JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
D-N02

SLIDE A: SIGNALMENT (JPC #2979264):  Rhesus macaque

 

HISTORY:  None

HISTOPATHOLOGIC DESCRIPTION:  Mandibular gingiva; alveolar bone; tooth: Expanding 90% of the submucosal connective tissue and compressing and replacing alveolar bone is a poorly demarcated, unencapsulated, moderately cellular neoplasm composed of islands, cords and trabeculae of odontogenic epithelium attempting to recapitulate teeth on a moderate fibrovascular stroma. Peripheral neoplastic cells are characterized by a prominent layer of tightly packed columnar cells with antibasilar, oval nuclei and prominent basilar cytoplasmic clearing (ameloblasts) which palisade along the basement membrane and occasionally surround foci of loosely arranged stellate to fusiform epithelial cells with prominent intercellular bridging (stellate reticulum). Ameloblasts have distinct cell borders, a moderate amount of pale eosinophilic cytoplasm, and a pale, oval to elongate nucleus with finely stippled chromatin and 1-2 distinct nucleoli. The mitotic count averages 1-5 per individual high power field, and there is multifocal single cell death.  Along the basilar aspects of the palisading ameloblasts are streams of variably thick, wedge-shaped homogeneous, brightly eosinophilic, extracellular matrix (atubular dentin), often directly adjacent to foci of fusiform to spindle cells, few of which are occasionally embedded in the matrix material (odontoblasts).  Rarely the stroma adjacent to neoplastic epithelial cells contains aggregates of loosely arranged, primitive mesenchyme resembling dental pulp.  Neoplastic trabeculae multifocally contain cystic areas (up to 3mm) filled with eosinophilic, granular fluid admixed with cellular debris and scattered degenerating neutrophils or macrophages. Neoplastic cells surround and compress foci of immature woven bone (pre-existing alveolar bone) with scalloped margins lined by few osteoblasts as well as osteoclasts in Howship’s lacunae (remodeling), and there are rare fragments of necrotic/lytic bone. There is multifocal ulceration of the oral epithelium with replacement by numerous viable and degenerate neutrophils, macrophages, and fewer lymphocytes admixed with necrotic bone fragments, cellular and karyorrhectic debris, basophilic granular mineral, plant material, and numerous colonies of cocci.

Tongue: Within normal limits.

 

MORPHOLOGIC DIAGNOSIS:  Gingiva; alveolar bone; tooth: Odontoameloblastoma, rhesus macaque (Macaca mulatta), nonhuman primate.

 

SYNONYMS:  Previously incorporated with ameloblastic odontoma (a term no longer recommended)

 

SLIDE B: SIGNALMENT (JPC# 4104211-01):  10 year old, male-neutered German shepherd dog

 

HISTORY:  Oral mass between teeth 405 and 407

HISTOPATHOLOGIC DESCRIPTION:  Gingival mucosa, mandibular mass:  Expanding the subepithelial connective tissue and elevating the hyperplastic mucosa is an unencapsulated, infiltrative, moderately cellular neoplasm composed of well-differentiated polygonal cells arranged in anastomosing cords, ribbons, and trabeculae separated by abundant, dense, well-vascularized, periodontal ligament-like, fibrous 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 nucleoli.  The mitotic count is 1 per 10 high power fields (2.37mm²).  Along the periphery of trabeculae, neoplastic cells palisade and often have antibasilar nuclei with frequent basilar cytoplasmic clearing, while nonbasilar neoplastic cells in the center of trabeculae often have prominent intercellular bridges (odontogenic epithelium/ameloblasts).  The periodontal ligament-like stroma surrounding neoplastic islands is characterized by evenly spaced stellate fibrocytes on a dense fibrous stroma with numerous evenly spaced, empty, small caliber blood vessels. The overlying mucosa is hyperplastic with deep, anastomosing rete ridges. There is mild submucosal inflammation composed of lymphocytes, plasma cells, and fewer histiocytes.

