Difference between revisions of "Angiosarcoma"

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(Natural History, Complications and Prognosis)
(Treatment)
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{{SK}}  Hemangiosarcoma; Pulmonary angiosarcoma; Vascular sarcoma  
 
{{SK}}  Hemangiosarcoma; Pulmonary angiosarcoma; Vascular sarcoma  
 
==Overview==
 
==Overview==
'''Angiosarcoma''' is a rare [[malignant]] vascular [[neoplasm]] of [[endothelial]]-type cells that line vessel walls. The peak age of incidence appears to be the 7th decade, and men are affected more than women.  Angiosarcoma was first described by Dr. Juan Rosai, in 1976. The pathogenesis of angiosarcoma is characterized by a rapid and extensively infiltrating overgrowth of vascular [[epithelial]] cells. Angiosarcoma may arise in any part of the body, but is more common in soft tissue than in bone. Common angiosarcoma locations include the  head and neck area, [[kidney]], [[liver]], [[lung]], and and the most common site of radiation-induced angiosarcoma development is the breast.  The [[PTPRB]]/[[Phospholipase C|PLCG1]] [[genes]] are associated with the development of angiosarcoma; [[mutation]] of these genes result in aberrant [[angiogenesis]]. The imaging modality of choice for diagnosing angiosarcoma will depend on the location. For [[pulmonary]] angiosarcoma, the imaging modality of choice is enhanced CT scan. For other types angiosarcoma, the imaging modality of choice is MRI. On CT scan, findings suggestive of angiosarcoma may include vascular invasion, nodular enhancement (common), and a hypoattenuating mass. The mainstay [[adjuvant therapy]] for angiosarcoma is a [[doxorubicin]]-based regimen. The response rate for [[chemotherapy]] in patients with angiosarcoma is poor.
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'''Angiosarcoma''' is a rare [[malignant]] vascular [[neoplasm]] of [[endothelial]]-type cells that line [[Vessel wall|vessel walls]]. The peak age of [[incidence]] appears to be the 7th decade, and men are affected more than women.  Angiosarcoma was first described by Dr. Juan Rosai, in 1976. The [[pathogenesis]] of angiosarcoma is characterized by a rapid and extensively infiltrating overgrowth of [[vascular]] [[epithelial]] cells. Angiosarcoma may arise in any part of the body, but is more common in [[soft tissue]] than in bone. Common angiosarcoma locations include the  head and neck area, [[kidney]], [[liver]], [[lung]], and and the most common site of [[radiation]]-induced angiosarcoma development is the [[breast]].  The [[PTPRB]]/[[Phospholipase C|PLCG1]] [[genes]] are associated with the development of angiosarcoma; [[mutation]] of these genes result in aberrant [[angiogenesis]]. The imaging modality of choice for [[Diagnose|diagnosing]] angiosarcoma will depend on the location. For [[pulmonary]] angiosarcoma, the imaging modality of choice is enhanced [[CT scan]]. For other types angiosarcoma, the imaging modality of choice is [[MRI]]. On [[CT scan]], findings suggestive of angiosarcoma may include [[vascular]] [[invasion]], nodular enhancement (common), and a hypoattenuating [[mass]]. The mainstay [[adjuvant therapy]] for angiosarcoma is a [[doxorubicin]]-based regimen. The response rate for [[chemotherapy]] in patients with angiosarcoma is poor.
 
==Historical Perspective==
 
==Historical Perspective==
 
[[Angiosarcoma]] was first discovered by Dr. Juan Rosai, M.D. and colleagues in 1976.<ref name="pmid24946325">{{cite journal |vauthors=Barber W, Scriven P, Turner D, Hughes D, Wyld D |title=Epithelioid angiosarcoma: Use of angiographic embolisation and radiotherapy to control recurrent haemorrhage |journal=J Surg Case Rep |volume=2010 |issue=5 |pages=7 |year=2010 |pmid=24946325 |pmc=3649120 |doi=10.1093/jscr/2010.5.7 |url=}}</ref>  
 
