Hemipelvectomy to treat sarcoma of the proximal portion of the femur in a rabbit

Laura M. Homer From Fitzpatrick Referrals Oncology and Soft Tissue, Guildford GU2 7AJ, England

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Nicholas J. Bacon From Fitzpatrick Referrals Oncology and Soft Tissue, Guildford GU2 7AJ, England

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Abstract

CASE DESCRIPTION

A 7-year-old sexually intact female rabbit was admitted to the hospital because of a 6-month history of chronic right pelvic limb lameness.

CLINICAL FINDINGS

Clinical examination revealed a prominent right pelvic limb lameness and signs of pain on manipulation of the right hip joint, with a focal, well-defined soft tissue mass palpable in the right pelvic area. Pelvic radiography revealed a lytic hip joint lesion and CT detailed an expansile lesion within the proximal portion of the femur with an appearance consistent with a soft tissue mass. Histologic evaluation of incisional biopsy samples of the soft tissue mass revealed a poorly differentiated sarcoma.

TREATMENT AND OUTCOME

A hemipelvectomy was performed, and histologic evaluation of the soft tissue mass confirmed the diagnosis, with tumor-free margins achieved. The patient recovered well from surgery and had good mobility. The patient survived 21 months after surgery and died of a non–cancer-related disease. Anatomic dissection was described in a cadaver rabbit to aid future surgeries.

CLINICAL RELEVANCE

To the authors’ knowledge, this was the first report of a hemipelvectomy performed in a rabbit. Hemipelvectomy is more routinely performed in canine and feline patients, but with the right candidate and owner commitment to aftercare, it may be safely and successfully performed in rabbits.

Abstract

CASE DESCRIPTION

A 7-year-old sexually intact female rabbit was admitted to the hospital because of a 6-month history of chronic right pelvic limb lameness.

CLINICAL FINDINGS

Clinical examination revealed a prominent right pelvic limb lameness and signs of pain on manipulation of the right hip joint, with a focal, well-defined soft tissue mass palpable in the right pelvic area. Pelvic radiography revealed a lytic hip joint lesion and CT detailed an expansile lesion within the proximal portion of the femur with an appearance consistent with a soft tissue mass. Histologic evaluation of incisional biopsy samples of the soft tissue mass revealed a poorly differentiated sarcoma.

TREATMENT AND OUTCOME

A hemipelvectomy was performed, and histologic evaluation of the soft tissue mass confirmed the diagnosis, with tumor-free margins achieved. The patient recovered well from surgery and had good mobility. The patient survived 21 months after surgery and died of a non–cancer-related disease. Anatomic dissection was described in a cadaver rabbit to aid future surgeries.

CLINICAL RELEVANCE

To the authors’ knowledge, this was the first report of a hemipelvectomy performed in a rabbit. Hemipelvectomy is more routinely performed in canine and feline patients, but with the right candidate and owner commitment to aftercare, it may be safely and successfully performed in rabbits.

Introduction

A 7-year-old sexually intact female Chinchilla rabbit was admitted to the hospital for investigation of a chronic right pelvic limb lameness. Previous trauma to the right pelvic limb had occurred from a fall 6 months prior to referral. Radiography performed at the primary care practice at that time revealed no abnormalities, and treatment with meloxicam was initiated. A second opinion for the persistent lameness was obtained at another primary care practice 4 months later. Reduced range of motion in the right hip joint was detected on physical examination, further radiography was offered but was declined by the owner, and treatment for suspected degenerative joint disease was continued. The lameness failed to improve, and radiography performed 2 months later revealed a lytic right hip joint lesion. The rabbit was then referred to our hospital. Retrospective review of radiographs from the original primary care practice at referral revealed early periacetabular lysis.

On physical examination, there was a moderate weight-bearing right pelvic limb lameness (comparable to a grade 3/5 on the canine lameness grading system) and signs of pain on manipulation of the right hip joint, with a focal, well-defined soft tissue mass palpable in the right pelvic area. Differential diagnoses included neoplasia or a periarticular abscess. Fine-needle aspirates taken under general anesthesia revealed prominent, well-differentiated osteoblasts, with moderate anisocytosis and anisokaryosis, but not to a sufficient degree to indicate neoplasia. There were occasional multinucleate osteoclasts, suggestive of bone lysis, with the overall pattern consistent with bone remodeling.

