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Abstract

With increasing numbers of pet rabbits living out their natural lifespan, rabbit oncology is stepping more and more into the limelight. On the other hand, rabbit tumors are less covered in recent editions of textbooks of veterinary pathology than before. We present 1238 cases with neoplastic and non-neoplastic masses in rabbit tissue, submitted from 2008 to 2019, supplemented by a review of the literature on neoplasms in rabbits. Cutaneous masses comprised 47% of submissions. Trichoblastoma was by far the most common skin neoplasm, and nodular suppurative panniculitis was the second most frequent skin nodule in this series. Epithelial as well as mesenchymal cutaneous neoplasms can be virally induced in rabbits (eg, Shope papilloma, myxomatosis) but were infrequent in the current cases. Mammary neoplasms comprised 21% of submitted masses and 94% of these had histologic features of malignancy. Tumors of the female reproductive tract were responsible for 9% of biopsies and were predominantly uterine adenocarcinoma. Polypoid proliferation of rectal mucosa was the most common lesion in the alimentary tract. A broad spectrum of other neoplasms was described, including sarcomas at vaccination sites and ocular posttraumatic sarcomas, comparable to lesions described in cats.

Keywords

mammary neoplasia skin panniculitis rabbits review trichoblastoma vaccination

Rabbits bred for meat and fur production or for research usually do not grow old, whereas pet rabbits are often allowed to live out their physiologic life span. As the patient population grows older, the incidence of neoplastic diseases increases and up-to-date medical care is requested for this species with increasing frequency. This has led to a considerable change in the focus of rabbit medicine. Here we present data on samples from privately owned pet rabbits submitted for routine histopathology to the IDEXX Surgical Pathology Laboratory in Ludwigsburg, Germany, and consider these findings in reference to the published literature. Cases originated from Northern, Central, and Eastern Europe, consisting of 1238 neoplastic and non-neoplastic masses received from 2008 to 2019 without prior selection, including 858 neoplasms.

The age at presentation was 5.2 ± 2.5 years (mean ± standard deviation) for all masses (range: 2 months to 18 years). Rabbits with neoplastic masses were older (5.7 ± 2.2 years, Fig. 1), and this can be regarded as middle-aged given the usual life span of approximately 9 years. However, age differences were statistically not significant. While skin tumors occurred earlier in life (mean: 5.0 years of age), mammary (mean: 5.7 years) and testicular tumors (mean: 6.8 years) were more frequent in older animals. Polypoid proliferation of rectal mucosa (so-called rectal papilloma) is a condition of older rabbits as described below.

Figure 1.

Age distribution of European pet rabbits with neoplastic and non-neoplastic masses of various body systems.

Both sexes were equally affected by neoplasia (Table 1), with the exception of lesions in genital organs and mammary gland. Of 226 mammary lesions in which the sex was known, only 1 adenocarcinoma occurred in a male. This is similar to feline⁹⁸ and canine⁹ mammary tumors but contrasts with the situation in guinea pigs, in which a high proportion of mammary neoplasms occur in males.³

Table 1.

Number of Pet Rabbits of Each Sex in the Study.

	All lesions	Neoplasia	Neoplasia without sex-related lesions^a
Male	404	213	181
Female	481	435	184
% affected males in all rabbits	46%	33%	49%

^a Without mammary, uterine, and testicular neoplasms.

Published reports¹⁰⁰ and our own data indicate that the condition of disseminated collagenous hamartomas (described in more detail below) occurs nearly exclusively in males (25/28 with known sex in our study). A tendency for skin tumors, especially sarcomas, to occur more in males was also described in a survey of American pet rabbits⁹⁹ and became evident in the analysis of our data (Table 2). Furthermore, in the current study population, melanomas occurred mostly in males (14/16, 88%).

Table 2.

Cutaneous Masses in 582 Pet Rabbits.

Type of lesion	Count (% of all lesions)	% of skin lesions	Age in years (mean, range)	Male/female ratio
Epithelial neoplasms
Epidermal
All	26 (2.1%)	4.48	4.8	0.69
Squamous cell carcinoma	4 (0.3%)	0.69	3–6	n/a
Basal cell carcinoma	8 (0.7%	1.37	4.4, 2–11	n/a
Basosquamous carcinoma	1 (0.1%)	0.17	n/a	n/a
Papilloma	10 (0.8%)	1.72	5, 2–7	4 male
Inverted papilloma	2 (0.2%)	0.34	n/a	n/a
Carcinoma metastasis	1 (0.1%)	0.17	n/a	n/a
Follicular
All	184 (14.9%	31.62	5.5	0.61
Trichoblastoma	162 (13.1%)	27.84	5.6, 2–11	0.77
Malignant trichoblastoma	4 (0.3%)	0.69	6	n/a
Trichoepithelioma	12 (0.7%)	2.06	3.8, 1–9	0.80
Tricholemmoma	2 (0.2%)	0.34	n/a	n/a
Trichofolliculoma	4 (0.3%)	0.69	n/a	n/a
Sebaceous
All	5 (0.4%)	0.86	4.00	2 male
Adenoma	3 (0.2%)	0.52	n/a	n/a
Carcinoma	2 (0.2%)	0.34	1–7	Both male
Apocrine
All	5 (0.4%)	0.86	n/a	All male
Adenoma	1 (0.1%)	0.17	7	n/a
Ductal adenoma	1 (0.1%)	0.17	n/a	n/a
Carcinoma	3 (0.2%)	0.52	n/a	n/a
Epithelial non-neoplastic lesions
All	9 (0.7%)	1.55	1–6	n/a
Keratoma/cutaneous horn	2 (0.2%)	0.34	n/a	n/a
Hair follicle cyst	4 (0.3%)	0.69	3–6	n/a
Apcrine cyst	3 (0.2%)	0.52	1–6	n/a
Mesenchymal neoplasms
All	191 (15.4%)	32.82	6.9, 0.3–13	2.41
Fibroma/collagenous hamartoma	41 (3.3%)	7.04	6.6, 2.5–14	7.33
Myxomatosis	6 (0.5%)	1.03	2.6, 0.5–5	0.67
Lipoma	1 (0.1%)	0.17	2–4	n/a
Fibrolipoma	1 (0.1%)	0.17	4	n/a
Myxoma	2 (0.2%)	0.34	n/a	n/a
Fibrosarcoma	49 (4.0%)	8.42	7.0, 0.3–13	0.67
Myxosarcoma	4 (0.3%)	0.69	7–10	3 female
Hemangiosarcoma	2 (0.2%)	0.34	4–6	n/a
Chondrosarcoma	1 (0.1%)	0.17	8	n/a
Liposarcoma	1 (0.1%)	0.17	n/a	n/a
Sarcoma NOS^a	18 (1.5%)	3.09	6.4, 4–11	3.00
Lymphoma	38 (3.0%)	6.53	4.2, 1–9	1.78
Melanoma	26 (2.1%)	4.47	5.4, 2–9	7.00
Melanocytoma	1 (0.1%)	0.17	6	n/a
Mesenchymal non-neoplastic lesions
All	162 (13.1%)	27.84	3.5, 0.25–10	1.52
Polyp	4 (0.3%)	0.69	1.00	n/a
Dermatitis	6 (0.5%)	1.03	n/a	n/a
Abscessating panniculitis	80 (6.5)	13.75	3.5, 0.25–10	1.55
Granulomas	29 (2.3%)	4.98	4.0, 1–9	2.00
Sarcoidosis-like lesion	3 (0.2%)	0.52	n/a	n/a
Necrosis of adipose tissue	26 (2.1%)	4.47	4.1, 0.8–9	0.80
Myositis	1 (0.1%)	0.17	n/a	n/a
Chondropathy of pinna	3 (0.2%)	0.52	1.00	n/a
Lymphatic cyst	1 (0.1%)	0.17	n/a	n/a
Scar tissue	4 (0.3%)	0.69	n/a	n/a
Xanthoma	2 (0.2%)	0.34	n/a	n/a
Altered lymph node	2 (0.2%)	0.34	n/a	n/a
Suppurative sialoadenitis	1 (0.1%)	0.17	n/a	n/a
Total	582 (47.0%)	100	5, 0.25–14	1.3

Abbreviation: n/a, data not available. ^aNOS denotes not otherwise specified.