[[Angiosarcoma]] was first discovered by Dr. Juan Rosai, M.D. and colleagues in 1976.<ref name="pmid24946325">{{cite journal |vauthors=Barber W, Scriven P, Turner D, Hughes D, Wyld D |title=Epithelioid angiosarcoma: Use of angiographic embolisation and radiotherapy to control recurrent haemorrhage |journal=J Surg Case Rep |volume=2010 |issue=5 |pages=7 |year=2010 |pmid=24946325 |pmc=3649120 |doi=10.1093/jscr/2010.5.7 |url=}}</ref>  
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*The up-regulation of these [[genes]] and [[over-expression]] of [[vascular]] [[endothelial]] [[growth factor receptors]] can cause [[endothelial cell]] expansion, [[angiogenesis]], and also vascular leaks in the structure of vessels. <ref name="pmid14746640">{{cite journal |vauthors=Amo Y, Masuzawa M, Hamada Y, Katsuoka K |title=Serum concentrations of vascular endothelial growth factor-D in angiosarcoma patients |journal=Br. J. Dermatol. |volume=150 |issue=1 |pages=160–1 |date=January 2004 |pmid=14746640 |doi=10.1111/j.1365-2133.2004.05751.x |url=}}</ref><ref name="pmid20008140">{{cite journal |vauthors=Manner J, Radlwimmer B, Hohenberger P, Mössinger K, Küffer S, Sauer C, Belharazem D, Zettl A, Coindre JM, Hallermann C, Hartmann JT, Katenkamp D, Katenkamp K, Schöffski P, Sciot R, Wozniak A, Lichter P, Marx A, Ströbel P |title=MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema |journal=Am. J. Pathol. |volume=176 |issue=1 |pages=34–9 |date=January 2010 |pmid=20008140 |pmc=2797867 |doi=10.2353/ajpath.2010.090637 |url=}}</ref><ref name="pmid20949568">{{cite journal |vauthors=Guo T, Zhang L, Chang NE, Singer S, Maki RG, Antonescu CR |title=Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions |journal=Genes Chromosomes Cancer |volume=50 |issue=1 |pages=25–33 |date=January 2011 |pmid=20949568 |pmc=3150534 |doi=10.1002/gcc.20827 |url=}}</ref><ref name="pmid22121953">{{cite journal |vauthors=Fernandez AP, Sun Y, Tubbs RR, Goldblum JR, Billings SD |title=FISH for MYC amplification and anti-MYC immunohistochemistry: useful diagnostic tools in the assessment of secondary angiosarcoma and atypical vascular proliferations |journal=J. Cutan. Pathol. |volume=39 |issue=2 |pages=234–42 |date=February 2012 |pmid=22121953 |doi=10.1111/j.1600-0560.2011.01843.x |url=}}</ref>
 
*The up-regulation of these [[genes]] and [[over-expression]] of [[vascular]] [[endothelial]] [[growth factor receptors]] can cause [[endothelial cell]] expansion, [[angiogenesis]], and also vascular leaks in the structure of vessels. <ref name="pmid14746640">{{cite journal |vauthors=Amo Y, Masuzawa M, Hamada Y, Katsuoka K |title=Serum concentrations of vascular endothelial growth factor-D in angiosarcoma patients |journal=Br. J. Dermatol. |volume=150 |issue=1 |pages=160–1 |date=January 2004 |pmid=14746640 |doi=10.1111/j.1365-2133.2004.05751.x |url=}}</ref><ref name="pmid20008140">{{cite journal |vauthors=Manner J, Radlwimmer B, Hohenberger P, Mössinger K, Küffer S, Sauer C, Belharazem D, Zettl A, Coindre JM, Hallermann C, Hartmann JT, Katenkamp D, Katenkamp K, Schöffski P, Sciot R, Wozniak A, Lichter P, Marx A, Ströbel P |title=MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema |journal=Am. J. Pathol. |volume=176 |issue=1 |pages=34–9 |date=January 2010 |pmid=20008140 |pmc=2797867 |doi=10.2353/ajpath.2010.090637 |url=}}</ref><ref name="pmid20949568">{{cite journal |vauthors=Guo T, Zhang L, Chang NE, Singer S, Maki RG, Antonescu CR |title=Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions |journal=Genes Chromosomes Cancer |volume=50 |issue=1 |pages=25–33 |date=January 2011 |pmid=20949568 |pmc=3150534 |doi=10.1002/gcc.20827 |url=}}</ref><ref name="pmid22121953">{{cite journal |vauthors=Fernandez AP, Sun Y, Tubbs RR, Goldblum JR, Billings SD |title=FISH for MYC amplification and anti-MYC immunohistochemistry: useful diagnostic tools in the assessment of secondary angiosarcoma and atypical vascular proliferations |journal=J. Cutan. Pathol. |volume=39 |issue=2 |pages=234–42 |date=February 2012 |pmid=22121953 |doi=10.1111/j.1600-0560.2011.01843.x |url=}}</ref>
 