The progressive lameness, soft tissue mass, and muscle loss, however, meant the suspicion for neoplasia remained high; therefore, thoracic and pelvic CT was performed and revealed an expansile lesion within the proximal portion of the femur, with an appearance consistent with a soft tissue mass rather than an abscess. No CT signs of pulmonary metastasis were evident. Soft tissue incisional biopsy samples of the mass were obtained from the proximolateral aspect of the proximal portion of the femur; histologic evaluation revealed that most of the normal tissue architecture was effaced by moderately cellular neoplastic tissue infiltrating into bone and muscle. The neoplastic cells were ovoid to polygonal, with a moderate to prominent degree of anisokaryosis and anisocytosis; 1 mitotic figure/10 hpf was observed. The results were consistent with a poorly differentiated sarcoma, for which the histogenesis was unclear.

A right-sided hemipelvectomy was discussed with the owner as a means to achieve resected margins free of neoplastic disease. Subsequently, the surgery was performed. The intended surgical margins were planned to take the entire right hemipelvis to the midline and the associated overlying soft tissue compartments. This would therefore allow surgical margins of ≥ 10 mm. A modification of the technique described by Bray1 was used. An initial ventral paramedian approach (Figure 1), with a curvilinear incision from the inguinal fold to the ischium, was used. The sartorius, adductor, gracilis, and pectineus muscles and the medial aspect of the tensor fascia latae muscle were transected proximally to expose the pubic symphysis. The femoral artery and vein were individually double ligated just proximal to the femoral triangle with 3-0 polydioxanone. The rectus abdominus muscle and linea alba were transected at their insertions on the cranial aspect of the pubic symphysis, and the iliopsoas muscle was transected close to its insertion on the lesser trochanter of the femur, several centimeters from the palpable tumor. A lateral skin incision was then made joining the ends of the previous medial incision. The superficial gluteal, biceps femoris, lateral aspect of the tensor fascia latae, and coccygeofemoral muscles were transected.

Figure 1
Figure 1

Photographs of a rabbit cadaver that was used to demonstrate the surgical approach for hemipelvectomy performed in a 7-year-old sexually intact female rabbit with a 6-month history of chronic right pelvic limb lameness. A—Through a ventral paramedian approach, the sartorius (A), adductor (B), gracilis (C), pectineus, and medial aspect of the tensor fascia latae (D) muscles are transected proximally to expose the pubic symphysis. B—Laterally, the superficial gluteal (A), biceps femoris (B), lateral aspect of the tensor fascia lata (C), and coccygeofemoral (D) muscles are transected.

Citation: Journal of the American Veterinary Medical Association 258, 2; 10.2460/javma.258.2.192

The pubis was cut paramedian at the cranial and caudal edges of the right obturator foramen, and the sacroiliac joint was disarticulated (Figure 2). The branches of the lumbosacral plexus were transected close to the pelvic limb, and the entire limb compartment was then removed en bloc. The resultant defect in the pelvic diaphragm was repaired by opposing the thoracolumbar fascia with the external abdominal oblique and rectus abdominus muscles with mattress sutures of 3-0 polydioxanone (Figure 3). The subcutaneous tissues were apposed with 3-0 poliglecaprone 25 in a continuous pattern. Tissue adhesive,a rather than permanent skin sutures, was used to seal the skin layer. No intraoperative complications were encountered other than mild hemorrhage, which was controlled with a combination of bipolar vessel sealing and direct pressure. Pelvic radiographs were obtained after surgery to document the osteotomy locations and to provide a baseline for evidence of local recurrence.

Figure 2
Figure 2

Photographs of the rabbit cadaver in Figure 1. Photographs were obtained following transection of the muscles described in Figure 1, ligation of the femoral artery, and transection of the rectus abdominus muscle and linea alba at their insertions on the cranial aspect of the pubic symphysis and the iliopsoas muscle at its insertion on the lesser trochanter of the femur, several centimeters from its insertion. A—The pubis is cut paramedian at the cranial (asterisk) and caudal (double asterisks) edges of the right obturator foramen. B—The sacroiliac joint (SI) is disarticulated.

