AFIP Systemic Pathology



October 2018




Signalment (JPC #1698960): Adult boxer


HISTORY: The animal presented with an oral mass


HISTOLOGIC DESCRIPTION: Gingiva: Expanding the subepithelial connective tissue, elevating the overlying hyperplastic mucosa, and extending to cut borders is an unencapsulated neoplasm composed of loosely arranged streams of evenly spaced spindle to stellate cells separated by an abundant collagen matrix. Neoplastic cells have indistinct borders with moderate amounts of eosinophilic fibrillar cytoplasm. Nuclei are irregularly oval to elongate with finely stippled to hyperchromatic chromatin and an indistinct nucleolus. The mitotic rate is less than 1 per 10 high power fields. Focally within the neoplasm is an island of osseous metaplasia composed of immature woven bone. Multifocally there are also few aggregates of homogenous, eosinophilic material up to 40 um in diameter (dental hard substance). There are multiple small subepithelial and perivascular accumulations of plasma cells, fewer lymphocytes and occasional neutrophils. The overlying epithelium is moderately hyperplastic forming anastomosing rete ridges up to 2 mm in length with moderate acanthosis, spongiosis, multifocal epithelial intracellular edema, multifocal hyperkeratosis, neutrophilic exocytosis, and a focal area of erosion.


MORPHOLOGIC DIAGNOSIS: Gingiva: Peripheral odontogenic fibroma, boxer, canine.


SYNONYM: Fibromatous epulis of periodontal ligament origin


Signalment (JPC #2749933): A dog


HISTORY: Mass from the mouth


HISTOLOGIC DESCRIPTION: Gingiva: Expanding the subepithelial connective tissue and multifocally extending from the hyperplastic mucosa, is an unencapsulated, infiltrative, moderately cellular neoplasm composed of anastomosing cords, ribbons, and trabeculae of well-differentiated polygonal cells separated by an abundant dense and well vascularized stroma. Neoplastic cells have distinct cell borders, a moderate amount of eosinophilic granular cytoplasm, and irregularly round to oval nuclei with finely stippled chromatin and 1-2 magenta nucleoli. The mitotic rate is 1 per 10 high power (40x) fields. Along the periphery of trabeculae neoplastic cells palisade, and often have antibasilar nuclei with frequent basilar cytoplasmic clearing, while nonbasilar neoplastic cells often have prominent intercellular bridges (odontogenic epithelium). Multifocally within cords and trabeculae are variably sized cysts filled with amphophilic flocculent material, few foamy macrophages and sloughed epithelial cells. Multifocally infiltrating the subepithelial connective tissue are large numbers of macrophages, lymphocytes, plasma cells and neutrophils. Diffusely the mucosal epithelium is hyperplastic with prominent rete ridge formation, acanthosis and spongiosis. There is a focal mucosal ulceration with replacement by eosinophilic cellular and karyorrhectic debris, abundant viable and degenerate neutrophils, fibrin, hemorrhage, and reactive fibroblasts, and multifocally moderate numbers of neutrophils transmigrate the mucosal epithelium.


·      MORPHOLOGIC DIAGNOSIS: Gingiva: Acanthomatous ameloblastoma, breed unspecified, canine.


·      SYNONYMS: Acanthomatous epulis; peripheral ameloblastoma



·      Epulis is a nonspecific term that designates a tumor-like growth of the gingiva of any origin that is common in dogs and infrequent in cats

·      Should not be used in morphologic diagnosis

·      Non-neoplastic gingival growths include pyogenic granuloma, peripheral giant-cell granuloma, and fibrous hyperplasia

·      Peripheral odontogenic fibroma is a tumor composed primarily of odontogenic mesenchyme

o   Common, benign

o   Local excision curative

o   Commonly has similar features of reactive fibrous hyperplasia or focal fibrous hyperplasia a lesion secondary to chronic gingival trauma and irritation; two are difficult to distinguish and hybrid lesions exist

·      Canine acanthomatous ameloblastoma is a common tumor of odontogenic epithelium arising from the gingiva or epithelial rests of dogs

o   Behaves aggressively – invades local alveolar bone, causes tooth loss, and can recur frequently following conservative treatment

o   Can arise intraosseously or peripherally

o   Aggressively infiltrative, no metastatic potential

o   Factors for differentiation include predominance of broad sheets of epithelium and the mitotic figures

o   SCC, fibromas, and osteosarcomas have been reported at sites of previously irradiated acanthomatous ameloblastoma



·      Peripheral odontogenic fibroma: Hard, pink, smooth, often lobulated mass that are always adjacent to teeth; the mass may displace teeth, but it does not invade bone

