JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

D-N11

 

Signalment (JPC #4083908): 4-year-old Manx cat

 

HISTORY: Right mandibular swelling 

 

HISTOPATHOLOGIC DESCRIPTION: Subcutis, right mandible: Infiltrating and effacing the salivary gland, compressing the adjacent salivary gland duct, and elevating the fibrovascular capsule is a multilobulated, unencapsulated, infiltrative, densely cellular neoplasm composed of polygonal cells arranged in glands, islands, nests, and short cords on a dense fibrous to myxomatous or scirrhous stroma. Neoplastic cells have distinct cell borders and either have a moderate amount of brightly eosinophilic granular cytoplasm with few clear vacuoles and a round nucleus with finely stippled chromatin and 1-2 distinct nucleoli, or have an abundant amount of microvacuolated cytoplasm and a compressed, peripheralized nucleus (mucinous differentiation) with dense chromatin and indistinct nucleoli. Anisocytosis and anisokaryosis are moderate and there are 0-2 mitotic figures per 2.37mm². Glandular lumina often contain eosinophilic homogenous material (secretory product) admixed with erythrocytes, viable and degenerate neutrophils, and sloughed neoplastic cells. Multifocally within the stroma, there are areas of cartilaginous metaplasia characterized by chondrocytes within lacunae, embedded in a pale amphophilic matrix. At the margins of the neoplasm there are multifocal aggregates of perivascular lymphocytes and plasma cells, and small to moderate amounts of hemorrhage, fibrin, and edema with few hemosiderin-laden macrophages. 

 

MORPHOLOGIC DIAGNOSIS: Subcutis, right mandible: Salivary adenocarcinoma, Manx, feline.

 

CONDITION: Salivary adenocarcinoma 

 

GENERAL DISCUSSION:

• All domestic animals have parotid, sublingual, and mandibular salivary glands.
  • Zygomatic glands are not found in all animals; present in dogs, cats, and ferrets
• Salivary glands contain lobules of tubuloalveolar adenomeres(which drain into intercalated ducts) consisting of various proportions of mucous and/or serous cells, surrounded by myoepithelial cells
• Neoplasia of salivary glands is rare in all species; occurs most often in parotid and mandibular salivary glands
  1. Salivary gland adenocarcinoma, while rare in the salivary gland of humans, is the most commonly reported malignant salivary gland neoplasm in veterinary species
  2. Cats tend to have more aggressive disease at the time of diagnosis, and metastasis to regional nodes and distant sites (especially the lungs) is more common 

 

TYPICAL CLINICAL FINDINGS:

• Mass in the salivary gland region
• Halitosis, weight loss, anorexia, dysphagia, exophthalmos, Horner’s syndrome, sneezing, and dysphonia

 

TYPICAL GROSS FINDINGS:

• Usually unilateral
• Variable appearance based on type: From cystic with mucinous exudate to white, firm, and multilobulated 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Various structural patterns: Neoplastic epithelial cells arranged in ducts, acini, or solidly cellular areas
• Malignant epithelial salivary gland neoplasms are graded as low or high grade based on: Mitotic rate, cellular pleomorphism, and glandular differentiation
  • Loss of glandular differentiation is associated with a higher-grade and more aggressive neoplasm
• Contains no features of the other subtypes of malignant salivary gland epithelial tumors (see discussion in Differential Diagnosis section)

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Mucus can be identified using mucicarmine, alcian blue, or PAS stains
• Cytology:
  1. Salivary carcinomas: Cohesive aggregations of epithelial cells with high N:C ratio (+/- retained cytoplasmic secretions), sometimes forming acinar structures 
  2. Can be well-differentiated to markedly pleomorphic
  3. Features of malignancy may be mild, and include: Anisocytosis and anisokaryosis, prominent nucleoli, mitotic figures
  4. Psammoma bodies may be seen due to tissue damage or as precursor to malignancy: spherical aggregation of nonpolarizing calcium appatite crystal
  5. Grading from cytology is not reliable for predicting survival time 

 

DIFFERENTIAL DIAGNOSIS: 

• Salivary gland adenomas, four subtypes:
  • Canalicular adenoma: Tubules or anastomosing trabeculae of epithelial cells on a loose stroma
  • Sebaceous gland adenomas: Arise from sebaceous glands associated with salivary gland ducts, encapsulated with lobules of well-differentiated sebocytes surrounded by reserve cells (similar to cutaneous sebaceous gland adenomas)
  • Ductal papillomas: Proliferation of ductal epithelium with a core of connective tissue extending into the lumen of the duct (exophytic) or periductular connective tissue (inverted)
  • Cystadenoma: Multiple cysts containing mucin and papillary ingrowths of epithelial cells
• Mixed tumors (AKA pleomorphic adenoma): Composed of neoplastic myoepithelial and epithelial cells as well as a mesenchymal component (myxoid, chondroid and/or osseus stroma)
  • Analagous to mixed mammary neoplasms
  • Considered benign, but complete excision is difficult and recurrence is common
• Oncocytomas: Large polygonal cells with bright eosinophilic granular cytoplasm
  • Granules are PAS and PTAH positive, but toluidine blue negative (distinguishing them from mast cells)
  • Can resemble rhabdomyomas
  • Ultrastructurally, granules represent mitochondria 

