Rabbit submissions are evenly distributed between inflammatory disease, neoplasms, and a combination of hyperplastic, metabolic, and degenerative lesions. Pneumonia, nephritis, dermatitis, hepatitis, myocarditis, enterocolitis, and encephalitis lesions in decreasing numbers were identified. Uterine and mammary gland tumors comprised the majority of the neoplasms. In decreasing order were basal cell tumors, lipomas, squamous cell carcinomas, Lymphomas, rectoanal papillomas, malignant melanomas, osteosarcomas, thymomas, testicular tumors, and osteomas. Miscellaneous lesions included collagen nevi, endometrial venous aneurysms, atherosclerosis, intestinal smooth muscle hypertrophy, and sebaceous adenitis.
Disease: Myxoma virus is a poxvirus of rabbits that is closely related to Rabbit (Shope) fibroma virus. Outbreaks in domestic rabbits in California and Oregon are due to a strain that is maintained in brush rabbits (Sylvilagus bachmani). All enzootic strains of virus in brush rabbits are highly lethal to domestic rabbits. The virus is transmitted by mosquitoes. The infections appear as dermal masses with gelatinous edema, especially around body orifices and face, ears and periorbital skin.
Lesion: The cells of the follicular epithelium and rarely the stratified squamous epithelial cells have intracytoplasmic eosinophilic granular inclusions. There is individual cell necrosis of the epithelium. Abundant mucinous degeneration is also noted within the dermis, which is characterized by lacy pale basophilic material widely separating cells. Mild fibroblastic proliferation is also noted.
Diagnosis: Clinical signs and biopsy.
Disease: This lesion is characteristic of the cutaneous papilloma caused by the rabbit (Shope) papilloma virus. Wild rabbits (Sylvilagus) are the natural reservoir; it is uncommon in domestic rabbits. The virus is transmitted by insects and by direct contact through skin trauma. The lesions are restricted to the skin around the eyelids and ears. It appears benign and may regress within months.
Lesion: The mass is characterized by multiple irregular papillary projections of hyperplastic stratified squamous epithelium. These papillary projections generally support thick dense overlying keratin. The lesion begins abruptly at the border with haired skin.
Transmission: Insects and direct contact.
Diagnosis: Clinical signs and biopsy.
Rabbit Fibromatosis (Shope)
Disease: This tumor-like lesion is induced by a poxvirus closely related to myxomatosis virus that is generally carried by arthropod vectors such as mosquitoes. The disease is endemic in wild cottontail rabbits (Sylvilagus floridanus) of the United States and Canada. In cottontail rabbits it is a benign, self-limiting disease. It has been sporadically reported as outbreaks in our domestic rabbits where the tumor-like masses develop on the legs, feet, muzzle, and perineal regions. These masses may persist for months. In young rabbits, metastases to abdominal organs may occur.
Lesion: Within the subcutaneous and dermal region there will be an infiltrative proliferative process comprised of sheets of cells that are plump, polygonal to occasionally elongate fibroblastic cell-types. There is great variation in the cell morphology with many of the cells having multiple nuclei and occasional lobes of the nucleus. The cell nuclei are variably sized, round to oval with a vesicular chromatin and one to occasionally two distinct amphophilic nucleoli. The cytoplasm of the cells is an eosinophilic and finely vacuolated cytoplasm. The mitotic rate is low at less than 1 per high power field. Occasionally, in the fibroblastic cells there may be an indistinct smudgy eosinophilic cytoplasmic inclusion.
Transmission: Insect vector.
Lesion: The raised, circumscribed, moist, crusted, and frequently ulcerated sores are typical for treponematosis or rabbit syphilis. These are most commonly found on the external genitalia, perianal region, and face (chin, nose, etc.). The bacteria is mainly transmitted horizontally during breeding in adults although can also spread vertically from dam to offspring during vaginal delivery or suckling. The bacteria can penetrate intact mucous membranes. The severity of the lesions will vary among rabbit breeds.
