Papilloma (Papillomatosis)

Veterinary Hospital of the University of Pennsylvania
Last Modified: July 18, 2005

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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

Sex

N

Percent

Female 101 21% (21%)
Female Spayed 150 32% (33%)
Male 108 23% (25%)
Male Castrated 111 24% (21%)
(Normal Population %)


Breeds at
Increased Risk
N Probability OR 95% Confidence
Interval
Whippet 5 <0.0001 12.1 4.95 29.4
Rhodesian Ridgeback 8 <0.0001 6.7 3.33 13.6
Weimeraner 10 0.0001 4.5 2.40 8.4
Mastiff 5 0.0062 4.4 1.83 10.8
Greyhound 8 0.0008 4.2 2.09 8.5
American Pit Bull Terrier 11 0.0001 4.2 2.30 7.6
Great Dane 13 <0.0001 4.1 2.33 7.0
Jack Russel Terrier 9 0.0006 4.0 2.09 7.8
Beagle 16 0.0507 1.7 1.01 2.7
Labrador Retriever 51 0.0331 1.4 1.04 1.9


Breeds at
Decreased Risk
N Probability OR 95% Confidence
Interval
Mixed Breed 75 <0.0001 0.6 0.47 0.8
Cocker Spaniel 8 0.0022 0.4 0.19 0.7
Miniature Poodle 3 0.0046 0.2 0.08 0.8
Shetland Sheepdog 1 0.0021 0.1 0.02 0.8


Site Percent
Head 52.13%
Forelimb 12.50%
Rearlimb 11.17%
Multiple Sites 10.64%
Abdomen 2.93%
Thorax 1.60%
Neck 1.33%
Perianal Region 0.80%
Tail 0.53%
Back 0.27%


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