Kaposi's sarcoma

Summary

• Kaposi's sarcoma (KS) is a type of malignant tumour of the blood vessels that develops most commonly on the skin and mucous membranes, but may also affect internal organs.
• Skin tumours or lesions, which range in colour from brown to reddish-purple, are usually the first sign of KS.
• KS is associated with human herpes virus 8 (HHV-8) infection, and people with weakened immune systems (such as those with HIV/AIDS) are particularly vulnerable.
• AIDS-related KS is the commonest and most aggressively developing type of KS.
• Treatment for KS may involve surgery, chemotherapy, radiation therapy or immunotherapy, and, most importantly, treatment of the underlying cause of immunodeficiency.

Description

Kaposi's sarcoma (KS) is a type of malignant tumour (cancerous growth that can spread to other parts of the body) that develops most commonly in the tissues of the skin or the mucous membranes that line the mouth, nose and anus. KS may also affect internal organs, particularly the lymph nodes (small structures found throughout the body that produce infection-fighting cells), lungs and organs of the digestive system such as the liver, stomach and intestine.

Although KS usually begins on the skin, it can develop in several parts of the body simultaneously - unlike most cancers, which start at one site and  then may spread to others.

KS was previously a very rare disease, found primarily in elderly Mediterranean and Jewish men, organ transplant patients, and men in parts of equatorial Africa. With the advent of the AIDS epidemic in the 1980s, doctors began to see more cases of the disease in homosexual men with AIDS.

Types of KS and possible causes and risk factors

The exact cause of KS is not yet fully understood in all groups of patients. However, in immunocompromised patients, KS is caused by co-infection with human herpes virus 8, previously called Kaposi’s sarcoma associated virus.

All forms of KS occur more commonly in men: about eight or nine men get KS for every woman who contracts the disease.

The four main types of KS are as follows:

• Classic KS is very rare and usually only occurs in older men of Mediterranean or Jewish descent, in whom there is a genetic predisposition. The tumours usually only occur on the skin, most commonly on the lower legs. Classic KS progresses slowly, sometimes over 10 to 15 years.
• Endemicor African KS occurs in parts of equatorial Africa. It tends to develop more rapidly than classic KS, and can affect people of all ages.
• AIDS-related or epidemic KS is the commonest and most aggressively developing form, often involving both the skin and the internal organs. KS appears in 15-20 percent of AIDS cases. As AIDS progresses, the immune system weakens and thus the risk of developing KS increases. Recent research suggests that AIDS-related KS may be caused by a combination of immune system suppression and exposure to certain viruses, such as one form of the herpes virus, human herpes virus 8 (HHV-8). The virus is apparently sexually transmitted, because people who contract AIDS through contaminated blood products or needles are far less likely to develop KS than those who acquired AIDS from a sexual partner.

Apart from AIDS-related KS, there have been no major outbreaks of KS, and there is no evidence that KS can be casually transmitted.

• Immunosuppressive treatment-related KS: Although it is rare, it may occur in transplant patients receiving drugs to suppress their immune systems (immunosuppressants), so as to reduce the risk of the transplanted organ being rejected.

Symptoms and signs

KS on the skin appears as a small, flat area or lump that is painless and does not itch. These growths, called lesions, are usually the first signs of KS, and range in colour from brown to reddish-purple. (They typically look red or purple on pale skin, and bluish, brownish or black on dark skin.) They may resemble bruises, but do not blanche (turn pale) when you apply pressure to them. Lesions often initially occur on the face, limbs and in the mouth, although any part of the skin may be affected. At first the lesions may be small, causing no problems other than cosmetic concerns. In some people, tumour growth is slow; in others, growth is rapid with new lesions appearing every week or fortnight. As the lesions progress, they grow together and form a larger tumour.

Symptoms and signs of internal KS depend on the site of the tumour:

• Swelling of the limbs, a condition called lymphoedema, may occur if the lymph nodes are affected, which is common in AIDS-related KS. The KS cells obstruct the lymph nodes and normal lymph fluid circulation. This may lead to stretched, painful skin in the swollen areas.
• Shortness of breath, coughing and bloody sputum (substance expelled by coughing or clearing the throat) may indicate the presence of pulmonary (lung) lesions.
• Nausea and vomiting may indicate gastrointestinal (digestive tract) lesions.

