Kaposi's Sarcoma at a Glance
- Multifocal tumor of endothelial cell origin with stage-dependent characteristic histopathology.
- Occurs in four clinical variants:
Classical Kaposi's sarcoma (KS)—in old men; starts as localized form; progresses slowly.
Endemic African KS—most frequent neoplasm in some Central African countries; also includes a rapidly progressive lymphadenopathic variant.
KS associated with immunosuppressive therapy—most frequently in organ-transplant recipients.
AIDS-related KS—rapidly progressive form in HIV-infected patients with early involvement of extracutaneous sites.
- KS development is invariably linked with human herpesvirus (HHV)-8 infection.
- Despite presumed viral pathogenesis, KS responds well to chemotherapy and radiation therapy.
In 1872, the Austro-Hungarian dermatologist Moriz Kaposi described five patients with multicentric cutaneous and extracutaneous neoplasm that primarily affected older individuals.1 This disease, originally described as “idiopathic multiple pigment sarcoma,” was later eponymously designated Kaposi's sarcoma (KS). Since then, different variants of this tumor have been described that have distinct epidemiologic features and run distinct clinical courses but show comparable histopathologies.
HHV-8 and Kaposi's Sarcoma
Several decades of epidemiological data and electron microscopic studies have suggested an infectious agent as an etiologic factor in KS.2,3 This suspicion was substantiated in 1994 when Chang and colleague discovered DNA of an unknown virus in KS lesions.4 This finding led to cloning, isolation, and characterization of a novel human herpesvirus now referred to as KS-associated herpesvirus (KSHV) or alternatively, human herpesvirus (HHV)-8.5,6
HHV-8 is a member of the γ-Herpesviridae subfamily, genus Rhadinovirus.5–9 Its 165-kb DNA genome has been entirely sequenced and shown to contain approximately 90 open reading frames.5,7,8 Many of the HHV-8 regulatory genes are homologous to genes of other Rhadinoviruses, and several are homologous to human genes involved in the regulation of apoptosis, cell proliferation, and angiogenesis.5,9,10 As with other herpesviruses, HHV-8 gene expression is tightly controlled and either associated with viral latency, such as LANA-1, V cyclin, and vFLIP, or lytic viral replication, such as vGPCR, vIL 6, and v-bcl-2.5,10 Several HHV-8 gene products, both of the lytic and the latent viral life cycles, have been shown to transform cells in vitro as well as in animal models in vivo.6,10–13 Therefore, it is generally accepted that this transforming capacity of HHV-8 plays a direct role in the development of KS.
The host range of HHV-8 in vivo and in vitro comprises vascular and lymphatic endothelial cells as well as different types of hemopoietic cells.6 The widely expressed 12-transmembrane light chain of the human cystine/glutamate exchange transporter system xc and the C-type lectin DC-SIGN have recently been proposed as receptors of HHV-8.14,15 The latter is of particular interest since in contrast to the former it is expressed by activated B cells, which are important host cells for HHV-8 in vivo.6,15...