JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

D-N12

 

Signalment (JPC #4035521): 8-month-old female Balb/c mouse

 

HISTORY: The mouse was culled during routine surveillance. It had a 3cm diameter, cystic, subcutaneous mass of the ventral neck and cranial chest composed of pale, friable tissue with a rich blood supply. The mass had a central cavity containing blood and viscous material. There were no other gross abnormalities.

HISTOPATHOLOGIC DESCRIPTION: Haired skin: Expanding the subcutis, elevating the overlying dermis and epidermis, and compressing atrophic pre-existing mucinous and mixed salivary glands, is a 1.25cm x 1.0cm expansile, well-demarcated, partially encapsulated, moderately cellular, multilobular, multicystic neoplasm composed of spindle cells arranged in short streams and bundles that form papillomatous projections, lobules on a moderate fibrovascular stroma. Neoplastic cells have indistinct cell borders, a moderate amount of finely vacuolated basophilic cytoplasm, and oval to elongate nuclei with finely clumped chromatin and 1-2 small basophilic nucleoli. Anisocytosis and anisokarysosis are moderate; mitoses average 1-2 per 400X high power field (0.237mm²). Multifocally, neoplastic lobules contain large central areas with loss of differential staining and cellular architecture (lytic necrosis). At one margin of the section, there is a focally extensive region of mature granulation tissue characterized by numerous fibroblasts, small-caliber blood vessels, and loose (immature) collagen. Additionally, the neoplasm is unilaterally bordered by a focally extensive region of granulation tissue which is mixed with granulomatous inflammation, hemorrhage, and hemosiderin-laden macrophages. Cystic spaces within the neoplasm contain necrotic debris and scant hemorrhage and fibrin.

MORPHOLOGIC DIAGNOSES: Haired skin, mixed and mucinous salivary glands: Myoepithelioma, Balb/c mouse, rodent.

 

CONDITION: Myoepithelioma

GENERAL DISCUSSION:

• Myoepitheliomas arise infrequently in most strains of mice, but are relatively common in some strains (BALB/c, BALB/cBy), especially females
• In mice, myoepitheliomas arise most frequently from submaxillary and parotid salivary glands, but may also be associated with mammary, preputial, and Harderian glands

PATHOGENESIS:

• Myoepitheliomas are subcutaneous tumors that arise from myoepithelial cells of various exocrine glands; the origin is from extraglandular ductal myoepithelial cells
• Metastasis to the lungs may occur with large tumors
• There is frequent concomitant bone marrow and splenic myeloid hyperplasia apparently related to a secretory product of the tumor

TYPICAL CLINICAL FINDINGS:

• Most animals with salivary gland neoplasia present due to the development of a mass
• Other symptoms include halitosis, weight loss, anorexia, dysphagia, exophthalmos, Horner’s syndrome, sneezing, and dysphonia

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Tumors are composed of large, pleomorphic, spindle cells with epithelial and mesenchymal features lining a cystic center
• Cystic areas due to necrosis

ADDITIONAL DIAGNOSTICS:

• Immunohistochemistry: 
  • Myoepithelioma are reactive with AE1/AE3, CK7, CK14, p63, GFAP, and S100, while showing more variable reactivity with smooth muscle actin, actin-HHF-35, SMMHC, and calponin 
  • A panel that includes AE1/AE3, p63, S100, and/or smooth muscle actin will help yield the best sensitivity and specificity; in general, it is unwise to rely on a single marker
  • Many antibodies highlight myoepithelial cells, including AE1/AE3, CD10, S100, GFAP, pg63, calponin, smooth muscle actin, and smooth muscle myosin heavy chain (SMMHC), all showing different sensitives and specificities

DIFFERENTIAL DIAGNOSIS:

• Salivary gland neoplasms: 
  • Epithelial: Pleomorphic adenoma (benign mixed tumor), oncocytoma, adenocarcinoma (see D-N11), malignant mixed tumor, cystadenocarcinoma, myoepithelial carcinoma, epithelial-myoepithelial carcinoma (Park, J Comp Pathol. 2018), squamous cell carcinoma, salivary duct carcinoma, basal cell adenocarcinoma
  • Non-epithelial: Rare reports of osteosarcoma, infiltrative angiolipoma, melanoma, and metastatic neoplasms of other origins
• Non-neoplastic salivary gland masses: Salivary gland cyst (pseudocyst AKA sialocele, true salivary cyst), salivary gland infarction (AKA necrotizing sialometaplasia, see D-M12), lipomatosis (rare, unilateral, slowly progressive enlargement of salivary gland by lobules of well-differentiated adipocytes)
• Sialoadenitis
  
  

COMPARATIVE PATHOLOGY:

• Salivary gland neoplasms are rare in all species; reported in cattle, sheep, goats, horses, dogs, cats, and rats but not swine; almost exclusively carcinomas (see D-N11); other rare neoplasms include epithelial (myoepithelioma, squamous cell carcinoma, cystadenocarcinoma) and mesenchymal (angiolipoma, fibrous histiocytoma, osteosarcoma, fibrosarcoma) malignancies that arise in salivary glands
• Rats: One case report of malignant myoepithelioma arising in the parotid gland (Schaudien, J Comp Pathol. 2020)
• Myoepitheliomas are generally considered rare in domestic animals and man; myoepitheliomas of non-salivary glands include:
  • Mammary myoepitheliomas (see R-N14) are described in dogs; rare, benign neoplasms composed of fusiform cells in short bundles on a myxoid matrix; also malignant variants (i.e. malignant myoepithelioma); mammary neoplasms are common in dogs, relatively uncommon in cats, and rare in other domestic species

References:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:114-115.
2. Foster RA, Premanandan C. Female reproductive system and mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1305-1307.
3. Goldschmidt M, Pena L, Rasotto R, Zappulli V. Classification and grading of canine mammary tumors. Vet. Pathol. 2011;48(1):117-131.
4. 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.; 2017:544-9.
5. Park CH, Shiwa N, Sumimoto J, Kimitsuki K. Epithelial-Myoepithelial Carcinoma in a Canine Salivary Gland. J Comp Pathol. 2018;165:52-56.
6. Schaudien D, Creutzenberg O, Wagner A, Dahlmann F, Rittinghausen S. Malignant Myoepithelioma of the Parotid Gland in a Rat. J Comp Pathol. 2020;176:162-164.
7. Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:459-461.
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; 2022:425.
9. Thompson, LDR. Immunohistochemistry of head and neck lesions. In: Dabbs DJ, ed. Diagnostic Immunohistochemistry. 5th ed. Philadephia, PA: Elsevier; 2019:313. 
10. 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: Elsevier Saunders; 2016:30.

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