JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

November 2016

I-V01

 

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

HISTORY:  None

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

GENERAL DISCUSSION:

 PATHOGENESIS:

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)

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

ULTRASTRUCTURAL FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS:

DIFFERENTIAL DIAGNOSIS:

COMPARATIVE PATHOLOGY:

Cats

Dogs

Horses

Bovine

Ovine

Rabbit

Others

REFERENCES:

  1. Bergin IL, Bell JD, Chen Z, et. al. Novel genital alphapapillomaviruses in baboons (Papio hamadryas anubis) with cervical dysplasia. Vet Pathol. 2013;50:200-208.
  2. Brandes K, Fritsche J, Mueller N, et. al. Detection of canine oral papillomavirus DNA in conjunctival epithelial hyperplastic lesions of three dogs. Vet Pathol. 2009;42:34-38.
  3. Cheville NF. Cytopathology of viral diseases. In: Ultrastructural Pathology the Comparative Cellular Basis of Disease. 2nd ed. Ames, IA: Wiley-Blackwell; 2009:343-346.
  4. Gaynor AM, Fish S, Duerr RS, Dela Cruz Jr. FN, Pesavento PA. Identification of a Novel Papillomavirus in a Northern Fulmar (Fulmarus galcialis) With Viral Production in Cartilage. Vet Pathol. 2015;52:553-561.
  5. Gross TL, Ihrke PJ, Walder EJ. Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis. Ames, IA: Blackwell; 2005:567-575.
  6. Ingle A, Ghim S, Joh J, et. al. Novel laboratory mouse papillomavirus (MusPV) infection. Vet Pathol. 2011;48:500-505.
  7. Labelle P. The eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier Mosby; 2016:1297.
  8. Lange CE, Tobler K, Lehner A, et. al. EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology. Vet Pathol. 2012;50:686-692.
  9. Luff J, Rowland P, Mader M, Orr C, Yuan H. Two Canine Papillomaviruses Associated With Metastatic Squamous Cell Carcinoma in Two Related Basenji Dogs. Vet Pathol. 2016;53:1160-1163.
  10. 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: Saunders Elsevier; 2016: 706-712.
  11. Munday JS, Kiupel M. Papillomavirus-associated cutaneous neoplasia in mammals. Vet Pathol. 2010;47:254-264.
  12. Munday JS, Fairley R, Atkinson K. The Detection of Felis catus papillomavirus 3 DNA in a fieline bowenoid in situ carcinoma with novel histologic features and benign clinical behavior. V Diagn Invest. 2016 28(5)612-615.
  13. Nambiar PR, Turnquist SE, Morton D. Spontaneous tumor incidence in rasH2 mice: Review of internal data and published literature. Tox Pathol. 2012;40:614-623.
  14. Ng TFF, Miller MA, Kondov NO, et al. Oral papillomavirus 1 (EIPV-1) in southern sea otters (Enhydra lutris nereis) in California, USA. J Wildl Dis. 2015;51(2):446-453.
  15. Nicholls PK, Stanley MA. The immunology of animal papillomaviruses. Vet Immunol Immunopathol. 2000;73:101-127.
  16. Orbell GB, Young S, Munday JS. Cutaneous sarcoids in captive African lions associated with feline sarcoid-associated papillomavirus infection. Vet Pathol. 2011;48:1176-1179.
  17. Root JJ, Hopken MW, Gidlewski T, Piaggio A. Cottontail rabbit papillomavirus infection in a desert cottontail (Sylvilagus audubonii) from Colorado, USA. J Wildl Dis. 2013;49(4):1060-1062.
  18. Roperto S, Ambrosio V, Borzacchiello G, et. al. Bovine papillomavirus type-2 (BPV-2) infection and expression of uroplakin IIIb, a novel urothelial marker, in urinary bladder tumors of cows. Vet Pathol. 2005;42:812-818.
  19. Sancak A, favrot C, Geisseler MD, Muller M, Lange CE. Antibodies titres against canine papillomavirus 1 peak around clinical regression in naturally occurring oral papillomatosis. Vet Dermatol. 2015;26(1):57-59.
  20. Scagliarini A, Casa G, Trentin B, et al. Evidence of zoonotic Poxviridae coinfections in clinically diagnosed papillomas using a newly developed mini-array test. J Vet Diagn Invest .2016;28(1):59-64.
  21. Silvestre O, Borzacchiello G, Nava D, et. al. Bovine papillomavirus type 1 DNA and E5 oncoprotein expression in water buffalo fibropapillomas. Vet Pathol. 2009;46:636-641.
  22. Zachary JF. Mechanisms of microbial infection. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier Mosby; 2016:227-228.
  23. Zhu KW, Affolter VK, Gaynor AM, Dela Cruz Jr. FN, Pesavento PA. Equine Genital Squamous Cell Carccinoma: In Situ Hybridization Identifies a Distinct Subset Containing Equus caballus Papillomavirus 2. Vet Pathol. 2015;52:1067-1072.

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

Animal species

Skin lesion

Papillomavirus

Cat

Feline viral plaque progressing to BISC

FdPV-1, -2

Cat

SCC

FdPV-2

Dog

Canine pigmented viral plaque progressing to ISC and SCC

CfPV-3, -4

Dog

Endophytic papilloma and SCC in immunosuppressed dogs

CfPV-2

Dog

Vaccine-induced cutaneous SCC

COPV

Horse

Equine sarcoid

BPV-1, -2

Horse

Equine papillomas, ISC and SCC

EcPV2

Rabbit

Cutaneous SCC

CRPV

Western barred Bandicoot

Cutaneous SCC

BPCV-1

Egyptian fruit bat

Basosquamous carcinoma

RaPV-1

Natal multimammate mouse

Keratoacanthoma and SCC

MnPV

European harvest mouse

Sebaceous carcinoma

MmPV

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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