November 2016



Slide A

Signalment (JPC #21474-35):  A dog

HISTORY:  Tissue from raised, pedunculated horny nodule from the head

HISTOPATHOLOGIC DESCRIPTION:  Haired skin: Extending from the epidermis is an exophytic neoplasm composed of epithelial cells that form papillary projections supported by fine fibrovascular cores.  Neoplastic cells progress from a hypertrophied stratum basale to a thickened stratum spinosum (acanthosis) and stratum granulosum.  Cells of the stratum basale are often elongate and aligned perpendicular to the stroma.  Cells have variably distinct cell borders, a moderate amount of eosinophilic cytoplasm, round to elongate nuclei with finely stippled chromatin and 1-4 distinct nucleoli.  Mitotic figures average 1 per HPF.  Numerous cells within the stratum spinosum and granulosum are enlarged with abundant finely granular, amphophilic cytoplasm with clear cytoplasmic vacuoles, eccentric vesiculate nuclei surrounded by a clear halo and 1-3 prominent magenta nucleoli (koilocytes).  Cells of the stratum granulosum contain many prominent, large and irregularly-shaped keratohyalin granules.  There is prominent orthokeratotic and parakeratotic hyperkeratosis with few multifocal aggregates of ghost cells.  Multifocally, the tips of papillary projections are necrotic with multiple foci of hemorrhage; and, within the superficial dermis, there are low numbers of scattered lymphocytes, neutrophils, and macrophages.

MORPHOLOGIC DIAGNOSIS:  Haired skin: Papilloma, viral, breed unspecified, canine.

Slide B
Signalment (JPC #2790107):  A dog


HISTOPATHOLOGIC DESCRIPTION:  Haired skin:  Focally extending from a 5mm deep crater in the dermis is an endophytic, well circumscribed neoplasm composed of epithelial cells that form papillary projections around a central keratin filled cavity. Neoplastic cells have distinct cell borders, moderate amounts of eosinophilic cytoplasm, round to oval nuclei with finely stippled chromatin and 1-4 prominent magenta nucleoli.  Mitotic figures average 2 per HPF.  There are numerous koilocytes and many irregular intracytoplasmic keratohyaline granules within the mid- to upper levels of the neoplastic epithelium.  There is prominent orthokeratotic and parakeratotic hyperkeratosis and few multifocal aggregates of ghost cells.  Multifocally, surrounding dermal adnexa and collagen are compressed with moderate numbers of lymphocytes, plasma cells, fewer macrophages, and small areas of hemorrhage.

MORPHOLOGIC DIAGNOSIS:  Haired skin:  Papilloma, inverted, viral, breed unspecified, canine.

ETIOLOGIC DIAGNOSIS:  Canine cutaneous papillomatosis

CAUSE:  Canine papillomavirus

Slide C
Signalment (JPC #1498137):  A cow

HISTORY:  Other animals of various ages in the herd had similar cutaneous lesions that persisted in some animals up to 4 years.

HISTOPATHOLOGIC DESCRIPTION:  Haired skin:  Projecting from the dermal-epidermal junction is a plaque-like, verrucous, exophytic neoplasm composed of squamous epithelial cells that form multiple, elongated, arborizing papillary projections widely separated by lamellated keratin and supported by long, thin fibrovascular cores.  Basal cells are columnar, have oval nuclei with stippled chromatin, and 1-3 magenta nucleoli.  Mitotic figures average 3 per HPF.  Cells of the stratum spinosum have moderate amounts of eosinophilic cytoplasm, distinct cell borders, prominent intercellular bridging, oval nuclei with finely stippled chromatin, and 1-4 bright magenta nucleoli.  There are rare koilocytes and numerous intracytoplasmic keratohyalin granules within the remaining superficial layers of the neoplasm.  Within the underlying superficial dermis there is a mild perivascular infiltrate composed of lymphocytes, plasma cells and few neutrophils.

MORPHOLOGIC DIAGNOSIS:  Haired skin:  Papilloma, viral, breed unspecified, bovine.

ETIOLOGIC DIAGNOSIS:  Bovine cutaneous papillomatosis

CAUSE:  Bovine papillomavirus (BPV)

CONDITION:  Cutaneous warts, verrucae vulgaris



Pathogenesis of human papillomatosis:

Proposed Action of Papillomaviruses (PVs) in promoting solar-induced cutaneous neoplasia:

  1. Keratinocytes are commonly asymptomatically infected by beta-PVs
  2. Infection is increased by immunosuppression and by some EVER2 gene subtypes
  3. Exposure to UV light damages DNA (note: In a normal cell, this damage is repaired or cell apoptosis is initiated)
  4. DNA repair and apoptosis are prevented by beta-PV infection and PV infection may promote epithelial proliferation (a proliferation of a population of cells unable to undergo apoptosis and containing damaged DNA promotes neoplastic transformation)
















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Papilloma viruses associated with pre-neoplastic and neoplastic skin lesions in animals (adapted from Munday and Kiupel):

Animal species

Skin lesion



Feline viral plaque progressing to BISC

FdPV-1, -2





Canine pigmented viral plaque progressing to ISC and SCC

CfPV-3, -4


Endophytic papilloma and SCC in immunosuppressed dogs



Vaccine-induced cutaneous SCC



Equine sarcoid

BPV-1, -2


Equine papillomas, ISC and SCC



Cutaneous SCC


Western barred Bandicoot

Cutaneous SCC


Egyptian fruit bat

Basosquamous carcinoma


Natal multimammate mouse

Keratoacanthoma and SCC


European harvest mouse

Sebaceous carcinoma


FdPV, Felis domesticus papillomavirus; CfPV, Canis familiaris papillomavirus; COPV, canine oral papillomavirus; BPV, bovine papillomavirus; CRPV, cotton-tail rabbit papillomavirus; RaPV, rousettus aegyptiacus papillomavirus type I; MnPV, Mastomys natalensis papillomavirus; EcPV2, equine papillomavirus type 2

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Click on image for diagnostic series.

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