All About Kaposi's Sarcoma

What is Kaposi's sarcoma?

Kaposi's sarcoma (KS) is a cancer that starts in the cells that line the blood vessels and the lymphatic system. Tumors appear on the skin or inside the mouth but can also start in the lymph nodes, lungs, or digestive tract. Kaposi's sarcoma first became recognized as an AIDS-defining illness before the use of medications to control HIV (Human Immunodeficiency Virus). Much more is known about Kaposi's sarcoma through research over the years since it first appeared. For example, in 1994, it was found that infection with the human herpes virus 8 (HHV-8) was responsible for Kaposi's sarcoma. Although you need to be infected with HHV-8 in order to develop KS, many people with HHV-8 infection will never develop the disease. This is because our immune systems work to control the virus and keep it from causing tumors.

Kaposi's sarcoma is classified according to the clinical circumstances in which it arises. The four types of Kaposi's sarcoma are as follows:

Classic

Classic Kaposi's sarcoma (CKS) often presents in middle-aged or elderly patients. Although it can be seen in other parts of the world, it is more often seen in the Mediterranean region, Middle East, or Eastern Europe. CKS presents more commonly in men, and the lesions often appear on the legs and feet (soles and toes) as red, purple, or deep blue patches that grow into larger plaques. Infection with HHV-8 is more common in these regions and is likely the cause of CKS cases. It has been suggested that as these people get older, their immune systems weaken, and Kaposi's sarcoma lesions develop. Because those with CKS tend to have stronger immune systems than those with other types of Kaposi's, the CKS lesions often develop slower and spread less quickly.

Epidemic (AIDS-related) Kaposi's Sarcoma

This subtype of Kaposi's sarcoma is the most common. It was first described during the 1980s during the AIDS epidemic before the discovery of HAART (highly active antiretroviral therapy). When someone is infected with HIV, they do not develop AIDS until the virus has damaged their immune system to the point that it is not working well or at all. As one's immune system is weakened, infections can develop. These are called opportunistic infections. It is thought that HHV-8 is sexually transmitted much like the HIV virus. Since the use of HAART, the incidence of KS has declined in the HIV-infected population.

When the immune system is weak, the HHV-8 virus is much more likely to lead to Kaposi's sarcoma. Because of this, Kaposi's sarcoma was one of the first AIDS-defining illnesses. The lesions tend to be very different than other forms of KS. These lesions tend to be found on the head, neck, chest, and back, but can also be found in mucous membranes, such as in the GI tract (stomach and intestines) and the lungs. AIDS-related KS is often more aggressive, with many more lesions that progress more quickly than other types.

Iatrogenic (Transplant-related) Kaposi's Sarcoma

After the transplant of an organ from a donor into a recipient, the transplant recipient must take medications to suppress their immune system. These medications protect the new organ from being attacked by the immune system. Kaposi's sarcoma arises when the transplant recipient harbors the HHV-8 virus or when the transplanted organ is infected with the virus prior to the transplant. After the transplant, suppression of the immune system is critical in maintaining a working organ, however, this allows the HHV-8 virus to develop KS lesions. Often, decreasing the immune-suppressing medications can control transplant-related KS. The lesions of transplant-related KS tend to be much less aggressive than AIDS-related KS.

Endemic (African-related) Kaposi's Sarcoma

This type of KS occurs in people living in Equatorial Africa. People living in Africa tend to have weakened immune systems due to malaria, chronic infections, and malnutrition. It is diagnosed in a broader age range than other types of KS. Endemic KS happens more often in those younger than 40 years of age. There is a rare, but more aggressive form of endemic KS seen in children, which affects the lymph nodes and organs, and tends to progress quickly.

What causes Kaposi’s sarcoma and am I at risk?

HHV-8 infection (Kaposi’s sarcoma-associated herpes virus or KSHV), is needed to develop KS. HHV-8 is not often tested for, and many are not aware that they are infected, nor will they ever develop KS. In the United States, less than 10% of the population has HHV-8. It is more common in those with HIV and more common in men who have sex with men than in men who only have sex with women. 

KS has become less common in the United States now that AIDS is better managed with medications. There are about 6 cases per million people each year and it's more common in men than women. It is more common in African Americans than in whites. About 1 in 200 organ transplant recipients develop KS in the United States each year. Please refer to the above sections for what causes each type of Kaposi’s sarcoma.

