JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1946348): Adult Sprague-Dawley rat
HISTORY: A 4 x 4 x 3 cm mass was present on the right external ear canal and right side of the head. On cut surface, it consisted mainly of a yellowish friable material with occasional cystic spaces.
HISTOPATHOLOGIC DESCRIPTION: Zymbal’s gland: Infiltrating subcutaneous tissue is a well-circumscribed, unencapsulated, multilobulated neoplasm that forms variably-sized cystic spaces. The neoplasm is composed of polygonal cells arranged in islands and trabeculae supported by a moderate fibrovascular stroma. Neoplastic islands often have a peripheral layer of basaloid reserve cells which have distinct cell borders, a small amount of eosinophilic, granular cytoplasm, round to oval nuclei with finely stippled chromatin and up to 4 distinct nucleoli; anisocytosis and anisokaryosis are mild and mitoses are 2/10 HPF. Mitotic figures are present both within basal cells and more mature sebocytes. Neoplastic cells exhibit both sebaceous and ductal (squamous) differentiation. Multifocally within the neoplasm, there are variably-sized areas of cystic degeneration (dilated ducts), characterized by cystic spaces filled with viable and degenerate neutrophils, eosinophilic granular material (sebum), cocci and/ or necrotic debris. Multifocally the neoplasm is infiltrated by numerous viable and degenerate neutrophils, epithelioid macrophages and scattered multinucleated giant cells admixed with acicular cholesterol clefts (pyogranulomatous inflammation) or aggregates of lymphocytes and plasma cells.
MORPHOLOGIC DIAGNOSIS: Zymbal’s gland: Carcinoma, Sprague-Dawley rat, rodent.
SYNONYMS: Carcinoma of the auditory sebaceous gland
- Zymbal’s gland or auditory sebaceous gland is a compound branched acinar gland located anteroventral to the external ear meatus
- The normal gland is composed of 3-4 triangular lobules with typical sebaceous morphology; clusters of saccular acini surround and empty near the tympanic membrane; ducts are lined by keratinizing squamous epithelium
- Often included as part of Zymbal’s gland are two simple sebaceous glands located within the lamina propria of the anterior and posterior ear canal
- Zymbal’s gland neoplasia occurs in 0.5% of control Fischer 344 rats
- Malignant neoplasia is the end process in a morphological continuum beginning with hyperplasia and advancing to adenoma and finally carcinoma
- Hyperplasia is usually focal and may involve glandular parenchyma or the squamous epithelium of the ducts; normal lobular pattern is retained
- Malignant tumors can be locally invasive but do not commonly metastasize
- Infrequent, spontaneous neoplasm of 18-24 month old rats without sex predilection
- Tumors may develop from glandular acini or from ductal epithelium
- Several carcinogens known to induce tumors, including benzene
- Cytochrome P-450 activity has been demonstrated in Zymbal’s glands suggesting direct formation of reactive metabolites within the gland
TYPICAL GROSS FINDINGS:
- Adenomas and squamous papillomas are often small and not visible or grow into the external ear canal
- Carcinomas often become large and form firm, movable subcutaneous mass anteroventral to the ear
- Ulceration and necrosis are frequent, producing caseous and purulent exudate
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Structural resemblance to normal gland, but without regular sebaceous gland architecture (in hyperplasia, the gland retains normal architecture)
- Well circumscribed but lacks encapsulation; mixture of basaloid cells and sebaceous cells
- Cystic degeneration and ductal differentiation can be present
- Mitotic activity is in basaloid cells
- Poorly differentiated sebaceous gland cells
- Invasive growth
- Cellular/nuclear atypia
- Nonneoplastic age related change: Acinar atrophy and ductal ectasia
- Mammary gland fibroadenoma: Gross differential; mammary masses can be almost anywhere on the body
- Keratoacanthoma: Encapsulated neoplasm with crateriform appearance, central pore, and keratin pearls
- Retention cysts are ectatic ducts filled with secretory product and lined by attenuated squamous or glandular epithelium; these may be associated with granulomatous inflammation
- Epidermoid cysts are cysts filled with lamellations of keratin and lined by stratified squamous epithelium
- Benign neoplasms include sebaceous adenomas arising from the skin and squamous papillomas from the epithelial lining of the ear: Differentiated by careful gross examination as to where the tumor arises from; glandular proliferation may be seen in squamous papilloma of the zymbals gland
- Squamous cell carcinoma of the skin or ear canal lining: Careful gross examination as to where the tumor arises from
- Preputial and clitoral gland neoplasms can resemble Zymbal’s gland tumors (these are also modified sebaceous glands)
- Zymbal’s glands occur in most rodents and insectivores
- These neoplasms are uncommon in mice
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley and Sons, Inc. 2016: 164.
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- Rudman D, Cardiff R, Chouinard L, Goodman D, Kuttler K, Marxfeld H, Molinolo A, et al. Proliferative and nonproliferative lesions of the rat and mouse mammary, Zymbal’s preputial and clitoral Glands. Toxicol Pathol. 2012 (40); 7S-39S.
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- Seely JC. Carcinoma of the auditory sebaceous glands. In: Jones TC, Mohr U, Hunt RD, eds. Monographs on Pathology of Laboratory Animals: Eye and Ear. Washington, DC: International Life Sciences Institute; 1989: 145-149.
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