Scholarly Articles on Rabbit Health

This is a curated set of references from recent scholarship on rabbit health. For articles on behavior, welfare, and the rabbit human relationship, visit this page.

Editor’s Note: We understand that many of these articles are done in the context of biomedical research laboratories and that the conditions are not sufficient to satisfy the well-being requirements of a group like House Rabbit Society. Although we do  not endorse such studies, we elected to include these studies to ensure that the most recent data on these issues are available to our readers.



Fischer, R. G., & Syverton, J. T. (1951). The Virus-induced Papilloma-to-Carcinoma Sequence: IV. Carcinomas in Domestic Rabbits Infected while in Utero. Cancer research, 11(9), 737-740.

(No abstract available)

IIZUKA, T., ICHIMURA, S., KAWACHI, T., HIROTA, T., & ITABASHI, M. (1977). Carcinoma of the esophagus of rabbits induced with N-methyl-benzylamine and sodium nitrite. GANN Japanese Journal of Cancer Research, 68(6), 829-835.

Abstract: Esophageal carcinomas were induced in three of five rabbits given 0.25% N-methylbenzylamine and 0.16% NaNO2 in their drinking water. The three rabbits with carcinoma had consumed more than 94 g of NaNO2 and had survived for more than 536 experimental days. The esophageal carcinomas were a slightly elevated type, and no polypoid lesions were seen. They were classified histologically as squamous cell carcinomas or adenosquamous carcinomas, or both. No metastases were found. The other two of the five rabbits died early in the experiment before any esophageal carcinoma had developed.

Elsinghorst, T. A., Timmermans, H. J. F., & Hendriks, H. C. J. (1984). Comparative pathology of endometrial carcinoma. Veterinary Quarterly, 6(4), 200-208.

Abstract: A review is given of the comparative pathology of endometrial carcinomas regarding the incidence, the morphology, and the relation with endometrial hyperplasia. Compared to man, endometrial carcinomas in animals are fairly rare, except in rabbits, in cattle, and in a stock of Han: Wistar rats. In rabbits the endometrial carcinomas are mostly primary multiple and present in both horns. Histologically they are almost always adenocarcinomas. The histological structure can vary considerably with regard to the degree of differentiation. In cattle the endometrial carcinomas are mostly singular. Histologically they are mostly adenocarcinomas, often accompanied by formation of much dense fibrous tissue. In rats the endometrial carcinomas are mostly primary multiple adenocarcinomas. In man as well as in the rabbit and in the rat, relationships have been described between endometrial hyperplasia and endometrial carcinoma. It is striking that in the dog, a species in which endometrial hyperplasia very often occurs, endometrial carcinomas should be rare. The endometrial carcinoma in the rabbit as an animal model for human endometrial carcinoma is discussed extensively. In both species there are signs indicating relationships between endometrial carcinomas and sex hormones, especially oestrogens. The incidence in rabbits is very high. Endometrial carcinomas in rabbits can be transplanted subcutaneously in the same rabbit. They can also be cultured in vitro. Moreover the rabbit is a suitable species to study the progesterone/progesterone-receptor complex by determining the synthesis of the progesterone-induced protein uteroglobin which may be important in studying endometrial carcinomas. Uteroglobin is a good marker for a functional ‘Progesterone-PR-DNA-mRNAug-Uteroglobin- System’ (or PUG-System).

Gillett, C. S., & Gunther, R. (1990). Mandibular mucoepidermoid carcinoma in a rabbit. Laboratory animal science, 40(4), 422-423.

(No abstract available)

Breitburd, F., Salmon, J., & Orth, G. (1997). The rabbit viral skin papillomas and carcinomas: a model for the immunogenetics of HPV-associated carcinogenesis. Clinics in dermatology, 15(2), 237-247.

(No abstract available)

Veeramachaneni, D. N., & Vandewoude, S. (1999). Interstitial cell tumour and germ cell tumour with carcinoma in situ in rabbit testes. International journal of andrology, 22(2), 97-101.

Abstract: Simultaneous occurrence of a well-demarcated interstitial cell tumour and an intratubular seminoma-like tumour, which was beginning to invade peritubular areas, in the contralateral testes of a 3-year-old Dutch-Belted rabbit is described. Morphological hallmarks of carcinoma in situ, which have not been reported previously for the rabbit, were observed in association with the seminoma. These observations indicate that carcinoma in situ, preceding a seminoma-like tumour, occurs in the rabbit and that the rabbit may serve as a practically useful animal model for studying testicular germ cell neoplasia.

Yilmaz, M., Kemaloğlu, Y. K., İnal, E., Kul, O., Yarim, M., Haziroğlu, R., & Ataoğlu, O. (2003). The beneficial effect of selenium against induction of squamous cell carcinoma of the tongue in rabbits. Kulak burun bogaz ihtisas dergisi: KBB= Journal of ear, nose, and throat, 11(4), 100-107.
[Article in Turkish]

Abstract: In a rabbit model of squamous cell carcinoma of the tongue, we monitored histopathologic changes and assessed the effect of selenium against carcinogenesis.
The study included 36 male albino New Zealand rabbits. To induce squamous cell carcinoma of the tongue, 9,10-dimethyl-1,2-benzanthracene (DMBA)-acetone solution was applied three times a week for a duration of 20 weeks under anesthesia with xylazine hydrochloride and ketamine. The rabbits were randomly assigned to receive either pure tap water (24 rabbits) or tap water supplemented with 4 ppm sodium selenite (12 rabbits). One rabbit in each group was sacrificed at the end of 4, 8, 12 and 16 weeks, and the remaining rabbits at the end of 20 weeks for macroscopic and microscopic examination of the tongue. By week 20, two rabbits in the selenium group, and nine rabbits receiving tap water died from acute necrotizing bronchopneumonia due to pasteurellosis. Dysplasia was significantly less in selenium-receiving rabbits (16.7% vs 66.7%, p < 0.0001), and its development manifested a delayed onset. Carcinoma in situ was detected in 25% of tap water-receiving rabbits that remained alive by week 19 to 20, while none of the rabbits had carcinoma in situ in the selenium group. Our data demonstrate that selenium has an inhibitory and preventive effect against chemically-induced rabbit tongue carcinogenesis.

