What Is Kaposi Sarcoma? Causes, Symptoms and Treatment

What Is Kaposi Sarcoma? Causes, Symptoms and Treatment

Kaposi’s sarcoma (KS) is a type of cancer. Tumors with tiny new blood vessels grow below the surface of the skin and in membranes of your mouth, nose, eyes, and anus. It can spread to your lungs, liver, stomach, intestines, and lymph nodes, which are glands that help you fight infection.

Kaposi sarcoma (KS) is a disease of blood vessels the lining of blood vessels and lymphatics. It was considered very rare before the start of the AIDS pandemic. AIDS is due to infection with human immunodeficiency virus (HIV).

There are four types of Kaposi sarcoma.

  • The classic type of Kaposi sarcoma affects elderly men of Mediterranean and Middle European descent and in men in Sub-Saharan Africa.
  • HIV-associated Kaposi sarcoma mainly affects men who have sex with men.
  • Endemic or African Kaposi sarcoma arises in some parts of Africa in children and young adults.
  • Iatrogenic Kaposi sarcoma is due to drug treatment causing immune suppression.

Classic Kaposi sarcoma is rare and unassociated with HIV infection. It most often arises in middle-aged to elderly men of Mediterranean or Jewish descent (less than 10% are women), particularly if they come from a rural environment. They have a higher than expected rate of diabetes mellitus.

In the United States, Kaposi sarcoma was particularly common in the 1980s especially amongst HIV-positive men who had sex with men, in which it has a very aggressive course. It occurs less frequently in intravenous drug users and is rare in women, haemophiliacs or their sexual partners. HIV-associated Kaposi sarcoma is more common in women in some parts of Africa. It has become less common in the US and Europe because of effective HAART treatment for HIVdisease.

African Kaposi sarcoma is becoming more prevalent with the rise in HIV infection. It is one of the most common forms of cancer, especially in children, in Uganda and Zambia.

Iatrogenic Kaposi sarcoma is a particular concern for organ transplant patients, especially in geographic areas associated with high levels of infection with KSHV. Most have the virus prior to transplantation, but the drugs causes it to reactivate. Use of corticosteroids and biologics like rituximabinfliximab, and abatacept, prescribed  for chronicinflammatory and autoimmune conditions, are also  prone to develop Kaposi sarcoma.

Researchers have found that Kaposi’s sarcoma is caused by a herpes virus, HHV-8, also called KSHV. It affects 8 times more men than women. It may spread through sexual contact, but we don’t know for sure.

KS was once rare, affecting older men from Eastern European or Mediterranean families, young African men, or people who had undergone organ transplants. Now HIV is the most common cause.

Kaposi’s Sarcoma and HIV

Because people with HIV have weakened immune systems, they’re more likely to develop certain cancers, including KS. Most severe cases happen when someone has AIDS, the late stage of HIV infection, but skin lesions can also show up earlier. They’re a sign your immune system isn’t at full strength.

Skin lesions tend to get worse when you also have other infections.

Treating the HIV virus with antiretroviral therapy (ART) is the best way to treat KS, too, especially early on. Anti-HIV drugs have dropped the rate of KS cases by 80%-90% from the beginning of the AIDS epidemic in the early 1980s.

Symptoms

Lesions in Kaposi sarcoma may involve the skin, oral mucosa, lymph nodes, and visceral organs. Most patients present with cutaneous disease (see the image below). Visceral disease may occasionally precede cutaneous manifestations.

See Clues in the Oral Cavity: Are You Missing the Diagnosis?, a Critical Images slideshow, to help identify the causes of abnormalities of the oral cavity.

