Veterinary Dermatology 2004, 15, 47 52

Case report

Blackwell Publishing Ltd.

Cutaneous vascular malformation in a guinea pig (Cavia porcellus)

Vascular malformation in a guinea pig

ANNA OSOFSKY*, HILDE E. V. DE COCK, LISA A. TELL, AIMEE J. NORRIS* and

STEPHEN D. WHITE
*Veterinary Medical Teaching Hospital, Department of Pathology, Microbiology, and Immunology,
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis,
CA 95616, USA
(Received 17 October 2002; accepted 15 July 2003)

Abstract A skin lesion classified as a vascular malformation is reported in a young-adult, female guinea pig.
The physical examination revealed a 3 2-cm irregularly shaped violaceous plaque located on the left caudal
flank. The surface of the plaque was ulcerated and bled intermittently, resulting in fatal blood loss. On histology
the mass consisted of variably sized vascular spaces filled with red blood cells and variable amounts of extramedullary haematopoietic cells, lined by well-differentiated endothelial cells often surrounded by one layer of spindleshaped cells. Based on immunohistochemistry, the spindle cell population was confirmed to be smooth muscle
cells and no proliferation of endothelial cells was found with the Ki67 proliferation marker. Histological and
immunohistochemical findings were consistent with a vascular malformation. Classification of vascular malformations and potential treatments are discussed. To the authors knowledge, this is the first reported case of a cutaneous vascular lesion in a guinea pig.
Keywords: arterial, guinea pig, skin, vascular malformation.

INTRODUCTION
Classification of cutaneous vascular anomalies is difficult because there is no consistent use of terms such as
nevi, hamartoma, malformation or haemangioma in the
medical literature. A recent review of the human literature on cutaneous vascular anomalies proposed a classification system wherein vascular malformations are
defined as congenital anomalies resulting from inborn
errors of vascular morphogenesis.1 Some of these malformations are subtle abnormalities of the vessel wall
and only become apparent over time, as the result of progressive ectasia. In such vascular malformations, while
there is no evidence of cellular proliferation, the childs
growth causes expansion of the lesion.
Vascular malformations are clinically important as
they can cause space-occupying lesions, predispose the
patient to inflammation and infection, and spontaneously haemorrhage.25 This report describes a case of a
vascular malformation in the skin of a young guinea
pig that resulted in fatal blood loss.

CASE REPORT
A 915-g, intact female young-adult guinea pig (Cavia
Correspondence: Lisa A. Tell, Department of Medicine and
Epidemiology, School of Veterinary Medicine, University of
California, Davis, CA 95616, USA. E-mail: latell@ucdavis.edu
2004 European Society of Veterinary Dermatology

porcellus) was presented to the Companion Avian and

Exotic Pet Medicine Service, Veterinary Medical
Teaching Hospital (VMTH), School of Veterinary
Medicine, University of California, for a hairless plaque
on the left caudal flank. The plaque had been present
since the owner had acquired the guinea pig from a pet
store 8 months previously. The guinea pig was pregnant
at the time of purchase; four pups were born, all normal on physical examination. Husbandry conditions,
including diet and vitamin C supplementation, were
considered adequate.
The plaque was a violaceous macular lesion at the
time of purchase, but 2 months prior to presentation
the owner noticed that the lesion had become raised
and bled periodically. The guinea pig also had become
progressively less active and more resistant to handling.
Its appetite remained normal. There was no known history of physical trauma or chemical or thermal burns.
The animal was examined by the referring veterinarian 4 weeks prior to referral and a fine needle aspirate
and cytology of the plaque revealed blood. A recheck
physical examination was performed 2 weeks later
because the plaque had bled profusely while the guinea
pig was in its enclosure. The mass appeared slightly
more ulcerated than at the first visit but was otherwise
unchanged.
Physical examination of the guinea pig at the VMTH
revealed a 3 2-cm irregularly shaped violaceous plaque
that was located on the left caudal flank (Fig. 1a,b).
The surface of the plaque was ulcerated and palpation
47

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A. Osofsky et al.

Figure 3. Skin; guinea pig with vascular malformation. Vascular

spaces distributed in the dermis follow the distribution of the
vascular plexi as shown by the dilated vascular space in the region of
the superficial vascular plexus. H&E. Bar = 100 m.

Figure 1. (a) Hairless plaque on the left caudal flank of a guinea pig.
(b) Close-up of plaque seen in Fig. 1(a).

Figure 4. Skin; guinea pig with vascular malformation. The mass

consists of variably sized vascular spaces with variable diameter,
lined by well-differentiated endothelial cells that are often
surrounded by smooth muscle cells. H&E. Bar = 160 m.