• Acinic cell carcinoma: Well-differentiated epithelial cells surrounded by a basement membrane arranged in small nests
  • Second most common salivary neoplasm (in dogs and cats)
  • Primarily involves serous salivary glands (parotid gland, mandibular)
  • Epithelial cells may have many different appearances, e.g.:
    • Resembling glandular acini with fine basophilic, PAS positive cytoplasmic granules
    • Resembling intercalated ductal epithelium (small cuboidal cells)
    • Large, vacuolated, clear cells with non-staining cytoplasm
  • In general, these are low-grade malignancies with few mitoses and little cell anaplasia
• Mucoepidermoid carcinoma: Composed of squamous epithelial cells, mucus-producing cells, and intermediate cells
  • Squamous epithelial cells have distinct intercellular bridges but rarely produce keratin
  • Mucus can be identified using mucicarmine, Alcian blue, or PAS stains
  • Neoplastic cells are arranged in solid masses, trabeculae, papillary patterns, or form cystic spaces
    • Cysts may rupture and stimulate granulomatous inflammation
    • Infiltrative growth pattern at periphery is indicative of likelihood of local recurrence or metastasis
• Malignant mixed tumors: Composed of either malignant or benign epithelial and mesenchymal populations
• Other malignant subtypes (5): 
  • Cystadenocarcinoma: Malignant epithelial neoplasm with a predominance of cysts; differentiated from cystadenoma by infiltrative growth pattern, higher mitotic rate, and cellular atypia
  • Myoepithelial carcinoma: Proliferation of spindle-shaped, plasmacytoid, or epithelioid cells in a solid or myxoid pattern
  • Salivary gland SCC: Rare; may be confused with invasive SCC from elsewhere in the oral cavity and squamous metaplasia of the salivary duct (in cases of salivary gland infarction)
  • Basal cell adenocarcinomas: Small, dark, basaloid cells arranged in nests with peripheral palisading
  • Salivary duct carcinomas: Intraductal cells that are invasive, forming papillary or solid masses with areas of central necrosis 

• Other neoplasms that may appear to originate in the salivary gland: angiolipoma, fibrous histiocytoma, osteosarcoma, fibrosarcoma
• Metastatic neoplasms: Lymphoma, SCC, fibrosarcoma, infiltrative lipoma, melanoma, mast cell tumor
• Non-neoplastic salivary gland lesions:

• Salivary gland cysts
  • Pseudocyst (AKA sialocele, D-M18): Develop in the subcutaneous tissue due to rupture of a salivary gland duct
  • True salivary gland cyst (AKA ranula): Dilations of the salivary duct or gland
    • Often secondary to blockage of the duct
• Salivary gland infarction (AKA necrotizing sialometaplasia, D-M12): coagulative necrosis of the salivary gland, possible thrombi of adjacent vessels, and marked dysplasia and squamous metaplasia of the salivary ducts adjacent to the areas of coagulative necrosis
• Lipomatosis: Slowly progressive unilateral enlargement of salivary glands by well-differentiated adipocytes, which can occur secondary to inflammation of the salivary gland

 

COMPARATIVE PATHOLOGY:

Salivary gland neoplasia in other species:

• Reported in cattle, sheep, goats, horses, dogs, and cats; not pigs
• Dogs:

• Pleomorphic adenomas are the most common benign neoplasm
• Adenocarcinomas and acinic cell carcinoma are the most common malignant varieties

• Cattle: 

• Adenocarcinoma, squamous cell carcinoma, and pleomorphic carcinoma have been reported in dairy cow (Alexander, J Vet Diagn Invest. 2023)
• Mucoepidermoid carcinoma (MEC) reported in one bull (Alexander, J Vet Diagn Invest. 2023)

• MEC is most frequently reported malignant salivary tumor in humans

• Rodents: Polyomaviruses may induce tumors in salivary glands (and other locations)
• Mice: 

• Myoepithelioma (see D-N12) is the most common salivary gland neoplasm (submaxillary and parotid glands), commonly affected BALB/c females
• Myoepitheliomas also affect mammary, preputial, and Harderian glands

 

REFERENCES:

1. Alexander K, Beam J, Baughman B, Morgan TW. High-grade mucoepidermoid carcinoma of the salivary gland in a bull. J Vet Diagn Invest. 2023;35(1):76-80.
2. Allison RW, Walton RM. Subcutaneous Glandular Tissue: Mammary, Salivary, Thyroid, and Parathyroid. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:111. 
3. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016:3,19-20.
4. Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:507. 
5. Deschuillers PL, Raskin RE. Chapter 16: Eyes and Ears. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:580-582.
6. Hostetter SJ. Chapter 7: Oral Cavity, Gastrointestinal Tract, and Associated Structures. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:294-296,299,300.
7. Munday JS, Lohr CV, Kiupel M. Tumors of the alimentary tract. In: Meuten DJ, ed. Tumors in Domestic Animals. 5^th ed. Ames, IA: John Wiley & Sons; 2017:544-549.
8. Spagnoli ST, Gelberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:397,425. 
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. Philadelphia, PA: Saunders Elsevier; 2016:28-30.

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