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.

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.

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.

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.

Acanthomatous ameloblastoma with atypical foci in five dogs.

Acanthomatous ameloblastoma is a common, locally invasive, nonmetastasizing tumor of the canine oral cavity. The long-term prognosis for canine acanthomatous ameloblastoma is good if complete excision can be achieved, usually by maxillectomy or mandibulectomy. A variant of acanthomatous ameloblastoma with atypical foci was noted in 5 dogs. There was no age, breed, or sex predisposition. Atypical cells were pleomorphic with a high mitotic rate. They were immunohistochemically negative for cytokeratin, vimentin, melan A, PNL2, CD3, Pax5, CD18, chromogranin A, and synaptophysin. Ultrastructurally, the atypical cells had modest amounts of electron-lucent cytoplasm, abundant rough endoplasmic reticulum, zonula adherens junctions, cleaved or irregular nuclei, and occasional cytoplasmic structures consistent with secretory granules or lysosomes. Complete excision was achieved by maxillectomy or mandibulectomy in 3 dogs; the lesion was incompletely excised in 2 dogs. No ancillary therapy was elected in any patient. No local recurrence or distant metastasis was reported in any case. One patient died of heart failure 20 mo following complete excision; all other patients were alive at last follow-up (average follow-up: 18.8 mo, range: 6-30 mo). The histogenesis of the atypical foci is unclear, but atypical foci within acanthomatous ameloblastoma do not appear to be associated with metastasis or with a poor prognosis relative to acanthomatous ameloblastoma with typical histologic morphology.

Spontaneous multi-cystic peripheral ameloblastoma in the freshwater angelfish, from the Brazilian state of Pará / Ameloblastoma periférico multicístico espontâneo em Acará Bandeira, no Estado do Pará, Brasil

Este trabalho registra a ocorrência espontânea de ameloblastoma em P. scalare. O tumor foi obtido a partir de um exemplar de Acará Bandeira, sendo fixado, seccionado, e os fragmentos processados para microscopia de luz e microscopia eletrônica de varredura (MEV). O exame macroscópico evidenciou uma massa tumoral que se estendia do rebordo alveolar do maxilar superior à face externa labial. À MEV, a neoplasia apresentou uma série de espículas. Microscopicamente, percebia-se um processo neoplásico constituído por tecido conjuntivo de característica mixoide, ricamente vascularizado, onde eram observados fragmentos de tecido osteoide. A amostra revelou proliferação neoplásica do epitélio odontogênico, onde as células neoplásicas se organizavam na forma de paliçada. Alterações histopatológicas em peixes têm sido úteis biomarcadores do efeito à exposição a substâncias tóxicas, sendo as neoplasias lesões específicas, comumente encontradas em peixes de áreas poluídas, revelando uma associação entre as lesões e a exposição a irritantes.(AU)

Ameloblastoma in a wild black rat snake (Pantherophis alleghaniensis).

Reports of neoplasia in captive reptiles are becoming more frequent; however, there is still scarce knowledge of the occurrence of neoplasia in wild reptiles. A wild black rat snake (Pantherophis alleghaniensis) was presented to the Zoological Medicine service of the University of Georgia's Veterinary Teaching Hospital with a 3 cm in diameter solid mandibular mass that was partially ulcerated. Radiographically, the mass was radiopaque with small bone spicules and partial osteolysis of the adjacent mandible. Histologic examination of the mass revealed a neoplasm composed of cuboidal to polygonal cells arranged in islands, anastomosing cords, and trabeculae of pseudostratified epithelium with a palisading peripheral layer of densely packed columnar cells with cytoplasmic clearing. The neoplastic tissue was separated from the mesenchyme by a prominent band of fine collagen. Neoplastic cells were positive for cytokeratin and negative for smooth muscle actin. Electron microscopy highlighted the presence of tonofilaments and microvilli. These findings led to the diagnosis of ameloblastoma, an odontogenic epithelial tumor known to occur in humans and most veterinary species.

Anaplastic mandibular carcinoma in a meerkat (Suricata suricatta).

An 8-yr-old female slender-tailed meerkat (Suricata suricatta) presented with a necrotic sublingual mass and osteolysis of the mandible. After 1 mo of palliative care, the meerkat was euthanized. The mass was diagnosed histologically as an anaplastic carcinoma with extensive rostral mandibular destruction. Immunohistochemistry for vimentin and cytokeratin was validated in this nontypical species and showed that neoplastic cells expressed both mesenchymal and epithelial characteristics, suggestive of a primitive and poorly differentiated tumor. A review of 150 adult slender-tailed meerkat histopathology reports showed a 2% prevalence of orofacial neoplasia, suggesting that oral neoplasms are uncommon in meerkats.

