14-year-old neutered male long haired domestic cat, Felis catsThe owner noticed a large, painless mass on the gingiva, which was surgically resected 6 days later at the local veterinary practice. The biopsy was sent to the R(D)SVS Veterinary Pathology Unit for histological examination.
Submitted for histological examination was a gingival lesion, lateral and adjacent to the left maxillary, third premolar tooth. This lesion was a 2cm x 1.4cm x 1.1cm, white nodule that was a little gritty and moderately firm. On cut section it was homogeneous and white with a small number of irregular dark red areas.
Gingival lesion (4 sections, slides A1 and A2): The submucosa is expanded and effaced by a densely cellular, poorly demarcated and locally invasive proliferation of epithelial cells arranged in anastomosing cords, ribbons and islands within a collagenous stroma. In this surrounding stroma there are moderate numbers of loosely spaced spindle cells. The cells at the periphery of the islands tend to palisade and range from cuboidal to low columnar. They have poorly defined cell borders, a small amount of basophilic cytoplasm, and a central, oval to indented nucleus with finely stippled chromatin and one nucleolus. The cells at the centre of the islands are stellate, with fibrillar cytoplasmic projections, indistinct cell borders and similar nuclear features to those described above. There is mild anisocytosis and anisokaryosis and mitotic figures average 2 per 10 high power fields (400X). Within the centre of many of the larger islands there are circular to globular aggregates of brightly eosinophilic, smudged to glassy, acellular and amorphous material which stains orange/red with apple green birefringence using a Congo red stain (amyloid). Some islands contain central squamous epithelial cells with associated refractile, lamellar, eosinophilic material, consistent with keratin. Cystic spaces within several islands are compatible with cystic degeneration and contain small numbers of neutrophils. A small number of small, irregular, deposits of eosinophilic material are superimposed with deeply basophilic material (mineralized bone, presumptive). The overlying mucosa is multifocally lost (ulcerated), with associated intense neutrophilic infiltration. Within the superficial submucosa there are clusters of lymphocytes and plasma cells, with neovascularisation and edema.
Amyloid-producing odontogenic tumor with extensive mucosal ulceration - left maxillary gingiva
Amyloid-producing odontogenic tumor
Amyloid-producing odontogenic tumors fall into the category of tumors of odontogenic epithelial origin which do not produce odontogenic mesenchyme.(2) Pertinent histological features include: Anastomosing cords and/or islands of odontogenic epithelium; peripheral palisading of those cells; apical crowding of the nucleus in the palisading cells; and loosely packed internal cells connected by long intercellular bridges, otherwise known as stellate reticulum; formation of extracellular deposits of eosinophilic glassy matrix in spherical nodular aggregates.(5)
In this case the overlying mucosa is ulcerated, with associated neutrophilic infiltration. Additionally, there is accumulation of smudged, pale eosinophilic hyaline material, both within the islands and cords as well as between them. This material is consistent with amyloid, as it stains strongly with Congo red, and is pale green under polarized light.(10)
Amyloid-producing odontogenic tumors (APOT) have been described in dogs, cats and a Bengali tiger.(8-10) They have been reported as focally extensive, infiltrating, firm to friable lesions, frequently involving the entire maxilla.(2,8) These tumors are slowly progressive, locally invasive and can recur locally after excision.(11) There are no reports of metastasis of APOT in the literature.(4)
The histological feature that sets APOTs apart from ameloblastoma and acanthomatous ameloblastoma is the accumulation of amyloid between neoplastic epithelial cells. Other features are shared between these tumors.(5) Recently, the amyloid found in a single case of feline APOT was typed as odontogenic ameloblast-associated protein (formerly termed APin).(2)
Ultrastructurally in APOTs, cords and islands are delimited by a basement membrane, to which cuboidal to polygonal cells attach by hemidesmosomes. There are also numerous desmosomes between adjacent cells (consistent with epithelial cells). All these cells contain numerous tonofilaments, and pseudoinclusions containing 10nm thick filaments are occasionally noted. The ultrastructural presentation of the amyloid noted on light microscopy consists of intercellular accumulations of haphazardly arranged, non-branching, 10nm diameter filaments, which are frequently in direct contact with the epithelial cells.(3)
With regards to terminology, APOTs have also been designated calcifying epithelial odontogenic tumors in the past.(4) This designation has fallen out of favor, as this term is used to name an odontogenic tumor in humans that has a different histological presentation. Calcifying epithelial odontogenic tumors in humans frequently contain sheets of polyhedral cells, with extracellular mineralization of amyloid deposits and intracellular mineralization. Although these features are present in APOTs of dogs and cats, they are rare.(5)
Gingiva, left maxillary: Amyloid-producing odontogenic tumor.
