Oral Pathology in Portuguese Dogs: An Eight-Year Biopsy-Based Retrospective Study.

The oral cavity of the dog can be the site of several types of pathology including both benign and malignant lesions. The aim of this study was to analyze the frequency and clinical-pathological characteristics of oral lesions present in a cohort of Portuguese dogs. A retrospective observational cross-sectional study on 704 canine oral lesions submitted for histopathological diagnosis to a Veterinary Pathology Center in the north of Portugal from 2010 to 2017 was performed. Gender, age, location of the lesion and the histopathological diagnosis was analysed. From the 704 cases included, 307 (43.6%) were females and 397 (56.4%) males. The mean age was 9.53 ± 3.6 years-old (range 3 to 240 months). The site most frequently affected was the gingiva (n = 283; 40.2%). 342 (48.6%) cases were malignant neoplasms, most represented by oral melanoma (n = 129; 37.7%). 256 (36.4%) cases were benign neoplasms, most represented by fibromatous epulis of periodontal ligament origin/peripheral odontogenic fibroma (FEPLO/POF) (n = 208;81.3%). 106 (15%) were non-neoplastic lesions, most represented by gingival hyperplasia (n = 25, 23.6%). This study provides useful information about frequency and distribution of oral lesions in dogs over a period of eight years allowing valuable comparison with other countries and other species. The most common benign tumours were FEPLO/POF while oral melanoma was the most common malignant tumour.

A canine case of malignant melanoma carrying a KIT c.1725_1733del mutation treated with toceranib: a case report and in vitro analysis.

BACKGROUND: Canine malignant melanoma is highly aggressive and generally chemoresistant. Toceranib is a kinase inhibitor drug that inhibits several tyrosine kinases including the proto-oncogene receptor tyrosine kinase KIT. Although canine malignant melanoma cells often express KIT, a therapeutic effect for toceranib has yet to be reported for this tumor, with only a small number of patients studied to date. This is a case report of a dog with malignant melanoma that experienced a transient response to toceranib. Furthermore, the KIT expressed in the tumor of this case was examined using molecular analysis. CASE PRESENTATION: A Shiba Inu dog presented with a gingival malignant melanoma extending into surrounding structures with metastasis to a submandibular lymph node. The dog was treated with toceranib (Palladia®; 2.6-2.9 mg/kg, orally, every other day) alone. Improvement of tumor-associated clinical signs (e.g., halitosis, tumor hemorrhage, trismus, and facial edema) with reduced size of the metastatic lymph node was observed on Day 15. The gingival tumor and associated masses in the masseter and pterygoid muscles decreased in size by Day 29 of treatment. Toceranib treatment was terminated on Day 43 due to disease progression and the dog died on Day 54. The tumor of this dog had a novel deletion mutation c.1725_1733del within KIT and the mutation caused ligand-independent phosphorylation of KIT, which was suppressed by toceranib. This mutation was considered to be an oncogenic driver mutation in the tumor of this dog, thereby explaining the anti-tumor activity of toceranib. CONCLUSIONS: This is the first report that presents a canine case of malignant melanoma that responded to toceranib therapy. KIT encoded by KIT harboring a mutation c.1725_1733del is a potential therapeutic target for toceranib in canine malignant melanoma. Further investigation of the KIT mutation status and toceranib therapy in canine malignant melanoma will need to be undertaken.

A blastema-predominant canine renal nephroblastoma with gingival metastasis: case report and literature review.

Nephroblastomas are uncommon embryonal tumors in dogs. We report herein a blastema-predominant nephroblastoma with gingival metastasis in an 8-y-old Miniature Pinscher dog. Histologically, the mass was composed mainly of blastemal elements with minor epithelial and mesenchymal differentiation. Metastatic masses in the gingiva had histologic and immunohistochemical features similar to those of the primary renal nephroblastoma. Neoplastic cells were extensively positive for both vimentin and PAX8, and scattered positive for cytokeratin. Using the clinical staging of human Wilms tumor, we staged our case as stage IV with <4 mo of survival time. We summarized previous studies of canine renal and spinal nephroblastomas, and analyzed the correlations among clinical staging, histologic classification, and mean survival time of dogs with renal nephroblastomas. Clinical staging was significantly correlated with survival time, as shown in humans. In dogs, however, additional factors can potentially influence the outcome of treatment and disease development.

Gingival Fibrosarcoma in a Horse.