Cutaneous lesions in Kaposi sarcoma are characterized as follows:

  • Cutaneous lesions may occur at any location but typically are concentrated on the lower extremities and the head and neck region
  • Lesions may have macular, papular, nodular, or plaquelike appearances
  • Nearly all lesions are palpable and nonpruritic
  • Lesions may range in size from several millimeters to several centimeters in diameter
  • Lesions may assume a brown, pink, red, or violaceous color and may be difficult to distinguish in dark-skinned individuals
  • Lesions may be discrete or confluent and typically appear in a linear, symmetrical distribution, following Langer lines
  • Mucous membrane involvement is common (palate, gingiva, conjunctiva)

Gastrointestinal lesions can occur anywhere in the gastrointestinal tract. Lesions are often asymptomatic and clinically indolent, but signs and symptoms can include the following:

  • Odynophagia, dysphagia
  • Nausea, vomiting, abdominal pain
  • Hematemesis, hematochezia, melena
  • Bowel obstruction

Pulmonary lesions may be an asymptomatic radiographic finding, but signs and symptoms can include the following:

  • Cough
  • Dyspnea
  • Hemoptysis
  • Chest pain

Classic Kaposi sarcoma

This form of the disease has a more indolent course than AIDS-related Kaposi sarcoma, progressing over 10-15 years or more, with very gradual enlargement of cutaneous lesions and development over years of new ones.

See Clinical Presentation for more detail.

The most visible signs of Kaposi’s sarcoma are lesions on the skin: flat, painless spots that are red or purple on white skin and bluish, brownish, or black on dark skin. Unlike bruises, they don’t turn white when you press on them. They aren’t itchy, and they don’t drain. They’re not life-threatening.

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

When KS spreads elsewhere, it can be life-threatening. You may have:

  • Trouble eating or swallowing
  • Queasiness, vomiting, and belly pain from bleeding and blockages inside
  • Severe swelling in your arms, legs, face, or scrotum
  • Serious coughing or shortness of breath

Diagnosis

Laboratory studies

CD4 lymphocyte counts and plasma HIV viral-load studies should be performed for patients with HIV infection.

Imaging studies

Chest radiographic findings in patients with Kaposi sarcoma are variable and nonspecific. They may include diffuse reticulonodular infiltrates, interstitial infiltrates, pleural effusions, hilar or mediastinal lymphadenopathy, or an isolated pulmonary nodule.

Thallium and gallium scans may help differentiate pulmonary Kaposi sarcoma from infection. Pulmonary Kaposi sarcoma lesions typically demonstrate intense thallium uptake and no gallium uptake, whereas infection is often gallium avid and thallium negative.

Procedures

  • Punch biopsy
  • Bronchoscopy
  • Esophagogastroduodenoscopy (EGD) or colonoscopy

Typical histologic findings in Kaposi sarcoma include proliferation of spindle cells; prominent, slitlike vascular spaces; and extravasated red blood cells.

Your doctor may diagnose Kaposi’s sarcoma simply by looking at your skin. To confirm it, he may take a sample of tissue from a spot and look at it under a microscope, which is called a biopsy.

If you have trouble breathing, your doctor may use a thin tube with a light (a bronchoscope) to look into your breathing passages. Or, if you have tummy troubles, he may want to look inside your guts through a lighted tube during a procedure called an endoscopy.

Treatment

Treatment for Kaposi sarcoma (KS) is more effective than it was a couple of decades ago. Doctors now better understand what causes KS and have much more experience treating KS than they did when this disease was quite rare. Many clinical trials have compared different approaches to treatment.

Choices about the best treatment options for each patient are based on the function of the immune system as well as the number, location, and size of the KS lesions. The patient’s general health is also a major factor. The presence and severity of other serious health problems can make some treatments a poor choice.

For patients with immune system problems, the most important treatment is keeping the immune system healthy and any related infections under control. Some of the other treatments used for KS are:

In some patients, 2 or more of these treatments are used together.

Based on your options, you may have different types of doctors on your treatment team. These doctors may include:

  • An infectious disease specialist: a doctor who treats infectious diseases such as HIV and AIDS.
  • A dermatologist: a doctor who treats diseases of the skin
  • A radiation oncologist: a doctor who treats cancer with radiation therapy.
  • A medical oncologist: a doctor who treats cancer with medicines such as chemotherapy.

Many other specialists may be involved in your care as well, including physician assistants, nurse practitioners, nurses, nutrition specialists, social workers, and other health professionals.

