Advances in the pathobiology and treatment of Kaposi sarcoma.

Abstract

Kaposi sarcoma, which has reached epidemic proportions in parts of Africa and in the Western world, continues to pose a problem in patients with AIDS receiving highly active antiretroviral therapy (HAART). This article reviews the new and important information regarding the epidemiology, biology, and management of Kaposi sarcoma that was published in the last year. Worldwide Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV8) seropositivity has been found to exceed the incidence of Kaposi sarcoma. Therefore, investigators have justifiably implicated other cofactors (eg, blood-sucking arthropods, angiotensin converting enzyme inhibitors, hemodialysis, and iron) in the development of Kaposi sarcoma. In the transplant setting, Kaposi sarcoma lesions have been shown to originate from the engraftment of donor tumor cells. The detection of HHV8 in Kaposi sarcoma lesions has provided a new diagnostic tool to help differentiate Kaposi sarcoma from its mimics. Kaposi sarcoma lesional cells, now confirmed to be of lymphatic origin, have been shown to express several chemokine receptors, some of which may help explain the predilection for skin. Regression of Kaposi sarcoma has been characterized histologically for the first time. The finding that some tumor cells can remain in an atrophic state even in completely regressed lesions suggests that they have the potential to recur. Protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based HAART regimens have been verified to be similarly effective. Although antiretrovirals have been noted to favorably alter the clinical characteristics of Kaposi sarcoma favorably, they seem not to alter the natural history of this disease. In the HAART era, because CD4 cell count was shown no longer to provide prognostic information about AIDS-related Kaposi sarcoma, the traditional classification system for staging AIDS-related Kaposi sarcoma has been refined. Also, a new staging system for classic Kaposi sarcoma has been proposed. Numerous advances have emerged regarding Kaposi sarcoma during the last year, many of which still need to be translated into clinically useful information. The results of new clinical trials involving antivirals purposely directed against HHV8 and antiretrovirals for HIV-uninfected people are anticipated. Finally, although investigators during this period did provide us with additional potential therapeutic targets, more novel approaches such as RNA interference and gene therapy have been also proposed as options in the future management of Kaposi sarcoma.