Citation: Journal of the American Veterinary Medical Association 258, 2; 10.2460/javma.258.2.192

Figure 3
Figure 3

Photographs of the rabbit cadaver in Figures 1 and 2. A—Notice the resultant defect in the pelvic diaphragm (PD) following procedures described in Figures 1 and 2, transection of the lumbosacral plexus branches close to the pelvic limb, and removal of the entire limb compartment en bloc. B—The defect is repaired by opposing the thoracolumbar fascia (A) with the external abdominal oblique and rectus abdominus muscles with mattress sutures of 3-0 polydioxanone.

Citation: Journal of the American Veterinary Medical Association 258, 2; 10.2460/javma.258.2.192

The patient made an unremarkable recovery from general anesthesia. After anesthesia, fluid therapy through an IV catheter in the left marginal ear vein was continued at maintenance rates until voluntary eating occurred. Analgesia was provided with buprenorphine (0.025 to 0.05 mg/kg [0.011 to 0.023 mg/lb], IV, q 6 to 8 h) for 48 hours and meloxicam (0.4 mg/kg [0.18 mg/lb], PO, q 24 h) for 7 days. Metoclopramide was given SC (1 mg/kg [0.45 mg/lb]) before anesthetic induction and continued while hospitalized every 8 hours; after hospital discharge, metoclopramide was continued PO for 3 days. Ranitidine (5 mg/kg [2.27 mg/lb]) was given IV every 8 hours during hospitalization and then continued PO for 7 days. Enrofloxacin (10 mg/kg [4.54 mg/lb]) was given SC perioperatively and continued PO once daily for 3 days. The morning after surgery, the patient was eating, was witnessed ambulating around the kennel, and appeared comfortable. The patient was discharged from the hospital 2 days after surgery.

Histologic examination of the tumor revealed a poorly defined neoplastic mass, which was widely infiltrating and destroying the bone of the proximal portion of the femur (Figure 4). It was also infiltrating into the adjacent deep connective tissue and muscle and was closely associated with the hip joint capsule. Poorly organized streams and sheets of the neoplastic cells were evident. The neoplastic cells were ovoid to spindle shaped with moderate to occasionally prominent anisokaryosis and anisocytosis, and 2 mitotic figures/10 hpf were observed. Evidence of multifocal remodeling and resorption of the infiltrated bone was found. Neoplastic cells were not found in the margins of the removed muscular, pelvic, or ilial tissues. The histopathologic diagnosis was a fully excised, poorly differentiated sarcoma. The histogenesis of the sarcoma remained unclear, with no evidence of osteoid or cartilaginous matrix deposition by the neoplastic cells. Potential differential diagnoses included fibrosarcoma or rhabdomyosarcoma, with a histiocytic sarcoma being less likely.

Figure 4
Figure 4

Photomicrograph of a section of a tumor removed by hemipelvectomy in a 7-year-old sexually intact female rabbit with a 6-month history of chronic right pelvic limb lameness. Neoplastic tissue where bone has been infiltrated and destroyed is evident. Notice the reactive bone formation, with spicules of bone lined by well-organized osteoblasts (arrows). H&E stain; bar = 500 µm.

Citation: Journal of the American Veterinary Medical Association 258, 2; 10.2460/javma.258.2.192

At follow-up examination 14 months after surgery, the owner reported that the patient would occasionally fall to the right side, although overall mobility remained good. Reduced whole-body flexibility was noted, and the rabbit struggled to bend to clean the perineum and perform coprophagia. The owner had been cleaning this area regularly, and no evidence of urine scald was present. Body weight and condition score were normal, and clinical physical examination findings were unremarkable.

The patient died at home 21 months after surgery at 9 years of age. Necropsy was declined by the owner. No palpable evidence of tumor recurrence at the surgical site was present.

Discussion

Hemipelvectomy has not been previously described in rabbits. Studies in canine and feline patients report infrequent complications, which are usually minor, with intraoperative hemorrhage being the main major complication recorded.2,3 Most canine and feline patients are ambulatory 24 hours after surgery, and long-term function is deemed as excellent by most owners.2 Limb amputation (without removing any of the associated pelvic bone) has been described in rabbits, with those that are of appropriate body weight, younger in age, and without pododermatitis before surgery having a longer survival time.4,5 Eighty-five percent of amputee rabbits have short- or long-term morbidity, but most concerns resolve within the first week after surgery. The most frequently seen complications in rabbits are difficulties ambulating and grooming. Despite this fact, 91% of owners are satisfied with the outcome of surgery, with most patients being discharged within a few days after surgery.4,5

