An Update on Kaposi’s Sarcoma: Epidemiology, Pathogenesis and Treatment

AIDS-Associated Kaposi’s Sarcoma

Kaposi’s sarcoma (KS) is a multi-focal, angioproliferative neoplasm that usually appears on the skin, but can also involve the visceral organs. In 1981, 26 cases of KS were reported as occurring in young homosexual men in New York and California. Many of these patients also had concomitant pneumocystis carinii pneumonia (PCP) and a variety of other “opportunistic infections” [1]. At that time, the underlying cause of AIDS was unknown, but, remarkably, one-third of these patients developed a disseminated form of KS. In 1983, it was postulated that KS was driven by the host’s profoundly immunocompromised state. Interestingly, 95% of these cases had occurred in homosexual men. Furthermore, it appeared that the clinical presentation of AIDS-associated KS (AIDS-KS) differed significantly from previously described clinical variants of this unusual neoplasm [2]. In these immunocompromised patients, KS behaved more aggressively, often involving mucosal tissues, and progressed to visceral involvement leading to organ dysfunction and death [3].

In the early 1980s, a significant proportion of homosexual men with AIDS were affected by KS; for example, in San Francisco, this opportunistic neoplasm occurred in 40% of homosexual men with AIDS. This suggested that a major risk factor for KS might be homosexual intercourse [4]. In fact, several early studies showed a connection between the number of sexual partners and the prevalence of KS. For example, in Vancouver, 56% of homosexual men with AIDS and more than 20 partners developed KS [5]. As the widespread use of highly active antiretroviral therapy (HAART) gained popularity in the early and mid-1990s, an 8.8% annual decline from 1990 to 1998 in KS incidence in the United States was observed, along with a 50% reduction in KS incidence among those on triple antiretroviral therapy [6]. A cancer surveillance program in San Francisco revealed similar patterns, with the incidence of KS in 1973 (prior to the AIDS epidemic) at 0.5 cases per 100,000 people, while during the peak of the AIDS epidemic in 1991, this number was 33.3 cases per 100,000 people and then declined in 1998 (post-HAART) to 2.8 cases per 100,000 people [7].

The Classic Form

In 1872, Moritz Kaposi first described the “classic” variant of KS that is typically observed in elderly men of Mediterranean or eastern European origin [8]. This form of KS generally presents with lesions confined to the lower extremity, affects men more commonly than women in a 15:1 ratio, and is usually indolent with patients living 10 years or more [9]. The incidence of KS in the Mediterranean is significantly higher than in the rest of Europe and the United States. For example, prior to the AIDS epidemic, there was a two- to threefold higher prevalence of KS among the Italian population compared to that of the USA, and a ten times greater prevalence compared to England [10].

The Endemic Form

In the 1950s, an endemic form of KS was reported to be one of the most common neoplasms observed in central Africa, affecting men, women and children [11]. Notably, following the AIDS epidemic, the incidence of KS in Africa increased markedly, and from 1968 to 1970, KS accounted for 6.6% of all cancers occurring in men; however, from 1989 to 1991, KS became the most commonly reported cancer occurring in men (48.6% of male cancer patients), while the prevalence in female cancer patients rose to 17.9% [12].

The Iatrogenic Form

In the 1970s, an “iatrogenic” form of KS was also observed among organ transplant recipients, as well as other patients on long-term immunosuppression for other diseases [2]. Recently, there have been a growing number of cases of this iatrogenic variant of KS. For example, there are an increasing number of reports in the literature describing individuals who develop KS arising in the context of long-term corticosteroid therapy and other biologic therapies, including rituximab, infliximab, and abatacept administered for chronic inflammatory and autoimmune conditions, including autoimmune thrombocytopenia, polyangiitis and pemphigus vulgaris [13, 14, 15]. The occurrence of KS in such patients frequently resolves spontaneously when the immunosuppressive therapies are discontinued [16]. As the increasing use of these immunomodulatory medications becomes more widespread, it is important to be aware of the possibility of KS occurring among these individuals who previously had not been considered “high-risk”.

New attention has been focused on the increased occurrence of KS among patients who are significantly immunosuppressed following organ transplantation. In fact, the incidence of KS is 400–500 times higher among such patients than the general population [17]. This may be due to reactivation of latent HHV-8 virus or perhaps through acquisition of the virus from the donor organ [18]. However, certain immunosuppressants may be less likely to put patients at risk for iatrogenic KS. For example, sirolimus or everolimus (mTOR inhibitors) appear to inhibit the occurrence and/or progression of KS in transplant recipients while preventing organ rejection [19, 20]. These drugs may reduce the effect of vascular endothelial growth factor (VEGF) which is believed to play a pivotal role in the pathogenesis of KS [20]. Therefore, clinicians need to be aware of the oncogenic potential of immunosuppressive therapy in these organ transplant recipients.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors.