Title: Hemangiosarcoma

{{Short description|Cancer of blood vessel lining}}
{{more citations needed|date=August 2018}}
{{Infobox medical condition (new)
| name            = Hemangiosarcoma
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| image           = Splenic hemangiosarcoma.JPG
| caption         = Hemangiosarcoma of the spleen in a dog, removed after surgery
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| field           = [[Veterinary medicine]]
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'''Hemangiosarcoma''' is a rapidly growing, highly invasive variety of [[cancer]] that occurs almost exclusively in dogs, and only rarely in cats, horses, mice,&lt;ref&gt;{{Cite web|url=https://www.nlm.nih.gov/toxnet/index.html|title = Toxnet Has Moved}}&lt;/ref&gt; or humans ([[vinyl chloride]] toxicity). It is a [[sarcoma]] 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 &quot;[[angiosarcoma]]&quot;, when used without a modifier, usually refers to hemangiosarcoma.&lt;ref&gt;{{cite journal|title=Beta Adrenergic Signaling: A Targetable Regulator of Angiosarcoma and Hemangiosarcoma|year=2015|doi=10.3390/vetsci2030270|doi-access=free|last1=Dickerson|first1=Erin|last2=Bryan|first2=Brad|journal=Veterinary Sciences |volume=2|issue=3|pages=270–292|pmid=29061946|pmc=5644640}}&lt;/ref&gt; However, [[glomangiosarcoma]] (8710/3) and [[lymphangiosarcoma]] (9170/3) are distinct conditions (in humans).

==Dogs==
[[File:Hemangiosarcoma of skin.JPG|thumb|Hemangiosarcoma of the skin in a dog]]
Hemangiosarcoma is quite common in [[dog]]s, and more so in certain breeds including [[German Shepherd]]s and [[Golden Retriever]]s.&lt;ref name=Ettinger_1995&gt;{{cite book|author1=Ettinger, Stephen J. |author2=Feldman, Edward C. |title=Textbook of Veterinary Internal Medicine |edition=4th|publisher=W.B. Saunders Company|year=1995|isbn=0-7216-6795-3}}&lt;/ref&gt; It also occurs in [[cat]]s, but much more rarely. Dogs with hemangiosarcoma rarely show clinical signs until the tumor has become very large and has [[metastasize]]d. Typically, clinical signs are due to [[hypovolemia]] 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]], right [[heart]] base, or [[liver]], 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]] or [[right auricular appendage]]. Here it can cause right-sided [[heart failure]], [[Heart arrhythmia|arrhythmia]]s, [[pericardial effusion]], and [[cardiac tamponade]]. Hemangiosarcoma of the spleen or [[liver]] is the most common tumor to cause [[hemorrhage]] in the [[abdomen]].&lt;ref name=Morrison_1998&gt;{{cite book|author=Morrison, Wallace B.|title=Cancer in Dogs and Cats |url=https://archive.org/details/cancerindogscats0000morr |url-access=registration |edition=1st|publisher=Williams and Wilkins |year=1998|isbn=0-683-06105-4}}&lt;/ref&gt; Hemorrhage secondary to splenic and hepatic tumors can also cause ventricular [[arrhythmia]]s. Hemangiosarcoma of the [[skin]] 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 [[sunlight|sun]] exposure.&lt;ref name=Morrison_1998/&gt; Occasionally, hemangiosarcoma of the skin can be a metastasis from visceral hemangiosarcoma. Other sites the tumor may occur include [[bone]], [[kidney]]s, the [[Urinary bladder|bladder]], [[muscle]], the [[mouth]], and the [[central nervous system]].

===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.&lt;ref&gt;{{cite book|author=Nelson|display-authors=etal|title= Manual of Small Animal Internal Medicine|publisher=  Elsevier Mosby|location= St. Louis, Missouri |date=2005}}&lt;/ref&gt;

Most common clinical signs of visceral hemangiosarcoma include loss of appetite, [[Heart arrhythmia|arrhythmia]]s, weight loss, weakness, lethargy, collapse, pale [[mucous membranes]], and/or sudden death. An enlarged abdomen is often seen due to hemorrhage. Metastasis is most commonly to the liver, [[Greater omentum|omentum]], [[lung]]s, or [[brain]].

