Difference between revisions of "Angiosarcoma"

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* Early [[clinical]] features may include nonspecific [[symptoms]], such as [[pain]], [[fatigue]], [[malaise]], and [[nausea]].
 
* Early [[clinical]] features may include nonspecific [[symptoms]], such as [[pain]], [[fatigue]], [[malaise]], and [[nausea]].
 
* If left untreated, the majority of [[patients]] with angiosarcoma may rapidly progress to develop [[metastases]].<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
 
* If left untreated, the majority of [[patients]] with angiosarcoma may rapidly progress to develop [[metastases]].<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
 
+
* Common [[complications]] of angiosarcoma include [[fractures|Pathologic fractures]], [[anemia]], and [[hepatic dysfunction]].<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>
* Common [[complications]] 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>
 
 
 
*[[Fractures|Pathologic fractures]]
 
*[[Anemia]]
 
*[[Hepatic dysfunction]]
 
 
*[[Prognosis]] is generally poor; the 5-­year survival rate of [[patients]] with angiosarcoma is approximately 12-33%.
 
*[[Prognosis]] is generally poor; the 5-­year survival rate of [[patients]] with angiosarcoma is approximately 12-33%.
 
* Poor [[prognostic]] factors include [[patient]] age (> 65 years), [[retroperitoneal]] location, and large [[tumor]] size.<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>
 
* Poor [[prognostic]] factors include [[patient]] age (> 65 years), [[retroperitoneal]] location, and large [[tumor]] size.<ref name="angio">Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52</ref>

Revision as of 13:58, 16 October 2019

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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

  • 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.[5][29]
  • Since angiosarcomas are histologically anthracycline-sensitive, then initial systemic chemotherapy for unresectable and/or metastatic angiosarcomas include doxorubicin-based therapy with or without ifosfamide.[30]
  • However, taxane-based regimen may be preffered for initial therapy.Paclitaxel is effective for advanced angiosarcoma.[31]
  • Gemcitabine-based regimen is preferable to doxorubicin with or without ifosfamide for patients with significant clinical haert failure, due to heart-toxicity of doxorubicin.[32]
  • 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.[33]

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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  2. Fury MG, Antonescu CR, Van Zee KJ, Brennan MF, Maki RG (2005). "A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy". Cancer J. 11 (3): 241–7. PMID 16053668.
  3. Schlemmer M, Reichardt P, Verweij J, Hartmann JT, Judson I, Thyss A, Hogendoorn PC, Marreaud S, Van Glabbeke M, Blay JY (November 2008). "Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group". Eur. J. Cancer. 44 (16): 2433–6. doi:10.1016/j.ejca.2008.07.037. PMID 18771914.
  4. Karanian M, Coindre JM (January 2015). "[Fourth edition of WHO classification tumours of soft tissue]". Ann Pathol (in French). 35 (1): 71–85. doi:10.1016/j.annpat.2014.11.003. PMID 25532684.
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  15. de Keizer RJ, de Wolff-Rouendaal D, Nooy MA (2008). "Angiosarcoma of the eyelid and periorbital region. Experience in Leiden with iridium192 brachytherapy and low-dose doxorubicin chemotherapy". Orbit. 27 (1): 5–12. doi:10.1080/01676830601168926. PMID 18307140.
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  20. Sturgis EM, Potter BO (May 2003). "Sarcomas of the head and neck region". Curr Opin Oncol. 15 (3): 239–52. doi:10.1097/00001622-200305000-00011. PMID 12778019.
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  22. Lydiatt WM, Patel SG, O'Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, Loomis AM, Shah JP (March 2017). "Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual". CA Cancer J Clin. 67 (2): 122–137. doi:10.3322/caac.21389. PMID 28128848.
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  30. 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 (February 2012). "Metastatic angiosarcomas: doxorubicin-based regimens, weekly paclitaxel and metastasectomy significantly improve the outcome". Ann. Oncol. 23 (2): 517–23. doi:10.1093/annonc/mdr138. PMID 21566149.
  31. Skubitz KM, Haddad PA (July 2005). "Paclitaxel and pegylated-liposomal doxorubicin are both active in angiosarcoma". Cancer. 104 (2): 361–6. doi:10.1002/cncr.21140. PMID 15948172.
  32. In GK, Hu JS, Tseng WW (August 2017). "Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations". Ther Adv Med Oncol. 9 (8): 533–550. doi:10.1177/1758834017712963. PMC 5524246. PMID 28794805.
  33. Vo KT, Matthay KK, DuBois SG (2016). "Targeted antiangiogenic agents in combination with cytotoxic chemotherapy in preclinical and clinical studies in sarcoma". Clin Sarcoma Res. 6: 9. doi:10.1186/s13569-016-0049-z. PMC 4896001. PMID 27274393.
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  38. Seinen JM, Styring E, Verstappen V, Vult von Steyern F, Rydholm A, Suurmeijer AJ, Hoekstra HJ (August 2012). "Radiation-associated angiosarcoma after breast cancer: high recurrence rate and poor survival despite surgical treatment with R0 resection". Ann. Surg. Oncol. 19 (8): 2700–6. doi:10.1245/s10434-012-2310-x. PMC 3404270. PMID 22466664.

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