Kaposi Sarcoma

Kaposi sarcoma is a vascular neoplasm caused by human herpesvirus 8 (Kaposi sarcoma associated herpesvirus). It occurs in several distinct clinical and epidemiological forms.

HIV associated (epidemic) Kaposi sarcoma is an AIDS defining malignancy and the form most frequently encountered in regions with significant HIV prevalence. It is characterised by vascular, purplish cutaneous and mucosal lesions, with the potential for visceral involvement in more advanced disease.

Management is fundamentally centred on restoration of immune function through effective antiretroviral therapy alongside disease specific treatment where required.

Classification and pathophysiology

• Classic Kaposi sarcoma occurs predominantly in older men of Mediterranean, Eastern European or Jewish ancestry, typically presenting with indolent lower limb lesions and a generally favourable prognosis.
• Endemic (African) Kaposi sarcoma occurs in HIV negative individuals in sub Saharan Africa, with a range of clinical patterns from indolent cutaneous disease to a more aggressive, lymphadenopathic form particularly affecting children.
• Iatrogenic (transplant associated) Kaposi sarcoma occurs in the context of therapeutic immunosuppression, typically following solid organ transplantation, and frequently regresses with reduction of immunosuppressive therapy.
• Epidemic (HIV associated) Kaposi sarcoma, the form of greatest global clinical significance given its association with the HIV epidemic, reflects the combined effect of human herpesvirus 8 infection and HIV related immunosuppression. Human herpesvirus 8 encodes viral proteins that drive endothelial cell proliferation and angiogenesis underlying the characteristic vascular tumour histology across all clinical forms of this disease.

• Cutaneous lesions present as characteristic violaceous, purplish or brown macules, papules, plaques or nodules, which may coalesce into larger lesions, with a predilection for the lower limbs, face and oral mucosa, though capable of affecting any cutaneous or mucosal site.
• Lesions are typically non tender and non pruritic in early disease, though can become painful, ulcerate, or bleed with progression, and significant lymphoedema, disproportionate to the apparent extent of visible cutaneous disease, can occur, reflecting lymphatic obstruction from the underlying vascular tumour process.
• Oral mucosal involvement, commonly affecting the hard palate, presents with similar characteristic violaceous lesions, and gastrointestinal involvement, which can be entirely asymptomatic or present with bleeding, obstruction or protein losing enteropathy, should be considered in patients with more extensive cutaneous disease or unexplained gastrointestinal symptoms.
• Pulmonary involvement represents the most serious and potentially rapidly life threatening visceral manifestation, presenting with breathlessness, cough and, on imaging, characteristic nodular or infiltrative changes, sometimes with associated pleural effusion, and warranting prompt recognition and urgent treatment given the potential severity.

• Diagnosis is confirmed by biopsy of a representative cutaneous, mucosal or visceral lesion, showing the characteristic histological features of spindle cell proliferation, vascular slit like spaces, and extravasated red blood cells. Human herpesvirus 8 immunohistochemical staining (latency associated nuclear antigen) supports and confirms the diagnosis.
• HIV testing should be performed in every newly diagnosed patient with Kaposi sarcoma where HIV status is not already known, given the strong association and the critical importance of establishing this underlying diagnosis. CD4 count and HIV viral load assessment form part of the initial staging and risk assessment for HIV associated disease.
• Staging assessment, including examination of the oral cavity and full skin survey, together with chest imaging and, where clinically indicated by symptoms, endoscopic evaluation of the gastrointestinal tract, assesses the extent of disease and specifically screens for visceral involvement. Visceral involvement carries important prognostic and treatment implications.
• AIDS Clinical Trials Group staging, incorporating the extent of tumour burden, degree of immune suppression (CD4 count), and presence of systemic illness, is used to formally stage HIV associated Kaposi sarcoma and guide overall prognostic assessment and treatment planning.

• Initiation or optimisation of effective antiretroviral therapy is the fundamental first line treatment for HIV associated Kaposi sarcoma. Restoration of immune function frequently produces substantial, and in some cases complete, regression of disease. Antiretroviral therapy alone is therefore appropriate initial management for limited, asymptomatic cutaneous disease without evidence of significant visceral involvement.
• Local treatment options for limited, symptomatic or cosmetically troublesome cutaneous lesions include intralesional chemotherapy (vinblastine), cryotherapy, radiotherapy (particularly effective for localised, symptomatic lesions, including oral disease), and topical alitretinoin gel, chosen according to the specific lesion characteristics and location.
• Systemic chemotherapy is indicated for extensive cutaneous disease, symptomatic lymphoedema, visceral involvement, or disease progressing despite antiretroviral therapy and initial local measures.
• Liposomal doxorubicin (typically 20 mg per square metre intravenously every two to three weeks) or paclitaxel are standard systemic chemotherapy options, chosen and sequenced according to specific clinical factors and prior treatment response.
• Pulmonary Kaposi sarcoma, given its potential for rapid, life threatening deterioration, generally warrants prompt initiation of systemic chemotherapy alongside antiretroviral therapy rather than a trial of antiretroviral therapy alone, given the urgency of achieving disease control in this specific, more dangerous presentation.
• Immune reconstitution inflammatory syndrome related Kaposi sarcoma flare, in which lesions paradoxically worsen or new lesions appear in the weeks following initiation of antiretroviral therapy, is a recognised phenomenon requiring careful distinction from true disease progression.
• It is generally managed by continuing antiretroviral therapy (rather than discontinuing it) alongside appropriate local or systemic treatment for the disease itself as clinically indicated.
• Long term follow up, incorporating ongoing HIV care with ongoing effective viral suppression, together with regular skin and mucosal surveillance for new or recurrent lesions, underpins full management of this condition.
• Overall prognosis for HIV associated disease has improved substantially in the antiretroviral therapy era compared with the pre antiretroviral therapy period. This reflects the central importance of sustained immune reconstitution in long term disease control.