In the present study, some neoplasms such as fibrosarcoma occurred in aging rabbits, whereas benign epithelial tumors were found in younger rabbits. Since female rabbits have a high risk of mammary and uterine adenocarcinoma, higher longevity of male rabbits might bias epidemiologic studies. Breed predisposition could not be determined because the breed was unspecified or nonspecific (eg, dwarf rabbit) in most submissions.

Skin

Cutaneous lesions represented the major group of submissions with 582/1238 (47%) cases in this study population (Supplemental Table S1 lists all of the lesions and their frequency). Of these, 411 (71%) were neoplasms including 220 epithelial and 191 mesenchymal neoplasms (Table 2). The remaining 171 cases represented inflammatory and degenerative conditions including 109 (18%) cases of panniculitis (Fig. 2). Panniculitis may be overrepresented among suspected tumors in rabbits because rabbit pus is of caseous consistency and may macroscopically resemble tumor necrosis.

Figure 2.

Subcutaneous abscess, rabbit. The mass is composed of cavitations filled with caseous debris with Splendore-Hoeppli material. Inset: Abscess capsule with pyogenic membrane, containing numerous heterophils. Hematoxylin and eosin (HE). Figure 3. Trichoblastoma, skin, rabbit. The tumor forms a well demarcated growth in the subcutis with multilobular architecture but lack of a capsule. Inset: the growth pattern forms trabeculae and nests resembling hair bulbs. HE. Figure 4. Collagenous hamartoma, skin, rabbit. The subcutis is locally expanded by a poorly demarcated accumulation of collagen fibers, compressing overlying adnexal structures. HE. Figure 5. Polyp, rectum, rabbit. There is a well-demarcated area of mucosal proliferation at the junction between the cutaneous and glandular mucosa. Papillomatous or fibropapillomatous structures are not present, but rather there is epithelial hyperplasia and granulation tissue. Inset: Marked heterophilic exocytosis into a hyperplastic epithelium with maintenance of regular stratification. HE. Figure 6. Abdominal cavity, rabbit. A parasitic structure contains 4 suckers (asterisks) and 2 rows (alternate small and large) of rostellar hooks (arrow) with hooks characterized by a long shaft (arrowhead). The localization and morphology are consistent with Cysticercus pisiformis, a metacestode of the tapeworm Taenia pisiformis. HE. Figure 7. Normal ovary, rabbit. The normal ovary contains high numbers of interstitial cells. Inset: interstitium and one corpus luteum; note the luteinized cells are less eosinophilic than the interstitial cells. Figure 8. Adenocarcinoma, endometrium, rabbit. The intraluminal mass has a scalloped and tubular pattern. Multifocally, this resembles hyperplasia.

Skin: Epithelial Tumors

Next to mammary carcinomas, trichoblastomas were the most frequent neoplasms in the rabbit, comprising 166/1238 (18%) of all neoplastic and non-neoplastic masses. About 35% were situated on the trunk, 20% on the neck, and the remaining in about equal proportions on head, hindlimb, and forelimb. As this distribution parallels the size of these areas, this might be designated as a random pattern, contrasting with the situation in the dog with a predisposition for the head and especially the ear base. Histologically, trichoblastoma in rabbits usually resembled trabecular-type trichoblastoma in dogs (Fig. 3), although 4/166 trichoblastomas (2.4%) had infiltrative growth as evidence of malignancy in our case series. Tumor cells in trichoblastomas in rabbits reportedly express cytokeratin 14 and 17.⁵⁸

Other follicular masses were uncommon (26/1238, 2%) and those of adnexal glands were rare (1%, 13/1238). The latter might be explained by the fact that apocrine glands in rabbits can hardly ever be found outside of glabrous areas and the region at the ventral part of the mandible, also termed the mandibular gland.⁹⁴ Consequently, most apocrine lesions in our series (3 out of 5 with known location) were situated at the chin.

Papillomas occurred on the pinna (n = 9) and on the nose (n = 1). The predominant occurrence on the pinna may suggest a viral cause as for equine aural plaque. One neoplasm exhibited a plaque-like morphology resembling this lesion in horses. Viral cytopathic effects were scant and inclusion bodies could not be detected. Foci with spongiosis and vacuolation were regularly present, but koilocytes were only noted in one neoplasm from the nose.

Actinic damage might be another predisposing factor, but gradual transition from dysplasia to carcinoma, as occurs in cats,³⁷ was not observed. A predominance on the head and pinna was also reported in pet rabbits from the United States of America.⁹⁹ Shope papilloma was diagnosed there, but the cottontail rabbit (Sylvilagus floridanus) is the reservoir for the causative virus and is not present in Europe, so that whether that causes the lesions in European rabbits is uncertain. Immunohistochemistry or polymerase chain reaction for papillomavirus in European rabbit papillomas require further investigation. Malignant transformation towards squamous cell carcinoma has been described for Shope papilloma^81,86 but was not observed in papillomas of our European case series.

Of the 4 squamous cell carcinomas, 3 were present in the hindleg around the tarsal joint, but numbers are too low to speculate on a correlation with the high prevalence of “sore hocks.”

Skin: Mesenchymal Tumors

Rabbits develop a specific multinodular condition characterized by well-differentiated collagenous nodules and plaques all over the body (Fig. 4), which is termed fibroma, collagenous hamartoma,¹⁰⁶ or scleroderma.⁵⁷ In the current case series, 8 of 12 cases of these disseminated collagenous hamartomas occurred in males and only one in a female (sexes of further cases were not given). In one case, testicular interstitial cell tumors were found simultaneously. Also, orchidectomy led to partial resolution of skin lesions in a rabbit with bilateral interstitial cell tumors and increased serum testosterone level prior to surgery.⁵⁷ Therefore, a hormonal pathogenesis has been suspected. It is uncertain whether this is a specific condition, or a stereotypic response toward metabolic imbalances. Over time, male rabbits may normally develop a thickened dermis on the back, suggesting a hormonal influence on collagen fiber synthesis in the rabbit.⁹⁵

Detecting a viral cause of neoplasms in rabbits was a major paradigm change in medicine in the 1930s.⁸⁷ Leporipoxvirus infection may cause fibrous proliferation, best known in Europe with myxomatosis, while Shope fibroma is induced by a different but related leporipoxvirus and is more frequent in North America. Theoretically, Shope fibroma virus might cause sporadic outbreaks if carried by travelling rabbit handlers into Europe. However, given the lack of the virus reservoir in Europe (wild rabbits of the Sylvilagus genus), viral spread can be excluded. A third related and highly aggressive poxvirus has been isolated from Shope fibroma tumors and designated malignant rabbit fibroma virus.⁹¹ It caused multiple myxosarcomas and rapid death due to opportunistic secondary infection. Correlation with a transplantable sarcoma from a rabbit at an injection site of Shope fibroma virus in the 1930s is uncertain.² Neither virus was reported to cause natural disease and both disappeared from the literature in recent decades. Viral mesenchymal neoplasms with histologic morphology of Shope fibroma were not represented in our caseload.

