Cutaneous Angiosarcoma Secondary to Lymphoedema or Radiation Therapy A Systematic Review

M. Co *y, A. Lee *y, A. Kwong *y Clinical Oncology February 2019

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Cutaneous Angiosarcoma Secondary to Lymphoedema or Radiation Therapy d A Systematic Review

Co *y, A. Lee *y, A. Kwong *y Clinical Oncology February 2019

Aims: Secondary angiosarcoma is known to be associated with lymphoedema or radiation after cancer treatment. This systematic review aims to evaluate the clinical features and outcomes of secondary angiosarcoma commonly arising after breast cancer treatment.

Materials and methods: A systematic review was carried out according to the PRISMA protocol. Medline, EMBASE, CINAHL and Cochrane databases were searched for English articles to April 2018 with predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by two researchers.

Results: There were 72 secondary angiosarcomas of the limbs. Most patients (n¼ 68, 94.4%) had a history of lymphoedema. The median latent period was 15 years (range 3e40 years). Thirty-eight (52.8%) patients received wide excision or amputation as a treatment for the angiosarcoma, two (2.8%) patients received isolated limb perfusion and one (1.4%) patient received systemic chemotherapy. The remaining patients received palliative care/undocumented treatment. The pooled median duration to mortality was 10.5 months (range 1e144 months). Of note, obesity was documented in seven (9.7%) patients. There were 83 breast angiosarcomas; all with known breast cancer history. Thirty-one (37.3%) patients received mastectomy as breast cancer treatment. Fifty-four (65.1%) patients had a history of adjuvant radiotherapy for the primary breast cancer. The median latent period was 6 years (range 2e50 years); the median size was 40 mm (range 8e200 mm). Forty-one (49.4%) patients received wide excision, 19 (22.9%) patients received completion mastectomy and 23 (27.7%) patients have undocumented treatment for angiosarcoma. The pooled median duration to mortality was 31 months (range 6e168 months).

Conclusion: Angiosarcoma in lymphedematous upper limbs or after breast cancer irradiation remains uncommon. However, its long latency and high mortality warrant long-term vigilant surveillance.

Main findings

  • Angiosarcomas of this region can be categorised into two groups e primary and secondary. Primary angiosarcomas occur spontaneously in younger patients without any known risk factors. Secondary angiosarcomas are known to develop in elder individuals who have previously received surgical treatment for primary breast cancer with adjuvant radiotherapy.
  • About 1000 in 100,000 breast cancer survivors suffer from the development of angiosarcoma 10e15 years after primary breast cancer therapy including surgery and radiotherapy. These tumours can occur at the primary site of the breast or develop on the ipsilateral upper limb (Stewart – Treves syndrome), which is often plagued by lymphoedema.
  • Lymphoedema is a recognised risk  factor for the development of angiosarcoma. It is also known as Stewart – Treves syndrome.
  • Another known risk factor is breast irradiation. The latency period from radiotherapy to angiosarcomatous development is quoted to be on average 6e7 years in most studies.
  • There were 83 patients with angiosarcoma of the breasts, all with a known breast cancer history.
  • There were 72 patients who had secondary angiosarcoma of the limbs.
  • The median latent period to the development of angiosarcoma (from the onset of lymphoedema) was 15 years (range 3-40 years).
  • The long-term breast cancer survivors are at risk of angiosarcoma secondary to breast cancer treatment. Angiosarcoma is rare but is nearly always fatal unless diagnosed and treated early.
  • Patients with limb angiosarcomas seemed to have one thing in common e almost 95% of the patients in this review had lymphoedema.
  • Lymphoedema is thought to induce an immunosuppressed environment that allows for abnormal angiomatosis and the development of malignancy.
  • Stasis in lymphatic drainage reduces effective removal of foreign antigen, affecting immunocyte production and causing local immunodeficiency. In such an environment, the development of lymphatic collaterals serves as the ‘precondition’ for neoplastic change.
  • In the breast some may still present as a palpable breast mass or diffuse swelling, many others first appear as abnormal skin changes such as an erythematous rash, plaque or even bluish skin discolouration. Usually, they are non-tender and fast growing. They are believed to arise from the cutaneous tissue rather than the breast parenchyma.
  • For the upper limb, often there is underlying lymphoedema with the variable appearance of swelling, bruising, nodular lesions and even ulceration. These skin lesions can merge and spread to adjacent tissue, e.g. from the arm to the chest wall, quite rapidly.
  • Tissue confirmation is still the most definite. Core biopsy is preferred to fine needle aspiration in order to avoid false negatives and to accurately examine the abnormal angiogenesis and histological abnormalities.
  • Surgical excision with a wide margin of the tumour is the mainstay of treatment, either by breast-conserving surgery or mastectomy for breast lesions. In the case of upper limb lesions, wide local excision or even forequarter amputation can be carried out, although the latter is falling out of favour as the main goal of surgery is to obtain negative resection margins.
  • The most commonly utilised chemotherapeutic agents are of the cytotoxic group. Taxanes and doxorubicin, in particular, have been found to be more effective with angiosarcomas.