Kaposi’s Sarcoma Pathogenesis Research Articles

Evaluation of interleukin-23 expression in classic kaposi’s sarcoma and AIDS-Associated

Kaposi’s sarcoma (KS) is a low-grade vascular tumor that presents most frequently with skin lesions. Multiple factors are related to KS pathogenesis. The interleukin-23 (IL-23) is an immunomodulatory cytokine with pro-carcinogenic role. The aim of this study was to evaluate the detection of IL-23 in cutaneous lesions of patients with KS classic and KS-AIDS. This was a cross-sectional study conducted at the public Hospital in Natal, Rio Grande do Norte, Brazil. This study included 13 biopsies of patients which presented KS with histopathological confirmation. For detection of IL-23, the immunohistochemical analysis was made with monoclonal antibody anti-IL-23. The immunostaining for IL-23 in biopsies was positive in 61.5% (8/13) of cases. Of seven lesions classified as patch-stage, three were positive for IL-23 (42.8%); two of three samples classified as plaque-stage were positive for IL-23 (66.7%); all the nodular-stage lesions were positive for IL-23. The positivity found in KS-AIDS lesions was 66.7% (6/9) and KS classic 50% (2/4). Our data supports the concept that IL-23 might be a pro-carcinogenic mediator, detected in KS lesions, probably favoring the progression of the tumor. KEY WORDS: Sarcoma; Kaposi; interleukin-23; tumor microenvironment.

Therapeutic Perspectives in the Systemic Treatment of Kaposi's Sarcoma.

Simple SummaryAlternative systemic treatments are needed for patients who develop chemotherapy-refractory KS. Anti-angiogenic therapies constitute interesting therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis, and could represent attractive alternatives. Immune checkpoints blockade could also be an interesting therapeutic approach in order to restore anti-HHV-8 immunity and tumor control.In patients with Kaposi’s sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.

A Case of Recurrent Kaposi’s Sarcoma in an HIV-Negative Patient

<strong>Background:</strong> Kaposi’s Sarcoma (KS) is an angioproliferative disease of endothelial tissue, as a result of Human Herpesvirus 8 (HHV-8) infection. Theoretically, there are four types of KS: Classic, Epidemic, Endemic, and Iatrogenic. The Classic variant is seen among men of 50–70 years of age, of Mediterranean or European descent. The Epidemic form is seen among HIV seropositive patients. The Endemic variant is seen among HIV seronegative men, of African American descent, typically 20–30 years of age, and lastly, the Iatrogenic subtype is seen among those undergoing immunosuppressive treatment. In this paper, we present a case of an HIV-negative, non-immunocompromised patient with recurrent Human Herpesvirus 8 (HHV-8) positive Kaposi’s Sarcoma, who does not resemble any of the aforementioned types. <strong>Presentation:</strong> A 65-year-old male presented to the outpatient clinic with the chief complaint of a nodular lesion over the left posterior thigh for the past two months. Past history was significant for biopsy-confirmed Kaposi’s sarcoma over the right thigh four months prior. There was no history of an immunocompromised state and testing for HIV returned negative. The patient’s complete blood count and complete metabolic panel were normal, and the patient had no signs of any underlying systemic illness. The patient underwent surgical excision of the lesion on the left lower extremity, which revealed Kaposi’s sarcoma, nodular type with immunohistochemical staining of lesional cells positive for HHV-8, and with clear margins. <strong>Conclusion:</strong> The pathogenesis of KS has been attributed to viral oncogenesis as a result of dysfunction of the p53 tumor suppressor gene. Establishing this mechanism required decades of research, and through this process, it has been elucidated that immunosuppression is necessary for KS tumorigenesis. However, data is now emerging on the occurrence of KS in immunocompetent individuals, thus highlighting the importance of further research in the understanding of this tumor’s pathogenesis. Additionally, to the best of our knowledge recurrent KS in an immunocompetent individual has been sparingly described, especially in a non-endemic population.

Cells of the Innate and Adaptive Immune Systems in Kaposi's Sarcoma.