The majority of epithelial skin lesions in the rabbit were benign (206/229, 90%), whereas the majority of mesenchymal neoplasms are malignant in our case series (139/191, 73%) and in the literature.⁹⁹ Fibrosarcoma is a disease of the aging rabbit (mean age 7 years, range 0.3–13 years). It has been postulated that these neoplasms might be vaccine-induced, similar to the cat, after aluminum particles were detected within a fibrosarcoma.⁷⁵

Of 49 fibrosarcomas, 28 (57%) occurred on the trunk and hindlimb in our series. The head and especially the lips were overrepresented with 20% of fibrosarcomas.

Skin: Melanomas

Of 411 cutaneous neoplasms in this series, 27 (6.6%) were of melanocytic origin. Most exhibited a spindle cell morphology with prominent pleomorphism, predominantly oval nuclei with coarse chromatin and moderately conspicuous nucleoli, a moderate amount of cytoplasm with variable numbers of brown pigment granules, and infiltrative growth. Interestingly, 15 of 26 melanomas with a known location were situated on the head, and at least 7 of these were on the pinna, and the pattern was similar in a US survey.⁹⁹ Prominent UV-exposure in this sparsely haired area might play a role. Melan-A, PNL-2, S100, and HMB-45 have been detected with immunohistochemistry in malignant melanomas of 2 rabbits.⁹³

Skin: Tumor-Like Lesions

Panniculitis most frequently affects the thorax and neck. These lesions present as multiple cavitations surrounded by heterophilic granulocytes and a variable amount of granulation tissue. A traumatic cause is likely and correlation with malocclusion is to be considered especially in the head and neck area. In contrast, panniculitis occurring in the limbs is usually diffuse and superficial rather than nodular. It causes a characteristic ulcerative and suppurative pododermatitis of the hind legs (“sore hocks”), and biopsies of such lesions are not submitted as potential neoplasia.

Especially in the neck region, nodular subcutaneous lesions occur in the adipose tissue, consisting of necrotic foci with moderate histiocytic inflammation. Eight of 24 cases of nodular necrosis with known location occurred in the dewlap, a skin fold most prominent in female rabbits but also occurring in obese bucks. A possible cause is blunt trauma.

Hematopoietic System

Cases of lymphoma in our series included 38 arising in the skin, 2 in lymph node, 1 in intestine, 1 in liver, and 1 in spleen. Systemic disease with involvement of multiple organs was not present in the submissions in this case series. Thymic lymphoma is also reported.⁷⁶

Cutaneous lymphomas are far more common in the European pet rabbit population (9.2% of skin neoplasms in this series) than that reported in the United States of America (0.5%⁹⁹ and 1.4%⁶⁶). A screening study did not find herpesviral or retroviral causes.⁷⁹ Cutaneous lymphoma may occur at any age.¹⁰⁹ Most cases are diffuse large B-cell lymphoma or T-cell-rich B-cell lymphoma.⁷⁹ Tumor cells are frequently of intermediate size, without epitheliotropism, and extend deeply into the subcutis and musculature. Mitotic count is variable. T-cell-rich B-cell lymphoma may be challenging because of its innocuous appearance with low mitotic count and mixed cellular composition. Poor demarcation and a lack of different zones or nodular structure might help differentiate it from inflammation.

Our series had only one case of thymoma, although this is reportedly the most common mediastinal neoplasm in the rabbit.⁶⁰ Most are benign, but malignant forms have been described.¹⁰¹ A hemophagocytic histiocytic sarcoma with disseminated growth has been described in a 7-year-old rabbit⁴⁶ with immunolabeling for vimentin, CD204, Iba-1, and lysozyme, but not for CD163. Myeloid leukemia was also reported in a rabbit.⁷⁰

Until recently, immunohistochemistry in rabbits was limited by an origin of the majority of primary antibodies in the rabbit. Development of increasing numbers of monoclonal antibodies will probably lead to rapid progress in immunophenotyping of tumors in rabbits.

Musculoskeletal System

Musculoskeletal masses in our series were exclusively inflammatory and degenerative lesions, especially nodular inflammation of the distal limbs, extending to tendons and bones. No neoplasms of this system were included in our series.

Osteosarcoma has been previously reported in rabbits.^{40,44,107,108,111} The age of affected rabbits ranged from 1 to 9 years with a bimodal distribution, with 5 rabbits below 3 years of age and 9 older than 6 years. Of 14 reported cases, 8 were situated in flat bones,^{1,42,48,67,82,102,107,111} 4 in the limbs,^40,45,59,106 and 1 each in soft tissue of the lip⁷⁸ and the forelimb.¹¹¹ The most common location was the head (6 cases) and especially the mandible (3 cases). Irradiation of the mandible in experimental rabbits resulted in osteosarcoma in 17 of 90 treated animals within a period of only 8 months,¹⁶ and 4 of 9 rabbits developed osteosarcoma within 1 year after irradiation of the hindlimbs.⁵³

Rhabdomyosarcomas have been described^74,99 on the abdomen and the hind limb, respectively. Diagnosis was confirmed by immunohistochemistry for desmin in both cases.

Alimentary System

Oral Cavity

Twenty-eight of 49 (57%) masses in the oral cavity in our series were non-neoplastic and this is explained by the high frequency of dental abscesses in rabbits. Eight other nodular masses of the head and neck had sialadenitis, most likely representing extension of periodontal inflammation to the salivary glands.

Our series included 21 oral neoplasms: 9 papillomas, 4 sarcomas, 3 ameloblastomas, 2 adenocarcinomas, 2 odontogenic fibromas, and 1 squamous cell carcinoma. Rabbits with oral neoplasia were older (5.7 years, statistically similar to 5.1 years for all oral lesions) with a roughly equal sex distribution (7 males, 5 females, further sexes unknown). It is notable that in rabbits, oral papillomatosis is not restricted to young animals but may occur at any age (mean age 4.5 years, range 2–9 years in our case series). Single reported cases of oral neoplasms include osteosarcoma (see above), fibrosarcoma,¹⁵ keratinizing ameloblastoma,⁴¹ ameloblastic fibroma,¹⁰⁴ ossifying fibroma,¹¹⁰ salivary gland adenocarcinoma,¹⁰ cementoma,⁷¹ and complex odontoma.⁷¹

Gastrointestinal Tract

Gastrointestinal neoplasms in our series comprised 1 leiomyoma in the stomach, 1 lymphoma in the intestine, 1 tubular adenocarcinoma in the colon, and 1 papillary adenocarcinoma in the cecum. Others have reported gastric adenocarcinoma and intestinal leiomyosarcoma,³⁶ and lymphoma of the stomach,⁷⁹ small intestine,^30,38 and cecum.⁴⁵ A cecal polyp caused intussusception in an aged rabbit.⁷⁷

