Endemic African Kaposi's Sarcoma Research Articles

A Case of Neglected Classıc Kaposı’s Sarcoma

Kaposi's sarcoma (KS) is a rare disease in the community. It was first described in 1872 as an idiopathic, multipigmented sarcoma of the skin [1]. It is a vascular or lymphatic-focused tumor type originating from the endothelium, caused by Human Herpes Virus 8 (HHV8), called KS-associated herpes virus (KSHV) [2]. There are 4 clinical subtypes of the disease. These are: Classical KS, African endemic KS, iatrogenic KS, and AIDS-related (epidemic) KS. It usually occurs with pink-red patch and blue-purple-black nodule, polyp or plaques. Most of the cases in classical KS are over 50 years old. Although the female/male ratio varies between studies, it is more common in males [3]. Here, a neglected case of Classic KS is presented.

Differential Immune Responses in Epidemic and Endemic Tanzanian Kaposi Sarcoma Patients

Background: Mechanisms underlying Kaposi sarcoma (KS) development are unclear. The high incidence of KS in HIV-1+ individuals implicates immune dysregulation in epidemic KS (EpKS) development. In African endemic KS (EnKS), the immune response is uncharacterized. Aim: The aim was to assess a comparative quantification between newly diagnosed Tanzanian EpKS and EnKS patients, and asymptomatic controls. We also report the first comparison of KSHV NAb prevalence and titer between EpKS and EnKS patients. Methods: To compare innate and adaptive immune responses, we recruited histologically confirmed Tanzanian EpKS and EnKS patients, as well as noncancer controls. After differential detection of KSHV nucleic acids in tissues, neutralizing antibody (NAb), levels of cytokines/chemokines, and T-cell differentiation subsets were quantified. The Mann-Whitney U-test was used to assess median differences between groups. All tests were 2-tailed and P-values < 0.05 were considered significant. Results: A total of 180 patients have been recruited in this study. In addition, a comparable 25 EpKS and 10 EnKS as well as 10 noncancer controls were recruited for this study. KSHV was significantly more frequently detected in EpKS patients than in EnKS. While all EpKS, and some EnKS patients mounted NAb responses, the EpKS patients had higher prevalence and titer of NAb compared with EnKS patients ( P = 0.001). Levels of the cytokines IP-10 and IL-10 were higher in EpKS vs EnKS patients ( P = 0.006 and P = 0.005 respectively), whereas, IL-4 was lower in EpKS vs EnKS patients ( P = 0.004). The levels of all 14 cytokines/chemokines measured were comparable between EnKS patients and HIV− controls ( P < .05 ). The distribution of CD4+ and CD8+ T-cells was similar between EpKS and EnKS such as naive and effector T-cells were depleted while central memory T-cells were elevated in both KS forms. Conclusion: The detection of similar abnormalities in T-cell differentiation subsets in both EpKS and EnKS as compared with controls, suggests that KSHV-induced T-cell dysfunction plays a major role in the disease, and that HIV-1 coinfection is only exacerbating and accelerating KSHV pathogenesis and KS development.

Therapeutic efficacy of topical timolol for treatment of African endemic Kaposi sarcoma of the penis

Therapeutic efficacy of topical timolol for treatment of African endemic Kaposi sarcoma of the penis

Classic Kaposi's Sarcoma: A Case Report and Literature Review

Kaposi's Sarcoma (KS) is a rare multifocal spindle cell tumor with four epidemiologic variants: classic KS, African endemic KS, AIDS related KS, and immunosuppressant therapy related KS. Classic KS remains a rare but challenging disease because of its protracted, indolent course. The authors describe a case recently observed in our clinic, emphasizing the clinical management of the disease.

AIDS-associated Kaposi's sarcoma in Sokoto, Nigeria.