 

MORPHOLOGIC DIAGNOSIS:  Right mandibular mass between teeth 405-407: Canine acanthomatous ameloblastoma, German shepherd dog, canine.

 

SLIDE C: SIGNALMENT (JPC# 2833327):  Tg.AC mouse

 

HISTORY:  Mandibular mass present at terminal necropsy following a non-carcinogenic study.  

HISTOPATHOLOGIC DESCRIPTION:  Mandibular mass: Expanding the mandible, effacing 90% of the alveolar and mandibular bone, surrounding and replacing the tooth and infiltrating the pulp cavity, and compressing adjacent atrophied skeletal muscle, is an unencapsulated, expansile, infiltrative, moderately cellular neoplasm composed of well-differentiated polygonal cells arranged in anastomosing cords and broad trabeculae separated by dense fibrovascular stroma.  Neoplastic cells have distinct cell borders, a moderate amount of eosinophilic granular cytoplasm, and round to oval nuclei with finely stippled chromatin and 1-3 nucleoli.  The mitotic count is 4 per 2.37mm².  Along the periphery of trabeculae, neoplastic cells palisade and often have antibasilar nuclei with occasional basilar cytoplasmic clearing (ameloblasts), while nonbasilar neoplastic cells at the central of trabeculae are loosely arranged, stellate to fusiform, and exhibit prominent intercellular bridging (stellate reticulum). Neoplastic cells invade and compress remaining foci of immature woven bone (pre-existing, remodeled alveolar bone) which have scalloped margins lined by few osteoblasts as well as osteoclasts in Howship’s lacunae (remodeling). Adjacent skeletal myocytes are shrunken (atrophic).

 

MORPHOLOGIC DIAGNOSIS:  Mandibular mass: Ameloblastoma, Tg.AC mouse, rodent.

 

SYNONYMS: Conventional ameloblastoma

 

GENERAL DISCUSSION:

• Odontogenic lesions are classified based on the process of odontogenesis and the presence or absence of the following tissue types: odontogenic epithelium, mineralized dental matrix, dental pulp, and dental follicle
• Classification of odontogenic tumors:
• Epithelial (not inductive):
  • Conventional ameloblastoma/keratinizing ameloblastoma
  • Calcifying epithelial odontogenic tumor/amyloid-producing odontogenic tumor
  • Canine acanthomatous ameloblastoma (CAA)
  • Mixed Epithelial and Mesenchymal (inductive):
  • Ameloblastic fibro-odontoma
  • Odontoameloblastoma
  • Ameloblastic fibroma
  • Feline inductive odontogenic tumor/inductive fibroameloblastoma
  • Complex odontoma
  • Compound odontoma
• Tooth development:
  • Develops from two embryonic tissues:  Dental laminae that forms enamel cap and embryonic mesenchyme that forms dentin, cementum, and pulp
  • Odontogenic induction:  Ameloblastic epithelium induces differentiation of dental papilla mesenchyme into odontoblasts > odontoblasts form dentin > dentin induces ameloblasts > ameloblasts form enamel
    • Brachydont: ameloblasts disintegrate once tooth erupts; enamel is incapable of repair; odontoblasts remain viable for the life of the tooth
    • Hypsodont (continuously growing) teeth, ameloblasts continue producing enamel after eruption (e.g. rodents)

• Most odontogenic epithelial tumors are considered benign, but they can be locally aggressive and displace/destroy bone and teeth and commonly recur following incomplete or narrow resection
• Conventional ameloblastoma (CA) occurs in a wide range of species, while (canine) acanthomatous ameloblastoma (CAA) is unique to dogs
• Odontoameloblastoma occurs in multiple mammalian species

 PATHOGENESIS:

• Odontogenic tumors originate from dental/odontogenic epithelium (rests of dental epithelium)
• Dental epithelium can induce maturation of undifferentiated mesenchyme of the dental papilla (as it does in tooth development) and production of dental matrix (i.e. in inductive dental tumors listed above)
• Differences between odontogenic tumors depend on the degree of differentiation and/or extent of interaction (and induction) between the epithelium and mesenchyme

 