**[[KDR]] [[mutations]] are seen in primary breast angiosarcoma regardless of exposure to [[radiation]].
 
**[[KDR]] [[mutations]] are seen in primary breast angiosarcoma regardless of exposure to [[radiation]].
** High level [[MYC]] amplification is seen is seen in radiation-induced and lymphedema-associated angiosarcoma.
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** High level [[MYC]] amplification is seen is seen in [[radiation]]-induced and lymphedema-associated angiosarcoma.
** [[FLT4]] amplification  has been detected in 25% of secondary angiosarcomas.
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**[[FLT4]] amplification  has been detected in 25% of secondary angiosarcomas.
 
{| align="right"
 
{| align="right"
 
|[[File:Angiosarcoma (5617087462) (1).jpg|thumb|right|200px|Image courtesy of Yale Rosen, contributed by Wikimedia commons]]
 
|[[File:Angiosarcoma (5617087462) (1).jpg|thumb|right|200px|Image courtesy of Yale Rosen, contributed by Wikimedia commons]]
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* On [[gross pathology]], characteristic findings of angiosarcoma may include red/dark tan [[papules]] or [[noduls]], which are ytpically poorly circumscribed with central earas of [[necrosis]] and hemoorrhage.<ref name="pmid20537949">{{cite journal |vauthors=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol. |volume=11 |issue=10 |pages=983–91 |year=2010 |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref>
 
* On [[gross pathology]], characteristic findings of angiosarcoma may include red/dark tan [[papules]] or [[noduls]], which are ytpically poorly circumscribed with central earas of [[necrosis]] and hemoorrhage.<ref name="pmid20537949">{{cite journal |vauthors=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol. |volume=11 |issue=10 |pages=983–91 |year=2010 |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref>
 
* On microscopic [[histopathological]] analysis, characteristic findings of angiosarcoma may include irregular anastomosing [[vascular]] spaces lined by endothelial cells.<ref name="pmid17998731">{{cite journal |vauthors=Mittal S, Goswami C, Kanoria N, Bhattacharya A |title=Post-irradiation angiosarcoma of bone |journal=J Cancer Res Ther |volume=3 |issue=2 |pages=96–9 |date=2007 |pmid=17998731 |doi= |url=}}</ref>
 
* On microscopic [[histopathological]] analysis, characteristic findings of angiosarcoma may include irregular anastomosing [[vascular]] spaces lined by endothelial cells.<ref name="pmid17998731">{{cite journal |vauthors=Mittal S, Goswami C, Kanoria N, Bhattacharya A |title=Post-irradiation angiosarcoma of bone |journal=J Cancer Res Ther |volume=3 |issue=2 |pages=96–9 |date=2007 |pmid=17998731 |doi= |url=}}</ref>
*[[Endothelial cells]] have hyperchromatic or vesicular nuclei with fast mitotic activity and necrotic spots.<ref name="pmid7569134">{{cite journal |vauthors=Murphey MD, Fairbairn KJ, Parman LM, Baxter KG, Parsa MB, Smith WS |title=From the archives of the AFIP. Musculoskeletal angiomatous lesions: radiologic-pathologic correlation |journal=Radiographics |volume=15 |issue=4 |pages=893–917 |date=July 1995 |pmid=7569134 |doi=10.1148/radiographics.15.4.7569134 |url=}}</ref>
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*[[Endothelial cells]] have hyperchromatic or vesicular nuclei with fast [[mitotic]] activity and [[necrotic]] spots.<ref name="pmid7569134">{{cite journal |vauthors=Murphey MD, Fairbairn KJ, Parman LM, Baxter KG, Parsa MB, Smith WS |title=From the archives of the AFIP. Musculoskeletal angiomatous lesions: radiologic-pathologic correlation |journal=Radiographics |volume=15 |issue=4 |pages=893–917 |date=July 1995 |pmid=7569134 |doi=10.1148/radiographics.15.4.7569134 |url=}}</ref>
 
