Kaposis sarcoma KS

Prior to the HIV epidemic, this tumour was seen in three clinical settings:

♦ The classical form affects predominantly the lower legs in men of East European or Jewish origin and often follows an indolent course, rarely requiring any specific treatment.

♦ An African variant, which has been endemic for many years. This can be indolent in nature or it may be more aggressive with widespread lymph node and visceral involvement.

♦ Patients receiving immunosuppressive therapy e.g. in organ transplant recipients. In this instance the tumour may regress when this treatment is reduced.

However, the commonest form of KS in the developing world is the epidemic form associated with AIDS. Due to the successful treatment and prophylaxis of opportunistic infections and effective anti-retroviral therapy, AIDS patients are now surviving longer. Although the incidence of KS is declining, the morbidity and mortality ascribed to KS has increased. Visceral KS now accounts for the death of one in four HIV-positive homosexuals.

KS affects male homosexuals in particular and rarely affects other groups at risk of AIDS, such as infected blood recipients and intravenous drug abusers. In those developing AIDS in an African environment, KS can be seen frequently in heterosexuals. A sexually transmitted co-factor may play an important role in its development. Recent research has identified a virus—the Kaposi's sarcoma herpes virus (KSHV), also known as human herpes virus 8(HHV8). DNA from this virus has been identified in KS lesions and in semen, blood, and bronchial washings from affected patients. However, its precise role in the development of KS is not yet fully understood.

KS is a multi-focal tumour and new lesions occur at various cutaneous and internal organ sites. The most likely cell of origin is mesenchymal with vascular or lymphatic cell markers and factor VIII antigen is often positive on immunocytochemistry staining. A diagnostic feature is the intradermal proliferation of abnormal vascular structures, lined with large, spindle-shaped endothelial cells. Frequent extravasation of red blood cells and mononuclear leukocytes occur.

Recent advances have identified that AIDS KS cells produce growth factors and cytokines, for example TNF and IL6, which appear to regulate their growth. This suggests an important role in the patho-genesis of KS, which may hold promise for the development of future treatments.

Presentation

♦ Cutaneous red purple multiple lesions

♦ Flat, then progress to plaques, nodules, with oedema

♦ Diagnosis—skin biopsy

♦ Systemic lesions—presents with lung, GI tract

—pain, dyspnoea, haemoptysis, bowel obstruction —diagnosis by endoscopy

Staging

Important prognostic factors relate not only to disease extent but to the patient's immune status and KS can occur as an early and late feature in AIDS patients. The Aids Clinical Trials Group (ACTG) has developed a staging classification.

Treatment

There is currently no cure for KS.Therefore, the primary goal oftreat-ment is to prolong life, while maintaining quality. The treatment should be tailored to the form of the disease. Localized treatment options include:

♦ Camouflage with cosmetics

♦ Cryotherapy and laser, especially if lesions are <1 cm diameter

♦ Intra-lesional chemotherapy with vinblastine or interferon

♦ Radiotherapy

KS is responsive to radiation treatment. A 70% response rate, equal to intra-lesional chemotherapy, can be achieved with single fraction doses of 8 Gy. This can be repeated if there is recurrence or insufficient regression. Palatal lesions can also be irradiated using iridium wire moulds.

Systemic treatment is required if there is widespread cutaneous or visceral involvement. Immunotherapy using interferon is most

Table 31.1 ACTG guidelines

Good prognosis—all of

Poor prognosis—any of

Tumour

Skin only ± lymph nodes and or minimal oral disease

Oedema/ulceration, extensive oral disease, visceral KS

Immunological

CD4 >200

CD4 <200

Symptoms

Nil, Karnofsky >70

Opportunistic infection or thrush, B symptoms, Karnofsky <70, other HIV-related illnesses

effective if the CD4 count is >200. This form of treatment results in less bone marrow suppression. The high doses required often result in fever, night sweats, and lethargy. If the CD4 count is below 200, treatment with vincristine and bleomycin can achieve response rates of 50-60%. Side-effects include some degree of bone marrow suppression, dose-related pulmonary fibrosis (in the case of bleomycin), and a peripheral neuropathy (with vincristine). The addition of doxorubicin may result in significant bone marrow suppression and alopecia.

Recent developments have led to liposomally packaged preparations that enable selective distribution to and retention in tumours, reducing uptake in unwanted sites such as the bone marrow. Response rates of 80% have been observed. Several new treatments are also being researched in clinical trials, including taxol, beta HCG, trans-retinoic acid, and anti-angiogenic agents such as thalidomide.

Table 31.2 Treatment options for KS

Local intervention

Systemic intervention

Cryotherapy/laser esp <1 cm

Interferon — if CD4 >200

Radiotherapy — 8 GY single fraction

Vincristine 2 mg and bleomycin 30 units every 3 weeks

Intra-lesional chemotherapy

Liposomal doxorubicin 20 mg/m2 every 3 weeks

Brachytherapy—palate

Liposomal daunorubicin 40 mg/m2 every 2 weeks

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