Editing Angiosarcoma

{{Short description|Cancer of the lining of the blood or lymphatic vessels}}
{{Infobox medical condition (new)
| name          = Angiosarcoma
| synonyms      =
| image         = Metastatic angiosarcoma in the brain.jpg
| alt           =
| caption       = [[MRI]] of a cardiac angiosarcoma that has metastasised to the brain.
| pronounce     =
| field         = [[Oncology]]
| symptoms      = Often [[asymptomatic]], non-specific symptoms common
| complications =
| onset         = Typically 60-70 however all age groups are affected
| duration      =
| types         = [[Hemangiosarcoma]], [[lymphangiosarcoma]], parenchymal angiosarcoma
| causes        = Unknown
| risks         = [[Lymphedema]], [[radiation therapy]], various chemicals
| diagnosis     = [[Imaging]], [[biopsy]]
| differential  =
| prevention    =
| treatment     = [[Chemotherapy]], [[radiation therapy]], surgery
| medication    =
| prognosis     = Depends on type, overall [[five-year survival]] ~ 30-38%<ref name ="robbins">{{Cite book|title=Robbins Basic Pathology|publisher=Elsevier/Saunders|year=2013|isbn=978-1437717815|veditors=Kumar V, Abbas AK, Aster JC|edition=Ninth|pages=361–362}}</ref><ref name="project" /><ref name="Angiosarcoma" />
| frequency     = 1 per million people (US)<ref name="cancer.gov">{{Cite web|date=2019-02-27|title=Angiosarcoma - National Cancer Institute|url=https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-vascular-tumors/angiosarcoma|access-date=2021-08-08|website=www.cancer.gov|language=en}}</ref>
| deaths        =
}}

'''Angiosarcoma''' is a rare and aggressive [[cancer]] that starts in the [[endothelial]] cells that line the walls of [[blood vessel]]s or [[lymphatic vessel]]s. Since they are made from [[Endothelium|vascular lining]], they can appear anywhere and at any age, but older people are more commonly affected, and the [[Human skin|skin]] is the most affected area, with approximately 60% of cases being [[wikt:cutaneous|cutaneous]] (skin). Specifically, the [[scalp]] makes up ~50% of angiosarcoma cases, but this is still <0.1% of all head and neck tumors.<ref name=":0">{{Cite journal|last1=Cao|first1=Jun|last2=Wang|first2=Jiale|last3=He|first3=Chiyu|last4=Fang|first4=Meiyu|date=2019-11-01|title=Angiosarcoma: a review of diagnosis and current treatment|journal=American Journal of Cancer Research|volume=9|issue=11|pages=2303–2313|issn=2156-6976|pmc=6895451|pmid=31815036}}</ref><ref name=":1">{{Cite journal|last1=Zhang|first1=Chao|last2=Xu|first2=Guijun|last3=Liu|first3=Zheng|last4=Xu|first4=Yao|last5=Lin|first5=Feng|last6=Baklaushev|first6=Vladimir P.|last7=Chekhonin|first7=Vladimir P.|last8=Peltzer|first8=Karl|last9=Mao|first9=Min|last10=Wang|first10=Xin|last11=Wang|first11=Guowen|date=2019-12-27|title=Epidemiology, tumor characteristics and survival in patients with angiosarcoma in the United States: a population-based study of 4537 cases|journal=Japanese Journal of Clinical Oncology|volume=49|issue=12|pages=1092–1099|doi=10.1093/jjco/hyz113|issn=1465-3621|pmid=31612920|doi-access=free}}</ref><ref name="headtotoe" /> Since angiosarcoma is an [[Hyponymy and hypernymy|umbrella term]] for many types of tumor that vary greatly in origin and location, many symptoms may occur, from completely asymptomatic to non-specific symptoms like [[Skin condition|skin lesions]], [[Ulcer (dermatology)|ulceration]], [[shortness of breath]] and [[abdominal pain]]. Multiple-organ involvement at time of diagnosis is common and makes it difficult to ascertain origin and how to treat it.<ref name="headtotoe" />

