Kaposi sarcoma

Definition

Kaposi's sarcoma produces pink, purple, or brown tumors on the skin, mucous membranes, or internal organs. It was a very rare form of cancer, primarily affecting elderly men of Mediterranean and eastern European background, until the 1980s, when it began to appear among AIDS patients. Milder forms of the disease can be managed successfully with topical agents and therapies; widespread disease requires chemotherapy.

Description

Investigators recognize four distinct forms of Kaposi's sarcoma (KS). The first form, called classic KS, was described by the Austrian dermatologist Moricz Kaposi more than a century ago. Classic KS usually affects older men of Mediterranean or eastern European backgrounds by producing tumors on the lower legs. Though at times painful and disfiguring, they are not generally life-threatening. The second form of the disease, African endemic KS, primarily affects boys and men. It can appear as classic KS, or in a more deadly form that quickly spreads to tissues below the skin, the bones and lymph system, leading to death within a few years of diagnosis. Another form of KS, iatrogenic KS, is observed in kidney and liver transplant patients who take immunosuppressive drugs to prevent rejection of their organ transplant. Iatrogenic KS usually reverses after the immunosuppressive drug is stopped. The fourth form of KS, AIDS-related KS, emerged as one of the first illnesses observed among those with AIDS. Unlike classic KS, AIDS-related KS tumors generally appear on the upper body, including the head, neck, and back. The tumors also can appear on the soft palate and gum areas of the mouth, and in more advanced cases, they can be found in the stomach and intestines, the lymph nodes, and the lungs.

Causes & symptoms

A variety of factors appear to contribute to the development of KS:

• Genetic predisposition. People with classic KS, and those who develop the tumors after transplantation, are more likely than others to possess a genetically determined immune factor called HLA-DR. Cases of KS that run in families, however, are rare.
• Sex hormones. The fact that the disease is more likely to afflict men than women suggests sex hormones, such as testosterone in men, may stimulate the growth of KS tumors, and that estrogen in women may retard their growth.
• Immune suppression. Liver, kidney, and bone marrow patients who take immunosuppressive drugs to prevent transplant rejection frequently develop KS lesions. Similarly, KS has been observed in patients receiving systemic treatment with high-dose corticosteroids, which also suppresses the immune system. Immune suppression is the hallmark of AIDS.
• Infectious, sexually transmitted agent. AIDS-related KS is ten times more likely to appear in homosexual or bisexual men with AIDS than it is to appear in IV drug users, hemophiliacs, or women. In addition, the proportion of AIDS patients who develop KS has decreased markedly as safer-sex practices have become more widespread. A number of viruses have been proposed as possible causes. They include cytomegalovirus and human papilloma virus, fragments of which have been found in KS tumor specimens. A more likely candidate, however, is a new herpes virus that has been called human herpes virus 8 (HHV-8) or KS-associated herpes virus (KSHV). Since fragments of the virus were first disclosed in KS samples in 1994, they have since been found in KS samples taken from patients with classic KS, African endemic KS, and KS in transplant patients. Fragments of HHV-8, however, have also been found in patients who have other skin diseases but who do not have KS.

Diagnosis

Many physicians will diagnose KS based on the appearance of the skin tumors and the patient's medical history. Unexplained cough or chest pain, as well as unexplained stomach or intestinal pain or bleeding, could suggest that the disease has moved beyond the skin. The most certain diagnosis can be achieved by taking a biopsy sample of a suspected KS lesion and examining it under high-power magnification. For suspected involvement of internal organs, physicians will use a bronchoscope to examine the lungs or an endoscope to view the stomach and intestinal tract.

Treatment

There is no single best treatment for KS. Treatments range from topical agents for mild disease with few tumors to more aggressive systemic chemotherapy for more serious KS that has spread to large areas of skin or the internal organs. Physicians will frequently combine topical, radiation, and various systemic chemotherapy drugs, depending on the sites of the body affected, the speed at which it is progressing, and the patient's overall health, among other considerations.

Local therapy

When the number of KS tumors is small and the disease appears to be progressing slowly, physicians will consider destroying the lesions with cryotherapy (using a liquid nitrogen spray or probe to freeze the tumor); injections directly into the tumor of vinblastine (a drug also used for systemic chemotherapy); or radiation therapy targeted at the tumor sites.

