JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 997552): Rabbit
HISTOPATHOLOGIC DESCRIPTION: Uterus: Multifocally and transmurally infiltrating and effacing the uterus is an unencapsulated, densely cellular, poorly demarcated neoplasm composed of polygonal cells arranged in tubules, acini, and solidly cellular areas on a variably dense collagenous to myxomatous matrix (desmoplasia). Neoplastic cells have indistinct cell borders, a small amount of eosinophilic cytoplasm, a round to oval nucleus with finely stippled chromatin, and indistinct nucleoli. There is mild anisocytosis and anisokaryosis, and less than one mitotic figure per ten 40x HPF. Tubules are ectatic with fronds of neoplastic cell bulging into the lumen, and are often filled with eosinophilic proteinaceous and/or mucinous material admixed with variable amounts of necrotic cellular debris. Multifocally, there are neoplastic cells within uterine lymphatic vessels. There are multifocal areas of coagulative necrosis with loss of differential staining and retention of architecture, as well as multifocal areas of lytic necrosis, characterized by loss of tissue architecture and replacement by eosinophilic cellular and karyorrhectic debris admixed with low numbers of lymphocytes, heterophils, and hemorrhage. Within several cross sections of the uterus, the endometrium is hyperplastic forming papillary projections often lined by epithelium that piles up two to three layers thick. Multifocally hyperplastic glands are markedly ectatic forming cystic structures and are lined by attenuated epithelium (cystic endometrial hyperplasia).
- Uterus: Adenocarcinoma, breed unspecified rabbit, lagomorph.
- Uterus, endometrium: Hyperplasia, cystic, diffuse, moderate.
- Most common spontaneous tumor of the domestic rabbit (Oryctolagus cuniculi)
- Incidence greatly increases with age (4% at 2-3 years, 80% by 5-6 years)
- Often arises in multiple sites within the uterus
- Metastasis to lung, liver, serosa of abdominal organs is common
- Rare in other domestic animals
- Rabbits are induced ovulators and are commonly housed individually
- Adenocarcinoma may arise from endometrial tissue subjected to long periods of unopposed estrogen stimulation
- Variable presence of Estrogen and Progesterone receptor in uterine adenocarcinoma has been documented in Fischer 344 rats (the majority were ER positive)
TYPICAL CLINICAL FINDINGS:
- Hematuria or a serosanguineous vaginal discharge
- Decreased fertility, reduced litter size, increased occurrence of fetal retention/resorption and stillbirths
TYPICAL GROSS FINDINGS:
- Multicentric nodular enlargements of the uterine wall, usually involving both horns
- Firm, cauliflower-like masses that are often ulcerated or papillary to polypoid masses that protrude into the uterine lumen
- May contain large areas of hemorrhage and/or necrosis
- Metastasis to peritoneal cavity early; later metastases to lungs, liver and bone
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Acinar/tubular structures lined by cuboidal cells on myxoid vascular stroma
- May protrude into the uterine lumen and/or invade the myometrium
- May secrete large amounts of mucus into uterine lumen
- Endometrial atrophy
Other causes of uterine enlargement:
- Endometrial hyperplasia
- Uterine polyps
- Uterine venous aneurysms
- Uterine adenocarcinoma is rare in most domestic and wild species, except rabbits and cattle
- Uterine carcinoma is the most common primary uterine neoplasm and is frequently recognized at slaughter as single or multiple, firm nodular, masses in the uterine wall with a strong scirrhous response
- Uterine lymphoma is the most common metastatic uterine neoplasm, and in the cow in the enzootic form, is caused by the bovine leukemia retrovirus; enzootic lymphoma commonly affects the heart, abomasum, lymph nodes and uterus
- BDII/Han, DA/Han, Donryu, and Wistar/Han rats have high incidence of endometrial adenocarcinoma
- Chinese hamsters also have high spontaneous incidence
- Spontaneous adenocarcinoma found in Guinea pigs uterus in 3 animals out of 83 in one study
- Mammary gland adenocarcinoma reported in one male Bornean Orangutan
- Asakawa MG, Goldschmidt MH, Une Y, Normura Y. The immunohistochemical evaluation of estrogen receptor-α and progesterone receptors of normal, hyperplastic, and neoplastic endometrium in 88 pet rabbits. Vet Pathol 2008;45:217-225.
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:320.
- Bertram CA, Muller K, Klopfleisch R. Gental Tact Pathology in Female Pet Rabbits (Oryctolagus cuniculus): Retrospective Study of 854 Necropsy Examinations and 152 Biopsy Samples. J Comp Pathol. 2018 Oct;164:17-26.
- Carpenter NA, Crook EK. Mammary Gland Adenocarcinoma in a Male Bornean Orangutan (Pongo Pygmaeus). J Zoo Wildl Med. 2017 Mar;48(1):224-227.
- Foster RA. Female Reproductive System and Mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1168, 1178.
- Kennedy PC, Cullen JM, Edwards JF, Goldschmidt MH, Larsen S, Munson L, Nielsen S. In: Schulman FY, ed. Histological classification of tumors of the genital system of domestic animals. Vol 4. 2nd ed. Washington, DC: The Armed Forces Institute of Pathology; 1998:31-33.
- Laik-Schandelmaier C, Klopfleisch R, Schoniger S, et al. Sponteneous Arising Tumors and Tumor-like Lesions of the Cervix and Uterus in 83 Pet Guinea Pigs (Cavia porcellus). J Comp Path. 2017 May;156(4):339-351.
- Pare JA, Paul-Murphy J. Disorders of the reproductive and urinary systems. In: Quesenberry KE, Carpenter JW, eds. Ferrets, Rabbits and Rodents: Clinical Medicine and Surgery. 2nd ed. Philadelphia, PA: W. B. Saunders; 2004:183-184.
- Schlafer DH, Foster RA. Female Genital System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St Louis, MO: Elsevier; 2016: 449-450.
- Weisbroth SH: Neoplastic diseases. In: Manning PJ, Ringler DH, Newcomer CE, eds. The Biology of the Laboratory Rabbit. 2nd ed. San Diego, CA: Academic Press; 1994: 262-265.
- Woodhouse SJ, Hanley CS. What is your diagnosis? Uterine Adenocarcinoma. J Am Vet Med Assoc. 2011: 238(3):289-90
- Willson CJ, Herbert RA, Cline JM. Hormone receptor expression in spontaneous uterine adenocarcinoma in Fischer 344 rats. Toxicol Pathol. 2015;43(6):865-71.