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CHAPTER 4 - NEOPLASMS ASSOCIATED WITH AIDS

KAPOSI’S SARCOMA

Several forms of Kaposi’s sarcoma (KS) exist: classic, endemic, immunosuppression or
transplantation-associated, and epidemic. The classic form of KS most often appears in persons
of Eastern European or Mediterranean ancestry, has a male: female ratio of 15:1, and has a
median age of 64 years. Classic KS typically appears on skin of hands and feet and progresses
up arms and legs. Lymphedema occurs in some cases. Visceral or mucosal involvement appears
in 10% of cases. The endemic form of KS is seen in sub-Saharan Africa and typically appears
on the skin of limbs in adults. An aggressive lymphadenopathic form of KS can be seen in
children. The immunosuppressive or transplantation-associated form of KS is most likely to be
seen in persons with ancestry from areas in which classic KS occurs. It appears on average 2.5
years after transplantation. The male: female ratio is 2 to 4:1. In half of cases there is mucosal,
nodal, or visceral involvement. The epidemic form of KS is associated with HIV infection.[543]
Kaposi's sarcoma (KS) was rarely seen prior to the AIDS epidemic but became one of the
most common diagnostic diseases seen with AIDS (Table 5). The incidence of KS is about 1 in
100,000 in the general population. Prior to antiretroviral therapy, the incidence of KS with AIDS
was about 1 in 20, and up to 1 in 3 for men having sex with men.[544] Kaposi's sarcoma occurs
most frequently in homosexual and bisexual males. Kaposi's sarcoma is infrequently seen in
children and in persons whose risk for AIDS is parenteral exposure to HIV. Kaposi's sarcoma
remains less common in women than men, with a male: female ratio of 6:1 in the United States,
though in Africa the ratio is 2:1.[214,545,546]
The incidence of KS appears to have declined by 10% per year in the U.S. in the decade
of the 1990’s. The increasing use of antiretroviral therapy regimens appears to have made the
greatest difference. Persons on a single antiretroviral agent show a 13% reduction in the
development of KS, while those persons receiving triple agent therapy have a 59%
reduction.[547,548]
A gamma human herpesvirus called human herpesvirus 8, (HHV-8) and also has been
identified in skin and visceral lesions in 90% of all forms of KS, including classical, iatrogenic,
endemic, and AIDS-associated forms. Thus, it has been called Kaposi’s sarcoma-associated
herpes virus (KSHV). KSHV appears to be restricted to infection of cord blood mononuclear
cells, adult CD19 positive B cells, macrophages, and endothelial cells.[549] The prevalence of
KSHV in males is less than 10% in the U.S. but greater than 30% in parts of sub-Saharan
Africa.[544]
KSHV contains many genes that alter cellular growth, including BCL-2 and cyclin
analogs. In addition, KSHV produces proteins that induce angiogenesis.[544] The mitogenic
effect of HIV tat gene protein may act synergistically with KSHV to induce spindle cell
growth.[547] KSHV has also been detected in the KS lesions of HIV negative homosexual
males. It is phylogenetically similar to human herpesviruses 6 and 7.[550] KSHV can be
identified in the progressive stages of KS as well, but it can also be found in about a third of
tissues of AIDS patients without KS, suggesting that it is disseminated and plays a permissive
role in development of KS. This agent may rarely be found in tissues of patients with AIDS who
do not yet have a diagnosis of KS.[551]