Figure 2. Skin; guinea pig with vascular malformation. Overview of

the dermis, subcutis, and skeletal muscle (arrow) showing the distribution of the mass in all three compartments. H&E. Bar = 0.4 mm.

revealed that it extended into the dermis and possibly

the subcutis. The lesion did not blanch on diascopy. The
mucous membranes were pale pink. A right basilar, III/
VI systolic cardiac murmur was auscultated. The remainder of the physical examination was unremarkable.
Phlebotomy was attempted without sedation or anaesthesia. Enough blood was obtained for a packed cell
volume (PCV) and total protein, which revealed a
moderate to severe anaemia (PCV 19%; normal 37
48%).6 Differential diagnoses for the plaque included a

benign or malignant vascular neoplasm, a congenital

vascular defect, or a haemorrhagic bullae due to staphylococcal pyoderma.
The guinea pig was discharged to the owner with instructions to return in 2 days for a complete work-up,
including sedation or anaesthesia for phlebotomy,
whole-body radiographs, abdominal ultrasound, and
fine-needle aspiration and cytology of the plaque. An
echocardiogram was also planned for that time.
Two days later the guinea pig was readmitted to the
hospital. There were no changes noted on physical examination. The guinea pig was sedated with midazolam
(Midazolam HCl injection, Ben Venue Laboratories
Inc., Bedford, OH, USA), 0.5 mg kg1 IM, prior to the
echocardiogram. The echocardiogram revealed benign
right ventricular outflow tract obstruction, which was
not considered to increase anaesthetic risk. The guinea

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Vascular malformation in a guinea pig

Figure 5. Skin; guinea pig with vascular malformation. The vascular

spaces do not invade or destroy the skeletal muscle but rather
separated adjacent muscle bundles. H&E. Bar = 160 m.

Figure 6. Skin; guinea pig with vascular malformation. The vascular

spaces are surrounded by a layer of smooth muscle. Inset: detail of
the negative staining endothelial cells. Immunohistochemical stain
for smooth muscle actin. Bar = 40 m.

pig was placed in a hospital cage pending the remainder of the diagnostic work-up. It was discovered 90 min
later with large amounts of blood inside the cage, around
the plaque, and around the mouth, as if it had chewed
at the lesion. The guinea pig was depressed and
hypothermic (rectal temperature 36.6 C; normal 37.2
39.4 C)7 with pale mucous membranes; supportive care
was initiated including subcutaneous lactated-ringers
solution (Lactated Ringers Injection USP, Baxter Healthcare Corporation, Deerfield, IL, USA), conductive warming with a warm-water blanket, and placement in an
oxygen cage with 40% oxygen. A blood transfusion was
declined by the owner. The guinea pig was clinically
normal by the following morning aside from pale
mucous membranes. It was discharged to the owner to

49

Figure 7. Skin; guinea pig with vascular malformation. The only

cells that show active proliferation are the large numbers of
haematopoietic cells in the vascular lumens. The endothelial cells
stain uniformly negative for the proliferation marker Ki67.
Immunohistochemical staining for Ki67. Bar = 25 m.

allow the guinea pig to recover from the bleeding episode prior to further work-up and potential surgical
excision of the plaque.
The owner returned the guinea pig to the hospital 10
days later following another severe bleeding episode.
The animal was nonresponsive at the time of presentation and began agonal breathing. Cardiopulmonary
resuscitation was attempted but was unsuccessful. The
body was submitted for necropsy.
At necropsy the guinea pig was in good nutritional
condition but was anaemic based on pale mucous
membranes. There was a 3 2-cm, firm, hairless plaque
on the left caudal flank that had a dried haemorrhagic
crust on the surface, as well as in the surrounding hair.
The liver was pale tan with an enhanced reticular pattern and was slightly friable. The spleen was diffusely
enlarged. The heart was normal in appearance. Thin
sections of all organs were fixed in 10% neutral buffered
formalin and processed by routine methods to provide
paraffin wax sections (4 m), which were stained with
haematoxylin and eosin (H&E).
Histologically, other signs of anaemia found in this
animal were centrilobular fatty degeneration in the
liver and severe, diffuse extramedullary haematopoiesis in the spleen and liver. The skin lesion consisted of
a circumscribed expansile mass that extended from the
superficial dermis, to the dermis, hypodermis and underlying skeletal muscle (Figs 2 and 3). The mass consisted
of variably sized vascular spaces with diameters ranging between 10 and 50 m (Fig. 4). A few larger vascular spaces with diameters up to 240 m were scattered
throughout the mass in the dermis and skeletal muscle
(Fig. 4). The vascular spaces were filled with red blood
cells and variable amounts of extramedullary haematopoietic cells. Thrombi were present in two of the larger
vascular spaces. The vascular spaces were lined by welldifferentiated endothelial cells often surrounded by
one to three layers of spindle-shaped cells, with spindle-