Saad-Hossne, R., Prado, R. G., & Hossne, W. S. (2007). Effects of acetylsalicylic acid and acetic acid solutions on VX2 liver carcinoma in rabbits: in vivo analysis. Acta cirurgica brasileira, 22(4), 299-308.

Abstract: To analyze, in vitro, the effects of acetylsalicylic acid (aspirin) and acetic acid solutions on VX2 carcinoma cells in the liver of rabbits with VX2 hepatic tumors; to determine the histolytic and anatomopathological characteristics of the solutions; and to evaluate the eventual biochemical and hepatic changes. A total of 48 rabbits were evaluated. The animals were randomized into two groups, protocol 3 (study group) and protocol 4 (controls), and each group was then subdivided into 3 subgroups. Four days after implantation of the tumor in the liver, median laparotomy was performed with a 0.4-ml injection of a solution of either aspirin (5.0%), acetic acid (5.0%) or saline. The animals were sacrificed after 24 hours (protocol 3) or after 11 days (protocol 4). Body weight, clinical evolution and biochemical levels, as well as the abdominal and thoracic cavities, were evaluated, and liver microscopy was performed. No changes in clinical evolution, body weight or biochemical levels were reported. However, an increase in alkaline phosphatase was observed in protocol 4 (controls). The tumor was eliminated in both protocols. Acetylsalicylic acid and acetic acid solutions cause the destruction of experimental hepatic tumors.

KUROTAKI, T., Kokoshima, H., KITAMORI, F., Kitamori, T., & Tsuchitani, M. (2007). A case of adenocarcinoma of the endometrium extending into the leiomyoma of the uterus in a rabbit. Journal of Veterinary Medical Science, 69(9), 981-984.

Abstract: In a pet rabbit, 2 tumor masses one on each horn were macroscopically seen in the wall of the uterus. On light microscopic examination, the right horn mass consisted of an admixture of neoplastic epithelial and mesenchymal element. The epithelial element was composed of neoplastic epithelial cells with numerous mitotic figures and formed varied sizes of acini, glandular, and solid structures. The tumor was diagnosed as an adenocarcinoma of the endometrium. The mesenchymal element was composed of well-differentiated smooth muscle cells and was diagnosed as a leiomyoma. While adenocarcinoma cells formed a protrusive mass in the uterine lumen, they also showed an extension into the leiomyoma of the myometrium. By immunohistochemistry, adenocarcinoma stained positive for cytokeratin (MNF116) and leiomyoma stained positive for smooth muscle actin, showing a substantial difference in the cytological nature of these tumor cells. The results may give a further evidence supporting the narrative of the tumor development that an adenocarcinoma of the endometrium extended into leiomyoma of the uterus. To the author’s knowledge, this is the first report describing this type of combination of two independent tumors in a pet rabbit.

Schulz, S., Häussler, U., Mandic, R., Heverhagen, J. T., Neubauer, A., Dünne, A. A., … & Bette, M. (2008). Treatment with ozone/oxygen‐pneumoperitoneum results in complete remission of rabbit squamous cell carcinomas. International journal of cancer, 122(10), 2360-2367.

Abstract: Head and neck squamous cell carcinomas (HNSCC) represent a group of metastasizing tumors with a high mortality rate in man and animals. Since the biomolecule ozone was found to inhibit growth of various carcinoma cells in vitro we here applied the highly aggressive and lethal VX2 carcinoma HNSCC tumor model of the New Zealand White rabbit to test whether ozone exerts antitumorous effects in vivo. Therapeutic insufflation of medical ozone/oxygen (O(3)/O(2)) gas mixture into the peritoneum (O(3)/O(2)-pneumoperitoneum) at an advanced stage of tumor disease led to a survival rate of 7/14 rabbits. Six of the seven surviving rabbits presented full tumor regression and the absence of local or distant lung metastases. Insufflation of pure oxygen (O(2)) resulted in a survival rate of 3/13 animals accompanied by full tumor remission in 2 of the 3 surviving animals. Of the 14 sham-treated animals only 1 had spontaneous tumor remission and survived. No adverse effects or changes in standard blood parameters were observed after repeated intraperitoneal insufflations of the O(3)/O(2) or O(2) gas. Animals with O(3)/O(2)-induced tumor eradication developed tolerance against reimplantation of the VX2 tumor. This could be reversed by immune suppression with a combination of dexamethasone and cyclosporin A suggesting an antitumorous effect of O(3)/O(2)-mediated activation of the body’s own immunosurveillance. Although the exact mechanisms of action are still unclear the present data point to O(3)/O(2)-pneumoperitoneum as a promising new strategy in anticancer therapy.