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.{{citation needed|date=May 2017}} The validity of this study is in dispute.&lt;ref&gt;Personal communication; Modiano, Sackmann&lt;/ref&gt;

===Clinicopathologic findings===
Hemangiosarcoma can cause a wide variety of hematologic and hemostatic abnormalities, including [[anemia]], thrombocytopenia&lt;ref&gt;{{Cite journal|last1=Ng|first1=C. Y.|last2=Mills|first2=J. N.|date=January 1985|title=Clinical and haematological features of haemangiosarcoma in dogs|journal=Australian Veterinary Journal|volume=62|issue=1|pages=1–4|doi=10.1111/j.1751-0813.1985.tb06029.x|issn=0005-0423|pmid=4039924}}&lt;/ref&gt; (low [[platelet]] count), [[disseminated intravascular coagulation]] (DIC); presence of nRBC, schistocytes, and acanthocytes in the blood smear; and leukocytosis with neutrophilia, left shift, and monocytosis.&lt;ref&gt;{{Cite journal |last1=Yamamoto |first1=Shinya |last2=Hoshi |first2=Katsuichiro |last3=Hirakawa |first3=Atsushi |last4=Chimura |first4=Syuuichi |last5=Kobayashi |first5=Masayuki |last6=Machida |first6=Noboru |date=2013 |title=Epidemiological, Clinical and Pathological Features of Primary Cardiac Hemangiosarcoma in Dogs: A Review of 51 Cases |url=https://www.jstage.jst.go.jp/article/jvms/advpub/0/advpub_13-0064/_article/-char/ja/ |journal=Journal of Veterinary Medical Science |volume=advpub |issue=11 |pages=13–0064 |doi=10.1292/jvms.13-0064|pmid=23811814 |pmc=3942993 }}&lt;/ref&gt;&lt;ref&gt;{{Cite journal |last1=Martins |first1=B. D. C. |last2=Torres |first2=B. B. J. |last3=Rodriguez |first3=A. a. M. |last4=Gamba |first4=C. O. |last5=Cassali |first5=G. D. |last6=Lavalle |first6=G. E. |last7=Martins |first7=G. D. C. |last8=Melo |first8=E. G. |date=April 2013 |title=Clinical and pathological aspects of multicentric hemangiosarcoma in a Pinscher dog |journal=Arquivo Brasileiro de Medicina Veterinária e Zootecnia |language=en |volume=65 |issue=2 |pages=322–328 |doi=10.1590/S0102-09352013000200003 |issn=0102-0935|doi-access=free }}&lt;/ref&gt;&lt;ref&gt;{{Cite journal |last1=Johannes |first1=Chad M. |last2=Henry |first2=Carolyn J. |last3=Turnquist |first3=Susan E. |last4=Hamilton |first4=Terrance A. |last5=Smith |first5=Annette N. |last6=Chun |first6=Ruthanne |last7=Tyler |first7=Jeff W. |date=2007-12-15 |title=Hemangiosarcoma in cats: 53 cases (1992–2002) |url=https://avmajournals.avma.org/view/journals/javma/231/12/javma.231.12.1851.xml |journal=Journal of the American Veterinary Medical Association |language=en |volume=231 |issue=12 |pages=1851–1856 |doi=10.2460/javma.231.12.1851|pmid=18081524 |doi-access=free }}&lt;/ref&gt;&lt;ref&gt;{{Cite journal |last=Smith |first=Annette N. |date=2003-05-01 |title=Hemangiosarcoma in dogs and cats |url=https://www.vetsmall.theclinics.com/article/S0195-5616(03)00002-0/abstract |journal=Veterinary Clinics: Small Animal Practice |language=English |volume=33 |issue=3 |pages=533–552 |doi=10.1016/S0195-5616(03)00002-0 |issn=0195-5616 |pmid=12852235|url-access=subscription }}&lt;/ref&gt;

===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 &quot;cytological diagnosis of splenic neoplasia is reliable, but a negative result cannot be used to exclude the possibility of splenic neoplasia.&quot;&lt;ref&gt;{{Cite journal|last1=Tecilla|first1=Marco|last2=Gambini|first2=Matteo|last3=Forlani|first3=Annalisa|last4=Caniatti|first4=Mario|last5=Ghisleni|first5=Gabriele|last6=Roccabianca|first6=Paola|date=2019-11-07|title=Evaluation of cytological diagnostic accuracy for canine splenic neoplasms: An investigation in 78 cases using STARD guidelines|journal=PLOS ONE|volume=14|issue=11|article-number=e0224945|doi=10.1371/journal.pone.0224945|issn=1932-6203|pmc=6837434|pmid=31697755|bibcode=2019PLoSO..1424945T|doi-access=free}}&lt;/ref&gt; This is because of frequent blood contamination and poor exfoliation.&lt;ref&gt;{{Cite journal|last=Sharma|first=Diya|date=August 2012|title=Hemangiosarcoma in a geriatric Labrador retriever|journal=The Canadian Veterinary Journal|volume=53|issue=8|pages=889–892|issn=0008-5286|pmc=3398530|pmid=23372199}}&lt;/ref&gt; Surgical biopsy is the typical approach in veterinary medicine.