We identified 36 anorectal polyps. Ages ranged from 1 to 11 years with a mean of 5.5 years and affecting 18 males and 15 females (sexes unknown for other cases). These lesions consisted of a polypoid expansion of the rectal mucosa at the junction between stratified squamous and glandular epithelium (ie, the anorectal transition). Nonkeratinizing stratified squamous epithelium predominated, but both parts were present in most cases. The surface was usually ulcerated and severely infiltrated with heterophils. Mass formation resulted predominantly from granulation tissue in the lamina propria (Fig. 5) and variable edema. We did not detect viral cytopathogenic effects. Clinically, this condition is referred to as rectal papilloma.⁹⁵ Histologically, however, the lesions suggest reactive proliferation due to chronic inflammation consistent with an inflammatory polyp rather than neoplasia. The opening of rectal glands in this area²⁸ might be a predisposing factor. In contrast, experimentally sensitized rabbits fed carrageenan developed diffuse and dysplastic, non-papillomatous lesions.⁵⁵

Liver and Pancreas

One case each of pancreatic acinar adenocarcinoma, hepatic lymphoma, hepatocellular carcinoma, and cholangiocarcinoma were in our series. Other reported neoplasms include bile duct adenoma³⁶ and biliary cystadenoma.²¹ Biliary neoplasms have been described as comparatively common in the rabbits from 4 to 8 years of age.⁹²

Abdominal Cavity

In 15 cases in our series, intraabdominal nodules were formed of necrotic adipose tissue. Trauma is a possible cause, because of nodular presentation in contrast to the diffuse pattern expected with saponification by pancreatic lipase. Mineralization was frequent, which is also common with abdominal fat necrosis in cats and dogs.⁸⁵ Intraabdominal neoplasia was not present in our series, but mesothelioma has been described in a 3.5-year-old rabbit.⁶³ Two intraabdominal masses in our series were caused by cestodal larvae (Fig. 6).

Respiratory System

Neither primary neoplastic nor non-neoplastic masses of the respiratory system were present in our submissions. In the literature, nasal adenocarcinoma,⁶² anaplastic sarcoma²³ and osteochodroma of the larynx,¹³ and adenocarcinoma of the trachea have been reported.¹³

Neoplasms of the lung are rarely described. Histiocytic sarcoma with frequent systemic spread to the lung has been described.¹¹ Pulmonary carcinoma has been reported.^7,23,27,83 Additionally, small fibropapillomas have been described in a population of rabbits, all of which were older than 2 years, with a mean age of 4 years, and without Shope papilloma virus exposure.²⁰ Lesions were characterized by epithelial papilliform proliferation with a prominent fibrous stalk.

Urinary Tract

Neoplasms of the urinary tract appear to be rare in the rabbit. In this case series, submissions from the urinary tract contained only degenerative and inflammatory lesions, and one inflammatory polyp of the urinary bladder from a 3-year-old male rabbit.

Renal neoplasms have been described in rabbits, especially nephroblastomas (also known as embryonic nephroma and Wilms’ tumor). We only found 1 case report each of renal adenocarcinoma⁴⁹ and nephroblastoma³⁹ in the literature in the last 50 years. Metastases were not detected. In an older compilation of case reports on rabbit neoplasms, embryonal nephroma was described with the second highest frequency next to uterine carcinoma.²⁶ However, this does not equal a high prevalence, because an uncommon neoplasm has a higher likelihood of publication than a well-known one.

Transitional cell carcinoma of the renal pelvis and ureter in combination with adrenal gland carcinoma has been described in a 9-year-old rabbit.⁸⁰ Transitional cell carcinoma of the bladder has been reported in a 6-year-old rabbit.¹⁸

Female Genital Tract

In 1938, the high incidence of uterine neoplasms in the rabbit was reported.³⁵ In a further study presenting necropsy data from 849 female rabbits, the same authors reported 142 uterine adenocarcinomas (16.7%).³³ In our series of biopsy material, uterine adenocarcinoma was the third most common neoplasm (84/1238, 6.8%), after mammary carcinoma (250/1238, 20.2%) and trichoblastoma (166/1238, 13.4%). This discrepancy might be explained by differences between frequency of occurrence and detection or between clinical presentation and actual submission for pathologic examination. Rabbits with uterine neoplasia were 5.6 ± 1.7 years of age (mean ± SD).

Of the 135 uterine masses in our case series, uterine adenocarcinoma was the most frequent with 84 cases (62%), followed by 13 cases (10%) of leiomyoma, 8 (6%) of leiomyosarcoma, and 1 teratoma. Ten of our cases had concurrent uterine adenocarcinoma and either leiomyoma or leiomyosarcoma in the uterus.

Rabbits have high numbers of polygonal finely vacuolated eosinophilic interstitial cells in the ovary. These can easily be mistaken for luteoma (Fig. 7), but we could not convincingly demonstrate luteoma in any submission. According to examinations of the last century, this so-called interstitial organ develops from degrading follicles.⁷² They are a continual source of progesterone, which might explain the high prevalence of neoplasia in the endometrium and mammary gland in aging does.

The mean age of rabbits with uterine adenocarcinoma was 5.6 years (range 3–9 years). In an investigation on uterine disorders in 59 pet rabbits, simultaneous occurrence of endometrial hyperplasia and adenocarcinoma was observed in 11 rabbits and the mean age of hyperplasia was 1.6 years lower than that for adenocarcinoma.¹⁰³ Diffuse endometrial hyperplasia is a common finding in rabbits.¹⁰³ In cases of uterine adenocarcinoma, the non-neoplastic endometrium usually exhibits diffuse hyperplasia, and multifocal progression to malignancy at different locations is common. All this is indicative of stepwise carcinogenesis and supports a hypothesis of a hormonal background. In an experimental study with repeated biopsies of uterine neoplasms, progression from acinary patterns via papillary and cystic structures to disorganized architecture was observed in the majority of neoplasms.³⁴ Further evidence was provided in a study of spontaneous uterine lesions in 88 pet rabbits showing the neoplastic endometrium had higher expression of estrogen and progesterone receptors, particularly in tubular/solid adenocarcinomas, compared with papillary adenocarcinoma, hyperplasia, or normal endometrium. This supports a hypothesis of a hormonal background in carcinogenesis in certain types of tumors in rabbits. However, this study failed to detect differences of clinical outcome.⁴

Intraluminal growth with formation of papillary structures and nests is the most frequent stage at the time of submission in this series (Fig. 8). Invasive growth is found with increasing frequency in larger neoplasms. Mitotic rate is low to moderately elevated, usually about 2 to 8 per 10 hpf (2.37 mm²) without obvious correlation to the growth pattern. In larger neoplasms, necrotic areas also occur, and resultant hemorrhagic discharge is often the reason for clinical detection.

Pulmonary metastases were present in nearly 80% of rabbits with uterine adenocarcinoma in a compilation of necropsy findings,¹⁴ although it should be noted that aggressive neoplasms may be overrepresented at necropsy. Uterine adenocarcinoma must be regarded as a serious threat to longevity in female rabbits, but follow-up investigations are necessary to determine lethality of the lesion without bias.