Wulong, J., Zhou, L., Xiaojian, Z., Jie, T., & Huilin, G. (2008). Establishment of a highly metastatic tongue squamous cell carcinoma cell line from New Zealand White rabbit. Archives of oral biology, 53(11), 1084-1090.

Abstract: Prior to this study, the widely used tongue squamous cell carcinoma cell lines could only initiate tumours in immunodeficient mice, which greatly delayed studies on immune function during carcinogenesis. This study established a new tongue squamous cell carcinoma cell line named ‘RSCC-1’, which can initiate tumours in both immunocompetent rabbits and immunodeficient nude mice and has high metastatic ability. Primary tongue cancer was induced by DMBA and local mechanical stimulation in New Zealand White rabbits. The induced cancer was serially transplanted into homogeneous rabbits to establish transplanted models. At the same time, cancer samples were collected, cultured and passaged in vitro. Finally, a cell line named ‘RSCC-1’ was established. Its growth behaviour, cell cycle distribution and tumourigenicity in rabbits and nude mice were investigated. RSCC-1 cells were cultured continuously in vitro for 19 months (165 passages). They contain between 54 and 196 chromosomes, with a modal number of 75. Tumourigenicity rates were 100% in both homogeneous rabbits and nude mice, with 20% lung metastasis and 50% cervical lymph node metastasis in homogeneous rabbits. RSCC-1 is a poorly differentiated, highly malignant rabbit tongue squamous cell carcinoma cell line. Its behaviour in the inoculated animal model closely resembles human tongue cancer, and could metastasize to local lymph nodes and remote organs.

Tang, L., Mei, L. J., Yang, X. J., Huang, C. Q., Zhou, Y. F., Yonemura, Y., & Li, Y. (2011). Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of gastric cancer with peritoneal carcinomatosis: evidence from an experimental study. Journal of translational medicine, 9(1), 53.

Abstract: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC). However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model. VX2 tumor cells were injected into the gastric submucosa of 42 male New Zealand rabbits using a laparotomic implantation technique, to construct rabbit model of gastric cancer with PC. The rabbits were randomized into control group (n = 14), CRS alone group (n = 14) and CRS + HIPEC group (n = 14). The control group was observed for natural course of disease progression. Treatments were started on day 9 after tumor cells inoculation, including maximal removal of tumor nodules in CRS alone group, and maximal CRS plus heperthermic intraperitoneal chemoperfusion with docetaxel (10 mg/rabbit) and carboplatin (40 mg/rabbit) at 42.0 ± 0.5°C for 30 min in CRS + HIPEC group. The primary endpoint was overall survival (OS). The secondary endpoints were body weight, biochemistry, major organ functions and serious adverse events (SAE). Rabbit model of gastric cancer with PC was successfully established in all animals. The clinicopathological features of the model were similar to human gastric PC. The median OS was 24.0 d (95% confidence interval 21.8 – 26.2 d ) in the control group, 25.0 d (95% CI 21.3 – 28.7 d ) in CRS group, and 40.0 d (95% CI 34.6 – 45.4 d ) in CRS + HIPEC group (P = 0.00, log rank test). Compared with CRS only or control group, CRS + HIPEC could extend the OS by at least 15 d (60%). At the baseline, on the day of surgery and on day 8 after surgery, the peripheral blood cells counts, liver and kidney functions, and biochemistry parameters were all comparable. SAE occurred in 0 animal in control group, 2 animals in CRS alone group including 1 animal death due to anesthesia overdose and another death due to postoperative hemorrhage, and 3 animals in CRS + HIPEC group including 1 animal death due to anesthesia overdose, and 2 animal deaths due to diarrhea 23 and 27 d after operation. In this rabbit model of gastric cancer with PC, CRS alone could not bring benefit while CRS + HIPEC with docetaxel and carboplatin could significantly prolong the survival with acceptable safety.

Jin, W., Gergen, T., & Yu, H. (2014). Establishment of an Orthotopic Transplantation Model of Tongue Carcinoma. Journal of Craniofacial Surgery, 25(3), 950-953.

Abstract: This study aims to establish an orthotopic transplantation model of rabbit tongue carcinoma and study its biological characteristics. Tongue carcinoma was induced in purebred New Zealand white rabbits by exposure to 7,12-dimethylbenz[a]anthracene and mechanical stimulation. Fresh tumor tissues obtained from the induced tongue carcinoma model were then serially transplanted orthotopically into tongues of healthy rabbits. The tumor formation rate, invasion to surrounding tissues, regional lymph node metastases, and distant-organ metastases were investigated. Morphological observation by optical and electron microscopy, immunohistochemical examination, and chromosome analysis were performed. An orthotopic transplantation model of rabbit tongue carcinoma, designated as RSCC-2, was established. The tongue cancer was poorly differentiated squamous cell carcinoma. The tumor cell was hypotetraploid with a chromosome mode of 70. Immunohisto chemical examination showed positive staining for keratin. The tongue carcinoma survived in rabbits for 73 rounds of transplantation, using 465 rabbits in total. The average latent period was 12.5 days, and the average rabbit survival period was 37.5 days. The tumor formation rate was 10% to 20% in the first 20 rounds and increased gradually thereafter. After the 45th transplantation, the tumor formation rate and success rate of preservation in liquid nitrogen reached 100%. Regional lymph node metastases (35%) and lung metastases (20%) occurred after 50 rounds. In the advanced stage, tumors invaded the entire tongue. Animals suffered from weight loss and died of cachexia. RSCC-2 is the first animal model for orthotopical transplantation of primary tongue carcinoma. It successfully simulates the clinical pathological process of primary tongue cancer in human, provides invaluable insights into the pathogenesis and metastasis mechanisms, and can be useful for evaluating new therapeutics for the treatment of tongue cancer.