The cause of angiosarcoma is not known, though several [[risk factor]]s are known, such as chronic [[lymphedema]], [[radiation therapy]] and various chemicals such as [[arsenic]] and [[vinyl chloride]]. Angiosarcomas have been reported in association with long standing foreign bodies.<ref>{{Cite journal |last1=Hayman |first1=J |last2=Huygens |first2=H |date=1983-05-01 |title=Angiosarcoma developing around a foreign body. |journal=Journal of Clinical Pathology |language=en |volume=36 |issue=5 |pages=515–518 |doi=10.1136/jcp.36.5.515 |issn=0021-9746 |pmc=498277 |pmid=6404947}}</ref><ref>{{Cite journal |last1=Schneider |first1=Tim |last2=Renney |first2=John |last3=Hayman |first3=John |date=August 1997 |title=Angiosarcoma occurring with chronic osteomyelitis and residual foreign material. A case report of a late World War wound complication. |journal=ANZ Journal of Surgery |language=en |volume=67 |issue=8 |pages=576–578 |doi=10.1111/j.1445-2197.1997.tb02045.x |issn=1445-1433|doi-access=free }}</ref> Infrequently they have occurred in association with breast implants.<ref>{{Cite journal |last1=Russo |first1=Daniela |last2=Campanino |first2=Maria Raffaela |last3=Cepurnaite |first3=Rima |last4=Gencarelli |first4=Annarita |last5=De Rosa |first5=Filippo |last6=Corvino |first6=Antonio |last7=Menkulazi |first7=Marsela |last8=Tammaro |first8=Vincenzo |last9=Fuggi |first9=Mariano |last10=Insabato |first10=Luigi |date=December 2020 |title=Primary High-Grade Angiosarcoma of the Breast in a Young Woman With Breast Implants: A Rare Case and a Review of Literature |url=http://journals.sagepub.com/doi/10.1177/1066896920924087 |journal=International Journal of Surgical Pathology |language=en |volume=28 |issue=8 |pages=906–912 |doi=10.1177/1066896920924087 |pmid=32423273 |issn=1066-8969|url-access=subscription }}</ref> [[Ultraviolet|Ultraviolet radiation]]<ref name="project" /> and [[Immunodeficiency|localized immunodeficiency]] may play a role in [[pathogenesis]] of angiosarcoma.<ref name="Angiosarcoma" /> Angiosarcoma can be seen on [[Magnetic resonance imaging|MRI]], [[CT scan|CT]] and [[Medical ultrasound|ultrasound]] scans, but it is usually difficult to discern it from other cancers, requiring confirmation of diagnosis by [[biopsy]] and [[Immunohistochemistry|immunohistochemical analysis]].

Treatment includes [[Surgical oncology|surgery]], [[chemotherapy]] and [[radiation therapy]], usually all three combined. Because these cancers arise from the [[Endothelium|cells lining the blood or lymphatic vessels]], they can easily [[Metastasis|metastasize]] to distant sites, particularly the [[liver]] and [[lung]]s.<ref name="headtotoe">{{cite journal|vauthors=Gaballah AH, Jensen CT, Palmquist S, Pickhardt PJ, Duran A, Broering G, Elsayes KM|date=July 2017|title=Angiosarcoma: clinical and imaging features from head to toe|journal=Br J Radiol|volume=90|issue=1075|pages=20170039|doi=10.1259/bjr.20170039|pmc=5594986|pmid=28471264}}</ref> This makes them especially lethal, and an early diagnosis is usually necessary for survival. Even with treatment, prognosis is poor, with a [[five-year survival rate]] of 30–38%.<ref name="robbins" /><ref name="Angiosarcoma" /> This is even worse in cardiac angiosarcoma and angiosarcoma of the liver, where [[prognosis]] may be as low as three months.<ref name="headtotoe" />

