Kaposi's Sarcoma- A Detailed Information

The trillions of the cells in the body grow normally, divide, and then die accordingly. Once adulthood is reached cells divide only to replace worn-out or dying cells or to repair injuries.

What happens to cells in cancer?

Cancer starts when cells in a certain organ or part of the start to grow out of control. Cells become cancer cells because of damage to DNA.

Different types of cancer can behave very differently – some may remain at one location while others spread rapidly to other major organs via blood stream or via lymphatic channels. (1-4)

How does Kaposi's sarcoma develop?

Kaposi's sarcoma is a cancer that develops from the cell lining the lymph or blood vessels. The cancer appears as red, purple, or brown raised tumors or spots over the skin.

These lesions are usually non-symptomatic but may cause painful swelling in some areas like legs, groin or skin around the eyes.

Kaposi's sarcoma may become life threatening when it affects major organ like lungs, liver, or the gastrointestinal tract. In the gastrointestinal tract it may lead to bleeding while in the lungs it may lead to severe difficulty in breathing.

Who discovered Kaposi's sarcoma?

Kaposi's sarcoma was first described by Moritz Kaposi, a Hungarian dermatologist in 1872. (2)

Who is at risk of Kaposi's sarcoma?

An HIV-infected person has a 20,000 times increased risk of developing Kaposi's sarcoma to a person without HIV. In the early 1990’s there were approximately 47 cases per million people per year among the HIV infected individuals of United States.

With the advent of anti-HIV drugs the numbers have fallen and it now occurs at a rate of about 7 cases per million people each year.

The rates are highest in Africa where Kaposi's sarcoma herpesvirus (KSHV) (also known as human herpesvirus type 8 - HHV-8) and HIV infection rates are high. About 1 in 200 transplant patients in the United States gets Kaposi's sarcoma. (1-4)

Type of Kaposi's sarcoma

The major types of Kaposi's sarcoma are (1-4):

• AIDS-related or Epidemic Kaposi's sarcoma – This is the commonest type of KS in the United States. It affects patients infected with HIV. An HIV positive patient may harbor the virus in his or her body for years before getting AIDS. AIDS begins when the virus has severely debilitated the immune system. This damage to immune system leads to infections and complications like Kaposi's sarcoma. The CD4 count in blood is a measure of the effect of HIV on the immunity. The lower the CD4 count, the more likely that the patient will get Kaposi's sarcoma. Kaposi's sarcoma indicates that an HIV positive individual officially has AIDS and thus is called an “AIDS defining” illness.
• Classic Kaposi's sarcoma or Mediterranean Kaposi's sarcoma – This affects the elderly living in Mediterranean, Eastern European, and Middle Eastern regions for generations and the Ashkenazi Jews. It affects men more than women. Ashkenazi Jews are people who are descended from Jewish communities that lived in Central and Eastern Europe. Most Jewish people in England are Ashkenazi Jews. Lesions typically begin as one in the legs, ankles, or the soles of the feet. The lesions are usually slow to grow. The immune system of people with classic Kaposi's sarcoma is not as weak as it is in those who have epidemic Kaposi's sarcoma.
• Endemic Kaposi's sarcoma or African Kaposi's sarcoma – this affects people living in Equatorial Africa. These people are more at risk of developing infection with Kaposi's sarcoma Herpes Virus (KSHV). This form of Kaposi's sarcoma affects younger people under age 40. Rarely an aggressive form of the illness may be seen in children before puberty.
• Organ transplant-associated Kaposi's sarcoma – In individuals whose immune systems have been suppressed after an organ transplantation to prevent the body from rejecting the new organ, there is a risk of Kaposi's sarcoma. Most transplant patients need to immunosuppressant drugs to keep the immune system from attacking and killing the new organ that is perceived as a foreign object. If drugs weaken the immunity there is a risk of infection with KSHV and development of Kaposi's sarcoma.
• Kaposi's sarcoma in HIV negative men who have sex with men – this group is found to get mild cases of Kaposi's sarcoma similar to classic Kaposi's sarcoma.

Kaposi's sarcoma and AIDS

The rise of number of cases of Kaposi's sarcoma occurred in the 1980s and 1990s as the number of AIDS cases soared.

After the advent of anti HIV drugs called the highly active antiretroviral therapy (HAART) the incidence of Kaposi's sarcoma has reduced. However Kaposi's sarcoma remains a commonly reported cancer in some African countries commonly due to untreated HIV infection.

Causes of Kaposi's sarcoma

Causes of Kaposi's sarcoma include (1-4):

• Endemic or African Kaposi's sarcoma affects young adult men in equatorial Africa with a normal immune system. Up to 9% of Ugandan men suffer from this condition. Sometimes children may be affected as well.

In them the cancer invades the lymph nodes and lymphatic channels and spares the skin. This is usually associated with spread to other organs may be fatal.

• Transplant-related or acquired Kaposi's sarcoma. Patients after an organ transplant need immunity suppressing drugs. This prevents the patient’s immunity from attacking and killing the newly transplanted organ. These patients on immunity suppressing drugs are at risk of Kaposi's sarcoma.
• Epidemic or HIV associated Kaposi's sarcoma. This is the commonest cause of Kaposi's sarcoma.
• Kaposi's sarcoma-associated herpes virus (KSHV) or Human herpes virus 8 (HH8) is a common infection that can lead to Kaposi's sarcoma. KSHV belongs to the herpes virus family.

This virus is similar to Epstein-Barr virus. The EB virus causes infectious mononucleosis or glandular fever and contributes to several types of cancer like lymphomas.

The KSHV brings in genetic material into the cells. These altered genes cause the cells to divide too much and unnecessarily leading to cancer. HHV-8 does not cause Kaposi's sarcoma in everyone who develops the virus. The virus only seems to cause Kaposi’s sarcoma in people with a high risk.

Risk factors of getting Kaposi's sarcoma

Risk factors of getting Kaposi's sarcoma include (1-4):

• Men are more commonly affected. In African countries male patients who are not HIV positive are more frequently affected with the virus than females.

• Men of the Mediterranean, Middle Eastern or African origin and of Ashkenazi Jewish descent are more at risk. This could be due to an inherited vulnerability to HH8 virus.
• Men who have sex with men are more at risk. Homosexual as well as heterosexual partners of Kaposi's sarcoma patients are at risk of HH8 infection.
• Those with a suppressed immunity with HIV AIDS infection are at a greater risk of Kaposi's sarcoma.
• Those with diabetes and on oral corticosteroid medications are at risk. These conditions lead to decrease in immunity and thus may lead to the predisposition.

Symptoms of Kaposi's sarcoma

Symptoms of Kaposi's sarcoma include (1-4):

• Node like raised or blotchy flat patches over the skin. These are red, purple, brown or black. These are usually the first symptoms of Kaposi's sarcoma. The lesions can develop quickly and enlarge in size.

Although there may be a single area at first, it is possible for more than one to appear. Often the lesions merge to form a larger tumor. They are most commonly seen over the face around the mouth, ears and tip of the nose. Lesions are also seen commonly over the legs and feet, and genital area.

In dark skinned individuals the lesions are noted as dark brown or black.

• Lesions similar to those on the skin are sometimes visible under or on mucous membranes especially in the mouth, nose, gums, tongue, over the tonsils, over the palate (roof of the mouth) or throat.
• The skin lesions are more often than not painless and non-itchy. They may become painful if there is inflammation or swelling.
• There may be a superimposed or secondary bacterial infection over the skin lesions. Since the patient usually has lowered immunity there is also a risk of secondary infections in other organs like lungs (e.g. pneumonia) etc.
• Some aggressive tumors may spread to other organs. If the spread is in lungs there are respiratory problems and associated symptoms. In case of liver metastasis there are signs of liver damage like jaundice etc.
• Lesions occurring in the oesophagus (food pipe) or respiratory tract may grow to obstruct feeding or breathing respectively.
• Lung affection may lead to breathing difficulties, blood in the sputum and respiratory failure, gastrointestinal tract affection may lead to bleeding (that may be fatal) and affliction of the lymphatic channels may lead to swollen lymph nodes and lymphatic channels.

Swollen and blocked lymphatic channels lead to swollen limbs and is called lymphedema. Lesions in the gastrointestinal tract may lead to nausea, diarrhea, bleeding with stools and vomiting in some individuals.

• Over a long term bleeding may lead to anemia. This is caused due to lowering in the number of red blood cells.

Who treats Kaposi's sarcoma?

