JPC SYSTEMIC VETERINARY PATHOLOGY
SIGNALMENT (JPC #2843592): Female rat
HISTOPATHOLOGIC DESCRIPTION: Haired skin with clitoral gland: Markedly expanding the clitoral gland is a 1.5 cm, encapsulated, well circumscribed neoplasm composed of polygonal to squamous epithelial cells with a peripheral basaloid reserve layer arranged in broad cords, variably sized acini, islands, and trabeculae surrounding a fine but markedly edematous fibrovascular stroma. Neoplastic cells have indistinct borders and moderate amounts of eosinophilic fibrillar to microvacuolated cytoplasm often obscured by numerous brightly eosinophilic, intracytoplasmic globules (secretory product). Nuclei are oval with finely stippled chromatin and a single distinct magenta nucleolus. Anisocytosis and anisokaryosis are mild. Mitoses average approximately 5 per HPF. The neoplastic projections surround central lumina which contains degenerating cells and an eosinophilic flocculent secretory product admixed with neutrophils and macrophages; multifocally basal cells progress toward a central duct lined by hyperkeratotic keratinizing stratified squamous epithelium containing the previously described secretory product composed of degenerating cells admixed with keratin low numbers of neutrophils, erythrocytes, and small colonies of cocci. The main clitoral gland excretory duct is markedly ectatic, hyperkeratotic, and confluent with the neoplasm and contains similar debris, keratin and secretory product. Within the adjacent subcutis and dermis, there are multifocal infiltrates of scattered Iymphocytes and plasma cells.
MORPHOLOGIC DIAGNOSIS: Clitoral gland: Adenoma, strain not specified rat, rodent.
SYNONYM(S): Preputial gland adenoma
- Clitoral, preputial, 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; these are not present in mice; however, the cytoplasm appears brightly eosinophilic
- Neoplasms 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:
- Firm subcutaneous masses in the perineum lateral to the penis or ventral to the vaginal orifice; sometimes ulcerated
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
- 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
- Dog: clitoral carcinomas are rare; however, overlapping features with apocrine gland anal sac adenocarcinoma make diagnosis challenging; may have neuroendocrine differentiation
- Histologic features consistent with malignant cells of apocrine gland origin
- Subtypes: tubular, solid, rosette type
- Immunohistochemistry: Neuron specific enolase was recently positive in 6 out of 6 cases
- Rare reports of spontaneous adenocarcinoma of the clitoral and preputial glands in mice
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th Ames, IA: John Wiley and Sons, Inc. 2016:164.
- 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.
- 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 Aug;40(6 Suppl):7S-39S.
- 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.
- Verin R, Cian F, Stewart J, Binanti D, MacNeill AL, Piviani M, Monti P, Baroni G, Le Calvez S, Scase TJ, Finotello R. Canine clitoral carcinoma: a clinical, cytologic, histopathologic, immunohistochemical, and ultrastructural study. Vet Pathol. 2018 Jul;55(4):501-509.