Kaposi's sarcoma (KS) is an angioproliferative malignancy whose associated etiologic agent is the Kaposi's sarcoma-associated herpesvirus (KSHV). KS is the most prevalent malignancy among HIV-infected individuals globally and is considered an AIDS-defining malignancy. The different forms of KS including HIV-associated KS, iatrogenic (immunosuppression-related) KS, and classical KS in elderly males suggest that immune cell dysregulation is among the key components in promoting KS development in KSHV-infected individuals. It is therefore expected that different cell types of the immune system likely play distinct roles in promoting or inhibiting KS development. This narrative review is focused on discussing cells of the innate and adaptive immune systems in KSHV infection and KS pathogenesis, including how these cells can be useful in the control of KSHV infection and treatment of KS.

The guanine exchange factor SWAP70 mediates vGPCR-induced endothelial plasticity.

BackgroundThe viral G protein-coupled receptor (vGPCR) is proposed to act as one of the predominant mediators of Kaposi’s sarcoma (KS), a human herpes virus 8 (HHV8)-elicited disease. The actions of vGPCR manifest pathogenesis, in part, through increased permeability of endothelial cells. Endothelial cell-cell junctions have indeed emerged as an instrumental target involved in the vasculature defects observed within the tumor microenvironment. The pathway leading to adherens junction destabilization has been shown to involve the activation of the small GTPase Rac, in the context of either latent infection or the sole expression of vGPCR. However, the precise molecular mechanisms governed by vGPCR in vascular leakage require further elucidation.FindingsGuanine exchange factors (GEFs) function as critical molecular switches that control the activation of small GTPases. We therefore screened the effects of 80 siRNAs targeting GEFs on vGPCR-driven endothelial permeability and identified switch-associated protein 70 (SWAP70) as necessary for its elevating effects. Pull-down experiments further showed that Rac activation by vGPCR was dependent on SWAP70. Examination of tissues and cells from HHV8-positive patients revealed that SWAP70 was ubiquitously expressed. Furthermore, SWAP70 was found to be crucial for vGPCR-driven endothelial tube formation and endothelial sprouting in vitro.ConclusionsSWAP70 appears to act as a molecular intermediate between vGPCR and endothelial activation. Because of the important role of vGPCR-mediated endothelial plasticity in KS pathogenesis, inhibition of SWAP70 function could be of interest for blocking vGPCR-driven activities in HHV8-defined diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12964-015-0090-1) contains supplementary material, which is available to authorized users.

Treatment of a Patient with Kaposi's Sarcoma Arising during Hemodialysis with the Multikinase Inhibitor Pazopanib

Kaposi’s sarcoma (KS) is an unusual multifocal neoplastic angioproliferative disorder. We herein report a case of classic KS that occurred in a patient receiving hemodialysis for 7 years. The patient had a history of chronic renal failure due to glomerulonephritis for 20 years. Multiple reddened violaceous patches, plaques, and nodules were found on the right knee. Biopsy revealed positivity for human herpesvirus 8 (KS-associated herpesvirus) consistent with KS. Pazopanib, a multitarget tyrosine kinase inhibitor, is an effective agent for treatment of advanced soft tissue sarcoma. The patient received pazopanib for 6 months investigate its effects on KS. The skin lesions and painful symptoms showed improvement. Further studies are required to determine the mechanism underlying the anticancer action of pazopanib and the pathogenesis of KS. (Korean J Med 2015;89:113-116)

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

Background: Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects. Methods: We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls. Results: HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 &plusmn; 2.4) versus plaque lesions (4.1 &plusmn; 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001). Conclusions: We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

Background: Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects. Methods: We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls. Results: HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 ± 2.4) versus plaque lesions (4.1 ± 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001). Conclusions: We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

Background: Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects. Methods: We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls. Results: HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 &plusmn; 2.4) versus plaque lesions (4.1 &plusmn; 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001). Conclusions: We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.

Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi’s sarcoma

Kaposi's sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV]) infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is sustained by viral and host-derived paracrine-acting factors primarily released under hypoxic conditions. We show that interactions between the regulatory lectin galectin-1 (Gal-1) and specific target N-glycans link tumor hypoxia to neovascularization as part of the pathogenesis of KS. Expression of Gal-1 is found to be a hallmark of human KS but not other vascular pathologies and is directly induced by both KSHV and hypoxia. Interestingly, hypoxia induced Gal-1 through mechanisms that are independent of hypoxia-inducible factor (HIF) 1α and HIF-2α but involved reactive oxygen species-dependent activation of the transcription factor nuclear factor κB. Targeted disruption of Gal-1-N-glycan interactions eliminated hypoxia-driven angiogenesis and suppressed tumorigenesis in vivo. Therapeutic administration of a Gal-1-specific neutralizing mAb attenuated abnormal angiogenesis and promoted tumor regression in mice bearing established KS tumors. Given the active search for HIF-independent mechanisms that serve to couple tumor hypoxia to pathological angiogenesis, our findings provide novel opportunities not only for treating KS patients but also for understanding and managing a variety of solid tumors.

KSHV-mediated ROS induction defines novel therapeutic targets in Kaposi's sarcoma

Background Kaposi’s sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS). Understanding the interplay of viral and host factors in KS carcinogenesis is critical for the rational development of new therapies. Reactive oxygen species (ROS) have a recognized broad function in oncogenesis mediated by signaling cascades leading to the Rac1 activation of NADPH oxidases (Nox) [1]. ROS play a role in cell cycle regulation and angiogenesis, yet the specific molecular events linking ROS and these cancer hallmarks are still elusive. KSHV encodes a constitutively active G protein-coupled receptor (vGPCR) [2], which triggers KS-like sarcomagenesis via Rac1 [3]. It has been shown that Rac1-activated mutant induces tumors resembling Kaposi’s sarcoma by a ROS-mediated mechanism in transgenic mice [4,5]. Moreover, Rac1 is overexpressed in AIDS-KS lesions and in KSHV-infected mECK36 tumors, pointing to a role for KSHV-induced Rac1-mediated production of ROS in KS pathogenesis [5]. The current study explored the induction of oxidative stress pathways in the KSHVinduced mouse model mECK36.

Evidence of COX-1 and COX-2 expression in Kaposi’s sarcoma tissues

Cyclooxygenases (COXs) are enzymes catalysing prostaglandin synthesis and are implicated in the carcinogenesis of some cancer types. In addition, an important role of these enzymes in herpesvirus infections was demonstrated and it has recently been proposed that COX-2 may participate in herpesvirus-induced neoplasia such as Kaposi’s sarcoma (KS). To date no immunohistochemical study has been performed to determine the identification of COX-1 and COX-2 in KS. We have investigated 35 cases of classic KS and 27 cases of epidemic KS form in order to study the distribution and localisation of COXs. We have examined by immunohistochemistry the expression of COX-1 and COX-2 in classic and epidemic forms of KS also in relationship to the characteristic morphological phases (patch, plaque and nodular stage) of KS and cell localisation by double immunostaining. Moreover, we have obtained COX-1 and COX-2 expression by Western blot analysis. Our results establish that (a) COX-1 and COX-2 are overexpressed significantly in classic and epidemic KS compared with control skin tissues ( P < 0.01 and P > 0.03, respectively, for COX-1; P < 0.01 and P > 0.03, respectively, for COX-2); (b) the extent and intensity staining for both COXs were higher in classic than in epidemic form of KS. Our data support the hypothesis that both COXs may be involved in the pathogenesis of KS.

Investigational agents for treatment of AIDS-related Kaposi’s sarcoma

AIDS-related Kaposi’s sarcoma (KS) is a neoplasm that results from the co-infection of HIV and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8). Targeting HIV with highly active antiretroviral therapy has attenuated the natural history of this disease. Recent discoveries have elucidated the role of multiple signaling pathways in the pathogenesis of AIDS-related KS. In particular, KSHV/HHV8-specific gene products, including a G-protein-coupled receptor (vGPCR) and a homolog of human IL-6 (vIL-6), have been implicated in the development of tumorigenesis and angiogenesis. In addition, KSHV/HHV8 can modulate cellular growth and angiogenic pathways to augment malignant transformation and potentiate growth. This article discusses the main signaling pathways that are implicated in the pathogenesis of AIDS-related KS, reviews recently completed clinical trials and anticipates the future direction of molecularly targeted agents in this disease.