Angiosarcomas make up 1–2% of [[Soft-tissue sarcoma|soft tissue sarcomas]], which in turn make up less than 1% of adult cancer.<ref name="project" /> Due to this, no large studies have ever been published on the disease, with few exceeding even 100 patients; however, many [[case report]]s and small [[Cohort study|cohort studies]] have been published, and they cumulatively provide enough information to get a useful understanding of the disease.<ref name="headtotoe" /> The rate of angiosarcoma is increasing in the US.<ref name=":1" />

== Classification ==
The classification of angiosarcoma is based on both its origin and the underlying [[risk factor]]s that may have contributed.<ref name="headtotoe" /> This is not a comprehensive list and case reports often go into further depth.<ref name="Angiosarcoma">{{Cite journal|last1=Young|first1=Robin J.|last2=Brown|first2=Nicola J.|last3=Reed|first3=Malcolm W.|last4=Hughes|first4=David|last5=Woll|first5=Penella J.|date=October 2010|title=Angiosarcoma|url=https://pubmed.ncbi.nlm.nih.gov/20537949/|journal=The Lancet. Oncology|volume=11|issue=10|pages=983–991|doi=10.1016/S1470-2045(10)70023-1|issn=1474-5488|pmid=20537949}}</ref>

=== Primary cutaneous angiosarcoma ===
Angiosarcoma in the [[Human skin|skin]] (usually the [[Human head|head]] or [[neck]] and specifically the [[scalp]]) with no underlying risk factors such as [[lymphedema]] or [[radiation therapy]].{{citation needed|date=October 2021}}

=== Lymphedema associated angiosarcoma ===
Also called [[Stewart–Treves syndrome|Stewart-Treves syndrome]], it is a [[lymphangiosarcoma]] resulting from chronic [[lymphedema]], swelling due to the build up of [[Lymph|lymphatic fluid]]. It typically happens in the breast following a [[mastectomy]] that removes the [[lymph node]]s of the breast. However it can happen anywhere.<ref name="Angiosarcoma" /><ref name="headtotoe" />

=== Parenchymal angiosarcoma ===
Angiosarcoma in [[Parenchyma|parenchymal organs]] such as the [[liver]], [[breast]] or [[heart]]. These makes up about 40% of angiosarcoma.{{citation needed|date=October 2021}}

==== Primary breast angiosarcoma ====
This refers to angiosarcoma of the breast [[Idiopathic disease|without underlying causes]] such as [[radiation therapy]] or [[lymphedema]]. It is rare and makes up only 0.04% of [[Breast cancer|breast tumors]] and 8% of breast [[sarcoma]]s. It is very aggressive, usually presents in younger females and is often noticeable by a [[Palpation|palpable]] mass. Prognosis is poor with a five-year survival between 8 and 50%.<ref name="headtotoe" />

==== Secondary breast angiosarcoma ====
These are angiosarcoma that arise in the [[breast]] from [[Risk factor|underlying causes]] such as [[lymphedema]] or radiation, usually from [[radiation therapy]] for [[breast cancer]]. The link between radiation therapy and angiosarcoma has been disputed by some who profess the angiosarcoma is caused by concurrent lymphedema. Secondary breast angiosarcoma tends to have a bad prognosis. Radiation-associated angiosarcoma has a five-year survival of 10 to 54%. Distant [[Metastasis|metastases]] are present in 27–42% of individuals and is associated with a far worse prognosis. Other prognostic factors include size of tumor, [[Ageing|age]] and how much can be removed by surgery.<ref name="Angiosarcoma" /><ref name="headtotoe" />