Since the advent of the HIV/AIDS pandemic, Kaposi's sarcoma (KS) is now seen in places not previously considered endemic for this disease. In Nigeria, the African-endemic KS had been known to be prevalent in the southern parts of the country, particularly the southeast. Until now, reports on the disease from northern Nigeria are few. To describe the prevalence ofKaposi's sarcoma in Sokoto, northwestern Nigeria. A retrospective review of 27 cases of histologically confirmed KS seen over an 11-year period (Jan.1994-Dec.2004) at the Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, Northwestern Nigeria. The average hospital incidence of KS in this review was 2.5 cases per annum (27 cases in 11 years). The modal age was the 4th decade of life (range 18-70 years). Fifteen percent were females; M: F = 5.8: 1. There was no case of childhood involvement identified. More cases of the disease were HIV-positive (59.3%). The commonest symptom was cutaneous nodules in 96.3% of cases. The body region with the highest affectation of the lesions was the lower limb (70.4%). Kaposi's sarcoma is still uncommon in the northwestern region of Nigeria. The epidemic variant of the disease predominates among the few cases diagnosed. The finding of nodular lesions and/or indurated leg swelling in any adult male in our environment must be considered to be KS until histologically investigated.

African Kaposi Sarcoma – Florid Lesions in a Nigerian Male in South Eastern Equatorial Rain Forest: A Case Report.

Endemic African Kaposi sarcoma is a clinically and epidemiologically distinct human immunodeficiency virus negative form of Kaposi sarcoma (KS) occurring in Africa. This condition runs a variable clinical course ranging from minimal-florid cutaneous disease to extensive organ involvement. We present this seronegetive patient with peculiar and striking florid chemo-sensitive cutaneous lesions with good response in patient performance post chemotherapy. Kaposi sarcoma is chemo-sensitive and should be offered to patients as cutaneous KS lesions may be disfiguring and often generate significant psychological distress. Nigerian Medical Practitioner Vol. 50 (3&4) 2006: pp. 72-76

Role of environmental factors in the pathogenesis of classic and African-endemic Kaposi sarcoma

Kaposi sarcoma (KS) is a mesenchymal tumour associated with human herpesvirus-8 (HHV-8) infection. However, the incidence of HHV-8 infection is far higher than the prevalence of KS, suggesting that viral infection per se is not sufficient for the development of aggressive phenotype and that one or more additional cofactors are required. The great geographical variation in African-endemic and classic KS incidence points to a role for environmental factors in the etiology of Kaposi sarcoma. However, there are few unequivocably established environmental factors involved in KS pathogenesis. This review focuses on the environmental factors thought to be associated with KS, more particularly iron exposure and facilitation of transmission of HHV-8 infection by contact with blood-sucking arthropods.

Epidemic and endemic Kaposi's sarcoma: A comparison of outcomes and survival after radiotherapy

We retrospectively studied the outcomes of 80 Epidemic and African-Endemic Kaposi's Sarcoma (EKS and AKS) patients treated with radiotherapy doses of 8.0 Gy. The objective response for EKS at one month was 74 and 58% for AKS while 5-year survival for EKS was 27 and 46% for AKS.

C-Kit (CD117) Expression in AIDS-Related, Classic, and African Endemic Kaposi Sarcoma

Kaposi sarcoma (KS) is a multicentric vascular neoplasm characterized histologically by the progressive proliferation of spindle-shaped tumor cells in all epidemiologic (AIDS-related, classic, endemic, and iatrogenic) forms. Human herpesvirus 8 (HHV8) is associated with all epidemiologic forms of KS and has been shown in vitro to induce the tyrosine receptor kinase c-kit in HHV8-infected cells. To date, c-kit immunoreactivity has not been systematically studied in KS lesions. Therefore, the aim of this study was to evaluate c-kit expression by immunohistochemistry in different proliferative stages and epidemiologic forms of KS. Archival cases of formalin-fixed, paraffin-embedded KS lesions, including 9 classic, 11 AIDS-related, and 15 African (endemic) forms at various histologic stages (5 patch, 8 plaque, 22 nodular), biopsied from different sites, were stained using immunohistochemistry with antibodies to HHV8 (LNA-1) and c-kit (CD117). C-kit immunoreactivity of lesional cells was demonstrated in 15 (43%) cases overall. A total of five (56%) classic, five (45%) AIDS-related, and five (33%) endemic KS cases were positive for c-kit. There was no difference in the intensity of c-kit staining between the different epidemiologic groups and histologic stages of KS. HHV8 (LNA-1) immunoreactivity was present in all (100%) classic, 10 (91%) AIDS-related, and 9 (60%) endemic cases. LNA-1 staining was demonstrated in 13 (93%) of the c-kit-positive and 15 (75%) of the c-kit-negative KS lesions. These findings indicate that c-kit expression in lesional cells can be detected by immunohistochemistry in different epidemiologic forms and histologic stages of KS. Furthermore, the expression of c-kit does not correspond with the presence of HHV8 (LNA-1) immunoreactivity in KS lesions.