Cytomegalovirus Co-infection in AIDS-associated Oral Kaposi’s Sarcoma

The increasing appearance of AIDS-associated oral Kaposi's sarcoma (KS) in South Africa may be ascribed to the later start of the HIV epidemic, more patients reaching stages III and IV, and the inaccessibility of most patients to anti-retroviral therapy. The objective of this study was to demonstrate cytomegalovirus (CMV) co-infection in oral KS and to consider its possible significance. We reviewed 20 cases of oral KS in known HIV-positive patients without active CMV disease. HHV8 PCR and CMV immunohistochemistry were performed. HHV8 DNA was present in all cases. CMV inclusions were detected in five cases. The significance of CMV co-infection in oral KS is unclear. The inclusions suggest active infection, although there is no evidence to support CMV in the pathogenesis of KS. Nonetheless, it is vital that physicians be alerted to active CMV infection, so that timely intervention and careful observation can be instituted, ensuring early diagnosis and treatment.

The kaposi’s sarcoma associated herpesvirus: a model for viral oncogenesis

Kaposi’s sarcoma (KS) is the most common tumor arising in HIV-infected patients and remains a significant cause of morbidity and mortality among the AIDS population in the developing world. The recent discovery of the etiologic agent of KS, the Kaposi’s sarcoma associated herpesvirus (KSHV), has invigorated new awareness of this unique neoplasm. Indeed, examination of the KSHV genome has revealed numerous genes that may contribute to the development of the spindle cell, the dominant cell in KS lesions.Here the authors survey the current knowledge on how KSHV-encoded genes play integral roles in transformation, cell survival, and neoangiogenesis through the transduction of signals from viral-encoded genes to the host cell nucleus. These signaling pathways likely affect the expression of cellular genes involved in KS pathogenesis. Since signaling pathways have proven to be successful drug targets in the past and their role in Kaposi’s sarcoma is becoming apparent, viral-encoded survival genes are emerging targets for the development of drug research. It is therefore of utmost importance to further define their involvement in KS pathogenesis.

Human immunodeficiency virus replication in a primary effusion lymphoma cell line stimulates lytic-phase replication of Kaposi's sarcoma-associated herpesvirus.

Human immunodeficiency virus (HIV) and Kaposi's sarcoma-associated herpesvirus (KSHV) coinfect many individuals in North America and in parts of Africa. Infection with HIV is a leading risk factor for the development of Kaposi's sarcoma (KS). In this study, we tested the hypothesis that HIV infection of common or adjacent cells would stimulate replication and spread of KSHV. Infection of a primary effusion lymphoma cell line by vesicular stomatitis virus type G-pseudotyped HIV type 1 led to a rapid induction of lytic-phase KSHV replication. Induction of lytic KSHV replication by HIV required active replication of HIV. The addition of the nucleoside reverse transcriptase inhibitor azidothymidine or the protease inhibitor indinavir to the culture prevented HIV spread and inhibited the associated induction of KSHV lytic replication. Lytic replication occurred in both HIV-infected and HIV-uninfected cells within the culture, and could be induced in uninfected cells via a soluble factor released from the HIV-infected cells. Transmission of infectious KSHV to an uninfected target cell was enhanced by HIV replication and was inhibited by antiretroviral drugs. These results may have implications for the pathogenesis and treatment of KS in individuals coinfected with KSHV and HIV.

Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8.

