Haemangiosarcoma
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Hemangiosarcoma is a rapidly growing, highly invasive variety of
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
that occurs almost exclusively in dogs, and only rarely in cats, horses, mice, or humans (
vinyl chloride Vinyl chloride is an organochloride with the formula H2C =CHCl. It is also called vinyl chloride monomer (VCM) or chloroethene. It is an important industrial chemical chiefly used to produce the polymer polyvinyl chloride (PVC). Vinyl chloride is a ...
toxicity). It is a
sarcoma A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues. Sarcom ...
arising from the lining of blood vessels; that is, blood-filled channels and spaces are commonly observed microscopically. A frequent cause of death is the rupturing of this tumor, causing the patient to rapidly bleed to death. The term "
angiosarcoma Angiosarcoma is a rare and aggressive cancer that starts in the endothelial cells that line the walls of blood vessels or lymphatic vessels. Since they are made from Endothelium, vascular lining, they can appear anywhere and at any age, but older ...
", when used without a modifier, usually refers to hemangiosarcoma. However,
glomangiosarcoma Glomangiosarcoma is a low grade tumor of the soft tissue. They rarely metastasize, but metastases are possible. It is also known as malignant glomus tumor. Positive staining for vimentin has been reported. Signs and symptoms Glomangiosarcoma u ...
(8710/3) and
lymphangiosarcoma Lymphangiosarcoma is a rare cancer which occurs in long-standing cases of primary or secondary lymphedema (swelling due to lymphatic system obstruction). It involves either the upper or lower lymphedematous extremities but is most common in upper ...
(9170/3) are distinct conditions (in humans).


Dogs

Hemangiosarcoma is quite common in
dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the gray wolf. Also called the domestic dog, it was selectively bred from a population of wolves during the Late Pleistocene by hunter-gatherers. ...
s, and more so in certain breeds including
German Shepherd The German Shepherd, also known in Britain as an Alsatian, is a German Dog breed, breed of working dog of medium to large size. The breed was developed by Max von Stephanitz using various Old German herding dogs, traditional German herding dog ...
s and Golden Retrievers. It also occurs in
cat The cat (''Felis catus''), also referred to as the domestic cat or house cat, is a small domesticated carnivorous mammal. It is the only domesticated species of the family Felidae. Advances in archaeology and genetics have shown that the ...
s, but much more rarely. Dogs with hemangiosarcoma rarely show clinical signs until the tumor has become very large and has
metastasize Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
d. Typically, clinical signs are due to
hypovolemia Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the loss ...
after the tumor ruptures, causing extensive bleeding. Owners of the affected dogs often discover that the dog has hemangiosarcoma only after the dog collapses. The tumor most often appears on the
spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
, right
heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
base, or
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
, although varieties also appear on or under the skin or in other locations. It is the most common tumor of the heart, and occurs in the
right atrium The atrium (; : atria) is one of the two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular mitral and tricuspid heart valves. ...
or right auricular appendage. Here it can cause right-sided
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
,
arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...
s,
pericardial effusion A pericardial effusion is an abnormal accumulation of fluid in the pericardial cavity. The pericardium is a two-part membrane surrounding the heart: the outer fibrous Connective tissue, connective membrane and an inner two-layered serous membrane ...
, and
cardiac tamponade Cardiac tamponade, also known as pericardial tamponade (), is a compression of the heart due to pericardial effusion (the build-up of pericardial fluid in the pericardium, sac around the heart). Onset may be rapid or gradual. Symptoms typically i ...
. Hemangiosarcoma of the spleen or
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
is the most common tumor to cause
hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...
in the
abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
. Hemorrhage secondary to splenic and hepatic tumors can also cause ventricular
arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...
s. Hemangiosarcoma of the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
usually appears as a small red or bluish-black lump. It can also occur under the skin. It is suspected that in the skin, hemangiosarcoma is caused by
sun The Sun is the star at the centre of the Solar System. It is a massive, nearly perfect sphere of hot plasma, heated to incandescence by nuclear fusion reactions in its core, radiating the energy from its surface mainly as visible light a ...
exposure. Occasionally, hemangiosarcoma of the skin can be a metastasis from visceral hemangiosarcoma. Other sites the tumor may occur include
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
,
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s, the
bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the bladder is a distens ...
,
muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...
, the
mouth A mouth also referred to as the oral is the body orifice through which many animals ingest food and animal communication#Auditory, vocalize. The body cavity immediately behind the mouth opening, known as the oral cavity (or in Latin), is also t ...
, and the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
.