HHV-8 subtypes in South Africa: identification of a case suggesting a novel B variant.

Human herpesvirus 8 (HHV-8) has been identified as the causative agent for all forms of Kaposi's sarcoma and is also associated with the development of body cavity-based B-cell lymphomas and multicentric Castleman's disease. HHV-8 genomes are now classified into five major subtypes (A-E) that reflect sequence heterogeneity in the highly variable open reading frame (ORF) K1. To identify HHV-8 subtypes associated with different forms of Kaposi's sarcoma, we compared the ORF 26 and ORF-K1 gene sequences from South African patients with the prototype strains of the major subtypes, as well as published sequences from other African strains. DNA prepared from Kaposi's sarcoma biopsies and/or peripheral blood lymphocytes were available from 14 patients with postrenal transplant (iatrogenic) Kaposi's sarcoma, six patients with the African endemic form, and one patient with AIDS-related body cavity-based B-cell lymphoma. We identified a B2 subtype in six patients, four of whom also had a novel B5 type ORF 26 polymorphism. Two patients had B2 type patterns for both the ORF 26 and ORF-K1 genes. The ORF-K1 subtype A5 was identified in samples from three patients with a B3/C2 type polymorphism in the ORF 26 gene. A novel ORF-K1 B variant strain was identified in a patient with African endemic Kaposi's sarcoma, who also had a B3/C2 class ORF 26 pattern. In 58.3% of iatrogenic Kaposi's sarcoma patients, a B5-type ORF 26 gene sequence pattern was identified. No association was found among particular subtypes, geographical origin of patients, or clinical presentation.

Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8): epidemiology and pathogenesis.

Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus type 8 (HHV-8), is a gamma2 herpesvirus (rhadinovirus) and the most recently discovered human tumour virus. It is involved in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma and the plasma cell variant of multicentric Castleman's disease. KSHV is not pathogenic in most otherwise healthy individuals but is highly oncogenic in HIV-1-infected and iatrogenically immunosuppressed individuals. It establishes a latent infection in most KS spindle (endothelial tumour) cells and in the neoplastic B cells of primary effusion lymphomas. The KSHV genome contains several homologues of cellular genes known to regulate cell growth and differentiation. Although some of these have transforming properties in vitro, their precise role in oncogenesis is still under investigation. Other co-factors may be involved in the pathogenesis of KS in HIV-uninfected, immunocompetent individuals, e.g. in African endemic KS, but none have been identified yet. Transmission of KSHV among homosexual men appears to occur through sexual contact, but in endemic countries transmission is frequent in childhood and may occur through close contact within families. Four major variants of KSHV have been defined, on the basis of variability in the K1 gene; they may have co-evolved with certain human populations. In addition, some KSHV strains may have resulted from a recombination event with a related, but not yet identified, gamma2 herpesvirus.

Detection and subtyping of human herpesvirus-8 in renal transplant patients before and after remission of Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a complication of renal transplantation. If the human herpesvirus-8 (HHV-8) causes KS, the virus should be present in all KS lesions and be drastically reduced or cleared from involved tissue on remission of the KS. Fourteen renal transplant patients with cutaneous KS, including autopsy material from two cases, were investigated for the presence of HHV-8. A second skin biopsy was taken from 11 survivors, after remission of KS, from normal skin in the same anatomical region as the first biopsy. Remission was induced by reduction or cessation of immunosuppression. A peripheral blood sample was collected simultaneously with the repeat biopsy. A nested polymerase chain reaction assay was used to detect HHV-8 DNA in the biopsy tissue and peripheral blood mononuclear cells followed by direct sequencing of polymerase chain reaction product to detect any nucleotide changes. HHV-8 DNA was detected in all the cutaneous KS and all the visceral KS samples, as well as a number of KS-free organs including the thyroid, salivary gland, and myocardium that have not been described before. Mutations in the viral DNA could be demonstrated in all patients. The mutations found were related more to that seen in AIDS-KS cases than that found in African endemic KS cases. HHV-8 sequences could be detected in follow-up frozen skin biopsies of five patients but were negative in the equivalent formalin-fixed specimens. Viral DNA was also detected in 2 of 11 peripheral blood mononuclear cell samples collected at the time of the follow-up skin biopsies. Reduction or withdrawal of immunosuppression allows the immune system to recover sufficiently to reduce viral replication with subsequent viral persistence and low grade viral replication that coincides with clinical remission of the KS lesions. This provides further evidence for the important etiological role played by HHV-8 in the pathogenesis of posttransplant KS.

