Kaposi's sarcoma

Kaposi's sarcoma (KS) is a kind of sarcoma in which cancerous cells, as well as abnormal growth of blood vessels, form solid lesions in connective tissue. KS was historically very rare and found mainly in older men of Mediterranean or African origin (classic KS) or patients with severely weakened immune systems, such as after an organ transplant (immunosuppressive treatment related KS). However, in the early 1980s a more aggressive form, epidemic KS, began to be seen in AIDS patients and was one of the first clues to the existence of the AIDS epidemic.

Symptoms

KS lesions are nodules or blotches that may be red, purple, brown, or black, usually painless but sometimes painful and swollen. They appear under the surface of the skin or on mucous membranes, but may also be found in internal organs, particularly the respiratory system or gastrointestinal system; internal lesions are most commonly seen in epidemic KS.

Skin or mucous membrane lesions are not fatal unless they cause enough swelling to obstruct circulation or breathing, or lesions in the mouth or esophagus prevent eating. Lesions affecting the internal organs are much more often fatal. KS can occur among transplant patients in whom the tumor can disseminate. Stopping immunosuppression can eliminate KS but also can cause rejection of the transplanted organ.

Pathophysiology and Diagnosis

KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells. The tumor is highly vascular, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color. Inflammation around the tumor may produce swelling and pain.

Although KS may be suspected from the appearance of lesions and the patient's risk factors, a definite diagnosis can only be made by biopsy and microscopic examination, which will show the presence of spindle cells. Detection of the viral protein LANA in tumor cells confirms the diagnosis.

Treatment

There is no known cure for KS. Treatment is focused on eliminating the existing lesions, by means of chemotherapy drugs such as paclitaxel and bleomycin, radiation therapy, or surgical removal. However, this does not prevent new lesions from developing. Treatment with drugs such as ganciclovir that target the virus causing Kaposi's sarcoma may prevent new tumors but do not adequately treat existing lesions.

History and Theories

The disease is named after Moritz Kaposi (1837-1902), a Hungarian dermatologist who first described the symptoms in 1872. Research over the next century suggested that KS, like other forms of cancer, might be caused by a virus or genetic factors, but no definite cause was found.

With the advent of the AIDS epidemic, KS, as one of the most common AIDS symptoms, was researched more intensively in hopes that it might reveal the cause of AIDS. Some researchers suspected that HIV itself directly caused KS; others thought that it was simply a result of the immune system losing its ability to protect against some common cancer-causing agent; and others took it as a sign that AIDS was not primarily a viral disease at all but an effect of toxic chemicals that can damage the immune and vascular systems, such as nitrite poppers.

Research since 1994 has led to a consensus that the primary cause of KS is the herpesvirus HHV-8, sometimes referred to as Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is almost always found in KS tissue samples. However, KSHV infection does not always lead to KS and it is still unclear what other factors may be required, such as pre-existing immune system damage, or a specific interaction with HIV or other viruses. KSHV is a unique human tumor virus that has incorported cellular genes that cause tumors into its genome ("molecular piracy"); the stolen cellular genes may help the virus escape from the immune system, but in doing so it also causes cells to proliferate. It is related to Epstein-Barr virus, a very common herpesvirus that can cause human cancers.

The fact that KS occurs much more often in males than in females has not been entirely explained. In the early years of the AIDS epidemic in North America and Western Europe, the incidence of KS almost exclusively among male homosexual AIDS patients suggested that it was spreading as a sexually transmitted infection within that population, or was due to other lifestyle factors. However, research in Africa has shown that even in the absence of HIV/AIDS, KS is more common in men than women although KSHV infection is equal between both sexes. This suggests that sex hormones may either protect from or predispose to KS in persons infected with the virus.

KS and AIDS

In AIDS patients, Kaposi's sarcoma is considered to be an opportunistic infection, i.e., a disease that is able to gain a foothold in the body because the immune system has been weakened. With the rise of AIDS in Africa, where KSHV is widespread, KS has become the most frequently reported cancer in some countries, such as Zimbabwe. KS appears to develop less often in the presence of the HIV-2 strain of HIV, which is the most common strain in Africa, than with HIV-1.

Because of their highly visible nature, external lesions are sometimes the presenting symptom of AIDS. Kaposi's sarcoma entered the awareness of the general public with the release of the film Philadelphia, in which the main character was fired after his employers found out he was HIV-positive due to visible lesions. Unfortunately, by the time KS lesions appear, it is likely that the immune system has already been severely weakened.

Current clinical practice in AIDS care is usually to avoid treating KS lesions directly unless they are causing pain, disfigurement, or internal organ damage. Reducing the HIV viral load and increasing the T-cell count appears to slow or stop the progression of KS in AIDS patients, and with the decrease in death rate among AIDS patients receiving new treatments in the 1990s, the incidence and severity of epidemic KS also decreased.