Kaposi's Sarcoma

Kaposi's sarcoma is the most frequent neoplastic manifestation of HIV infection and is one of the CDC criteria that define an HIV-infected individual as having AIDS. AIDS-associated KS more frequently is seen among homosexual or bisexual men with HIV than in other HIV transmission risk groups. This epidemiologic observation led to a search for a second transmissible factor, which resulted in the identification of a new member of the gamma herpesvirus family, Kaposi's sarcoma herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). This virus has now been associated not just with KS, but also with a subset of B-cell lymphomas (discussed below), Castleman's disease and, perhaps, multiple myeloma.

The epidemiologic data indicate that exposure to this virus is more common in promiscuous homosexual men and in populations with higher frequencies of "classic" or "endemic" KS not associated with HIV-1. It is found in KS tissue regardless of the epidemiologic background, but the mechanism by which the virus participates in tumor development is unclear. There are a number of KSHV genes with human homologues that suggest possible direct effects of the virus (cyclin D, bcl-2 or activated G-protein coupled receptor homologues) or effects at a distance (interleukin-6, chemokine and Ox-2 homologues). Hypotheses for how this virus is oncogenic are wide ranging and the mechanisms involved may be quite distinct from other tumor viruses. The nature of the immunologic response to KSHV remains ill defined, but clearly plays an important role in the control of KSHV-related tumors. KS in the setting of organ transplant often regresses with reduction of immunosuppressive medication. Similarly, in AIDS, patients treated with potent antiretroviral drug combinations have both a markedly reduced incidence of KS and often have pre-existing KS regress.

Histopathologically, KS lesions are a mixture of different cell types. Endothelial cells are quite present within the KS lesions, as is a prominent spindle-cell proliferation surrounded by extravasated erythrocytes and macrophages. The cell of origin of the neoplasm is still debated, as is the clonality of the disease. There are some patients who have multiple independent clones of tumor, whereas a subset of patients appear to have metastatic lesions derived from a single clone. In general, however, aggressive treatment of the original lesion has not had substantial impact on the ultimate development of other lesions.

KS often is a cutaneous nonblanching red macule. As lesions increase in size, they often have surrounding ecchymoses and acquire more of a violet hue. At times, the lesions may become nodular and, with advanced disease, the lesions may become confluent with large plaques developing, particularly on the legs. There is no orderly pattern of tumor progression, and presentation may be with lesions at multiple sites. The rate of growth of the primary lesions, as well as the appearance of new lesions, is quite variable. The lesions may occur on any cutaneous site and on mucous membranes. Lymphatic involvement is not unusual, and KS may present as lymphadenopathy. Visceral involvement, particularly of the trachea, lungs, and gastrointestinal tract, occurs commonly and may be seen in the absence of cutaneous disease. The most striking morbidity associated with KS is that of lymph node involvement and consequent lymphedema involving the lower extremities, groin, and head and neck. Extensive parenchymal or pleural involvement of the lung may result in life-threatening respiratory compromise.