Uterine leiomyosarcoma is more frequent in rabbits than in other species (38% of all 21 uterine smooth muscle neoplasms vs less than 10% in the dog).⁹⁶ This might reflect a tendency to detect these neoplasms late in their progression, as tumors are commonly large at the time of submission. An extreme case weighing 500 g in our series had extensively infiltrated into the abdominal cavity. Myxosarcoma with similarly invasive growth has been described in a 4-year-old rabbit.⁷³

Diagnosis of deciduosarcoma was made in a rabbit, appearing as a spindle cell tumor with large epithelial cells, karyomegaly, and anisocytosis.¹⁹ Two cases of malignant mixed Müllerian tumor (also known as carcinosarcoma) have been described.^31,103

Ovarian neoplasms of rabbits are rarely reported. Individual cases of granulosa cell tumor,⁴⁷ hemangioma,³⁶ adenoma,¹² adenocarcinoma,¹⁰³ and choriocarcinoma⁵⁰ have been described in the ovary, and one adenoma in the uterine tube.¹⁷

Male Genital Tract

Our series included 32 testicular neoplasms in 31 rabbits. The 3 main types of testicular tumors found in other domestic animals were also detected in the rabbit; that is, Sertoli cell tumor, interstitial cell tumor, and seminoma. Mean age was higher in rabbits with interstitial cell tumors and seminomas than for those with other neoplastic conditions. However, overall low case numbers preclude statistical analysis of this difference. The neoplasms were usually in an advanced stage at the time of submission, having replaced major parts of the testicular parenchyma. Compared to those of dogs, testicular neoplasms of rabbits had a higher percentage of neoplasms with histomorphologic evidence of malignancy, specifically invasive growth in all tumor types as well as increased pleomorphism in interstitial tumors (Table 3).⁹⁷ In this study, invasion of blood vessels was present with all 3 types of neoplasms. Metastases have been described in a seminoma.⁶ Neoplastic cryptorchid testicles may also result in testicular torsion.¹¹²

Table 3.

Testicular Neoplasms in Pet Rabbits.

	Number of tumors	Age in years: mean (range)	Histologic features (%)
	Number of tumors	Age in years: mean (range)	Infiltration	Vascular invasion	Necrosis	Inflammation
Interstitial cell	21	7.0 (1–11)	19	5	67	24
Sertoli cell	6	5.6 (3–7)	67	50	67	50
Seminoma	5	7.8 (7–9)	100	80	60	60

In recent publications, interstitial cell tumors in rabbits have been designated as granular cell tumors due to occurrence of PAS-positive cytoplasmic granules in these neoplasms otherwise identical to interstitial cell tumors in other species.¹⁰⁵ It is questionable whether this neoplasm is in fact different from interstitial cell tumor, or instead there is species-specific staining behavior.

Further neoplasms of the male genital tract were restricted to one scrotal melanoma in our series. The literature presents a testicular teratoma.⁶⁹

Mammary Gland

The mammary gland is the second most frequent location of neoplasms in rabbits in our series, after the skin. Unlike the dog, all mammary complexes have an identical risk for the development of neoplasia in the rabbit. In our study, distribution between cranial, central, and caudal gland were 41%, 19%, and 41% (for 341 neoplastic nodules), and right and left were nearly even with 49% and 51%, respectively (331 nodules). Development from hyperplastic lesions over time was already suspected in 1939.³² Influence of hormonal stimulation is highly likely, but correlation between tumor type and expression of hormonal receptors could not be detected using immunohistochemistry.²²

Most mammary neoplasms in rabbits were simple and histologically malignant in our series (250/265, 94%). Malignant tumors are represented by tubular, papillary, tubulopapillary, solid, adenosquamous, comedo type, complex, ductal, cribriform, anaplastic, spindle-cell carcinomas, and malignant myoepitheliomas. Benign tumors—papillomas, adenomas, and rarely complex adenomas—are uncommon. Mammary neoplasms are exhaustively described in the literature,^8,84,89 but with the limitation of unknown significance of different morphologic patterns for prognosis.

In our series, follow-up was available for only 22 rabbits with mammary tumors (Table 4). There is no obvious correlation between the histologic type and the survival time, not even a tendency of longer survival with better differentiated neoplasms. Of rabbits with mammary adenocarcinoma, 45% survived for longer than one year. This is an unexpectedly high percentage considering the usually obvious evidence of malignancy. Four cases surviving 1 year or longer were euthanized or died with lung metastasis despite there being no reported further neoplasms in the mammary gland, but postmortem examination apparently did not occur. This suggests either slow growth of metastases or a tendency for first diagnosis at a late stage of disease in rabbits in comparison with the situation in dogs and cats. However, metastasis may be widespread, including the uvea.²⁹

Table 4.

Survival Times for Different Types of Mammary Tumors in Pet Rabbits. The Data Show the Number of Cases.^a

	<3 months	3–12 months	>1 year
Papillary	2		3
Tubulopapillary			2
Tubular	2	2	2
Ductal			2
Solid	1	1
Comedo			1
Adenosquamous	3
Anaplastic		1

^a Survival times were as provided by the submitting veterinarian and represent the time from surgery until death. They were based on a survey after a minimum time span of 1 year after submission of the neoplasm. Twenty-six (of 112 submitted) questionnaires were returned. Of those rabbits, 2 died during and 4 days after surgery, respectively, and 2 were lost to follow-up.

Endocrine System

There were no endocrine tumors in our series. In the literature, adenoma⁵ and carcinoma of the adrenal gland⁴³ were described, the latter after administration of a dye. Hyperplasia of the adrenal gland is reportedly frequent.⁹² Neoplasia and hyperplasia of the adrenal cortex may induce hyperandrogenism and aggressive behavior.⁶¹ Similar to ferrets, lack of feedback inhibition due to spaying has been suspected as possible pathogenesis.⁵ Other reported endocrine neoplasms are prolactin-secreting acidophilic adenoma of the pituitary gland, with hyperplasia and neoplasia of the mammary gland,^64,88 as well as teratoma of the pituitary gland,⁶⁵ and carcinoma of the thyroid gland.²⁵

Nervous System and Sensory Organs

Four intraocular neoplasms were present in our series. One adenocarcinoma in a 7-year-old rabbit was suspicious for iridociliary adenocarcinoma and infiltrated strongly into the surrounding soft tissue of the orbit. One iridal lymphoma occurred in a 7-year-old rabbit. A round cell tumor and a spindle cell tumor in 2- and 3-year-old rabbits formed metastases in the skin of the head and neck, respectively; these were both suspicious for amelanotic melanoma, but immunohistochemistry was not performed.

Eight epithelial neoplasms were present in the conjunctiva with a broad spectrum between benign lesions, in situ carcinoma, and infiltrative carcinoma. Four rabbits aged between 4 and 9 years presented with melanoma of the eyelid, and all neoplasms had evidence of malignancy, specifically infiltration and increased cellular pleomorphism.

Intraocular sarcomas were reported in combination with lens rupture²⁴ and presumably occurred posttraumatically as for the feline neoplasm.⁶⁸ B-cell lymphoma has also been observed in 3 rabbits following trauma.⁵¹ Teratoma at the optic chiasm has been described.⁵²

Malignant peripheral nerve sheath tumors apparently occur with some frequency,⁹⁹ but neoplasms of the central nervous system of rabbits are rarely reported. One schwannoma extended from the spinal roots to the brachial plexus.⁹⁰ Ependymoma was described⁵⁴ and various glial tumors could be experimentally induced in young rabbits.⁵⁶

Supplemental Material

Supplemental Material, sj-pdf-1-vet-10.1177_03009858211002190 - Not Just Uterine Adenocarcinoma—Neoplastic and Non-Neoplastic Masses in Domestic Pet Rabbits (Oryctolagus cuniculus): A Review

Supplemental Material, sj-pdf-1-vet-10.1177_03009858211002190 for Not Just Uterine Adenocarcinoma—Neoplastic and Non-Neoplastic Masses in Domestic Pet Rabbits (Oryctolagus cuniculus): A Review by Berit Baum in Veterinary Pathology

Footnotes

Acknowledgements

The author would like to thank Drs Nora Berghoff, Jaco van der Lugt, Melissa Behr, and Janice Harvey for their valuable input; Dr Nikola Pantchev for parasitologic consultation; and Dr Annika Lehmbecker for help with figures.