TYPICAL GROSS FINDINGS:

• Conventional ameloblastoma (CA): Focal swelling within the jawbone (maxilla more common than mandible) that may have cystic/fluctuant areas
  • Central (intraosseous) CA is more common than peripheral gingival CA
• Canine acanthomatous ameloblastoma (CAA): Exophytic mass that arises immediately adjacent to teeth anywhere in the jaw (most common at the rostral mandible)
  • Peripheral (gingival) CAA is more common than central (intraosseous or periodontal ligament) CAA
• Odontoameloblastoma: Expansile lesion of the jaw and alveolus (more common in mandible); can be unilocular or multilocular with hard white material resembling teeth with the mass

 

TYPICAL MICROSCOPIC FINDINGS:

• Key histologic features of odontogenic epithelium:
  • Odontogenic islands have centrally located stellate cells with 1) long intercellular bridges (reminiscent of stellate reticulum of the enamel organ) surrounded by 2) palisading basilar epithelium with characteristic 3) antibasilar nuclei and 4) basilar cytoplasmic clearing
  • Architectural arrangement – plexiform ribbons, round follicles, anastomosing trabeculae, or “ink drop” formations

 

• Conventional ameloblastoma:
  • Proliferating odontogenic epithelium with the key histologic features and arrangements (as listed above) +/- areas of keratinization which may be calcified and/or exhibit cystic degeneration
  • Stroma is fibrovascular with features of the periodontal ligament (stellate cells on a background of collagen with evenly spaced empty blood vessels) and lacks features of pulp ectomesenchyme

 

• Canine acanthomatous ameloblastoma:
  • Islands of odontogenic epithelium with central acanthotic epithelial cells with prominent intercellular bridges that resemble the stratum spinosum of the skin rather than resembling stellate reticulum +/- areas of keratinization which may be calcified and/or exhibit cystic degeneration
    • The lack of central stellate cells reminiscent of stellate reticulum distinguishes this tumor from conventional ameloblastoma
  • Stroma is fibrovascular, often with features of periodontal ligament +/- islands of cemento-osseous matrix, and lacks features of pulp ectomesenchyme

 

• Odontoameloblastoma:  
• Cords or bands of odontogenic epithelium resembling the enamel organ palisading on thin, eosinophilic ribbons of dental matrix (osteodentin) or dysplastic tooth-like structures which are lined on the opposing side by induced spindle cells (odontoblasts)
• The majority of the tumor is neoplastic odontogenic epithelium
• Structures may appear like normal or atypical tooth germs or enamel organ
• Does not have as much stroma or pulp ectomesenchyme as ameloblastic fibro-odontoma
• May have enamel present adjacent to dentin (between dentin and neoplastic ameloblasts), but often lost in processing

 

DIFFERENTIAL DIAGNOSIS:

 

Tumor	Odontogenic epithelium	Stroma	Mesenchyme	Matrix	Species affected	Misc
Odontoameloblastoma	Yes	Variable	Small amounts of pulp-like ectomesenchyme or fibrovascular stroma	Osteodentin in close relationship with odontogenic epithelium +/- enamel	Horses, dog, llamas, rats, macaques, sheep, ox, guinea pig	Cords of odontogenic epithelium around dental matrix
Ameloblastoma	Yes	Not essential for diagnosis	None	None	Dog, cat, horse	Keratinization may occur
Amyloid producing odontogenic tumor	Yes	Not essential for diagnosis	None	Amyloid	Dog, cat, horse	Matrix composed of enamel proteins which are still Congophilic and exhibit apple-green birefringence; IHC + for laminin
Canine acanthomatous ameloblastoma	Yes	Stellate fibroblasts in dense collagen; regularly spaced dilated, empty blood vessels	Periodontal ligament	None	Dog	Interconnected sheets of odontogenic epithelium
Ameloblastic fibroma	Yes (amount variable)	Loose, collagen poor, resembles dental pulp	Abundant pulp ectomesenchyme	None	Young cattle; rarely dog (Huang, J Vet Diagn Invest, 2019), cat	Most common oral neoplasm in cattle (often in mandibular incisor region)
Ameloblastic fibro-odontoma	Yes (amount variable)	Loose, collagen poor, resembles dental pulp	Abundant pulp ectomesenchyme	Dentin or Enamel; unorganized	Young animals, rarely dog (Huang, J Vet Diagn Invest, 2019), cattle
Complex odontoma	Yes (amount variable)	Well-differentiated dentinal tissue	Dental pulp variable	Dentin, enamel (may be mineralized); unorganized denticles	Dog, rodent, primates, horse	Horse, rodents produce cementum; “balls of disorganized dental hard substance”
Compound odontoma	Yes (amount variable)	Well-differentiated dentinal tissue; dense collagen and vascular connective tissue	Dental pulp variable	Dentin, mineralized enamel; organized denticles	Young dogs, horses, rodents, cats, fish (especially angelfish), cattle, primates, White tailed deer, frogs	Multiple tooth-like structures (denticles)