Rossmann, A., Mandic, R., Heinis, J., Höffken, H., Küssner, O., Kinscherf, R., … & Bette, M. (2014). Intraperitoneal oxidative stress in rabbits with papillomavirus-associated head and neck cancer induces tumoricidal immune response that is adoptively transferable. Clinical Cancer Research, clincanres-0677.

Abstract: How tumors evade or suppress immune surveillance is a key question in cancer research, and overcoming immune escape is a major goal for lengthening remission after cancer treatment. Here, we used the papillomavirus-associated rabbit auricular VX2 carcinoma, a model for studying human head and neck cancer, to reveal the mechanisms underlying the antitumorigenic effects of intraperitoneal oxidative stress following O3/O2-pneumoperitoneum (O3/O2-PP) treatment. Solid auricular VX2 tumors were induced in immune-competent adult New Zealand White Rabbits. Animals were O3/O2-PP- or sham-treated, after which they underwent tumor ablation upon reaching no-go criteria. CD3(+) tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry, and expression levels of 84 immune response genes were measured by quantitative real-time PCR. Adoptive transfer of peripheral blood leukocytes (PBL)-derived from animals with tumor regression-into control animals with progressing tumors was implemented to assess acquired tumor resistance functionally. Auricular VX2 tumors regressing after O3/O2-PP treatment exhibited increased levels of CD3(+) TILs; they also exhibited enhanced expression of genes that encode receptors involved in pattern recognition, molecules that are required for antigen presentation and T cell activation, and inflammatory mediators. Adoptive cell transfer of PBLs from donor rabbits with regressing tumors to recipient rabbits with newly implanted VX2 carcinoma resulted in acquired tumor resistance of the host and tumor regression. Intraperitoneal oxidative stress effectively converts the immune response against the papillomavirus-associated rabbit VX2 carcinoma from tumor permissive to tumoricidal and leads to a sustainable, adoptively transferable oncolytic immune response.

Nakata, M., Miwa, Y., Tsuboi, M., & Uchida, K. (2014). Surgical and localized radiation therapy for an intranasal adenocarcinoma in a rabbit. Journal of Veterinary Medical Science, 76(12), 1659-1662.

Abstract: An 8-year-old spayed female Netherland Dwarf rabbit presented with a two-month history of dyspnea and snoring. A computed tomography (CT) scan of the head revealed mass lesions in the right nasal cavity. Surgical exenteration of the lesions was performed, and the histopathological diagnosis was an intranasal adenocarcinoma. On the basis of this diagnosis, radiotherapy was planned and consisted of eight fractions of 6 Gy administered once a week. After the completion of radiation therapy, the soft tissue density in the right nasal cavity, as detected by CT, significantly decreased. The prognosis has remained good for over 3 years after treatment. This paper is the first to describe the clinical and pathological features of an intranasal tumor in a rabbit.

Baum, B., & Hewicker-Trautwein, M. (2015). Classification and epidemiology of mammary tumours in pet rabbits (Oryctolagus cuniculus). Journal of comparative pathology, 152(4), 291-298.

Abstract: Mammary tumours are common in pet rabbits; however, published studies are predominantly derived from laboratory and meat rabbits. This study reports basic data on type and location of 119 separate tumours from 109 pet rabbits. The animals were aged 2-14 years (mean 5.5 years) and all 90 rabbits of known gender were female. Cranial and caudal mammary glands were affected equally. The majority of lesions (n = 105) were classified as carcinomas with 32 tubular, 16 papillary, 12 tubulopapillary, 11 solid, nine adenosquamous, nine comedo type, five complex, four ductal, three cribriform, three anaplastic and one spindle -cell carcinoma. Twelve percent of the lesions were benign, with eight intraductal papillary adenomas, three simple tubular adenomas and one complex adenoma. One non-neoplastic lesion was found in the form of cystic duct ectasia.

Ambery AG, Cary C, Hickman DL, Blickman A, Roberts CS. (2015). Pathology in Practice. Mammary tubulopapillary adenocarcinoma in a rabbit. Journal of American Veterinary Medical Association, 247(3):251-3.

(No abstract available)

Pascale, F., Fazel, A., Namur, J., Ghegediban, S. H., D’Inca, H., Wassef, M., … & Laurent, A. (2017). Laparoscopic subperitoneal injection of chemo-loaded particles lowers tumor growth on a rabbit model of peritoneal carcinomatosis. Tumor Biology, 39(5), 1010428317698381.

Abstract: The purpose of our study was to assess the effect of controlled-release chemotherapy on the growth and viability of peritoneal carcinomatosis treated by subperitoneal injection in a rabbit VX2 model. A model of peritoneal carcinomatosis was created by laparoscopic injection of VX2 tumor in the left and right broad ligaments of 12 White New Zealand rabbits. At day 12, each tumor was randomly treated with a peritumoral injection of 0.5?mL microspheres loaded with doxorubicin (DEM-DOX) or unloaded (DEM-BLAND). Seven days after treatment, tumor volume, tumor viability in histology, local tumor necrosis in contact with DEM, and doxorubicin concentration profile around the drug eluting microspheres (DEM) were measured. Tumor volume was significantly lower in the DEM-DOX group (3.6?±?3.2?cm3) compared with the DEM-BLAND group (8.9?±?5.4?cm3) (p?=?0.0425). The percentage of viable tumor tissue was significantly lower in the DEM-DOX group (38%?±?17%) compared with the DEM-BLAND group (56%?±?20%) (p?=?0.0202). Tissue necrosis was observed around all DEM-DOX up to a distance of 1.094?±?0.852?mm and never observed around DEM-BLAND. Drug concentration was above the therapeutic level of 1.0?µM up to a distance of 1.4?mm from the DEM to the tumor. Laparoscopic subperitoneal injection of chemo-loaded particles is feasible and lowers tumor growth and viability in a rabbit model of peritoneal carcinomatosis after 1?week.

