JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 2830560): A 12-year-old spayed female greyhound
HISTORY: This dog had a mass in the mammary gland area.
HISTOPATHOLOGIC DESCRIPTION: Mammary gland: Expanding and effacing the mammary gland is a 1 x 2 cm, unencapsulated, infiltrative, multilobulated neoplasm with multifocal areas of necrosis, hemorrhage, mineralization, and acicular (cholesterol) clefts. The neoplasm incorporates and compresses adjacent ducts and elevates the overlying epidermis. Lobules are separated by variably thick bands of collagen and are composed of polygonal to fusiform cells arranged in islands and solidly cellular areas supported by fine fibrovascular stroma. Neoplastic cells have variably distinct cell borders and abundant eosinophilic vacuolated cytoplasm. Larger vacuoles (up to 50 um in diameter) peripheralize the nucleus. Nuclei are vesiculate with one prominent magenta nucleolus. Mitoses average 5 per 10 HPF. There is moderate anisokaryosis and anisocytosis. Focally, cyst-like spaces are lined by attenuated to cuboidal neoplastic cells and contain homogenous eosinophilic material and cellular debris. Multifocally, there is scattered single cell necrosis, mineral, and small foci of cartilaginous metaplasia with neoplastic cells in lacunae. In the surrounding tissue, there are low numbers of lymphocytes and plasma cells. There is mild epidermal orthokeratotic hyperkeratosis.
MORPHOLOGIC DIAGNOSIS: Mammary gland: Malignant myoepithelioma, greyhound, canine.
SYNONYM: Spindle cell carcinoma
- Mammary gland tumors are the most commonly occurring neoplasm in intact female dogs
- Myoepitheliomas are rare neoplasms derived solely from myoepithelial cells of the mammary gland; they may be benign or malignant
- Myoepithelial cells are contractile cells with smooth muscle and epithelial components; they are normally located between the luminal epithelial cell layer and the basal lamina of various secretory structures (sweat glands, salivary glands, lacrimal glands, and mammary glands)
- Canine mammary tumors are hormone-dependent; early ovariectomy has a major protective effect
- p53 defects have been associated with the development of canine mammary tumors
- p63 (a homologue of the p53 gene) has been associated with and is overexpressed in many human epithelial neoplasms; it has been suggested that p63 is an oncogene in this type of neoplasm
- Cyclooxygenase-2 (COX-2) expression is increased in canine mammary tumors; COX-2 promotes expression of the anti-apoptotic protein bcl-2, thereby inhibiting cellular senescence; COX-2 also helps promote tumor invasiveness that is mediated through increased activity of matrix metalloproteinases 2 and 9
- It has been hypothesized that progenitor cells (CK5+, CK14+, p63+and VIM+) differentiate into terminally- differentiated myoepithelial cells (CALP+, SMA+ and VIM+) via intermediary myoepithelial cells (CK5+, CK14+, p63+, SMA+, CALP+ and VIM+)
- Neoplastic myoepithelial cells in canine complex carcinomas have labelling similar to that of terminally-differentiated myoepithelial cells, while those of malignant myoepitheliomas were comparable with intermediary myoepithelial cells and had significantly higher Ki67 expression
TYPICAL CLINICAL FINDINGS:
- Mammary gland neoplasia occurs most commonly in older bitches that are sexually intact or ones that were spayed later in life
- Most dogs are clinically healthy when initially presented for evaluation of mammary tumors
TYPICAL GROSS FINDINGS:
- Mammary gland tumors may be small, large, ulcerated, fixed, well circumscribed, and involve one or multiple glands
- The caudal 4th and 5th mammary glands are more commonly involved than the more cranial glands
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Bundles and whorls of fusiform oval or spindle cells without a lobular pattern
- Lack of glandular or tubular differentiation
- Neoplastic cells resemble plump fibroblasts with round or elongated vesicular nuclei and frequently vacuolated cytoplasm
- Anisocytosis and anisokaryosis can be marked with variable mitotic figures
- Cells are frequently embedded in or surrounded by a pink to light blue myxoid or chrondromatous matrix
Spindle cells in short bundles surrounded by myxoid matrix
Similar basic features as malignant counterpart but minimal anisocytosis and anisokaryosis and low mitotic index
ADDITIONAL DIAGNOSTIC TESTS:
- Myoepithelial cells
- Smooth muscle components: Positive for calponin, smooth muscle actin and vimentin
- Epithelial components: Positive for cytokeratin
- Alkaline phosphatase: Positive (fibrocytes are ALP negative)
- p63: Sensitive and highly specific marker of myoepithelial cells in canine mammary tissue
- Cytokeratin 5 is a myoepithelial- and squamous-cell differentiating marker in canine tumors
Benign mammary tumors:
- Simple: Proliferation of well-differentiated luminal epithelial cells
- Complex: Mixed proliferation of secretory epithelial cells and cells resembling myoepithelial cells in a mucinous stroma
- Basaloid: Proliferation of monomorphic basaloid epithelial cells
- Fibroadenoma: Mixture of epithelial (luminal and myoepithelial cells) and stromal cells
- Benign mixed tumor: Proliferation of glandular (luminal and myoepithelial) and mesenchymal elements (e.g. cartilage or cartilage and bone)
- Duct papilloma: Papillomatous projections in distended ducts lined by epithelial and resting myoepithelial cells; supported by stalks of vascularized connective tissue
Malignant mammary tumors:
- Tubulopapillary: Proliferation of cells resembling luminal epithelial cells with tubular or papillary arrangement
- Solid: Luminal epithelial tumor cells; usually uniform in size/shape; in solid sheets, cords or nests
- Spindle-cell: Spindle cells usually arranged in solid epithelial patterns with formation of bundles and nests
- Osteosarcoma: Mammary gland is the most common site of extraskeletal soft tissue osteosarcoma in dogs
- Carcinosarcoma: Also called malignant mixed tumor; malignant epithelial and mesenchymal components
- Fibrosarcoma: Uncommon; fusiform cells with distinct interwoven pattern; can arise from preexisting mammary neoplasm or from the interstitial stroma of the mammary gland
- Complex carcinoma: Composed of two cell populations; malignant epithelial component and benign myoepithelial component
- Carcinoma and malignant myoepithelioma: Composed of two cell populations; malignant features in both the myoepithelial and epithelial components
- Primates: One cynomolgus macaque with a malignant myoepithelioma with a squamous epithelial component in the mammary gland
- Mice: Myoepithelioma most frequently arises from the submaxillary and parotid salivary glands; occasionally associated with mammary, preputial or Harderian glands; most common in BALB/c and BALB/cBy mice
- Often associated with concomitant bone marrow/splenic myeloid hyperplasia, likely due to secretory produce from tumor; large tumors may metastasize to lung; often cystic due to necrosis
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