Adult, female, European rabbit (Oryctolagus cuniculus).A member of the public found the collapsed rabbit in a field close to their home and presented it to the local veterinary practice where the rabbit was euthanized on humane grounds.

Gross Description:  

The eyelids were bilaterally severely swollen with an exudate lightly adhered to the surface. The nostrils had a bilateral discharge. The vulva was severely swollen.

Histopathologic Description:

The slide consists of a section of haired skin and vulva including mucocutaneous junction. There is diffuse moderate to severe hyperplasia of the mucosal epithelium. Multifocally epithelial cells throughout all the layers of the epithelium are enlarged, often degenerate, with clear intracytoplasmic spaces (intra-cellular edema). Often, epidermal cells contain large, approximately 15 to 20 μm diameter, round to oval, homogenous, brightly eosinophilic cyto-plasmic inclusions. The same inclusions may also be observed in sloughed epithelial cells and within the thickened stratum corneum showing moderate orthokeratotic hyperkeratosis. Randomly scattered throughout the epidermis there are occasional keratinocytes with hyper-eosinophilic cytoplasm and karyorrhectic nuclei (single cell necrosis). There are diffusely scattered basophilic granules within keratinocytes (keratohyaline granules) of the stratum granulosum and rarely deep within the stratum basale (dyskeratosis). Multifocally, the epithelial cells of the vaginal mucosa are expanded by a single large clear vacuole (intracellular edema / ballooning degeneration).

Diffusely the lamina propria is characterized by a loosely arranged slightly basophilic myxoid matrix admixed with edematous areas. Multifocally in the dermis there are plump elongated to polygonal fibroblasts with stellate processes. These cells have finely granular basophilic cytoplasm, a single distinct, round to elongate and centrally placed large nucleus with finely stippled chromatin and a single evident nucleolus. Anisocytosis and anisokaryosis are moderate and mitotic figures are rare.

Within the superficial dermis and surrounding the blood vessels in the deeper dermis there are moderate, multifocal to coalescing aggregates of lymphocytes, plasma cells, heterophils, and macrophages. Occasionally, in the superficial dermis, the inflammatory process is predominately heterophilic.

Morphologic Diagnosis:  

1. Vulva, mucocutaneous junction: Diffuse, subacute, moderate to severe epidermal hyperplasia with intracellular edema and intracytoplasmic viral inclusions.

2. Vulva, mucocutaneous junction: Multifocal to coalescing, subacute, moderate lymphoplasmacytic and heterophilic proliferative dermatitis and sub-mucosal proliferation with diffuse myxoid changes and edema.

Lab Results:  



Vulvar myxomatosis/Myxomatosis virus (Leporipoxvirus)

Contributor Comment:  

Myxomatosis is a common, worldwide distribution disease of rabbits and is now endemic in the wild rabbit population in Europe. Hares may be carriers of the infection but very rarely exhibit clinical signs.2 Originally myxo-matosis was introduced in Europe to control the wild rabbit population.9 Initially the disease had a very high mortality rate, but due to natural selection the wild rabbit population began to develop immunity to the disease and mortality rate is now approximately 25% in the European rabbits.9

Myxomatosis is caused by the Myxoma virus, a leporipoxvirus from the family of poxviruses.6 Transmission of the virus requires a mosquito or flea vector, but it is possible for the virus to spread by direct contact. Due to transmission routes, domestic rabbits, especially the ones kept outdoors are at risk of contracting the virus from the wild rabbit population and therefore a vaccine has been developed.

There are two recognized forms of the disease: the classical, nodular form (as in this case); and the respiratory, amyxomatous form of the disease. The nodular form is often transmitted by vector route and causes the classical swelling of the eyelids, nodules over the skin, and edema of the genitalia. Usually, there is ocular and nasal discharge associated with the disease. The infection causes a severe depression of the host’s immune system causing secondary infections to take hold and often the secondary infections are the ultimate cause of death. The amyxomatous form is usually due to a mild or attenuated strain of the virus;6 this causes respiratory signs and rarely nodular lesions.

Other skin disease that may be confused for myxomatosis is Shope fibroma caused by the rabbit Shope fibroma virus (SFV, Leporipoxvirus). Shope fibroma virus induces discrete fibromas usually restricted to the distal limbs but occasionally may be found in the head.

JPC Diagnosis:  

Mucocutaneous junction, vulva Atypical mesenchymal proliferation, diffuse, moderate, with epithelial and epidermal hyperplasia, ballooning degeneration, lymphoplasmacytic and heterophilic dermatitis, and epithelial intracytoplasmic eosinophilic inclusions, European rabbit, Oryctolagus cuniculus.