Clinical features

Presenting complaints and clinical signs are usually related to the site of origin of the primary tumor or to the presence of metastases, spontaneous tumor rupture, coagulopathies, or cardiac arrhythmias. More than 50% of patients are presented because of acute collapse after spontaneous rupture of the primary tumor or its metastases. Some episodes of collapse are a result of ventricular arrhythmias, which are relatively common in dogs with splenic or cardiac HSA. Most common clinical signs of visceral hemangiosarcoma include loss of appetite,
arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...
s, weight loss, weakness, lethargy, collapse, pale
mucous membranes A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
, and/or sudden death. An enlarged abdomen is often seen due to hemorrhage. Metastasis is most commonly to the liver, omentum,
lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
s, or
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
. A retrospective study published in 1999 by Ware, et al., found a five times greater risk of cardiac hemangiosarcoma in spayed vs. intact female dogs and a 2.4 times greater risk of hemangiosarcoma in neutered dogs as compared to intact males. The validity of this study is in dispute.


Clinicopathologic findings

Hemangiosarcoma can cause a wide variety of hematologic and hemostatic abnormalities, including
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
, thrombocytopenia (low
platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
count),
disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking Microvessel, small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems ...
(DIC); presence of nRBC, schistocytes, and acanthocytes in the blood smear; and leukocytosis with neutrophilia, left shift, and monocytosis.


Diagnosis

A definitive diagnosis requires biopsy and histopathology. Cytologic aspirates may be inconclusive with studies reporting various specificity, and negative results may not correlate with absence of disease, as one study concludes "cytological diagnosis of splenic neoplasia is reliable, but a negative result cannot be used to exclude the possibility of splenic neoplasia." This is because of frequent blood contamination and poor exfoliation. Surgical biopsy is the typical approach in veterinary medicine. Imaging modalities may include one ore more of ultrasound, CT, MRI and FDG-PET/CT. FGD-PET/CT may show some benefit over traditional CT for staging and detection of metastasis.


Symptoms

Dogs rarely show symptoms of hemangiosarcoma until after the tumor ruptures, causing extensive bleeding. Then symptoms can include short-term lethargy, loss of appetite, enlarged abdomen, weakness in the back legs, paled colored tongue and gums, rapid heart rate, and a weak pulse.


Treatments

Treatment includes
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
and, where practical, removal of the tumor with the affected organ, such as with a
splenectomy A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal of ...
. Splenectomy alone gives an average survival time of 1–3 months. The addition of
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
, primarily comprising the drug
doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...
, alone or in combination with other drugs, can increase the average survival time by 2–4 months beyond splenectomy alone. A 2012 paper published the University of Pennsylvania Veterinary School, in dogs treated with a compound derived from the
Coriolus versicolor ''Trametes versicolor''also known as ''Coriolus versicolor'' and ''Polyporus versicolor''is a common polypore mushroom found throughout the world. Owing to its shape being similar to that of a wild turkey's tail feathers, ''T. versicolor' ...
(commonly known as "Turkey Tail") mushroom showed a favorable response to the agent compared to historical controls of dogs treated with splenectomy and Doxorubicin .:. A controlled, randomized study in 101 dogs was later conducted by the University of Pennsylvania Veterinary School which showed that the Coriolus versicolor mushroom did not have the same outcome noted in the 2012 paper with 15 dogs. In the 2022 paper by Gednet et al. dogs treated with splenectomy followed by Doxorubicin did better than dogs treated with splenectomy and mushroom agent. Combination of Doxorubicin with the Turkey Tail mushroom also did not improve survival when compared to Doxorubicin alone. However, as noted in the 2012 study, the Turkey Tail mushroom extract did not cause any systemic adverse reactions, even when combined with Doxorubicin.:. Immune therapy based on cultivation of tumor tissue is being developed for dogs. A preventive vaccine based on several proteins commonly found in dog cancers, including hemangiosarcomas, is also being developed. In the skin, it can be cured in most cases with complete surgical removal as long as there is not visceral involvement. Median survival times for stage I is 780 days, where more advanced stages can range from 172 to 307 days.


References


External links

* * - includes links to current studies * * {{Vascular tumors Vascular neoplasia Dog diseases Rare cancers Sarcoma Dermal and subcutaneous growths