Cutaneous angiosarcoma

A cutaneous angiosarcoma (AS) is a rare kind of tumour with an aggressive course and a poor prognosis that accounts for approximately 1 - 2 % of soft tissue sarcomas. A cutaneous AS may be more likely to develop in patients with a congenital or acquired chronic lymphoedema (the most common type is Stewart-Treves syndrome, which develops in chronic lymphoedema of the arm after mastectomy, axiliary lymph node removal and radiotherapy to treat breast cancer) irradiation site, chronic ulceration (such as arteriovenous fistula in kidney transplant patients) etc. It has been suggested that the current conservative breast cancer treatments with radiotherapy play a role in encouraging angiosarcomas to develop but this is controversial. However, approximately 78 - 95% of patients who develop a cutaneous AS have no predisposing factors. It is thought the human herpes virus 8 may be involved but this has not been confirmed. Cutaneous AS usually affect the head and the neck (with the scalp being affected in 50% of cases), and it is usually patients over the age of 60 who develop them, at a proportion of 2.5 – 3 men to 1 woman. It has been suggested that UV rays may be involved in head and neck location. The prognosis of cutaneous AS remains very poor, with 10 - 35% patients surviving after five years. Furthermore, AS is a multifocal tumour which spreads beyond the clinically visible boundaries of the lesions with histological occult extension, total surgical removal is often not achieved. In addition, excision attempts may be bothered by the presence of vital structures when the tumour is located in the head and neck. There is often local recurrence, mainly in the first two years after the initial treatment, and it seems to correlate to tumour size. In a multivariate analysis, the factors used to assess prognosis were tumour size and thickness, mitotic index, and the surgical margins.

1 - DIAGNOSTIC

Clincally, cutaneous angiosarcomas usually present as nodules or angiomatous, erythematous and purplish plaques which may be confused with haematoma, localised inflammatory oedema, pseudorhinophyma, purpuric patches, keratotic lesions, verrucous lesions, or pyogenic granuloma.

The diagnosis is made by histological examination and immunohistochemistry testing. A biopsy (preferably a surgical biopsy) ( a surgical) is necessary. The histological features of AS range from high tumour differentiation to a very undifferentiated anaplastic appearance. When the proliferation is minimally differentiated or not differentiated at all, immunohistochemistry is useful to confirm whether the proliferation is vascular.

2 - PRE-OPERATIVE ASSESSMENT

This assessment is used for patients with all types of soft tissue sarcomas.

Local spread of the primary tumour is assessed using MRI. Systemic spread is assessed by a CT scan of the lungs with views of the liver, these areas being the common sites for metastases. A PET scan may also be carried out. Other radiology investigations may be considered depending on the presenting signs.

3 - TREATMENT

Patients with this type of tumour need to be managed by a multidisciplinary team including a specialist doctor, a surgeon, a radiotherapist, and a chemotherapy specialist.

3.1 - METHODS

Surgical treatment

The standard treatment is wide and conservative surgical removal, (with either a 2 cm margin, or along a healthy anatomical plane such as an aponeurosis).

For sarcomas of the limbs that are large or are invading the blood vessel and nerve structures or the bones, there are a number of options: compartment excision, amputation, or a combination of conservative surgery and radiotherapy. Compartment excision must remove the entire compartment together with its delineating anatomical structures (muscles, aponeuroses, blood vessel, nerve trunks and any bones that are encompassed or in contact). Only 15% of patients with sarcomas of the limbs can benefit from this kind of treatment (those with proximal and intracompartmental tumours). The disadvantages of this treatment are consequences involving loss of limb function and the fact that there is still a relapse rate of between 2 and 20% (all types of soft tissue sarcoma included). It is more and more uncommon for immediate amputation to be suggested, as this tends to be replaced by conservative surgery combined with radiotherapy.

Radiotherapy

Radiotherapy may be considered either as a neoadjuvant treatment (if the tumour is initially inoperable) so that surgical removal will be possible as a next step, or as adjuvant treatment after surgery to reduce the risk of recurrence. External radiotherapy is generally preferable to brachytherapy because of side effects (delayed wound healing).

The radiation dose is 50 Gy; the addition of another dose of 10 Gy over a reduced area is recommended if the excision margins are incomplete on histological examination. There is no well-established standard concerning the volume to irradiate, but the entire excision site and the length of any drains must be included with a safety margin of 2 - 5cm.