Declaration of Conflicting Interests

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this study.

Funding

The author received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Berit Baum

Supplemental material for this article is available online.

References

Amand

Riser

Biery

. Spontaneous osteosarcoma with widespread metastasis in a belted Dutch rabbit. J Am Anim Hosp Assoc. 1973;9:577–581.

Andrewes

Ahlstrom

. A transplantable sarcoma occurring in a rabbit inoculated with tar and infectious fibroma virus. J Pathol Bacteriol. 1938;47(1):87–99.

Andrews

. Mammary neoplasia in the guinea pig (Cavia porcellus). Cornell Vet. 1976;66(1):82–96.

Asakawa

Goldschmidt

Une

, et al. The immunohistochemical evaluation of estrogen receptor-α and progesterone receptors of normal, hyperplastic, and neoplastic endometrium in 88 pet rabbits. Vet Pathol. 2008;45(2):217–225.

Baine

Newkirk

Fecteau

, et al. Elevated testosterone and progestin concentrations in a spayed female rabbit with an adrenal cortical adenoma. Case Rep Vet Med. 2014;2014:239410. doi:10.1155/2014/239410 10.1155/2014/239410

Banco

Stefanello

Giudice

, et al. Metastasizing testicular seminoma in a pet rabbit. J Vet Diagn Invest. 2012;24(3):608–611.

Barile

. Cancer du poumon chez le lapine. Rev Pathol Comp. 1920;13:180–183.

Baum

Hewicker-Trautwein

. Classification and epidemiology of mammary tumours in pet rabbits (Oryctolagus cuniculus). J Comp Pathol. 2015;152(4):291–298.

Bearss

Schulman

Carter

. Histologic, immunohistochemical, and clinical features of 27 mammary tumors in 18 male dogs. Vet Pathol. 2012;49(4):602–607.

10.

Bercier

Guzman

DSM

Stockman

, et al. Salivary gland adenocarcinoma in a domestic rabbit (Oryctolagus cuniculus). J Exot Pet Med. 2013;22(2):218–224.

11.

Bertram

Garner

Reavill

, et al. Giant cell sarcomas in domestic rabbits (Oryctolagus cuniculus). Vet Pathol. 2020;57(4):490–496.

12.

Bertram

Klopfleisch

Müller

. Ovarian lesions in 44 rabbits (Oryctolagus cuniculus). J Vet Med Sci. 2017;79(12):1994–1997.

13.

Bertram

Klopfleisch

Müller

. Tracheal and laryngeal tumors in two domestic rabbits. J Exot Pet Med. 2019;29:142–146.

14.

Bertram

Müller

Klopfleisch

. Genital tract pathology in female pet rabbits (Oryctolagus cuniculus): a retrospective study of 854 necropsy examinations and 152 biopsy samples. J Comp Pathol. 2018;164:17–26.

15.

Brower

Goldstein

Ziegler

, et al. Spontaneous oral fibrosarcoma in a New Zealand rabbit. J Vet Dent. 2006;23(2):96–99.

16.

Buchholz

McCabe

Cobb

, et al. TP53 overexpression in radiation-induced osteosarcoma of the rabbit mandible. Radiat Res. 1999;15(3):278–282.

17.

Chambers

Uchida

Ise

, et al. Cystic rete ovarii and uterine tube adenoma in a rabbit. J Vet Med Sci. 2014;76(6):909–912.

18.

Cikanek

Eshar

Nau

, et al. Diagnosis and surgical treatment of a transitional carcinoma in the bladder apex of a pet rabbit (Oryctololagus cuniculus). J Exot Pet Med. 2018;27(2):113–117.

19.

Cooper

Adelsohn

Gilbertson

. Spontaneous deciduosarcoma in a domestic rabbit (Oryctolagus cuniculus). Vet Pathol. 2006;43(3):377–380.

20.

Cooper

Griffith

Chroneos

, et al. Spontaneous lung lesions in aging laboratory rabbits (Oryctolagus cuniculus). Vet Pathol. 2017;54(1):178–187.

21.

DeCubellis

Kruse

McCarthy

, et al. Biliary cystadenoma in a rabbit (Oryctolagus cuniculus). J Exot Pet Med. 2010;19(2):177–182.

22.

Degner

Schoon

Laik-Schandelmaier

, et al. Estrogen receptor-α and progesterone receptor expression in mammary proliferative lesions of female pet rabbits. Vet Pathol. 2018;55(6):838–848.

23.

Di Girolamo

Selleri

Collarile

, et al. Endoscopic identification of a laryngeal anaplastic sarcoma in a pet rabbit. J Small Anim Pract. 2017;58(11):664.

24.

Dickinson

Bauer

Gardhouse

, et al. Intraocular sarcoma associated with a rupture lens in a rabbit (Oryctolagus cuniculus). Vet Ophthalmol. 2013;16(suppl 1):168–172.

25.

Dinges

Kovac

. Metastasierendes Schilddrüsenkarzinom bei einem Kaninchen. Z Versuchstierkd. 1972;14(4):197–204.

26.

Dobberstein

Tamaschke

. Tumoren. In: Cohrs

Jaffee

Meessen

, eds. Pathologie der Laboratoriumstiere. Springer; 1958;782–799.

27.

Doerr

. A spontaneous bronchogenic carcinoma of the domesticated rabbit. Frankf Z Pathol. 1952;63(1):82–87.

28.

El-Ghazali

Ali

. Rectal, anal gland: a corrective morphological study in New Zealand rabbit (Oryctolagus cuniculus). Benha Vet Med J. 2018;34(2):221–233.

29.

Eördöhg

Szikszaia

Fuchs-Baumgartinger

, et al. Bilateral uveal metastasis due to a mammary carcinoma in a rabbit: a case report. J Exot Pet Med. 2019;29:123–127.

30.

Gómez

Gázquez

Roncero

, et al. Lymphoma in a rabbit: histopathological and immunohistochemical findings. J Small Anim Pract. 2002;43(5):224–226.

31.

Goto

Nomura

Une

, et al. Malignant mixed Mullerian tumor in a rabbit (Oryctolagus cuniculus): case report with immunohistochemistry. Vet Pathol. 2006;43(4):560–564.

32.

Greene

HSN

. Familial mammary tumors in the rabbit. III. Factors concerned in their genesis and development. J Exp Med. 1939;70(2):167–184.

33.

Greene

HSN

. Uterine adenomata in the rabbit III. Susceptibility as a function of constitutional factors. J Exp Med. 1942;73(2):273–292.

34.

Greene

HSN

Newton

. Evolution of cancer of the uterine fundus in the rabbit. Cancer. 1948;1(1):82–99.

35.

Greene

HSN

Saxton

. Uterine adenomata in the rabbit: I. Clinical history, pathology and preliminary transplantation experiments. J Exp Med. 1938;67(5):691–708.

36.

Greene

HSN

Strauss

JSS

. Multiple primary tumors in the rabbit. Cancer. 1949;2(4):673–691.

37.