Diagnosis: Serological tests include the hemagglutination test, Rapid Plasma Reagin (RPR), or fluorescent Treponema antigen preparation. The bacteria can also be seen with silver stains on histologic biopsies.
Disease: Intestinal coccidial infections are common in rabbits; however, disease (diarrhea) is typically associated only with young rabbits. Several Eimeria spp. are responsible for the intestinal infections and vary in pathogenicity and level of intestinal tract they affect. The transmission is fecal-oral and can be self-perpetuating, even with wire floors.
Lesion: The different developmental forms of the Apicomplexa coccidial parasite can be seen within the intestinal mucosal epithelium.
Diagnosis: Fecal examination.
Disease: Encephalitozoon cuniculi is a microsporidian parasite that in rabbits causes a granulomatous encephalitis and nephritis. This obligate intracellular parasitic protozoa is transmitted by urinary and fecal shedding. The organism has a preference for renal tubular epithelium and endothelium of the CNS capillaries. The common clinical signs include posterior paralysis and a head tilt when present. Although the infection is asymptomatic in many rabbits, the dwarf breeds and immunosuppressed rabbits appear most susceptible to clinical disease.
Lesion: Nonsuppurative encephalitis, myocarditis, and interstitial nephritis.
Diagnosis: Diagnostic tests for use in live rabbits and include enzyme immunoassay (ELISA) and IFA. A positive result does not indicate the rabbit will develop the disease. Histology.
Disease: The larval tapeworm cyst, coenurus, is the larval tapeworm of Taenia taenemulticeps. The definitive hosts for this tapeworm are dogs and foxes. The larval cysts in the rabbit can be found in the connective tissue, abdomen, and brain. Transmission to the definitive host is through ingestion of infected rabbits. Systemic evaluation of the rabbit is recommended and the potential exists for rare zoonotic transmission (from the definitive host!) and subsequent disease in human beings and other accidental intermediate hosts.
Adenocarcinoma of the Uterus
Disease: This tumor is the most commonly reported neoplasia of female rabbits. There is a difference in tumor incidence by breeds. Some breeds (Tan, French silver, Havana and Dutch) can have up to 50-80% incidence rate of tumor development. New Zealand white and California rabbits have a moderately high incidence and it is rare in Belgium and Rex rabbits. The average age is 5-6 years. The tumor develops slowly before there is local invasion of the uterine myometrium and peritoneal cavity. Generally hematogenous metastasis to the lungs, liver, and bones occur within 1-2 years. The clinical signs include; a marked reduction in fertility, small litter sizes, and maternal care, hematuria or serosanguineous vaginal discharge, and progressive weight loss.
Basal Cell Tumor
Disease: These tumors arise from basal cells (epidermal) and often are pigmented. In general, basal cell tumors are solitary, well circumscribed intradermal masses. They are a relatively common skin tumor of rabbits based on our submissions; however, they are infrequently reported. Descriptions of basal cell tumors in domestic dogs and cats, and the few reports from the literature, indicate that these tumors are usually benign, but may become very large and ulcerated.
Lesion: The skin lesions are partially encapsulated discrete expansile neoplasm composed of numerous closely placed cords to small nests of basaloid cells. These cords are comprised of closely placed cells with scant amounts of a finely granular pale eosinophilic cytoplasm and a round cell nucleus with a densely stippled chromatin pattern and indistinct nucleoli. These small cords and occasional nests are separated and supported by fine fibrovascular stroma.
Interstitial Cell Tumor, Testicle
Disease: These have been infrequently described in rabbits; however, this may be a function of a lack of reporting as opposed to a rarity of the tumor. Based on the domestic animal literature, the vast majority of these tumors are benign and cured by castration. Malignancy is extremely rare. We commonly see tumors bilaterally.
