Female rabbit (Orytolagus cuniculus), adult (unknown age)The rabbit was found outdoors with a mammary mass (sub-Q mass about 5-6 cm diameter) in the caudal ventral abdomen that turned out to be a malignant hair follicle tumor. The uterus was removed at a later date because an abdominal mass was palpated and to spay the rabbit.

Gross Description:  

Firm pale masses, thickened friable mucosa, and multiple mucosal cysts.

Histopathologic Description:

Histologically, there are two distinctly different masses present within the same section adjacent to the mesometrial insertion; the first located in the endometrium, the second located within the myometrium. The masses are located adjacent to one another and in some areas are in direct contact. The endometrial mass is multilobulated and well demarcated but unencapsulated. It is composed of thick papillary projections expanding into the uterine lumen, as well as lobules of densely packed tubular and glandular structures infiltrating into the subjacent myometrium (Fig. 2-1). Within the papillary projections and lobules, cuboidal to columnar neoplastic epithelial cells form a single, albeit crowded, layer supported by variable amounts of loose vascular collagenous stroma (Fig. 2-2). Lobules are separated by moderate amounts of loose collagenous or myxomatous stroma, while within lobules, cells are supported by scant stroma. The neoplastic population has moderate anisocytosis and anisokaryosis. There are 1-3 mitotic figures per 400X field. Minimal amounts of sloughed cells, inflammation and necrosis are present within the mass. In some sections there are lobules of neoplastic cells within uterine lymphatic vessels covered by a layer of endothelium. Microscopic features of this mass are consistent with an adenocarcinoma.2

Microscopically, the second mass, located in the myometrium, is multilobulated, unencapsulated, poorly demarcated in some areas and infiltrative. It is composed of densely cellular, broad interlacing fascicles of medium sized spindloid cells (Fig. 2-3). These neoplastic cells have indistinct cytoplasmic borders, moderate amounts of vacuolated or fibrillar eosinophilic cytoplasm, a bluntended oval nucleus with finely granulated chromatin and a single eosinophilic nucleolus. In general, there is slight anisocytosis and anisokaryosis, however, rare karyomegalic and multinucleated cells are present. Mitotic figures are uncommon (1 per ten 400X fields). There are several large areas of necrosis with hemorrhage present within the mass (not present in all sections, Images 1 and 2). Although the mitotic rate is low and the neoplastic cells are well-differentiated, the presence of areas of necrosis is consistent with a diagnosis of leiomyosarcoma rather than leiomyoma.2

Morphologic Diagnosis:  

Uterus: Adenocarcinoma
Uterus: Leiomyosarcoma


Uterine adenocarcinoma, leiomyoma

Contributor Comment:  

In contrast to other domestic species where uterine adenocarcinomas are a rare occurrence, the incidence of uterine adenocarcinomas has been reported to be up to 79% in female rabbits over the age of five years, with variation in breed predisposition. In fact, this tumor type is the most common tumor of Orytolagus cuniculus overall.6 Uterine adenocarcinomas in rabbits are often multicentric and affect both uterine horns.1Most are slow growing and present with bloody discharge and/or decreased fertility in breeding animals.5,6 The pathogenesis of these tumors is unclear and appears to be different from those occurring in humans, although there is controversy over this subject in the literature. Uterine leiomyosarcomas are much less common than adenocarcinomas with reported incidences of 1% in aging Dutch rabbits, and 2% in rabbits presenting to veterinarians with uterine disorders.1,5 The submitted case represents a simultaneous occurrence of two spontaneous uterine tumors in a female rabbit. Recently a similar case of concurrent adenocarcinoma and leiomyoma in an individual animal was reported by Kurotaki et al.4 The case report describes two endometrial adenocarcinomas, one of which was closely associated with a myometrial leiomyoma. These cases are similar in the presence of both primary epithelial and mesenchymal tumors within the uterus, with a close physical association between the two. They are different in that the smooth muscle tumor is malignant in the submitted case.

JPC Diagnosis:  

Uterus: Adenocarcinoma
Uterus: Leiomyosarcoma

Conference Comment:  

The cow is the only other domesticated animal that commonly gets uterine adenocarcinomas. This tumor is often seen in abbatoirs and grossly appears as single or multiple firm masses in the wall of the uterus.3 These tumors are often umbilicated and are known to metastasize to the internal iliac lymph nodes and lungs.3 Histologically, this tumor often causes an intense fibrous response with numerous mitoses, cellular pleomorphism, and vascular and lymphatic invasion.3

Other differentials for a neoplastic growth in the uterus of domesticated animals include adenoma, fibroma, leiomyoma, and leiomyosarcoma as mentioned by the contributor. Adenomas are generally rare in domesticated species and can be difficult to distinguish from focal endometrial hyperplasia.3 Fibromas are generally firm, white, expansile masses that histologically appear as very bland, sparsely cellular, densely collagenous growths.3 Fibromas are seen most commonly in dogs and cattle, but they are not prevalent tumors.3 Leiomyomas are composed of interwoven bundles of smooth muscle originating in the myometrium. The amount of connective tissue can be highly variable.3 These tumors are seen in dogs, cats, and cattle.3


1. Baba N, von Haam E: Animal Model: Spontaneous adenocarcinoma in aged rabbits. Am J Path 68:653-656, 1972
2. Cooper BJ, Valentine BA: Tumors of Muscle. In: Tumors of Domestic Animals, ed Meuten DJ, 4th ed., 319- 363, 2002
3. Kennedy PC, Cullen JM, Edwards JF, Goldschmidt MH, Larsen S, Munson L, Nielsen S: Histological classification of tumors of the genital system of domestic animals. In: World Health Organization Histological Classification of Tumors of Domestic Animals, ed. Schulman FY, Second Series, vol. 4, pp. 32-33, 72. Armed Forces Institute of Pathology,Washington, DC, 1999
4. Kurotaki T, Kokoshima H, Kitamori F, Kitamori T, Tsuchitani M: A case of adenocarcinoma of the endometrium extending into the leiomyoma of the uterus in a rabbit. J Vet Med Sci 69:981-984, 2007
5. Saito K, Nakanishi M, Hasegawa A: Uterine disorders diagnosed by ventrotomy in 47 rabbits. J Vet Med Sci 64(6)495-497, 2002
6. Weisbroth SH: Neoplastic Diseases. In: The Biology of the Laboratory Rabbit, eds. Manning PJ, Ringler DH, Newcomer CE, 2nd ed., 259292, Academic Press, New York, NY, 1994

Click the slide to view.

2-1. Uterus

2-2. Uterus

2-3. Uterus

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