Imaging modalities may include one ore more of ultrasound, CT, MRI&lt;ref&gt;{{Cite journal|last1=Carloni|first1=Andrea|last2=Terragni|first2=Rossella|last3=Morselli-Labate|first3=Antonio Maria|last4=Paninarova|first4=Michaela|last5=Graham|first5=John|last6=Valenti|first6=Paola|last7=Alberti|first7=Monica|last8=Albarello|first8=Giulia|last9=Millanta|first9=Francesca|last10=Vignoli|first10=Massimo|date=2019|title=Prevalence, distribution, and clinical characteristics of hemangiosarcoma-associated skeletal muscle metastases in 61 dogs: A whole body computed tomographic study|url= |journal=Journal of Veterinary Internal Medicine|language=en|volume=33|issue=2|pages=812–819|doi=10.1111/jvim.15456|issn=1939-1676|pmc=6430957|pmid=30793807}}&lt;/ref&gt;&lt;ref&gt;{{Cite journal|last1=Lee|first1=Mokhyeon|last2=Park|first2=Jiyoung|last3=Choi|first3=Hojung|last4=Lee|first4=Haebeom|last5=Jeong|first5=Seong Mok|date=November 2018|title=Presurgical assessment of splenic tumors in dogs: a retrospective study of 57 cases (2012–2017)|journal=Journal of Veterinary Science|volume=19|issue=6|pages=827–834|doi=10.4142/jvs.2018.19.6.827|issn=1229-845X|pmc=6265589|pmid=30173499}}&lt;/ref&gt; and FDG-PET/CT.&lt;ref&gt;{{Cite journal|last=|first=|date=2020-08-22|title=Characterization of canine hemangiosarcoma by 18F-Fluorodeoxyglucose Positron Emission Tomography|url=https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/79939/1/JJVR68-4_257-262_PreetiKumariChaudhary.pdf|journal=Japanese Journal of Veterinary Research|volume=|pages=|via=}}&lt;/ref&gt;&lt;ref name=&quot;:0&quot;&gt;{{Cite journal|last1=Borgatti|first1=Antonella|last2=Winter|first2=Amber L.|last3=Stuebner|first3=Kathleen|last4=Scott|first4=Ruth|last5=Ober|first5=Christopher P.|last6=Anderson|first6=Kari L.|last7=Feeney|first7=Daniel A.|last8=Vallera|first8=Daniel A.|last9=Koopmeiners|first9=Joseph S.|last10=Modiano|first10=Jaime F.|last11=Froelich|first11=Jerry|date=2017-02-21|title=Evaluation of 18-F-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) as a staging and monitoring tool for dogs with stage-2 splenic hemangiosarcoma – A pilot study|journal=PLOS ONE|language=en|volume=12|issue=2|article-number=e0172651|doi=10.1371/journal.pone.0172651|issn=1932-6203|pmc=5319762|pmid=28222142|bibcode=2017PLoSO..1272651B|doi-access=free}}&lt;/ref&gt; FGD-PET/CT may show some benefit over traditional CT for staging and detection of metastasis.&lt;ref name=&quot;:0&quot; /&gt;&lt;ref&gt;{{Cite journal|last1=Spriet|first1=Mathieu|last2=Willcox|first2=Jennifer L.|last3=Culp|first3=William T. N.|date=2019|title=Role of Positron Emission Tomography in Imaging of Non-neurologic Disorders of the Head, Neck, and Teeth in Veterinary Medicine|journal=Frontiers in Veterinary Science|language=English|volume=6|page=180|doi=10.3389/fvets.2019.00180|pmid=31245395|pmc=6579945|issn=2297-1769|doi-access=free}}&lt;/ref&gt;

===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.&lt;ref&gt;{{cite web |last1=Farricelli |first1=Adrienne |title=The Silent Killer: Hemangiosarcomas or a Ruptured, Bleeding Spleen in Dogs |url=https://pethelpful.com/dogs/Dog-Ruptured-Bleeding-Tumor-on-Spleen-the-Silent-Killer |website=PetHelpful |access-date=23 March 2019}}&lt;/ref&gt;

