptomatic lesions that are characterized radiographically as a unilocular lucency with well-defined corticated borders. Canine acanthomatous ameloblastoma (CAA) is the most common odontogenic neoplasm in dogs and rarely presents as a cystic lesion. This case report describes the diagnosis and treatment of a cyst that occurred as a swelling apical to a gingival mass that was diagnosed histologically as CAA. Surgical management by conservative gingivectomy, cyst enucleation, and bone grafting was an effective treatment in this patient.

Mandibular odontoameloblastoma in a rat and a horse.

Odontoameloblastoma (OA) is a mixed odontogenic tumor that is an ameloblastoma with concurrent histologic evidence of odontoma differentiation. As a mixed tumor, OA is a tripartite lesion comprised of neoplastic odontogenic epithelium, induced dental ectomesenchyme (dental pulp), and mineralized dental matrix. Although rare, OA represents a diagnostic conundrum, as it is histologically closely related to 2 other mixed odontogenic tumors: odontoma (complex and compound) and ameloblastic fibro-odontoma. Herein we describe an OA arising from the mandible of a 4-mo-old Fischer 344 rat that had been exposed in utero to the mutagen ENU (N-ethyl-N-nitrosourea), and a naturally occurring lesion in a 2-y-old Appaloosa horse. In order to satisfy the diagnostic criteria for this lesion, mineralized dental matrix in relationship to neoplastic odontogenic epithelium must be identifiable within the OA lesion. This group of odontogenic tumors is differentiated by the degree to which the dental matrix is organized and the relative proportions of pulp ectomesenchyme, odontogenic matrix, and odontogenic epithelium.