Elsevier

Clinical Oncology

Volume 31, Issue 4, April 2019, Pages 225-231
Clinical Oncology

Overview
Cutaneous Angiosarcoma Secondary to Lymphoedema or Radiation Therapy — A Systematic Review

https://doi.org/10.1016/j.clon.2019.01.009Get rights and content

Highlights

  • Angiosarcoma arising from lymphoedematous limbs or after irradiation remains uncommon.

  • The latency period of developing angiosarcoma from the time of primary cancer treatment can be very long (in years).

  • Initial presentation can be subtle, imaging can be non-specific.

  • High index of suspicion is needed for early detection.

Abstract

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 (n = 68, 94.4%) had a history of lymphoedema. The median latent period was 15 years (range 3–40 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 1–144 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 2–50 years); the median size was 40 mm (range 8–200 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 6–168 months).

Conclusion

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

Introduction

Angiosarcoma is a rare but fatal tumour, comprising less than 1% of all sarcomas. It arises from the vascular endothelium, with aggressive behaviour and tends to infiltrate locally and metastasise. It is, however, difficult to diagnose on initial presentation and, hence, carries a poor prognosis. These tumours can occur anywhere in the body, but usually take preference on the skin or deep tissues.

In general, angiosarcomas of this region can be categorised into two groups – 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 10–15 years after primary breast cancer therapy including surgery and radiotherapy [1], [2]. 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 [3].

Lymphoedema is a recognised risk factor for the development of angiosarcoma. This condition, also known as Stewart–Treves syndrome, describes a cutaneous angiosarcoma arising from chronic lymphoedema after mastectomy and lymphadenectomy. Another known risk factor is breast irradiation. In fact, radiotherapy-induced fibrosis in itself can also cause chronic lymphatic obstruction. The latency period from radiotherapy to angiosarcomatous development is quoted to be on average 6–7 years in most studies.

Although uncommon, the incidence of secondary angiosarcomas is rising, due to the increased incidence of breast cancer and improved long-term breast cancer survival. As a result, long-term consequences of radiotherapy and lymphoedema were more commonly seen among breast cancer survivors.

This systematic review aims to evaluate the clinical features and outcomes of secondary angiosarcoma, commonly arising after breast cancer treatment.

Section snippets

Materials and Methods

The systematic review was conducted in accordance with the PRISMA statement and current methodological literature. As this was a systematic review/meta-analysis, institutional review board approval was not required (see Figure 1 for the PRISMA flowchart).

Results

In total, 148 studies or reports were identified using the preset key words defined in the study protocol. After excluding irrelevant papers (such as editorials or commentaries without case presentation, or conference abstracts), 39 studies or reports were included in the review [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38],

Discussion

With increased breast cancer awareness globally, breast cancer patients are being diagnosed and successfully treated at early stages. These long-term breast cancer survivors are at risk of angiosarcoma secondary to the breast cancer treatment. Angiosarcoma is rare but is nearly always fatal unless diagnosed and treated early. Unfortunately, they are easily missed on presentation and difficult to diagnose, even with proper imaging. Thus, it is important to understand this disease and to have a

Conclusion

Angiosarcoma secondary to lymphoedema/radiotherapy remains a deadly disease with a long latent period (see Table 2 for a summary).

Conflict of interest

The authors declare no conflict of interest.

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