JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2022

I-N11

 

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 the subcutaneous tissue and effacing 90% of the normal Zymbal’s gland is an unencapsulated, well-circumscribed, multilobulated, densely cellular neoplasm that forms variably-sized cysts. 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, and round to oval nuclei with finely stippled chromatin and up to 4 distinct nucleoli. Anisocytosis and anisokaryosis are mild and mitoses average 2 per 2.37 sq. mm. Mitotic figures are present both within basal cells and differentiated sebocytes. Neoplastic cells often exhibit either sebaceous or ductal (squamous) differentiation. Multifocally within the neoplasm, there are variably sized areas of cystic degeneration filled with viable and degenerate neutrophils, eosinophilic granular material (sebum), lamellated keratin, cocci, and/ or necrotic debris. Multifocally the neoplasm is infiltrated by numerous viable and degenerate neutrophils, epithelioid macrophages, and scattered multinucleate giant cells admixed with acicular cholesterol clefts or aggregates of lymphocytes and plasma cells. 

 

MORPHOLOGIC DIAGNOSIS: Zymbal’s gland: Carcinoma, Sprague-Dawley rat, rodent.

 

SYNONYMS: Carcinoma of the auditory sebaceous gland 

 

GENERAL DISCUSSION: 

• Zymbal’s gland or auditory sebaceous gland is a compound branched acinar gland located anterior-ventral 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
• There is progression from hyperplasia to adenoma and finally malignant transformation to 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

 

PATHOGENESIS:

• Infrequent, spontaneous neoplasm of rats between 18-24 months of age; no sex predilection
• Tumors may develop from glandular acini or from ductal epithelium
• Several carcinogens are known to induce tumors, including benzene

 

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:

• Adenomas:
  • Structural resemblance to normal gland, but without regular sebaceous gland architecture (vs. hyperplasia in which 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
• Carcinomas:
  • Poorly differentiated sebaceous gland and ductal epithelium origin
  • Invasive growth
  • Cellular/nuclear atypia 
  • Two subtypes (carcinomas are often mixtures of the two): 
    • Sebaceous cell type: Large irregular acini; usually lack ducts; may contain cystic cavities filled with leukocytes and sebaceous material that may contain papillary projections of squamous epithelium protruding into the cystic cavities; often ulcerated; variable proportions of squamous and sebaceous cells, including possible squamous metaplasia of sebaceous epithelium
    • Squamous cell type: Invasive growth of squamous cells through basal lamina, dermis, and striated muscle; varying amounts of squamous cell differentiation; may be keratinized; atypical mitotic figures; loss of intercellular bridges

 

DIFFERENTIAL DIAGNOSIS:

• Sebaceous gland tumors of the skin (which can be located at the base of the ear)
• 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: Ectatic ducts filled with secretory product and lined by attenuated squamous or glandular epithelium; these may be associated with granulomatous inflammation
• Epidermoid cysts: Cysts filled with lamellations of keratin and lined by stratified squamous epithelium
• Squamous papilloma of the Zymbal’s gland 
  • Papillary cornified squamous epithelium extending into the lumen of ducts
  • Absence of sebaceous differentiation
  • Cystic areas contain entirely keratinaceous material 
• Squamous cell carcinoma of the adjacent skin or ear canal lining: Careful gross examination as to where the tumor arises from; may be difficult to differentiate from the squamous cell subtype of Zymbal’s gland carcinoma
• Preputial and clitoral gland neoplasms can resemble Zymbal’s gland tumors histologically & grossly except location and potential eosinophilic granular material in the cytoplasm (these are also modified sebaceous glands)

 

COMPARATIVE PATHOLOGY:

• Zymbal’s glands are present in most rodents and insectivores
• Zymbal’s gland neoplasms are uncommon in mice (small Zymbal’s gland present)

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH.  Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley and Sons, Inc. 2016: 164-165. 
2. King-Herbert AP, Janardhan KS, Herbert RA. Neoplastic Disease. In: Suckow MA, Hankenson FC, Wilson RP, Foley PL, eds. The Laboratory Rat. 3^rd ed. San Diego, CA: Elsevier Inc; 2020:611-612.
3. 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. 
4. Schafer KA, Bolon B. Special Senses-Ear. In: Walling MA, Haschek WM, Rousseaux CG, Bolden B, Mahler BW. Fundamentals of Toxicologic Pathology. 3rd ed. San Diego, CA: Elsevier; 2018: 736.  
5. Yoshizawa K. Specialized Sebaceous Glands. In: Suttie AW, Leninger JR, Bradley AE, eds. Boorman’s Pathology of the Rat: Reference and Atlas. 2^nd ed. San Diego, CA: Academic Press Inc; 2018:347-348, 354-356.

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