Lesions (cancerous)

Kaposi sarcoma

What is Kaposi sarcoma?

Kaposisarcoma (KS) is a disease of theendothelial cells ofblood vessels and thelymphatic system.Despite its name, it is no longer classified as a sarcoma (which is amalignanttumour of mesenchymal origin) as it is due tomulticentricvascularhyperplasia.

There are four types of Kaposi sarcoma.

• Classic type of Kaposi sarcoma — this affects older men of Mediterranean and Middle European descent and in men in Sub-Saharan Africa. It is associated with diabetes mellitus, but is not associated withHIVinfection.
• Human immunodeficiency virus (HIV)-associated Kaposi sarcoma — this mainly affects men who havesex with men (MSM). Kaposi sarcoma is one of the most common forms ofcancer in Uganda and Zambia, especially in children.
• Endemic or African Kaposi sarcoma — this arises in some parts of Africa in children and young adults.
• Iatrogenic Kaposi sarcoma — as a result of drug treatment causingimmune suppression.

In the United States, Kaposi sarcoma was particularly common in the 1980s. It remainsprevalent amongst HIV-positive men who have had sex with men (MSM), 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 than in men in some parts of Africa. It has become less common in the US and Europe because of effective highly active antiretroviral treatment (HAART) for HIV.

Iatrogenic Kaposi sarcoma is a particular concern fororgan transplant patients, especially in geographic areas associated with high levels of infection withKaposi sarcoma herpesvirus (KSHV). Most have the virus beforetransplantation, but the drugs cause it to reactivate. Use ofcorticosteroids and biologics likerituximab,infliximab, and abatacept, prescribed forchronicinflammatory andautoimmune conditions, are also prone todevelop Kaposi sarcoma.

What is the cause of Kaposi sarcoma?

Kaposi sarcoma has several causes.

• Infection with Kaposi sarcoma herpesvirus (KSHV). This virus is also called human herpesvirus 8 (HHV8). It is most often found in MSM but has been seen in heterosexuals. Data is emerging that non-sexual modes of transmission can occur, possibly viasaliva orarthropod bites.
• It is also associated with the production of specificcytokines or cell signallingproteins,genetic factors, hormonal factors andimmunodeficiency. Decreasing CD4 cell count has a strong association with AIDS-associated and classic Kaposi sarcoma.

KSHV may lie dormant, or replicate and cause disease. KSHV may also cause some forms of non-Hodgkinlymphoma and Castleman disease.

How does Kaposi sarcoma present?

Kaposi sarcoma presents as red to purplishmacules,papules andnodules anywhere on the skin ormucous membranes lining the mouth, nose, and throat;lymph nodes; or other organs. Initially, thelesions are small and painless, but they can ulcerate and become painful.

There are various forms:

• Localisednodular KS
• Locally aggressive KS
• Generalisedlymphadenopathic KS
• Patch stage KS
• Localisedplaques of KS
• Exophytic KS
• Infiltrative plaques of KS
• Disseminatedcutaneous andvisceral KS
• Telangiectatic KS
• Keloidal KS
• Ecchymotic KS
• Lymphangioma-like/cavernous KS.

Kaposi sarcoma often starts as flat patches on one or both lower legs, often in association withlymphoedema. The patches evolve into plaques, nodules orscalytumours.

Kaposi sarcoma in association withHIV infection may develop at any time during the illness. Generally, the greater theimmunosuppression (eg, 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 such as:

• Discomfort with swallowing
• Bleeding
• Haematemesis
• Haematochezia
• Melaena
• Bowel obstruction
• Shortness of breath
• Swollen legs.

Patch stage KS 

Plaque stage KS 

Classic KS 

Palatal KS 

Plaque stage KS 

Tumour stage KS 

See more images of Kaposi sarcoma.

How is Kaposi sarcoma diagnosed?

Blood tests may show noabnormality, depending on whether there are associated disorders such as AIDS.Anaemia may arise if there is bleeding. KSHV assays orantibodytitres to KSHV are challenging to interpret. CD4lymphocyte counts andplasma HIV load studies are performed in patients withHIV infection.