*The tumor cells in solid area are characterized by a spindled appearance and contain Weibel-Palade bodies.<ref name="pmid28477885">{{cite journal |vauthors=Marušić Z, Billings SD |title=Histopathology of Spindle Cell Vascular Tumors |journal=Surg Pathol Clin |volume=10 |issue=2 |pages=345–366 |date=June 2017 |pmid=28477885 |doi=10.1016/j.path.2017.01.006 |url=}}</ref>
 
*The tumor cells in solid area are characterized by a spindled appearance and contain Weibel-Palade bodies.<ref name="pmid28477885">{{cite journal |vauthors=Marušić Z, Billings SD |title=Histopathology of Spindle Cell Vascular Tumors |journal=Surg Pathol Clin |volume=10 |issue=2 |pages=345–366 |date=June 2017 |pmid=28477885 |doi=10.1016/j.path.2017.01.006 |url=}}</ref>
*Immunohistochemical staining of spindle cells highlights [[CD31]], [[CD34]] and [[von-Willebrand factor]] related antigens which define the [[vascular]] origin of [[tumor]] cells.<ref name="pmid12150140">{{cite journal |vauthors=Kiyohara T, Kumakiri M, Kobayashl H, Itoh K, Lao LM, Ohkawara A, Nakmura H |title=Spindle cell angiosarcoma following irradiation therapy for cervical carcinoma |journal=J. Cutan. Pathol. |volume=29 |issue=2 |pages=96–100 |date=February 2002 |pmid=12150140 |doi=10.1034/j.1600-0560.2002.290206.x |url=}}</ref>
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*Immunohistochemical staining of spindle cells highlights [[CD31]], [[CD34]] and von-Willebrand factor related [[antigens]] which define the [[vascular]] origin of [[tumor]] cells.<ref name="pmid12150140">{{cite journal |vauthors=Kiyohara T, Kumakiri M, Kobayashl H, Itoh K, Lao LM, Ohkawara A, Nakmura H |title=Spindle cell angiosarcoma following irradiation therapy for cervical carcinoma |journal=J. Cutan. Pathol. |volume=29 |issue=2 |pages=96–100 |date=February 2002 |pmid=12150140 |doi=10.1034/j.1600-0560.2002.290206.x |url=}}</ref>
 
==Causes==
 
==Causes==
*Common causes of angiosarcoma include:<ref name="pmid20537949">{{cite journal |vauthors=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol. |volume=11 |issue=10 |pages=983–91 |year=2010 |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref>
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*Common [[causes]] of angiosarcoma include:<ref name="pmid20537949">{{cite journal |vauthors=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol. |volume=11 |issue=10 |pages=983–91 |year=2010 |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref>
 
**Exposure to [[vinyl chloride]] monomer (VCM) for prolonged periods
 
**Exposure to [[vinyl chloride]] monomer (VCM) for prolonged periods
**Exposure to [[polyvinyl chloride]] (PVC) polymerisation plants
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**Exposure to [[polyvinyl chloride]] ([[PVC]]) polymerisation plants
**Exposure to [[arsenic]]-containing [[insecticides]]  
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**Exposure to [[arsenic]]-containing [[insecticides]]
 
**Previous exposure to [[thorium dioxide]] [[irradiation]]
 
**Previous exposure to [[thorium dioxide]] [[irradiation]]
 
==Differentiating Angiosarcoma from Other Diseases==
 
==Differentiating Angiosarcoma from Other Diseases==
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:*[[Malignant fibrous histiocytoma]] of soft tissue
 
