JPC SYSTEMIC PATHOLOGY
ENDOCRINE SYSTEM
January 2022
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 a non-encapsulated, 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
• 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 express CK7 and 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: overall 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:

• Rare
• Mice: Ovarian papillary cystadenomas and ovarian tubular adenomas arise in aged mice (Barthold, Pathology of Laboratory Rodents and Rabbits, 2016), and rats (Dixon, J Toxicol Pathol, 2014)
• Pet guinea pigs: Adenoma of the rete ovarii and papillary adenoma occur without adjacent hyperplasia or cysts (Bertram, Jour Comp Path, 2018)
• 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 (Ossiboff, Pathology of Wildlife and Zoo Animals, 2018)
• Birds: 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 Ames, IA: John Wiley & Sons; 2017:690-694.
2. Banco B, Antuofermo E, Borzacchiello G, Cossu-Rocca P, Grieco V. Canine ovarian tumors: an immunohistochemical study with HBME-1 antibody. J Vet Diagn Invest. 2011;23(5):977-981.
3. Banco B, Ferrari R, Stefanello D, et. al. Ovarian embryonal carcinoma in a dog. J Comp Pathol. 2017;157(4):291-295.
4. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits, 4^th Ames, IA:John Wiley & Sons. 2016:115.
5. Bertram CA, Muller K, Klopfleisch R. Genital tract pathology in female pet guinea pigs (Cavia porcellus): a retrospective study of 655 post-mortem and 64 biopsy cases. J Comp Pathol. 2018;165:13-22.
6. Dixon D, Alison R, Bach U, et al. Nonproliferative and proliferative lesions of the rat and mouse female reproductive system. J Toxicol Pathol. 2014;27:1S-107S.
7. Foster RA. Female reproductive system and mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1162.
8. 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.
9. 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.
10. 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.
11. 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.
12. Shivaprasad HL. Miscellaneous Diseases. In: Boulianne M, ed. Avian Disease Manual. 8th ed., Jacksonville, FL; AAAP Inc.;2019:174.

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