• Oral squamous cell carcinoma (OSCC): Odontogenic epithelium is not a feature of OSCC
• Ameloblastic carcinoma (ACa): Similar features as ameloblastoma with pleomorphism, anaplasia, invasion through basement membrane, loss of odontogenic features, increased mitotic rate, and necrosis
  • ACa and OSCC can be difficult to distinguish histologically due to loss of odontogenic features and non-specific keratinization in ACa; immunohistochemical stains are lacking to distinguish these two malignancies

 

COMPARATIVE PATHOLOGY:

• Feline inductive odontogenic tumor (FIOT): 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
• Dentigerous cysts: Young horses; congenital but not hereditary; often near base of ear; an epithelium-lined cyst forming around tooth remnants
• Transgenic TG×AC (v-Ha-ras) mice have a high incidence of odontogenic tumors
• Odontomas are reported in several species of frogs (LaDouceur, Vet Pathol. 2020)

 

REFERENCES:

1. Bell CM, Soukup JW. Nomenclature and classification of Odontogenic Tumors – Part II: Classification of Specific Nomenclature. J Vet Dent. 2014;31:234-243.
2. Delaney MA, Singh K, Murphy CL, Solomon A, Nel S, Boy SC. Immunohistochemical and biochemical evidence of ameloblastic origin of feline amyloid-producing odontogenic tumors in cats. Vet Pathol. 2013;50(2):238-242.
3. Huang P, Bell C, Wallace V, Murphy BG. Mixed odontogenic tumors in four young dogs: ameloblastic fibroma and ameloblastic fibro-odontoma. J Vet Diagn Invest. 2019;31(1):98-102.
4. Kok MK, Chambers JK, Ushio N, Miwa Y, Nakayama H, Uchida K. Amyloid-producing Odontoameloblastoma in a Black-tailed Prairie Dog (Cynomys ludovicianus). J Comp Pathol. 2018;159:26-30.
5. LaDouceur EEB, Hauck AM, Garner MM, Cartoceti AN, Murphy BG. Odontomas in Frogs. Vet Pathol. 2020;57(1):147-150.
6. 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; 2017:530-543.
7. Murphy, BG, Bell CM, Soukup JW. Odontogenic Tumors. In: Veterinary Oral and Maxillofacial Pathology. 1st ed. John Wiley & Sons, Inc: 2020: 91-127
8. Murphy B, Bell C, Koehne A, Dubielzig RR. Mandibular odontoameloblastoma in a rat and a horse. J Vet Diagn Invest. 2017: 29(4):536-540.
9. 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; 2016:22-25.
10. Vorbach BS, Wolf JC, Yanong RP. Odontomas in two long-finned ocellaris clownfish (Amphiprion ocellaris). J Vet Diagn Invest. 2018: 30(1):136-139.
11. Wong HE, Hedley J, Stapleton N, Murphy B, Priestnall SL. Odontoameloblastoma with extensive chondroid matrix deposition in a guinea pig. J Vet Diagn Invest. 2018: 30(5):793-797.

 

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