Introduction

Definition: A benign exophytic neoplastic proliferation of the squamous epithelium caused by infection with papillomavirus

Synonyms: warts or verruca vulgaris

Epidemiology and Etiology

• caused by a papovavirus, which is a double stranded DNA virus. Two different papovaviruses are thought to be present in the dog:
• Canine Oral Papilloma Virus (COPV)- responsible for the oral papilloma
• Canine Papilloma Virus (CPV)- responsible for the cutaneous and inverted papilloma
• occur most commonly in dogs less than 3 years of age
• does not show any sex predilection

Papilloma Age Distribution

Clinical Presentation/Physical Exam Findings

They are usually solitary lesions.

There are three different presentations of canine papilloma virus.

1. Cutaneous Papilloma - solitary or multiple lesions found on the skin surface.
2. Inverted Papilloma - a benign endophytic (growing inward) proliferation of the epidermis.
3. Oral Papillomatosis- with multiple papillomas found in the oral cavity

• Upon physical examination, the majority of cutaneous papillomas appear as a narrow base mass projecting upward and outward from a thickened epidermis.
• On cut section these lesions often consist of multiple fronds with keratinous material accumulating on the surface and between the fronds.
• The skin that surrounds the papillomas is usually normal but secondary bacterial infections may be found
• Inverted papillomas are usually larger than cutaneous papillomas, solitary and endophytic.
• They are located within the dermis and can extend into the subcutaneous as the tumor grows.
• Keratinous material may accumulate in the center of the mass obscuring the finger-like projections that may be seen on clinical presentation.
• These masses are usually well demarcated from the surrounding epidermis and dermis.

Tumor Pathology

Microscopic findings:

Three different histopathologic findings may be found with canine cutaneous papillomas. It is unclear at present whether this represents differences in virus subtypes of canine papillomavirus.

Papilliferous subtype

Papilloma- Papilliferous Subtype

This is the most commonly encountered papilloma and is characterized by:

• the elongated rete at the periphery of the papilloma are slanted towards the center
• papillae are supported by a thin core of dermal fibrous connective tissue
• epidermal hyperplasia
• thickened stratum corneum, may be orthokeratotic or parakeratotic
• granular cell layer is either absent or has very prominent enlarged keratohyaline granules in the cytoplasm
• in some cells the normal cell eosinophilic (red) cytoplasm of the cells of the spinous layer is replaced by a grey-blue finely granular material (viral cytopathic effect)
• occasional intranuclear pale basophilic inclusions (virus)
• lymphoplasmacytic and neutrophilic infiltration of the dermis.

Infundibular subtype

Papilloma- Infundibular Subtype

This subtype affects the infundibulum of the hair follicle and not the overlying epidermis. The histopathology is characterized by:

• the overlying epidemis is hyperplastic
• the follicular infundibulum is filled with parakeratin
• there is an abrupt transition from normal epidermal keratinocyes to affected/infected cells
• hyperplasia of basal and lower spinous layer
• cells in the hyperplastic upper spinous layer have an abundant grey-blue cytoplasm
• Fairly numerous intranuclear viral inclusion bodies, more readily seen on immunohistochemistry

Le Net subtype

Papilloma- Le Net Subtype

This subtype was originally described as pigmented popular lesions but other non-pigmented, non-papular lesions have been seen. The lesions may be exophytic or endophytic.

The histopathology of this subtype is characterized by:

• intracytoplasmic, brightly eosinophilic fibrillar material (keratin) that occupied most of the cell
• peripheral nucleus with basophilic intranuclear inclusion bodies

Inverted papillomas appear similar histologically to the papillerous subtype of cutaneous papillomas.

Cytology:

• intranuclear eosinophilic inclusion bodies may be seen in some cells from the granular cell layer.
• lymphocytes, plasma cells, and neutrophils may be seen, which is indicative of secondary inflammatory changes.

Clinical Behavior

• Many papillomas will regress spontaneously; however, regression may take anywhere from weeks to months to occur.
• Spontaneous regression is due to cell mediated immunity and humoral immunity.
• Failure to regress may be an indication of an underlying immunodeficiency or an immunocompromised animal (receiving corticosteroid therapy).
• Some papilloma virus infections have been known to progress into carcinomas, primarily squamous cell carcinomas.

Dermatopathology References

1. Goldschmidt, M.H., & Hendrick, M.J. (2002). Tumors of the skin and soft tissue. In D.J. Meuten (Ed.), Tumors in domestic animals 4 th ed (pp. 45-119). Iowa: Iowa State Press
2. Goldschmidt, M.H., & Shofer, F.S. (1998). Skin tumors of the dog and cat. Woburn, MA: Butterworth-Heinemann
3. Gross, T.L., Ihrke, P.J., & Walder, E.J. (1992). Veterinary dermatopathology: A macroscopic and microscopic evaluation of canine and feline skin disease. (pp. 327-485). St. Louis, Missouri: Mosby Year Book
4. Scott, D.W., Miller Jr., W.H., & Griffin, C.E. (1995). Muller and Kirk’s small animal dermatology 5 th ed. (pp. 990-1126). Philadelphia, PA: W.B. Saunders Company
5. World Health Organization (1998). Histological classification of epithelial and melanocytic tumors of the skin of domestic animals (2 nd series, vol 3). Washington, DC: Armed Forces Institute of Pathology

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