Yang, Y., Ma, W. W., Zhou, M. W., Chen, Z. Y., Xiang, J. B., Li, Z. Y., … & Gu, X. D. (2018). Application of cryoablation to treat peritoneal carcinomatosis from gastric cancer in a rabbit model. Cryobiology, 85, 12-16.

Abstract: Peritoneal carcinomatosis is one of the causes of death in patients with advanced gastric cancer. We assumed that cryoablation could be applied as adjuvant therapy to control peritoneal carcinomatosis from gastric cancer. We investigated the feasibility of cryoablation technique in rabbit model using a novel cryoablation balloon probe. The cryozones were harvested 7 days after cryoablation for histological evaluation. The levels of cytokines in the peripheral blood of rabbits were also detected. The results demonstrated that cryoablation could be applied in a rabbit model of peritoneal carcinomatosis from gastric cancer. Seven days after cryoablation, necrotic tumor cells could be seen the cryozones. Higher level of IFN-? was observed. The level of IL-10 was decreased after treatment. The findings provided the experimental basis for the future application of cryoablation in patients.


Gomez, L., Gazquez, A., Roncero, V., Sanchez, C., & Duran, M. E. (2002). Lymphoma in a rabbit: histopathological and immunohistochemical findings. Journal of small animal practice, 43(5), 224-226.

Abstract: Lymphoma is a very common lymphoid neoplasm in domestic animals, but few naturally occurring cases have been reported in rabbits. It presents at different sites within rabbits and, although the macroscopic pattern tends to be similar, different cell populations may be involved. This report describes a case of spontaneous lymphoma ocurring in a two-and-a-half-year-old pet Dutch dwarf rabbit. T and B lymphocyte infiltrates were observed in skin, lung, kidney, liver, intestine and lymph nodes, in each case affecting one or more tissue structures. The diagnosis, based on microscopic and immunocytochemical findings, was multicentric, T cell-rich B cell lymphoma with skin involvement.

ISHIKAWA, M., Maeda, H., Kondo, H., Shibuya, H., Onuma, M., & Sato, T. (2007). A case of lymphoma developing in the rabbit cecum. Journal of Veterinary Medical Science, 69(11), 1183-1185.

Abstract: A rare lymphoma that developed in the cecum of a domestic pet rabbit (6 years old, male, crossbred) was examined pathologically. The tumor consisted of proliferating neoplastic lymphoid cells, which were strongly stained with anti-CD79alpha monoclonal antibody. Electron microscopy revealed the tumor cells were composed of rough endoplasmic reticula and/or dilated rough endoplasmic reticula filled with moderately electron-dense material. These findings indicated the present case was rare digestive tract lymphoma originated from B-lymphocytic lineage in the cecum.

Reed, S. D., Shaw, S., & Evans, D. E. (2009). Spinal lymphoma and pulmonary filariasis in a pet domestic rabbit (Oryctolagus cuniculus domesticus). Journal of veterinary diagnostic investigation, 21(2), 253-256.

Abstract: Spinal lymphoma and concurrent pulmonary filariasis are reported in a pet rabbit. The rabbit presented for pelvic limb paralysis resulting from extradural spinal lymphoma, presumably rising from the body of the sixth lumbar vertebra. The neoplasm was subsequently immunophenotyped as a B-cell lymphoma. Pulmonary filariasis was an incidental finding at necropsy.

Ritter, J. M., Bomhard, W. V., Wise, A. G., Maes, R. K., & Kiupel, M. (2012). Cutaneous lymphomas in European pet rabbits (Oryctolagus cuniculus). Veterinary pathology, 49(5), 846-851.

Abstract: Cutaneous lymphoma is a common skin neoplasm of pet rabbits in Europe but is rarely reported in pet rabbits in North America. These neoplasms have not been previously characterized, nor has the cause for the apparent predilection for cutaneous lymphoma in European pet rabbits compared with North American pet rabbits been investigated. In this retrospective study, the authors morphologically and immunohistochemically characterized 25 cutaneous lymphomas in European pet rabbits according to the World Health Organization classification. Tumors were classified as diffuse large B cell lymphomas, with 14 lymphomas exhibiting a centroblastic/centrocytic subtype and 11 tumors exhibiting a T cell-rich B cell subtype. To investigate a potential viral etiology of these lymphomas, 3 diffuse large B cell and 3 T cell-rich B cell lymphomas were evaluated by polymerase chain reaction for retroviral and herpesviral genes. Neither virus was detected. In contrast to other domestic animals, cutaneous lymphomas in European pet rabbits were highly pleomorphic and frequently contained multinucleated giant cells. Unexpectedly, the second most common subtype was T cell-rich B cell lymphoma, a subtype that is rare in species other than horses. Based on a limited number of samples, there was no support for a viral etiology that would explain the higher incidence of lymphoma in European pet rabbits compared with American pet rabbits. Further investigation into genetic and extrinsic factors associated with the development of these tumors is warranted.

