Classic Kaposi's Sarcoma Research Articles

C-Kit (CD117) expression in classic Kaposi’s sarcoma

Kaposi's sarcoma is a multicentric, low-grade, vascular neoplasia. Human herpesvirus 8 is associated with all epidemiological forms of KS and has been shown in vitro to induce the tyrosine receptor kinase c-Kit in infected cells. To investigate the expression of c-Kit in cases of classic KS and to clarify its association with clinicopathological parameters and HHV8 latency-associated nuclear antigen-1 expression. In total, 35 cases of classic KS at various histological stages were included in the study. Age and gender of the patients and location and histological stage of the tumours were recorded. Formalin-fixed, paraffin wax-embedded tissue sections were stained by immunohistochemistry with antibodies to c-Kit and HHV8. c-Kit immunoreactivity was found in 22 cases and HHV8 immunoreactivity was present in all cases. There was no correlation in c-Kit immunoreactivity between clinicopathological parameters and HHV8 immunoreactivity. The results of our study show that in cases of classic KS there is a high rate of c-Kit immunoreactivity, but c-Kit expression does not show any correlation with HHV8 immunoreactivity.

Kaposi's sarcoma responding to topical imiquimod 5% cream: a case report.

Kaposi's sarcoma, a virus-associated neoplasm, can be treated with systemic therapy such interferon or chemotherapy, although a local alternative is possible in localized disease.Topical imiquimod is a ligand of the toll-like receptors 7 and 8 on dendritic cells, increasing immune responses and showing antiviral and antitumoral activities. We report a spectacular response to imiquimod 5% cream in a patient with classic Kaposi's sarcoma of the leg.

Cause-specific mortality in classic Kaposi's sarcoma: a population-based study in Italy (1995–2002)

Background:Little information is available on the causes of death among persons with classic Kaposi's sarcoma (CKS).Methods:We conducted a population-based study in Italy to identify deceased persons with CKS and the underlying causes of death among them, by reviewing multiple-causes-of-death records. Standardised mortality ratios (SMRs) and 95% confidence intervals were calculated to compare the distribution of causes to that among the same-age general population of deceased persons. The geographical distribution was also evaluated.Results:Of the 946 deaths among persons with CKS, 65.9% were attributable to non-neoplastic conditions and 21.9% to malignancies. For 12.2%, no lethal pathology was identified and CKS was considered as the underlying cause. In 90% of these cases, there was visceral/nodal involvement, therapy-related complications, or neoplastic cachexia. Among persons with CKS who died of other causes, an excess for lymphoid malignancies emerged (SMR=4.40) (chronic lymphocytic leukaemia (11.03), non-Hodgkin's lymphoma (4.22), Hodgkin's lymphoma (11.80), and multiple myeloma (2.3)), balanced by a deficit for all solid cancers (0.56), with a marked deficit for lung cancer (0.41). We found an excess for respiratory diseases (chronic obstructive pulmonary disease (1.86)) and genitourinary diseases (chronic renal failure (6.47)). There was marked geographical heterogeneity in the distribution of deaths.Conclusions:Though referring specifically to Italy, the results are informative for other countries and populations and all cases of CKS in general.

Distribution of ‘promoter’ sandflies associated with incidence of classic Kaposi's sarcoma

The patchy geographical distributions of classic Kaposi's sarcoma (KS) and human herpesvirus type 8 (HHV-8), better known as Kaposi's sarcoma-associated herpesvirus (KSHV) remain unexplained. It has been proposed that certain species of bloodsucking insects ('promoter arthropods') promote the reactivation of HHV-8/KSHV and facilitate both HHV-8/KSHV transmission and KS development. This hypothesis was tested by sampling the presence and density of human-biting Diptera with CDC light traps in two areas of Sardinia with contrasting incidence rates of classic KS. In total, 11,030 specimens (99.9% sandflies and 0.1% mosquitoes) belonging to 10 species were collected from 40 rural sites. Five of these species are considered to be possible promoter arthropods because of the irritation their bites cause: Phlebotomus perniciosus Newstead; Phlebotomus perfiliewi Parrot (Diptera: Psychodidae); Aedes berlandi Seguy; Culiseta annulata (Schrank) and Culex theileri Theobald (Diptera: Culicidae). Five species are probable 'non-promoters' because their bites are not particularly irritating: Culiseta longiareolata (Macquart); Culex pipiens s.l.; Anopheles algeriensis Theobald; Anopheles maculipennis s.l., and Anopheles plumbeus Stephens. A significant correlation was found between the geographical distribution of promoter arthropods and incidence rates of KS (Spearman's r = 0.59,P < 0.01). Promoter arthropods were more likely to be caught in areas with cutaneous leishmaniasis and a past high prevalence of malaria, and in areas of limestone, acid volcanic soil and cereal cultivation. The study supports the association between promoter arthropods and classic KS, which may explain the geographic variability of KS and HHV-8/KSHV, and highlights the links with a number of variables previously associated with the incidence of KS.

