Kaposi's sarcoma

Kaposi's sarcoma (KS) is a kind of sarcoma caused by a herpesvirus infection 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. The infectious agent responsible for all forms of the disease is known as Kaposi's sarcoma-associated herpesvirus (KSHV).

Contents

Symptoms

KS lesions are nodules or blotches that may be red, purple, brown, or black, usually painless but sometimes painful and swollen. They most often appear under the surface of the skin or on mucous membranes, where they are only dangerous if they cause enough swelling to obstruct circulation, breathing, or eating. They may also be found in internal organs, particularly the respiratory system or gastrointestinal system; internal lesions are most commonly seen in epidemic KS, and can cause fatal bleeding.

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 and prevention

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.

In KS associated with immunodeficiency or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In AIDS patients, this means reducing the HIV viral load and increasing the T-cell count. With the decrease in death rate among AIDS patients receiving new treatments in the 1990s, the incidence and severity of epidemic KS also decreased. The current clinical practice for AIDS or organ transplant patients is usually to avoid treating KS lesions directly, unless they are causing pain, disfigurement, or internal organ damage.

Blood tests to detect antibodies against KSHV have been developed and can be used to determine if a patient is at risk for transmitting infection to his or her sexual partner, or if an organ is infected prior to transplantation.

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 some 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.

In 1994, Yuan Chang and Patrick Moore, a wife and husband team at Columbia University in New York City, isolated genetic pieces of a virus from a KS lesion, and used representational difference analysis (a method to subtract out all of the human DNA from a sample) to isolate the viral genes; they then used these small DNA fragments as starting points to sequence the rest of the viral genome in 1996. This, the eighth human herpesvirus (HHV-8)—now known as Kaposi's sarcoma-associated herpesvirus (KSHV)—has since been found in all KS lesions tested, and is considered the cause of the disease. KSHV is a unique human tumor virus that has incorporated 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 also cause human cancers.

KSHV infection does not always lead to KS; 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. 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.

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.

External links

es:Sarcoma de Kaposi fr:Maladie de Kaposi nl:Kaposisarcoom

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