SHIBUYA, K., TAJIMA, M., KANAI, K., IHARA, M., & NUNOYA, T. (1999). Spontaneous lymphoma in a Japanese White rabbit. Journal of Veterinary Medical Science, 61(12), 1327-1329.

Abstract: Lymphoma was observed in a 4-month-old female Japanese White rabbit. Grossly, the markedly enlarged mesenteric lymph nodes, prominent Peyer’s patches of jejunum, splenomegaly, and enlargement of tracheobronchial lymph nodes, adrenal glands and ovaries were observed. Histologically, neoplastic lymphoid cells proliferated diffusely showing frequent mitotic figures and a characteristic ‘starry sky’ appearance. Their basophilic cytoplasm contained a few lipid droplets. The mesenteric lymph nodes, Peyer’s patches of jejunum, and tracheobronchial lymph nodes were largely replaced by the tumor tissues. The stomach, small intestines, especially the jejunum, liver, spleen, ovaries, and adrenal glands were heavily infiltrated with neoplastic cells. These results suggest that the present lymphoma may have originated from the gastrointestinal lymphoid tissue.

Volopich, S., Gruber, A., Hassan, J., Hittmair, K. M., Schwendenwein, I., & Nell, B. (2005). Malignant B‐cell lymphoma of the Harder’s gland in a rabbit. Veterinary ophthalmology, 8(4), 259-263.

Abstract: A 22-month-old, female rabbit was presented with a 1-day history of acute unilateral exophthalmos. Ultrasonography and computed tomography (CT) of the orbit revealed an orbital mass. Retrobulbar lymphoma was diagnosed following fine-needle aspiration biopsy (FNAB). Thoracic radiographs were normal, and ultrasonography of the abdomen showed focal hypoechoic thickening of the bowel wall and hypoechoic enlarged lymph nodes. The rabbit was euthanized and histopathology identified the retrobulbar mass as B-cell malignant lymphoma of the Harder’s gland. Mesenteric lymph nodes, caecum, and both kidneys were also affected. This is the first documented case of malignant lymphoma of the Harder’s gland in a rabbit.

White, S. D., Campbell, T., Logan, A., Meredith, A., Schultheiss, P., Van Winkle, T., … & Mallon, F. (2000). Lymphoma with cutaneous involvement in three domestic rabbits (Oryctolagus cuniculus). Veterinary Dermatology, 11(1), 61-67.

Abstract: Three domestic rabbits (Oryctolagus cuniculus) with cutaneous lymphoma are described. Two rabbits were young (7 weeks and 1 years) and were euthanized within 1 week of showing clinical signs. Lymphoma was found in the skin and internal organs. The third rabbit was 9.5 years of age, and lived for more than 1 year after diagnosis. No response was seen to either 2 months of alpha-interferon administration or a 2.5-week course of isotretinoin treatment. After 1 year the rabbit died suddenly; the owner refused necropsy. Immunologic stains of the tumour in all three rabbits showed T cells to be the lymphoma cell type.


Mancinelli, E., Keeble, E., Richardson, J., & Hedley, J. (2014). Husbandry risk factors associated with hock pododermatitis in UK pet rabbits (Oryctolagus cuniculus). Veterinary Record, 174, 429.

Abstract: Pododermatitis, often called ‘sore hocks’, is a chronic, granulomatous, ulcerative dermatitis which most commonly affects the plantar aspect of the caudal metatarsal and tarsal areas. Pododermatitis is a common clinical finding in the pet rabbit population, but no data is available regarding the actual prevalence of this condition in the UK pet rabbit population or possible husbandry-related factors which may predispose pet rabbits to development of this condition. It was the aim of this study to determine the prevalence of pododermatitis within a sample pet rabbit population, and study possible correlations with husbandry, sex, breed and origin of the rabbits. Findings suggested that young rabbits are at a lower risk of pododermatitis compared with older rabbits; female domestic rabbits are more predisposed to pododermatitis than males; and 100 per cent of the neutered females examined showed clinical evidence of pododermatitis. The effect that different types of bedding may have on the prevalence of pododermatitis was also investigated. This study also produced a scoring system which can be used to score clinical cases. Our study is of clinical importance because it helps to recognise many of the factors which predispose pet rabbits to pododermatitis, representing the first step towards increased awareness of this extremely common problem.


Von Bomhard, W., Goldschmidt, M. H., Shofer, F. S., Perl, L., Rosenthal, K. L., & Mauldin, E. A. (2007). Cutaneous neoplasms in pet rabbits: a retrospective study. Veterinary pathology, 44(5), 579-588.
Abstract: Over a 16-year period, 190 tumors and tumorlike lesions from 179 pet rabbits were submitted for histopathologic examination. A total of 23 different tumor types and 1 tumorlike lesion were diagnosed. The most common diagnoses were trichoblastoma, collagenous hamartoma, and Shope fibroma. Viral-induced tumors were Shope fibroma (19) and Shope papilloma (2). Common nonviral epithelial tumors included trichoblastoma (59), squamous cell carcinoma (5), squamous papilloma (4), trichoepithelioma (3), and apocrine carcinoma (3). Common mesenchymal tumors were lipoma (10), liposarcoma (3), myxosarcoma (9), malignant peripheral nerve sheath tumor (8), fibrosarcoma (7), and leiomyosarcoma (4). Malignant melanoma was diagnosed in 8 rabbits. Collagenous hamartomas were diagnosed in 26 rabbits. Mesenchymal proliferations occurred significantly more often in male rabbits than in females. Collagenous hamartomas and myxosarcomas occurred exclusively in male animals, and 3 rabbits had multiple collagenous hamartomas. Immunohistochemistry was applied in cases in which a definite diagnosis could not be reached on hematoxylin and eosin slides. Follow-up information was received in 19 cases. Carcinomas recurred (2 of 3) or metastasized (1 of 3), whereas sarcomas frequently recurred (7 of 12). One malignant melanoma (1 of 3) and one poorly differentiated round cell neoplasm recurred (1 of 1). This is the first comprehensive retrospective analysis on skin neoplasia in pet rabbits.

