Kaposi Sarcoma – Types, Symptoms, Diagnosis, and Treatment.

What is Kaposi sarcoma?

Kaposi sarcoma is a rare cancer that gained widespread attention during the early days of Human Immunodeficiency Virus/Acquired Immune Deficiency (HIV/AIDS) infections. Since then, innovative medical research and treatment significantly reduced the number of Kaposi sarcoma cases.

People with weakened immune systems are susceptible to Kaposi sarcoma. That said, people only develop Kaposi sarcoma if they are infected with human herpesvirus 8 (HHV-8). HHV-8 is a rare virus. Less than 10% of people in the United States carry HHV-8. This virus is believed to be transmitted via saliva.

Kaposi sarcoma’s most common visible symptom is dark-colored flat or bumpy blotches or patches that appear on a person’s arms, legs and face. The patches or blotches, called lesions, can be blue, black, pink, red or purple. Lesions might also appear in a person’s mouth, nose and throat. Lesions can spread to internal organs such as the liver, lungs, stomach and the digestive tract.

Types

There are four main typesTrusted Source of KS:

• Epidemic KS: This is the most common form of KS. This type develops in people who have a diagnosis of stage 3 HIV. Doctors consider KS to be an AIDS-defining illness. This means that once a person develops KS, it is likely that they will have a diagnosis of AIDS rather than HIV. However, some people with well managed HIV and an undetectable viral load still develop KS.
• Classic KS: This occurs mainly in older adults of Eastern European, Mediterranean, and Middle Eastern descent. Men experience classic KS more than women. This type presents lesions that grow more slowly than other types.
• Endemic KS: Also known as African KS, this form is relatively common in equatorial Africa. It generally develops in people under 40 years of age. This used to be the most common type of KS in Africa, but with the increase in AIDS incidence throughout Africa, epidemic KS is now the most widespread.
• Latrogenic KS: This is also known as transplant-related KS. People may develop this type after taking drugs that suppress the immune system after an organ transplant. If a person carries KSHV, taking immunosuppressant medications may cause them to develop KS.

What is the pathophysiology of Kaposi sarcoma (KS)?

The discovery of Kaposi sarcoma human herpes virus (KSHV) in 1994 led to rapid progress in understanding the disease’s pathophysiology. Different epidemiologic and clinical presentations of the disease may be related to modifiable risk factors, such as uncontrolled HIV and immunosuppressive medications used in transplantation. This knowledge has helped spur individualized therapeutic approaches to the disease.

Kaposi sarcoma is caused by an excessive proliferation of spindle cells that are thought to have an endothelial cell origin. Despite their heterogeneity, the tumors are predominantly composed of KSHV genomic material with immunohistochemical markers of both lymphoid, spindle, and endothelial cells.

Although the cell of origin is still unknown, increased endothelial factor VIIIa antigen, spindle cell markers such as smooth muscle alpha-actin, and macrophage markers such as PAM-1, CD68, and CD14 expressed by these spindlecells have been observed. This suggests a pluripotent mesenchymal progenitor. The spindle cells proliferate in a background of reticular fibers, collagen, and mononuclear cells including macrophages, lymphocytes and plasma cells. They tend to be vascular, involving either the reticular dermis (patch stage) or the entire thickness of the dermis (plaque or nodular stage).

KSHV contains a large genome with greater than 85 antigenically competent genes. Immunofluorescent assays in KSHV-infected primary effusion lymphoma and an enzyme-linked immunoassay (ELISA) to major antigens have been developed to measure antibodies to KSHV.

Causes

In most cases, it’s not clear what causes soft tissue sarcoma.

In general, cancer occurs when cells develop errors (mutations) in their DNA. The errors make cells grow and divide out of control. The accumulating abnormal cells form a tumor that can grow to invade nearby structures and the abnormal cells can spread to other parts of the body.