Expression of HHV-8 latency-associated T0.7 RNA in spindle cells and endothelial cells of AIDS-associated, classical and African Kaposi's sarcoma.

Analysis by polymerase chain reaction (PCR) and serological studies have demonstrated a close association between the novel human herpes virus, Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) and the development of Kaposi's sarcoma (KS). To clarify the role of HHV-8 in KS pathogenesis, we investigated at the cellular level by in situ hybridization the expression of a recently described 0.7-kb HHV-8-encoded mRNA (T0.7 mRNA) in KS tissues of different epidemiological origin (AIDS-KS, African endemic KS and classical KS). The T0.7 mRNA likely encodes a small membrane protein, supposedly expressed in latently HHV-8-infected cells. Indeed, we detected T0.7 mRNA in virtually all cells of the cell line BCBL-1 established from a body cavity-based lymphoma (BCBL) and latently infected with HHV-8. In all KS biopsies examined, independent of their epidemiological type, the late-stage (nodular) KS tissues showed a high level of T0.7 mRNA expression in typical KS spindle cells but also in endothelial cells lining blood vessels, indicating latent HHV-8 infection of these cells. The presence of T0.7-expressing cells was restricted to KS tumor tissue and therefore appears to indicate an important role of latent HHV-8 infection in KS pathogenesis.

Expression of HHV‐8 latency‐associated T0.7 RNA in spindle cells and endothelial cells of AIDS‐associated, classical and African Kaposi's sarcoma

Analysis by polymerase chain reaction (PCR) and serological studies have demonstrated a close association between the novel human herpes virus, Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) and the development of Kaposi's sarcoma (KS). To clarify the role of HHV-8 in KS pathogenesis, we investigated at the cellular level by in situ hybridization the expression of a recently described 0.7-kb HHV-8-encoded mRNA (T0.7 mRNA) in KS tissues of different epidemiological origin (AIDS-KS, African endemic KS and classical KS). The T0.7 mRNA likely encodes a small membrane protein, supposedly expressed in latently HHV-8-infected cells. Indeed, we detected T0.7 mRNA in virtually all cells of the cell line BCBL-1 established from a body cavity-based lymphoma (BCBL) and latently infected with HHV-8. In all KS biopsies examined, independent of their epidemiological type, the late-stage (nodular) KS tissues showed a high level of T0.7 mRNA expression in typical KS spindle cells but also in endothelial cells lining blood vessels, indicating latent HHV-8 infection of these cells. The presence of T0.7-expressing cells was restricted to KS tumor tissue and therefore appears to indicate an important role of latent HHV-8 infection in KS pathogenesis. Int. J. Cancer 72:68–71, 1997. © 1997 Wiley-Liss Inc.

HHV8 and Kaposi's sarcoma: a time cohort study.

AIMS: The recent finding that human herpes virus 8 (HHV8) is found in the majority of Kaposi's sarcoma (KS) cases supports the epidemiological observation that the tumour may be caused...

Kaposi Sarcoma-Associated Herpesvirus/Human Herpesvirus Type 8 and Epstein-Barr Virus in latrogenic Kaposi Sarcoma

Kaposi sarcoma (KS) occurs in 4 distinct settings categorized as classic KS, African-endemic KS, epidemic (acquired immunodeficiency syndrome [AIDS]—related) KS, and iatrogenic (immunosuppressive drug—associated) KS. 1 A new human herpesvirus, designated KS—associated herpesvirus (KSHV) or human herpesvirus type 8 (HHV-8), was first identified by Chang et al 2 in tissue from patients with epidemic KS. Subsequent studies demonstrated KSHV in tissue from patients with the other 3 forms of KS. 3,4 However, the reported cases of iatrogenic KS have all been in patients receiving organ transplants. Recently, KSHV has also been found in AIDS—related body cavity—based lymphomas, Castleman disease, and various cutaneous squamoproliferative lesions in patients receiving organ transplants. 5-7 Interestingly, some cases of AIDS-related body cavity—based lymphomas were also shown to contain Epstein-Barr virus (EBV) DNA sequences. To our knowledge, the association of KSHV and EBV has not been reported previously in lesional KS tissue. We describe an

Short report: herpes-like DNA sequences in African-endemic and acquired immunodeficiency syndrome-associated Kaposi's sarcoma.