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A. Osofsky et al.

shaped to oval nuclei and a moderate amount of pale

eosinophilic cytoplasm. These cells were interpreted as
smooth muscle cells. A few of the larger vascular spaces
had a thick smooth muscle wall composed of at least
five layers of smooth muscle cells. The vascular spaces
did not invade or destroy the skeletal muscle but rather
separated adjacent muscle bundles (Fig. 5). The overlying epidermis was regionally ulcerated and covered
with a thin haemorrhagic crust.
In order to confirm the smooth muscle origin of the
perivascular spindle-shaped cells, an immunohistochemical staining indirect immunoperoxidase method
with an anti-smooth muscle actin antibody (clone 1A4,
Biogenex, San Ramon, CA, USA) was applied on a
4-m thin section of the mass. This showed that all
vascular spaces were surrounded by a layer of smooth
muscle and highlighted the presence of several larger
arterial structures (Fig. 6). In order to help differentiate
between a vascular malformation and a haemangioma,
the mass was evaluated for evidence of actively proliferating endothelial cells by means of an indirect
immunoperoxidase with an anti-Ki67 antibody (clone
MIB-I, DAKO, Carpinteria, CA, USA). The only cells
that showed active proliferation were the large numbers of haematopoietic cells in the vascular lumens.
The endothelial cells uniformly stained negative for
the proliferation marker Ki67 (Fig. 7).
Cutaneous vascular malformations were not evident
in the four pups of this guinea pig as of 14 months of age.

DISCUSSION
The diagnosis and management of vascular lesions are
hindered by confusing and inconsistent nomenclature
in both the veterinary and human medical literature.
Vascular nevus, hamartoma and haemangioma are terms
that have been used to describe an array of vascular
lesions. Vascular malformations of the skin are among
the most commonly reported cutaneous congenital
disorders of children.810 The true prevalence of vascular malformations in veterinary medicine is difficult to
assess as vascular malformations have historically been
confused with vascular hamartomas and haemangiomas
and have also been called vascular nevi. Reports of
congenital vascular lesions in the skin of animals are
rare. A congenital vascular nevus near the coronary
band of a foal and a congenital hamartoma at the nasal
mucocutaneous junction in a dog are two of the few
reported cases.2,3,12 In contrast, there are many reports
of congenital vascular hamartomas of domestic animals in various anatomic locations, such as gingival
hamartomas in a kitten and three calves, cerebral vascular hamartomas in five dogs, and a vascular hamartoma in a goat with paraparesis.25,1317 In dogs, the
most commonly recognized vascular hamartomas are
in the scrotum. The term vascular hamartoma for these
lesions is probably a misnomer, as the lesions occur in
middle-aged to older dogs and therefore are probably
acquired rather than congenital in nature.1821

Recently, a complete and elucidating review on vascular anomalies in humans has been published and this
classification was used to characterize the lesion found
in this guinea pig.1 The proposed categories include
hamartomas, malformations, hyperplasias and benign
and malignant neoplasms. According to this classification, vascular malformations are those anomalies that
result from inborn errors of vascular morphogenesis
and therefore are always congenital, although not always
visible at birth. There is no evidence of vascular proliferation in tissue specimens of enlarging malformations,
although they expand with the individuals growth
because of progressive ectasia resulting from changes
in blood flow and pressure. In contrast, hyperplasias
and neoplasms such as haemangiomas are the result of
active proliferation of endothelial cells, and therefore
are distinctly different from malformations. Hamartomas are referred to as lesions that result from an error
in embryological development and are characterized
by an abnormal arrangement of tissues indigenous to
an organ. Hamartomas usually include more than one
tissue type.
The lesion in this guinea pig consisted of a mass of
vascular spaces that did not invade or destroy the surrounding tissues. The Ki67 stain demonstrated that
there was no active proliferation of endothelial cells in
this lesion. Based on this finding, both hyperplasia and
neoplasia (e.g. haemangioma) were ruled out. This
lesion was not considered a hamartoma because the
vascular spaces were evenly distributed throughout the
dermis, hypodermis and skeletal muscle and therefore
were more consistent with normal vascular structures
that had dilated due to abnormal intravascular pressure. There was no abnormal arrangement or aberrant
location of these vascular spaces, which is expected in
hamartomas.1 However, based on histology alone and
without antemorten echography or Doppler examination, a hamartoma cannot be completely ruled out.
Vascular malformations in humans usually occur
sporadically but can be familial.10,11 The exact aetiology
and pathogenesis are not known. In several inherited
autosomal dominant vascular disorders in humans,
defective genes have been identified; however, the pups
of this guinea pig were normal at 14 months of age.11 In
humans, it is speculated that the involved vessels are
abnormal at birth in either function or structural
arrangement.10 The eventual appearance and size of
the lesion depends on the intravascular pressure.1,10 In
this guinea pig, the lesion was noticed at the time of
purchase and the owner reported that it changed from
a macular lesion to a slightly raised plaque.
Profuse haemorrhage, as seen in this animal, has also
been recognized as a complication in vascular malformations in humans. Bleeding into the lesion itself, as
was evident on the histopathology, is probably the
reason why the lesion did not blanch during diascopy.
At necropsy, the animal proved to be chronically and
severely anaemic with extramedullary haematopoiesis,
not only in the liver and spleen but also within the
lesion. The anaemia in this animal was attributed to