Odontogenic tumors of dogs and cats are considered a diverse group of entities often with overlapping and controversial nomenclature. Amyloid-producing odontogenic tumors (APOT), calcifying epithelial odontogenic tumors (CEOT), and keratinizing ameloblastoma share all of the following features: benignity, odontogenic epithelium, and potential for both keratinization and amyloid deposition.(1) The amyloid in APOT has been demonstrated to be derived from ameloblasts, lending credence to its reclassification as amyloid-producing ameloblastoma.(7) The subjective distinguishing criteria and overlapping microscopic features indicate the possibility that all three of these oral tumors may be variants of a single entity.(1)
The majority of, if not all, odontogenic tumors can fit into one of three categories: epithelial, mixed or inductive, and mesenchymal. All of the various manifestations of ameloblastoma, including canine acanthomatous ameloblastoma, solid/multicystic ameloblastoma and the tumors discussed above are epithelial derived. Mixed or inductive tumors consist of ameloblastic fibroma/fibro-odontoma and feline inductive odontogenic tumors. These are composed of proliferative odontogenic epithelium and odontogenic ectomesenchyme, often with inductive change, and may all occur along a single continuum. Finally, mesenchymal proliferations are perhaps most common, and consist of peripheral odontogenic fibroma (POF) and focal fibrous hyperplasia. The term POF has replaced the use of fibromatous epulis of periodontal ligament origin (FEPLO) among many veterinary surgical pathologists because epulis is a nonspecific term, and the lesion is derived from periosteal stroma rather than periodontal ligament. Both POF and FFH are recognized as separate entities, but also share overlapping clinical and pathologic features.(1)
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. Bock P, Hach V, Baumg+â-ñrtner W: Oral Masses in Two Cats. Vet Pathol (ahead of print, 2011).
3. Breuer W, Geisel O, Linke RP, Hermanns W: Light microscopic, ultrastructural, and immunohistochemical examinations of 2 calcifying epithelial odontogenic tumors (CEOT) in a dog and a cat. Vet Pathol 31:415420, 1994.
4. Gardner, DG, Dubielzig, RR: The so-called calcifying epithelial odontogenic tumour in dogs and cats (amyloid-producing odontogenic tumor) J Comp Pathol 111:221230. 1994.
5. Head KW, Cullen JM, Dubielzig RR, Else RW, Misdorp W, Patnaik AK, Tateyama S, van der Gaag I: Histological Classification of Tumors of the Alimentary System of Domestic Animals, 2nd ed., Vol. X. pp. 46-57. Armed Forces Institute of Pathology, Washington DC, 2003.
6. Head KW, Else RW, Dubielzig RR: Tumors of the Alimentary Tract. In: Tumors in Domestic Animals, ed. Meuten DJ, 4th ed., pp. 402-410. Iowa State Press, Iowa, 2002.
7. Hirayama K, Miyasho T, Ohmachi T, et al. Biochemical and immunohistochemical characterization of the amyloid in canine amyloid-producing odontogenic tumor. Vet Pathol. 2010;47:915-922.
8. Kang MS, Park MS, Kwon SW, Ma SA, Cho DY, Kim DY, Kim Y: Amyloid-producing odontogenic tumour (calcifying epithelial odontogenic tumour) in the mandible of a Bengal tiger (Panthera tigris tigris). J Comp Pathol 134:236240, 2006.
9. Langham RF, Bennett R, Koestner A: Amyloidosis associated with a calcifying ameloblastoma (calcifying epithelial odontoma) in a cat. Vet Pathol 21:549550. 1984.
10. Myers RK and McGavin MD: Cellular and Tissue responses to Injury. In: Pathological Basis of Veterinary Disease, ed. McGavin MD and Zachary JF, 4th ed., pp.45-46. Mosby, Inc., Washington DC, 2003.
11. Poulet FM, Valentine, BA, Summers, BA: A survey of epithelial odontogenic tumors and cysts in dogs and cats. Vet Pathol 29:369380. 1992.