It is important to discuss all of your treatment options as well as their possible side effects with your doctors to help make the decision that best fits your needs. If time permits, it is often a good idea to seek a second opinion. A second opinion can provide more information and help you feel confident about your chosen treatment plan.

Thinking about taking part in a clinical trial

Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to get state-of-the art cancer treatment. In some cases they may be the only way to get access to newer treatments. They are also the best way for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

If you would like to learn more about clinical trials that might be right for you, start by asking your doctor if your clinic or hospital conducts clinical trials. You can also call our clinical trials matching service at 1-800-303-5691 for a list of studies that meet your medical needs, or see the Clinical Trials section to learn more.

Considering complementary and alternative methods

You may hear about alternative or complementary methods that your doctor hasn’t mentioned to treat your cancer or relieve symptoms. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

Complementary methods refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor’s medical treatment. Although some of these methods might be helpful in relieving symptoms or helping you feel better, many have not been proven to work. Some might even be dangerous.

Be sure to talk to your cancer care team about any method you are thinking about using. They can help you learn what is known (or not known) about the method, which can help you make an informed decision. See the Complementary and Alternative Medicine section to learn more.

Help getting through cancer treatment

Your cancer care team will be your first source of information and support, but there are other resources for help when you need it. Hospital- or clinic-based support services are an important part of your care. These might include nursing or social work services, financial aid, nutritional advice, rehab, or spiritual help.

The American Cancer Society also has programs and services – including rides to treatment, lodging, support groups, and more – to help you get through treatment. Call our National Cancer Information Center at 1-800-227-2345 and speak with one of our trained specialists on call 24 hours a day, every day.

Your treatment will depend on how many lesions you have and how big they are and where they are, as well as how well your immune system is working.

In many cases, ART is the best way to treat active Kaposi’s sarcoma. It may even clear up the skin lesions.

If you have just a few, you could have them removed. That won’t cure you, but it can make your skin look better. Your doctor can cut the tissue out or freeze it to destroy it.

Radiation can kill the cancer cells or keep them from growing. A machine can direct it toward your body, or your doctor may put radioactive needles, seeds, or wires inside you near the cancer.

Once KS has spread, you’ll need meds that go throughout your whole body to kill the cancer. Chemotherapy drugs for Kaposi’s sarcoma include:

  • Doxorubicin (Dox-SL, Doxil, Evacet, LipoDox)
  • Paclitaxel (Taxol)
  • Vinblastine (Velban, Velsar)

Chemotherapy can have side effects, including hair loss, vomiting, and fatigue. If you’re HIV-positive, you also need to consider that chemo can lower your platelet and white-blood-cell counts, and raise your chances of an infection.

Another type of drug treatment, called biological therapy, works by boosting your immune system. Your doctor may prescribe interferon alfa (Intron A) if your CD4 cell count is over 200 and you have a fairly healthy immune system.

Targeted therapies, such as monoclonal antibody therapy and tyrosine kinase inhibitors (TKIs), are being tested in clinical trials. These try to attack the cancer and keep it from growing without harming healthy cells.

In HIV disease, if the lesions are not widespread or troublesome, often the best approach is simply to treat the underlying HIV infection with highly active antiretroviral drug combinations that suppress HIV replication (HAART).

  • HAART drugs reduce the frequency of Kaposi sarcoma and may also prevent its progression or the development of new lesions.
  • The improvement in immune function is thought to result in reduced levels of tumour growth-promoting proteins.
  • HAART plus chemotherapy is found to be more effective than HAART alone or of chemotherapy alone in treating Kaposi sarcoma.

Iatrogenic Kaposi sarcoma may improve or clear if it is possible to stop immune suppressive medication.

The choice of more specific treatment depends largely on the extent of the disease.

After Treatment for Kaposi Sarcoma?

For some people with Kaposi sarcoma (KS), treatment may completely remove or destroy the cancer. Completing treatment can be both stressful and exciting. You will be relieved to finish treatment, yet it is hard not to worry about cancer coming back. (When cancer returns, it is called recurrence.) This is a very real concern for those who have KS, since treatments often do not cure the disease completely.