The prevalence of neoplasia in rabbits has been estimated at 0.5% to 2.7%, with uterine adenocarcinoma being the most commonly documented tumor.6,7 Mesenchymal tumors of the skeleton and soft connective tissues are not widely reported in rabbits. Published cases of neoplasia in rabbits are largely osteosarcoma, with a combination of both skeletal and extraskeletal variants reported.5,8,9,10,11,12,13

The present clinical report documented a previously undescribed surgical procedure in a rabbit with long-term follow-up. Rabbits have some key anatomic and physiologic differences from cats and dogs, which are important to consider for surgical procedures such as hemipelvectomy. The muscle mass surrounding the femur is proportionally larger than that in cats and dogs, along with a lighter skeleton and longer pelvic limbs in comparison with the thoracic limbs.14 These factors give rabbits their speed and unique hopping gait. The sartorius muscle has a much smaller diameter in rabbits and has 1 segment rather than 2. The lateral musculature of rabbits includes the coccygeofemoral muscle, which originates from the craniolateral aspect of the sacrum and inserts on the lateral condyle of the tibia.15,16 The skin in rabbits is much thinner and more friable, compared with that of cats and dogs, so a skin adhesive was used rather than skin sutures. In the postoperative period, gastrointestinal mobility is extremely important in rabbits because of hindgut fermentation and risk of gastrointestinal stasis. Our patient was administered a combination of metoclopramide for its prokinetic properties and ranitidine for its combined inhibition of histamine H2 receptors and prokinetic effects via the simulation of local muscarinic acetylcholine receptors, along with a high-fiber diet and IV fluid therapy after surgery. Gastrointestinal sounds and fecal output were closely monitored in the immediate postoperative period, and no abnormalities were found.

Although originally the lameness that the rabbit of the present report developed was thought to be caused by a previous fall, retrospective review of the radiographs taken by the primary care practice 4 days after the fall revealed early periacetabular lysis. This strengthens the argument that the previous injury and inflammation were not correlated with induction of the neoplastic process, as it was preexisting.

For the rabbit of the present report, definitive histogenesis was unfortunately not possible because immunohistochemistry could not be performed in our laboratory.17 A diagnosis of poorly differentiated sarcoma was therefore made on the basis of the available histologic information. The exact histogenesis of the mass would not have necessarily changed the overall surgical plan for the patient because a curative-intent approach was undertaken, resulting in tumor excision with tumor-free margins.

The rabbit of the present report did not undergo chemotherapy after surgery primarily because of owner financial constraints, but also because of the lack of exact histogenesis. This lack of information hindered the ability to accurately predict tumor behavior and choose a chemotherapeutic agent. Also, limited information exists for rabbits on the benefit of adjuvant chemotherapy, making recommendations more difficult. The rabbit was macroscopically free of metastasis at the time of diagnosis, but the ultimate cause of death after 21 months was unknown. The possibility remains that death may have been the result of metastatic disease.

The most commonly reported complications after limb amputation in rabbits are difficulty ambulating, hygiene issues, and podermatitis.4 These complications occurred in the rabbit of the present report, but they were mild and did not impact the patient's quality of life. Although hemipelvectomy is more routinely performed in dogs and cats, findings in the rabbit of the present report demonstrated that with the right candidate and owner commitment to aftercare, hemipelvectomy may be a safe and viable option for rabbits with a potential for long-term success.

Acknowledgments

No external funding was used for this report. The authors declare that there were no conflicts of interest related to a company mentioned or any product used in this report.

The authors thank Drs. Tim Scase and Sean Haugland for their histopathologic assistance in the evaluation of tissue specimens.

Footnotes

a.

Vetbond, 3M, Saint Paul, Minn.

References

  • 1.

    Bray JP. Hemipelvectomy: modified surgical technique and clinical experiences from a retrospective study. Vet Surg 2014;43:1926.

  • 2.

