Veterinary Dermatology 2004, 15, 240 244

Equine congenital papilloma: pathological findings and results

of papillomavirus immunohistochemistry in five cases

Blackwell Publishing, Ltd.

KELLY S. WHITE*, REINA N. FUJI, BETH A. VALENTINE

and ROBERT J. BILDFELL
*Class of 2004, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University,
Ithaca, New York, USA
Department of Biomedical Sciences, College of Veterinary Medicine, Magruder Hall 142,
Oregon State University, Corvallis, OR 97331, USA
(Received 9 September 2003; accepted 12 December 2003)

Abstract Congenital cutaneous papillomas were identified in five foals. Age at diagnosis ranged from 305 days
gestation to 2 days of age. Breeds were thoroughbred (2), standard-bred (1), warmblood (1) and paint (1). Two
were female, one was male and the gender of two cases was not specified. Masses were pedunculated with a roughened, wart-like (verrucous) or a smoother, cauliflower-like surface. Masses occurred as single lesions on the forelimb, lip and face, or as multiple lesions on the trunk. Histological features included relatively uniform epidermal
papillary hyperplasia with variable melanin pigment within basal layers and vacuolization of keratinocytes in all
layers, but with no evidence of nuclear or cytoplasmic changes (koilocytes) characteristic of viral infection. One
case showed epidermal proliferation with proliferation of pilosebaceous units. Results of immunohistochemical
studies for the detection of papillomavirus antigens were negative in all cases. These results suggest that equine
congenital papilloma may be a hamartomatous lesion (epidermal nevus) and not a viral-induced growth.
Keywords: congenital papilloma, epidermal nevus, equine, hamartoma, immunohistochemistry, papillomavirus.

I N TRO D U CTI ON
Cutaneous papillomas in horses occur as acquired and
congenital forms. Acquired cutaneous papilloma in
horses is a common viral-induced neoplasm similar to
viral papilloma in other species. Two distinct forms are
recognized: viral papillomatosis and ear papilloma (aural
plaque). Equine viral papillomatosis occurs most often
in horses < 34 years of age. Tumours are most common on the muzzle, are often multiple and will eventually
undergo spontaneous regression. Equine ear papilloma (aural plaque) occurs at any age and does not
regress.1 3 Papillomavirus is readily detected in these
acquired lesions,5,10 and the presence of keratinocytes
with nuclear atypia, cytoplasmic vacuolization, and
keratohyaline granule abnormalities (koilocytes) is
characteristic.3
Congenital equine papillomas are much less common
than acquired papillomas.29 Rare spontaneous regression of equine congenital papilloma has been suggested,1 but has not been documented. Surgical excision
is curative.1 3 In utero infection by a latent papillomavirus in the dam has been proposed as a possible
cause.1,4 8 A study that included five cases of equine
Correspondence: B. A. Valentine, Department of Biomedical
Sciences, College of Veterinary Medicine, Magruder Hall 142,
Oregon State University, Corvallis, OR 97331, USA. E-mail:
beth.valentine@oregonstate.edu
240

congenital papilloma found no immunohistochemical

evidence of papillomavirus,6 which supports the suggestion that these lesions are a form of epidermal nevus.3
The purpose of this study is to describe gross pathological and histopathological findings and results of
immunohistochemistry for detection of papillomavirus
in five additional cases of equine congenital papilloma,
including one case in a foetus. Findings are compared
with those in four confirmed equine papillomavirusinduced cutaneous papillomas.

M AT E R IA L S A N D M E T H O D S
A retrospective search of the pathology files at the College of Veterinary Medicine, Cornell University for a
5-year period (199398) identified five foals with congenital papilloma. Cases are summarized in Table 1.
Cases 14 were single tumours and case 5 had multiple
tumours, one of which was selected for study. Case 1
was a foetus from a mare that had died due to colic,
case 2 was a stillbirth due to dystocia, and tumours
from cases 35 were present at birth and removed
shortly thereafter.
All tumours had been removed either surgically or
at necropsy, fixed in 10% neutral-buffered formalin,
embedded in paraffin, sectioned and stained with haematoxylin and eosin (H&E). Serial sections were incubated for 2 h at 37 C with a prediluted polyclonal
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Table 1. Summary of five cases of equine congenital papilloma

Case no.

