AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

November 2019

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 4‑10um diameter, round, eosinophilic intracytoplasmic viral inclusion bodies. 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 4-10um eosinophilic intracytoplasmic viral inclusion bodies. There is a focal intracorneal pustule.

 

MORPHOLOGIC DIAGNOSIS: Haired skin: Atypical mesenchymal proliferation, dermal, diffuse, marked, with multifocal epidermal hyperplasia and 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 5-10um, round, intracytoplasmic, brightly eosinophilic viral inclusion body. Nuclei are irregularly round to oval, have moderately stippled chromatin, and indistinct nucleoli. The mitotic rate averages 1 per 10 HPF. There are few scattered multinucleated viral syncytial cells with up to 10 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 10um eosinophilic intracytoplasmic viral inclusion bodies. There is diffuse mild parakeratotic hyperkeratosis and multifocal intracorneal pustules.

 

MORPHOLOGIC DIAGNOSIS: Haired skin: Atypical mesenchymal proliferation, dermal, multifocal to coalescing, with chronic-active 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:

·      Genus Leporipoxvirus: like other poxviruses, these are large, enveloped, double-stranded DNA viruses; genus includes rabbit (Shope) fibroma virus, hare fibroma virus, squirrel fibroma virus, myxoma virus (I-V10), and malignant rabbit fibroma virus (a recombination of Shope fibroma and myxoma viruses)

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.); other rabbit species are resistant

·       Antigenically related to myxoma virus; European rabbits that have recovered from infection are considered immune to myxomatosis

·     One of the three most common neoplasms in pet rabbits (other two most common are trichoblastoma and collagenous hamartoma)

Squirrel fibroma virus

·         Leporipoxvirus that creates similar benign, self-limiting disease in grey squirrels mainly in North America, also reported in a fox squirrel and red squirrels

 

PATHOGENESIS:

Rabbit fibroma virus

·      Transmitted via a vector bite (mosquito, flea, triatome, bedbug) or into the skin by mechanical trauma

·      Adult cottontails: Virus confined to epidermis surrounding inoculation site; no viremia

·      Young cottontails: Develop viremia and fatal systemic infection

·      Spontaneous tumor regression occurs within weeks to months

Squirrel fibroma virus

·      Believed to be transmitted by mosquitoes

·      Lesions often spontaneously regress

·      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, well demarcated, cutaneous lesion most commonly on the limbs, head, pinna, periorbital, genital, and perineal areas; up to 7cm diameter and 2cm thick

·      Metastasis to abdominal viscera and bone marrow may occur in young rabbits

Squirrel fibroma virus

·      Similar to rabbit fibroma virus; firm, tan, subcutaneous/cutaneous nodules on all areas of the body and/or marked epidermal thickening around eyes and ears; can be internal as well (lungs, lymph nodes, liver, kidney); progress to plaque-like to pedunculated masses

 

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), characteristically fusiform to polygonal; mitoses are rare

·      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)

·      Overlying epidermis may become necrotic due to pressure ischemia and slough

·      May have mononuclear perivascular cuffing in adjacent vessels and/or a pronounced lymphocyte accumulation at the base of the tumor

·      May have myxoid variant, which can be confused with myxomatosis

Squirrel fibroma virus

·      Resemble rabbit fibroma virus: proliferation of atypical spindle cells, epithelial hyperplasia, large prominent eosinophilic intracytoplasmic viral inclusion bodies in epithelial and spindle cells

 

ULTRASTRUCTURAL FINDINGS:

·      Poxviruses: intracytoplasmic, large (200-400 nm), brick-shaped virions

 

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

·      Myxoid change is a feature common to both, and is a frequent feature of mesenchymal proliferations in rabbits

Viral diseases that cause similar gross lesions in rabbits:

·      Myxomatosis (leporipoxvirus, I-V10)

·      Severe generalized disease in the European rabbit (Oryctolagus sp.)

·      Localized benign fibroma in wild rabbits (Sylvilagus sp.) at the site of inoculation (typically not the limbs or face)

·      Cottontail rabbit papillomavirus (Shope papillomavirus [different from Shope fibroma virus]): Pedunculated or hornlike mass often on the pinna and eyelids; heavily keratinized; spontaneously regress in Sylvilagus sp. rabbits, but when inoculated in Oryctolagus rabbits lesions often progress to squamous cell carcinoma

·      Rabbit pox (orthopoxvirus): Rare disease; confluent papules present in skin, respiratory tract, spleen, and liver

Squirrel fibroma virus

·      Cuterebra spp. larval infestation (warbles): nodules are typically larger than those caused by SFV, contain an opening through which the larva can breathe and often seeps a serosanguineous discharge

·      Squirrel poxvirus (reclassified into its own clade): not currently in North America, lesions typically severe, ulcerative, and hemorrhagic

 

COMPARATIVE PATHOLOGY:

Fibromas caused by viruses in other species:

·      Cutaneous fibromas / fibropapillomas in deer (deer papillomavirus, I-V02): Transmitted through biting insects or direct contact with abraded skin; single or multiple, black/gray, hairless masses

 

Other Leporipoxviruses:

·      Myxoma virus (I-V10)

·      Hare fibroma virus: affects European hares

·      Malignant rabbit fibroma virus: recombination of Shope fibroma and myxoma viruses; causes generalized infection, tumors, and immunosuppression and is usually fatal

 

REFERENCES:

1.    Bangari DS, Miller MA, Stevenson GW, Thacker HL, Sharma A, Mittal SK. Cutaneous and systemic poxviral disease in red (Tamiasciurus hudsonicus) and gray (Sciurus carolinensis) squirrels. Vet Pathol. 2009;46(4):667-72.

2.    Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA; 2016: 260, 263-264.

3.    Brabb T, DiGiacomo RF. Viral Diseases. In: Suckow MA, Stevens KA, Wilson RP, ed. The laboratory rabbit, guinea pig, hamster, and other rodents, 1st ed. Waltham, MA: Academic Press; 2012: 373-376.

4.    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.

5.    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.

6.    Hess L, Tater K. Dermatologic Diseases. In: Quesenberry KE, Carpenter JW, ed. Ferrets, Rabbits, and Rodents Clinical Medicine and Surgery, 3rd ed. St. Louis, MO: Elsevier Limited; 2012: 240.

7.    Himsworth CG, Musil KM, Bryan L, Hill JE. Poxvirus infection in an American red squirrel (Tamiasciurus hudsonicus) from northwestern Canada. J Wild Dis. 2009;45(4):1143-9.

8.    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.

9.    Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier Inc; 2015:616.

10. Miller WH, Griffin CE, Campbell KL. Muller & Kirk’s Small Animal Dermatology, 7th ed. St. Louis, MO: Elsevier Limited; 2013: 867.

11. Williams ES, Barker IK. Infectious Diseases of Wild Mammals. 3rd ed. Ames, IA:Iowa State University Press; 2001:182-190.


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