Computed tomographic characteristics of odontogenic neoplasms in dogs.

Odontogenic neoplasms are locally invasive oral tumors in dogs. The purpose of this retrospective study was to describe CT characteristics for varying histopathologic types of canine odontogenic neoplasms. A board-certified veterinary radiologist who was unaware of histologic findings reviewed and scored imaging studies. A total of 29 dogs were included in the study. Twenty-three of these dogs had concurrent dental radiographs. The most common CT characteristics for all tumor types were a direct association with or in the region of multiple teeth in 96.4% (27/28), contrast enhancement in 96.3% (26/27), alveolar bone lysis in 93.1% (27/29), and mass-associated tooth displacement in 85.2% (23/27). Mass-associated cyst-like structures were identified in 53.6% (15/28) and were only present in tumors containing odontogenic epithelium. Canine acanthomatous ameloblastomas (n = 15) appeared as extra-osseous (10/15) or intra-osseous (5/15) masses. Intra-osseous canine acanthomatous ameloblastomas were more likely to have mass-associated cyst-like structures and were subjectively more aggressive when compared with extra-osseous canine acanthomatous ameloblastomas. Amyloid-producing odontogenic tumors (n = 3) had subjectively uniform CT imaging characteristics and consisted of round soft tissue and mineral attenuating masses with multiple associated cyst-like structures. Fibromatous epulides of periodontal ligament origin (n = 4) were contrast enhancing extra-osseous masses that were rarely referred for CT examinations and 25% (1/4) were not visible with CT. Other odontogenic tumors were less represented or had more variable CT imaging characteristics. Mass-associated tooth destruction was appreciated more often with dental radiographs and extra-oral tumor extension was identified more often with CT.

The expression of calretinin and cytokeratins in canine acanthomatous ameloblastoma and oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) and canine acanthomatous ameloblastoma (CAA) represent two epithelium-derived neoplasms that affect the oral cavity of dogs. The expression of cytokeratins (CKs) and calretinin has been previously established in the canine tooth bud and odontogenic tumours. The aim of this study was to characterize the CK and calretinin expression profile of OSCC in comparison to CAA and canine tooth bud tissues. Samples from 15 OSCC and 15 CAA cases, as well as 6 tooth buds and 2 normal gingival tissues were examined. OSCC CK expression was consistent with the CK expression profile of CAA and canine tooth bud tissue. Calretinin was positively expressed in 10 of 15 OSCC cases, with 5 cases demonstrating high staining intensity. Only 2 of 15 CAA cases demonstrated mild-moderate staining intensity. The statistically significant difference in staining pattern and intensity of calretinin in OSCC and CAA can help distinguish between these two tumour types.

Spindle cell ameloblastic carcinoma in a labrador retriever dog.

A 13-year-old castrated male Labrador retriever dog presented with a mass caudal to the first molar of his left mandible. Although the tumor was excised, a recurrent tumor was detected one month later and resected. Both tumors displayed invasive growth and were composed of neoplastic proliferation arranged in irregular lobules, nests and cords continuous with mucosal epithelium. The most prominent feature of the tumors was the presence of many proliferating spindle cells admixed with palisading basal-like cells, acanthocytes and stellate cells. In immunohistochemical examinations, the spindle cells were found to be positive for vimentin; cytokeratin AE1/AE3, 5/6, 14 and 19; and p63. The other neoplastic cells were positive for all of these markers shown above except vimentin. Based on these findings, the tumors were diagnosed as spindle cell ameloblastic carcinoma.

[Computed tomographic characteristics of canine acanthomatous ameloblastoma - a retrospective study in 52 dogs]. / Computertomographische Erscheinungsformen akanthomatöser Ameloblastome - eine retrospektive Untersuchung bei 52 Hunden.

OBJECTIVE: Investigation of the computed tomographic appearance of canine acanthomatous ameloblastoma to describe characteristic imaging features of this neoplasia within the jaw bone. MATERIAL AND METHODS: Retrospective evaluation of epidemiological data and imaging results in 70 dogs with histologically confirmed acanthomatous ameloblastoma. In 52 dogs a computed tomography study was available, while radiographs of the rostral maxilla or mandible were available in 18 dogs. RESULTS: The neoplasia was most commonly located in the rostral parts of the mandible. Dogs of medium and large breeds were most commonly affected with no apparent breed predisposition. A bimodal age distribution could be demonstrated. 19% of the dogs were under 5 years of age. In 45 (86%) of 52 dogs examined by computed tomography osteolysis was present, which in some cases was extensive. An expansile bone destruction of the dental alveolar cavity with osteolysis of the apical border was recognized as the characteristic computed tomographic feature. CONCLUSION AND CLINICAL RELEVANCE: Canine acanthomatous ameloblastoma commonly displays a characteristic computed tomographic appearance, which in combination with histopathological confirmation helps in the diagnosis of this tumour.

