What is Kaposi sarcoma?

Related conditions:
Human herpesvirus 8 (HHV-8), acquired immunodeficiency syndrome (AIDS), organ transplant

Definition:
Kaposi sarcoma is a cancer of connective tissue named for dermatologist Moritz Kaposi, who first described endothelial raised lesions that develop in connective tissues and mucosal membranes. There are four known types of Kaposi sarcoma: classic Kaposi sarcoma, which is mostly found in older Italian or eastern European Jewish men; endemic or African Kaposi sarcoma, which mainly afflicts young men who live in equatorial Africa; acquired or immunosuppressive-therapy-related Kaposi sarcoma, found in posttransplant patients; and epidemic Kaposi sarcoma, which develops in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). Epidemic Kaposi sarcoma is the most clinically aggressive and most prevalent form of the disease.

Risk factors: Risk factors differ for each type of Kaposi sarcoma but include ethnicity, age, and disease state. Men are much more prone to the disease than women. In the United States, African American men are much more likely to develop Kaposi sarcoma than are Caucasian or Hispanic men. HIV is a distinct risk factor for epidemic Kaposi sarcoma. Human herpesvirus 8 (HHV-8), a deoxyribonucleic (DNA) virus, is believed to be the cause of all types of Kaposi sarcoma.

Etiology and the disease process: Kaposi sarcoma develops as a result of infection with HHV-8, also known as the Kaposi sarcoma–associated herpesvirus (KSHV).The virus infects the endothelial cells, which line the insides of blood vessels and lymphatic vessels, and causes them to live longer and divide more rapidly than they otherwise would. HHV-8 is much more common than Kaposi sarcoma; the sarcoma typically only develops when an infected person becomes or is already immunocompromised.

Lesions initially develop as flat or raised colored blotches under the skin or mucous membranes, most often on the face or legs. Swelling or bleeding may impair nearby organ function, especially in the lungs, liver, and gastrointestinal (GI) tract.

Classic, African, and immunosuppressive-therapy-related Kaposi sarcoma lesions usually occur on the skin and only occasionally spread into the mucous membranes or the lymph or gastrointestinal systems, although aggressive African Kaposi sarcoma tumors may also penetrate bone or manifest in lymph nodes and organs. In contrast, epidemic Kaposi sarcoma lesions are nodular, widespread, and rapidly multiplying. They develop in the skin, mouth, lymph nodes, and organs, especially the GI tract, lungs, liver, and spleen. In most cases, untreated epidemic Kaposi sarcoma will spread extensively throughout the patient's organs.

Incidence: Classic Kaposi sarcoma is rare. While its incidence has increased in women, it still occurs in an approximate 4:1 ratio of men to women. In the 1950s, African Kaposi sarcoma accounted for approximately 9 percent of all cancer found in Ugandan men; following the advent of HIV/AIDS, African Kaposi sarcoma and epidemic Kaposi sarcoma together were found to account for approximately 37,000 new cases (many in prepubescent children, most often boys) and 25,000 deaths in sub-Saharan Africa each year. Immunosuppressive-therapy-related Kaposi sarcoma develops in an estimated 0.5 percent of organ-transplant recipients in the United States.

Epidemic Kaposi sarcoma is one of three types of cancer classified as AIDS-defining cancers, the other two being non-Hodgkin lymphoma and cervical cancer. (An AIDS-defining condition is one whose presence in an HIV patient indicates that the disease has progressed to full-blown AIDS.) It is found in approximately 10 to 15 percent of HIV patients and is the most common AIDS-related cancer in the United States. The overall incidence of epidemic sarcoma among AIDS patients in the United States was once as high as 25 percent, but it has decreased steadily with the use of highly active antiretroviral therapy (HAART). Prior to the development of HAART, and for those without access to HAART today, AIDS patients were (or are) approximately 20,000 times more likely to develop Kaposi sarcoma than the general population; with HAART, that risk decreases to 3,600 times more likely.

Symptoms: Lesions are often disfiguring, palpable, and painful when swollen. Tumors bleed easily, causing ulceration, necrosis, and tissue discoloration. Symptoms are directly related to lesion location; for example, speech and feeding problems occur with palate tumors. Common symptoms of lesions in organs include bleeding from gastrointestinal lesions, nausea, vomiting, bowel obstruction, cough, dyspnea, and hemoptysis. Symptoms unique to epidemic Kaposi sarcoma are swollen lymph nodes, fever, and weight loss.

Screening and diagnosis: Although HHV-8 is directly associated with Kaposi sarcoma, routine screening is not recommended for the general population. However, people with HIV/AIDS should be screened regularly.

Endoscopies, bronchoscopies, and chest x-rays may be used to screen for KS lesions. Identifiable diagnostic features include purple nodules along skin tension lines, green-yellow discoloration secondary to hemorrhage, surrounding edema, and lesion dissemination. Diagnostic histology shows an intact epidermis, new blood-vessel formation with extravasated red blood cells, hemosiderin deposits, infiltrates of spindle-shaped cells, and lymphocytic inflammatory infiltrate. Lesion biopsies are definitive but carry a bleeding risk. Detection of HHV-8 in tumor tissue can confirm an uncertain diagnosis.

Kaposi sarcoma lesions are hard to measure and cannot be staged by traditional cancer classification methods. However, the AIDS Clinical Trials Group has developed staging for HIV-related Kaposi sarcoma that accounts for lesion size and presence and for HIV stability.

Treatment and therapy: Treatment for Kaposi sarcoma involves local, systemic, and antiretroviral treatments or any combination of these. Surgical treatment is limited to diagnostic biopsies and often requires concomitant radiation to prevent spreading.

Local treatment with radiation, cryosurgery, or topical retinoids is best for palliation, for cosmetically unacceptable lesions, or for refractory disease. Radiation, the primary method, has a response rate of 80 to 90 percent.

Systemic treatment for progressive disease includes interferon (INF) alpha, liposomal anthracyclines or paclitaxel, and investigational signal transduction or cytokine inhibitors. INF alpha is an immunomodulatory agent associated with 45 to 70 percent remission rates. Palliative chemotherapeutics may eradicate some lesions and decrease morbidity. Ganciclovir, foscarnet, and cidofovir antivirals are active against HHV-8 and are being studied to reduce lesion size or progression.

First-line treatment of HIV-related Kaposi sarcoma is HAART, which decreases HIV replication and thereby decreases the frequency of Kaposi sarcoma lesion development. In addition, protease inhibitors such as saquinavir, indinavir, and ritonavir have direct antitumor and antiproliferative effects that can improve Kaposi sarcoma even without an observed increase in the CD4 count. Additional treatments are reserved for visceral disease progression despite HAART.

Prognosis, prevention, and outcomes: Kaposi sarcoma may resolve spontaneously or with treatment; however, prepubescent patients with the aggressive lymphadenopathic form of African Kaposi sarcoma face a 100 percent mortality rate within three years. Approximately 33 percent of patients with classic Kaposi sarcoma risk development of secondary tumors, typically non-Hodgkin lymphoma. Although AIDS-related Kaposi sarcoma with respiratory failure was once associated with fatality within weeks, HIV-suppressive therapy has made stabilization, complete remission, and prevention of new lesions possible. In the United States, the overall five-year relative survival rate for patients with Kaposi sarcoma is approximately 72 percent.

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