Michael H. Goldschmidt, MSc, BVMS, MRCVS, Diplomate ACVP Professor and Head, Laboratory of Pathology and Toxicology Chief, Surgical Pathology Department of Pathobiology
Frances S. Shofer, PhD, Adjunct Associate Professor of Epidemiology and Biostatistics

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

Clinical Presentation/Physical Exam Findings

Papillomas are usually small 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 based mass projecting upward and outward from a thickened epidermis.
• On cut section, these lesions often consist of multiple finger-like projections with keratinous material accumulating on the surface and between them.
• 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:

• elongated rete at the periphery of the papilloma which 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:

• a hyperplastic overlying epidermis layer
• the follicular infundibulum is filled with parakeratin
• 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.

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. Le Net, J.L., Orth, G., Sundberg, J.P., Cassonnet, P., Poisson, L., Masson, M.T., & Longeart, L. (1997). Multiple pigmented cutaneous papules associated with a novel canine papillomavirus in an immunosuppressed dog. Vet Pathol 34:8-14.
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
6. Yager, J.A. & Wilcock, B.P. (1994). Color atlas and text of surgical pathology of the dog and cat. Ontario, Canada: Mosby Year Book

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