    Bray JP, Worley DR, Henderson RA, et al. Hemipelvectomy: outcome in 84 dogs and 16 cats. A Veterinary Society of Surgical Oncology retrospective study. Vet Surg 2014;43:2737.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Barbur LA, Coleman KD, Schmiedt CW, et al. Description of the anatomy, surgical technique, and outcome of hemipelvectomy in 4 dogs and 5 cats. Vet Surg 2015;44:613626.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Northrup NC, Barron GHW, Aldridge CF, et al. Outcome for client-owned domestic rabbits undergoing limb amputation: 34 cases (2000–2009). J Am Vet Med Assoc 2014;244:950955.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Higgins S, Guzman DS, Sadar MJ, et al. Coxofemoral amputation in a domestic rabbit (Oryctolagus cuniculus) with tibiofibular osteoblastic osteosarcoma. J Exot Pet Med 2015;24:455463.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Weisbroth SH. Neoplastic diseases. In: Manning PJ, Ringler DH, Newcomer CE, eds. The biology of the laboratory rabbit. 2nd ed. San Diego: Academic Press Inc, 1994;259292.

    • Search Google Scholar
    • Export Citation
  • 7.

    Tinkey PT, Uthamanthil RK, Weisbroth SH. Rabbit neoplasia. In: Suckrow MA, Stevens KA, Wilson RP, eds. The laboratory rabbit, guinea pig, hamster, and other rodents. San Diego: Elsevier Inc, 2012;447501.

    • Search Google Scholar
    • Export Citation
  • 8.

    Renfrew H, Rest JR, Holden AR. Extraskeletal fibroblastic osteosarcoma in a rabbit (Oryctolagus cuniculus). J Small Anim Pract 2001;42:456458.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Mazzullo G, Russo M, Niutta PP, et al. Osteosarcoma with multiple metastases and subcutaneous involvement in a rabbit (Oryctolagus cuniculus). Vet Clin Pathol 2004;33:102104.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Kondo H, Ishikawa M, Maeda H, et al. Spontaneous osteosarcoma in a rabbit (Oryctolagus cuniculus). Vet Pathol 2007;44:691694.

  • 11.

    Weiss ATA, Müller K. Spinal osteolytic osteosarcoma in a pet rabbit. Vet Rec 2011;168:266.

  • 12.

    Ishikawa M, Kondo H, Onuma M, et al. Osteoblastic osteosarcoma in a rabbit. Comp Med 2012;62:124126.

  • 13.

    Wijesundera KK, Izawa T, Fujita D, et al. Spontaneous extra-skeletal osteosarcoma in a rabbit (Oryctolagus cuniculus): histopathological and immunohistochemical findings. J Toxicol Pathol 2013;26:309312.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Brewer NR. Historical special topic overview on rabbit comparative biology. Biology of the rabbit. J Am Assoc Lab Anim Sci 2006;45:824.

    • Search Google Scholar
    • Export Citation
  • 15.

    Karamürsel S, Gündeşlioğlu AO, Oztürk MH, et al. Free microvascular transfer of coccygeofemoral muscle in rabbits. Microsurgery 2004;24:332334.

  • 16.

    Popesko P, Rajitová V, Horák J. A colour atlas of the anatomy of small laboratory animals. Volume 1: rabbit, guinea pig. London: Saunders,1992;124134.

    • Search Google Scholar
    • Export Citation
  • 17.

    Ramos-Vara JA. Technical aspects of immunohistochemistry. Vet Pathol 2005;42:405426.

  • Figure 1

    Photographs of a rabbit cadaver that was used to demonstrate the surgical approach for hemipelvectomy performed in a 7-year-old sexually intact female rabbit with a 6-month history of chronic right pelvic limb lameness. A—Through a ventral paramedian approach, the sartorius (A), adductor (B), gracilis (C), pectineus, and medial aspect of the tensor fascia latae (D) muscles are transected proximally to expose the pubic symphysis. B—Laterally, the superficial gluteal (A), biceps femoris (B), lateral aspect of the tensor fascia lata (C), and coccygeofemoral (D) muscles are transected.

  • Figure 2

    Photographs of the rabbit cadaver in Figure 1. Photographs were obtained following transection of the muscles described in Figure 1, ligation of the femoral artery, and transection of the rectus abdominus muscle and linea alba at their insertions on the cranial aspect of the pubic symphysis and the iliopsoas muscle at its insertion on the lesser trochanter of the femur, several centimeters from its insertion. A—The pubis is cut paramedian at the cranial (asterisk) and caudal (double asterisks) edges of the right obturator foramen. B—The sacroiliac joint (SI) is disarticulated.