:*[[Malignant fibrous histiocytoma]] of soft tissue
 
==Epidemiology and Demographics==
 
==Epidemiology and Demographics==
*The incidence of angiosarcomas can be calculated approximately 1.2 per 1,000.000 person.<ref name="pmid20537949">{{cite journal |vauthors=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol. |volume=11 |issue=10 |pages=983–91 |date=October 2010 |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref><ref name="pmid21793180">{{cite journal |vauthors=Ferrari A, Sultan I, Huang TT, Rodriguez-Galindo C, Shehadeh A, Meazza C, Ness KK, Casanova M, Spunt SL |title=Soft tissue sarcoma across the age spectrum: a population-based study from the Surveillance Epidemiology and End Results database |journal=Pediatr Blood Cancer |volume=57 |issue=6 |pages=943–9 |date=December 2011 |pmid=21793180 |pmc=4261144 |doi=10.1002/pbc.23252 |url=}}</ref>
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*The [[incidence]] of angiosarcomas can be calculated approximately 1.2 per 1,000.000 person.<ref name="pmid20537949">{{cite journal |vauthors=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol. |volume=11 |issue=10 |pages=983–91 |date=October 2010 |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref><ref name="pmid21793180">{{cite journal |vauthors=Ferrari A, Sultan I, Huang TT, Rodriguez-Galindo C, Shehadeh A, Meazza C, Ness KK, Casanova M, Spunt SL |title=Soft tissue sarcoma across the age spectrum: a population-based study from the Surveillance Epidemiology and End Results database |journal=Pediatr Blood Cancer |volume=57 |issue=6 |pages=943–9 |date=December 2011 |pmid=21793180 |pmc=4261144 |doi=10.1002/pbc.23252 |url=}}</ref>
*Angiosarcoma is more commonly observed among patients aged between 40 to 75 years old.The peak age of incidence appears is the 7th decade,<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
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*Angiosarcoma is more commonly observed among patients aged between 40 to 75 years old.The peak age of [[incidence]] appears is the 7th decade,<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
 
*Males are more commonly affected with angiosarcoma than females.<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
 
*Males are more commonly affected with angiosarcoma than females.<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
 
*The male to female ratio is 2:1.<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
 
*The male to female ratio is 2:1.<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
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== Treatment ==
 
