JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

November 2022

I-V09

 

SLIDE A:

Signalment (JPC# 1851282):  8-week-old male New Zealand white rabbit

 

HISTORY:  This rabbit developed a single large nodular cutaneous mass on the top of the head that grew rapidly over a 3-week period.

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin: Markedly expanding the dermis, abutting and elevating the overlying epidermis, separating and replacing adnexa, and extending to all cut borders, is a densely cellular proliferation of spindle cells arranged in interlacing streams and bundles on a moderate collagenous matrix. Spindle cells have indistinct cell borders and a moderate amount of pale, eosinophilic, fibrillar to microvacuolated cytoplasm that infrequently contains 4‑10µm diameter, round, eosinophilic intracytoplasmic viral inclusion bodies frequently surrounded by a clear halo. Nuclei are round to oval and vesiculate with finely stippled chromatin and 1 to 3 variably distinct nucleoli.  Mitotic figures average 1 per HPF, and there is moderate anisokaryosis. Scattered throughout the spindle cell proliferation and more pronounced at the periphery are aggregates of moderate numbers of lymphocytes, plasma cells, heterophils, and macrophages. The epidermal and follicular epithelium is moderately hyperplastic with occasional foci of ballooning degeneration, and epithelial cells rarely contain 4-10µm eosinophilic intracytoplasmic viral inclusion bodies. There is a focal intracorneal pustule 450µm in diameter.  

 

MORPHOLOGIC DIAGNOSIS:  Haired skin: Atypical mesenchymal proliferation, dermal, diffuse, marked, with multifocal epidermal hyperplasia, epithelial ballooning degeneration, and epithelial and mesenchymal eosinophilic intracytoplasmic inclusion bodies, New Zealand White rabbit (Oryctolagus cuniculus), lagomorph.

 

ETIOLOGIC DIAGNOSIS: Leporipoxviral fibroma

 

CAUSE:  Rabbit (Shope) fibroma virus

 

CONDITION:  Rabbit fibromatosis

 

SYNONYMS:  Shope fibroma

 

SLIDE B:

SIGNALMENT (JPC# 1850942):  Gray squirrel

 

HISTORY:  This squirrel had cutaneous tumor-like lesions involving the ears, lips, face, footpads, genital orifices, and perianal region.

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin:  Markedly expanding the dermis and extending to the epidermis and cut borders is an unencapsulated, multilobulated, densely cellular proliferation of atypical mesenchymal cells arranged in streams and bundles on a moderate collagenous matrix. Mesenchymal cells have indistinct cell borders and a moderate amount of eosinophilic fibrillar cytoplasm that often contains a 5-10µm, round, intracytoplasmic, brightly eosinophilic viral inclusion body frequently surrounded by a clear halo. Nuclei are irregularly round to oval, have coarsely stippled chromatin, and indistinct nucleoli. The mitotic rate averages 1 per 10 HPF. There are few scattered multinucleated viral syncytial cells with up to 18 nuclei and occasionally contain intracytoplasmic viral inclusions. There is a prominent band of lymphocytes surrounding lobules of spindle cells and, more diffusely throughout the dermis, lymphocytes are admixed with plasma cells, macrophages, and neutrophils. There is moderate diffuse epidermal hyperplasia and marked ballooning degeneration; epithelial cells frequently contain 10µm eosinophilic intracytoplasmic viral inclusion bodies frequently surrounded by a clear halo. There is diffuse mild parakeratotic hyperkeratosis and multifocal intracorneal pustules.

 

MORPHOLOGIC DIAGNOSIS:  Haired skin: Atypical mesenchymal proliferation, dermal, multifocal to coalescing, with lymphoplasmacytic dermatitis, epidermal hyperplasia, epithelial ballooning degeneration, and epithelial and mesenchymal eosinophilic intracytoplasmic viral inclusion bodies, Eastern gray squirrel (Sciurus carolinensis), rodent.