Important Role of Gemcitabine in the Treatment of Classic Kaposi's Sarcoma

Important Role of Gemcitabine in the Treatment of Classic Kaposi's Sarcoma

Risk of Classic Kaposi Sarcoma with Residential Exposure to Volcanic and Related Soils in Sicily

Before AIDS, endemic (African) Kaposi sarcoma (KS) was noted to occur in volcanic areas and was postulated to result from dirt chronically embedded in the skin of the lower extremities. The primary cause of all KS types is KS-associated herpesvirus (KSHV) infection, but cofactors contribute to the neoplasia. We investigated whether residential exposure to volcanic or related soils was associated with the risk of classic Kaposi sarcoma (cKS) in Sicily. Risk of incident cKS (N=141) compared with population-based KSHV seropositive controls (N=123) was estimated for residential exposure to four types of soil, categorized with maps from the European Soil Database and direct surveying. Questionnaire data provided covariates. Residents in communities high in luvisols were approximately 2.7 times more likely to have cKS than those in communities with no luvisols. Risk was not specific for cKS on the limbs, but it was elevated approximately four- to five-fold with frequent bathing or tap water drinking in communities with high luvisols. Risk was unrelated to communities high in andosols, tephra, or clay soils. Iron and alumino-silicate clay, major components of luvisols, may increase cKS risk, but formal investigation and consideration of other soil types and exposures are needed.

A comparative study of the frequency of antibody and titers against human herpesvirus 8 latent and lytic antigens in “at‐risk” individuals and among patients with Kaposi's sarcoma

Differences in the prevalence of human herpesvirus 8 (HHV-8) and Kaposi's sarcoma (KS) have been described, depending on the study population and their geographic origin. A cross- sectional study aimed at detecting the frequency and titers of antibodies against HHV-8 latent and lytic antigens in serum samples from individuals with different risk-factors for HHV-8 infection, as well as predictive marker identification in patients with KS, was conducted. Serum samples were collected from seven groups of individuals: 75 patients with AIDS-KS, 5 with classic KS, 16 with African KS, 495 with HIV/AIDS, 805 patients with chronic kidney disease, 683 handicapped individuals, and 757 health care workers. Samples were evaluated for the presence and titers of HHV-8-specific antibodies to latent and lytic antigens using "in house" immunofluorescence assays. The results were analyzed by the Chi-square, Fisher's exact test, Kruskal-Wallis and/or Mann-Whitney U-tests. The frequencies of HHV-8 antibodies were as follows: 87.5-100% in patients with KS, 20.4% in patients with HIV/AIDS, 18% in patients with chronic kidney disease, 1.6% in handicapped individuals, and 1.1% in health care workers. A greater number of samples were antibody positive to lytic antigens. Elevated titers of antibodies to latent and lytic antigens, mostly among patients with KS, were detected. Using established serological assays, different "at-risk" populations for HHV-8 infection/disease were detected in this geographic area, confirming HIV/AIDS and identifying patients with chronic kidney disease as high-risk groups. It is suggested that a longitudinal evaluation of antibody titers in patients with chronic kidney disease be undertaken to confirm their predictive value in the development of KS.

An Unusual Cause of a Parotid Mass in an Immunocompetent Host: Classic Kaposi's Sarcoma

Kaposi's sarcoma (KS) is a virally driven vascular tumor that usually has a multifocal origin, with multiple vascular nodules in the skin and other organs, particularly the gastrointestinal tract. Four variants of KS have been described: HIV-related, African, iatrogenic and classic. Primary classic KS of the head and neck is rare in any case, but KS arising in intraparotid lymph nodes, especially with no cutaneous involvement, is exceptionally rare. We report the case of an immunocompetent 71-year-old man who presented with a three-month history of a slowly progressive swelling in the right parotid region. After parotidectomy and histopathological diagnosis of lymph node localization of KS, a thorough dermatological examination did not reveal any skin lesions, and chest and abdominal computed tomography scans, esophagogastroduodenoscopy, and fecal occult blood test were all negative for visceral and other lymph node localizations. We here discuss the peculiarity of the presentation, the differential diagnosis, and the management strategy of such a rare disease.