Gross

Ihrke

Walder

, et al. Epidermal tumors. In: Gross

Ihrke

Walder

, eds. Skin Diseases of the Dog and Cat: Clinical and Histopathological Diagnosis. 2nd ed. Blackwell Science; 2005:562–577.

38.

Harcourt-Brown

. Gastric dilation and intestinal obstruction in 76 rabbits. Vet Rec. 2007;161(12):409–414.

39.

Hassan

Katic

Klang

, et al. Treatment of nephroblastoma with polycythaemia by nephrectomy in a rabbit. Vet Rec. 2012;170(18):465.

40.

Higgins

Sanchez-Migallon Guzman

Sadar

, et al. Coxofemoral amputation in a domestic rabbit (Oryctolagus cuniculus) with tibiofibular osteoblastic osteosarcoma. J Exot Pet Med. 2015;24(4):455–463.

41.

Hinzmann

Volker

Kammeyer

, et al. Peripheres keratinisierendes Ameloblastom bei einem Zwergkaninchen (Oryctolagus cuniculus f. dom) [in German]. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2014;42(5):331–335.

42.

Hoover

Paulsen

Quallis

, et al. Osteogenic sarcoma with subcutaneous involvement in a rabbit. J Am Vet Med Assoc. 1986;189(9):1156–1158.

43.

Hueper

Ichniowski

. Carcinoma of the adrenal cortex in a rabbit. Cancer Res. 1944;4(3):176–178.

44.

Ishikawa

Kondo

Onuma

, et al. Osteoblastic osteosarcoma in a rabbit. Comp Med. 2012;62(2):124–126.

45.

Ishikawa

Maeda

Kondo

, et al. A case of lymphoma developing in the rabbit cecum. J Vet Med Sci. 2007;69(11):1183–1185.

46.

Ishimori

Michishita

Yoshimura

, et al. Disseminated histiocytic sarcoma with hemophagocytosis in a rabbit. J Vet Med Sci. 2017;79(9):1503–1506.

47.

Iyer

Majumdar

. Note on spontaneous granulosa cell tumour of ovary in a rabbit (Oryctolagus cuniculus). Indian J Anim Sci. 1979;49:242–244.

48.

Jacobson

. Comparative Pathology of the Tumors of Bone. Thomas

Charles C

; 1971.

49.

Kaufman

Quist

. Spontaneous renal carcinoma in a New Zealand white rabbit. Lab Anim Care. 1970;20(3):530–532.

50.

Kaufmann-Bart

Fischer

. Choricocarcinoma with metastasis in a rabbit (Oryctolagus cuniculi). Vet Pathol. 2008;45(1):77–79.

51.

Keller

Guzman

Reilly

, et al. Posttraumatic ocular lymphoma in three rabbits (Oryctolagus cuniculus). J Exot Pet Med. 2019;28:154–161.

52.

Kersting

Hammersen

. Ein Teratom der Chiasmagegend bei einem Kaninchen. Zenteralbl Veterinärmed. 1958;5(6):601–608.

53.

King

Casarett

Weber

. A study of irradiated bone. I. Histopathologic and physiologic changes. J Nucl Med. 1979;20(11):1142–1149.

54.

Kinkler

Jepsen

. Ependymoma in a rabbit. Lab Anim Sci. 1979;29(2):255–256.

55.

Kitano

Matsumoto

Hiki

, et al. Epithelial dysplasia of the rabbit colon induced by degraded carrageenan. Cancer Res. 1986;46(3):1374–1376.

56.

Kleihues

Zülch

Matsumoto

, et al. Morphology of malignant gliomas induced in rabbits by systemic application of N-methyl-N-nitrosourea. Z Neurol. 1970;198(1):65–78.

57.

Kojimoto

Naitoh

Ozaki

, et al. A scleroderma-like lesion in a rabbit with Leydig cell tumors. Jap J Vet Anesthesia Surg. 2006;37:39–42.

58.

Kok

Chambers

Ushio

, et al. Histopathological and immunohistochemical study of trichoblastoma in the rabbit. J Comp Pathol. 2017;157(2-3):126–135.

59.

Kondo

Ishikawa

Maeda

, et al. Spontaneous osteosarcoma in a rabbit (Oryctolagus cuniculus). Vet Pathol. 2007;44(5):691–694.

60.

Künzel

Hittmair

Hassan

, et al. Thymomas in rabbits: clinical evaluation, diagnosis, and treatment. J Am Anim Hosp Assoc. 2012;48(2):97–104.

61.

Lennox

Chitty

. Adrenal neoplasia and hyperplasia as a cause of hypertestosteronism in two rabbits. J Exot Pet Med. 2006;15(1):56–58.

62.

Lennox

Reavill

. Nasal mucosal adenocarcinoma in a pet rabbit. J Exot Pet Med. 2014;23(4):397–402.

63.

Lichtensteiger

Leathers

. Peritoneal mesothelioma in a rabbit. Vet Pathol. 1987;24(5):464–466.

64.

Lipman

Zhao

Andrutis

, et al. Prolactin-secreting pituitary adenomas with mammary dysplasia in New Zealand white rabbits. Lab Anim Sci. 1994;44(2):114–120.

65.

Marguliès

. Über ein Teratom der Hypophyse bei einem Kaninchen. Neurol Centralbl. 1901;20:1026–1031.

66.

Mauldin

Goldschmidt

. A retrospective study of cutaneous neoplasms in domestic rabbits (1990–2001). Vet Dermatol. 2002;13(4):211–229.

67.

Mazzullo

Russo

Niutta

, et al. Osteosarcoma with multiple metastases and subcutaneous involvement in a rabbit (Oryctolagus cuniculus). Vet Clin Pathol. 2004;33(2):102–104.

68.

McPherson

Newman

McLean

, et al. Intraocular sarcomas in two rabbits. J Vet Diagn Invest. 2009;21(4):547–551.

69.

Meier

Meyers

Fox

, et al. Occurrence, pathological features, and propagation of gonadal teratomas in inbred mice and rabbits. Cancer Res. 1970;30(1):30–34.

70.

Meir

Fox

Crary

. Myeloid leukemia in the rabbit (Oryctoloagus cuniculus). Cancer Res. 1972;32(8):1785–1787.

71.

Miwa

Nakata

Takimoto

, et al. Spontaneous oral tumours in 18 rabbits (2005–2015). J Small Anim Pract. 2021;62(2):156–160. doi:10.1111/jsap.13082

72.

Mori

Matsumoto

. Development of the secondary interstitial gland in the rabbit ovary. J Anat. 1973;116(pt 3):417–430.

73.

Hajdu

Nagy

Gál

, et al. A case of primary uterine myxosarcoma with generalized metastasis in rabbit. Pathological case report. Magy Allatorvosok. 2012;134(2):89–96.

74.

Park

Nakajima

Kimitsuki

, et al. Subcutaneous rhabdomyosarcoma in an old rabbit. J Vet Med Sci. 2016;78(9):1525–1528.

75.

Petterino

Modesto

Strata

, et al. A case of interscapular fibrosarcoma in a dwarf rabbit (Oryctolagus cuniculus). J Vet Diagn Invest. 2009;21(6):900–905.

76.

Pilny

Reavill

. Chylothorax and thymic lymphoma in a pet rabbit (Oryctolagus cuniculus). J Exot Pet Med. 2008;17(4):295–299.

77.

Pizzi

Hagen

Meredith

. Intermittent colic and intussusception due to a cecal polyp in a rabbit. J Exot Pet Med. 2007;16(2):113–117.