Diagnosis

If there are signs of KS, your doctor will examine the entire skin surface and lymph nodes. He or she will also most likely perform a general examination and a blood test. KS may be suspected if the characteristic skin lesions are present, but a biopsy (tissue sample) is usually necessary to confirm the diagnosis.

Biopsy

The doctor numbs the area with local anaesthetic and takes a small sample of tissue from a lesion for examination. If the biopsy confirms the diagnosis of KS, additional tests are performed to check for signs of malignancy elsewhere in your body. These may include:

• Chest X-ray: To check for KS in your lungs and respiratory passages. Lung infections with various causes often occur in people with AIDS, so it may be difficult in these cases to ascertain whether respiratory changes shown by X-ray are caused by KS. A bronchoscopy or CT scan may be performed to confirm the diagnosis.
• Endoscopy: Performed with an endoscope, a device consisting of a tube and optical system for viewing inside the body through a natural body opening or a small incision. The endoscope is usually passed down your throat. You will receive a mild sedative, and local anaesthetic will be sprayed on your throat to relieve discomfort. The following types of endoscopy are used to examine different parts of the body:
  • Bronchoscopy - windpipe and lungs
  • Gastroscopy - oesophagus and stomach
  • Oesophagogastroduodenoscopy – in which a flexible tube is used to examine the oesophagus, stomach and upper duodenum (upper intestine)
  • Colonoscopy - lower intestine (colon). Your bowel must be empty for colonoscopy, so you will be asked to follow a specific diet and are given a bowel wash-out before the test.
• Lung function tests: If other tests show lung involvement, you may undergo lung function tests - you blow into a machine that takes measurements to check lung capacity and efficiency.
• CT scan: A specialised type of X-ray, for which you lie still for about half an hour, while an area of your body is scanned from different angles. The scans are compiled into a detailed picture to show any signs of KS. This test is especially useful for diagnosing KS in the lymph nodes.

Treatment

Treatment options depend on different factors, including the type of KS you have, your age and general health and the location and extent of the tumours.

There are basically four kinds of treatment for KS: surgery (removing the tumours), chemotherapy (using drugs to kill cancer cells), radiation therapy (using high-energy rays to kill cancer cells), and biological or immunotherapy (using the body's immune system to fight the cancer): 

• Surgery: KS skin lesions, particularly small ones, may be surgically removed. Local anaesthetic is injected into the skin around the lesion to numb the area. The lesion and some of the surrounding tissue is cut out, usually leaving a small scar that will fade in time. This simple procedure can be done on an out-patient basis.

Skin lesions can also sometimes be removed by other methods such as cryotherapy (destroying tissue by freezing it with liquid nitrogen) or electrodesiccation (destroying tissue by drying it out with electric sparks).

• Radiotherapy/radiation therapy: Administered locally to kill cancer cells. This painless treatment is usually given in one dose. It may cause small skin lesions to fade completely and larger lumps to shrink, and helps reduce symptoms of internal KS, such as swelling, pain and breathlessness.

Radiotherapy to the skin produces minor side-effects: skin around the treated area may become red, sore or itchy, and hair loss in the affected area will probably occur. The hair may grow back after treatment. Radiotherapy to tumours of the digestive system may cause nausea and vomiting. Tiredness is another common side-effect, so ensure you get sufficient rest.

• Chemotherapy:  Used if KS has spread throughout your system. Chemotherapy is a systemic treatment, because the drug travels throughout the body via the bloodstream. It may be taken orally or intravenously (injected into a vein), usually every week or fortnight.

For skin KS, chemotherapy is also usually received intravenously, but may be injected directly into a skin lesion. The latter is called local or intralesional chemotherapy. It is only used for small lesions, and may be considered as an alternative to radiotherapy for sites or skin types where radiotherapy might cause unsightly darkening.

If you are receiving chemotherapy, your doctor will watch for any side-effects that need treatment. Chemotherapy can affect the heart and suppress bone marrow function, causing a drop in the number of white blood cells. This makes you more vulnerable to infections and fatigue. Other side-effects include hair loss, nausea and vomiting, diarrhoea and nerve damage in the feet, legs and hands. Chemotherapy can make your mouth sore and cause small mouth ulcers. Local chemotherapy may cause temporary skin inflammation. There are treatments to help relieve many of these side-effects: for example, you can receive a blood transfusion if you develop anaemia, or antibiotics for infections.

