JPC SYSTEMIC PATHOLOGY

REPRODUCTIVE SYSTEM

January 2025

R-N17

 

SIGNALMENT (JPC #4087194): Female Shih tzu dog

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Ovary: Arising from the ovarian surface epithelium, filling the ovarian bursa, and compressing periovarian adipose tissue is an unencapsulated, well demarcated, 6 x 3 mm, densely cellular neoplasm composed of neoplastic cuboidal to columnar epithelial cells arranged in single to multilayered cords, arborizing fronds, and papillary projections supported on a fine to moderate fibrovascular stroma. Neoplastic cells have indistinct cell borders, a scant to moderate amount of eosinophilic fibrillar cytoplasm, and a round to oval nucleus with finely stippled to clumped strands of chromatin and 1-2 distinct nucleoli. Anisocytosis and anisokaryosis are moderate and mitotic count averages 1 per 2.37 mm². Multifocally scattered throughout the neoplasm, there are few cysts that contain eosinophilic, proteinaceous fluid.

 

MORPHOLOGIC DIAGNOSIS: Ovary: Papillary carcinoma, Shih Tzu, canine.

 

SYNONYMS: papillary cystadenoma / cystadenocarcinoma 

 

GENERAL DISCUSSION:

• Ovary origin tumors include:
  • Ovarian epithelial tumors: Surface epithelium, SES, and the rete
    • Papillary and cystic adenomas
    • Papillary adenocarcinomas
  • Sex cord stromal tumors
    • Granulosa cell tumors
    • Thecoma, luteoma
  • Germ cell tumors
    • Dysgerminoma
    • Teratoma
  • Gonadal stromal tumors (uncommon)
• Epithelium of the ovary includes:
  • Lining (surface epithelium) of modified mesothelium
  • Rete ovarii
  • Subsurface epithelial structures (SES)
• Ovarian carcinomas occur in all domestic species but are more common in the bitch; tumors arise from one of the sources of ovarian epithelium
  • Bitches: SES origin carcinomas are more common
• Metastasis to the oviduct or uterus is rare
• Tumor induction is reported in bitches by diethylstilbestrol administration
• May be associated with sex cord-stromal tumors

 

TYPICAL GROSS FINDINGS: 

• Uni- or bilateral; cystic, multinodular enlargements
  • Cut surface: Exposes multiple cysts with yellow to brown fluid contents
• Carcinoma:
  • Cauliflower-like growths extending from the surface of the ovary with involvement of the bursa; may be cystic
• Possible carcinomatosis if cyst rupture occurs
• Possible ascites if diaphragmatic lymphatic flow is obstructed

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Papillae lined by single to multiple layers of cuboidal to columnar cells on fibrovascular to connective tissue stalks
• May form single to multilayered cyst walls with lumen that contain proteinaceous material
• Carcinoma: Larger size, areas of necrosis and hemorrhage, cellular atypia, neoplastic cell piling, increased mitotic count, stromal invasion
  • Bursal and/or peritoneal invasion denotes malignancy

 

ADDITIONAL DIAGNOSTICS:

• Immunohistochemistry:
  • SES and surface epithelium express CK7 (sex cord stromal tumors are CK-7 negative) 
  • SES expresses Hector Battifora mesothelial epitope (HBME-1)
  • Placental alkaline phosphatase expression (PLAP) in SES cells may be useful in differentiation of carcinomas of rete ovarii origin
  • Sex cord-stromal tumors often express inhibin-α; ovarian epithelial tumors do not express inhibin-α

 

DIFFERENTIAL DIAGNOSIS: 

• Carcinomas of the ovary: Papillary carcinomas/adenomas differentiated from tumors of the rete ovarii based on location; origin is determined by location of the largest mass if there are multiple sites
  • Subepithelial surface structure origin carcinomas are located mostly in the ovarian cortex
  • Rete ovarii origin carcinomas are most confined to the medulla adjacent to the ovarian hilus; do not express PLAP
• Subepithelial surface structure hyperplasia: May be concurrent with neoplasia
  • Incidence increases with age
  • Rarely extends inward beyond the primary follicles
  • Multicentric whereas adenoma or carcinoma is focal
• Carcinoma originating in the oviduct or uterus: Rare in domestic animals
• Other causes of enlarged ovary:
  • Germ cell tumors
  • Sex cord stromal tumors: often express inhibin-α; ovarian epithelial tumors do not express inhibin-α
  • Oophoritis
  • Ovotestes
  • Ovarian cysts
  • Anovulatory follicles

 

COMPARATIVE PATHOLOGY:

• Both ovarian cystadenoma and cystadenocarcinoma are extremely rare in cats
• Mice: Ovarian papillary cystadenomas and ovarian tubular adenomas arise in aged mice and rats 
• Pet guinea pigs: Adenoma of the rete ovarii and papillary adenoma occur without adjacent hyperplasia or cysts; in a retrospective of small pet mammal reproductive tract tumors, ovarian lesions were found only in guinea pigs  (Paździor-Czapula, J of Comp Path, 2024) 
• White rhinoceros: Report of ovarian carcinoma with metastases to the uterus, lung, and diaphragm (Kim, J Vet Diagn Invest, 2021)
• Asian elephant: In a recent description of reproductive neoplasia (80 elephants), there was a single report of ovarian carcinoma, and is considered uncommon in this species (Landolfi, Vet Pathol, 2021)
• Snakes: Ovarian carcinomas have been reported in snakes, as well as oviductal adenocarcinomas 
• Birds: Cystadenomas occur infrequently within the lumen of the infundibulum Ovarian and oviductal carcinomas are very common in chickens (R-N13)
• Uterine carcinomas: although rare occur more frequently in cattle
  • Metastasis is frequent
  • Histology: located deep in the endometrium with extension into the myometrium
  • Adenomas are rare

 

REFERENCES:

1. Agnew DW, MacLachlan NJ. Tumors of the genital system. In: Meuten DJ, ed. Tumors in Domestic Animals. 5^th ed. Ames, IA: John Wiley & Sons; 2017:690-694.
2. Barnes HJ, Fletcher OJ, Abdul-Aziz T. Chapter 13: Reproductive System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016: 587.
3. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits, 4^th Ed. Ames, IA:John Wiley & Sons. 2016:115.
4. Foster RA. Female reproductive system and mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1162, 1275.
5. Kim SH, Seung BJ, Cho SH, et al. Ovarian adenocarcinoma with metastases in a white rhinoceros. J Vet Diagn Invest. 2021;33(2):366-369.
6. Landolfi JA, Gaffney PM, McManamon R, et al. Reproductive tract neoplasia in adult female Asian elephants (Elephas maximus). Vet Pathol. 2021;58(6):1131-1141.
7. Ossiboff RJ. Serpentes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA:Elsevier. 2018:906-907.
8. Paździor-Czapula K, Mikiewicz M, Fiedorowicz J, et al. Mammary and reproductive tract tumours and tumour-like lesions of 286 small pet mammals: a retrospective study. J Comp Pathol. 2024;213:46-58. 
9. Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:375-377.
10. Shivaprasad HL. Miscellaneous Diseases. In: Boulianne M, ed. Avian Disease Manual. 8th ed., Jacksonville, FL; AAAP Inc.;2019:174.
11. Solano-Gallego L, Masserdotti C. Chapter 13: Reproductive System. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:453.

 

Click the slide to view.

---