The team of physicians and health care providers treating Kaposi's sarcoma includes:

• HIV specialists
• skin specialists
• plastic surgeon
• clinical oncologist or specialist in cancer
• radiotherapy oncologist
• a virologist (who deals with viruses)
• a pathologist
• a social worker
• psychologists and a counsellor

Types of treatment of Kaposi's sarcoma

Treatment of Kaposi's sarcoma includes drugs against HIV if the person is HIV positive; radiotherapy, chemotherapy and so forth. (1-5)

Antiretroviral therapy

If the Kaposi's sarcoma is detected in an HIV positive individual then drugs against HIV are prescribed. These are known as highly active antiretroviral therapy (HAART).

Normally administration of these drugs resolves the skin lesions of Kaposi's sarcoma. HAART works by reducing the level of the virus in the body. Resolution of the symptoms of Kaposi's sarcoma may take a few months.

During this time low dose Radiotherapy may be used to shrink the lesions. Radiotherapy uses high-energy rays to destroy the cancer cells. If the disease is more widespread with general symptoms like fever or weight loss chemotherapy with anticancer drugs may be needed.

Radiotherapy

Treatment of classic Kaposi's sarcoma is slow growing and does not cause problems. Radiotherapy may be prescribed for treat large or very visible lesions.

Radiotherapy employs high energy beams to destroy the lesions. Small lesions fade completely but larger, raised and deeper lesions become smaller and flatter.

Radiotherapy also reduces swelling, pain and bleeding of the lesions especially if the lesions are present within the body.

For radiotherapy, multiple hospital visits are needed. Each treatment takes 10–15 minutes. For smaller areas 1–5 treatments or visits are suggested but larger lesions may need up to 12 sessions.

Common side effects of therapy include reddening, darkening and burning of the skin. There may be fatigue and tiredness. These side effects go away after therapy is complete.

Chemotherapy

Endemic or African Kaposi's sarcoma is generally treated with chemotherapy.

Chemotherapy uses anticancer drugs. If there are small lesions drugs may be injected into the lesion. This is called intralesional chemotherapy. It may be used instead of radiotherapy on areas such as around the eyes or face.

Intralesional chemotherapy can shrink skin lesions and make them lighter in colour. The most commonly used drug is Vinblastine. This drug may also be given intravenously for wider spread lesions. This is called systemic chemotherapy.

Common side effects include:

• loss of appetite,
• loss or hair,
• weakness,
• anemia,
• propensity to get infections,
• nausea,
• bleeding tendencies,
• sore mouth ulcers etc.

There is another systemic therapy called liposomal chemotherapy. The molecules of the drugs in this method are enveloped in a fat-based coating known as a liposome. These liposomes move to the tumour site, where they release the drug. This method has fewer side effects.

Drugs like Doxorubicin and Daunorubicin may be used in this manner. Other systemic agents include Vincristine, bleomycin, Etoposide and Paclitaxel.

Treatment for Kaposi's sarcoma after organ transplant

Kaposi's sarcoma after an organ transplant is controlled by stopping or changing the immunosuppressant drugs.

If the symptoms do not resolve then treatment with chemotherapy or radiotherapy should be initiated.

Cryotherapy

This is a procedure that uses liquid nitrogen or other extremely cool chemicals to freeze the affected tissues. This destroys the cancer.

Surgical excision of the lesions

Surgical excision of the lesions is an option that is not widely used due to fears of spread of the cancer to wound edges and surrounding tissues.

When only a few, small Kaposi's sarcoma lesions are present, they may be removed with surgical therapy.

Interferon therapy

This is a new therapy under the term biological therapy. Biologic therapy uses chemicals produced naturally by the body. These molecules are then manufactured in the laboratory.

They help the immune system to attack the cancer cells.

Interferons are highly toxic molecules that may be tried in treatment of wide spread Kaposi's sarcoma. The injections are needed daily and are given into the muscles (Intramuscular injections) or subcutaneously (under the skin).

Side effects include fever, chills, loss of appetite, headaches, nausea, fatigue and body aches.

Preventive measures

Preventive measures include practicing safe sex to reduce the risk of acquiring HIV.

Sources:

1. http://www.patient.co.uk/doctor/Kaposi's-Sarcoma.htm
2. documents.cancer.org/.../003106-pdf.pdf
3. http://www.tumorvirology.pitt.edu/lab%20pubs/Antman-Chang%20NEJM.pdf