The appearance of Kaposi sarcoma lesions is often typical, but askin biopsy of alesion allows a definite diagnosis, as other conditions such asmelanoma,fungal infections, andmycetoma mimic Kaposi sarcoma in appearance and location. The histopathology of Kaposi sarcoma shows red cells in slit-like spaces formed byatypicalspindle cellproliferation 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 alymph 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 while others have extensive external and internal disease. The latter lesions may result in fatal complications from bleeding, obstruction orperforation of an organ. Kaposi sarcoma is not curable, but it can be treated and its symptoms controlled.

What is the treatment for Kaposi sarcoma?

In HIV disease, if the lesions are notwidespread or troublesome, often the best approach is 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 thedevelopment of new lesions.
• The improvement in immune function is thought to result in reduced levels of tumour growth-promoting proteins.
• HAART pluschemotherapy is found to be more effective than HAART alone or chemotherapy alone in treating Kaposi sarcoma.

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

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

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 torecur after local treatments. Treatments include:

• Cryotherapy with liquid nitrogen
• Radiotherapy. This is most useful for classic Kaposi sarcoma and is less effective for HIV-associated disease.
• Surgicalexcision of individual nodules.
• Laser therapy usingpulsed dye laser or pulsed carbon dioxidelaser
• Injection with anti-cancer drugs such as vinblastine
• Topical application ofalitretinoin gel (Panretin®). This drug is not yet available in New Zealand
• Electrochemotherapy, a new treatment that uses electrical impulses to enhance effectiveness ofbleomycin or 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 isimmunosuppression.

Other chemotherapy treatments that are used in some international centres includebleomycin, etoposide, paclitaxel, docetaxel and liposomal forms of the conventional 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 cardiactoxicity 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 andimiquimod,sirolimus andthalidomide.

Kaposi sarcoma may arise in organtransplant patients. Switching fromciclosporin tosirolimus (rapamycin) has resulted in resolution of the sarcoma. This is primarily attributed to the anti-proliferative and anti-angiogenic effects of sirolimus (mTORinhibitor).

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

• Photodynamic therapy is a combination of a photosensitiser and light energy.
• Isotretinoin is a vitamin-A derivative usually used to treatacne.
• Bexarotene is used to treatcutaneous T-cell lymphoma.
• Cytokineinhibitors (biologics)
• The pregnancy hormone, human chorionic gonadotropin (HCG); Kaposi sarcoma lesions disappear in some women when they become pregnant.
• Ganciclovir,cidofovir and 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 endothelialgrowth factor (VEGF): drugs acting on VEGF receptors such as bevacizumab and sorafenib are being evaluated.
• The immune-modulating agent lenalidomide is also under trial.

References

• Schwartz RA, Micali G, Nasca MR, Scuderi L. Kaposi sarcoma: a continuing conundrum. J Am Acad Dermatol. 2008 Aug; 59(2): 179–206.PubMed
• Curtiss P, Strazzulla LC, Friedman-Kien AE. An update on Kaposi’s sarcoma: Epidemiology, pathogenesis and treatment. Dermatol Ther (Heidelb). 2016; 6(4): 465–70. doi:10.1007/s13555-016-0152-3.Journal.
• Uldrick TS, Whitby D. Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett. 2011; 305(2): 150–62. doi:10.1016/j.canlet.2011.02.006.PubMed.
• Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, Ranieri E, Gesualdo L, Schena FP, Grandaliano G. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med. 2005; 352: 1317–23.PubMed.
• Kobayashi M, Takoori-Kondo A, Shindo K, et al. Successful treatment with paclitaxel of advanced AIDS-associated Kaposi's sarcoma. Intern Med. 2002; 41: 1209–12.PubMed.

On DermNet

• Human immunodeficiency virus
• Kaposi sarcoma pathology
• Viral infections

Other websites

• Kaposi's Sarcoma — Medline Plus
• Kaposi Sarcoma — Medscape Reference

Books about skin diseases

• Books about the skin
• Dermatology Made Easy - second edition