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Case report
Cutaneous presentation of canine intravascular
lymphoma (malignant angioendotheliomatosis)
YVONNE A. VANGESSEL,* SEAN P. M C DONOUGH,* HANNAH J. M C CORMICK{
and BRIAN A. SUMMERS*
*Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
{Saranac Veterinary Clinic, 3900 Route 3, PO Box 67, Saranac, NY 12981, USA
(Received 12 May 1999; accepted 16 June 1999)
Abstract A 9-year-old female spayed Boxer dog presented with variably sized, rm, black, raised, exudative
subcutaneous masses on her head, neck and trunk, that tended to uctuate in size and frequently ulcerate.
Skin biopsy showed that the dermis was expanded by a densely cellular mass of proliferative capillaries
distended with large pleomorphic neoplastic round cells mixed with brin and erythrocytes. Intravascular
lymphoma was diagnosed and immunostains were compatible with a CD8+ T lymphocyte histogenesis
(CD3+/CD79a7/TCRab+/CD8a+). Post-mortem examination, four months after diagnosis, revealed
neoplastic T-cells within meningeal arteries. We are unaware of other reports of a cutaneous presentation
and ante-mortem diagnosis of intravascular lymphoma in the dog. Additionally, this vasoproliferative form of
intravascular lymphoma has not been previously described in dogs.
Keywords: CD3 complex, dog, intravascular lymphoma, immunohistology, malignant angioendotheliomatosis,
skin disease.
INTRODUCTION
Intravascular lymphoma (IVL), originally called
neoplastic or malignant angioendotheliomatosis due
to a suspected endothelial histogenesis, is a rare fatal
disease characterized by intravascular proliferation of
neoplastic lymphocytes in the absence of a solid
primary tumour or detectable neoplastic cells in
peripheral blood. This intravascular proliferation
ultimately results in vascular compromise of the
aected tissue secondary to thrombus formation and
luminal occlusion.
IVL has been reported in dogs,17 one cat8 and more
frequently in humans.9,10 Aected dogs most commonly present with acute central nervous system signs.
In all reported canine cases, diagnosis of IVL was
made at necropsy by the histological identication of
neoplastic lymphocytes lling variably sized cerebromeningeal arteries and veins. In most cases there was
also widespread but clinically silent involvement of the
vessels of parenchymal organs. There is no description
of skin lesions in any of these reports.
Two clinically distinct presentations of IVL are
described in humans: neurologic and cutaneous.
Patients with the neurologic form of IVL often
present with mental sluggishness, dementia, cerebrovascular accidents or seizures. In the cutaneous form
patients typically present with painful plaques or
nodules resembling phlebitis, panniculitis or vasculitis.10 In both instances there is generally widespread
involvement of parenchymal organs and ante-mortem diagnosis is usually made via skin or lung biopsy.
The majority of reported cases of canine IVL
resemble the neurologic form of IVL described in
people with no reported description of a cutaneous
manifestation. In all reported cases of canine IVL
diagnosis was made at post-mortem examination.
Here we describe a case of ante-mortem diagnosis of
IVL in a dog with cutaneous lesions, which was
conrmed four months later at necropsy.
CASE REPORT
A 9-year-old female spayed 25 kg Boxer dog was
presented to the Saranac Veterinary Clinic (Saranac,
NY) with a one-month history of multiple, variablysized, black, raised cutaneous masses. Initially the
dog had approximately 12 1.5 cm diameter alopecic
dark red to black hyperpigmented areas distributed
dorsally over the head and neck, and randomly on
the trunk. These areas were nonpruritic and nonpainful, and developed into rm black plaque-like
masses, which tended to uctuate in size, ooze serum,
scab and ulcerate.
291
Y. A. vanGessel et al.
(Fig. 1). The dermal mass dissected both into the
subcutaneous adipose tissue and the overlying supercial dermis. The central area of the neoplasm
featured a dense disorderly proliferation of thinwalled vascular channels lined by plump fusiform
cells (Fig. 2a). These vascular channels contained
large round pleomorphic cells mixed with red blood
cells and brin. The vasoformative nature of this
lesion was claried by immunohistochemical stains
for smooth muscle actin, which identies vascular
pericytes (Fig. 2b).