Lesion: The expansile tumor is characterized by large polygonal cells arranged in trabeculae separated by thin fibrous connective tissue. These polygonal cells have moderate amounts of a fine granular eosinophilic cytoplasm with an oval cell nucleus that has a densely stippled chromatin pattern and one, occasionally more basophilic nucleoli. The mitotic rate is low at less than one per high power field.
Disease: Lymphoma is reported to be the second most commonly occurring neoplastic condition of rabbits. In general, the reports describe young rabbits (8 months of age) with multiple organ involvement (liver, kidney, spleen, adrenal gland, ovary, and mesenteric lymph nodes). From our submissions, the majority of cases are mature rabbits (> 5 years) and also have multiple organ involvement. A severe anemia occurs late in the disease course.
Disease: Based on our case submissions, we see these tumors in older rabbits, age 9 to 11 years. They have been located on the head and around the rectum. One case resulted in metastases. The tumors were commonly locally invasive.
Mammary Gland Carcinoma
Disease: Mammary gland adenocarcinomas are not uncommonly reported in rabbits and are generally associated with ovarian and uterine disease processes. From studies, it is felt there is a direct correlation between the incidence of uterine tumors and mammary carcinomas in domestic rabbits. Both of these neoplasms may be the result of endocrinologic disturbances. The rabbits are generally middle-aged (6 to 7 years from our case submissions). Mammary gland adenocarcinomas in rabbits do have a moderate to high potential for both local recurrence and metastasis and generally the prognosis is considered guarded. Thoracic radiographs, lymph node evaluations and follow-ups would be recommended.
Disease: Osteosarcomas are uncommon in rabbits but are expected to act like bone tumors of other mammals. These tumors are locally aggressive and have a moderate to high potential for metastasis.
Disease: Thymomas are neoplasms arising from the thymus. They can be classified based on the cells undergoing neoplastic transformation (epithelial and/or lymphocytic). These anterior mediastinal masses are slow-growing, encapsulated, and metastases have not been reported in rabbits. Clinical signs associated with the thymomas include hyperpnea, open-mouth breathing, swelling of the head, and exophthalmos. Generally the rabbits are middle-aged to older (6-8 years). Surgical removal has been described.
Diagnosis: Cytology and biopsy.
Disease: Collagen nevi are characterized by focal excess of dermal collagen and lack a discrete growth. These may be variations of fibromas. They usually are solitary dome- or gumdrop-shaped firm nodules in the skin. Based on our case submissions, the lesions occur most frequently on the body and proximal limbs, and the affected animals are generally male and middle-aged or older (average 6 years). A slight majority develops multiple lesions although complete surgical removal seems curative.
Lesion: The dermis is comprised of numerous irregular, variably thick bundles of collagen. This collagen proliferation blends into the normal surrounding dermal collagen and into the normal superficial dermal collagen. The follicular units are somewhat atrophic and elevated.
Disease: The mucosal rectoanal papilloma is an uncommonly reported lesion in rabbits. It has been described primarily in older male rabbits and demonstrated to be non-viral in origin. These are usually well-differentiated growths and the few cases are reported to be benign. Complete surgical removal is recommended.
Lesion: The biopsy sections are of papillary proliferations of hyperplastic stratified squamous epithelium supported on inflammatory fibrous connective tissue stroma.
Disease: This is an uncommon chronic skin disease of rabbits. The rabbits usually present with a history of non-pruritic scale production and variable alopecia. Multiple skin biopsies are generally necessary. Successful treatment has not been identified, but could include vitamin A or retinoids as reported in other species.
Lesion: The typical lesions are of inflammation directed at the sebaceous gland, and/or an absence of sebaceous glands, a perifollicular lymphocytic infiltrate at the level of the absent sebaceous glands, hyperkeratosis, follicular keratosis, follicular dystrophy, perifollicular fibrosis, and a mural infiltrative lymphocytic folliculitis. Histologic changes not consistent with sebaceous adenitis in other species include interface dermatitis and interface folliculitis with single cell necrosis and basal cell hydropic degeneration.