Hemangiosarcoma (HSA) is a highly malignant cancer originating from vascular endothelial cells. More frequent in dogs than
in any other domestic species, with a reported prevalence of 2 % of all canine tumors, it is associated with a high fatality
rate. Hemangiosarcoma typically affects older dogs, averaging 10 years of age at diagnosis, and a strong sex overrepresentation
has not been identified. While any canine breed can be affected with HSA, large and giant breeds are overrepresented, and
Golden retrievers and German shepherds seem predisposed. Though not as frequent in cats, HSA is nevertheless occasionally
diagnosed and recent studies helped describe the disease better.
While the strong breed association suggests a genetic predisposition in dogs, the definitive etiology of HSA remains elusive.
Chronic ultraviolet (UV) irradiation is a recognized risk factor for dermal HSA (superficial, stage I) in lightly pigmented
short-haired breeds of dogs (Whippet, Am Staff, etc.). Similarly, in recent studies, chronic UV light exposure was suggested
to predispose to HSA of the conjunctiva (nictitating membrane) of both dogs and cats.
A study demonstrated overexpression of the STAT3 protein, a transcription factor playing a role in many human cancers (oncoprotein),
to be common in canine vascular tumors, and a higher percentage of positive cells was observed in HSA than hemangiomas. In
contrast, a study on 19 canine HSA samples failed to reveal Cox-2 positive immunostaining. Mutations in p53 and PTEN, two important tumor suppressor genes, were recently demonstrated in canine HSA, and may play a role in the progression
of the disease.
Studies showed vascular endothelial growth factor (VEGF), one of the most potent angiogenic factors, to be elevated in the
plasma and effusions of dogs with HSA when compared to healthy dogs. Similarly splenic HSA samples showed overexpression of
angiopoietins, proteins playing a key role in the regulation of angiogenesis, when compared to normal canine spleen. Interestingly
endostatin, a negative modulator of angiogenesis, was found to be elevated in the serum of dogs with HSA. In vitro research outlined the capacity of HSA cells to produce many angiogenic factors, including VEGF and the potent basic fibroblastic
growth factor (bFGF). Furthermore, in vivo exposure to interleukin-12 (IL-12), a cytokine known to possess antiangiogenic properties, inhibited the growth of canine
HSA in immunodeficient mice.
Arising from endothelial cells, HSA may involve any tissue in the body. The four most frequent primary sites in dogs are the
spleen, heart (right atrium or auricle), skin or SQ tissues, and liver. In cats, the most common site is skin and SQ tissues,
followed by visceral organs. Many other primary sites are known to occur. Metastatic dissemination and local infiltration
occur early in the disease progression via local seeding following tumor rupture, or hematogenously. The most frequent sites
of metastasis are the omentum, liver, and lungs. Being one of sarcomas most commonly spreading to the CNS, HSA has been found
to cause brain metastasis detected in up to 15% of dogs on post-mortem examinations. Dermal and conjunctival HSA, possibly
UV-induced, are associated with a better prognosis and lower metastatic rate than other locations. In general, a more advanced
clinical stage predicts shorter survival times. When multiple sites are involved, it is often impossible to identify the primary
site, and the prognosis is guarded, although occasional responses to therapy are observed. In cats, visceral HSA appears to
be more frequently associated with metastasis than cutaneous and SQ disease, with 77% of cats having multifocal disease in