Human herpesvirus 8 (HHV8) infects Kaposi's sarcoma (KS) spindle cells in situ, as well as the lesional endothelial cells considered to be spindle cell precursors. The HHV8 genome contains several oncogenes, suggesting that infection of endothelial and spindle cells could induce cellular transformation and tumorigenesis and promote the formation of KS lesions. To investigate the potential of HHV8 infection of endothelial cells to contribute to the development of KS, we have developed an in vitro model utilizing dermal microvascular endothelial cells that support significant HHV8 infection. In contrast to existing in vitro systems used to study HHV8 pathogenesis, the majority of dermal endothelial cells are infected with HHV8 and the viral genome is maintained indefinitely. Infection is predominantly latent, with a small percentage of cells supporting lytic replication, and latency is responsive to lytic induction stimuli. Infected endothelial cells develop a spindle shape resembling that of KS lesional cells and show characteristics of a transformed phenotype, including loss of contact inhibition and acquisition of anchorage-independent growth. These results describe a relevant model system in which to study virus-host interactions in vitro and demonstrate the ability of HHV8 to induce phenotypic changes in infected endothelial cells that resemble characteristics of KS spindle cells in vivo. Thus, our results are consistent with a direct role for HHV8 in the pathogenesis of KS.

Identification of human herpesvirus 8-specific cytotoxic T-cell responses.

Human herpesvirus 8 (HHV-8) (or Kaposi's sarcoma-associated herpesvirus) is implicated in the etiopathogenesis of Kaposi's sarcoma (KS) and certain lymphoproliferations. The introduction of more effective therapies to treat human immunodeficiency virus infection has led to a decline in the incidence of KS and also in the resolution of KS in those already affected. This suggests that cellular immune responses including cytotoxic T lymphocytes (CTLs) could play a vital role in the control of HHV-8 infection and in KS pathogenesis. Here we elucidate HLA class I-restricted, HHV-8-specific cellular immune responses that could be important in the control of HHV-8 infection and subsequent tumor development. We show the presence of CTLs against HHV-8 latent (K12), lytic (K8.1), and highly variable (K1) proteins in infected individuals.

Expression of the open reading frame 74 (G-protein-coupled receptor) gene of Kaposi's sarcoma (KS)-associated herpesvirus: implications for KS pathogenesis.

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) encodes a G-protein-coupled receptor (GCR) homolog. This protein is a potent, constitutively active signalling molecule that can influence both proliferation and angiogenesis when ectopically expressed in fibroblasts in vitro. Here we have examined the expression of the KSHV GCR gene in virus-infected lymphoid cells and in KS tumors. Our results show that in both situations the gene is expressed primarily during lytic replication; its transcription is unaffected by inhibition of viral DNA synthesis, indicating that it is expressed in the early phases of the lytic program. The major transcript bearing GCR sequences is bicistronic, harboring coding sequences for another viral gene, K14, at its 5' end. Extensive searches for monocistronic GCR mRNAs using nuclease mapping and reverse transcription-PCR failed to detect such species. The 5' end of K14/GCR mRNA maps to nucleotide (nt) 127848, and its poly(A) addition site maps to nt 130546; a 149-nt intron is present in the K14/GCR intergenic region. These results suggest that the KSHV GCR is translated by unconventional mechanisms involving either translational reinitiation, internal ribosomal entry, or leaky ribosomal scanning. The restriction of GCR expression to the lytic cycle has important implications for the potential role(s) of the GCR in KS pathogenesis.

Kaposi’s sarcoma–associated herpesvirus/human herpesvirus-8: A new virus in human pathology

The discovery of a new human herpesvirus in Kaposi’s sarcoma (KS) tissue of patients with AIDS has opened up new vistas in virology and oncology. This herpesvirus was first descriptively named KS-associated herpesvirus (KSHV), but was recently renamed human herpesvirus 8 (HHV8). KSHV/HHV8 DNA has been found in all forms of KS, suggesting that it might be involved in the pathogenesis of KS. In addition, KSHV/HHV8 can be detected in both malignant and benign lymphoproliferative diseases, such as body cavity–based B-cell lymphomas and multicentric Castleman’s disease. KSHV/HHV8 was also found in patients with angiosarcoma of the face and angiolymphoid hyperplasia with eosinophilia. Although only a limited portion of the virus has been sequenced, KSHV/HHV8 is equipped with genes that could confer oncogenic potential. The virus can now be cultured, providing the possibility for studies of viral replication and the mode of transmission. The recently developed serologic assays for antiviral antibodies suggest that infection with KSHV/HHV8 is not ubiquitous because KSHV/HHV8 seropositivity is limited to a small proportion of the population. (J Am Acad Dermatol 1997;37:107–13.)