Kaposi sarcoma (KS) is a vascular proliferation that is caused by HHV8 infection and that occurs in distinct epidemiologic subgroups. Clinical characteristics vary by subgroup. 

KS affects patients in four clinically distinct epidemiologic subgroups: (1) elderly men of Mediterranean, eastern European or Ashkenazi Jewish heritage, in whom HHV8 infection is endemic ("classic KS"); (2) middle-aged adults and children in equatorial Africa, in whom HHV8 infection is endemic ("endemic KS"); (3) AIDS patients ("AIDS-related KS"); and (4) solid-organ transplant recipients ("iatrogenic KS"). ¹A fifth subtype – in HIV-negative men who have sex with men – is emerging and is characterized by indolent cutaneous lesions. ^2,3

Classic KS presents as multiple cutaneous plaques and nodules, most commonly in the distal extremities. These follow an indolent course. In contrast, the endemic lymphadenopathic form that occurs in equatorial African children follows a rapidly progressive course if untreated. ⁴Endemic KS in African adults resembles classic KS, with cutaneous lesions predominantly affecting the limbs. ⁵ AIDS-associated KS frequently involves the skin, especially of the face, lower extremities, and genitals, as well as oral mucosa. About 15% of patients with AIDS-associated KS present with involvement of extra-mucocutaneous sites, most commonly the gastrointestinal tract, lymph nodes, and lung.⁶ Iatrogenic KS is an uncommon complication of transplant-associated immunosuppression. Typically, this subtype is localized, although disseminated visceral disease can occur. 

All forms of KS are comprised of small vascular proliferations with admixed mildly atypical spindle cells. Cutaneous KS progresses through characteristic patch, plaque, and, finally, nodular stages. In the patch stage, there are proliferations of vessels that dissect through the reticular dermis, with associated lymphocytic infiltrates and extravasated red blood cells; this stage can sometimes be deceptively lymphangioma-like. ⁷ In the plaque stage, the vessels and spindle cells become more confluent, there are more prominent inflammatory infiltrates, and intracellular and extracellular hyaline globules become apparent. In the nodular stage, a fascicular spindle cell component predominates.

Nuclear expression of HHV8 latent nuclear antigen-1 is essentially 100% sensitive and specific for KS, making it a useful diagnostic marker in challenging cases.⁸ KS also expresses non-specific vascular markers, such as CD31, CD34, and ERG, as well as lymphatic markers such as D2-40.

The prognosis of KS depends on the epidemiologic subtype and presence of visceral involvement. The aggressive endemic lymphadenopathic form, which is highly lethal in the absence of treatment, is also highly sensitive to chemotherapy and thus has a good prognosis if diagnosed and treated early. ⁹Patients with AIDS-associated KS are treated with combined HAART and systemic chemotherapy.⁸ Patients with iatrogenic KS can be treated with immunosuppression withdrawal, although this could have adverse effects on the transplanted organ.¹ Extensive visceral disease and degree of immunosuppression are associated with a poorer prognosis.^9,10

• KS is caused by HHV8, a DNA virus that is primarily sexually transmitted; most patients infected with HHV8 do not develop KS.⁵

• Gill et al. demonstrated that some lesions are monoclonal while others, especially early lesions, are polyclonal; they concluded that KS might start as a polyclonal proliferative process, out of which dominant clones arise.¹⁰

• Comparative genomic hybridization studies have demonstrated recurrent alterations to 11q13, which contains FGF3 and FGF4 loci. ¹¹

• Copy number variations of chromosomes 16 ,17, 21, and X have been demonstrated in more advanced lesions.¹²

• Viral transformation leads to expression of viral and host cellular microRNAs, which suppress expression of tumor suppressor thrombospondin 1.¹³

• Transformation of host endothelial cells by HHV8 leads to expression of a variety of genes related to tumorigenesis, including KIT.^14,15