Chemotherapy

Chemotherapy for soft tissue sarcoma in adults consists of an optimum dose of anthracycline (doxorubicin > 60mg/m²) which has a response rate of less than 40%. If ifosfamide is added to the regimen, then the response rate improves. However, several series have reported that pegylated liposomal doxorubicin and taxanes are effective to treat cutaneous AS either used alone, or combined with radiotherapy, as neoadjuvant treatment, or to treat metastatic forms. Gemcitabine (Gemzar), Bevacizumab, and Sunotinid malate are some other treatment options that are currently being researched.

In large tumours that are initially inoperable, neoadjuvant chemotherapy to shrink the tumour may be considered, allowing surgery or radiotherapy to follow.

3.2 - INDICATIONS

The standard treatment is wide and conservative surgical excision, (with either a 2cm margin, or along a healthy anatomical plane such as an aponeurosis), combined with adjuvant radiotherapy of the tumour bed as soon as the tumour measures over 5cm. For tumours that are initially operable, there is no evidence that neoadjuvant or adjuvant chemotherapy improves overall survival rates.

For sarcomas of the limbs that are large or are invading the blood vessel and nerve structures or bones, the majority of specialised teams will offer a combination of conservative surgical removal followed by adjuvant radiotherapy because this avoids excessively disfiguring surgery, and in terms of overall survival rates, the results are equivalent to those of patients who have had an amputation. This means that limb fonction can be preserved in over 85% of cases. In any case, in forms that can be operated on it is not proven that neoadjuvant or adjuvant chemotherapy affects overall survival rates, even though these treatments do improve disease-free survival. These treatments should be carried out, if possible, in the setting of a treatment trial.

For sarcomas that cannot be operated on initially, preoperative (neoadjuvant) radiotherapy or chemotherapy can be offered so that surgical removal can be carried out as the next step. There are no studies that compare these two techniques when treating this condition. The types of chemotherapy currently used most often for AS are taxanes or pegylated liposomal doxorubicin. When these sarcomas affect the extremities, one option for neo-adjuvant treatment is intra-arterial infusion of the affected limb with TNF-a, possibly combined with Melphalan and/or with radiotherapy. Adjuvant radiotherapy or chemotherapy may be considered after surgery depending on what treatment was used before the surgery. Amputation is therefore only carried out when a tumour has invaded the blood vessel and nerve structures that are essential to preserving the limb, or when several compartments are affected and there is a risk that functional complications related to wide excision and radiotherapy will be greater than those associated with amputation. Radiotherapy alone is only used for patients who have a tumour that cannot be operated on and who refuse all other types of treatment.

For angiosarcomas of the scalp, systematic adjuvant irradiation of the whole scalp with electron beam therapy is recommended after surgical management by some authors due to the multifocal character of the tumour . However, although this additional radiotherapy reduces the frequency of relapses it does not affect overall survival rates. First line of chemotherapy (taxanes or pegylated liposomal doxorubicin) is often offered if the lesions are extensive, followed by surgical removal or radiotherapy.

For angiosarcomas of the breast that develop after a patient has had a carcinoma treated with conservative surgery and radiotherapy, the treatment offered is mastectomy. Adjuvant chemotherapy may be offered in the setting of a treatment trial.

In metastatic forms:

Any operable metastatic lesion must be removed surgically. Sometimes this will be preceded by chemotherapy (if the lesion is initially too large).

If the lesions cannot be operated on, single-drug chemotherapy regimens are preferable to those using a combination of drugs, as this will allow the patient to have a better quality of life.

4 - FOLLOW-UP

There is currently no consensus (how doctors should monitor patients with any type of soft tissue sarcomas (how often should appointments be and what type of examinations other than clinical ones should be carried out, and there is even less agreement concerning angiosarcoma monitoring) on the follow up of soft tissue sarcomas of all types in terms of how frequently patients should be reviewed and what type of radiological exams should be carried out, and there is even less agreement concerning angiosarcoma monitoring. For non-metastatic forms, review consists of clinical examination and chest X-ray (possibly with an ultrasound scan of the liver). One option that may be suggested, depending on the location of the tumour, is either an MRI or CT scan of the primary tumour site, and a CT scan of the lungs with views of the liver. Depending on the stage of the disease, reviews could take place every two to four months for two to three years, then every six months.