What is Kaposi sarcoma?
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 HIV disease.
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 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 is associated with:
- 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 hyperplasia rather 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 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 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 melanoma, fungal 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.
Treatment of Kaposi sarcoma
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.
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 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 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.
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 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 like bevacizumab and sorafenib are being evaluated.
- The immune modulating agent lenolidamide is also under trial.