Kaposi's Sarcoma

Kaposi's sarcoma (KS) is a connective tissue cancer caused by human herpes virus 8 - now called Kaposi's sarcoma-associated herpesvirus (KSHV). The malignant lesion is characterised by neoplastic cells and abnormally growing blood vessels. KS is named after the Hungarian dermatologist, Moritz Kaposi who discovered it in 1872. The viral gene sequence was only determined in 1995-1996. KS is different to other neoplasms by virtue of the fact that lesions may begin in more than one place at the same time.^[1] There are two other malignancies associated with KSHV - primary effusion lymphoma and multicentric Castleman's disease, which will not be discussed here.^[2]

Epidemiology

Previous to the occurence of HIV, KS was very rare - being mostly isolated to elderly men of Mediterranean, Jewish or African descent.^[3] Patients on immunosuppressants following organ transplantation also accounted for a small number of cases.

During the 1980s the increased number of cases of AIDS was associated with an increased incidence of KS. Fortunately, the widespread use of highly active antiretroviral therapy (HAART) has reduced the number of patients who develop KS. However, KS remains the most frequently reported cancer in some African countries, due to untreated HIV - eg, Zimbabwe.

Interestingly, KSHV infection alone does not lead to KS and, in Africa, male patients who are not HIV-positive are more frequently affected than females. Furthermore, familial clustering of KSHV infection has been suggested to occur via nonsexual transmission.^[4]

Risk factors for KS^[1]

• Gender - men are more often affected than women.
• Ethnicity - Caucasian men and those of Mediterranean, Middle Eastern or African origin.
• Men who have sex with men.
• Immune deficiency - eg, post-transplant or HIV infection.
• Being a spouse of a patient with KS is a risk factor for HHV8 seropositivity.^[5]
• Positive risk factors for classical KS also include non-smoking, diabetes and oral corticosteroids.^[6]

Types of Kaposi's sarcoma

• Classic KS - rare; progresses slowly over years and tends to affect elderly men of Mediterranean or Jewish origin.
• Endemic or African KS - affects young adult men who live near the African equator and have a normal immune system. Reported to occur in up to 9% of Ugandan men. In some, KS can be aggressive with rapid spread. Children can also be affected with a form that invades the lymphatics and lymph nodes but not the skin. This is associated with spread to other organs and is usually fatal.
• Transplant-related or acquired KS - associated with rapid dissemination.
• Epidemic KS - occurrence of KS in patients infected with HIV.
• Non-epidemic KS - occurs in men who have sex with men who do not have HIV; lesions tend to affect arms, legs and genitalia. It characteristically has a slow progression.^[7]
• Recurrent KS.

Presentation^{[1, 3]}

• Skin lesions may be nodular, papular or blotchy; they may be red, purple, brown or black.
• Lesions can also be seen under or on mucous membranes, with similar characteristics.
• The most common sites include the mouth, nose and throat.
• Usually painless but may become painful if inflamed or swollen.
• Lesions may also involve internal organs - eg, lungs (leading to dyspnoea), gastrointestinal tract (it can cause fatal bleeding) and lymphatics, resulting in lymphoedema.^[8]
• There may be superimposed bacterial infection.
• The tumour may disseminate in transplant recipients.
• Very rarely, lesions at the oesophagus or respiratory tract may lead to obstruction.

Pathological findings

• Spindle cells - elongated tumour cells.
• Highly vascular - with dense and irregular blood vessels which leak blood into the tumour, causing the red hue.
• There may also be surrounding inflammation.

Investigations

Definitive diagnosis is based on biopsy features with the presence of spindle cells. Detection of the latency-associated nuclear antigen (LANA) from the virus also confirms the diagnosis.^[9]

Other assessment

This should include:

• Full history - including sexual history.
• Full examination - specifically including lymph node examination and looking at the mucous membranes.
• CXR, which should be performed to pick up any lung involvement.
• Other investigations, which will depend on the presentation - for example, endoscopy or bronchoscopy.

Staging^[10]

There is no official system but the AIDS clinical trials group (ACTG) system is most often used. Three elements are used:

• T = extent of tumour.
• I = status of immune system according to the CD4 count.
• S = extent of involvement of organs or systemic illness.

Management^{[3, 12]}

• KS is incurable but can be controlled with palliative treatment.
• Treat any underlying causes if possible - eg, immunodeficiency or immunosuppression.
• AIDS-associated KS (epidemic KS) - starting HAART will usually lead to a reduction of lesions in almost 40% of patients, although there are a few in whom the KS will continue to grow despite antiretrovirals.
• If there are only a few lesions then the following can be considered:
  • Radiotherapy.
  • Cryotherapy/cryosurgery.
  • Surgery - this carries the risk of KS appearing in wound edges and is probably only appropriate for small surface lesions. Electrodessication with curettage can also be used (tumour cut and edges burnt).
• More widespread KS or organ involvement requires systemic therapy - eg, interferon alfa, liposomal anthracyclines, paclitaxel.
• There is a case report describing worsening of KS lesions in HIV-positive individuals when they begin HAART. This has been termed 'immune reconstitution inflammatory syndrome' (IRIS). The KS was controlled with chemotherapy and ongoing HAART.^[13]

Prognosis

Prognosis depends on the type of KS, status of the patient's immune system, presence of dissemination and whether this is the first appearance of KS or a recurrence. The reduction in death rate from AIDS since the 1990s has paralleled a reduction both in the number of cases of KS and in its severity.

Prevention

It is unclear how KSHV is acquired. There is some research suggesting that the presence of antibodies against KSHV increases the risk of transmission to any sexual partners and is associated with the development of solid organ involvement.