Schöniger, S., Horn, L. C., & Schoon, H. A. (2014). Tumors and tumor-like lesions in the mammary gland of 24 pet rabbits: a histomorphological and immunohistochemical characterization. Veterinary pathology, 51(3), 569-580.
Abstract: The aim of this retrospective study (2004-2011) was to examine mammary tumors and tumor-like lesions in 24 pet rabbits by histopathology and immunohistochemistry. Rabbits were aged 2 to 8 years. Seventeen were female and 7 female-spayed. Diagnosed tumor-like lesions were lobular hyperplasia (2 rabbits) and multiple cysts (10 rabbits). Tumors included cystadenoma (7 tumors; 3 rabbits), intraductal papilloma (2 tumors; 1 rabbit), intraductal papillary carcinoma (1 tumor), adenocarcinoma (14 tumors; 13 rabbits), adenosquamous carcinoma (2 tumors; 2 rabbits), and matrix-producing carcinoma (1 tumor). The most frequently diagnosed lesion was invasive carcinoma (n = 17). Ten rabbits had several lesions. Immunohistochemistry for calponin and p63 showed that the diagnosed tumor-like lesions, benign tumors, and noninvasive carcinoma had a peripheral myoepithelial layer that was lacking in the invasive carcinomas. In 13 of 14 (93%) of the invasive carcinomas, however, there were variable numbers of calponin- and/or p63-immunopositive cells ranging from 0.1% to 40% with morphological features of either retained nonneoplastic myoepithelial cells or neoplastic epithelial cells with a myoepithelial differentiation. Tumor recurrence was reported in the rabbit with the matrix-producing carcinoma and in 3 rabbits with mammary adenocarcinomas displaying =20 mitotic figures in 10 high-power fields and high numbers of neoplastic cells with a myoepithelial differentiation (19%-39%). The rabbit with the matrix-producing mammary carcinoma developed cutaneous metastases confirmed by histopathology. This study shows that different types of mammary tumor-like lesions and tumors can occur in pet rabbits.

Budgeon, C., Mans, C., Chamberlin, T., Stein, J., Drees, R., Robat, C., … & McAnulty, J. (2014). Diagnosis and surgical treatment of a malignant trichoepithelioma of the ear canal in a pet rabbit (Oryctolagus cuniculus). Journal of the American Veterinary Medical Association, 245(2), 227-231.
Abstract: A 10-year-old spayed female Holland Lop-mix pet rabbit (Oryctolagus cuniculus) was evaluated because of purulent-hemorrhagic discharge from the right ear canal and a suspected mass within that ear canal. Results of contrast-enhanced CT, video otoscopy, and histologic examination of endoscopic tissue biopsy samples indicated severe otitis media and externa and a benign trichoepithelioma of the right ear canal. Total ear canal ablation and lateral bulla osteotomy were performed. Histologic examination of a surgical biopsy sample of the mass indicated malignant trichoepithelioma. Tumor recurrence was detected 22 weeks after surgery. The rabbit was euthanized 33 weeks after surgery because of the large size of the recurrent tumor and declining quality of life. Necropsy findings indicated a malignant trichoepithelioma with local and lymphatic invasion into the right mandibular lymph node.
This was the first report of the clinical diagnosis, surgical treatment, and outcome for a domestic rabbit with a diagnosis of a malignant trichoepithelioma of the ear canal and associated otitis media and externa. Neoplasia should be included as a differential diagnosis for pet rabbits with otitis externa and media. Although such tumors are typically benign, trichoepitheliomas in rabbits can be malignant. Computed tomography and histologic examination of tissue samples were useful diagnostic techniques, but histologic examination of an endoscopic biopsy sample did not allow identification of malignant characteristics of the trichoepithelioma.

Golbar, H. M., Izawa, T., Kuwamura, M., Fujita, D., Sasai, H., & Yamate, J. (2014). A collision tumour consisting of malignant trichoblastoma and melanosarcoma in a rabbit. Journal of comparative pathology, 151(1), 63-66.
Abstract: A 7-year-old mixed breed neutered female rabbit (Orytolagus cuniculus) developed a solitary black nodular mass (1 cm in diameter) in the skin of the right flank. Microscopically, the mass consisted of an admixture of neoplastic trichoblasts and melanocytes. The former were arranged as solid, trabecular, island-like and gland-like structures and the cells had oval nuclei with prominent nucleoli and lightly eosinophilic scant cytoplasm. The latter population exhibited prominent nuclear atypia and high mitotic index in the clusters of a few cells or single cells. Immunohistochemically, the neoplastic trichoblasts expressed cytokeratins and E-cadherin, while the neoplastic melanocytes expressed vimentin, S100 protein, melan-A and melanoma antigen. A diagnosis of collision tumour involving malignant trichoblastoma and melanosarcoma was made.

