Kaposi sarcoma is a cancer that forms in the lining of blood and lymph vessels, most often appearing as purple, red, or brown lesions on the skin. It is caused by infection with Human Herpesvirus 8 (HHV-8), also called Kaposi sarcoma-associated herpesvirus. Not everyone infected with HHV-8 develops the cancer, but a weakened immune system dramatically raises the risk.
What Causes Kaposi Sarcoma
HHV-8 infects the cells that line blood and lymph vessels. Once inside, the virus can remain dormant for years, producing a protein called LANA that keeps it hidden in every infected cell. Under certain conditions, particularly when the immune system is suppressed, the virus drives these cells to multiply abnormally. One viral protein, vCyclin, helps infected cells bypass the natural aging process that would normally stop them from dividing. Over time, this uncontrolled growth forms the characteristic tumors of Kaposi sarcoma.
HHV-8 infection alone isn’t enough. The immune system typically keeps the virus in check, which is why most people who carry HHV-8 never develop cancer. The disease emerges when something weakens immune surveillance: HIV infection, organ transplant medications, or the natural decline of immune function with age.
How HHV-8 Spreads
The virus is primarily spread through saliva, which appears to be the most important route of transmission. People with asymptomatic HHV-8 infection frequently shed the virus in their saliva and occasionally in genital secretions. Sexual contact, particularly among men who have sex with men, is another significant route. In parts of sub-Saharan Africa where the virus is very common, mother-to-child transmission during pregnancy or birth also occurs. Blood transfusion has been documented as a transmission route in Uganda, though studies in the United States and Western Europe have not found evidence of this.
The prevalence of HHV-8 varies enormously by region. In the general U.S. population, roughly 3% to 7% of people carry the virus. That rises to 10% to 20% in Mediterranean countries, 16% in China, and 30% to over 90% in parts of sub-Saharan Africa. Among men who have sex with men in the U.S., seroprevalence ranges from 13% to 20% in those without HIV, jumping to 30% to 68% in those with HIV.
The Four Types of Kaposi Sarcoma
Classic
Classic Kaposi sarcoma typically affects men over 50 of Eastern European or Mediterranean descent, with a male-to-female ratio of 17 to 1. Lesions usually appear on the lower legs and progress slowly over years. This form tends to stay localized to the skin for a long time before potentially involving internal organs in later stages.
Endemic (African)
Endemic Kaposi sarcoma occurs in sub-Saharan Africa and has an unusual predilection for children, mirroring the high rates of HHV-8 infection in these regions. It often involves generalized lymph node swelling rather than the skin-dominant pattern seen in other types. This form can be aggressive, particularly in younger patients.
AIDS-Related (Epidemic)
This is the most well-known type and the second most common tumor in people with HIV. It is classified as an AIDS-defining illness, meaning its presence signals advanced immune suppression. Up to 30% of HIV patients not taking antiretroviral therapy will develop Kaposi sarcoma, and the risk is highest when the immune cell count drops below 200 cells per cubic millimeter. HIV-positive men who have sex with men face a 5- to 10-fold increased risk compared to other HIV-positive individuals. Even among people with HIV who are on antiretroviral therapy, the estimated incidence is 289 per 100,000 person-years.
Iatrogenic (Transplant-Related)
People taking immune-suppressing drugs after organ transplantation face a 400- to 500-fold increased risk of Kaposi sarcoma compared to the general population. Over 5% of transplant patients who develop any new cancer will develop this one. The male-to-female ratio is 3 to 1. Patients who receive bone marrow or blood stem cell transplants have a much lower risk than those who receive solid organ transplants, likely because the immunosuppression required is different.
What the Lesions Look Like
Kaposi sarcoma lesions typically begin as small, flat patches or nodules on the lower legs. They range in color from violaceous (a deep purple-red) to dusky reddish-brown, and they can be mistaken for bruises in early stages. Over time, the lesions grow larger and thicken into raised plaques that can spread quickly across large areas of the legs. In advanced disease, lesions may appear anywhere on the body, including the face, torso, and inside the mouth.
The cancer doesn’t always stay on the skin. It can involve the gastrointestinal tract, lungs, liver, kidneys, spleen, and lymph nodes. In some cases, internal organs are affected without any visible skin lesions at all. GI involvement can cause bleeding or obstruction, while lung involvement may lead to shortness of breath or bloody cough. Staging generally moves from localized skin nodules (stage one) through widespread plaques (stage two) to visceral and GI tract involvement (stages three and four).
How It Is Diagnosed
Diagnosis requires a skin biopsy, typically a small punch biopsy taken from a suspicious lesion. Under the microscope, pathologists look for the characteristic “spindle cells,” the abnormal vessel-lining cells driven by HHV-8. To confirm the diagnosis, the tissue is stained with a marker that detects a specific viral protein (LNA-1), which is present in every HHV-8 infected tumor cell. A second marker called D2-40, which highlights lymphatic vessel cells, helps distinguish Kaposi sarcoma from other vascular tumors. These two stains are more reliable than older, less specific markers.
If visceral involvement is suspected, imaging studies of the chest, abdomen, or GI tract may follow. An endoscopy can identify lesions in the stomach or intestines that might not cause symptoms until they’re advanced.
Treatment Approaches
Treatment depends heavily on which type of Kaposi sarcoma is present and how widespread it is.
For AIDS-related Kaposi sarcoma, the cornerstone of treatment is starting or optimizing antiretroviral therapy. Rebuilding the immune system can lead to significant regression of lesions, sometimes without any cancer-specific treatment. When lesions are extensive or involve internal organs, chemotherapy is added alongside antiretroviral therapy.
For iatrogenic Kaposi sarcoma, reducing or switching immunosuppressive medications is the first step when safely possible. This alone can sometimes cause lesions to shrink or disappear, though it requires careful balancing against the risk of organ rejection.
Classic Kaposi sarcoma, which tends to grow slowly, may be managed with local treatments for isolated lesions, including radiation therapy or surgical removal. More widespread classic disease may require systemic chemotherapy.
A newer treatment avenue involves immunotherapy drugs that block a protein called PD-1, which cancer cells use to hide from the immune system. A pooled analysis of 91 patients treated with these drugs found that 61% had their tumors shrink meaningfully, with 17% achieving complete disappearance of detectable disease. The overall disease control rate was 91%. Side effects were common but generally manageable, with itching, fatigue, and joint pain being the most frequent. These results are particularly relevant for patients whose cancer has not responded to standard chemotherapy or radiation.
Living With Kaposi Sarcoma
The outlook for Kaposi sarcoma has improved dramatically since the introduction of effective HIV treatment in the mid-1990s. For people with HIV, consistent antiretroviral therapy is both prevention and treatment. Many patients with limited skin disease live for years with manageable symptoms, particularly when the underlying immune suppression is addressed.
Lesions that have flattened or faded may leave behind permanent discoloration of the skin. Swelling in the legs, caused by the cancer disrupting lymphatic drainage, can persist even after successful treatment and may require compression garments. Regular monitoring is important because the cancer can recur, especially if immune function declines again. For transplant patients, any new skin lesion warrants prompt evaluation, given their elevated baseline risk.