A 4-year-old thoroughbred cross mare was referred to the University of Edinburgh Veterinary School Equine Hospital for treatment of a soft tissue tumor on the buccal gingival margin of the rostral right maxillary cheek teeth. The lesion was initially surgically excised and diagnosed as a fibrosarcoma via histopathology. Adjunctive treatment with intralesional cisplatin chemotherapy was begun. The tumor recurred and was repeatedly treated with intralesional cisplatin injections and additional surgical resection over the course of 14 weeks. Despite the initial poor response to treatment, no further regrowth of the tumor occurred 3 months following its final treatment. The horse remained free of visible evidence of tumor nearly 5 years later.

Malignant epithelioid schwannoma of the oral cavity in a cat.

A malignant epithelioid schwannoma of the oral cavity was diagnosed in an 8-year-old domestic short-hair cat. The mass was located in the gingiva of the upper left premolar to molar region and showed multinodular growth patterns. The mass comprised epithelioid cells arranged in densely packed sheets. Tumor cells had large, round to oval nuclei with prominent nucleoli and an abundant eosinophilic cytoplasm. Immunohistochemically, most of the tumor cells were positive for S-100 protein, glial fibrillary acidic protein and vimentin, but all lacked melanoma-associated antigen and muscle and neuroendocrine markers. Stains for type IV collagen showed linear immunoreactivity around single cells and groups of cells. Ultrastructurally, tumor cells were separated by a well-defined basement membrane, and interdigitating cell processes were observed. To our knowledge, this is the first report of feline malignant epithelioid schwannoma.

Gingival rhabdomyosarcoma accompanied by an immature myogenic population immunoreactive for α-smooth muscle actin in a dog.

A 3-year-old female shih tzu was presented with a white to dark red mass arising from the gingiva. Because of the rapid and invasive growth of the mass, the dog was humanely destroyed. Microscopically, round to polygonal anaplastic cells with strongly eosinophilic cytoplasm grew in an alveolar pattern separated by fibrous stroma. Mitotic figures were numerous. Multinucleated cells and 'strap cells' were observed, but cross striation and glycogen accumulation were absent. Immunohistochemically, the tumour cells were positive for vimentin, desmin, muscle-specific actin and MyoD1, and a small number of tumour cells were positive for α-smooth muscle actin (α-SMA). Based on the morphological and immunohistochemical features, the gingival mass was diagnosed as alveolar rhabdomyosarcoma accompanied by α-SMA-positive immature myogenic cells.

Neoadjuvant chemoradiotherapy and surgery as treatment for oral maxillary squamous cell carcinoma in a dog.

A gingival maxillary squamous cell carcinoma was diagnosed in a 12-year-old male Yorkshire Terrier. After a complete diagnostic work-up, including a computed tomography scan, the tumour was staged as T3bN1aM0 and considered non-resectable at presentation. The combination of neoadjuvant megavoltage radiotherapy and neoadjuvant and adjuvant chemotherapy with carboplatin and doxorubicin decreased the size of the tumour, allowing for surgery. The dog was free from local disease for 421 days after which it was euthanased at the owners' request.

Expression of cytokeratins in the epithelium of canine odontogenic tumours.

Odontogenic tumours are considered to be relatively rare; however, several histologically distinct types have been identified in dogs. The more common canine odontogenic tumours are peripheral odontogenic fibroma and canine acanthomatous ameloblastoma. The expression of cytokeratins (CKs) has been established for the human dental germ and odontogenic tumours. The aim of the present study was to describe the immunohistochemical expression of a panel of CKs in the epithelium of the canine dental germ, normal gingiva and odontogenic tumours arising in this species. Samples from 20 odontogenic tumours, 12 tooth germs and three normal gingival tissues were obtained. Each sample was stained with haematoxylin and eosin and subjected to immunohistochemistry for CK expression. The typical expression pattern of CKs in the odontogenic epithelium and gingiva of dogs was CK14 and CK5/6. CKs 7, 8, 18 and 20 were generally absent from the canine dental germ, gingiva and odontogenic tumours. Dogs and man therefore exhibit similar CK expression in the odontogenic epithelium.

Odontogenic myxoma in an 8-year-old Labrador Retriever dog.

Odontogenic myxoma (OM) was diagnosed in an 8-year-old Labrador Retriever dog with an ulcerohemorrhagic mass located on the caudal area of the right maxillary gingiva. The neoplasm was characterized by a low mitotic index and moderate numbers of spindle, stellate, and round cells that were sparsely distributed in an alcian blue reactive myxomatous matrix. Individual neoplastic cells were characterized by small amounts of faintly eosinophilic staining cytoplasm, prominent nucleoli, and stippled amphophilic staining chromatin that was immunoreactive for vimentin but negative for cytokeratin and actin. To the authors' knowledge, this is the first reported case of canine OM from North America, and it shares histomorphologic and histochemical features with 3 other cases reported in dogs elsewhere. Whereas, a literature review suggests untreated canine OM is insidious and locally aggressive, the prognosis in the present dog remains unknown. These findings support previous recommendations for inclusion of canine OM on the World Health Organization list of odontogenic tumors.