A multicancer-like syndrome in a dog characterized by p53 and cell cycle-checkpoint kinase 2 (CHK2) mutations and sirtuin gene (SIRT1) down-regulation.

INTRODUCTION: We have investigated SIRT1, p53 and cell cycle-checkpoint kinase 2 (CHK2) gene dysfunction in a dog with a multicancer syndrome-like in order to evaluate their potential role in the determinism of the disease and to establish a possible correlation between SIRT1 transcript level and p53 expression status. MATERIAL AND METHODS: Blood sample and tumour samples from a pure breed English Setter dog with different tumours were used for this study. Nucleotide sequence analysis was performed with a DNA autosequencer in order to examine p53 and CHK2 mutations. In addition, the expression level of SIRT1 was quantified by Southern Blot analysis of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). RESULTS: Cytological examination revealed five different tumours: a cutaneous sebaceous epithelioma, a cutaneous mast cell tumour, a testicular Sertoli cell tumour, an oral malignant melanoma, and a cutaneous squamous cell carcinoma. Sequencing analysis revealed the presence of a nucleotide substitution, (CGG>CAG) exon 7 of the p53 gene in DNA from peripheral blood mononuclear cells (PBMCs) as well as in the melanoma; whereas the other four cancers showed the loss of the wild-type allele. Furthermore, CHK2 mutation at codon 311 has been identified in the melanoma and sebaceous epithelioma. In addition, SIRT1 cDNA expression decreased in all tumour samples compared to cDNA SIRT1expression level in peripheral blood mononuclear cells (PBMCs) in the same dog. CONCLUSIONS: These results suggest that the germ line mutation of the p53 gene at codon 248 might be, at least, one cause of the multicancer syndrome-like in our dog; furthermore, we show a possible correlation between SIRT1 transcript level and p53 mutations status. The regulatory role of SIRT1 in tumour suppressor pathways suggests that the net effect seen may represent both direct and indirect downstream regulation and it is likely to depend on the presence or absence of functional p53.

Nuclear morphometry in canine acanthomatous ameloblastomas and squamous cell carcinomas.

The aim of this study was to evaluate whether morphometrical analysis can be of diagnostic value for canine acanthomatous ameloblastoma. We calculated, by means of an automated image analyser, some morphometric nuclear parameters, in particular: mean nuclear area (MNA), mean nuclear perimeter (MNP), maximum and minimum diameters (MDx and MDm) coefficient of variation of the nuclear area (NACV), largest to smallest dimension ratio (LS ratio), and form factor (FF), in 8 canine acanthomatous ameloblastomas, and we compared these morphometric data to those of 13 squamous cell carcinomas of canine gingiva. The results indicated a progressive increase of the MNA, NACV, MNP and MDm proceeding from acanthomatous ameloblastomas (MNA: 42.11+/-8.74; NACV: 28,36+/-7,23; MNP: 24.18+/- 2.68; MDm: 5.69+/-0.49) to squamous cell carcinomas (MNA:49,69+/-9,10; NACV: 30,89+/-7,75; MNP: 25.63+/-2.54; MDm: 6.64+/-0.73). On the contrary, the LS ratio and the FF resulted greater in acanthomatous ameloblastomas (LS ratio: 1,63+/-0,12; FF: 1,13+/-0,002) than in SCCs (LS ratio: 1,40+/-0,12; FF:0.91+/-0.38). Moreover, the MNA, MNP,MDx and MDm resulted similar (MNA: p=0.89; MNP: p=0,65; MDm: p=0,16; MDx: p=0,13) in a subset of four acanthomatous ameloblastomas with cellular atypia (MNA:49,01+/-6,88; MNP: 26,28+/-1,99; MDm: 6.08+/-0.41; MDx: 10.18+/-0.88) and in squamous cell carcinomas (MNA:49.69+/-9,10; MNP: 25.63+/-2.54; MDm: 6.64+/-0.73; MDx: 9.26+/-1.05). While the NACV values resulted higher in typical acanthomatous ameloblastoma (29,99+/-6,06) than in atypical acanthomatous ameloblastoma (26,74+/-8,84) and similar to those of the SCCs (30,89+/-7,75). These results seem to confirm that acanthomatous ameloblastoma is a malignant or potentially malignant lesion and emphasizes that nuclear morphometry analysis can be an useful diagnostic and prognostic method in canine oral pathology.