==== Primary brain angiosarcoma ====
Primary brain angiosarcoma are angiosarcoma that arise in the brain (i.e. not metastasised from elsewhere). They are exceedingly rare with only a few cases reported. Imaging is non specific and differential diagnosis includes most other brain tumors such as [[glioma]]s or [[Cavernous hemangioma|cavernomas]],<ref name="Angiosarcoma" /> requiring biopsy to confirm diagnosis, usually after surgery. Prognosis is generally poor with a median survival rate of eight months. However it varies greatly depending on whether or not the tumor has metastasised, some individuals may be rid of the disease following surgery, chemotherapy and radiation therapy.<ref>{{Cite journal|last1=La Corte|first1=Emanuele|last2=Acerbi|first2=Francesco|last3=Schiariti|first3=Marco|last4=Broggi|first4=Morgan|last5=Maderna|first5=Emanuela|last6=Pollo|first6=Bianca|last7=Nunziata|first7=Raffaele|last8=Maccagnano|first8=Elio|last9=Ferroli|first9=Paolo|date=April 2015|title=Primary central nervous system angiosarcoma: a case report and literature review|url=https://pubmed.ncbi.nlm.nih.gov/25388456/|journal=Neuropathology |volume=35|issue=2|pages=184–191|doi=10.1111/neup.12178|issn=1440-1789|pmid=25388456|s2cid=21199506}}</ref>

==== Primary cardiac angiosarcoma ====
Primary cardiac angiosarcoma is an angiosarcoma that arises in the [[heart]]. Despite being very rare they are the most common malignant [[Primary tumors of the heart|primary heart tumor]] with 10–25%<ref name=":2">{{Cite journal|last1=Patel|first1=Swetal Dilip|last2=Peterson|first2=Ashley|last3=Bartczak|first3=Artur|last4=Lee|first4=Sarah|last5=Chojnowski|first5=Sławomir|last6=Gajewski|first6=Piotr|last7=Loukas|first7=Marios|date=2014|title=Primary cardiac angiosarcoma – a review|journal=Medical Science Monitor|language=en|volume=20|pages=103–109|doi=10.12659/MSM.889875|pmid=24452054|pmc=3907509}}</ref><ref name="Angiosarcoma" /> of cases being angiosarcomas. Symptoms may include shortness of breath, chest pain (46%<ref name=":2" />), [[hypotension]] and [[Syncope (medicine)|syncope]]. [[Superior vena cava syndrome]] is reportedly a [[Complication (medicine)|complication]] of cardiac angiosarcoma.<ref name="headtotoe" /> Due to the non-specificity of symptoms and rarity of the disease it is often missed by doctors and initial diagnosis may be delayed. A 2012 study reported that 56% of patients presented with [[pericardial effusion]] with or without [[cardiac tamponade]].<ref name=":2" /> The most common finding on [[Medical imaging|imaging]] is [[cardiomegaly]]. Prognosis is generally very poor with a mean survival rate of three months to four years following diagnosis.<ref name="headtotoe" /> Metastasis at time of diagnosis is common.<ref name=":2" />

==== Primary liver angiosarcoma ====
{{Main|Liver angiosarcoma}}
Primary angiosarcoma of the liver is the third most common type of [[liver cancer]] however it only makes up 0.1–2.0% of all liver cancers. It is rapidly fatal with most individuals dying within six months or a year even with [[Segmental resection|surgical resection]]. Despite being associated with [[arsenic]], [[vinyl chloride]], [[thorotrast]] and other chemicals, 75% of liver angiosarcomas have [[Idiopathic disease|no known cause]]. Men are more commonly affected in a ratio of 3–4:1 however in children girls are more often affected. If symptomatic it often presents with non-specific liver related symptoms such as [[abdominal pain]], [[jaundice]], [[fatigue]], [[Weight loss|unintended weight loss]] and [[Abdominal distension|distension]].<ref name=":3" />

=== Deep soft tissue angiosarcoma ===
Angiosarcoma in the deep [[soft tissue]] such as [[adipose tissue]], [[ligament]]s or [[Skeletal muscle|muscles]]. These make up about 10% of angiosarcoma.{{citation needed|date=October 2021}}