Acanthomatous ameloblastoma in dogs treated with intralesional bleomycin.

Acanthomatous ameloblastoma (AA) is a benign gingival tumour that often invades bone. This retrospective study evaluated the efficacy of intralesional (IL) bleomycin as a treatment for AA. Six dogs received weekly or bimonthly IL bleomycin injections (dose range, 10-20 U m(-2)). A seventh dog presented with advanced, nonresectable AA was treated palliatively. One to sixteen treatments were administered (median, 5). Six of the seven dogs had a complete response within 4 months from initial IL injection (median, 1.5 months), whereas the palliative case had approximately 25% decrease in tumour volume 14 days from initial injection. Local recurrence was not observed during the study period, with a median follow-up time of 842 days. Adverse effects were limited to wound formation with bone exposure (n = 4), mild tissue reactions (n = 3), local swelling (n = 2) and local infection (n = 1). The conclusions of this study show IL bleomycin is an effective treatment for canines with AA.

The use of rim excision as a treatment for canine acanthomatous ameloblastoma.

This study reviews rim excision as a treatment for canine acanthomatous ameloblastomas (CAA) in dogs with <3 mm of bone involvement. Removal of a canine tooth was involved in 47% of the cases; 33% cases involved the caudal dentition. Follow-up ranged from 3 months to 5 years. No evidence of recurrence was seen. Client satisfaction with cosmesis and the animal's ability to masticate was judged to be good. With appropriate case selection, rim excision appears to be a viable option for CAA and results in improved dental occlusion, cosmesis, and no evidence of epulis recurrence.

Gingival osteogenic melanoma in two dogs.

Osteogenic melanoma is a rare variant of metaplastic malignant melanoma in human medicine and appears to be a similarly rare variant in dogs. Two dogs with oral malignant melanoma with neoplastic bone formation are reported in this study. Both tumors were characterized by malignant melanocytes that transitioned into neoplastic bone at the deep margins of the neoplasm. Immunohistochemical analysis revealed S100- and Melan-A-positive neoplastic cells adjacent to, and occasionally embedded within, an osteoid and chondroblastic matrix. Scattered clusters of neoplastic cells were also positive for osteocalcin. The findings indicate that in dogs, as in humans, neoplastic melanocytes have metaplastic potential and can be osteogenic.

Insulinoma and squamous cell carcinoma with peripheral polyneuropathy in an aged Sprague-Dawley rat.

Pancreatic islet cell adenoma, oral squamous cell carcinoma, peripheral polyneuropathy, and multiple age-associated degenerative lesions were diagnosed in an aged Sprague-Dawley rat presenting with polyuria, polydypsia, dehydration, anorexia, weight loss, and posterior weakness. Microscopically, the islet cell adenoma was encapsulated by fibrous tissue and composed of packets of oval-to-polygonal monomorphic cells in a fibrovascular stroma. Immunohistochemically, the majority of cells within the mass expressed insulin. In light of the histologic and immunohistochemical findings, a diagnosis of insulinoma was made. The oral squamous cell carcinoma, grossly presenting as gingival ulceration, was composed of nests and cords of squamous epithelial cells that focally eroded and infiltrated the hard palate and resulted in degeneration of the maxillary nerve. The peripheral polyneuropathic lesions were characterized by extensive axonal degeneration and microangiopathic changes that were highly suggestive of a hypoglycemic etiopathogenesis secondary to insulinoma.

Amyloid-producing odontogenic tumor and its immunohistochemical characterization in a Shih Tzu dog.

A 10-year-old, male, Shih-Tzu dog presented with swelling of the right lower jaw caused by a mass arising from the right mandibular gingiva. Radiographic examination revealed bone lysis of the right wing of the mandible. Histopathologically, the growth was characterized by indistinctly lobulated nests, islands, and strands of proliferating odontogenic and squamous epithelial cells, intermingled in close association with large numbers of irregular extracellular deposits of amyloid and amorphous calcified substance. Immunohistochemically, both epithelial components stained strongly positive for cytokeratin (AE1/AE3); the squamous epithelial cells also reacted strongly with neuron-specific enolase (NSE) and S-100 protein, whereas the odontogenic epithelial cells displayed weak immunoreactivity to NSE and partial reactivity to S-100 protein. The amyloid deposits were AE1/AE3-negative. The growth was diagnosed as an amyloid-producing odontogenic tumor.