== Treatment ==
 
=== Medical Therapy ===
 
=== Medical Therapy ===
* The role of adjuvant chemotherapy, is unclear. Adjuvant chemotherapy and/or radiotheray provide less mutilating surgery, and for patients with unresectable tumors or those who refuse surgery is an option.<ref name="pmid20537949">{{cite journal |vauthors=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol. |volume=11 |issue=10 |pages=983–91 |date=October 2010 |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref><ref name="pmid20485141">{{cite journal |vauthors=Lahat G, Dhuka AR, Hallevi H, Xiao L, Zou C, Smith KD, Phung TL, Pollock RE, Benjamin R, Hunt KK, Lazar AJ, Lev D |title=Angiosarcoma: clinical and molecular insights |journal=Ann. Surg. |volume=251 |issue=6 |pages=1098–106 |date=June 2010 |pmid=20485141 |doi=10.1097/SLA.0b013e3181dbb75a |url=}}</ref>
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* The role of [[adjuvant chemotherapy]], is unclear. [[Adjuvant chemotherapy]] and/or [[radiotheray]] provide less mutilating surgery, and for [[patients]] with unresectable [[tumors]] or those who refuse [[surgery]] is an option.<ref name="pmid20537949">{{cite journal |vauthors=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol. |volume=11 |issue=10 |pages=983–91 |date=October 2010 |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref><ref name="pmid20485141">{{cite journal |vauthors=Lahat G, Dhuka AR, Hallevi H, Xiao L, Zou C, Smith KD, Phung TL, Pollock RE, Benjamin R, Hunt KK, Lazar AJ, Lev D |title=Angiosarcoma: clinical and molecular insights |journal=Ann. Surg. |volume=251 |issue=6 |pages=1098–106 |date=June 2010 |pmid=20485141 |doi=10.1097/SLA.0b013e3181dbb75a |url=}}</ref>
*Since angiosarcomas are histologically anthracycline-sensitive, then initial systemic chemotherapy for unresectable and/or metastatic angiosarcomas include doxorubicin-based therapy with or without ifosfamide.<ref name="pmid21566149">{{cite journal |vauthors=Penel N, Italiano A, Ray-Coquard I, Chaigneau L, Delcambre C, Robin YM, Bui B, Bertucci F, Isambert N, Cupissol D, Bompas E, Bay JO, Duffaud F, Guillemet C, Blay JY |title=Metastatic angiosarcomas: doxorubicin-based regimens, weekly paclitaxel and metastasectomy significantly improve the outcome |journal=Ann. Oncol. |volume=23 |issue=2 |pages=517–23 |date=February 2012 |pmid=21566149 |doi=10.1093/annonc/mdr138 |url=}}</ref>
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*Since angiosarcomas are [[histologically]] [[anthracycline]]-sensitive, then initial systemic [[chemotherapy]] for unresectable and/or [[metastatic]] angiosarcomas include [[doxorubicin]]-based therapy with or without [[ifosfamide]].<ref name="pmid21566149">{{cite journal |vauthors=Penel N, Italiano A, Ray-Coquard I, Chaigneau L, Delcambre C, Robin YM, Bui B, Bertucci F, Isambert N, Cupissol D, Bompas E, Bay JO, Duffaud F, Guillemet C, Blay JY |title=Metastatic angiosarcomas: doxorubicin-based regimens, weekly paclitaxel and metastasectomy significantly improve the outcome |journal=Ann. Oncol. |volume=23 |issue=2 |pages=517–23 |date=February 2012 |pmid=21566149 |doi=10.1093/annonc/mdr138 |url=}}</ref>
*However, taxane-based regimen may be preffered for initial therapy.Paclitaxel is effective for advanced angiosarcoma.<ref name="pmid15948172">{{cite journal |vauthors=Skubitz KM, Haddad PA |title=Paclitaxel and pegylated-liposomal doxorubicin are both active in angiosarcoma |journal=Cancer |volume=104 |issue=2 |pages=361–6 |date=July 2005 |pmid=15948172 |doi=10.1002/cncr.21140 |url=}}</ref>
+
*However, [[taxane]]-based regimen may be preferred for initial therapy.
*Gemcitabine-based regimen is preferable to doxorubicin with or without ifosfamide for patients with significant clinical haert failure, due to heart-toxicity of doxorubicin.<ref name="pmid28794805">{{cite journal |vauthors=In GK, Hu JS, Tseng WW |title=Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations |journal=Ther Adv Med Oncol |volume=9 |issue=8 |pages=533–550 |date=August 2017 |pmid=28794805 |pmc=5524246 |doi=10.1177/1758834017712963 |url=}}</ref>
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*[[Paclitaxel]] is effective for advanced angiosarcoma.<ref name="pmid15948172">{{cite journal |vauthors=Skubitz KM, Haddad PA |title=Paclitaxel and pegylated-liposomal doxorubicin are both active in angiosarcoma |journal=Cancer |volume=104 |issue=2 |pages=361–6 |date=July 2005 |pmid=15948172 |doi=10.1002/cncr.21140 |url=}}</ref>
*In addition, some vascular biologic molecules, with antiangiogenic characteristics including bevacizumab, sunitinib, and sorafenib, and with or without cytotoxic chemotherapy have shown dramatic responses in a small number of angiosarcoma patients.<ref name="pmid27274393">{{cite journal |vauthors=Vo KT, Matthay KK, DuBois SG |title=Targeted antiangiogenic agents in combination with cytotoxic chemotherapy in preclinical and clinical studies in sarcoma |journal=Clin Sarcoma Res |volume=6 |issue= |pages=9 |date=2016 |pmid=27274393 |pmc=4896001 |doi=10.1186/s13569-016-0049-z |url=}}</ref>
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*[[Gemcitabine]]-based regimen is preferable to [[doxorubicin]] with or without [[ifosfamide]] for [[patients]] with significant clinical [[heart failure]], due to heart-[[toxicity]] of [[doxorubicin]].<ref name="pmid28794805">{{cite journal |vauthors=In GK, Hu JS, Tseng WW |title=Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations |journal=Ther Adv Med Oncol |volume=9 |issue=8 |pages=533–550 |date=August 2017 |pmid=28794805 |pmc=5524246 |doi=10.1177/1758834017712963 |url=}}</ref>
 +
*In addition, some vascular biologic molecules, with antiangiogenic characteristics including [[bevacizumab]], [[sunitinib]], and [[sorafenib]], and with or without [[cytotoxic]] [[chemotherapy]] have shown dramatic responses in a small number of angiosarcoma [[patients]].<ref name="pmid27274393">{{cite journal |vauthors=Vo KT, Matthay KK, DuBois SG |title=Targeted antiangiogenic agents in combination with cytotoxic chemotherapy in preclinical and clinical studies in sarcoma |journal=Clin Sarcoma Res |volume=6 |issue= |pages=9 |date=2016 |pmid=27274393 |pmc=4896001 |doi=10.1186/s13569-016-0049-z |url=}}</ref>
 