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Vascular malformation in a guinea pig

the chronic blood loss from the lesion. Since these
lesions protrude above the normal skin surface, they
are especially prone to accidental trauma. Self-induced
trauma was also considered a possible cause for the
haemorrhaging in this animal as it was found with
blood around its mouth. In the human literature, vascular malformations are occasionally associated with
vascular neoplasms, especially haemangiomas or haemangioendotheliomas.22 Necropsy revealed no signs
of other disease or neoplastic processes.
The heart murmur identified in this guinea pig was
attributed to benign right ventricular outflow tract
obstruction based on echocardiography. However, no
cardiac lesions were identified at necropsy or on
histopathology. The authors were unable to find any
reports on right ventricular outflow obstruction in
guinea pigs. In cats, dynamic right ventricular outflow
obstruction is considered a physiological cause of murmurs and, therefore, no changes would be expected at
necropsy or on histopathology.23
Treatment options for cutaneous vascular malformations vary. As the lesions are fairly benign, conservative management can include simple monitoring of
the lesion for change in character, excessive bleeding,
and chronic infection.3,12 However, if the lesion is causing significant blood loss, is interfering with normal
function due to location, or is becoming repeatedly
infected, removal is recommended.12,14,19 In human
medicine, congenital cutaneous vascular lesions are
removed via surgical excision or via laser therapy
(flash-lamp pumped pulsed dye laser, neodynium:YAG
laser, or carbon dioxide laser); lasers have the advantage of causing less scarring.9 The authors were unable
to find any reports in the veterinary literature of laser
use in the treatment of vascular malformations. Surgical
excision was therefore recommended in this case as the
best treatment modality.

6.

7.

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9.

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17.

18.

19.

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1. Requena, L., Sangueza, O.P. Cutaneous vascular anomalies. Part I. Hamartomas, malformations, and dilatation
of preexisting vessels. Journal of the American Academy
of Dermatology 1997; 37: 523 49.
2. Smith, S.H., Van Winkle, T. Cerebral vascular hamartomas
in five dogs. Veterinary Pathology 2001; 38: 108 12.
3. Roudebush, P., MacDonald, J.M. Mucocutaneous
angiomatous hamartoma in a dog. Journal of the
American Animal Hospital Association 1984; 20: 16870.
4. Middleton, J.R., Valdez, R., Britt, L.G. et al. Progressive
hindlimb paraparesis in a goat associated with a vascular
hamartoma. Veterinary Record 1999; 144: 264 5.
5. Njoku, C.O., Henry, J.D., Cook, J.E. et al. Pulmonary