===Treatments===
Treatment includes [[chemotherapy]] and, where practical, removal of the tumor with the affected organ, such as with a [[splenectomy]]. Splenectomy alone gives an average survival time of 1–3 months. The addition of [[chemotherapy]], primarily comprising the drug [[doxorubicin]], 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]] (commonly known as &quot;Turkey Tail&quot;) mushroom showed a favorable response to the agent compared to historical controls of dogs treated with splenectomy and Doxorubicin .:.&lt;ref&gt;{{cite web|url=https://penntoday.upenn.edu/news/compound-derived-mushroom-lengthens-survival-time-dogs-cancer-penn-vet-study-finds |title=Compound Derived From a Mushroom Lengthens Survival Time in Dogs With Cancer, Penn Vet Study Finds|website=University of Pennsylvania|date=10 September 2012 }}&lt;/ref&gt; 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.:.&lt;ref&gt;{{cite journal|url=https://onlinelibrary.wiley.com/doi/10.1111/vco.12823|doi=10.1111/vco.12823 |title=Evaluation of the anti-tumour activity of Coriolus versicolor polysaccharopeptide (I'm-Yunity) alone or in combination with doxorubicin for canine splenic hemangiosarcoma |year=2022 |last1=Gedney |first1=Allison |last2=Salah |first2=Pascale |last3=Mahoney |first3=Jennifer A. |last4=Krick |first4=Erika |last5=Martins |first5=Reenie |last6=Scavello |first6=Heather |last7=Lenz |first7=Jennifer A. |last8=Atherton |first8=Matthew J. |journal=Veterinary and Comparative Oncology |volume=20 |issue=3 |pages=688–696 |pmid=35442554 |s2cid=248263381 |url-access=subscription }}&lt;/ref&gt;

Immune therapy based on cultivation of tumor tissue is being developed for dogs.&lt;ref&gt;{{cite journal |last1=Ludcroy &amp; al. |title=Evaluation of an autologous cancer vaccine for the treatment of metastatic canine hemangiosarcoma: a preliminary study |journal=BMC Veterinary Research |date=2020 |volume=16 |issue=1 |article-number=447 |doi=10.1186/s12917-020-02675-y |doi-access=free |pmid=33208160 |pmc=7672887 }}&lt;/ref&gt; A preventive vaccine based on several proteins commonly found in dog cancers, including hemangiosarcomas, is also being developed.&lt;ref&gt;{{cite web |title=Immunotherapy treatment |url=https://www.vet.cornell.edu/departments-centers-and-institutes/riney-canine-health-center/canine-health-information/immunotherapy-treatment |website=Riney Canine Health Center |publisher=Cornell University College of Veterinary |access-date=1 June 2023}}&lt;/ref&gt;

In the skin, it can be cured in most cases with complete surgical removal as long as there is not visceral involvement.&lt;ref name=&quot;Morrison_1998&quot; /&gt; Median survival times for stage I is 780 days, where more advanced stages can range from 172 to 307 days.&lt;ref&gt;{{Cite journal|last1=Ward|first1=H.|last2=Fox|first2=L. E.|last3=Calderwood-Mays|first3=M. B.|last4=Hammer|first4=A. S.|last5=Couto|first5=C. G.|date=September 1994|title=Cutaneous hemangiosarcoma in 25 dogs: a retrospective study|journal=Journal of Veterinary Internal Medicine|volume=8|issue=5|pages=345–348|doi=10.1111/j.1939-1676.1994.tb03248.x|issn=0891-6640|pmid=7837111}}&lt;/ref&gt;

==References==
{{reflist}}

== External links ==
{{Medical resources
|  DiseasesDB     = 
|  ICD10          = 
|  ICD9           = {{ICD9|155}}, others
|  ICDO           = 9120/3
|  OMIM           = 
|  MedlinePlus    = 
|  eMedicineSubj  = 
|  eMedicineTopic = 
|  MeshID         = D006394
}}
* {{cite web|url=http://www.petcancercenter.org/Cancer_Types_heart_hemangiosarcoma.html |title=Heart hemangiosarcoma in Cats and Dogs|website=Pet Cancer Center}}
* {{cite web|url=http://www.caninecancerawareness.org/html/CanineCancerHemangiosarcoma.html |website=Canine Cancer Awareness |title=Hemangiosarcoma}} - includes links to current studies
* {{cite web|url=http://www.marvistavet.com/html/body_hemangiosarcoma.html|website=Mar Vista Animal Medical Center|title=Hemangiosarcoma|access-date=2004-01-27|archive-url=https://web.archive.org/web/20040203051007/http://www.marvistavet.com/html/body_hemangiosarcoma.html|archive-date=2004-02-03}}
* {{cite web|url=http://www.petcancercenter.org/Cancer_Types_soft_tissue_hemangiosarcoma.html |title=Hemangiosarcoma in Cats and Dogs|website= Pet Cancer Center}}

{{Vascular tumors}}

[[Category:Vascular neoplasia]]
[[Category:Dog diseases]]
[[Category:Rare cancers]]
[[Category:Sarcoma]]
[[Category:Dermal and subcutaneous growths]]