=== Surgery ===
 
=== Surgery ===
 
* The mainstay of treatment for angiosarcoma is complete [[surgical]] resection with wide margins for local and locoregional [[disease]] in combination with preoperative or postoperative radiotherapy.<ref name="pmid7977971">{{cite journal |vauthors=Lydiatt WM, Shaha AR, Shah JP |title=Angiosarcoma of the head and neck |journal=Am. J. Surg. |volume=168 |issue=5 |pages=451–4 |date=November 1994 |pmid=7977971 |doi=10.1016/s0002-9610(05)80097-2 |url=}}</ref><ref name="pmid27182479">{{cite journal |vauthors=Arifi S, Belbaraka R, Rahhali R, Ismaili N |title=Treatment of Adult Soft Tissue Sarcomas: An Overview |journal=Rare Cancers Ther |volume=3 |issue= |pages=69–87 |date=2015 |pmid=27182479 |pmc=4837937 |doi=10.1007/s40487-015-0011-x |url=}}</ref>
 
* The mainstay of treatment for angiosarcoma is complete [[surgical]] resection with wide margins for local and locoregional [[disease]] in combination with preoperative or postoperative radiotherapy.<ref name="pmid7977971">{{cite journal |vauthors=Lydiatt WM, Shaha AR, Shah JP |title=Angiosarcoma of the head and neck |journal=Am. J. Surg. |volume=168 |issue=5 |pages=451–4 |date=November 1994 |pmid=7977971 |doi=10.1016/s0002-9610(05)80097-2 |url=}}</ref><ref name="pmid27182479">{{cite journal |vauthors=Arifi S, Belbaraka R, Rahhali R, Ismaili N |title=Treatment of Adult Soft Tissue Sarcomas: An Overview |journal=Rare Cancers Ther |volume=3 |issue= |pages=69–87 |date=2015 |pmid=27182479 |pmc=4837937 |doi=10.1007/s40487-015-0011-x |url=}}</ref>

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List of terms related to Angiosarcoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]; Associate Editor(s)-in-Chief: Mohsen Basiri M.D.
Synonyms and Keywords: Hemangiosarcoma; Pulmonary angiosarcoma; Vascular sarcoma

Overview

Angiosarcoma is a rare malignant vascular neoplasm of endothelial-type cells that line vessel walls. The peak age of incidence appears to be the 7th decade, and men are affected more than women. Angiosarcoma was first described by Dr. Juan Rosai, in 1976. The pathogenesis of angiosarcoma is characterized by a rapid and extensively infiltrating overgrowth of vascular epithelial cells. Angiosarcoma may arise in any part of the body, but is more common in soft tissue than in bone. Common angiosarcoma locations include the head and neck area, kidney, liver, lung, and and the most common site of radiation-induced angiosarcoma development is the breast. The PTPRB/PLCG1 genes are associated with the development of angiosarcoma; mutation of these genes result in aberrant angiogenesis. The imaging modality of choice for diagnosing angiosarcoma will depend on the location. For pulmonary angiosarcoma, the imaging modality of choice is enhanced CT scan. For other types angiosarcoma, the imaging modality of choice is MRI. On CT scan, findings suggestive of angiosarcoma may include vascular invasion, nodular enhancement (common), and a hypoattenuating mass. The mainstay adjuvant therapy for angiosarcoma is a doxorubicin-based regimen. The response rate for chemotherapy in patients with angiosarcoma is poor.

Historical Perspective

Angiosarcoma was first discovered by Dr. Juan Rosai, M.D. and colleagues in 1976.[1]

Classification

  • Angiosarcoma may be classified according to the clinical heterogeneity into two main groups, and every group can be subdivided into subtypes according to the anatomical location and etiology:[2][3][4]
Angiosarcoma
Primary Secondary
Cutaneous Post Radiation Angiosarcoma
Breast Lymphedema-associated Angiosarcoma
Soft tissue and Bone Angiosarcoma due to exposure to mutatgens
Visceral

Pathophysiology

Image courtesy of Yale Rosen, contributed by Wikimedia commons
  • On gross pathology, characteristic findings of angiosarcoma may include red/dark tan papules or noduls, which are ytpically poorly circumscribed with central earas of necrosis and hemoorrhage.[5]
  • On microscopic histopathological analysis, characteristic findings of angiosarcoma may include irregular anastomosing vascular spaces lined by endothelial cells.[10]
  • Endothelial cells have hyperchromatic or vesicular nuclei with fast mitotic activity and necrotic spots.[11]
  • The tumor cells in solid area are characterized by a spindled appearance and contain Weibel-Palade bodies.[12]
  • Immunohistochemical staining of spindle cells highlights CD31, CD34 and von-Willebrand factor related antigens which define the vascular origin of tumor cells.[13]