At the margins of the neoplasm, the diagnostic
pattern of conspicuous large round mononuclear cells
occluding the lumen of capillaries could be discerned
(Fig. 3a). The intraluminal cells were approximately
1215 mm in diameter and had sparse cytoplasm and
a round to oval indented stippled nucleus occasionally containing 12 prominent nucleoli. The mitotic
rate was variable, averaging 1 mitosis per high power
eld. The proliferative vascular channels were lined
by von Willebrand Factor (vWF) antigen positive
endothelial cells (Fig. 3b) and smooth muscle actin
positive cells, presumably pericytes or myocytes. In
contrast, the intravascular cells were negative for
vWF antigen and smooth muscle actin. Consistent
with an IVL of T-cell origin, the intravascular
neoplastic cells were CD45RA and CD3 positive
(Fig. 3c) and CD79a negative. Additionally, the
neoplastic cells were strongly positive for the newly
described canine b2-integrin ad.11
A diagnosis of cutaneous IVL was made and oral
prednisone therapy (10 mg given orally three times
daily tapered to 10 mg given orally every other day
Paran
embedded
tissue
sections
Antigen
Antibody
Antigen
Retrieval
Dilution
Source
vWF
pAb
Rabbit
mAb
1A4
mAb
CA4.1D3
mAb
HM57
pAb
Rabbit
mAb
CA18.3C6
Trypsin
1: 1000
NT
1: 40
MW
CSA
MW
CSA
Trypsin
1: 200
1: 200
1: 200
CSA
1: 200
mAb
CA17.2A12
mAb
CA15.8G7
mAb
CA20.8H1
mAb
CA13.1E4
mAb
CA9.JD3
mAb
CA15.4G2
NT
1: 10
NT
1: 10
NT
1: 10
NT
1: 10
NT
1: 10
NT
1: 10
SMA
CD45RA
CD79a
CD3
ad
Frozen
tissue
sections
CD3
TCRab
TCRgd
CD4
CD8a
CD8b
vWF = vonWillebrand's Factor, SMA = Smooth muscle actin, MAb = monoclonal antibody, PAb = polyclonal antibody,
NT = no treatment, MW = microwave, CSA = catalysed signal amplication (DAKO, Carpinteria, CA).
# 2000 Blackwell Science Ltd, Veterinary Dermatology, 11, 291297
293
Y. A. vanGessel et al.
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Y. A. vanGessel et al.
ACKNOWLEDGEMENTS
The authors would like to thank Dr Peter Moore,
Department of Pathology, Immunology and Microbiology, UC Davis for providing leukocyte markers,
Christina A. Smith, Department of Biomedical
Sciences, Cornell University, for excellent quality
immunohistology, and Alexis Wenski-Roberts, Image Lab, Cornell University, for assistance with
illustrations. This work was partially funded by the
Alumni Association, Cornell University.
3.
4.
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11.
REFERENCES
1. Dargent, F.J., Fox, L.E., Anderson, W.I. Neoplastic
angioendotheliomatosis in a dog: an angiotropic
lymphoma. Cornell Veterinarian 1988; 78: 25362.
2. Kilrain, C.G., Saik, J.E., Jeglum, K.A. Malignant
angioendotheliomatosis with retinal detachment in a
# 2000 Blackwell Science Ltd, Veterinary Dermatology, 11, 291297
12.