Although side-effects from chemotherapy or radiotherapy may have a negative impact on your quality of life during treatment, most will resolve gradually once the course of treatment is completed.

• Immunotherapy/biological therapy/biological response modifier therapy: Uses substances made by the body or in a laboratory to boost or direct the body's immune system. This form of therapy is sometimes used to treat KS, often together with another treatment, such as chemotherapy. The compound used most commonly in immunotherapy is interferon, usually injected three times a week under the skin or into a lesion. You will be shown how to administer these injections yourself at home. At the start of therapy, interferon can bring on flu-like symptoms, such as chills, fever, headache, fatigue and joint and muscle aches. Interleukin, a drug similar to interferon, is also sometimes used to treat KS.

Early or slow-growing KS, involving only a few small skin lesions, may not require treatment. However, if you feel your lesions are unsightly and causing you distress, you may prefer to have them treated. Cosmetic products are also available to make lesions less noticeable.

Classic KS, especially in the early stage of the disease, may not require treatment. If treatment is considered necessary, however, for example for larger or unsightly lesions, it may take one of the following forms:

• Radiation therapy
• Local excision (surgical removal)
• Systemic or intralesional chemotherapy
• Chemotherapy and radiation therapy

Endemic or African KS is often treated with chemotherapy.

AIDS-related KS: Treatment decisions often depend on your general health. As your immune system is already weakened, it is important to ensure that any treatment side-effects will not lead to further deterioration. Treatment may involve one of the following options:

• Excision of skin lesions with or without radiation therapy
• Systemic chemotherapy
• Immunotherapy
• Involvement in a clinical trial evaluating new treatments. (A clinical trial is a carefully controlled programme to test a new treatment and compare its efficiency with standard treatments.)

Immunosuppressive treatment-related KScan sometimes be controlled by stopping or reducing the immunosuppressant drugs. This depends on your general condition: if you cannot stop taking these drugs, or if stopping them does not improve the KS, treatment may be one of:

• Radiation therapy
• A clinical trial of chemotherapy

New treatments and research directions

Several new treatments for KS are being investigated and their effectiveness ascertained. These include

• Infra-red coagulation: Infra-red light is targeted at a skin lesion with the aim of halting its growth.
• Photodynamic therapy: A light-sensitive drug is injected into the skin lesion, after which a laser is directed onto it to activate the drug and destroy the cancer cells.
• Liposomal chemotherapy: Standard chemotherapy drugs used to treat KS are put inside microscopic fat bubbles (liposomes). The drugs seem to move to the tumour site, where they are released. This treatment appears to cause fewer side-effects, and therefore can be continued for longer.
• Anti-HHV-8 drugs: Antiviral drugs, including the anti-herpes drug foscarnet, are being studied for use in KS treatment.
• Anti-cytokine research: Cytokines are proteins the immune system uses to stimulate cell growth. Substances that inhibit such growth factors may also be able to retard KS growth.
• Anti-angiogenesis drugs: KS cells stimulate excessive growth of small blood vessels, a process called angiogenesis - one area of research is investigating compounds that retard angiogenesis and could be suitable for use in KS treatment.

Outcome

The outcome of KS depends on which type you have, your age and general health, and whether or not you have AIDS.

KS skin lesions are not life-threatening, but KS tumours in other parts of the body can cause serious problems. As mentioned previously, internal KS can cause blockages and internal bleeding in the digestive tract; breathing difficulties or bleeding in the lungs; and lymphoedema. There is no cure for lymphoedema, which can be distressing and uncomfortable, but it may be relieved through methods such as exercise and massage. Lesions in the mouth lining can cause difficulty eating.

AIDS-related KS can be fatal. The most important part of the treatment is the treatment of the HIV infection with highly active antiretroviral therapy (HAART). Treatment of the lesions without treating HIV may improve the lesions, but does not necessarily improve survival, and tumours can recur even after apparently successful treatment.

Prevention

There is no known way to prevent KS. However, practising safe sex can help prevent infection with HHV-8 and HIV, the virus that leads to AIDS and vulnerability to diseases such as KS.

When to call the doctor

Consult your doctor if you notice any new dark spots on your skin.

Previously reviewed by Prof Helmuth Reuter, FRCP (Edinburgh), FCP (SA), MMed (Int), Department of Internal Medicine, University of Stellenbosch and Tygerberg Academic Hospital.

Reviewed by Dr David Eedes, Oncologist, February 2011