Breed

Sex

Age at removal (days)

Location

1
2
3
4
5

Standard-bred
Thoroughbred
Warmblood
Thoroughbred
Paint

Not given
Female
Male
Female
Not given

Foetal 305 days gestation

0 (full-term stillbirth)
1
1
2

Lower left lip, near commissure

Right foreleg, medial carpus
Face, between nostrils
Right foreleg, medial crus
Trunk, multiple sites

antibody to papillomavirus antigen (Zymed Laboratories Inc., South San Francisco, CA, USA) using a
streptavidinbiotin procedure. Sections from two cases
of cutaneous papilloma arising after birth in young
horses and from two equine aural plaques served as
positive immunohistochemical controls, and serial sections of all cases incubated with nonimmune serum
served as negative controls.

RESU LTS
Congenital papillomas varied from 2 to 4 cm in diameter. All tumours were pedunculated on a narrow to
broad stalk. Tumours from cases 1, 3 and 5 were verrucous (wart-like; Fig. 1), whereas those from cases 2
and 4 were more smooth-surfaced and cauliflower-like
(Fig. 2).
Histological features were of relatively uniform
papillary epidermal hyperplasia with marked expansion
of the stratum spinosum. Tumours were supported
by fibrovascular stroma with no evidence of dermal

Figure 2. Congenital papilloma in the skin of a full-term stillborn

thoroughbred filly (case 2). The mass is pedunculated with a
cauliflower-like surface. The tumour has been hemisected.

Figure 1. Multiple congenital papillomas, fixed in formalin solution,

from a 2-day-old paint foal (case 5). Masses are pedunculated with
a verrucous surface. Bar = 1 cm.

fibroblast proliferation (Fig. 3). Surface hyperkeratosis,

either orthokeratotic or parakeratotic, was common.
There was variable vacuolization of keratinocytes in all
layers, but no koilocytes were seen. Melanin pigment
within basal epithelium was variable, from none to
intense. Mitoses were not seen and superficial inflammation was rare. The lesion from case 2 also contained
multiple enlarged sebaceous glands associated with
hair follicles within the dermal portion of the tumour
(Fig. 4).
Papillomavirus antigen was detected by immunohistochemistry in the positive control sections of acquired
papillomas recognized to be viral in origin.6,10 Epidermal hyperplasia in these cases was markedly irregular,
with atypical keratinocytes characteristic of koilocytes
within superficial epidermal layers. Viral antigen in
these cases was most consistently found within nuclei
of koilocytes (Fig. 5), but also occurred within nuclei
of other epidermal cells within the stratum granulosum. Papillomavirus antigen was not detected in any of
the five cases of congenital papilloma (Fig. 6).

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KS White et al.

Figure 3. Congenital papilloma from a 305-day gestation standardbred foetus (case 1) showing relatively uniform epidermal papillary
hyperplasia with marked expansion of the stratum spinosum and no
evidence of koilocytosis or keratohyalin granule abnormalities.
Hypermelanosis is present in the basal epithelium. Papillary projections
are supported by dermal fibrovascular stroma with no evidence of
dermal fibroblast proliferation. Bar = 100 m, H&E stain.

Figure 4. Congenital papilloma from a full-term stillborn

thoroughbred filly (case 2). Pilosebaceous units are present within
the dermis at the base of the epidermal papillae. Bar = 75 m,
H&E stain.

DISCU SSIO N
Papillomas are common cutaneous tumours in animals. Papillomavirus infection is the most common
cause. Epidermal proliferation only is characteristic of
squamous papilloma, whereas dermal fibroblast proliferation in addition to epidermal proliferation is characteristic of fibropapilloma.2 Altered keratinocytes known
as koilocytes are characteristic of papillomavirus infection.3,11 These cells exhibit nuclear enlargement and
atypia, with sharply defined perinuclear vacuolization
and dense and irregular staining of peripheral cytoplasm. These cells occur only within maturing keratinocytes in the superficial or intermediate layers of
the epidermis and must be distinguished from keratinocytes with cytoplasmic vacuolar change due to
other causes, such as glycogen accumulation.11 Other
papillomavirus-induced changes in keratinocytes
include increased number, size and clumping of keratohyalin granules.3 Hypomelanosis is a feature of experimentally induced viral papillomas in horses.12 Melanin
pigmentation in these congenital papillomas was variable and included hypermelanosis.
Congenital papillomas are less common than acquired
papillomas. Congenital squamous papilloma occurs

Figure 5. Acquired ear papilloma from a 6-year-old quarter horse

with characteristic koilocytes with abnormal keratohyalin granules
within superficial epidermal layers. Nuclei of koilocytes express
papillomavirus antigen (brown stain). Bar = 25 m.
Immunohistochemistry for papillomavirus expression,
counterstained with Mayers haematoxylin.

