Description

• Synonym(s): KS; multiple idiopathic hemangiosarcoma
• KS is a low-grade vascular tumor associated with human herpesvirus 8 (HHV-8), a γ-herpesvirus.
• Kaposi sarcoma–associated herpesvirus (KSHV), another name for HHV-8, is the etiologic agent of all clinical forms of KS and several other lymphoproliferative diseases, including primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD).
• Four major forms are seen:
  • Epidemic/AIDS-associated KS: seen primarily in patients with lower CD4 counts, especially among patients who are not on highly active antiretroviral therapy (HAART)
  • Iatrogenic/transplant-associated KS: seen in patients who are posttransplant and/or on immunosuppressive medication regimens
  • Endemic/African KS: seen in equatorial Africa, especially sub-Saharan countries
  • Classic/sporadic KS: rare, mostly seen in elderly men in the Mediterranean and Eastern European regions
• Systems affected: hemolytic/lymphatic/immunologic; skin/exocrine; gastrointestinal; pulmonary
• Fulminant lymphadenopathic disease is a subtype of endemic KS occurring in young children.

Epidemiology

• Predominant age: 16 to 70 years; African KS predominant age: 35 to 40 years; classic KS age: 50 to 70 years; AIDS-related KS age: 20 to 54 years
• Predominant sex: in the United States, epidemic KS: male > female ~50:1; classic and endemic KS: male > female ~10:1

Incidence

• ~2,500 cases occur yearly in the United States, most often in people infected with HIV.
• The U.S. incidence of KS after transplantation is estimated to be 1 in 200; renal transplant recipients are most frequently affected.
• Incidence of KS has decreased greatly since the advent of HAART; KS in the United States peaked at 47 cases per million at the height of the AIDS epidemic and now occurs at rate of 6 cases per million people each year.

Prevalence

• Before HAART, KS was >20,000 times more common in AIDS patients than in the general population.
• The seroprevalence of KSHV in the United States is <1–5%, but among MSM, prevalence is 20–77%; in certain parts of Africa, rates can reach >80%.
• AIDS-related KS may occur at normal CD4 cell counts but is more common at CD4 <200 cells/mL.
• In sub-Saharan Africa, KS remains the most frequent cancer among men, the third most frequent cancer among women, and the most common HIV-associated malignancy.

Etiology and Pathophysiology

• HHV-8 can be transmitted through blood transfusions, solid-organ transplants, and possibly through saliva.
• HHV-8 is necessary, but not sufficient, to induce KS.
• HHV-8 activates signaling pathways that promote an angiogenic-inflammatory state, leading to vascular proliferation that is the hallmark of KS.
• HIV infection may promote KS progression by inducing cytokines and impairing host immunity.
• Certain HIV gene products may play a role in tumorigenesis in KS.

Genetics
Genetic predisposition is suggested by the occurrence of classic KS in men of Mediterranean or Eastern European Ashkenazi descent.

Risk Factors

• HIV infection
• Living in endemic areas (e.g., Zimbabwe, Uganda)
• Immunosuppression (e.g., immunosuppressant medications, transplantation, chemotherapy)
• High-risk sexual practices
• Maternal–child transmission
• Injection drug use
• Exposure to infectious saliva
• Contact with KS skin lesions
• Blood transfusions and solid-organ transplants
• HHV-8 viremia (associated with 9-fold increased risk of developing KS)
• High antibody titers to HHV-8 related to faster development of KS and possibly to higher maternal–child transmission

General Prevention

Safe sex practices, avoid needle sharing, and careful screening of transplant organs; no anti–HHV-8 therapy is currently recommended for prevention.

Commonly Associated Conditions

HIV infection/AIDS; lymphoma