·      Canine acanthomatous ameloblastoma: Gray-pink papillary to sessile mass in the vicinity of the alveolus



·      Peripheral odontogenic fibroma (POF): Neoplasm of odontogenic mesenchyme; regularly positioned stellate mesenchymal cells and smooth fibrillar collagen matrix; localized deposition of collagen matrix is often seen and can have characteristics of osteoid/bone, cementum, or dentin; cords of odontogenic epithelium may be present; has considerable overlap with focal fibrous hyperplasia

o   Distinguished from fibrous hyperplasia by the immaturity of the stroma and their tendency to contain less inflammatory tissue and more hard tissue

·      Canine acanthomatous ameloblastoma: Solid sheets, islands, nodules and anastomosing cords of polygonal epithelial cells bordered by a row of palisading cuboidal to columnar cells with round to oval nuclei

o   Prominent intercellular bridges

o   Palisading epithelial cells at the margin of neoplastic islands often have an antibasilar nucleus and basilar clearing

o   Solid sheets/cords of acanthocytic neoplastic cells and prominent intercellular bridges distinguish this tumor from ameloblastoma

o   Interepithelial cysts and small masses of hard tissue can develop

·      Odontogenic epithelium and gingiva express CK14 and CK5/6


For oral/gingival mass:

·      Fibrous hyperplasia: Secondary to localized chronic inflammation that produces a mass of mature fibrous tissue, often with a band of plasma cells adjacent to the overlying hyperplastic epithelium; common in dogs and usually does not recur following surgical excision; diffuse gingival hypertrophy is familial in boxer dogs

·      Pyogenic granuloma: Reactive lesion of the gingival or mucosa; exuberant connective tissue proliferation in response to injury; bright red or blue mass; vascular granulation tissue covered by gingival epithelium; rare; usually does not recur

·      Peripheral giant cell granuloma: Hyperplastic connective tissue response to gingival injury; smooth and sessile or pedunculated; dense, well-vascularized stroma with hemosiderin and numerous multinucleated giant cells with overlying hyperplastic epithelium; associated with the site of tooth extraction; rare with little chance of recurrence in the dog (similar behavior to POF)

·      Ameloblastoma: Tumor composed of proliferating, palisading odontogenic epithelium, (may or may not have keratinization) with features of embryonic enamel organ; predominantly intraosseous; rare

·      Amyloid-producing odontogenic tumors: Characterized by odontogenic epithelium with aggregates of amyloid and +/- trabeculae of osteoid/dentinoid, +/- keratinization; rare

·      Complex odontoma: Composed of disorganized dental tissue (tooth like structures); rare but less so in horses and cattle

·      Compound odontoma: Denticles (tooth like structures) within tumor containing enamel, dentin, cementum, and pulp (looks like more normal tooth); rare but less so in horses and cattle

·      Feline inductive odontogenic tumor; Most common odontogenic neoplasm in kittens; typically occur in maxilla and cause osteolysis; rare; similar to ameloblastic fibroma but with distinctive features consisting of nodules of fibroblasts resembling dental papilla in a connective tissue stroma with clusters of odontogenic epithelium

·      Squamous cell carcinoma (SCC): In dogs usually involves the gingiva or tonsils, locally invades bone and metastasizes to regional lymph nodes (second most common oral tumor); papillary form can appear similar but IHC (p63, AEI/AE3), and 34βE12) can differentiate; in cats SCC is the most common oral malignancy and is usually located on the frenulum of the tongue

·      Melanoma: Most common oral tumor of dogs; usually located on the gingiva, gums, buccal mucosa, lips, and palate; up to 90% metastasize to regional lymph nodes or lungs

·      Fibrosarcoma: Occur on the gums of the upper molars and anterior half of the mandible; more common in younger dogs; about 35% metastasize to regional lymph nodes or lungs; second most common oral malignant neoplasm in cats



·      Cats: Epulides occur less frequently compared to dogs; with multiple epulides, recurrence following excision is more common in cats than in dogs



·      Bell CM, Soukup JW. Nomenclature and Classification of Odontogenic Tumors – Part II: Clarification of Specific Nomenclature. J Vet Dent. 2014; 31(4):234-243.

·      Munday JS, Lohr CV, Kiupel M. Tumors of the alimentary tract. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: John Wiley & Sons, Inc.; 2017:533-543.

·      Thaiwong T, Sledge DG, Collins-Webb A, Kiupel M. Immunohistochemical Characterization of Canine Oral Papillary Squamous Cell Carcinoma. Vet Pathol. 2018; Mar;55(2):224-232.

·      Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:20-27.

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