The type of cell that develops the genetic mutation determines what type of soft tissue sarcoma you have. For example, angiosarcoma begins in the lining of blood vessels, while liposarcoma arises from fat cells. Some types of soft tissue sarcoma include:

• Angiosarcoma
• Dermatofibrosarcoma protuberans
• Epithelioid sarcoma
• Gastrointestinal stromal tumor (GIST)
• Kaposi’s sarcoma
• Leiomyosarcoma
• Liposarcoma
• Malignant peripheral nerve sheath tumor
• Myxofibrosarcoma
• Rhabdomyosarcoma
• Solitary fibrous tumor
• Synovial sarcoma
• Undifferentiated (pleomorphic sarcoma)

What are the risk factors for Kaposi sarcoma?

You must already be infected with Kaposi sarcoma-associated herpesvirus (KSHV) to develop Kaposi sarcoma. However, most people who have the virus will never get Kaposi sarcoma. The cancer is usually triggered by a weakened immune system in people who are HIV-positive, who have received an organ transplant or whose immune systems are weakened for other reasons, including age.

Kaposi’s Sarcoma Symptoms

You could have a number of symptoms, depending on which parts of your body are affected by the disease.

Skin

The most visible signs of KS are lesions on your skin: flat, painless spots that are red or purple on light skin and bluish, brownish, or black on dark skin. Unlike bruises, they don’t change color when you press on them. They aren’t itchy, and they don’t drain. They’re not dangerous.

New spots may show up each week. For some people, these lesions change slowly. They may grow into raised bumps or merge together.

Mucous membranes

KS lesions can form inside your mouth and throat, causing trouble eating or swallowing. They might also happen on your eyes and under your eyelids.

Lymph nodes

When lesions block the flow of lymphatic fluid around your body, they can lead to severe swelling in your arms, legs, face, or scrotum.

Respiratory tract

Lesions inside your lungs may cause serious coughing and shortness of breath.

Digestive tract

Lesions in your stomach and intestines can lead to bleeding and blockages. You may have:

• An upset stomach
• Vomiting
• Belly pain
• Diarrhea
• Bloody or black poop
• Low red blood cell counts (anemia)

Possible Complications

Complications can include:

• Cough (possibly bloody) and shortness of breath if the disease is in the lungs
• Leg swelling that may be painful or cause infections if the disease is in the lymph nodes of the legs

The tumors can return even after treatment. KS can be deadly for a person with AIDS.

An aggressive form of endemic KS can spread quickly to the bones. Another form found in African children does not affect the skin. Instead, it spreads through the lymph nodes and vital organs, and can quickly become deadly.

Diagnosing Kaposi Sarcoma

After asking about your medical history and examining your skin for the appearance of lesions (including your nose and rectum if you have symptoms in these areas), we will likely order a biopsy, in which a highly trained pathologist examines small tissue samples from one or more of these lesions under a microscope.

Your doctor also may recommend the following tests:

Bronchoscopy: In this procedure, performed while patients are under anesthesia, a pulmonologist places a small tube through the nose or mouth into the bronchial passages to examine the lungs.

Endoscopy: A gastroenterologist passes a thin, flexible tube with a light and camera at the tip, called an endoscope, into the throat and gastrointestinal tract to look for lesions in the stomach and intestines. This procedure is performed while patients are sedated.

Colonoscopy: This involves following a special clear-liquid diet and taking medicine to clear the bowel, after which a gastroenterologist inserts a tube with a light and camera on its tip through the rectum into the colon. It is also performed while patients are sedated.

CT scan: This test allows doctors to determine if the cancer has spread to the lungs, lymph nodes, or liver.

Treatment

The treatment for Kaposi’s sarcoma varies, depending on these factors:

• Type of disease. Historically, AIDS-related Kaposi’s sarcoma has been more serious than classic or transplant-related disease. Thanks to increasingly effective antiviral drug combinations and improved prevention of other AIDS-related infections, Kaposi’s sarcoma has become less common and less severe in people with AIDS.
• Number and location of lesions. Widespread skin lesions and internal lesions require different treatment from isolated lesions.
• Effects of the lesions. Lesions in the mouth and throat make eating difficult, while lesions in the lung can cause shortness of breath. Large lesions, particularly on the upper legs, can lead to painful swelling and difficulty moving around.
• General health. The immune system impairment that makes you vulnerable to Kaposi’s sarcoma also makes certain treatments, such as powerful chemotherapy drugs, too risky to try. The same is true if you also have another type of cancer, poorly controlled diabetes or any serious, chronic disease.