most often in horses.19 Congenital fibropapilloma

occurs rarely in pigs13 and cattle.14 The gross pathological findings in these five cases of equine congenital
papilloma are similar to those described previously.1,4,79 Growths are pedunculated with a verrucous (wart-like) to cauliflower-like (smoother) surface.
Characteristic histological features are relatively uniform

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243

attachment of the amnion to the foetal epidermis

during gestation.7
Papillomavirus may not be detectable using immunohistochemistry during certain stages of tumour
development,6 and the possibility of papillomavirus
infection not expressing viral protein causing congenital
papillomas in horses still cannot be entirely ruled out
without additional molecular studies. But, the failure
to detect papillomavirus in these five foetal and neonatal
foal lesions and in a previous study of lesions in five
neonatal foals,6 the lack of koilocytes or alteration in
keratohyalin granules, and the presence of adnexal as
well as epidermal proliferation in case 2, strongly support
the hypothesis that equine congenital papilloma is a
hamartomatous lesion consistent with epidermal nevus,
and is not associated with papillomavirus infection.

AC K N OW L E D G E M E N T S
The authors thank Dr Barry Cooper, Ms Joy Cramer
and Ms Kay Fischer for technical assistance.

R E FE R E N C E S
Figure 6. Congenital papilloma from a 1-day-old thoroughbred filly
(case 4) demonstrating diffuse keratinocyte vacuolization without
nuclear atypia or keratohyalin granule abnormalities, and no
expression of papillomavirus antigen. Bar = 25 m.
Immunohistochemistry for papillomavirus expression,
counterstained with Mayers haematoxylin.

epidermal papillary hyperplasia with variable epidermal vacuolar change but with no evidence of koilocyte
formation or other papillomavirus-associated changes.
Pilosebaceous units may also be present.
Two of these five cases and seven of nine previously
reported cases9 occurred in the skin of the head, indicating that this is a common site. The most commonly
reported breed affected is thoroughbred,9 and two of
five of these cases were thoroughbreds. But, these lesions
can occur in many breeds, including mules (B.A. Valentine,
unpublished observation). The question of whether
these congenital lesions can spontaneously regress remains
unresolved, as the lesions present on live foals in this
study were excised soon after birth.
Although a viral cause for equine congenital papilloma has been proposed,1,48 the results of this study
support the findings of previous histological4,5,79 and
immunohistochemical6 studies in which no evidence of
viral infection was found. In addition, the finding of
pilosebaceous units as well as epidermal proliferation
in case 2 is more consistent with a hamartomatous
lesion than with viral-induced growth. Congenital
papillomas not associated with viral infection occur in
children, and proposed causes include a developmental
abnormality causing dysplasia of skin adjacent to
the first branchial cleft leading to lesions on the head,
and focal epidermal dysplasia induced by areas of

