JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

September 2024

D-N01

 

 

Signalment (JPC #1698960): Adult boxer

 

HISTORY: The animal presented with an oral mass

 

HISTOPATHOLOGIC DESCRIPTION: Gingiva: Expanding the subepithelial connective tissue, elevating the overlying hyperplastic mucosa, and extending to cut margins is an unencapsulated, moderately cellular neoplasm composed of spindle to stellate cells that are evenly spaced, arranged in loose, haphazard streams, and separated by an abundant collagenous matrix. Neoplastic cells have indistinct cell borders, a scant to moderate amount of eosinophilic, fibrillar cytoplasm, and an irregularly oval to elongate nucleus with finely stippled to hyperchromatic chromatin and an indistinct nucleolus. The mitotic count is less than 1 per 2.37mm². Focally within the neoplasm is an island of immature, woven bone (osseous metaplasia). Multifocally, there are also few aggregates of homogenous, eosinophilic material up to 40 µm in diameter (cemento-osseous matrix). 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 intracellular edema, multifocal hyperkeratosis, neutrophilic exocytosis, and a focal area of erosion.

 

MORPHOLOGIC DIAGNOSIS: Gingiva: Peripheral odontogenic fibroma (POF), boxer, canine.

 

SYNONYMS: Fibromatous epulis of periodontal ligament origin (FEPLO)

 

GENERAL DISCUSSION: 

• Epulis is a nonspecific term that designates a tumor-like growth of the gingiva of any origin (i.e. neoplastic or non-neoplastic) that is common in dogs and infrequent in cats. – WE DO NOT USE THIS TERM ANYMORE
• Epulis should not be used in morphologic diagnosis because it is non-specific
• Non-neoplastic gingival growths include pyogenic granuloma, peripheral giant-cell granuloma, and fibrous hyperplasia
• Peripheral odontogenic fibroma (POF) is a tumor composed primarily of odontogenic mesenchyme (proliferative mesenchymal cells w/ features of periodontal ligament (PDL)-derived fibroblasts) 
  • Common lesion in dogs older than 3yo; benign
  • Local excision curative
  • Unknown and chronically debated histogenesis and naming of this tumor; the name will likely be changed again in the future
  • Commonly has similar features of reactive fibrous hyperplasia or focal fibrous hyperplasia, a lesion secondary to chronic gingival trauma and irritation; the two are difficult to distinguish, and hybrid lesions exist

 

PATHOGENESIS

• Pathogenesis likely involves a form of reactive hyperplasia
  • In Boxers with diffuse gingival hyperplasia, can have multiple concurrent FEPLO/POFs – Supports reactive/hyperplastic pathogenesis 
• Likely derived from PDL/gingival ligament at site of gingival attachment to the tooth 
• Canine POF/FEPLO is NOT analogous to human lesion POF

 

TYPICAL GROSS FINDINGS:

• Hard, white to pale pink, smooth, exophytic, often lobulated, “cauliflower-like” mass that are always adjacent to teeth; the mass may displace teeth, but it does not invade bone
• Anatomic predisposition for rostral maxilla and caudal mandible 
• Can vary markedly in size and appearance; can be solitary or multiple 
• Usually covered with intact epithelium, but can be ulcerated if traumatized 
• DOES NOT grow into periodontal ligament (PDL) space like other, more aggressive differential diagnoses 

 

TYPICAL MICROSCOPE FINDINGS:

• Three concurrent histo features:

1. Variably dense and proliferative mesenchymal cells embedded in collagenous stroma similar to PDL/gingival ligament 
2. +/- Variable amounts of odontogenic epithelium in scattered follicles or anastomosing plexiform ribbons 
3. +/- Islands, lakes, or conjoining trabeculae of variably mineralized cemento-osseous matrix (osteoid/bone, cementum, dentin)

• Regularly positioned angular, stellate to “kite-shaped” mesenchymal cells
• Considerable overlap with focal fibrous hyperplasia 
  • Distinguished from fibrous hyperplasia by the immaturity of the stroma and their tendency to contain less inflammatory tissue and more hard tissue

DIFFERENTIAL DIAGNOSIS: 

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; little chance of recurrence in the dog (similar behavior to POF)
• Fibroepithelial polyps (FEPs): “Chewing gum granuloma”; pedunculated mass with irregular/cauliflower-like, smooth surface; most commonly arise under or lateral to tongue, but also found in labial and gingival mucosa, soft palate, and hard palate; histologically characterized by a thick fibrovascular stalk consisting of bundles of fibrocytes and fibroblasts embedded in a collagenous matrix rich in blood vessels (Nordio, Vet Pathol, 2022). 
• Ameloblastoma: Tumor composed of proliferating, palisading odontogenic epithelium, (may or may not have keratinization) with features of embryonic enamel organ; predominantly intraosseous; rare; generally exhibits locally aggressive behavior
• Amyloid-producing ameloblastoma (APA): Odontogenic epithelium with aggregates of amyloid at apical surface of neoplastic epithelial cells +/- cemento-osseous matrix, +/- keratinization; rare; formerly known as amyloid-producing odontogenic tumor (APOT) 
• Complex odontoma: Composed of disorganized dental tissue (poorly formed 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 canine oral tumor); papillary form can appear similar; 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, or 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

 

COMPARATIVE PATHOLOGY:

• Cats: Epulides occur less frequently compared to dogs; recurrence following excision is more common in cats than in dogs
• Lions: FEPLO is common in lions (Scott, Vet Pathol. 2020)
• Camelids: Histologically similar lesions have been rarely found in camelids 

 

REFERENCES:

1. Bell CM, Soukup JW. Nomenclature and Classification of Odontogenic Tumors – Part II: Clarification of Specific Nomenclature. J Vet Dent. 2014;31(4):234-243.
2. Monday 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.
3. Murphy, BG, Bell CM, Soukup JW. Tumor-Like Proliferative Lesions of the Tooth Bearing Regions of the Jaw. In: Murphy, BG, Bell CM, eds. Veterinary Oral and Maxillofacial Pathology. 1^st ed. John Wiley & Sons;2020:197-201.
4. Nordio L, Stefanello C, Gasparini S. Oral fibroepithelial polyps (“chewing granulomas”) in 21 dogs: Histomorphology, immunohistochemical characterization, and clinical outcome. Vet Pathol. 2023;60(2):172-177. 
5. Scott KL, Garner MM, Murphy BG, LaDouceur EEB. Oral Lesions in Captive Nondomestic Felids With a Focus on Odontogenic Lesions. Vet Pathol. 2020;57(6):880-884.
6. 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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