What is Kaposi sarcoma?
Kaposi sarcoma (KS) is a disease of the endothelial cells of blood vessels and the lymphatic system. Despite its name, it is no longer classified as a sarcoma (which is a malignant tumour of mesenchymal origin) as it is due to multicentric vascular hyperplasia.
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 with HIV infection.
- Human immunodeficiency virus (HIV)-associated Kaposi sarcoma — this mainly affects men who have sex with men (MSM). Kaposi sarcoma is one of the most common forms of cancer 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 causing immune suppression.
In the United States, Kaposi sarcoma was particularly common in the 1980s. It remains prevalent 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 for organ transplant patients, especially in geographic areas associated with high levels of infection with Kaposi sarcoma herpesvirus (KSHV). Most have the virus before transplantation, but the drugs cause it to reactivate. Use of corticosteroids and biologics like rituximab, infliximab, and abatacept, prescribed for chronic inflammatory and autoimmune conditions, are also prone to develop 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 via saliva or arthropod bites.
- It is also associated with the production of specific cytokines or cell signalling proteins, genetic factors, hormonal factors and immunodeficiency. 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-Hodgkin lymphoma and Castleman disease.
How does Kaposi sarcoma present?
Kaposi sarcoma presents as red to purplish macules, papules and nodules anywhere on the skin or mucous membranes 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 on one or both lower legs, often in association with lymphoedema. The patches evolve into plaques, nodules or scaly tumours.
Kaposi sarcoma in association with HIV infection may develop at any time during the illness. Generally, the greater the immunosuppression (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
- Bowel obstruction
- Shortness of breath
- Swollen legs.
How is Kaposi sarcoma diagnosed?
Blood tests may show no abnormality, depending on whether there are associated disorders such as AIDS. Anaemia may arise if there is bleeding. KSHV assays or antibody titres to KSHV are challenging 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 other conditions such as melanoma, fungal infections, and mycetoma mimic Kaposi sarcoma in appearance and location. The histopathology of Kaposi sarcoma 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 a 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 while others have extensive external and internal disease. The latter lesions may result in fatal complications from bleeding, obstruction or perforation 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 not widespread 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 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 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 to recur 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.
- Surgical excision of individual nodules.
- Laser therapy using pulsed dye laser or 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 of bleomycin 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 is immunosuppression.
Other chemotherapy treatments that are used in some international centres include bleomycin, 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 cardiac toxicity and myelotoxicity. Paclitaxel is approved for use in Kaposi sarcoma in advanced stages or as a second-line option.
Kaposi sarcoma may arise in organ transplant patients. Switching from ciclosporin to sirolimus (rapamycin) has resulted in resolution of the sarcoma. This is primarily 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 therapy is a combination of a photosensitiser and light energy.
- Isotretinoin is a vitamin-A derivative usually used to treat acne.
- Bexarotene is 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, 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 endothelial growth factor (VEGF): drugs acting on VEGF receptors such as bevacizumab and sorafenib are being evaluated.
- The immune-modulating agent lenalidomide is also under trial.