1. Pascoe RRR, Knottenbelt DC. Manual of Equine

Dermatology. London: W.B. Saunders, 1999: 945.
2. Scott DW. Large Animal Dermatology. Philadelphia:
W.B. Saunders, 1988: 4208.
3. Scott DW, Miller WH. Equine Dermatology. St. Louis,
MO: Saunders, 2003: 7007, 7789.
4. Atwell RB, Summers PM. Congenital papilloma in a
foal. Australian Veterinary Journal 1977; 53: 299.
5. Garma-Avia A, Vallie VE, Lumsden JH. Equine congenital cutaneous papillomatosis. A report of 5 cases.
Equine Veterinary Journal 1981; 13: 5961.
6. Junge RE, Sundberg JP, Lancaster WD. Papillomas and
squamous cell carcinomas of horses. Journal of the American Veterinary Medical Association 1984; 185: 6569.
7. Njoku CO, Burwash WA. Congenital cutaneous papilloma in a foal. Cornell Veterinarian 1972; 62: 54 7.
8. Schueler RL. Congenital equine papillomatosis. Journal
of the American Veterinary Medical Association 1973;
162: 640.
9. Misdorp W. Congenital tumours and tumour-like lesions
in domestic animals. 3. Horses. A review. Veterinary Quarterly 2003; 25: 6171.
10. Fairley RA, Haines DM. The electron microscopic and
immunohistochemical demonstration of a papillomavirus in equine aural plaques. Veterinary Pathology 1992;
29: 7981.
11. Rosai J. Ackermans Surgical Pathology, 8th edn.
St. Louis, MO: Mosby-Year Book, 1996: 1358.
12. Hamada M, Itakura C. Ultrastructural morphology of
hypomelanosis in equine cutaneous papilloma. Journal
of Comparative Pathology 1990; 103: 199213.
13. Vitovec J, Kursa J, Kratochvil P, Sklov A. Congenital
fibropapillomatosis in a piglet. Veterinary Pathology
1999; 36: 835.
14. Desrocher A, St-Jean G, Kennedy GA. Congenital cutaneous papillomatosis in a one-year-old Holstein. Canadian
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KS White et al.
Rsum Des papillomes cutans congnitaux ont t identifis chez 5 foals. Lge au diagnostic variait entre
305 jours de gestation et 2 jours. Deux femelles, un ma^le et deux animaux de sexe non prcis taient atteints.
Les masses se prsentaient sous forme pdoncule, avec un aspect paissi, verruqueux ou un aspect en chou-fleur.
Les masses taient soit uniques sur les membres, les lvres ou la face, soit multiples sur le tronc. Lexamen histopathologique a montr une hyperplasie pidermique papillaire, avec des dpts variables de pigments dans la
couche basale et une vacuolisation des kratinocytes dans toutes les couches pidermiques, sans vidence de modification nuclaire ou cytoplasmique pouvant voquer une infection virale. Un cas prsentait une prolifration pidermique associe une prolifration des units pilosbaces. La recherche de papillomavirus par immunohistochimie tait ngative dans tous les cas. Ces rsultats suggrent que le papillome quin congnital pourrait
correspondre une lsion dhamartome (naevus pidermique) et ne serait pas dorigine virale.
Resumen Se identificaron papilomas cutneos congnitos en 5 potros. La edad en el momento del diagnstico
estaba entre 305 das de gestacin y 2 das de edad. Las razas fueron Purasangre (2), standard (1), sangre caliente
(1) y pinto (1). Dos eran hembras, uno macho, y el gnero de 2 casos no se encontraba especificado. Las masas
eran pedunculadas con una superficie rugosa, verrucoide, o ms lisa, semejante a una coliflor. Se presentaban
como masas aisladas en la extremidad anterior, el labio, la cara, o como lesiones mltiples en el tronco. Las
caractersticas histolgicas incluan una hiperplasia papilar epidrmica relativamente uniforme con pigmento
melnico variable en las capas basales, y vacuolizacin de queratinocitos en todas las capas, pero sin evidencia
de alteraciones nucleares o citoplasmticas (coilocitos) caractersticas de infeccin vrica. Un caso mostr
proliferacin epidrmica con proliferacin de glndulas sebceas. Los resultados de los estudios
inmunohistoqumicos para la deteccin de antgenos de papilomavirus fueron negativos en todos los casos. Estos
resultados sugieren que el papiloma congnito equino pude ser una lesin hamartomatosa (nevo epidrmico) y
no una proliferacin inducida por un virus.
Zusammenfassung Bei 5 Fohlen wurden congenitale kutane Papillome identifiziert. Alter bei Diagnose rangierte zwischen 305 Tage nach Gestation bis 2 Tage. Rassen waren Vollblutpferd (2), Standardbred (1), Warmblut
(1) und Paint (1). Zwei waren weiblich, eines war mnnlich und in zwei Fllen war das Geschlecht spezifiziert.
Die Umfangsvermehrungen waren gestielt mit einer abgerauhten, warzenhnlichen (verruksen) oder einer glatteren, blumenkohlhnlichen Oberflche. Die Umfangsvermehrungen traten als Einzellsion an Vorderbein,
Lippe und Gesicht oder als multiple Lsionen im Bereich des Stammes auf. Histologische Merkmale umfaten
relativ uniforme epidermale papillre Hyperplasie mit unterschiedlichem Melaninpigment innerhalb der Basalschichten und Vakuolisierung der Keratinozyten in allen Schichten, aber kein Hinweis auf fr virale Infektionen
charakteristische nuklere oder zytoplasmatische Vernderungen (Koilozyten). Ein Fall zeigte epidermale Proliferation mit Proliferation der Haar-Talgdrsen-Einheit. Immunhistochemische Untersuchungen zum Nachweis von Papillomavirus-Antigen war in allen Fllen negativ. Diese Ergebnisse legen nahe, dass das equine
congenitale Papillom eine hamartomatse Lsion (epidermaler Nevus) sein kann und nicht viral induziertes
Wachstum.

2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 240 244