How can I prevent Kaposi’s sarcoma?

Kaposi sarcoma is caused by the HHV-8 infection. There are no vaccines to protect against it. Preventing the transmission of HHV-8 is the best way to prevent KS. Most cases of KS in the United States are in people who have AIDS. To prevent the transmission of HIV and HHV-8, it is important to practice safe sex through the use of condoms. People who inject recreational drugs should stop, or at least use clean needles and injection supplies. An HIV-infected mother can pass the virus to her baby. Both the mother and baby should be treated with anti-HIV medications. For those who are already infected with HIV and HHV 8, medications to strengthen the immune system can be given, which include highly active antiretroviral therapy (HAART). These medications, along with the early treatment of infections can reduce the likelihood of KS.

What screening tests are used for Kaposi’s sarcoma?

There are no recommended screening tests to monitor for KS in people who are not at risk for the disease. However, since those infected with HIV are at a higher risk for developing KS, they should be examined regularly by health care providers who are experienced in recognizing KS and other diseases linked with HIV and AIDS.

What are the signs of Kaposi's sarcoma?

A sign of KS is red, purple, or deep blue lesions most often found on the skin and mucosa. The lesions do not hurt or itch and their color comes from the blood vessels in the lesions. As noted above, classic KS and endemic KS are often seen on the legs and feet. AIDS-related KS and iatrogenic KS can be seen on mucosa-lined surfaces (GI and respiratory tract) as well as on inner organs (like the lungs).

KS lesions often start as small flat lesions that can range in size from millimeters to several centimeters. These lesions are known as macules, which can stay unchanged for years in classic KS. In rare cases, they will progress very rapidly. As the lesions grow, they will often grow together (coalesce), forming larger lesions known as plaques. As the plaques grow, they can form even larger lesions known as nodules. Nodular lesions can tear and bleed. In the endemic form of KS, lesions can form as fluid-filled cysts due to invasion of lymphatic vessels.

Finally, in AIDS-related KS, the lesions can be seen on the legs and feet, the face, the genitalia, and the mouth. The lesions have a similar appearance as other forms of KS. However, the natural progression of AIDS-related KS tends to be much more rapid with nodules developing rather quickly. AIDS-related KS in the GI tract can present as lesions with no symptoms, found on radiology tests for something else or can present with symptoms including weight loss, stomach pains, bleeding, or diarrhea. Lesions within the respiratory tract can also be asymptomatic. If symptoms develop, they can be shortness of breath, cough, chest discomfort, or coughing up blood (hemoptysis).

How is Kaposi's sarcoma diagnosed?

A diagnosis is made by looking at the lesions and clinical setting in which they are found. A skin biopsy may be done. Either a tiny round piece of tissue will be removed through a procedure called a punch biopsy or the entire lesion is removed, which is called an excisional biopsy. Both can be done with local anesthesia in your provider’s office. Though a lesion may appear to be KS, it could be other diagnoses such as angiosarcoma, hemangiomas, and bacterial infections (i.e. Bartonella). These possible diagnoses are called "differential diagnoses" and you may hear the medical team say they need to rule out differential diagnoses.

For those with immunosuppression and symptoms, GI tract involvement can be seen with an upper or lower endoscope. Respiratory involvement may be seen with a chest X-Ray or CT scan but a bronchoscopy to get a biopsy to confirm the diagnosis may be needed.

How is Kaposi's sarcoma staged?

KS is not staged like other cancers and there is no officially accepted system. For AIDS-related KS, the AIDS Clinical Trials Group (ACTG) system is the most widely used staging system. The ACTG considers three factors in this staging system: 

• The extent of the tumor (T). 
• The status of the immune system is measured by the CD4 cell count. 
• The extent of involvement within this body known as system illness (S). 

Within each heading, there are also 2 subgroups, which are either 0 (good risk), or 1 (poor risk). It also considers the Karnofsky Performance Status scale. This is a measurement of a cancer patient's ability to perform daily tasks. 

How is Kaposi's sarcoma treated?