For AIDS-related Kaposi’s sarcoma, the first step in treatment is to start or switch to an antiviral drug combination that will reduce the amount of the virus that causes HIV/AIDS and increase the number of certain immune cells in your body. Sometimes, this is the only treatment needed.

When possible, people with transplant-related Kaposi’s sarcoma may be able to stop taking immune system-suppressing medication. This allows the immune system to eliminate the cancer in some cases. Switching to a different immunosuppressive medication can also bring improvement.

Treatments for small skin lesions include:

• Minor surgery (excision)
• Burning (electrodessication) or freezing (cryotherapy)
• Low-dose radiation, which is also helpful for lesions in the mouth
• Injection of the chemotherapy drug vinblastine directly into lesions
• Application of a vitamin A-like drug (retinoid)

Lesions treated in any of these ways are likely to return within a couple of years. When this happens, treatment can often be repeated.

Radiation is the usual treatment for those with multiple skin lesions. The type of radiation used and the locations of lesions being treated vary from person to person. When more than 25 lesions are present, chemotherapy with standard anti-cancer drugs may be helpful. Chemotherapy is also used to treat Kaposi’s sarcoma in the lymph nodes and digestive tract.

Can Kaposi Sarcoma be prevented?

Kaposi sarcoma (KS) is caused by the Kaposi sarcoma–associated herpesvirus (KSHV). There are no vaccines at this time to protect people against KSHV. For now, preventing KS depends on reducing the chance of becoming infected with KSHV and reducing the chance that people who are infected with KSHV will develop KS.

Most cases of KS in the United States occur in people with HIV and AIDS. Taking measures to avoid becoming infected with HIV could prevent most cases of KS in this country.

• Since HIV can be spread through sex, avoiding unprotected sex with people infected with HIV could help prevent these infections. Many people with HIV don’t know that they are infected, so many public health workers recommend using a condom during any sexual contact.
• Another way to lower the risk of getting HIV is to take a pill every day that contains ant-viral drugs. This is called pre-exposure prophylaxis (PrEP). At this time, the Centers for Disease Control and Prevention (CDC) recommends PrEP for people who are HIV negative and at very high risk for HIV. The CDC has more information about who should use PrEP.
• HIV can also be spread through the use of contaminated (dirty) needles to inject recreational drugs. For people who inject drugs, the safest way to avoid HIV is to quit. However, some people are unable to quit on their own or get help in quitting, and they may not be able to stop using drugs right away. For these people, clean needles and injection supplies can help protect them. In some areas, there are programs to make sure that drug users can get clean needles and syringes.
• HIV-infected mothers can pass the virus to their babies during pregnancy, delivery, or breastfeeding. Treating the mothers and infants with anti-HIV drugs and avoiding breastfeeding can greatly reduce the risk of these infections.
• In the past, blood product transfusions and organ transplants were responsible for some HIV infections. As a result of improved testing for HIV, there is now a very low risk of HIV infection from blood products or organ transplants in the United States.

For people who are infected with HIV and KSHV, taking the right medicines can reduce the chance of developing KS.

• Testing for HIV can identify people infected with this virus. People with HIV should get treatment to help strengthen their immune system, which usually includes highly active antiretroviral therapy (HAART). HAART reduces the risk that people with HIV will develop KS (and AIDS). Treating infections that commonly occur in people with weakened immunity also reduces the likelihood of developing problems with KS.
• HIV-infected people who take drugs to treat herpesvirus infections (such as ganciclovir or foscarnet) are less likely to develop KS because these drugs also work against KSHV (which is a type of herpesvirus). Still, these drugs can have serious side effects, so they are only taken to treat certain viral infections, not to prevent KS.

For people who are at risk of developing KS after an organ transplant (iatrogenic KS), using certain types of immune suppressive drugs, such as sirolimus or everolimus (mTOR inhibitors), may reduce the chances of KS while still helping prevent rejection of the new organ.