Clinical course of classic Kaposi's sarcoma in HIV-negative patients treated with the HIV protease inhibitor indinavir

HIV protease inhibitors have been shown to exert antiangiogenic and antitumor actions independently from their antiretroviral effect. Based on these studies, HIV-seronegative patients with classic Kaposi's sarcoma were treated with indinavir and followed for clinical evolution, drug pharmacokinetics and Kaposi's sarcoma biomarkers. A favorable clinical course was associated with high drug plasma levels, reduced production of basic fibroblast growth factor, lower numbers of circulating endothelial cells, and a decrease in antibody titers against human herpesvirus 8.

Penile Ulceration During Pegylated Doxorubicin Chemotherapy of Classical Kaposi's Sarcoma

This article does not have an abstract.

Results of Radiation Therapy for Treatment of Classic Kaposi Sarcoma

Classic Kaposi sarcoma (CKS) is a vascular neoplasm that primarily affects men of Mediterranean and Ashkenazi Jewish descent. A variety of therapeutic options exist, and choice of treatment depends on clinical form and stage, as well as lesion location and size; options include surgical excision, intralesional interferon alpha-2b, local or extended field radiotherapy, and chemotherapy. The aim of this study was to review the outcome of radiation therapy in the treatment of CKS at a single institution. This retrospective study reviewed patients who receive radiation therapy for histologically confirmed CKS between 1994 and 2006. Sixteen patients were reviewed; the mean age at diagnosis was 74 years, and 13 patients were male. Fifteen patients (94%) presented with leg lesions, and two patients (12.5%) presented with arm lesions. The most commonly prescribed radiation dose was 30 Gy in 15 daily fractions of 2 Gy. All lesions responded to treatment, with a complete response rate of 88% and a partial response rate of 12%. Toxicity was limited to grade I dermatitis (four patients) and grade II dermatitis (two patients). Radiation therapy is an effective treatment modality for CKS and is associated with minimal toxicity.

Classic Kaposi Sarcoma in the United States over the last two decades: A clinicopathologic and molecular study of 438 non-HIV-related Kaposi Sarcoma patients with comparison to HIV-related Kaposi Sarcoma

Classic Kaposi Sarcoma in the United States over the last two decades: A clinicopathologic and molecular study of 438 non-HIV-related Kaposi Sarcoma patients with comparison to HIV-related Kaposi Sarcoma

Kaposi's sarcoma responding to topical imiquimod 5% cream: a case report

Kaposi's sarcoma, a virus-associated neoplasm, can be treated with systemic therapy such interferon or chemotherapy, although a local alternative is possible in localized disease.Topical imiquimod is a ligand of the toll-like receptors 7 and 8 on dendritic cells, increasing immune responses and showing antiviral and antitumoral activities. We report a spectacular response to imiquimod 5% cream in a patient with classic Kaposi's sarcoma of the leg.

Weekly paclitaxel for advanced aggressive classic Kaposi sarcoma: experience in 17 cases

Weekly paclitaxel for advanced aggressive classic Kaposi sarcoma: experience in 17 cases

Asymmetrical transmission of human herpesvirus 8 among spouses of patients with Kaposi sarcoma

Among heterosexuals, the sexual transmission of human herpesvirus 8 (HHV8) has not been established. To assess HHV8 seroprevalence in spouses of patients with classic and endemic Kaposi sarcoma (KS) and to suggest possible routes of transmission. A case-control study was carried out in a teaching hospital among spouses of human immunodeficiency virus-negative patients with KS (cases - exposed subjects) and controls who did not have KS nor were related to patients with KS (nonexposed subjects). HHV8 seroprevalence in spouses of patients with KS was compared with HHV8 seroprevalence in controls matched for age, gender and place of birth. Other serology tests were compared between cases and controls. Among heterosexual couples, HHV8-seropositive and HHV8-seronegative spouses were compared for possible risk factors for virus transmission. HHV8 seroprevalence was significantly higher among spouses of patients with KS (13 of 22; 59%) than among matched controls (19 of 58; 33%; P = 0.043). Among heterosexual couples, five of five (100%) male spouses were HHV8 positive vs. six of 15 (40%) female spouses (P = 0.04). There was no significant difference between HHV8-seropositive and HHV8-seronegative spouses for all other factors screened for among heterosexual couples. Being a spouse of a patient with KS is a risk factor for HHV8 seropositivity. Our results suggest that female-to-male HHV8 transmission could be more efficient than male-to-female transmission among couples including a patient with KS. Transmission could involve distinctive behaviours, or currently unknown biological properties of HHV8.

