9/12/2007 Kaposi Sarcoma Background: Kaposi sarcoma (KS) was described initially in 1872 by a Hungarian dermatologist, Moritz Kaposi. KS is a spindle-cell tumor thought to be derived from endothelial cell lineage. This condition carries a variable clinical course ranging from minimal mucocutaneous disease to extensive organ involvement. KS can occur in several different clinical settings. Epidemic AIDS-related KS: This entity occurs in patients with advanced HIV infection, and is the most common presentation of KS. In the United States, KS serves as an AIDS-defining illness in 10-15% of HIV-infected homosexual men. In Africa and developing regions, epidemic AIDS-related KS is common in heterosexual adults and occurs less often in children. Visceral involvement is common. AIDS-related KS is the most clinically aggressive form of KS. Immunocompromised KS: This entity can occur following solid-organ transplantation or in patients receiving immunosuppressive therapy. However, individuals with congenital immunodeficient states are not at increased risk for developing KS. The average time to development of KS following transplantation is 30 months. Visceral involvement is common. Classic KS: This entity typically occurs in elderly men of Mediterranean and Eastern European background. Classic KS usually carries a protracted and indolent course. Common complications include venous stasis and lymphedema. As many as 30% of patients with classic KS subsequently may develop a second malignancy. Visceral involvement is uncommon. Endemic African KS: This entity occurs in men who are HIV seronegative in Africa and may carry an indolent or aggressive course. Pathophysiology: KS is caused by an excessive proliferation of spindle cells thought to have an endothelial cell origin. Molecular studies suggest that KS originates from a single cell clone rather than a multifocal origin. Human herpes virus 8 (HHV-8) genomic sequences have been identified by polymerase chain reaction in more than 90% of all types of KS lesions (including epidemic and endemic forms), suggesting a causative role. These sequences additionally have been associated with body cavity–based lymphomas, Castleman disease, and leiomyosarcomas that occur in individuals infected with HIV. Factors that are thought to contribute to the development of KS in individuals infected with HHV-8 and HIV include an abnormal cytokine milieu associated with HIV infection (interleukin [IL]-6, IL-1, granulocyte-macrophage colony-stimulating factor [GM-CSF], basic fibroblast growth factor [bFGF], oncostatin M, tumor necrosis factor [TNF]) and the HIV-tat protein, which acts as a mitogen for KS cells. Frequency: In the US: KS currently is the most common AIDS-associated malignancy. KS serves as the presenting manifestation of AIDS in approximately 15% of homosexual men and in approximately 2% of patients with HIV infection in other risk groups. Internationally: In Europe, the highest rates of classic KS are in Sicily (Ragusa, 30.1 cases per million in men/5.4 cases per million in women) and Sardinia (24.3 cases per million in men/7.7 cases per million in women). Mortality/Morbidity: AIDS-related KS, unlike other forms of KS, tends to have an aggressive clinical course. Morbidity may occur from extensive cutaneous, mucosal, or visceral involvement. In patients receiving highly active antiretroviral therapy (HAART), the disease often has a more indolent clinical course or may regress spontaneously. The most common causes of morbidity include cosmetically disfiguring cutaneous lesions, lymphedema, gastrointestinal involvement, or pulmonary involvement. Pulmonary involvement is the most common cause of mortality. Race: In Africa and developing regions, epidemic AIDS-related KS is common in heterosexual adults and occurs less often in children. Classic KS typically occurs in elderly men of Mediterranean and Eastern European background. Endemic African KS occurs in HIV seronegative men in Africa. Sex: AIDS-related KS: In the United States, this condition occurs primarily in homosexual males, bisexual men, and in the female sexual partners of bisexual men. African KS occurs in heterosexual men and women with equal frequency. Classic KS occurs primarily in males, with a male-to-female ratio of 10:1. Age: AIDS-related KS generally occurs in adults. Classic KS typically occurs in patients aged 50-70 years. African KS occurs in people of a younger age (35-40 y).