It may take a while before your fears lessen. But it may help to know that many cancer survivors have learned to live with this uncertainty and are leading full lives. See Understanding Recurrence for more detailed information on this.

For many people with KS, the cancer never goes away completely. These people may get regular treatments with chemotherapy, radiation therapy, or other therapies to try to help keep the cancer in check. Learning to live with cancer that does not go away can be difficult and very stressful. It has its own type of uncertainty. See Managing Cancer As a Chronic Illness for more about this.

Follow-up care

Even if your treatment ends, your doctors will still want to watch you closely. It is very important to go to all of your follow-up appointments. During these visits, your doctors will ask questions about any problems you are having and may do exams and order lab tests or x-rays and scans to look for signs of cancer or treatment side effects. Almost any cancer treatment can have side effects. Some may last for a few weeks to months, but others can last the rest of your life. This is the time for you to talk to your cancer care team about any changes or problems you’ve noticed and any questions or concerns you have.

After your cancer treatment is finished, you will probably need to still see your cancer doctor for many years. Talk with your doctor about what kind of follow-up schedule you can expect.

It is important to keep health insurance. Tests and doctor visits cost a lot, and even though no one wants to think of their cancer coming back, this could happen.

Should your cancer come back, see Coping with Cancer Recurrence for information on how to manage this phase of your treatment.

Seeing a new doctor

At some point after your cancer diagnosis and treatment, you may find yourself seeing a new doctor who does not know anything about your medical history. It is important that you be able to give your new doctor the details of your diagnosis and treatment. Gathering these details soon after treatment may be easier than trying to get them at some point in the future. Make sure you have this information handy:

  • A copy of your pathology report(s) from any biopsies or surgeries
  • Copies of imaging tests (CT or MRI scans, etc.), which can usually be stored on a CD, DVD, etc.
  • If you had surgery, a c opy of your operative report
  • If you stayed in the hospital, a copy of the discharge summary that doctors prepare when patients are sent home
  • If you were treated with radiation, a copy of the treatment summary
  • If you had drug treatment (including chemotherapy, antiviral drugs, and/or biologic therapy), a list of the drugs, drug doses, and when you took them

 

If Treatment for Kaposi Sarcoma Stops Working

Treatment for Kaposi sarcoma (KS) can often help control the disease or even make the lesions go away, but there is no guarantee that KS will not come back. It is important to be aware that there is always a chance that KS lesions will return, either at the original site or in other places on the skin or internal organs. Advanced KS usually means a person has advanced AIDS, with all its problems. Still, treatment for KS is very effective at taking care of the symptoms of the disease. It can shrink or get rid of bulky, painful lesions and can relieve swelling. It can also reduce problems that arise when tumors affect the lungs or gastrointestinal tract. Treatment for KS can bring about important improvements in your quality of life.

If cancer keeps growing or comes back after one kind of treatment, it is possible that another treatment plan might at least shrink it enough to help you live longer and feel better. But when a person has tried many different treatments and the cancer is not getting any better, it tends to become resistant to all treatment. If this happens, it’s important to weigh the possible limited benefits of a new treatment against the possible downsides. Everyone has their own way of looking at this.

This is likely to be the hardest part of your battle with cancer — when you have been through many medical treatments and nothing’s working anymore. Your doctor may offer you new options, but at some point you might need to consider that treatment is not likely to improve your health or change your outcome or survival.

If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. In many cases, your doctor can estimate how likely it is the cancer will respond to treatment you are considering. For instance, the doctor may say that more treatment might have about a 1 in 100 chance of working. Some people are still tempted to try this. But it is important to think about and understand your reasons for choosing this plan.

No matter what you decide to do, you need to feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.

Palliative care helps relieve symptoms, but is not expected to cure the disease. It can be given along with cancer treatment, or can even be a cancer treatment. The difference is its purpose — the main goal of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Sometimes, though, the treatments used to control your symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve pain caused by the cancer. Or chemo might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer.