Treatment of Classic Kaposi's Sarcoma with Topical Imiquimod

Treatment of Classic Kaposi's Sarcoma with Topical Imiquimod

Risk Factors for Classical Kaposi Sarcoma in a Population-based Case-control Study in Sicily

Classical Kaposi sarcoma is a rare complication of Kaposi sarcoma-associated herpes virus (KSHV) infection. We conducted a population-based, frequency-matched case-control study in Sicily to further investigate the reported inverse relationship between smoking and classical Kaposi sarcoma and to identify other factors associated with altered risk. All incident, histologically confirmed classical Kaposi sarcoma cases in Sicily were eligible. A two-stage cluster sample design was applied to select population controls. KSHV seropositivity was determined using four antibody assays (K8.1 and orf73 enzyme immunoassays and two immunofluorenscence assays). Using SAS-callable SUDAAN, we compared the characteristics of classical Kaposi sarcoma cases and KSHV-seropositive controls. Odds ratios (OR) and 95% confidence intervals (CI) are presented. In total, 142 classical Kaposi sarcoma cases and 123 KSHV-seropositive controls were recruited. Current cigarette smoking was associated with reduced risk of classical Kaposi sarcoma amongst males (OR, 0.20; 95% CI, 0.06-0.67). Edema was associated with classical Kaposi sarcoma, but only when it presented on the lower extremities (OR, 3.65; 95% CI, 1.62-8.23). Irrespective of presentation site, diabetes and oral corticosteroid medications were associated with increased risk (OR, 4.73; 95% CI, 2.02-11.1 and OR, 2.34; 95% CI, 1.23-4.45, respectively). Never smoking, diabetes, and oral corticosteroid medication use were all independently associated with classical Kaposi sarcoma risk. We confirmed previous reports that cigarette smoking was associated with a reduced risk of classical Kaposi sarcoma, and we found that risk was lowest among current smokers. We also found that classical Kaposi sarcoma risk was strongly and independently associated with oral corticosteroid use and diabetes. Corroboration of these observations and investigation of possible underlying mechanisms are warranted.

HHV8 a subtype is associated with rapidly evolving classic Kaposi's sarcoma.

The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real-time PCR, an in-house developed IFA assay, and sequence analysis of ORF K1-VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p = 0.006 and p = 0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III-IV compared to stages I-II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A-supported infection.

Treatment of classic Kaposi sarcoma with a nicotine dermal patch: a phase II clinical trial

Kaposi sarcoma (KS), a malignancy of dermal endothelial cells that is caused by human herpesvirus 8 (HHV8) infection, is sensitive to perturbations of immunity. Nicotine might be effective against KS because of its immunologic and vascular effects and because smoking is associated with a low risk of KS. We conducted a masked, randomized phase 2 clinical trial of transdermal nicotine and placebo patches to assess the safety and efficacy of nicotine against classic KS (cKS). Three cKS lesions, predominantly nodules, in each of 24 non-smoking patients were randomly assigned to 15 weeks continuous treatment with nicotine patch (escalated to 7 mg), identical masked placebo patch or no patch. Changes in lesion area and elevation from baseline through six follow-up visits, by direct measurement and by two independent readers using digital photographs of the lesions, were compared using non-parametric and regression methods. Changes in longitudinal levels of HHV8 antibodies and DNA in blood cells were similarly assessed. There were no systemic or serious adverse events, and compliance was good. One patient resumed smoking and discontinued patches, and two patients withdrew at week 12 for unrelated indications. Six (29%) of the remaining 21 suspended use of patches to relieve local skin irritation; four of these six completed the trial at reduced dose. Treatment assignment was not associated with significant or consistent changes in cKS lesion area or elevation, HHV8 viral load or antibodies. Transdermal nicotine and placebo patches caused no serious toxicities but had no demonstrable effect on nodular cKS lesions or HHV8 levels.

The effects of human herpesvirus 8 infection and interferon-γ response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals

Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV-8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary. To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS). We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART). CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS. Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.