Recently, the unique nucleic acid closely related to the herpes-like sequences has been found in acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). We have confirmed the presence of herpes-like DNA sequences in six cases of AIDS-associated KS and three of the nine cases of African-endemic KS in adults, but not in eight cases of KS in children from the same area. These sequences were seen in a histologically early stage of KS. Our results suggest that herpes-like DNA sequences may play an important role in the pathogenesis of AIDS-associated KS.

Antibodies to human herpesvirus type 8 in the general population and in Kaposi's sarcoma patients

Much of the evidence that human herpesvirus type 8 (HHV-8) is associated with Kaposi's sarcoma (KS) has come from molecular studies of HHV-8 DNA. Seroepidemiological studies have been hampered by the lack of a reliable assay. The serological data reported here were obtained by means of a mouse monoclonal antibody-enhanced immunofluorescence assay for antibodies to lytic and latent HHV-8 antigens. 1435 single samples of serum (or plasma) from many different disease groups and parts of the world were assayed. All patients with African endemic KS and 96% of American patients with AIDS-associated KS were seropositive for lytic antigen, as were 90% of American HIV-infected homosexual men; by contrast only 23% of HIV-seropositive drug users and 21% of HIV-seropositive women were positive for HHV-8 antibody. Factor VIII treatment before 1983 did not increase the risk of HHV-8 infection in patients with haemophilia. In the American general population, about 25% of adults (including volunteer blood donors) and 2-8% of children had antibodies to HHV-8. Our data are consistent with HHV-8 being primarily associated with sexual transmission, but the HHV-8 seropositivity rate in American children suggests that there is a non-sexual route of HHV-8 infection also. On the evidence available so far, the risk of parenteral transmission is low.

The importance of clinical features in differentiating HIV related from non-HIV related Kaposi's sarcoma: experience from Dar es Salaam, Tanzania.

HIV-associated Kaposi's sarcoma (KS) is reported to be the most common tumor among people infected with HIV and accounts for significant morbidity and mortality. A study was conducted at Muhimbili Medical Center among consecutive patients presenting at the skin clinic or admitted to the surgical or medical wards during April-December 1992 and suspected to have KS. Patients completed a questionnaire, had venous blood samples and biopsies of the suspicion skin lesion taken, and were tested for infection with HIV. 81 adult patients with histologically proven KS were seen during the study period. Epidemic KS (EKS) was diagnosed in 72 patients of whom 49 were male, while African endemic Kaposi's sarcoma (AEKS) was diagnosed in nine patients of whom seven were male. No patient presented with classical KS. Compared to AEKS, EKS was more aggressive and disseminated in patients. The mean duration of illness for patients with AEKS was 37.3 months compared to 8.3 months for those with EKS. The presenting symptoms and past history of HIV-related illness were most pronounced among patients with EKS. Patients with EKS also demonstrated profound T4 lymphopenia and inverted T4:T8 ratio suggestive of advanced HIV infection.

Oncogenesis in HIV-infection

The presence of human Kaposi's sarcoma associated herpesvirus-like sequences (KSHV) was examined in different epidemiological variants of Kaposi's sarcoma (KS) and in KS-derived cell cultures by polymerase chain reaction (PCR). KSHV DNA was present in all tumor biopsies of AIDS-associated KS (59 biopsies), endemic KS (26 biopsies; 21 African endemic KS, 5 Greek endemic KS), sporadic/classical KS (28 biopsies) and post-transplant/iatrogenic KS (6 of 7 biopsies). On the contrary, these sequences were only detected rarely in non-involved skin of KS patients (3 positive specimens of 12), in the peripheral blood mononuclear cells of HIV-infected patients (3 positive specimens of 54) and in lymphoma-biopsies (3 positive specimens of 47). Cell cultures derived from KS skin lesions were positive for KSHV DNA only in the first two passages. However, two longer-term positive cultures from a biopsy of a patient affected with sporadic KS and a biopsy of a patient affected with epidemic KS was identified. A strong association of KSHV with KS tissue was observed in all the different epidemiological variants of KS. Long-term positive KS-derived cell cultures will be an important tool to study the herpesvirus-like agent and to investigate its functional role in the initiation and progression of KS.