At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it is given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn’t mean you can’t be treated for the problems caused by your cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time. You can learn more about hospice and this phase of cancer in Hospice Care and Nearing the End of Life.

Staying hopeful is important, too. Your hope for a cure may not be as bright, but there is still hope for good times with family and friends — times that are filled with happiness and meaning. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life. Now is the time to do some things you’ve always wanted to do and to stop doing the things you no longer want to do. Though the cancer may be beyond your control, there are still choices you can make.

Cause

  • Infection with Kaposi sarcoma herpes virus (KSHV). This virus is also called human herpes virus 8. It is most often found in men who have sex with men but it can also occur in heterosexuals. Data is emerging that non-sexual modes of transmission can occur, possibly via saliva or arthropod bites.
  • Production of certain cytokines or cell signalling proteins
  • Genetic factors
  • Hormonal factors
  • Immunodeficiency. Decreasing CD4 cell count has a strong association with AIDS-associated and classic kaposi sarcoma.

Kaposi sarcoma is a multicentric, ie, it appears on more than one part of the body at once. It is a reactive hyperplasiarather than a neoplasm (cancer). Despite its name, it is no longer classified as a sarcoma (malignant tumour of mesenchymal origin).

KSHV may lie dormant, or replicate and cause disease. As well as causing Kaposi sarcoma, it may also be the cause of some forms of non-Hodgkin lymphoma and Castelman disease.

How does Kaposi sarcoma present?

Kaposi sarcoma presents as red to purplish macules, papules and nodules anywhere on the skin or mucousmembranes lining the mouth, nose, and throat; lymph nodes; or other organs. Initially, the lesions are small and painless but they can ulcerate and become painful. There are various forms.

  • Localised nodular KS
  • Locally aggressive KS
  • Generalised lymphadenopathic KS
  • Patch stage KS
  • Localised plaques of KS
  • Exophytic KS
  • Infiltrative plaques of KS
  • Disseminated cutaneous and visceral KS
  • Telangiectatic KS
  • Keloidal KS
  • Ecchymotic KS
  • Lymphangioma-like / cavernous KS

Kaposi sarcoma often starts as flat patches one or both lower legs, often in association with lymphoedema. The patches evolve into plaques, nodule or scaly tumours.

Kaposi sarcoma in association with HIV infection may develop at any time during the course of illness. Generally, the greater the immunosuppression (e.g. with CD4 cell counts less than 200/mm3) the more extensive and aggressive the Kaposi sarcoma will be.

Kaposi sarcoma lesions can also occur internally; in the gut, lungs, genitals, lymphatic system and elsewhere. These internal lesions may cause symptoms, eg, discomfort with swallowing, bleeding, haematemesis, haematochezia, melaena, bowel obstruction, shortness of breath, swollen legs, etc.

Diagnosis of Kaposi sarcoma

Blood tests may show no abnormality, depending whether there are associated disorders such as AIDS. Anaemia may arise if there is bleeding. KSHS assays or antibody titres to KSHS are difficult to interpret. CD4 lymphocyte counts and plasma HIV load studies are performed in patients with HIV infection.

The appearance of Kaposi sarcoma lesions is often typical but a skin biopsy of a lesion allows a definite diagnosis, as various lesions such as melanomafungal infections, and mycetoma mimic Kaposi sarcoma  in appearance and location. Histopathology shows red cells in slit-like spaces formed by atypical spindle cell proliferation of endothelial cells and associated with inflammatory cells.

Staging and prognosis in Kaposi sarcoma

There have been various attempts to classify Kaposi sarcoma, depending on whether it is localised or disseminated in the skin, and if there is lymph node or internal organ involvement. The degree of immunosuppression present may also be used in staging systems.

Kaposi sarcoma has a variable course. Some patients develop only a few minor skin lesions whilst others have much more extensive external and internal disease. The latter lesions may result in fatal complications, e.g., from bleeding, obstruction or perforation of an organ. Kaposi sarcoma is not curable, but it can be treated and its symptoms controlled.