Conference Comment:  

Poxviruses are a large family of epitheliotropic double-stranded DNA viruses that cause several important cutaneous and systemic lesions in wild and domestic mammals, birds, and humans.8 Most poxviruses cause a mild localized cutaneous lesion, but some can cause generalized systemic and fatal disease. An example of the latter is the rabbit myxoma virus, a member of the genus Leporipoxvirus, which can cause up to 90% mortality in naïve susceptible strains of wild rabbits.2,8,9 However, through natural selection, genetically resistant strains of wild rabbits now have only about 25% mortality when infected with virulent strains of the virus in endemic areas.9 Readers are encouraged to review 2012 for a brief review of the fascinating history of this virus, and its use during attempted European rabbit (Oryctolagus cuniculus) eradication programs in Australia and France in the early 1950’s.

Following inoculation, typically by an arthropod vector, susceptible rabbits develop localized skin tumors resembling fibromas caused by the rabbit (Shope) fibroma virus discussed above by the contributor.3,9 Other characteristic gross lesions are pronounced gelatinous subcutaneous edema surrounding mucocutaneous junctions. In this case, the contributor noted severe swelling around the eyelids and vulva with nasal discharge grossly.9

While the microscopic staining of the tissue section of vulva is somewhat pale, this case nicely illustrates the classic histologic poxviral epithelial intracytoplasmic in-clusions and ballooning degeneration.8 In addition, there is a subepithelial proliferation of large stellate mesenchymal cells within a homogenous mucinous matrix. Conference participants also noted a moderate lympho-plasmacytic inflammatory infiltrate admixed with the atypical mesenchymal cells. In addition to being epitheliotropic, the myxoma virus is T-lymphocytotrophic and systemic spread occurs via lymphocytes and monocytes to draining lymph nodes.9 Myxoma stellate cells are typically present in lymph nodes, bone marrow, spleen, and centrilobular areas of the liver. Degenerative and necrotizing lesions are usually confined to the lymphoid tissue in lymph nodes, lungs, and spleen with lymphoid depletion, particularly in the T-cell zones.9

Recently, there has been a great deal of interest in the rabbit myxoma virus as one of the promising new oncolytic viruses used in virotherapy for human cancer. Oncolytic viruses are engineered to preferentially infect and kill cancer cells while sparing normal host cells.4,7 Several other oncolytic viruses originated from human pathogens (herpes simplex-1, measles, etc) and still retain some ability to replicate in normal host tissue. Myxoma virus is attractive to researchers because its pathogenicity is restricted to lagomorphs and thus it will not replicate or kill normal human host cells; but the virus does have significant oncolytic potential for a large variety of neoplasms in several animal species and humans.4,7


1. Bangari DS, Miller MA, Stevenson GW, et. al. Cutaneous and systemic poxviral disease in red (Tamiasciurus hudsonicus) and gray (Sciurus carolinensis) squirrels. Vet Patho.l 2009; 46:667-672.
2. Barlow A., et al. Confirmation of myxomatosis in a European brown hare in Great Britain. Vet Rec. 2014; 175(3):75-6.
3. Berto-Moran A, Pacios I, Serrano E, Moreno S, Rouco C. Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits. J Wildl Dis. 2013; 49(1):10-17.
4. Chan WM, McFadden G. Oncolytic poxviruses. Annu Rev Virol. 2014; 1:119-141.
5. DiGiacomo RF, Mare CJ.  Viral diseases. In: Manning PJ, Ringler DH, Newcomer CE, eds.  The Biology of the Laboratory Rabbit. 2nd ed. San Diego, CA: Academic Press; 1994:178-180.
6. Kerr, P.J., et al., Myxoma virus and the Leporipoxviruses: An evolutionary paradigm. Viruses. 2015; 7(3):1020-61.
7. Kinn VG, Hilgenberg VA, MacNeill AL. Myxoma virus therapy for human embryonal rhabdo-myosarcoma in a nude mouse model. Oncolytic Virother. 2016; 5:59-71.
8. Mauldin E, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA:Elsevier; 2016:616-625.
9. Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. rd ed. Ames, IA: Blackwell Publishing; 2016:261-263.

Click the slide to view.

1-1. Vulva, mucocutaneous junction, rabbit.

1-2. Vulva, rabbit.

1-3. Vulva, rabbit.

1-4. Vulva, rabbit.

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