 

ETIOLOGIC DIAGNOSIS:  Leporipoxviral fibroma

 

CAUSE:  Squirrel fibroma virus

 

CONDITION:  Squirrel fibromatosis

 

GENERAL DISCUSSION:  

Rabbit fibroma virus

• Tumor-inducing Leporipoxvirus virus that causes benign, self-limiting disease in adult wild cottontail rabbits (Sylvilagus sp.) and European rabbits (Oryctolagus sp.)
• Antigenically related to myxoma virus

Squirrel fibroma virus

 

PATHOGENESIS:

Rabbit fibroma virus

• Transmitted via a vector bite 
• Spontaneous tumor regression occurs within weeks to months

Squirrel fibroma virus

• Believed to be transmitted by biting arthropods (ticks, fleas, and mosquitoes)
• Some squirrels, likely more commonly in immunocompromised or juvenile, may develop viremia and fatal systemic infection

 

TYPICAL GROSS FINDINGS:  

Rabbit fibroma virus

• Firm, flattened, freely moveable, cutaneous tumors most commonly on the legs and feet, head, pinna, periorbital, genital, and perineal areas; up to 7cm diameter
• Metastasis to abdominal viscera and bone marrow may occur in young rabbits
• Subcutaneous masses vary from myxoid to typical fibromas in European domestic rabbits

Squirrel fibroma virus

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Rabbit fibroma virus

• Initially acute inflammation progressing to localized fibroblastic proliferation with variable mixed inflammatory infiltrates (heterophils, macrophages, lymphocytes, and plasma cells)
• Proliferation of highly pleomorphic ovoid to stellate-shaped cells with abundant pale eosinophilic cytoplasm (fibroblasts)
• Epithelial hyperplasia with rete pegs projecting into the fibroblastic mass with ulceration
• Large eosinophilic intracytoplasmic viral inclusion bodies in epithelial and mesenchymal cells (inclusions characteristic of poxvirus infections)
• May have myxoid variant, which can be confused with myxomatosis

Squirrel fibroma virus

 

ULTRASTRUCTURAL FINDINGS:  

 

DIFFERENTIAL DIAGNOSIS:

Rabbit fibroma virus

• Fibrosarcoma or collagenous hamartoma 

• Differentiate histologically by presence in the viral-induced lesions: cell morphology (atypical mesenchymal cells), inflammation, and inclusion bodies  

Viral diseases that cause similar gross lesions in rabbits:

• Myxomatosis (leporipoxvirus, I-V10)

• Severe generalized disease in the European rabbit (Oryctolagus sp.); subcutaneous myxoid mass at the site of inoculation (typically not the limbs or face) that progresses to mucopurulent conjunctivitis, facial edema, scrotal edema, and multiple myxomas, often at the base of the ears
• Localized benign fibroma in wild rabbits (Sylvilagus sp.) at the site of inoculation
• Can be distinguished from myxomatosis because of presence on face and limbs

• Cottontail rabbit papillomavirus (Shope papillomavirus [different from Shope fibroma virus]):  Pedunculated or raised, hornlike mass often on the pinna and eyelids; heavily keratinized overlying a fleshy central core; numerous large cutaneous horns can be debilitating; spontaneously regress in Sylvilagus sp. rabbits, but when inoculated in Oryctolagus rabbits lesions often progress to squamous cell carcinoma; spread by insect vectors
• Rabbit pox (orthopoxvirus):  Rare disease; confluent papules present in skin, respiratory tract, spleen, and liver

Squirrel fibroma virus

 

COMPARATIVE PATHOLOGY:

Fibromas caused by viruses in other species:

Other Leporipoxviruses:

• Myxoma virus (I-V10)
• Hare fibroma virus: affects ears and legs of European hares; transmitted by insects and contact; spontaneously regress in adult hares

 

References:

1. Barthold SW, Griffey SM, Percy DH.  Pathology of Laboratory Rodents and Rabbits. 4th ed.  Ames, IA; 2016: 260-264.
2. Delaney MA, Treuting PM, Rothernburger JL. Lagomorpha. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018: 487-488.
3. Delaney MA, Treuting PM, Rothernburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018: 506-507.
4. Howerth EW, Nemeth NM, Ryser-Degiorgis MP.  Cervidae.  In: Terio KA, McAloose D, Leger JS, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:154-155.
5. Mauldin EA, Peters-Kennedy J.  Integumentary system.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6^th ed. St. Louis, MO: Elsevier Inc; 2015:616.

 

 

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