Signalment:  

Adult rabbit of unknown age and breed.

Gross Description:  

The rabbit showed severely swollen eyelids.

Histopathologic Description:

: Complete eyelid with epidermis and conjunctiva: The epidermis is generally hyperplastic and invades the dermis at the conjunctival-epidermal junction in a lobular pattern, extending into the lamina propria of the palpebral conjunctiva. The hyperplasia is predominantly acanthosis, but the non-invading epidermis exhibits orthokeratotic hyperkeratosis. Keratinocytes within the invading portion of the epidermis show widespread hydropic degeneration. Some keratinocytes contain a 10-15 μm long, eosinophilic cytoplasmic inclusion body surrounded by a clear halo (Splendore inclusions or bodies). 

In the dermis, multiple large, stellate or polygonal cells with finely granular, basophilic cytoplasm and one or more large nuclei with finely granular to fragmented chromatin and one clear nucleolus are present. Mitoses are less than 1 per HPF. There is a slight infiltration of eosinophils, macrophages and some lymphocytes and plasma cells. The surrounding collagen fibers are loosely arranged and interspersed with a moderate amount of basophilic amorphous substance (proteoglycans). 

Part of the conjunctival mucosa is desquamated due to autolysis. 

Morphologic Diagnosis:  

Proliferative dermatitis with myxomatous changes.

Condition:  

Myxomatosis

Contributor Comment:  

Myxomatosis is a disease of wild and domestic rabbits or, rarely, hares caused by the myxoma virus, which belongs to the Leporipoxvirus genus of the family Poxviridae. Transmission of the virus occurs through direct contact or via vectors such as mosquitos or fleas.(1,4)

Three to five days after infection, affected animals first show signs of fever, depression and loss of appetite. Subsequently, edematous or firm skin nodules (mostly around the eye, mouth, nose, ear or genitalia), conjunctivitis and severe depression are seen. Death occurs within one to two weeks after the first symptoms appear.(5)

Histologically, one of the first apparent changes is an increase in number and size of the epidermal cells. After this, granular, pink cytoplasmic inclusions appear in these cells. The disease progresses until cell lysis occurs and epidermal vesicles develop. In the dermis, large stellate or polygonal cells with swollen nuclei and fragmented chromatin, polymorphonuclear leukocytes and multinucleated cells appear. Histological changes can also be seen in other organs. The lymph nodes, for example, first become activated, while, as the disease progresses, lymphocytes are replaced with the large stellate or polygonal cells previously described. The same cellular infiltration can be seen in the spleen.(5)

JPC Diagnosis:  

Eyelid: Atypical mesenchymal proliferation, diffuse, moderate, with epithelial ballooning degeneration and necrosis, intraepithelial eosinophilic intracytoplasmic viral inclusions, and mild myxedema. 

Conference Comment:  

Conference participants discussed the interesting history of myxomatosis, which was first recognized in European rabbits (Oryctolagus cuniculus ) in a South American laboratory in the late 1800s. Myxomatosis was first recognized in California in 1930, and remains enzootic in the western United States to this day. In the 1950s, the virus was implemented as a biological control in Australia, where it was introduced to cull the ballooning population of nonnative European rabbits. Mortality rates in the European rabbits at the time of introduction were as high as 99%; however, mortality dropped to around 25% in the years that followed, likely due to natural selection of resistant rabbits as well as the emergence of less virulent viral strains. In 1953, myxomatosis was introduced into the wild rabbit population in France, reportedly by a disgruntled individual; from there the virus spread to other parts of Western Europe, including England.(3)

Conference participants also discussed the pathogenesis of myxomatosis. As the contributor stated, myxoma virus is spread via arthropod vectors. The virus replicates in the host at the site of inoculation, resulting in a subcutaneous myxoid mass. In susceptible animals, the virus can then spread via cell-associated viremia (also known as leukocyte trafficking) and cause systemic disease. In less susceptible rabbit species, such as Sylvilagus brasiliensis and S. bachmani, viremia does not develop, and lesions are generally restricted to localized cutaneous fibromas. 

A closely-related leporipoxvirus, rabbit fibroma virus (RFV, also known as Shope fibroma virus), occurs naturally in the eastern cottontail (Sylvilagus floridanus) and causes similar lesions, referred to as Shope Fibromas, in both cottontails and European rabbits.2 Shope fibromas appear grossly as flattened subcutaneous tumors on the legs, feet, and occasionally the face. Histologically, Shope fibromas are composed of a localized proliferation of reactive fibroblasts that may contain large intracytoplasmic eosinophilic inclusion bodies. The inclusion bodies can also be found in the cells of the overlying epidermis. These well-circumscribed fibrous masses are generally easily distinguishable from myxomatosis, which is characterized by proliferation of stellate mesenchymal cells on a mucinous matrix with epithelial hypertrophy. 

Participants noted that this case features a comparatively milder atypical mesenchymal spindle cell proliferation, and more severe epithelial proliferation and loss of normal epithelial stratification than is usually observed in this disease. 

References:

1. Day MF, Fenner F, Woodroofe GM. Further studies on the mechanism of mosquito transmission of Myxomatosis in the European rabbit. J Hyg. 1956;54:258-83.
2. Kerr PJ. Myxomatosis in Australia and Europe: a model for emerging infectious diseases. Antiviral Res. 2012;93(3):387-415.
3. Percy DH, Bathrold SW. Rabbit. In: Pathology of Laboratory Rodents and Rabbits. 3rd ed. Ames, Iowa: Blackwell; 2007:256-258.
4. Sobey WR, Conolly D. Myxomatosis: the introduction of the European rabbit flea Spilopsyllus cuniculi (Dale) into wild rabbit populations in Australia. J Hyg. 1971;69:331-346. 
5. Rivers TM. Infectious myxomatosis of rabbits. J Exp Med.1930;51:965-976.

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2-1. Haired skin, eyelid

2-2. Haired skin, eyelid

2-3. Haired skin, eyelid

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