Systemic chemotherapy

With widespread KS lesions over the body surface, or evidence of spread to other parts of the body, physicians will consider systemic chemotherapy drugs, either alone or in a variety of combinations. Combination therapy generally produces a better response, with fewer toxic side effects associated with large doses of any single drug. Among the chemotherapy agents that physicians will consider using are vinblastine, bleomycin, and doxorubicin. A new class of chemotherapy drugs, called liposomally encapsulated drugs, appears to produce good results with fewer toxic side effects than do more conventional chemotherapy drugs.

Antiviral therapy

Evidence suggests that for some individuals, the class of AIDS drugs called protease inhibitors, in combination with other anti-HIV drugs, can reduce the levels of detectable HIV in the blood to nearly zero, and in some patients stabilize or reverse KS tumors. More research is needed in this area. Since the discovery of HHV-8, interest in an antiviral approach to KS has increased. There is no evidence, however, that two antiviral drugs commonly prescribed for herpes, acyclovir and ganciclovir, have any effect on the disease. One study of 20,000 patients with HIV and AIDS found that those who took foscarnet, another antiviral medication that works in a different way than acyclovir and ganciclovir, were less likely to develop KS tumors.

A number of other treatments for KS are under investigation, including:

• Interferon-alpha. Interferon-alpha is made by the body and has powerful effects on the immune system. Investigators have tried injecting it directly into lesions, and also in combination with other anti-HIV drugs such as zidovudine, with some success.
• Retinoids. These derivatives of vitamin A have long been used to treat acne and other skin diseases. Investigators are evaluating both topical preparations of these drugs as well as systemic versions.
• Laser therapy. In patients with small tumors, some investigators report success using lasers to destroy KS lesions. The reappearance of new tumors, may be high, however.

Alternative treatment

The Bastyr University AIDS Research Study has been investigating and collecting data on treatment for KS and other opportunistic conditions that are AIDS-related. Among the treatments under investigation are nutritional and herbal therapies (both internal and external). Bastyr University is located in Seattle, Washington.

Prognosis

The prognosis for patients with classic KS is good. Tumors can frequently be controlled and patients frequently die of other causes before any serious spread. African endemic KS can progress rapidly and lead to premature death, despite treatment. In AIDS-related KS, milder cases can frequently be controlled; the prognosis for more advanced and rapidly progressing cases is less certain and dependent on the patient's overall medical condition. There are indications that KS can be stabilized or reversed in patients whose level of HIV in the blood is reduced to undetectable levels via antiretroviral therapy.

Prevention

Safer sex practices may help to prevent AIDS-related KS by decreasing the risk of transmission of HHV-8. Treatment with antiretrovirals and protease inhibitors may help to preserve the function of the immune system in HIV patients and delay the appearance and progression of KS lesions.

Key Terms

African endemic Kaposi's sarcoma

Affects men and boys; can appear like classic KS or in a more lethal form.

AIDS-related Kaposi's sarcoma

Emerged as one of the first illnesses associated with AIDS patients. These tumors usually appear on the upper body, the soft palate and gum areas, and, as the disease advances, in the lymph nodes, stomach, intestines, and lungs.

Classic Kaposi's sarcoma

Usually affects older men of Mediterranean or eastern European backgrounds, and produces tumors on the lower legs.

Human herpesvirus 8

Also called Kaposi's sarcoma-associated herpesvirus (KSHV). Thought to be a viral cause for KS.

Iatrogenic Kaposi's sarcoma

Develops in transplant patients who take immunosuppressive drugs to prevent rejection of their organ transplant.

Further Reading

For Your Information

Books

• Fitzpatrick, Thomas B., et al. Color Atlas and Synopsis of Clinical Dermatology. New York: McGraw-Hill, 1997.
• Sams, W. Mitchell Jr., et al. Principles and Practice of Dermatology. New York: Churchill Livingstone, 1996.

  Periodicals

• Krown, Susan E. "Acquired Immunodeficiency Syndrome-Associated Kaposi's Sarcoma." Medical Clinics of North America 81(March 1997): 471-494.
• Myskowski, Patricia L., and Rosaline Ahkami. "Advances in Kaposi's Sarcoma." Dermatologic Clinics 15(January 1997): 177-188.
• Sung, Jennifer C.Y., et al. "Kaposi's Sarcoma: Advances in Tumor Biology and Pharmacotherapy." Pharmacotherapy 17(1997): 670-683.

  Organizations

• American Academy of Dermatology. 930 N. Meacham Road, PO Box 4014, Schaumburg, IL 60168-4014. (847) 330-0230. http://www.aad.org.
• Gay Men's Health Crisis. 119 West 24th Street, New York, NY 10011. (212) 807-6664. http://www.gmhc.org.

Gale Encyclopedia of Medicine. Gale Research, 1999.