JPC SYSTEMIC VETERINARY PATHOLOGY

REPRODUCTIVE SYSTEM

January 2025

R-N09 

 

SIGNALMENT (JPC #2843592): Female rat

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Haired skin with clitoral gland: Markedly expanding the clitoral gland and centered on the markedly ectatic, keratin-filled main clitoral gland excretory duct is a 1.5 cm, encapsulated, well circumscribed, moderately cellular neoplasm composed of epithelial cells forming a peripheral basaloid reserve layer that progresses into either secretory glandular epithelial cells or squamous (ductal) epithelial cells. Neoplastic cells are arranged in broad trabeculae, variably sized acini and cysts, and islands on a fine, markedly edematous fibrovascular stroma. Neoplastic cells have indistinct borders and a moderate amount of eosinophilic, fibrillar to microvacuolated cytoplasm that in secretory glandular cells is often obscured by numerous brightly eosinophilic, intracytoplasmic globules (secretory product) and in squamous epithelial (ductular) cells often contains basophilic keratohyaline granules (gradual keratinization). Nuclei are oval with finely stippled chromatin and a single distinct magenta nucleolus. Anisocytosis and anisokaryosis are mild. Mitoses average 5 per 0.237mm² (1 HPF). The neoplastic cyst and acinar lumina contain degenerating cells and eosinophilic, flocculent secretory product admixed with neutrophils, macrophages, and hemorrhage, fibrin, and edema. Neoplastic cells undergoing ductal (squamous) differentiation surround a central duct containing the previously described secretory product and degenerating cells as well as lamellated keratin, low numbers of neutrophils, scant hemorrhage, fibrin, and edema, and small colonies of cocci. The main clitoral gland excretory duct is markedly ectatic, hyperkeratotic, and confluent with the neoplasm and contains similar debris, lamellated keratin, and secretory product. Within the overlying subcutis and dermis, there is mild, multifocal lymphoplasmacytic inflammation. 

 

MORPHOLOGIC DIAGNOSIS: Clitoral gland: Adenoma, strain not specified rat, rodent.

 

SYNONYM(S): Preputial gland adenoma

 

GENERAL DISCUSSION:

• Clitoral, preputial, perianal (circumanal), and Zymbal’s glands are specialized sebaceous glands; they are compound, holocrine, branched, and tubuloalveolar 
• Female clitoral glands are located lateral to the vaginal opening; male preputial glands are craniolateral to the penis and often appear more cystic than female clitoral glands
• Acini open into numerous lateral ducts that fuse into a wide central duct, which becomes the excretory duct 
• Ducts are lined by keratinizing stratified squamous epithelium
• In rats, cells have large intracytoplasmic eosinophilic granules that contain pheromones and beta-glucuronidase; granules are not present in mice, but the cytoplasm appears brightly eosinophilic
• Neoplasms can develop from the acinar cells, basal cells, or the squamous epithelium
  • Adenoma and adenocarcinoma from acinar cells 
  • Squamous cell papillomas from ductal cells
  • Basal cell carcinoma from basal cells
• Aged rats (15 to 30 months) of various strains are affected
• Spontaneous clitoral gland neoplasms: 15% in F344 rats; 21% in Wistar rats; <1% in Harlan Sprague-Dawley rats

 

TYPICAL GROSS FINDINGS: 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Adenomas and carcinomas may be subdivided by pattern (solid, cystic, and papillary) and cellular differentiation (glandular, basal, squamous, and mixed), but subtyping is not recommended in regulatory toxicity studies
• No differences in biologic behavior between the patterns
• Neoplasms with more than one pattern are classified by the predominant cell type
• Adenomas are well circumscribed
• Carcinomas are locally invasive; metastases to regional lymph nodes and lungs occur rarely
• Acinar cell neoplasms have cells with brightly eosinophilic cytoplasmic granules

 

DIFFERENTIAL DIAGNOSIS:

• Hyperplasia: Cells more uniform, no capsule 
• Carcinoma, mixed cell subtype: mixture of squamous and sebaceous cells, invasion of surrounding tissue, cellular atypia, frequent mitoses
• Carcinoma, squamous cell: Derived from ductal cells, no acinar involvement, rare
• Preputial gland abscess

 

COMPARATIVE PATHOLOGY:

• Dog: Clitoral carcinomas are rare; however, overlapping features with apocrine gland anal sac adenocarcinoma make diagnosis challenging; may have neuroendocrine differentiation
• Mice: Rare reports of spontaneous adenocarcinoma of the clitoral and preputial glands

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4^th ed. Ames, IA: John Wiley and Sons, Inc. 2016:164.  
2. Brix AE, Nyska A, Haseman JK, Sells DM, Jokinen MP, Walker NJ. Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program. Toxicol Pathol; 2005(33):477-83.
3. Rudmann D, Cardiff R, Chouinard L, Goodman D, Küttler K, Marxfeld H, Molinolo A, Treumann S, Yoshizawa K; INHAND Mammary, Zymbal's, Preputial, and Clitoral Gland Organ Working Group. Proliferative and nonproliferative lesions of the rat and mouse mammary, Zymbal's, preputial, and clitoral glands. Toxicol Pathol. 2012;40(6 Suppl):7S-39S.
4. Seely JC, Boorman GA. Mammary gland and specialized sebaceous glands. In: Maronpot RR, Boorman GA, Gaul BW, eds. Pathology of the Mouse. Vienna, IL: Cache River Press; 1999:624-633.

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