297
Resume Une femelle Boxer, sterilisee, agee de 9 ans, est presentee pour l'apparition de masses sous-cutanees
fermes, noires, en relief et exudatives, de taille variable, localisees sur la tete, le cou et le tronc, ayant tendance
a uctuer et a s'ulcerer. Des biopsies cutanees ont montre une invasion cellulaire dermique par des masses
denses de capillaires proliferatifs et distendus par de grandes cellules rondes neoplasiques, pleomorphes,
melangees a de la brine et a des erythrocytes. Un diagnostic de lymphome intravasculaire est fait. Les
immunomarquages sont compatibles avec une origine lymphocytaire T CD8+ des cellules neoplasiques
(CD3+/CD79a/TCRab+/CD8a+). Une autopsie realisee 4 mois apres le diagnostic a montre des cellules T
neoplasiques dans les arteres des meninges. Il s'agit du premier rapport de lymphome intravasculaire associe a
des signes cutanes diagnostique ante-mortem chez le chien. En outre, cette forme vasoproliferative de
lymphome intravasculaire n'a pas ete precedemment rapportee chez le chien. [vanGessel, Y. A., McDonough,
S. P., McCormick, H. J. et Summers, B. A. Cutaneous presentation of canine intravascular lymphoma
(malignant angioendotheliomatosis). (Signes cutanes d'un lymphome intravasculaire (angioendotheliomatose
maligne) chez un chien.) Veterinary Dermatology 2000; 11: 291297.]
Resumen Una perra Boxer de 9 anos, castrada, se presento con masas subcutaneas exudativas de tamano
variable, duras, negras y elevadas, en la cabeza, cuello y tronco, que tend an a uctuar de tamano y
frecuentemente ulceraban. La biopsia cutanea mostro que la dermis se encontraba engrosada por una masa
celular densa de capilares proliferativos dilatados con celulas redondas pleomorcas, neoplasicas, de gran
tamano, mezcladas con brina y eritrocitos. Se diagnostico un linfoma intravascular y las inmunotinciones
fueron compatibles con una histogenesis de linfocitos T CD8+ (CD3+/CD79a/TCRab+/CD8a+). El
examen post-mortem, cuatro meses despues del diagnostico, revelo celulas T neoplasicas en las arterias
men ngeas. No tenemos conocimiento de otras descripciones de diagnostico ante-mortem de linfoma
intravascular en el perro. Por otra parte, esta forma vasoproliferativa de linfoma intravascular no ha sido
descrita anteriormente en el perro. [vanGessel, Y. A., McDonough, S. P., McCormick, H. J. e Summers), B.
A. Cutaneous presentation of canine intravascular lymphoma (malignant angioendotheliomatosis).
(Presentacion cutanea del linfoma intravascular canino (angioendoteliomatosis maligna).) Veterinary
Dermatology 2000; 11: 291297.]
Zusammenfassung Eine neunjahrige, kastrierte Boxerhundin wurde mit harten, schwarzen, exsudativen,
subkutanen, in der Grosse variierenden und haug ulzerierenden Knoten am Kopf, Nacken und Rumpf
vorgestellt. Hautbiopsien ergaben, dass die Dermis durch eine dichte, zellulare Masse proliferierender
Kapillaren, die mit grossen, pleomorphen, neoplastischen, mit Fibrin und Erythrozyten vermischten
Rundzellen angefullt und erweitert waren, ausgedehnt wurde. Intravaskulares Lymphom wurde
diagnostiziert und Immunfarbungen waren mit einer CD8+ T-Lymphozytenhistiogenese kompatibel
(CD3+/CD79a/TCRab+/CD8a+). Postmortale Untersuchung vier Monate nach der Diagnose ergab
neoplastische T Zellen in menigealen Arterien. Berichte von kutanen Symptomen und ante-mortem Diagnose
von intravaskularem Lymphom beim Hund sind uns nicht bekannt. Ausserdem wurde diese vasoproliferative
Form eines intravaskularen Lymphoms bisher beim Hund nicht beschrieben. [vanGessel, Y. A., McDonough,
S. P., McCormick, H. J. und Summers, B. A. Cutaneous presentation of canine intravascular lymphoma
(malignant angioendotheliomatosis). (Kutane Symptome eines kaninen, intravaskularen Lymphoms (maligne
Angioendotheliomatose.) Veterinary Dermatology 2000; 11: 291297.]