78.

Renfrew

Rest

Holden

. Extraskeletal fibroblastic osteosarcoma in a rabbit (Oryctolagus cuniculus). J Small Anim Pract. 2001;42(9):456–458.

79.

Ritter

von Bomhard

Wise

, et al. Cutaneous lymphomas in European pet rabbits (Oryctolagus cuniculus). Vet Pathol. 2012;49(5):846–851.

80.

Rose

Vergneau-Grosset

Steffey

, et al. Adrenalectomy and nephrectomy in a rabbit (Oryctolagus cuniculus) with adrenocortical carcinoma and renal and ureteral transitional cell carcinoma. J Exot Pet Med. 2016;25(4):332–341.

81.

Rous

Beard

. The progression to carcinoma of virus-induced rabbit papillomas (Shope). J Exp Med. 1935;62(4):523–548.

82.

Salm

Field

. Osteosarcoma in a rabbit. J Pathol Bacteriol. 1965;89(1):400–402.

83.

Schmorl

. Carcinome des poumons chez le lapine (carcinoma simplex). Tumeur primitive de l’estomac. Verh Dtsch Ges Pathol. 1903;6:136.

84.

Schöniger

Horn

Schoon

. Tumors and tumor-like lesions in the mammary gland of 24 pet rabbits: a histomorphological and immunohistochemical characterization. Vet Pathol. 2014;51(3):569–580.

85.

Schwarz

Morandi

Gnudi

, et al. Nodular fat necrosis in the feline and canine abdomen. Vet Radiol Ultrasound. 2000;41(4):335–339.

86.

Selbie

Robinson

RHM

. Incidence of carcinoma in transmissible papillomatosis of the domestic rabbit. Br J Cancer. 1948;2(1):48–59.

87.

Shope

. A transmissible tumor-like condition in rabbits. J Exp Med. 1932;56(6):793–802.

88.

Sikoski

Trybus

Cline

, et al. Cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a New Zealand white rabbit (Oryctolagus cuniculus). Comp Med. 2008;58(3):297–300.

89.

Silva

Oliveira

Horta

, et al. Mammary gland malignant myoepithelioma in a domestic rabbit (Oryctolagus cuniculus). Acta Sci Vet. 2019;47(suppl 1):388.

90.

Stern

Guzman

DSMLV

Gleeson

, et al. Cervical spinal nerve and brachial plexus schwannoma in a rabbit (Oryctolagus cuniculus). J Exot Pet Med. 2019;31:75–78.

91.

Strayer

Skaletsky

Cabirac

, et al. Malignant rabbit fibroma virus causes secondary immunosuppression in rabbits. J Immunol. 1983;130(1):399–404.

92.

Tinkey

Uthamantil

Weisbroth

. Rabbit neoplasia. In: Suckow

Stevens

Wilson

, eds. The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents. Academic Press; 2012:447–501.

93.

Ueda

Kiyukazu

. Cutaneous malignant melanoma in two rabbits (Oryctolagus cuniculus). J Vet Med Sci. 2018;80(6):973–976.

94.

Van Praag

. Skin Diseases of Rabbits. MediRabbit; 2010.

95.

Varga

. Textbook of Rabbit Medicine. Elsevier; 2014.

96.

Veterinary Society of Surgical Oncology. Uterine tumors canine. Accessed October 1, 2020. https://vsso.org/uterine-tumors-canine

97.

Veterinary Society of Surgical Oncology. Testicular seminoma. Accessed March 23, 2021. https://vsso.org/testicular-seminoma

98.

Viste

Myers

Singh

, et al. Feline mammary adenocarcinoma: tumor size as a prognostic indicator. Can Vet J. 2002;43(1):33–37.

99.

Von Bomhard

Goldschmidt

Shofer

, et al. Cutaneous neoplasms in pet rabbits: a retrospective study. Vet Pathol. 2007;44(5):579–588.

100.

Von Bomhard

Mauldin

Pfleghaar

. Disseminated collagenous hamartomas in rabbits—a new entity. Kleintierpraxis. 2008;53(4):224–230.

101.

Wagner

Beineke

Fehr

, et al. Recurrent bilateral exophthalmos associated with metastatic thymic carcinoma in a pet rabbit. J Small Anim Pract. 2005;46(8):393–397.

102.

Walberg

. Osteogenic sarcoma with metastasis in a rabbit (Oryctolagus cuniculus). Lab Anim Sci. 1981;31(4):407–408.

103.

Walter

Poth

Böhmer

, et al. Uterine disorders in 59 rabbits. Vet Rec. 2010;166(8):230–233.

104.

Walter

Göbel

Schauer

. Ameloblastisches Fibrom bei einem juvenilen Kaninchen. Kleintierpraxis. 1992;37(9):633–638.

105.

Webb

Reavill

Garner

, et al. Characterization of testicular granular cell tumors in domestic rabbits (Oryctolagus cuniculus). J Exot Pet Med. 2019;29:159–165.

106.

Weisbroth

. Neoplastic diseases. In: Manning

Ringler

Newcomer

, eds. The Biology of the Laboratory Rabbit. 2 nd ed. Academic Press; 1994:259–292.

107.

Weisbroth

Hurvitz

. Spontaneous osteogenic sarcoma in Oryctolagus cuniculus with elevated serum alkaline phosphatase. Lab Anim Care. 1969;19(2):263–265.

108.

Weiss

ATA

Muller

. Spinal osteolytic osteosarcoma in a pet rabbit. Vet Rec. 2011;168(10):266.

109.

White

Campbell

Logan

, et al. Lymphoma with cutaneous involvement in three domestic rabbits (Oryctolagus cuniculus). Vet Dermatol. 2000;11(1):61–67.

110.

Whitten

Popielarczyk

Belote

, et al. Ossifying fibroma in a miniature rex rabbit (Oryctolagus cuniculus). Vet Pathol. 2006;43(1):62–64.

111.

Wijesundera

Izawa

Fujita

, et al. Spontaneous extraskeletal osteosarcoma in a rabbit (Oryctolagus cuniculus): histopathological and immunohistochemical findings. J Toxicol Pathol. 2013;26(3):309–312.

112.

Wong

Di Girolamo

Kuzma

, et al. Intra-abdominal torsion of a neoplastic testicle in a rabbit (Oryctolagus cuniculus) with cryptorchidism. J Exot Pet Med. 2020;33:38–41.

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Not Just Uterine Adenocarcinoma—Neoplastic and Non-Neoplastic Masses in Domestic Pet Rabbits ( Oryctolagus cuniculus ): A Review

Abstract

Keywords

Skin

Skin: Epithelial Tumors

Skin: Mesenchymal Tumors

Skin: Melanomas

Skin: Tumor-Like Lesions

Hematopoietic System

Musculoskeletal System

Alimentary System

Oral Cavity

Gastrointestinal Tract

Liver and Pancreas

Abdominal Cavity

Respiratory System

Urinary Tract

Female Genital Tract

Male Genital Tract

Mammary Gland

Endocrine System

Nervous System and Sensory Organs

Supplemental Material

Supplemental Material, sj-pdf-1-vet-10.1177_03009858211002190 - Not Just Uterine Adenocarcinoma—Neoplastic and Non-Neoplastic Masses in Domestic Pet Rabbits (Oryctolagus cuniculus): A Review

Footnotes

Acknowledgements

Declaration of Conflicting Interests

Funding

ORCID iD

References

Supplementary Material