Treating localised lesions

Small, localised lesions are generally only treated if they are painful or they are causing cosmetic problems. It should be noted that lesions tend to recur after local treatments. Treatments include:

  • Cryotherapywith liquid nitrogen
  • Radiotherapy. This is most useful for classic Kaposi sarcoma and is less effective for HIV-associated disease.
  • Surgical excision of individual nodules.
  • Laser therapy, using pulsed dye laseror pulsed carbon dioxide laser
  • Injection with anti-cancer drugs such as vinblastine
  • Topical application of alitretinoin gel(Panretin®). This drug is not yet available in New Zealand
  • Electrochemotherapy, a new treatment that uses electrical impulses to enhance effectiveness bleomycinor cisplatin injected into tumours.

Treating extensive or internal lesions with systemic therapy

A combination of anti-cancer drugs are given, but at lower than usual dosages if there is immunosuppression.

Other chemotherapy treatments that are used in some international centres include bleomycin, etoposide, paclitaxel, docetaxel and liposomal forms of the standard anti-cancer drugs, doxorubicin or daunorubicin. Liposomal means that the drugs are coated in small fat bubbles, or liposomes, which allows better absorption, resulting in less cardiac toxicity and myelotoxicity. Paclitaxel is approved for use in Kaposi sarcoma in advanced stages or as a second-line option.

Immunotherapy includes the use of interferon-alpha and imiquimodsirolimus and thalidomide.

Kaposi sarcoma may arise in organ transplant patients. Switching from ciclosporin to sirolimus (rapamycin) has resulted in resolution of the sarcoma. This is largely attributed to the anti-proliferative and anti-angiogenic effects of sirolimus (mTor inhibitor).

Clinical trials into a wide range of other therapies are ongoing.

  • Photodynamic therapyis a combination of a photosensitiser and light energy.
  • Isotretinoinis a vitamin-A derivative usually used to treat acne.
  • Bexaroteneis used to treat cutaneous T-cell lymphoma.
  • Cytokine inhibitors (biologics)
  • The pregnancy hormone, human chorionic gonadotropin (HCG); Kaposi sarcoma lesions disappear in some women when they become pregnant.
  • Ganciclovir, cidofovirand foscarnet (antiviral medications) have been recently reported to result in lower rates of Kaposi sarcoma amongst those being treated for CMV retinitis (inflammation of the retina caused by cytomegalovirus) and are currently being studied. Aciclovir, another antiviral, has been tried, but does not appear to work.
  • Targeting vascular endothelial growth factor (VEGF): drugs acting on VEGF receptors like bevacizumab and sorafenib are being evaluated.
  • The immune modulating agent lenolidamide is also under trial.

Management

Antiretroviral therapy

Optimal control of HIV infection using highly active antiretroviral therapy (HAART) is an integral part of successful Kaposi sarcoma therapy. HAART may be tried as the sole modality in nonvisceral disease. For visceral disease, chemotherapy may be added.

Local therapy

The following local therapies can be used for palliation of locally advanced symptomatic disease or in individuals who have cosmetically unacceptable lesions:

  • Radiation therapy
  • Cryotherapy
  • Laser therapy
  • Surgical excision
  • Intralesional vinca alkaloid therapy
  • Topical retinoids

Immunomodulation

Immunomodulation with interferon-alfa has clinical activity in Kaposi sarcoma that may be mediated by its antiangiogenic, antiviral, and immunomodulatory properties.

Combination therapy

Combination therapy with regimens such as ABV (actinomycin D, bleomycin, vincristine) produces higher response rates than does single-agent therapy (such as doxorubicin), but time to progression and overall survival rates are similar.

Cytotoxic agents

Several single cytotoxic agents have been approved by the Food and Drug Administration (FDA) for AIDS-related Kaposi sarcoma; they include the following:

  • Liposomal doxorubicin (Doxil)
  • Liposomal daunorubicin (DaunoXome)
  • Paclitaxel (Taxol) or oral etoposide (VePesid)

Liposomal technology has resulted in higher response rates with less cardiac toxicity and myelotoxicity for liposomal doxorubicin and liposomal daunorubicin. [

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