== Signs and symptoms ==
[[File:Three types of scalp angiosarcoma.jpg|thumb|Three different types of scalp angiosarcoma. (a) ulcer type (b) bruise type (c) nodular type]]
Cutaneous angiosarcoma may initially look like a [[bruise]] or a purplish-red [[papule]]. It may look like a [[benign tumor]] which can delay correct diagnosis and treatment. [[Fungating lesion|Fungation]], [[Ulcer (dermatology)|ulceration]] and [[bleeding]] may develop.<ref name="Angiosarcoma" />

Cardiac angiosarcoma may present with [[shortness of breath]], [[chest pain]] (46%), [[Unintentional weight loss|weight loss]], [[anemia]]-like symptoms,<ref name=":2" /> [[Hypotension|low blood pressure]] and [[Syncope (medicine)|syncope]].<ref name="headtotoe" />

Angiosarcomas principally metastasises through the blood with the most common site for metastasis being the lungs; this may present as [[pleural effusion]], [[pneumothorax]] or other pleural disease. Other common sites of metastasis include the liver, bone and lymph nodes.<ref name="Angiosarcoma" />

== Causes ==
Angiosarcoma develops when damage to the [[DNA]] of [[Endothelium|endothelial cells]] causes them to [[Cell proliferation|divide uncontrollably]] and prevents [[Programmed cell death|programmed death]]. This allows them to grow into a [[Neoplasm|mass]] invading other parts of the body and consuming its resources. If part of the mass breaks off and enters the [[Circulatory system|circulatory]] or [[lymphatic system]] (which is very common due to angiosarcomas arising from the [[Endothelium|lining]] of said systems) it allows them to lodge elsewhere in the body. This process is called [[metastasis]] and is a negative prognostic factor.<ref>{{Cite web|date=2007-09-17|title=What Is Cancer? - National Cancer Institute|url=https://www.cancer.gov/about-cancer/understanding/what-is-cancer|access-date=2021-08-09|website=www.cancer.gov|language=en}}</ref> The underlying causes of DNA damage is not understood but several risk factors are widely accepted.{{citation needed|date=October 2021}}

Accepted risk factors include [[lymphedema]], [[radiation therapy]], [[neurofibromatosis]], [[Maffucci syndrome]], [[Klippel–Trénaunay syndrome|Klippel-Trenaunay syndrome]]<ref name="Angiosarcoma" /> and chemicals such as [[arsenic]], [[thorotrast]] and [[vinyl chloride]].<ref name="cancer.gov" />

A 2020 study analyzing the [[genome]] of cutaneous angiosarcomas suggests that [[Ultraviolet|ultraviolet radiation]] may be a [[Carcinogen|causative agent]] of angiosarcomas.<ref name="project">{{Cite journal|last1=Painter|first1=Corrie A.|last2=Jain|first2=Esha|last3=Tomson|first3=Brett N.|last4=Dunphy|first4=Michael|last5=Stoddard|first5=Rachel E.|last6=Thomas|first6=Beena S.|last7=Damon|first7=Alyssa L.|last8=Shah|first8=Shahrayz|last9=Kim|first9=Dewey|last10=Gómez Tejeda Zañudo|first10=Jorge|last11=Hornick|first11=Jason L.|date=February 2020|title=The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research|url=https://pubmed.ncbi.nlm.nih.gov/32042194/|journal=Nature Medicine|volume=26|issue=2|pages=181–187|doi=10.1038/s41591-019-0749-z|issn=1546-170X|pmid=32042194|s2cid=211074464}}</ref>

[[Immunosuppression]] may play a role in the [[pathogenesis]] of angiosarcoma. There have been reports of angiosarcoma in [[Immunosuppression|immunosuppressed]] individuals following [[kidney transplantation]]. The association between lymphedema and angiosarcoma may be due to localized [[immunodeficiency]], however this [[hypothesis]] has not been confirmed. Some studies suggest a link between [[HIV/AIDS|AIDS]] and angiosarcoma though this may be due to [[Medical error|misdiagnosed]] [[Kaposi's sarcoma]].<ref name="Angiosarcoma" />