Causes

Differentiating Angiosarcoma from Other Diseases

  • Angiosarcoma must be differentiated from other diseases that cause a highly vascular mass or non-healing cutaneous ulcerations.
  • Cutaneous angiosarcoma must be differentiated from other diseases with non-healing cutaneous ulcerations such as:[14][15][16]
  • Angiosarcoma must be differentiated from other diseases that cause a highly vascular mass such as:[17]

Epidemiology and Demographics

  • The incidence of angiosarcomas can be calculated approximately 1.2 per 1,000.000 person.[5][18]
  • Angiosarcoma is more commonly observed among patients aged between 40 to 75 years old.The peak age of incidence appears is the 7th decade,[19]
  • Males are more commonly affected with angiosarcoma than females.[19]
  • The male to female ratio is 2:1.[19]
  • There is no racial predilection for angiosarcoma. however, African-Americans in the U.S are rarely affected.[20]

Risk Factors

Common risk factors in the development of angiosarcoma include chronic lymphedema, chronic exposure to polyvinyl chloride (PVC), radiation exposure, and exposure to Thorotrast.[5]

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

Staging

  • According to the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) and by Enneking classification, soft tissue sarcomas are classified to different stages based on the primary tumor characteristics, histological grading and the local or distant tumor involvement.
  • Table below provides summarized information regarding staging of angiosarcoma:[22][23]
Stage Grade Site Metastasis
Ia Low grade (G1) Intracompartmental (T1) No metastasis (M0)
Ib Low grade (G1) Extracompartmental (T2) No metastasis (M0)
IIa High grade (G2) Intracompartmental (T1) No metastasis (M0)
IIb High grade (G2) Extracompartmental (T2) No metastasis (M0)
IIIa Low or High grade (G1-G2) Intracompartmental (T1) Metastasis (M1)
IIIb Low or High grade (G1-G2) Extracompartmental (T2) Metastasis (M1)

History and Symptoms

  • Angiosarcomas occur at different anatomic sites and grow insidiously, then they can present with various misleading symptoms.[24]
  • The most common clinical manifestation is a gradually enlarging, painless mass.[21]
  • Some patients complain of pain or symptoms due to compression of adjacent neurovascular structures that causes pain or edema in an extremity.
  • Secondary angiosarcomas include radiation-Induced and lymphedema-associated angiosarcoma have a distinct feature, presenting as single or several ecchymotic maculopapular cutaneous lesions in the radiation field or in areas exposed to chronic lymphedema.[25]

Physical Examination

  • Patients with angiosarcoma may appear cachexic or normal. In cutaneous angiosarcoma, physical examination findings may include:

Laboratory Findings

  • There are no specific laboratory findings associated with angiosarcoma.

Electrocardiogram

Echocardiography or Ultrasound

X-ray

Imaging Findings

  • The imaging modality of choice for angiosarcoma will depend on the location.
  • For pulmonary angiosarcoma, the imaging modality of choice is enhanced CT scan.[19]
  • For other types angiosarcoma, the imaging modality of choice is MRI.

CT Scan

On CT, findings of angiosarcoma may include:[19]

MRI

On MRI, findings of angiosarcoma may include:[21]

  • T1/T2: heterogeneous areas of hyperintensity suggestive of a mixed tumor and hemorrhage
  • T1 C+ (Gd): heterogeneous enhancement

Other Imaging Findings

  • There are no other imaging findings associated with angiosarcoma.

Other Diagnostic Studies

  • There are no other diagnostic studies associated with angiosarcoma.

Treatment

Medical Therapy

Surgery

  • The mainstay of treatment for angiosarcoma is complete surgical resection with wide margins for local and locoregional disease in combination with preoperative or postoperative radiotherapy.[34][35]
  • Surgical resection in combination with radiation therapy is the treatment of choice for small angiosarcomas.[5]
  • Complete surgical resection with wide margins is preferred for local and locoregional angiosarcoma.[5]
  • Owing to the tendency for local infiltration, surgical resection should be associated with preoperative or postoperative radiotherapy.[36]
  • Surgery is not recommended on patients with large sized angiosarcomas.
  • It usually occurs after a median of six months locally or distantly and the three-year disease-free and overall survival rates both are low.[37][38]

Primary Prevention

Secondary Prevention

References

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