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Veterinary Medical Association 1972; 161: 37881.
Harkness, J.E., Wagner, J.E. The Biology and Medicine of
Rabbits and Rodents, 4th edn. Philadelphia: Williams &
Wilkins, 1995.
Donnelly, K.E. Guinea pigs and chinchillas: biology, husbandry, and clinical techniques. In: Quesenberry, K.E.
ed. Ferrets, Rabbits, and Rodents. Philadelphia: W.B.
Saunders, 1997: 24359.
Margileth, A.M. Developmental vascular abnormalities.
Pediatric Clinics of North America 1971; 18: 773 800.
Wirth, F.A., Lowitt, M.H. Diagnosis and treatment of
cutaneous vascular lesions. American Family Physician
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Handfield-Jones, S.E. Vascular nevi. Pediatrician 1991;
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Enjolras, O., Mulliken, J.B. Vascular tumors and vascular malformations (new issues). Advances in Dermatology
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Jabara, A.G., Hazard, G.H., OShea, J.D. A congenital
vascular naevus in a foal. Australian Veterinary Journal
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McGavin, M.D., Henry, J. Canine hepatic vascular
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Padgett, S.L., Tillson, D.M., Henry, C.J. et al. Gingival
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Wilson, R.B. Gingival vascular hamartoma in three
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Lee, C.G., Ladds, P.W. Vascular hamartoma of the ovary
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tissues. In: Moulton, J. ed. Tumors in Domestic Animals,
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Weipers, W.L., Jarrett, F.H. Haemangioma of the scrotum of dogs. Veterinary Record 1954; 66: 1067.
Gross, T.L., Walder, E.J. Vascular tumors. In: Walder, E.J.
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Rsum Une lsion cutane classifie comme une malformation vasculaire est rapporte chez un Cobaye. Lexamen clinique a montr la prsence dune plaque de 3.0 cm 2.0 cm, de forme irrgulire, localise sur la face caudale gauche du flanc. La surface de la plaque tait ulcre et saignait par intermittence, ce qui a provoqu une
perte sanguine fatale. A lexamen histologique, la masse tait constitue despaces vasculaires de taille variable,
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A. Osofsky et al.
remplis de cellules sanguines et de cellules hmatopoitiques extramdullaires, cern par des cellules endothliales
bien diffrencies, souvent entoures dune couche de cellules fusiformes. Ces cellules fusiformes se sont avres
tre des cellules musculaires sur la base dune tude immunohistochimique. Aucune prolifration des cellules
endothliales na t observe avec lutilisation du marqueur de prolifration Ki67. Les examens histologiques
et immunohistochimiques taient en faveur dune malformation vasculaire. La classification des malformations
vasculaires et leurs traitements potentiels sont rapports. A la connaissance des auteurs, il sagit de la premire
description dune lsion cutane vasculaire chez le Cobaye.
Resumen Se describe una lesin cutnea clasificada como una malformacin vascular en una hembra de cobaya
adulta joven. El examen fsico mostr una placa violcea de forma irregular de 3.0 cm 2.0 cm localizada en el
flanco izquierdo caudal. La superficie de la placa se encontraba ulcerada y sangraba intermitentemente,
resultando en una prdida de sangre fatal. Histolgicamente la masa consista en espacios vasculares llenos de
eritrocitos y cantidades variables de clulas hematopoyticas, internamente recubiertas por clulas endoteliales
bien diferenciadas, a menudo rodeadas por una capa de clulas fusiformes. Mediante tcnicas de inmunohistoqumica, se confirm un origen muscular liso en la poblacin de clulas fusiformes y no se hall proliferacin
de clulas endoteliales con el marcador de proliferacin Ki67. Los hallazgos histolgicos e inmunohistoqumicos
fueron compatibles con una malformacin vascular. Se discute la clasificacin de las malformaciones vasculares
y los tratamientos potenciales. Segn nuestros conocimientos, ste es el primer caso publicado de una lesin
vascular cutnea en un cobaya.
Zusammenfassung Eine Hautvernderung, die als vaskulre Missbildung klassifiziert wurde, wird bei einem
gerade erwachsenen weiblichen Meerschwein beschrieben. Die klinische Untersuchung zeigte eine 3,0 cm 2,0 cm
grosse, unregelmig geformte blau-rote Plaque an der linken caudalen Flanke. Die Oberflche der Plaque war
ulzeriert und blutete intermittierend, was zu einem fatalen Blutverlust fhrte. Histologisch bestand die Masse
aus unterschiedlich groen Gefrumen, die mit roten Blutzellen und variablen Mengen an extramedullren
hmatopoetischen Zellen angefllt und mit gut differenzierten endothelialen Zellen, die oft von einer Lage von
spindelfrmigen Zellen umgeben waren, ausgekleidet waren. Durch Immunhistochemie konnte die Spindelzellpopulation als Zellen der glatten Muskulatur besttigt werden und mit Ki67-Proliferationsmarker konnte keine
Proliferation von endothelialen Zellen gefunden werden. Die Klassifikation von vaskulren Malformationen und
potentielle Behandlungen werden diskutiert. Dem Wissen des Autors zufolge ist dies der erste Fall, bei dem von
einer kutanen vaskulren Lsion bei einem Meerschwein berichtet wurde.

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