Because there is no cure for HHV-8, there is no cure for Kaposi's sarcoma. The disease can often be controlled with treatment. The goal when treating Kaposi's sarcoma is to improve your symptoms and prevent progression to more aggressive lesions. Due to the rare nature of classic KS, there is no standard treatment. Often the treatment is based on the experiences of the treating provider, patient preference, and the clinical picture (i.e. AIDS-related, classic KS in elderly man, etc.). Your provider will talk to you about your treatment options. 

Treatments for Classic and Endemic KS

For classic and endemic KS, surgery, radiation therapy, and topical therapies are used. If lesions are limited and not causing symptoms, you may just be watched. Surgery can be done to remove a single lesion if it is causing symptoms, but more lesions often develop. Radiation therapy uses high-energy x-rays to damage the DNA of cells. This kills the cancer cells, or at least stops them from reproducing, and works to treat all forms of KS. Lesions can start outside of where the radiation was used and limit its use. Cryotherapy is the use of liquid nitrogen to freeze and kill cancer cells. It clears most lesions but can cause blistering and pain. Laser ablation is used on lesions on the face and in the mouth.

Chemotherapy may be put directly into the lesions using a needle. The most common is vinblastine. Alitretinoin and imiquimod are topical medications that can be put on the lesion to stop cell growth. These medications can be put on by the patient, but tend to be costly and can cause skin reactions. 

Chemotherapy can also be given into a vein so that it works throughout the whole body. It can be used to treat aggressive and advanced classic KS. You may be given more than one type of chemotherapy, called a regimen. The most often used systemic chemotherapies used are gemcitabine, doxorubicin, daunorubicin, vinorelbine, bleomycin, vinblastine, vincristine, etoposide, and paclitaxel. Treatment with immunotherapy medications such as thalidomide, pomalidomide, and lenalidomide, can be useful. These medications stimulate the immune system and can kill cancer cells. 

Immunosuppression Related KS Treatment

In cases of KS related to immunosuppression, immune function needs are closely watched. Treatment of the cause can often stop the progression of lesions. For those with AIDS-related KS, highly active antiretroviral (HAART) is often used. HAART helps prevent and treat KS as it improves CD4 counts as well as keeps the viral load low (amount of virus found in the blood). When KS is caused by intentional immunosuppression, as in the case of an organ transplant, a decrease in the level of immune suppression is recommended.

Local therapy is used for symptomatic lesions and palliation (helping with symptoms). Like classic KS, local therapies include radiation therapy, topical medications, and intralesional (into the lesion) chemotherapy. Prior to the use of HAART, radiation therapy was often used for locally advanced disease. Intralesional chemotherapy, chemotherapy that is injected directly into the lesion, is generally only used in smaller lesions.

Chemotherapy is only used in patients with widespread skin lesions, edema (swelling) from the lesions, lesions on internal organs causing symptoms, skin lesions that don’t respond to local treatments, and immune reconstitution inflammatory syndrome. Immune reconstitution inflammatory syndrome is the acute worsening of KS that can happen within weeks of starting HAART. The chemotherapies used include paclitaxel, doxorubicin, and daunorubicin. If HAART is no longer controlling the KS, pomalidomide, an immunomodulatory drug, may be used. 

Clinical Trials

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow-Up Care and Survivorship

Survivors of Kaposi’s sarcoma require lifelong monitoring and survivorship care because in some cases the treatment has not completely removed and destroyed the cancer. Your provider will watch you closely after treatment and during your visits your provider will determine how to monitor the disease and how, if necessary, to continue treatment. The treatment(s) you have already received can cause long-term side effects and you should report any new or recurrent symptoms to your care team immediately.

Fear of recurrence, financial impact of cancer treatment, employment issues, changes in appearance, and coping strategies are common emotional and practical issues experienced by Kaposi’s sarcoma survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With nearly 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More Information

American Cancer Society

Information and support services available for patients and family members.

www.cancer.org

Sarcoma Alliance

This website, started by a sarcoma survivor, is based on the mantra "guidance, education, and support". They also maintain a list of specialty centers.

http://www.sarcomaalliance.org

Sarcoma Foundation of America

The SFA raises money for sarcoma research and aims to raise awareness of sarcoma. The site has information for patients as well.

http://www.curesarcoma.org/