Park, C. H., Nakajima, C., Kimitsuki, K., Shiwa, N., Tsuchida, Y., & Boonsriroj, H. (2016). Subcutaneous rhabdomyosarcoma in an old rabbit. Journal of Veterinary Medical Science, 78(9), 1525-1528.
Abstract: An 11-year-old castrated male rabbit presented with a subcutaneous mass in the right hind limb. The mass comprised solid and myxoid areas. Solid areas were characterized by a storiform or interlacing pattern of spindle cells, strap cells, multinucleated giant cells and round cells with eccentrically located nuclei, whereas the myxoid areas were composed predominantly of elongated fusiform cells with hyperchromatic nuclei embedded in Alcian Blue-positive myxoid stroma. Immunohistochemically, tumor cells in both areas were positive for desmin and vimentin. Ultrastructurally, the tumor cells in the solid areas had abundant myofilaments with electron dense Z-band structures. Based on these pathological findings, this case was diagnosed as rhabdomyosarcoma in a rabbit.

Karim, M. R., Izawa, T., Pervin, M., Sasai, H., Kuwamura, M., & Yamate, J. (2017). Cutaneous histiocytic sarcoma with regional lymph node metastasis in a Netherland dwarf rabbit (Oryctolagus cuniculus). Journal of comparative pathology, 156(2-3), 169-172.
Abstract: A 10-year-old male Netherland dwarf rabbit (Oryctolagus cuniculus) was presented with a red nodular mass (1 cm in diameter) with ulceration and hair loss in the skin of the left upper lip. Cytological examination revealed atypical round cells. The mass was excised surgically. Histologically, the mass was composed of large round to polyhedral neoplastic cells with marked cytological atypia. The neoplastic cells were often binucleated or multinucleated. Immunohistochemically, the neoplastic cells were intensely positive for Iba1 and vimentin, but fewer neoplastic cells expressed E-cadherin. Nuclear immunoreactivity for Ki67 was detected in approximately 41% of the neoplastic cells. Metastasis to the left cervical lymph nodes was detected 6 months after the surgical excision. Based on clinical, histopathological and immunohistochemical findings, the present case was diagnosed as cutaneous histiocytic sarcoma. To the authors’ knowledge cutaneous histiocytic disease has not been reported previously in lagomorphs.

Kok, M. K., Chambers, J. K., Ushio, N., Watamori, A., Miwa, Y., Nakayama, H., & Uchida, K. (2017). Histopathological and Immunohistochemical Study of Trichoblastoma in the Rabbit. Journal of comparative pathology, 157(2-3), 126-135.
Abstract: Trichoblastoma is the most common skin tumour in the rabbit. The aim of the present study was to characterize the histological and immunohistochemical features of trichoblastoma in 27 rabbits. Common sites of tumour occurrence were the neck (6/30, 20%), head (5/30, 16.7%), flank (4/30, 13.3%) and hindlimb (4/30, 13.3%). Histologically, rabbit trichoblastoma was categorized into ribbon (10/30, 33.3%), trabecular (8/30, 26.7%) and mixed types (12/30, 40%). The tumour tissue showed close interaction with the surrounding stroma where prominent fibroblastic aggregation, known as papillary mesenchymal bodies, was frequently observed (24/30; 80%). Peritumoural stroma of all cases was stained by Alcian blue (at pH 2.5 with weaker staining at pH 1.0). Immunohistochemically, the peripheral palisading basal-type cells of the tumour were positive for cytokeratin (CK) 14 while the inner cells were typically positive for CK17, differing from the immunohistochemical profile of the rabbit epidermis and hair follicle. The present study suggests that uncontrolled embryonic trichogenesis is involved in the development of trichoblastoma in the rabbit.

Ishimori, M., Michishita, M., Yoshimura, H., Azakami, D., Ochiai, K., Ishiwata, T., & Takahashi, K. (2017). Disseminated histiocytic sarcoma with hemophagocytosis in a rabbit. Journal of Veterinary Medical Science, 17-0297.
Abstract: A 7-year-old female domestic rabbit suffered from labored respiration, poor appetite, mild anemia and thrombocytopenia. Radioscopic examination revealed masses in multiple locations including the intrapleural cavity and spleen. Forty-three days after the first visit to a private veterinary clinic, the rabbit died of severe respiratory distress. Microscopically, all of the masses were composed of round to polygonal neoplastic cells with distinct cell borders that were arranged in a sheet pattern. Multinucleated giant neoplastic cells were often observed. Some neoplastic cells had phagocytozed one or more erythrocytes. Immunohistochemical staining revealed that the neoplastic cells expressed vimentin, CD204, Iba-1 and lysozyme, but not CD163. Based on the morphological and immunohistochemical findings, this case was diagnosed as disseminated histiocytic sarcoma with hemophagocytosis.

Di Girolamo, N., Selleri, P., Collarile, T., Del Duca, V., & Binanti, D. (2017). Endoscopic identification of a laryngeal anaplastic sarcoma in a pet rabbit. Journal of Small Animal Practice, 58(11), 664-664.
(No abstract available)

Munasinghe, L., Dougherty, C., Sridharan, S., Philibert, H., & Kidney, B. (2017). What is your diagnosis? A mass on the right tarsus in a rabbit. Veterinary clinical pathology, 46(1), 187-188.
(No abstract available)

E. Cuniculi


This post was last updated March 4, 2019