== Diagnosis ==
[[File:Cutaneous angiosarcoma (4) CD31.jpg|left|thumb|[[Immunostaining|Immunostained]] [[CD31]] in a cutaneous angiosarcoma]]
The diagnosis of angiosarcoma can be difficult due to its asymptomatic nature or non-specific symptoms. Initial diagnosis is typically done by [[Magnetic resonance imaging|MRI]], [[CT scan|CT]] or [[Medical ultrasound|ultrasound]] scan, however it is typically difficult to discern if a [[Neoplasm|mass]] is an angiosarcoma or other type of tumor such as a [[melanoma]] or [[carcinoma]]. This means that while the initial diagnosis is typically done via imaging, conclusive diagnosis has to be performed via biopsy and subsequent [[Histology|histological]] and [[Immunohistochemistry|immunohistochemical analysis]].<ref name=":0" />

The [[Tumor marker|marker]] [[CD31]] is often considered the gold standard for angiosarcoma diagnosis due to its high sensitivity and specificity. Other [[Tumor marker|markers]] typically used include [[von Willebrand factor]], [[CD34]], and [[vascular endothelial growth factor]].<ref name=":0" /> The absence of [[Tumor marker|markers]] present in [[melanoma]]s such as [[S100 protein|S100]] and [[HMB-45]] can help in differentiating angiosarcomas from [[melanoma]]s.<ref name="Angiosarcoma" />

== Epidemiology ==
Angiosarcomas are rare with one in a million people being diagnosed with it each year in the US.<ref name="cancer.gov" /> Older adults are more commonly affected and there is no gender bias,<ref name="robbins" /> except in angiosarcoma of the liver where males are affected in a ratio of 3-4:1<ref name=":3">{{Citation|last1=Kumar|first1=Anila|title=Liver Angiosarcoma|date=2021|url=http://www.ncbi.nlm.nih.gov/books/NBK538224/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=30855812|access-date=2021-08-08|last2=Sharma|first2=Bashar|last3=Samant|first3=Hrishikesh}}</ref> and cutaneous angiosarcoma where males are again affected more commonly, particularly elderly white men.<ref name="Angiosarcoma" /><ref name="headtotoe" />

== Other animals ==
In dogs, [[hemangiosarcoma]] is relatively common with the [[golden retriever]], [[Boxer (dog)|boxer]] and [[Labrador Retriever|labrador retriever]] at higher risk of the disease than other breeds. It occurs primarily in the [[spleen]], [[liver]], [[heart]], [[skin]] and [[Subcutaneous tissue|subcutaneous layer of the skin]]. It is rapidly fatal and [[Metastasis|metastatic]] and can present with anything from [[Nonspecific symptom|nonspecific signs]] to imminent death from tumor rupture.<ref name="Gustafson 2018">{{cite journal | vauthors = Gustafson DL, Duval DL, Regan DP, Thamm DH | title = Canine sarcomas as a surrogate for the human disease | journal = Pharmacol Ther | volume = 188 | issue = | pages = 80–96 | date = August 2018 | pmid = 29378221 | pmc = 6432917 | doi = 10.1016/j.pharmthera.2018.01.012 }}</ref>

==See also==
* [[Glomangiosarcoma]]
* [[List of cutaneous conditions]]

==References==
{{Reflist}}

{{Medical resources
|  DiseasesDB      =
|  ICD10           = C49.9
|  ICD9            =
|  ICDO            = {{ICDO|9120|3}}
|  OMIM            =
|  MedlinePlus     =
|  eMedicineSubj   = med <!-- deprecated parameter -->
|  eMedicineTopic  = 138 <!-- deprecated parameter -->
|  MeSH            = D006394
|  GeneReviewsNBK  =
|  GeneReviewsName =
|  Orphanet        = 263413
}}

{{Vascular tumors}}
{{Authority control}}

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