  • Figure 3

    Photographs of the rabbit cadaver in Figures 1 and 2. A—Notice the resultant defect in the pelvic diaphragm (PD) following procedures described in Figures 1 and 2, transection of the lumbosacral plexus branches close to the pelvic limb, and removal of the entire limb compartment en bloc. B—The defect is repaired by opposing the thoracolumbar fascia (A) with the external abdominal oblique and rectus abdominus muscles with mattress sutures of 3-0 polydioxanone.

  • Figure 4

    Photomicrograph of a section of a tumor removed by hemipelvectomy in a 7-year-old sexually intact female rabbit with a 6-month history of chronic right pelvic limb lameness. Neoplastic tissue where bone has been infiltrated and destroyed is evident. Notice the reactive bone formation, with spicules of bone lined by well-organized osteoblasts (arrows). H&E stain; bar = 500 µm.

  • 1.

    Bray JP. Hemipelvectomy: modified surgical technique and clinical experiences from a retrospective study. Vet Surg 2014;43:1926.

  • 2.

    Bray JP, Worley DR, Henderson RA, et al. Hemipelvectomy: outcome in 84 dogs and 16 cats. A Veterinary Society of Surgical Oncology retrospective study. Vet Surg 2014;43:2737.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Barbur LA, Coleman KD, Schmiedt CW, et al. Description of the anatomy, surgical technique, and outcome of hemipelvectomy in 4 dogs and 5 cats. Vet Surg 2015;44:613626.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Northrup NC, Barron GHW, Aldridge CF, et al. Outcome for client-owned domestic rabbits undergoing limb amputation: 34 cases (2000–2009). J Am Vet Med Assoc 2014;244:950955.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Higgins S, Guzman DS, Sadar MJ, et al. Coxofemoral amputation in a domestic rabbit (Oryctolagus cuniculus) with tibiofibular osteoblastic osteosarcoma. J Exot Pet Med 2015;24:455463.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Weisbroth SH. Neoplastic diseases. In: Manning PJ, Ringler DH, Newcomer CE, eds. The biology of the laboratory rabbit. 2nd ed. San Diego: Academic Press Inc, 1994;259292.

    • Search Google Scholar
    • Export Citation
  • 7.

    Tinkey PT, Uthamanthil RK, Weisbroth SH. Rabbit neoplasia. In: Suckrow MA, Stevens KA, Wilson RP, eds. The laboratory rabbit, guinea pig, hamster, and other rodents. San Diego: Elsevier Inc, 2012;447501.

    • Search Google Scholar
    • Export Citation
  • 8.

    Renfrew H, Rest JR, Holden AR. Extraskeletal fibroblastic osteosarcoma in a rabbit (Oryctolagus cuniculus). J Small Anim Pract 2001;42:456458.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Mazzullo G, Russo M, Niutta PP, et al. Osteosarcoma with multiple metastases and subcutaneous involvement in a rabbit (Oryctolagus cuniculus). Vet Clin Pathol 2004;33:102104.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Kondo H, Ishikawa M, Maeda H, et al. Spontaneous osteosarcoma in a rabbit (Oryctolagus cuniculus). Vet Pathol 2007;44:691694.

  • 11.

    Weiss ATA, Müller K. Spinal osteolytic osteosarcoma in a pet rabbit. Vet Rec 2011;168:266.

  • 12.

    Ishikawa M, Kondo H, Onuma M, et al. Osteoblastic osteosarcoma in a rabbit. Comp Med 2012;62:124126.

  • 13.

    Wijesundera KK, Izawa T, Fujita D, et al. Spontaneous extra-skeletal osteosarcoma in a rabbit (Oryctolagus cuniculus): histopathological and immunohistochemical findings. J Toxicol Pathol 2013;26:309312.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Brewer NR. Historical special topic overview on rabbit comparative biology. Biology of the rabbit. J Am Assoc Lab Anim Sci 2006;45:824.

    • Search Google Scholar
    • Export Citation
  • 15.

    Karamürsel S, Gündeşlioğlu AO, Oztürk MH, et al. Free microvascular transfer of coccygeofemoral muscle in rabbits. Microsurgery 2004;24:332334.

  • 16.

    Popesko P, Rajitová V, Horák J. A colour atlas of the anatomy of small laboratory animals. Volume 1: rabbit, guinea pig. London: Saunders,1992;124134.

    • Search Google Scholar
    • Export Citation
  • 17.

    Ramos-Vara JA. Technical aspects of immunohistochemistry. Vet Pathol 2005;42:405426.

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